U.S. patent application number 11/484219 was filed with the patent office on 2006-11-09 for compounds containing quaternary carbons, medical devices, and methods.
This patent application is currently assigned to Medtronic, Inc.. Invention is credited to Michael Eric Benz, Edward DiDomenico, Christopher M. Hobot, John E. Schwendeman, Randall V. Sparer, Kenneth B. Wagener.
Application Number | 20060252905 11/484219 |
Document ID | / |
Family ID | 56290354 |
Filed Date | 2006-11-09 |
United States Patent
Application |
20060252905 |
Kind Code |
A1 |
Benz; Michael Eric ; et
al. |
November 9, 2006 |
Compounds containing quaternary carbons, medical devices, and
methods
Abstract
Compounds that include diorgano groups having quaternary carbons
and optionally urethane groups, urea groups, or combinations
thereof (i.e., polyurethanes, polyureas, or polyurethane-ureas), as
well as materials and methods for making such compounds.
Inventors: |
Benz; Michael Eric; (Ramsey,
MN) ; DiDomenico; Edward; (Anoka, MN) ; Hobot;
Christopher M.; (Tonka Bay, MN) ; Sparer; Randall
V.; (Andover, MN) ; Wagener; Kenneth B.;
(Gainesville, FL) ; Schwendeman; John E.;
(Pittsburgh, PA) |
Correspondence
Address: |
MUETING, RAASCH & GEBHARDT, P.A.
P.O. BOX 581415
MINNEAPOLIS
MN
55458
US
|
Assignee: |
Medtronic, Inc.
Minneapolis
MN
|
Family ID: |
56290354 |
Appl. No.: |
11/484219 |
Filed: |
July 11, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10292993 |
Nov 13, 2002 |
7101956 |
|
|
11484219 |
Jul 11, 2006 |
|
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|
60332695 |
Nov 14, 2001 |
|
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60361254 |
Mar 1, 2002 |
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Current U.S.
Class: |
528/73 ; 525/123;
528/85 |
Current CPC
Class: |
A61L 27/18 20130101;
C08L 75/00 20130101; C08L 101/02 20130101; C08F 236/20 20130101;
C08G 18/6204 20130101; A61L 27/18 20130101; A61L 27/18
20130101 |
Class at
Publication: |
528/073 ;
528/085; 525/123 |
International
Class: |
C08G 18/77 20060101
C08G018/77; C08G 18/00 20060101 C08G018/00 |
Claims
1. A medical device comprising a polymer comprising a group of the
formula: --(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p-- wherein:
n=0 or 1; m=0 or 1; p=1-100,000; R.sup.1 and R.sup.2 are each
independently a saturated or unsaturated aliphatic group, an
aromatic group, or combinations thereof, optionally including
heteroatoms, with the proviso that R.sup.2 includes at least two
carbon atoms; and Z is --C(R.sup.3).sub.2-- wherein each R.sup.3 is
independently a saturated or unsaturated aliphatic group, an
aromatic group, or combinations thereof, optionally including
heteroatoms, wherein the two R.sup.3 groups within
--C(R.sup.3).sub.2-- can be optionally joined to form a ring.
2. The medical device of claim 1 wherein p=1-5000.
3. The medical device of claim 2 wherein p=2-12.
4. The medical device of claim 1 wherein R.sup.1 and R.sup.2 are
each independently a straight chain alkylene group, an arylene
group, or combinations thereof.
5. The medical device of claim 4 wherein R.sup.1 and R.sup.2 are
each independently a straight chain alkylene group.
6. The medical device of claim 1 wherein R.sup.1 and R.sup.2 are
each independently groups containing up to 100 carbon atoms.
7. The medical device of claim 6 wherein R.sup.1 and R.sup.2 are
each independently groups containing up to 20 carbon atoms.
8. The medical device of claim 7 wherein R.sup.1 and R.sup.2 are
each independently groups containing 2 to 20 carbon atoms.
9. The medical device of claim 1 wherein each R.sup.3 is
independently a straight chain alkyl group, an aryl group, or
combinations thereof, optionally including heteroatoms.
10. The medical device of claim 9 wherein each R.sup.3 is
independently a straight chain alkyl group, optionally including
heteroatoms.
11. The medical device of claim 10 wherein each R.sup.3 is
independently a straight chain alkyl group containing 1 to 20
carbon atoms.
12. The medical device of claim 1 wherein the polymer further
comprises a urethane group, a urea group, or combinations
thereof.
13. The medical device of claim 12 wherein the polymer comprises a
segmented polyurethane.
14. The medical device of claim 1 wherein the polymer is a
biomaterial.
15. The medical device of claim 14 wherein the polymer is
substantially free of ether, ester, and carbonate linkages.
16. The medical device of claim 1 wherein the polymer is linear,
branched, or crosslinked.
17. A medical device comprising a polymer prepared from a compound
of the formula: Y--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--Y
wherein: each Y is independently OH or NR.sup.4H; n=0 or 1; m=0 or
1; p=1-2000; R.sup.1 and R.sup.2 are each independently a saturated
or unsaturated aliphatic group, an aromatic group, or combinations
thereof, optionally including heteroatoms; Z is
--C(R.sup.3).sub.2-- wherein each R.sup.3 is independently a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms, wherein the
two R.sup.3 groups within --C(R.sup.3).sub.2-- can be optionally
joined to form a ring; and each R.sup.4 is independently H or a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof; with the proviso that at least one of the
repeat units -Z-(R.sup.2).sub.m-- is not a
--C(CH.sub.3).sub.2CH.sub.2-- group when both Y groups are OH.
18. The medical device of claim 17 wherein p=1-100.
19. The medical device of claim 18 wherein p=2-12.
20. The medical device of claim 17 wherein the number average
molecular weight of the compound of the formula
Y--(R.sup.1)-(-Z-(R.sup.2).sub.m--).sub.p--Y is no greater than
about 100,000.
21. The medical device of claim 20 wherein the number average
molecular weight of the compound of the formula
Y--(R.sup.1)-(-Z-(R.sup.2).sub.m--).sub.p--Y is about 1000 to about
1500.
22. The medical device of claim 17 wherein R.sup.1 and R.sup.2 are
each independently a straight chain alkylene group, an arylene
group, or combinations thereof.
23. The medical device of claim 22 wherein R.sup.1 and R.sup.2 are
each independently a straight chain alkylene group.
24. The medical device of claim 17 wherein R.sup.1 and R.sup.2 are
each independently groups containing up to 100 carbon atoms.
25. The medical device of claim 24 wherein R.sup.1 and R.sup.2 are
each independently groups containing up to 20 carbon atoms.
26. The medical device of claim 25 wherein R.sup.1 and R.sup.2 are
each independently groups containing 2 to 20 carbon atoms.
27. The medical device of claim 17 wherein each R.sup.2 includes at
least two carbon atoms.
28. The medical device of claim 17 wherein each R.sup.3 is
independently a straight chain alkyl group, an aryl group, or
combinations thereof, optionally including heteroatoms.
29. The medical device of claim 28 wherein each R.sup.3 is
independently a straight chain alkyl group, optionally including
heteroatoms.
30. The medical device of claim 29 wherein each R.sup.3 is
independently a straight chain alkyl group containing 1 to 20
carbon atoms.
31. The medical device of claim 17 wherein the polymer further
comprises a urethane group, a urea group, or combinations
thereof.
32. The medical device of claim 31 wherein the polymer comprises a
segmented polyurethane.
33. The medical device of claim 17 wherein the polymer is a
biomaterial.
34. The medical device of claim 33 wherein the polymer is
substantially free of ether, ester, and carbonate linkages.
35. The medical device of claim 17 wherein each Y is OH.
36. The medical device of claim 17 wherein each R.sup.4 is
independently H or a straight chain alkyl group.
37. The medical device of claim 36 wherein each R.sup.4 is
independently a straight chain alkyl group containing 1 to 20
carbon atoms.
38. The medical device of claim 36 wherein each R.sup.4 is H.
39. The medical device of claim 17 wherein the polymer is linear,
branched, or crosslinked.
40-44. (canceled)
45. A copolymer comprising a group of the formula:
--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p-- wherein: n=0 or 1;
m=0 or 1; p=1-100,000; R.sup.1 and R.sup.2 are each independently a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms, with the
proviso that R.sup.2 includes at least two carbon atoms; and Z is
--C(R.sup.3).sub.2-- wherein each R.sup.3 is independently a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms, wherein the
two R.sup.3 groups within --C(R.sup.3).sub.2-- can be optionally
joined to form a ring.
46. The copolymer of claim 45 wherein p=1-5000.
47. The copolymer of claim 46 wherein p=2-12.
48. The copolymer of claim 45 wherein R.sup.1 and R.sup.2 are each
independently a straight chain alkylene group, an arylene group, or
combinations thereof.
49. The copolymer of claim 48 wherein R.sup.1 and R.sup.2 are each
independently a straight chain alkylene group.
50. The copolymer of claim 45 wherein R.sup.1 and R.sup.2 are each
independently groups containing 2 to 20 carbon atoms.
51. The copolymer of claim 45 wherein each R.sup.3 is independently
a straight chain alkyl group, an aryl group, or combinations
thereof, optionally including heteroatoms.
52. The copolymer of claim 51 wherein each R.sup.3 is independently
a straight chain alkyl group, optionally including heteroatoms.
53. The copolymer of claim 52 wherein each R.sup.3 is independently
a straight chain alkyl group containing 1 to 20 carbon atoms.
54. The copolymer of claim 45 wherein the coplymer is linear,
branched, or crosslinked.
55-61. (canceled)
62. A copolymer prepared from a compound of the formula:
Y--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--Y wherein: each Y
is independently OH or NR.sup.4H; n=0 or 1; m=0 or 1; p=1-2000;
R.sup.1 and R.sup.2 are each independently a saturated or
unsaturated aliphatic group, an aromatic group, or combinations
thereof, optionally including heteroatoms; Z is
--C(R.sup.3).sub.2-- wherein each R.sup.3 is independently a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms, wherein the
two R.sup.3 groups within --C(R.sup.3).sub.2-- can be optionally
joined to form a ring; and each R.sup.4 is independently H or a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof; with the proviso that at least one of the
repeat units -Z-(R.sup.2).sub.m-- is not a
--C(CH.sub.3).sub.2CH.sub.2-- group when both Y groups are OH.
63. The copolymer of claim 62 wherein p=1-100.
64. The copolymer of claim 63 wherein p=2-12.
65. The copolymer of claim 62 wherein the number average molecular
weight of the compound of the formula
Y--(R.sup.1).sub.n--(-Z-(R.sup.2).sub.m--).sub.p--Y is no greater
than about 100,000.
66. The copolymer of claim 62 wherein R.sup.1 and R.sup.2 are each
independently a straight chain alkylene group, an arylene group, or
combinations thereof.
67. The copolymer of claim 66 wherein R.sup.1 and R.sup.2 are each
independently groups containing up to 100 carbon atoms.
68. The copolymer of claim 67 wherein R.sup.1 and R.sup.2 are each
independently groups containing up to 20 carbon atoms.
69. The copolymer of claim 68 wherein R.sup.1 and R.sup.2 are each
independently groups containing 2 to 20 carbon atoms.
70. The copolymer of claim 62 wherein each R.sup.2 includes at
least two carbon atoms.
71. The copolymer of claim 62 wherein each R.sup.3 is independently
a straight chain alkyl group, an aryl group, or combinations
thereof, optionally including heteroatoms.
72. The copolymer of claim 71 wherein each R.sup.3 is independently
a straight chain alkyl group containing 1 to 20 carbon atoms.
73. The copolymer of claim 62 wherein each Y is OH.
74. The copolymer of claim 62 wherein each R.sup.4 is independently
H or a straight chain alkyl group.
75. The copolymer of claim 62 wherein the copolymer is linear,
branched, or crosslinked.
76-87. (canceled)
88. A copolymer prepared from a compound of the formula:
Y--R.sup.5--(--R.sup.6-Z-R.sup.7--).sub.q--R.sup.8--Y wherein: each
Y is independently OH or NH.sub.2; q=1-2000; Z is
--C(R.sup.9).sub.2--; R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are
each independently a straight chain alkylene group having 1-20
carbon atoms; and each R.sup.9 is independently a straight chain
alkyl group having 1-20 carbon atoms.
89. The copolymer of claim 88 wherein q=1-100.
90. The copolymer of claim 89 wherein q=2-12.
91. The copolymer of claim 88 wherein each Y is OH.
92. The copolymer of claim 91 wherein each R.sup.9 is methyl.
93. A compound of the formula:
Y--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--Y wherein: each Y
is independently OH, NR.sup.4H, or protected forms thereof; n=0 or
1; m=0 or 1; p=1-2000; R.sup.1 and R.sup.2 are each independently a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms; Z is
--C(R.sup.3).sub.2-- wherein each R.sup.3 is independently a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms, wherein the
two R.sup.3groups within --C(R.sup.3).sub.2-- can be optionally
joined to form a ring; and each R.sup.4 is independently H or a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof; with the proviso that at least one of the
repeat units -Z-(R.sup.2).sub.m-- is not a
--C(CH.sub.3).sub.2CH.sub.2-- group when both Y groups are OH.
94. The compound of claim 93 wherein p=1-100.
95. The compound of claim 94 wherein p=2-12.
96. The compound of claim 93 wherein the number average molecular
weight of the compound of the formula
Y--(R.sup.1)-(-Z-(R.sup.2).sub.m--).sub.p--Y is no greater than
about 100,000.
97. The compound of claim 93 wherein R.sup.1 and R.sup.2 are each
independently a straight chain alkylene group, an arylene group, or
combinations thereof.
98. The compound of claim 93 wherein R.sup.1 and R.sup.2 are each
independently groups containing up to 100 carbon atoms.
99. The compound of claim 98 wherein R.sup.1 and R.sup.2 are each
independently groups containing 2 to 20 carbon atoms.
100. The compound of claim 93 wherein each R.sup.2 includes at
least two carbon atoms.
101. The compound of claim 93 wherein each R.sup.3 is independently
a straight chain alkyl group, an aryl group, or combinations
thereof, optionally including heteroatoms.
102. The compound of claim 101 wherein each R.sup.3 is
independently a straight chain alkyl group containing 1 to 20
carbon atoms.
103. The compound of claim 93 wherein each Y is OH.
104. The compound of claim 93 wherein each R.sup.4 is independently
a straight chain alkyl group containing 1 to 20 carbon atoms.
105. The compound of claim 93 wherein each R.sup.4 is H.
106. A compound of the formula:
Y--R.sup.5--(--R.sup.6-Z-R.sup.7--).sub.q--R.sup.8--Y wherein: each
Y is independently OH, NH.sub.2, or protected forms thereof;
q=1-2000; Z is --C(R.sup.9).sub.2--; R.sup.5, R.sup.6, R.sup.7, and
R.sup.8 are each independently a straight chain alkylene group
having 1-20 carbon atoms; and each R.sup.9 is independently a
straight chain alkyl group having 1-20 carbon atoms.
107. The compound of claim 106 wherein q=1-100.
108. The compound of claim 107 wherein q=2-12.
109. The compound of claim 106 wherein each Y is OH.
110. The compound of claim 109 wherein each R.sup.9 is methyl.
111-116. (canceled)
117. A method of making a compound of the formula:
Y--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--Y wherein: each Y
is independently OH or NR.sup.4H; n=0 or 1; m=0 or 1; p=1-2000;
R.sup.1 and R.sup.2 are each independently a saturated or
unsaturated aliphatic group, an aromatic group, or combinations
thereof, optionally including heteroatoms; Z is
--C(R.sup.3).sub.2-- wherein each R.sup.3 is independently a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms, wherein the
two R.sup.3 groups within --C(R.sup.3).sub.2-- can be optionally
joined to form a ring; and each R.sup.4 is independently H or a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof, with the proviso that at least one of the
repeat units -Z-(R.sup.2).sub.m-- is not a
--C(CH.sub.3).sub.2CH.sub.2-- group when both Y groups are OH; the
method comprising: polymerizing a diene compound having a
quaternary carbon in the presence of a metathesis catalyst to form
an intermediate polymer; depolymerizing the intermediate polymer in
the presence of a chain transfer agent to form an unsaturated
telechelic polymer; wherein the chain transfer agent comprises
protecting groups; and converting the unsaturated telechelic
polymer to a compound of the formula
Y--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--Y.
118. The method of claim 117 wherein converting the unsaturated
telechelic polymer to a compound of the formula
Y--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m).sub.p--Y comprises:
hydrogenating the unsaturated telechelic polymer to form a
saturated telechelic polymer; and deprotecting the saturated
telechelic polymer.
119. The method of claim 117 wherein converting the unsaturated
telechelic polymer to a compound of the formula
Y--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--Y comprises:
deprotecting the unsaturated telechelic polymer; and hydrogenating
the unsaturated telechelic polymer to form a saturated telechelic
polymer.
120. The method of claim 117 wherein polymerizing the diene
compound comprises polymerizing the diene compound in the presence
of a chain extender and a metathesis catalyst to form an
intermediate polymer.
121. A method of making an alcohol and/or an amine comprising a
quaternary carbon, the method comprising: polymerizing a compound
having a quaternary carbon in the presence of a metathesis catalyst
to form an intermediate polymer, wherein the compound having a
quaternary carbon has the formula:
R.sup.10HC.dbd.CH--(R.sup.11).sub.r-Z-(R.sup.12).sub.s--CH.dbd.CHR.sup.13
wherein: r=0 or 1; s=0 or 1; Z is --C(R.sup.3).sub.2--, wherein
each R.sup.3 is independently a saturated aliphatic group, an
aromatic group, or combinations thereof, optionally including
heteroatoms, wherein the two R.sup.3 groups within
--C(R.sup.3).sub.2-- can be optionally joined to form a ring;
R.sup.10 and R.sup.13 are each independently hydrogen or straight
chain, branched, or cyclic alkyl groups containing up to 6 carbon
atoms; and R.sup.11 and R.sup.12 are each independently a saturated
aliphatic group, an aromatic group, or combinations thereof,
optionally including heteroatoms; depolymerizing the intermediate
polymer in the presence of a chain transfer agent to form an
unsaturated telechelic polymer; wherein the chain transfer agent
comprises protecting groups and has the formula:
Y--R.sup.17--HC.dbd.CH--R.sup.18--Y wherein: each Y is
independently a protected form of OH or NR.sup.4H; and R.sup.17 and
R.sup.18 are each independently a saturated aliphatic group, an
aromatic group, or combinations thereof; and converting the
unsaturated telechelic polymer to an alcohol and/or an amine.
122. The method of claim 121 wherein converting the unsaturated
telechelic polymer to an alcohol and/or an amine comprises:
hydrogenating the unsaturated telechelic polymer to form a
saturated telechelic polymer; and deprotecting the saturated
telechelic polymer.
123. The method of claim 121 wherein converting the unsaturated
telechelic polymer to an alcohol and/or an amine comprises:
deprotecting the unsaturated telechelic polymer; and hydrogenating
the unsaturated telechelic polymer to form a saturated telechelic
polymer.
124. The method of claim 121 wherein polymerizing the compound
having a quaternary carbon comprises polymerizing the compound
having a quaternary carbon in the presence of a chain extender and
a metathesis catalyst to form an intermediate polymer.
125. The method of claim 124 wherein the chain extender is a
compound having the formula:
R.sup.14HC.dbd.CH--R.sup.15--CH.dbd.CHR.sup.16 wherein: R.sup.14
and R.sup.16 are each independently hydrogen or straight chain,
branched, or cyclic alkyl groups containing up to 6 carbon atoms;
and R.sup.15 is a saturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms.
126. A method of making an alcohol and/or an amine comprising a
quaternary carbon, the method comprising: polymerizing a compound
having a quaternary carbon in the presence of a chain transfer
agent and a metathesis catalyst to form an unsaturated telechelic
polymer; wherein the compound having a quaternary carbon has the
formula:
R.sup.10HC.dbd.CH--(R.sup.11).sub.r-Z-(R.sup.12).sub.s--CH.dbd.CHR.sup.13
wherein: r=0 or 1; s=0 or 1; Z is --C(R.sup.3).sub.2--, wherein
each R.sup.3 is independently a saturated aliphatic group, an
aromatic group, or combinations thereof, optionally including
heteroatoms, wherein the two R.sup.3groups within
--C(R.sup.3).sub.2-- can be optionally joined to form a ring;
R.sup.10 and R.sup.13 are each independently hydrogen or straight
chain, branched, or cyclic alkyl groups containing up to 6 carbon
atoms; and R.sup.11 and R.sup.12 are each independently a saturated
aliphatic group, an aromatic group, or combinations thereof,
optionally including heteroatoms; wherein the chain transfer agent
comprises protecting groups and has the formula:
Y--R.sup.17--HC.dbd.CH--R.sup.18--Y wherein: each Y is
independently a protected form of OH or NR.sup.4H; and R.sup.17 and
R.sup.18 are each independently a saturated aliphatic group, an
aromatic group, or combinations thereof; and converting the
unsaturated telechelic polymer to an alcohol and/or an amine.
127. The method of claim 126 wherein converting the unsaturated
telechelic polymer to an alcohol and/or an amine comprises:
hydrogenating the unsaturated telechelic polymer to form a
saturated telechelic polymer; and deprotecting the saturated
telechelic polymer.
128. The method of claim 126 wherein converting the unsaturated
telechelic polymer to an alcohol and/or an amine comprises:
deprotecting the unsaturated telechelic polymer; and hydrogenating
the unsaturated telechelic polymer to form a saturated telechelic
polymer.
129. The method of claim 126 wherein polymerizing the compound
having a quaternary carbon comprises polymerizing the compound
having a quaternary carbon in the presence of a chain transfer
agent, a chain extender, and a metathesis catalyst to form an
unsaturated telechelic polymer.
130. The method of claim 129 wherein the chain extender is a
compound having the formula:
R.sup.14HC.dbd.CH--R.sup.15--CH.dbd.CHR.sup.16 wherein: R.sup.14
and R.sup.16 are each independently hydrogen or straight chain,
branched, or cyclic alkyl groups containing up to 6 carbon atoms;
and R.sup.15 is a saturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms.
131. A method of making an alcohol and/or an amine comprising a
quaternary carbon, the method comprising: polymerizing a compound
having a quaternary carbon in the presence of a metathesis catalyst
to form an intermediate polymer, wherein the compound having a
quaternary carbon has the formula:
R.sup.10HC.dbd.CH--(R.sup.11).sub.r-Z-(R.sup.12).sub.s--CH.dbd.CHR.sup.13
wherein: r=0 or 1; s=0 or 1; Z is --C(R.sup.3).sub.2--, wherein
each R.sup.3 is independently a saturated aliphatic group, an
aromatic group, or combinations thereof, optionally including
heteroatoms, wherein the two R.sup.3 groups within
--C(R.sup.3).sub.2-- can be optionally joined to form a ring;
R.sup.10 and R.sup.13 are each independently hydrogen or straight
chain, branched, or cyclic alkyl groups containing up to 6 carbon
atoms; and R.sup.11 and R.sup.12 are each independently a saturated
aliphatic group, an aromatic group, or combinations thereof,
optionally including heteroatoms; depolymerizing the intermediate
polymer by reaction with a compound of the following formula to
form an unsaturated telechelic polymer:
CH.sub.2.dbd.CH--R.sup.21--Y wherein: each Y is independently a
protected form of OH or NR.sup.4H; and R.sup.21 is a saturated
aliphatic group, an aromatic group, or combinations thereof; and
converting the unsaturated telechelic polymer to an alcohol and/or
an amine.
Description
FIELD OF THE INVENTION
[0001] This invention relates to compounds containing quaternary
carbons, preferably such compounds are polymers containing urethane
and/or urea groups, particularly elastomers. Such materials are
particularly useful as biomaterials in medical devices.
BACKGROUND OF THE INVENTION
[0002] The chemistry of polyurethanes and/or polyureas is extensive
and well developed. Typically, polyurethanes and/or polyureas are
made by a process in which a polyisocyanate is reacted with a
molecule having at least two functional groups reactive with the
polyisocyanate, such as a polyol or polyamine. The resulting
polymer can be further reacted with a chain extender, such as a
diol or diamine, for example. The polyol or polyamine is typically
a polyester, polyether, or polycarbonate polyol or polyamine, for
example.
[0003] Polyurethanes and/or polyureas can be tailored to produce a
range of products from soft and flexible to hard and rigid. They
can be extruded, injection molded, compression molded, and solution
spun, for example. Thus, polyurethanes and polyureas, particularly
polyurethanes, are important biomedical polymers, and are used in
implantable devices such as artificial hearts, cardiovascular
catheters, pacemaker lead insulation, etc.
[0004] Commercially available polyurethanes used for implantable
applications include BIOSPAN segmented polyurethanes, manufactured
by Polymer Technology Group of Berkeley, Calif., PELLETHANE
segmented polyurethanes, sold by Dow Chemical, Midland, Mich., and
TECOFLEX segmented polyurethanes sold by Thermedics, Inc., Woburn,
Mass. Polyurethanes are described in the article "Biomedical Uses
of Polyurethanes," by Coury et al., in Advances in Urethane Science
and Technology, 9, 130-168, edited by Kurt C. Frisch and Daniel
Klempner, Technomic Publishing Co., Lancaster, Pa. (1984).
Typically, polyether polyurethanes exhibit more biostability than
polyester polyurethanes and polycarbonate polyurethanes, as these
are more susceptible to hydrolysis. Thus, polyether polyurethanes
are generally preferred biopolymers.
[0005] Polyether polyurethane elastomers, such as PELLETHANE
2363-80A (P80A) and 2363-55D (P55D), which are prepared from
polytetramethylene ether glycol (PTMEG) and methylene
bis(diisocyanatobenzene) (MDI) extended with 1,4-butanediol (BDO),
are widely used for implantable cardiac pacing leads. Pacing leads
are electrodes that carry stimuli to tissues and biologic signals
back to implanted pulse generators. The use of polyether
polyurethane elastomers as insulation on such leads has provided
significant advantage over silicone rubber, primarily because of
the higher tensile strength of the polyurethanes.
[0006] There is some problem, however, with biodegradation of
polyether polyurethane insulation, which can cause failure.
Polyether polyurethanes are susceptible to oxidation in the body,
particularly in areas that are under stress. When oxidized,
polyether polyurethane elastomers can lose strength and can form
cracks, which might eventually breach the insulation. This,
thereby, can allow bodily fluids to enter the lead and form a short
between the lead wire and the implantable pulse generator (IPG). It
is believed that the ether linkages degrade, perhaps due to metal
ion catalyzed oxidative attack at stress points in the
material.
[0007] One approach to solving this problem has been to coat the
conductive wire of the lead. Another approach has been to add an
antioxidant to the polyurethane. Yet another approach has been to
develop new polyurethanes that are more resistant to oxidative
attack. Such polyurethanes include only segments that are resistant
to metal induced oxidation, such as hydrocarbon- and
carbonate-containing segments. For example, polyurethanes that are
substantially free of ether and ester linkages have been developed.
This includes the segmented aliphatic polyurethanes of U.S. Pat.
No. 4,873,308 (Coury et al.). Another approach has been to include
a sacrificial moiety (preferably in the polymer backbone) that
preferentially oxidizes relative to all other moieties in the
polymer, which upon oxidation provides increased tensile strength
relative to the polymer prior to oxidation. This is disclosed in
U.S. Pat. No. 5,986,034 (DiDomenico et al.), U.S. Pat. No.
6,111,052 (DiDomenico et al.), and U.S. Pat. No. 6,149,678
(DiDomenico et al.).
[0008] Although such materials produce more stable implantable
devices than polyether polyurethanes, there is still a need for
biostable polymers, particularly polyurethanes suitable for use as
insulation on pacing leads.
SUMMARY OF THE INVENTION
[0009] The present invention relates to compounds, preferably
polymers, that include diorgano groups having quaternary carbons.
Particularly preferred polymers include urethane groups, urea
groups, or combinations thereof (i.e., polyurethanes, polyureas, or
polyurethane-ureas). This includes materials and methods for making
such compounds. Preferably, the polymer is a segmented
polyurethane. Certain embodiments of the polymers of the present
invention can be used as biomaterials in medical devices. The
polymer is also preferably substantially free of ester, ether, and
carbonate linkages.
[0010] The present invention provides a polymer, and a medical
device incorporating such polymer, which includes a group of the
formula: --(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p-- wherein:
n=0 or 1; m=0 or 1; p=1-100,000; R.sup.1 and R.sup.2 are each
independently a saturated or unsaturated aliphatic group, an
aromatic group, or combinations thereof, optionally including
heteroatoms, (preferably, the aromatic groups are within the
backbone); and Z is --C(R.sup.3).sub.2-- wherein each R.sup.3 is
independently (i.e., they may be the same or different) a saturated
or unsaturated aliphatic group, an aromatic group, or combinations
thereof, optionally including heteroatoms, wherein the two R.sup.3
groups within --C(R.sup.3).sub.2-- can be optionally joined to form
a ring.
[0011] The present invention also provides a polymer, and a medical
device that incorporates such polymer, wherein the polymer is
prepared from a compound (typically a polymeric starting material)
of the formula: Y--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--Y
wherein: each Y is independently OH or NR.sup.4H; n=0 or 1; m=0 or
1; p=1-2000; R.sup.1 and R.sup.2 are each independently a saturated
or unsaturated aliphatic group, an aromatic group, or combinations
thereof, optionally including heteroatoms (preferably, the aromatic
groups are within the backbone); Z is --C(R.sup.3).sub.2-- wherein
each R.sup.3 is independently a saturated or unsaturated aliphatic
group, an aromatic group, or combinations thereof, optionally
including heteroatoms, wherein the two R.sup.3 groups within
--C(R.sup.3).sub.2-- can be optionally joined to form a ring; and
each R.sup.4 is independently H or a saturated or unsaturated
aliphatic group, an aromatic group, or combinations thereof.
[0012] In certain preferred embodiments, the polymer is prepared
from an isocyanate-containing compound and a compound of the
formula: Y--R.sup.5--(--R.sup.6-Z-R.sup.7--).sub.q--R.sup.8--Y
wherein: each Y is independently OH or NH.sub.2; q=1-2000; Z is
--C(R.sup.9).sub.2--; R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are
each independently a straight chain alkylene group having 1-20
carbon atoms; and each R.sup.9 is independently a straight chain
alkyl group having 1-20 carbon atoms.
[0013] Also provided is a compound of the formula:
Y--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--Y wherein: each Y
is independently OH, NR.sup.4H, or protected forms thereof; n=0 or
1; m=0 or 1; p=1-2000; R.sup.1 and R.sup.2 are each independently a
saturated or-unsaturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms,
(preferably, the aromatic groups are within the backbone); Z is
--C(R.sup.3).sub.2-- wherein each R.sup.3 is independently a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms, wherein the
two R.sup.3groups within --C(R.sup.3).sub.2-- can be optionally
joined to form a ring; and each R.sup.4 is independently H or a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof.
[0014] In certain preferred embodiments of the present invention,
there is a compound of the formula:
Y--R.sup.5--(--R.sup.6-Z-R.sup.7--).sub.q--R.sup.8--Y wherein: each
Y is independently OH or NH.sub.2; q=1-2000; Z is
--C(R.sup.9).sub.2--; R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are
each independently a straight chain alkylene group having 1-20
carbon atoms; and each R.sup.9 is independently a straight chain
alkyl group having 1-20 carbon atoms.
[0015] It should be understood that in the formulas presented
herein, the repeat units (e.g., R.sup.1, -Z-(R.sup.2).sub.m--, and
--R.sup.6-Z-R.sup.7--) can vary within any one molecule.
[0016] As written, the formulas provided herein (for both the
resultant polymers and the polymeric starting materials) encompass
alternating, random, block, star block, segmented copolymers, and
combinations thereof (e.g., wherein certain portions of the
molecule are alternating and certain portions are random). With
respect to star block copolymers, it should be understood that the
polymeric segments described herein could form at least a part of
one or more arms of the star, although the segment itself would not
necessarily include the core branch point of the star.
[0017] Preferably, the polymers, and compounds used to make them,
described herein have substantially no tertiary carbons in the main
chain (i.e., backbone) of the molecules.
[0018] Methods of preparation of such polymers and compounds are
also provided.
[0019] For example, a method of making a polymer that includes a
urethane group, a urea group, or combinations thereof, and a group
of the formula --(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--
includes combining an isocyanate-containing compound and a compound
of the formula Y--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--Y,
which are described in greater detail herein. A method of making a
polymer that includes a urethane group, a urea group, or
combinations thereof, and a group of the formula
--C(R.sup.9).sub.2-- includes combining an isocyanate-containing
compound and a compound of the formula
Y--R.sup.5--(--R.sup.6-Z-R.sup.7--).sub.q--R.sup.8--Y, which are
described in greater detail herein.
[0020] The present invention also provides a method of making a
compound of the formula
Y--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--Y, described
herein, which includes: polymerizing a diene compound having a
quaternary carbon in the presence of a metathesis catalyst to form
an intermediate polymer; depolymerizing the intermediate polymer in
the presence of a chain transfer agent to form an unsaturated
telechelic polymer; wherein the chain transfer agent includes
protecting groups; and converting the unsaturated telechelic
polymer to a compound of the formula
Y--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--Y. The step of
polymerizing preferably includes polymerizing the diene compound in
the presence of a chain extender and a metathesis catalyst to form
an intermediate polymer. The step of converting the unsaturated
telechelic polymer preferably includes: hydrogenating the
unsaturated telechelic polymer to form a saturated telechelic
polymer; and deprotecting the saturated telechelic polymer.
Alternatively, the step of converting the unsaturated telechelic
polymer preferably includes: deprotecting the unsaturated
telechelic polymer; and hydrogenating the unsaturated telechelic
polymer to form a saturated telechelic polymer.
[0021] The present invention also provides methods of making an
alcohol and/or an amine that includes a quaternary carbon.
[0022] One method of making an alcohol and/or amine includes:
polymerizing a compound having a quaternary carbon in the presence
of a metathesis catalyst to form an intermediate polymer, wherein
the compound having a quaternary carbon has the formula:
R.sup.10HC.dbd.CH--(R.sup.11).sub.r-Z-(R.sup.12).sub.s--
CH.dbd.CHR.sup.13 wherein: r=0 or 1; s=0 or 1; Z is
--C(R.sup.3).sub.2--, wherein each R.sup.3 is independently a
saturated aliphatic group, an aromatic group, or combinations
thereof, optionally including heteroatoms, wherein the two R.sup.3
groups within --C(R.sup.3).sub.2-- can be optionally joined to form
a ring; R.sup.10 and R.sup.13 are each independently hydrogen or
straight chain, branched, or cyclic alkyl groups containing up to 6
carbon atoms; and R.sup.11 and R.sup.12 are each independently a
saturated aliphatic group, an aromatic group, or combinations
thereof, optionally including heteroatoms; depolymerizing the
intermediate polymer in the presence of a chain transfer agent to
form an unsaturated telechelic polymer; wherein the chain transfer
agent includes protecting groups and has the formula:
Y--R.sup.17--HC.dbd.CH--R.sup.18--Y wherein: each Y is
independently a protected form of OH or NR.sup.4H; and R.sup.17 and
R.sup.18 are each independently a saturated aliphatic group, an
aromatic group, or combinations thereof; and converting the
unsaturated telechelic polymer to an alcohol and/or an amine.
Preferably, the step of polymerizing the compound having a
quaternary carbon includes polymerizing the compound having a
quaternary carbon in the presence of a chain extender and a
metathesis catalyst to form an intermediate polymer. Preferably,
the step of converting the unsaturated telechelic polymer to an
alcohol and/or an amine includes: hydrogenating the unsaturated
telechelic polymer to form a saturated telechelic polymer; and
deprotecting the saturated telechelic polymer. Alternatively, the
step of converting the unsaturated telechelic polymer to an alcohol
and/or an amine preferably includes: deprotecting the unsaturated
telechelic polymer; and hydrogenating the unsaturated telechelic
polymer to form a saturated telechelic polymer.
[0023] Another method of making an alcohol and/or amine includes:
polymerizing a compound having a quaternary carbon in the presence
of a chain transfer agent and a metathesis catalyst to form an
unsaturated telechelic polymer; wherein the compound having a
quaternary carbon has the formula:
R.sup.10HC.dbd.CH--(R.sup.11).sub.r-Z-(R.sup.12).sub.s--CH.dbd.CHR.sup.13-
, as described herein, wherein the chain transfer agent includes
protecting groups and has the formula:
Y--R.sup.17--HC.dbd.CH--R.sup.18--Y, as described herein; and
converting the unsaturated telechelic polymer to an alcohol and/or
an amine. Preferably, the step of polymerizing the compound having
a quaternary carbon includes polymerizing the compound having a
quaternary carbon in the presence of a chain transfer agent, a
chain extender, and a metathesis catalyst to form an unsaturated
telechelic polymer. Preferably, the step of converting the
unsaturated telechelic polymer to an alcohol and/or an amine
includes: hydrogenating the unsaturated telechelic polymer to form
a saturated telechelic polymer; and deprotecting the saturated
telechelic polymer. Alternatively, the step of converting the
unsaturated telechelic polymer to an alcohol and/or an amine
preferably includes: deprotecting the unsaturated telechelic
polymer; and hydrogenating the unsaturated telechelic polymer to
form a saturated telechelic polymer.
[0024] Another method of making an alcohol and/or amine includes:
polymerizing a compound having a quaternary carbon in the presence
of a metathesis catalyst to form an intermediate polymer, wherein
the compound having a quaternary carbon has the formula:
R.sup.10HC.dbd.CH--(R.sup.11).sub.r-Z-(R.sup.12).sub.s--CH.dbd.CHR.sup.13-
, as described herein; depolymerizing the intermediate polymer by
reacting with a compound of the following formula to form an
unsaturated telechelic polymer: CH.sub.2.dbd.CH--R.sup.21--Y
wherein each Y is independently a protected form of OH or
NR.sup.4H, and R.sup.21 is a saturated aliphatic group, an aromatic
group, or combinations thereof; and converting the unsaturated
telechelic polymer to an alcohol and/or an amine. Preferably, the
step of converting the unsaturated telechelic polymer to an alcohol
and/or an amine includes: hydrogenating the unsaturated telechelic
polymer to form a saturated telechelic polymer; and deprotecting
the saturated telechelic polymer. Alternatively, the step of
converting the unsaturated telechelic polymer to an alcohol and/or
an amine preferably includes: deprotecting the unsaturated
telechelic polymer; and hydrogenating the unsaturated telechelic
polymer to form a saturated telechelic polymer.
[0025] As used herein, the terms "a," "an," "one or more," and "at
least one" are used interchangeably.
[0026] As used herein, the term "aliphatic group" means a saturated
or unsaturated linear (i.e., straight chain), cyclic (i.e.,
cycloaliphatic), or branched organic hydrocarbon group. This term
is used to encompass alkyl (e.g., --CH.sub.3, which is considered a
"monovalent" group) (or alkylene if within a chain such as
--CH.sub.2--, which is considered a "divalent" group), alkenyl (or
alkenylene if within a chain), and alkynyl (or alkynylene if within
a chain) groups, for example. The term "alkyl group" means a
saturated linear or branched hydrocarbon group including, for
example, methyl, ethyl, isopropyl, t-butyl, heptyl, dodecyl,
octadecyl, amyl, 2-ethylhexyl, and the like. The term "alkenyl
group" means an unsaturated, linear or branched hydrocarbon group
with one or more carbon-carbon double bonds, such as a vinyl group.
The term "alkynyl group" means an unsaturated, linear or branched
hydrocarbon group with one or more carbon-carbon triple bonds. The
term "aromatic group" or "aryl group" means a mono- or polynuclear
aromatic organic hydrocarbon group. These hydrocarbon groups may be
substituted with heteroatoms, which can be in the form of
functional groups. The term "heteroatom" means an element other
than carbon (e.g., nitrogen, oxygen, sulfur, chlorine, etc.).
[0027] As used herein, a "biomaterial" may be defined as a material
that is substantially insoluble in body fluids and tissues and that
is designed and constructed to be placed in or onto the body or to
contact fluid or tissue of the body. Ideally, a biomaterial will
not induce undesirable reactions in the body such as blood
clotting, tissue death, tumor formation, allergic reaction, foreign
body reaction (rejection) or inflammatory reaction; will have the
physical properties such as strength, elasticity, permeability and
flexibility required to function for the intended purpose; can be
purified, fabricated and sterilized easily; and will substantially
maintain its physical properties and function during the time that
it remains implanted in or in contact with the body. A "biostable"
material is one that is not broken down by the body, whereas a
"biocompatible" material is one that is not rejected by the
body.
[0028] As used herein, a "medical device" may be defined as a
device that has surfaces that contact blood or other bodily tissues
in the course of their operation. This can include, for example,
extracorporeal devices for use in surgery such as blood
oxygenators, blood pumps, blood sensors, tubing used to carry blood
and the like which contact blood which is then returned to the
patient. This can also include implantable devices such as vascular
grafts, stents, electrical stimulation leads, heart valves,
orthopedic devices, catheters, shunts, sensors, replacement devices
for nucleus pulposus, cochlear or middle ear implants, intraocular
lenses, and the like.
BRIEF DESCRIPTION OF THE DRAWINGS
[0029] FIG. 1 is a schematic showing a preferred method of
preparation of various compounds of the present invention.
[0030] FIG. 2 lists examples of catalysts suitable for use in
methods of the invention.
[0031] FIG. 3 is a schematic showing a preferred method of
preparation of a diene suitable for use in the methods of the
present invention.
DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS OF THE
INVENTION
[0032] The present invention provides polymers (preferably,
segmented polyurethanes), compounds used to prepare such polymers
(preferably, they form the soft segments of segmented polymers),
and medical devices that include such polymers (preferably,
biomaterials). Preferably, the polymers are generally resistant to
oxidation and/or hydrolysis, particularly with respect to their
backbones, as opposed to their side chains.
[0033] The polymers include one or more diorgano groups. These
diorgano (e.g., gem-dialkyl) groups are of the general formula
--C(R.sup.3).sub.2-- wherein C is a quaternary carbon and each
R.sup.3 is independently (i.e., may be the same or different) a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms (which may
be in the chain of the organic group or pendant therefrom as in a
functional group). Preferably, each R.sup.3 is independently a
straight chain alkyl group optionally including heteroatoms. Most
preferably, each R.sup.3 is independently a straight chain alkyl
group without heteroatoms.
[0034] The polymers suitable for forming biomaterials for use in
medical devices according to the present invention include
quaternary carbons, and are preferably polyurethanes, polyureas, or
polyurethane-ureas. These polymers can vary from hard and rigid to
soft and flexible. Preferably, the polymers are elastomers. An
"elastomer" is a polymer that is capable of being stretched to
approximately twice its original length and retracting to
approximately its original length upon release.
[0035] Polymers of the present invention can be homopolymers or
copolymers, although preferably, they are random, alternating,
block, star block, segmented copolymers, or combinations thereof.
Most preferably, the polymers are segmented copolymers (i.e.,
containing a multiplicity of both hard and soft domains or segments
on any polymer chain) and are comprised substantially of
alternating relatively soft segments and relatively hard
segments.
[0036] For segmented polymers either the hard or the soft segments,
or both, include a diorgano moiety, thereby providing a polymer
that has reduced susceptibility to oxidation and/or hydrolysis, at
least with respect to the polymer backbone. As used herein, a
"hard" segment is one that is either crystalline at use temperature
or amorphous with a glass transition temperature above use
temperature (i.e., glassy), and a "soft" segment is one that is
amorphous with a glass transition temperature below use temperature
(i.e., rubbery). A crystalline or glassy moiety or hard segment is
one that adds considerable strength and higher modulus to the
polymer. Similarly, a rubbery moiety or soft segment is one that
adds flexibility and lower modulus, but may add strength
particularly if it undergoes strain crystallization, for example.
The random or alternating soft and hard segments are linked by
urethane and/or urea groups and the polymers may be terminated by
hydroxyl, amine, and/or isocyanate groups.
[0037] As used herein, a "crystalline" material or segment is one
that has ordered domains. A "noncrystalline" material or segment is
one that is amorphous (a noncrystalline material may be glassy or
rubbery). A "strain crystallizing" material is one that forms
ordered domains when a strain or mechanical force is applied.
[0038] An example of a medical device for which the polymers are
particularly well suited is a medical electrical lead, such as a
cardiac pacing lead, a neurostimulation lead, etc. Examples of such
leads are disclosed, for example, in U.S. Pat. No. 5,040,544
(Lessar et al.), U.S. Pat. No. 5,375,609 (Molacek et al.), U.S.
Pat. No. 5,480,421 (Often), and U.S. Pat. No. 5,238,006
(Markowitz).
Polymers and Methods of Preparation
[0039] A wide variety of polymers are provided by the present
invention. They can be homopolymers or alternating, random, block,
star block, or segmented copolymers (or combinations thereof),
preferably they are copolymers (including terpolymers,
tetrapolymers), that can include olefins, amides, esters, imides,
epoxies, ureas, urethanes, carbonates, sulfones, ethers, acetals,
phosphonates, and the like. These include moieties containing
diorgano (preferably, gem-dialkyl) groups of the general formula
--C(R).sub.2-- wherein C is a quaternary carbon.
[0040] Such polymers can be prepared using a variety of techniques
from polymerizable compounds (e.g., monomers, oligomers, or
polymers) containing diorgano (preferably, gem-dialkyl) moieties of
the general formula --C(R.sup.3).sub.2-- wherein C is a quaternary
carbon. Such compounds include dienes, diols, diamines, or
combinations thereof, for example.
[0041] Although certain preferred polymers are described herein,
the polymers used to form the preferred biomaterials in the medical
devices of the present invention can be a wide variety of polymers
that include urethane groups, urea groups, or combinations thereof.
Such polymers are prepared from isocyanate-containing compounds,
such as polyisocyanates (preferably diisocyanates) and compounds
having at least two functional groups reactive with the isocyanate
groups, such as polyols and/or polyamines (preferably diols and/or
diamines). Any of these reactants can include a diorgano moiety
(preferably in the polymer backbone), although preferably a
diorgano moiety is provided by the polyols and/or polyamines,
particularly diols and/or diamines (including the diols or diamines
of the dimer acid described below).
[0042] The presence of the diorgano moiety provides a polymer that
is typically more resistant to oxidative and/or hydrolytic
degradation but still has a relatively low glass transition
temperature (Tg). Furthermore, preferably, both the hard and soft
segments are themselves substantially ether-free, ester-free, and
carbonate-free polyurethanes, polyureas, or combinations
thereof.
[0043] Preferred polymers of the present invention include a group
of the formula --(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--
wherein -Z- is a diorgano moiety --C(R.sup.3).sub.2--. In one
embodiment, particularly preferred polymers also include one or
more urethane groups, urea groups, or combinations thereof
(preferably, just urethane groups). In another embodiment,
particularly preferred polymers are copolymers (i.e., prepared from
two or more monomers, including terpolymers or tetrapolymers).
Thus, the present invention provides polymers with these
--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p-- groups randomly
distributed or ordered in blocks or segments.
[0044] Polymers of the present invention can be linear, branched,
or crosslinked. This can be done using polyfunctional isocyanates
or polyols (e.g., diols, triols, etc.) or using compounds having
unsaturation or other functional groups (e.g., thiols) in one or
more monomers with radiation crosslinking. Such methods are well
known to those of skill in the art.
[0045] Preferably, polymers of the present invention (and the
compounds used to make them) have substantially no tertiary carbons
in the main chain (i.e., backbone).
[0046] In the group of the formula
--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--, n=0 or 1; m=0 or
1; p=1-100,000; R.sup.1 and R.sup.2 are each independently a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms (which may
be in the chain of the organic group or pendant therefrom),
preferably with the proviso that the aromatic groups are within the
backbone; and Z is a diorgano moiety --C(R.sup.3).sub.2-- wherein
each R.sup.3 is independently (i.e., may be the same or different)
a saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms (which may
be in the chain of the organic group or pendant therefrom), wherein
the two R.sup.3 groups within a --C(R.sup.3).sub.2-- moiety can be
optionally joined to form a ring. It should be understood that the
repeat unit -Z-(R.sup.2).sub.m-- can vary within any one
molecule.
[0047] A preferred source of the group of the formula
--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p-- is a compound of
the formula (Formula I):
Y--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--Y wherein: each Y
is independently OH or NR.sup.4H; n=0 or 1; m=0 or 1; p=1-2000;
R.sup.1 and R.sup.2 are each independently a saturated or
unsaturated aliphatic group, an aromatic group, or combinations
thereof, optionally including heteroatoms (which may be in the
chain of the organic group or pendant therefrom), preferably with
the proviso that the aromatic groups are within the backbone; Z is
--C(R.sup.3).sub.2-- wherein each R.sup.3 is independently a
saturated or unsaturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms (which may
be in the chain of the organic group or pendant therefrom), wherein
the two R.sup.3 groups within a --C(R.sup.3).sub.2-- moiety can be
optionally joined to form a ring; and each R.sup.4 is independently
H or a saturated or unsaturated aliphatic group, an aromatic group,
or combinations thereof.
[0048] It should be understood that any repeat unit can vary within
any one molecule. That is, R.sup.6 and R.sup.7, for example, can be
the same or different between repeat units in any one molecule.
Similarly, R.sup.3, as well as R.sup.9, for example, can be the
same or different between repeat units in any one molecule. Also,
in addition to each R.sup.2 being the same or different within each
Z(R.sup.2).sub.m groups, the Z(R.sup.2).sub.m groups can be the
same or different in any one molecule. Furthermore, each R.sup.1
can be the same or different in any molecule.
[0049] The R.sup.3 groups are selected such that the ultimate
product (e.g., a segmented polyurethane polymer) has the following
properties relative to a polymer without the diorgano (Z) moieties:
reduced glass transition temperature (Tg) of the polymer; enhanced
strength as a result of hydrogen bonding between the polymer
chains; suppressed crystallization of soft segments at room
temperature under zero strain; increased strain crystallization;
greater ability to control phase separation for balancing
elastomeric properties versus strength; greater ability to control
melt rheology; and/or greater ability to modify the polymers using
functional groups within the R.sup.3 groups.
[0050] Although the diorgano moieties reduce the susceptibility of
the compound of Formula I and the ultimate polymer to oxidation or
hydrolysis, the R.sup.3 groups could themselves be susceptible to
oxidation or hydrolysis as long as the main chain (i.e., the
backbone) is not generally susceptible to such reactions.
Preferably, the R.sup.3 groups are each independently a straight
chain alkyl group, an aryl group, or combinations thereof. More
preferably, the R.sup.3groups are each independently a straight
chain alkyl group.
[0051] Optionally, the R.sup.3groups can include heteroatoms, such
as nitrogen, oxygen, phosphorus, sulfur, and halogen. These could
be in the backbone of the organic group or pendant therefrom as in
the form of functional groups, as long as the polymer is generally
resistant to oxidation and/or hydrolysis, particularly with respect
to its backbone, as opposed to its side chains. Such functional
groups include, for example, an alcohol, ether, acetoxy, ester,
aldehyde, acrylate, amine, amide, imine, imide, and nitrile,
whether they be protected or unprotected. Most preferably, each
R.sup.3 is independently a straight chain alkyl group without
heteroatoms.
[0052] Preferably, R.sup.1 and R.sup.2 are each independently a
straight chain alkylene group (e.g., a divalent aliphatic group
such as --CH.sub.2--CH.sub.2-- and the like), an arylene group, or
combinations thereof, preferably with the proviso that the aromatic
groups are within the backbone. More preferably, R.sup.1 and
R.sup.2 do not include tertiary carbon atoms in the main chain
(i.e., backbone) of the molecule. Most preferably, R.sup.1 and
R.sup.2 are each independently a straight chain alkylene group.
[0053] Preferably, each R.sup.4 is independently hydrogen, a
straight chain alkyl group, an aryl group, or combinations thereof.
More preferably, each R.sup.4 group is independently hydrogen or a
straight chain alkyl group.
[0054] The R.sup.1, R.sup.2, R.sup.3 and R.sup.4 groups are
selected such that the number average molecular weight of a
compound of Formula I is no greater than about 100,000 grams per
mole (g/mol or Daltons). Preferably, the molecular weight is about
1000 g/mol to about 1500 g/mol.
[0055] Preferably, R.sup.1 and R.sup.2 are each independently an
organic group that includes at least one carbon atom, and more
preferably at least two carbon atoms (this is particularly true for
R.sup.2). Preferably, R.sup.1 and R.sup.2 are each independently an
organic group that includes no more than 100 carbon atoms, more
preferably no more than 50 carbon atoms, and most preferably no
more than 20 carbon atoms.
[0056] Preferably, R.sup.3 is an organic group that includes at
least one carbon atom. Preferably, R.sup.3 is an organic group that
includes no more than 100 carbon atoms, more preferably no more
than 50 carbon atoms, and most preferably no more than 20 carbon
atoms.
[0057] Preferably, R.sup.4 is hydrogen or an organic group that
includes at least one carbon atom. Preferably, R.sup.4is an organic
group that includes no more than 100 carbon atoms, more preferably
no more than 50 carbon atoms, even more preferably no more than 20
carbon atoms, and most preferably no more than 4 carbon atoms. Most
preferably, R.sup.4 is hydrogen.
[0058] The values for n, m, and p are average values. Preferably,
at least one n or m is one. More preferably, both n and m are one.
In increasing order of preference, p is 1-100,000, 1-50,000,
1-10,000, 1-5000, 1-2000, 1-1000, 1-500, 1-200, 1-100, 1-50, 1-20,
2-20, and 2-12.
[0059] Preferably, the Y groups are OH of NH.sub.2. More
preferably, the Y groups are both OH.
[0060] In Formula I, preferably at least one of the repeat units
-Z-(R.sup.2).sub.m-- is not a --C(CH.sub.3).sub.2CH.sub.2-- group
when both Y groups are OH. Thus, preferably, the repeat unit
-Z-(R.sup.2).sub.m-- is not derived solely from isobutylene (in
which R.sup.2 is a --CH.sub.2-- and each R.sup.3 group is a
--CH.sub.3), particularly when both Y groups are OH. Rather, each
R.sup.2 group preferably has greater than one carbon atom (e.g.,
ethylene, propylene, butylene, etc.), even more preferably, greater
than five carbon atoms, and most preferably, greater than eight
carbon atoms. A polymer derived solely from isobutylene would not
be expected to exhibit strain crystallization, although the
polymers with longer R.sup.2 groups would. Strain crystallization
is desirable because the resultant polymer would have enhanced
strength. That is, the mechanical properties of isobutylene-based
polyurethanes are poor compared to conventional polyurethanes. Lack
of soft segment crystrallization and excessive phase separation
under strain has been suggested for explanations for the
unexpectedly low tensile properties. See, J. P. Kennedy et al.,
Designed Polymers by Carbocationic Macromolecular Engineering
Theory and Practice, Hanser Publishers, 1992, page 192, and
Speckhard et al., Rubber Chem. Technol., 59, 405 (1986).
[0061] A preferred subset of Formula I are compounds of the formula
(Formula II): Y--R.sup.5--(--R.sup.6-Z-R.sup.7--).sub.q--R.sup.8--Y
wherein: each Y is independently OH or NH.sub.2; Z is
--C(R.sup.9).sub.2--; and R.sup.5, R.sup.6, R.sup.7, and R.sup.8
are each independently a straight chain alkylene group having 1-20
carbon atoms. Each R.sup.9 is independently a straight chain alkyl
group having 1-20 carbon atoms. Preferably, each R.sup.9 is methyl.
In such compounds, the repeat units --R.sup.6-Z-R.sup.7-- can vary
within any one molecule. In increasing order of preference, q is
1-2000, 1-1000, 1-500, 1-200, 1-100, 1-50, 1-20, 2-20, and
2-12.
[0062] The polymers of the present invention can be prepared using
standard techniques. Certain polymers can be made using one or more
of the compounds of Formula I (preferably Formula II). Typically, a
compound of Formula I is combined with an organic compound
containing two or more groups capable of reacting with hydroxyl or
amine groups. Other polymers can be made using the dienes of
Formula III used to form these compounds, which are described in
greater detail below.
[0063] For example, if Y in Formula I (or II) is an amine
(NR.sup.4H), one could react those amines with di-, tri- or
poly(acids), di-, tri, or poly(acyl chlorides), or with cyclic
amides (lactams) to form poly(amides). Alternatively, one could
react those amines with di-, tri- or poly(anhydrides) to make
poly(imides). Alternatively, one could react those amines with
glycidyl-containing compounds to form epoxies.
[0064] If Y in Formula II (or II) is hydroxyl (OH), one could react
those hydroxyl groups with di-, tri-, or poly(acids), di-, tri-, or
poly(acyl chlorides), or with cyclic esters (lactones) to form
poly(esters). Alternatively, one could react those hydroxyl groups
with vinyl ether-containing compounds to make poly(acetals).
Alternatively, one could react those hydroxyls with sodium
hydroxide to form sodium salts, and further react those salts with
phosgene to form poly(carbonates). Reacting those sodium salts with
other alkyl halide containing moieties can lead to poly(sulfones)
and poly(phosphates) and poly(phosphonates).
[0065] For the dienes of Formula III (below), one could react the
terminal alkenes with di-, tri- or poly(amines) to make
poly(imines). One could react the terminal alkenes with di-, tri-,
or poly(alcohols) to make poly(ethers). Alternatively, one could
convert the terminal alkenes to carbocations, anions or radicals
and react these moieties with other alkenes to make polyolefin
block copolymers.
[0066] Typically, the preferred urethane- and/or urea-containing
polymers are made using polyisocyanates and one or more compounds
of Formula I (preferably Formula II). It should be understood,
however, that diols or diamines that do not contain such diorgano
(Z) moieties can also be used to prepare the urethane- and/or
urea-containing polymers of the present invention, as long as the
resultant polymer includes at least some diorgano (Z) moieties
either from diols or diamines or other reactants. Also, other
polyols and/or polyamines can be used, including polyester,
polyether, and polycarbonate polyols, for example, although such
polyols are less preferred because they produce less biostable
materials. Furthermore, the polyols and polyamines can be aliphatic
(including cycloaliphatic) or aromatic, including heterocyclic, or
combinations thereof.
[0067] Examples of suitable polyols (typically diols) include those
commercially available under the trade designation POLYMEG and
other polyethers such as polyethylene glycol and polypropylene
oxide, polybutadiene diol, dimer diol (e.g., that commercially
available under the trade designation DIMEROL (from Uniqema, New
Castle, Del.), polyester-based diols such as those commercially
available from STEPANPOL (from Stepan Corp., Northfield, Ill.),
CAPA (a polycaprolactone diol from Solvay, Warrington, Cheshire,
United Kingdom), TERATE (from Kosa, Houston, Tex.), poly(ethylene
adipate)diol, poly(ethylene succinate) diol, poly(1,4-butanediol
adipate)diol, poly(caprolactone)diol, poly(hexamethylene
phthalate)diol, and poly(1,6-hexamethylene adipate)diol, as well as
polycarbonate-based diols such as poly(hexamethylene
carbonate)diol.
[0068] Other polyols can be used as chain extenders in the
preparation of polymers, as is conventionally done in the
preparation of polyurethanes, for example. Examples of suitable
chain extenders include 1,10-decanediol, 1,12-dodecanediol,
9-hydroxymethyl octadecanol, cyclohexane-1,4-diol,
cyclohexane-1,4-bis(methanol), cyclohexane-1,2-bis(methanol),
ethylene glycol, diethylene glycol, 1,3-propylene glycol,
dipropylene glycol, 1,2-propylene glycol, trimethylene glycol,
1,2-butylene glycol, 1,3-butanediol, 2,3-butanediol,
1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol,1,2-hexylene
glycol, 1,2-cyclohexanediol, 2-butene-1,4-diol,
1,4-cyclohexanedimethanol, 2,4-dimethyl-2,4-pentanediol,
2-methyl-2,4-pentanediol, 1,2,4-butanetriol,
2-ethyl-2-(hydroxymethyl)-1,3-propanediol, glycerol,
2-(hydroxymethyl)-1,3-propanediol, neopentyl glycol,
pentaerythritol, and the like.
[0069] Examples of suitable polyamines (typically diamines) include
ethylenediamine, 1,4-diaminobutane, 1,10-diaminodecane,
1,12-diaminododecane, 1,8-diaminooctane, 1,2-diaminopropane,
1,3-diaminopropane, tris(2-aminoethyl)amine, lysine ethyl ester,
and the like.
[0070] Examples of suitable mixed alcohols/amines include
5-amino-1-pentanol, 6-amino-1-hexanol, 4-amino-1-butanol,
4-aminophenethyl alcohol, ethanolamine, and the like.
[0071] Suitable isocyanate-containing compounds for preparation of
polyurethanes, polyureas, or polyurethanes-ureas, are typically
aliphatic, cycloaliphatic, aromatic, and heterocyclic (or
combinations thereof) polyisocyanates. In addition to the
isocyanate groups they can include other functional groups such as
biuret, urea, allophanate, uretidine dione (i.e., isocyanate
dimer), and isocyanurate, etc., that are typically used in
biomaterials. Suitable examples of polyisocyanates include
4,4'-diisocyanatodiphenyl methane (MDI),
4,4'-diisocyanatodicyclohexyl methane (HMDI),
cyclohexane-1,4-diisocyanate, cyclohexane-1,2-diisocyanate,
isophorone diisocyanate, tolylene diisocyanates, naphthylene
diisocyanates, benzene-1,4-diisocyanate, xylene diisocyanates,
trans-1,4-cyclohexylene diisocyanate, 1,4-diisocyanatobutane,
1,12-diisocyanatododecane, 1,6-diisocyanatohexane,
1,5-diisocyanato-2-methylpentane, 4,4'-methylenebis(cyclohexyl
isocyanate), 4,4'- methylenebis(2,6-diethyphenyl isocyanate),
4,4'-methylenebis(phenyl isocyanate), 1,3-phenylene diisocyanate,
poly((phenyl isocyanate)-co-formaldehyde),
tolylene-2,4-diisocyanate, tolylene-2,6-diisocyanate, dimer
diisocyanate, as well as polyisocyanates available under the trade
designations DESMODUR RC, DESMODUR RE, DESMODUR RFE, and DESMODUR
RN from Bayer, and the like.
[0072] The relatively hard segments of the polymers of the present
invention are preferably fabricated from short to medium chain
diisocyanates and short to medium chain diols or diamines, all of
which preferably have molecular weights of less than about 1000
g/mol. Appropriate short to medium chain diols, diamines, and
diisocyanates include straight chain, branched, and cyclic
aliphatics, although aromatics can also be used. Examples of diols
and diamines useful in these more rigid segments include both the
short and medium chain diols or diamines discussed above.
[0073] In addition to the polymers described herein, biomaterials
of the invention can also include a variety of additives. These
include, antioxidants, colorants, processing lubricants,
stabilizers, imaging enhancers, fillers, and the like.
Starting Materials and Methods of Preparation
[0074] The novel compounds of Formula I and II above can be made by
the synthetic route shown in FIG. 1 for preferred compounds. This
typically involves a novel intermediate in which Y is a protected
group such as an acetoxy (--OC(O)CH.sub.3), a benzyl ether
(--OCH.sub.2phenyl), a tertiary butyl carbamate
(--NR.sup.4--C(O)-t-butyl), or a benzyl carbamate
(--NR.sup.4--C(O)OCH.sub.2phenyl).
[0075] Thus, the present invention provides a compound of the
formula (Formula I):
Y--(R.sup.1).sub.n-(-Z-(R.sup.2).sub.m--).sub.p--Y as described
above.
[0076] Preferably, the present invention provides a compound of the
formula (Formula II):
Y--R.sup.5(--R.sup.6Z-R.sup.7).sub.q--R.sup.8--Y as described
above.
[0077] Such compounds can be made starting with a diene compound
having a quaternary carbon (i.e., a diorgano group referred to
herein as Z or a --C(R.sup.3).sub.2-- group), a chain transfer
agent, and optionally a chain extender. The quaternary
carbon-containing diene compound is polymerized, optionally with a
chain extender, in the presence of an ADMET (Acyclic Diene
Metathesis) catalyst followed by incorporation of a chain transfer
agent yielding an unsaturated telechelic polymer.
[0078] The two carbon-carbon double bonds of the diene compound can
be either internal or terminal as long as they are separated by the
Z group. Preferably, the diene is a compound of the formula
(Formula III):
R.sup.10HC.dbd.CH--(R.sup.11)Z-(R.sup.12).sub.s--CH.dbd.CHR.sup.13
wherein: r=0 or 1; s=0 or 1; Z is a --C(R.sup.3).sub.2-- group as
defined above; R.sup.10 and R.sup.13 are each independently
hydrogen or straight chain, branched, or cyclic alkyl groups
containing up to 6 carbon atoms; and R.sup.11 and R.sup.12 are each
independently a saturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms, preferably
with the proviso that the aromatic groups are within the chain.
Preferably, using this synthetic procedure R.sup.3 does not include
unsaturated aliphatic groups, although it can include aromatic
groups. The resultant polymers, however, could be subsequently
modified to include aliphatic unsaturation.
[0079] Preferably, R.sup.11 and R.sup.12 are each independently a
straight chain alkylene group, an arylene group, or combinations
thereof, preferably with the proviso that the aromatic groups are
within the chain. More preferably, R.sup.11 and R.sup.12 are each
independently a straight chain alkylene group. Preferably, R.sup.11
and R.sup.12 are each independently an organic group that includes
at least one carbon atom, and more preferably at least two carbon
atoms. Preferably, R.sup.11 and R.sup.12 are each independently an
organic group that includes no more than 100 carbon atoms, more
preferably no more than 50 carbon atoms, and most preferably no
more than 20 carbon atoms. Preferably, at least one of r or s is
one. More preferably, both r and s are one. Most preferably, the
quaternary carbon-containing starting material is Compound 1 in
FIG. 1.
[0080] A chain extender can be optionally used to alter the spacing
between the Z groups in the resultant polymer. This also has the
added advantage of allowing for a broader range of glass transition
temperatures (Tg's) than can normally be realized upon polymerizing
one monomer. The chain extender is a diene wherein the two
carbon-carbon double bonds are either internal or terminal.
Preferably, it is a compound of the formula (Formula IV):
R.sup.14HC.dbd.CH--R.sup.15--CH.dbd.CHR.sup.16 wherein: R.sup.14
and R.sup.16 are each independently hydrogen or straight chain,
branched, or cyclic alkyl groups containing up to 6 carbon atoms;
and R.sup.15 is a saturated aliphatic group, an aromatic group, or
combinations thereof, optionally including heteroatoms, preferably
with the proviso that the aromatic groups are within the chain.
[0081] Preferably, R.sup.15 is a straight chain alkylene group, an
arylene group, or combinations thereof, preferably with the proviso
that the aromatic groups are within the chain. More preferably,
R.sup.15 is a straight chain alkylene group. Preferably, R.sup.15
is an organic group that includes at least one carbon atom, and
more preferably at least two carbon atoms. Preferably, R.sup.15 is
an organic group that includes no more than 100 carbon atoms, more
preferably no more than 50 carbon atoms, and most preferably no
more than 20 carbon atoms. Most preferably, the chain extender
starting material is Compound 2 in FIG. 1.
[0082] The chain transfer agent (CTA) includes protecting groups
and is preferably a compound of the formula (Formula V):
Y--R.sup.17--HC.dbd.CH--R.sup.18--Y wherein: each Y is
independently a protected form of an OH or an NR.sup.4H group
(e.g., wherein Y is an acetoxy, a benzyl ether, a tertiary butyl
carbamate, or a benzyl carbamate); R.sup.17 and R.sup.18 are each
independently a saturated aliphatic group, an aromatic group, or
combinations thereof, preferably with the proviso that the aromatic
groups are within the chain.
[0083] Preferably, R.sup.17 and R.sup.18 are each independently a
straight chain alkylene group, an arylene group, or combinations
thereof, preferably with the proviso that the aromatic groups are
within the chain. More preferably, R.sup.17 and R.sup.18 are each
independently a straight chain alkylene group. Preferably, R.sup.17
and R.sup.18 are each independently an organic group that includes
at least one carbon atom, and more preferably at least two carbon
atoms. Preferably, R.sup.17 and R.sup.18 are each independently an
organic group that includes no more than 100 carbon atoms, more
preferably no more than 50 carbon atoms, and most preferably no
more than 20 carbon atoms. Examples of chain transfer agents
include 1,8-diacetoxy-4-octene and 1,20-diacetoxyeicosa-10-ene.
Most preferably, the chain transfer agent starting material is
Compound 3 in FIG. 1 (1,8-diacetoxy-4-octene).
[0084] Alternatively, the chain transfer agent can include one
alkene group and only one protected alcohol or amine. The alkene
can be terminal or, if not terminal, it can include a relatively
small alkyl substituent that forms a volatile compound under the
metathesis conditions. An example of this type of chain transfer
agent is 10-undecene-1-yl-acetate. Such a compound is generally of
the formula (Formula VI): R.sup.19--HC.dbd.CH--R.sup.20--Y wherein:
Y is a protected form of an OH or an NR.sup.4H group (e.g., wherein
Y is an acetoxy, a benzyl ether, a tertiary butyl carbamate, or a
benzyl carbamate); R.sup.19 and R.sup.20 are each independently a
saturated aliphatic group, an aromatic group, or combinations
thereof, preferably with the proviso that the aromatic groups are
within the chain; R.sup.19 can also be hydrogen. Preferably,
R.sup.19 is (C1-C6)alkyl-group, and more preferably R.sup.19 is H.
If a compound of Formula IV is reacted with a compound of Formula
III, the metathetic byproduct would be of the formula
R.sup.10HC.dbd.CHR.sup.19, which should have sufficiently small
R.sup.10 and R.sup.19 groups to be volatile under the conditions of
the polymerization reaction.
[0085] Alternatively, the alcohol and/or amine groups can be
introduced using a compound of the formula (Formula VII):
CH.sub.2.dbd.CH--R.sup.21--Y wherein: each Y is independently a
protected form of an OH or an NR.sup.4H group (e.g., wherein Y is
an acetoxy, a benzyl ether, a tertiary butyl carbamate, or a benzyl
carbamate); R.sup.21 is a saturated aliphatic group, an aromatic
group, or combinations thereof, preferably with the proviso that
the aromatic groups are within the chain. Preferably, R.sup.21 is a
straight chain alkylene group, an arylene group, or combinations
thereof, preferably with the proviso that the aromatic groups are
within the chain. More preferably, R.sup.21 is a straight chain
alkylene group. Preferably, R.sup.21 is an organic group that
includes at least one carbon atom, and more preferably at least two
carbon atoms. Preferably, R.sup.21 is an organic group that
includes no more than 100 carbon atoms, more preferably no more
than 50 carbon atoms, and most preferably no more than 20 carbon
atoms.
[0086] The ADMET catalyst can be any of a variety of catalysts
capable of effecting metathesis polymerization. Examples include
Schrock's molybdenum alkylidene catalyst, Grubbs' ruthenium
benzylidene catalyst, and Grubbs' imidazolium catalyst
("Super-Grubbs"), as shown in FIG. 2.
[0087] Preferably, the quaternary carbon-containing diene compound
is combined with an ADMET catalyst under conditions effective to
cause polymerization to a high molecular weight intermediate (e.g.,
a number average molecular weight of about 10,000 g/mol to about
1.times.10.sup.6 g/mol). Optionally, a chain extender can be added
to the quaternary carbon-containing diene compound before the
catalyst is added. Typically, conditions of this polymerization
include reduced pressure (e.g., less than about 1.33 Pascals (Pa))
at a temperature of about 0.degree. C. to about 100.degree. C.
(preferably, about 25.degree. C. to about 60.degree. C.) and a time
of about 1 hour to about 10 days (preferably, about 48 hours to
about 120 hours). The reduced pressure is desired to remove
metathetic by-products and reduce the number of terminal olefins.
This high molecular weight intermediate can be stored for later
reaction if desired.
[0088] This high molecular weight intermediate is then combined
with a chain transfer agent in the presence of the same or a
different ADMET catalyst under conditions effective to depolymerize
the high molecular weight intermediate and form an unsaturated
telechelic polymer. Typically, such conditions include an inert
atmosphere (e.g., argon) or under reduced pressure (e.g., less than
about 1.33 Pascals) and a temperature of about 0.degree. C. to
about 100.degree. C. (preferably, about 50.degree. C. to 60.degree.
C.) and a time of about 1 hour to about 10 days (preferably, about
24 hours to about 96 hours). The amount of chain transfer agent
controls the molecular weight of the unsaturated telechelic
polymer. Optionally, this depolymerization reaction is carried out
in an organic solvent (e.g., toluene) to reduce the viscosity.
[0089] Optionally, the unsaturated telechelic polymer could be
formed in a one-step reaction in which the quaternary
carbon-containing diene compound, optional chain extender, and a
chain transfer agent are combined prior to the addition of the
ADMET catalyst to the mixture. This may or may not be carried out
in an organic solvent.
[0090] The unsaturated telechelic polymer is then subjected to a
hydrogenation reaction. This is preferably carried out in the
presence of a hydrogenation catalyst under conditions effective to
form a fully saturated telechelic polymer. The hydrogenation
catalyst is preferably palladium on activated carbon, but could be
others well known in the art. Typically, such conditions include
the use of a hydrogen pressure of about 1 psig (0.068 atmospheres,
6.89 Pa) to about 1000 psig (68 atmospheres, 6.89 MPa) (preferably,
about 300 psig (20 atmospheres, 2.03 MPa) to about 500 psig (34
atmospheres, 3.45 MPa) and a temperature of about 0.degree. C. to
about 200.degree. C. (preferably, about 60.degree. C. to about
100.degree. C.) and a time of about 1 hour to about 10 days
(preferably, about 3 days to about 5 days).
[0091] Alternatively, the hydrogenation reaction can be carried out
using para-toluenesulfonhydrazide in the presence of a base
(typically, tributylamine) in a refluxing organic solvent such as
xylene.
[0092] The saturated telechelic polymer is then deprotected using a
reaction scheme specific to the protecting group used. For example,
if the protecting group is an acetate, the polymer is hydrolyzed
under conditions effective to convert the acetate end groups to
hydroxyl groups. Typically, such conditions include the use of
sodium methoxide in an organic solvent (e.g., methanol) at a
temperature of about 0.degree. C. to about 100.degree. C.
(preferably, about 0.degree. C. to about 25.degree. C.) and a time
of about 1 minute to about 1 day (preferably, about 4 hours to
about 1 day).
[0093] Alternatively, the unsaturated telechelic polymer could be
deprotected prior to being hydrogenated to the saturated telechelic
polymer.
[0094] The invention has been described with reference to various
specific and preferred embodiments and will be further described by
reference to the following detailed examples. It is understood,
however, that there are many extensions, variations, and
modification on the basic theme of the present invention beyond
that shown in the examples and detailed description, which are
within the spirit and scope of the present invention.
EXAMPLES
Instrumentation:
[0095] All .sup.1H NMR and .sup.13C NMR spectra were recorded using
either a Varian Associates Gemini 300 spectrometer or a JEOL
Eclipse 400 spectrometer. Chemical shifts for .sup.1H NMR were
referenced to tetramethylsilane and those for .sup.13C NMR were
referenced to residual signals from CDCl.sub.3 solvent. Reaction
conversions and purity of products were monitored by
chromatography. Gas chromatography was performed on a Shimadzu
GC-17A gas chromatograph equipped with a Hewlett Packard HP-5
cross-linked 5% phenyl methyl siloxane column (length=25 meters
(m), film thickness=0.33 micrometers (.mu.m), internal diameter
(ID)=0.2 millimeters (mm)) and a flame ionization detector. Thin
layer chromatography (TLC) was performed on WHATMAN aluminum
backed, 250 mm silica gel coated plates, using mixtures of hexanes
and ethyl acetate as the mobile phase. TLC plates were stained with
phosphomolybdic acid (10%) in ethanol to see UV inactive products
and impurities. High resolution mass spectra (HRMS) were obtained
on a Finnegan 4500 gas chromatograph/mass spectrometer using the
electron ionization (El) mode. GPC data were obtained using a
Waters Associates 6000A liquid chromatograph apparatus equipped
with a HP refractive index detector. HPLC grade chloroform was used
as the mobile phase, and a column bank consisting of two PLgel 5
.mu.m MIXED-C columns (300 mm length each) was used as the
stationary phase. A constant flow rate of 1 milliliter per minute
(mL per minute) at 35.degree. C. was maintained, and the instrument
was calibrated using polystyrene standards from Polymer
Laboratories. Elemental analyses were performed by Atlantic
Microlabs Inc., Norcross, Ga. The tensile properties of polymer
specimens were determined using a MTS Sintech 1/D tensile tester
with extensometer with a crosshead speed of 12.7 cm per minute
using a 45.5 kg (100 pound) load cell. The spinning band column
used for distillations was the B/R 36/100A Automatic Distillation
System with Vacuum Regulation, manufactured by B/R Instrument
Corporation, Easton, Md. Polyurethane polymerizations were
performed under an inert atmosphere using oven- or flame-dried
glassware, with care used to maintain anhydrous conditions.
Materials:
[0096] The Grubbs' imidazolium catalyst (FIG. 2) was synthesized
following a literature procedure or purchased from Strem Chemicals,
Inc. (Newburyport, Mass.). 5-Bromo-1-pentene was purchased from
Aldrich and distilled from CaH.sub.2 (3840.degree. C. at 12.4 kPa)
prior to use. Propionic acid was purchased from Aldrich and
distilled from anhydrous Na.sub.2SO.sub.4 (71-72.degree. C. at 8.7
kPa), then redistilled from a few crystals of KMnO.sub.4 prior to
use. Diethyl ether and tetrahydrofuran (THF) were distilled from
Na/K alloy using benzophenone as the indicator. Chloroform was
distilled from P.sub.2O.sub.5, and hexamethylphosphoramide (HMPA)
was distilled from CaH.sub.2 prior to their use. One of the chain
transfer agents (1,4-diacetoxy-2-butene) was purchased from Aldrich
and distilled from CaH.sub.2 (63.degree. C. at 13 Pa) prior to use.
The monomer for the new chain transfer agent (acetic acid
4-pentenyl ester) was purchased from TCI America (Portland, Oreg.)
and used as received. The 10-undecen-1-yl acetate was purchased
from Bedoukian Research, Incorporated (Danbury, Conn.) and used as
received. QO POLYMEG 1000 was purchased from Penn Specialty
Chemicals, Inc., Memphis, Tenn. The POLYMEG was dried under full
oil pump vacuum at 100.degree. C. prior to use. Flaked MONDUR M
("MDI", 4,4'-methylenebis(phenyl isocyanate)) was purchased from
Bayer Corporation, Rosemount, Ill. and stored in a freezer until
use. Anhydrous dioxane was purchased from Aldrich and was used as
received. EPON 815c epoxy resin is available from Resolution
Performance Products (Houston, Tex.). 1,4-Butanediol was produced
by Mitsubishi Chemical Company (Japan). 1,9-Decadiene was purchased
from Aldrich and distilled from calcium hydride prior to use, using
the spinning band column described under "Instrumentation" above.
All other reagents were obtained from Aldrich and used as
received.
Example 1
Diene Synthesis
Step 1: Dialkenylation of Propionic Acid. Synthesis and
Characterization of 6-Methyl-1,10-undecadiene-6-carboxylic Acid
(Compound 7, FIG. 3)
[0097] One hundred thirty one mL (262 millimolar (mmol)) of a 2.0 M
solution of lithium diisopropylamide (LDA) in THF (Aldrich) was
placed in a flame-dried, argon-purged 1000 mL 3-neck round-bottomed
flask equipped with a magnetic stir bar, 125 mL addition funnel,
250 mL addition funnel, and a condenser. The solution was cooled to
-35.degree. C. and 9.48 gram (g, 128 mmol) of propionic acid was
added via syringe to the 125 mL addition funnel, followed by about
10 mL of THF. The propionic acid solution was added dropwise over
about 50 minutes, and then the addition funnel was washed with THF.
The reaction smoked considerably early on in the addition, and
white salts formed. Approximately 25 mL of HMPA (about 1.1
equivalent to propionic acid) was added by syringe, and the mixture
turned from a pale yellow to orange (salts still present). The
mixture was allowed to warm to 10.degree. C. over approximately 1
hour, followed by heating to 50.degree. C. for 1.5 hours. The
mixture was a reddish-orange with salts. The mixture was slowly
chilled to -35.degree. C. and 20.3 g (136 mmol) of
5-bromo-1-pentene was added to the 125 mL addition funnel via
syringe. This was slowly dripped into the reaction mixture over 15
minutes. The mixture cleared after about 1 mL was added (colorless
solution), then gradually turned yellowish with white salts. The
mixture was slowly brought to 50.degree. C. (salts dissolved and
solution became pale yellow during heating) and was stirred for 2.5
hours. After 2.5 hours, the mixture had completely salted up. THF
was slowly added by cannula with manual stirring until the salts
had dissolved and the mixture became a pale yellow color again
(about 200 mL of THF was added). The solution was again chilled to
-35.degree. C., and 65.5 mL (161 mmol) of the 2.0 M LDA solution
was added to the reaction mixture dropwise from the 250 mL addition
funnel over 40 minutes. The reaction mixture was allowed to warm to
room temperature (solution turned more yellow), followed by heating
to 50.degree. C. for 1.5 hours (solution turned orange). The
mixture was chilled to -35.degree. C., and 21.4 g (144 mmol) of
5-bromo-1-pentene was slowly added from the 125 mL addition funnel
over 25 minutes, and was then rinsed down with THF. The color
lightened to yellow after the first few drops. The mixture was
allowed to warm to room temperature, followed by heating to
50.degree. C. for 12 hours (became pale yellow again).
[0098] After 12 hours, the mixture was allowed to cool to room
temperature and then it was slowly poured over about 500 mL of ice
in a 1000 mL beaker with stirring. Three molar HCl was added with
stirring until all salts had dissolved. After concentration on a
rotary evaporator, the quenched reaction mixture was extracted
three times with 150 mL of diethyl ether. The combined organic
layers were washed three times with 150 mL of 3 M hydrochloric acid
(HCl), and then dried over anhydrous magnesium sulfate, gravity
filtered, and evaporated under reduced pressure.
[0099] The percent yield was calculated to be about 70% based on
the mass of the crude product and a GC analysis. The product was
not purified before taking it on to the next step in this latest
synthesis. If desired, the monoalkenylated product can be recovered
by column chromatography using a 5:1 mixture of methylene chloride
and ethyl acetate (or 74:25:1 hexanes:ethyl acetate:acetic acid) as
the mobile phase.
[0100] The following spectral properties were observed: .sup.1H NMR
(CDCl.sub.3): .delta.1.14 (s, 3H), 1.30-1.51 (m, 4H), 1.63 (dt,
4H), 2.04 (q, 4H), 4.93-5.04 (m, 4H), 5.72-5.83 (m, 2H), 11.95 (s,
br, 1H); .sup.13C NMR: 621.07, 23.75, 34.10, 38.46, 45.61, 114.67,
138.46, 184.38; EI/HRMS: [M+1].sup.+ calcd. for
C.sub.13H.sub.22O.sub.2: 211.1698; found: 211.1698. Elemental
analysis calcd. for C.sub.13H.sub.22O.sub.2: 74.23 C, 10.55 H;
found: 73.97 C, 10.59 H.
Step 2: Reduction of the Carboxylic Acid to the Alcohol. Synthesis
and Characterization of 6-Hydroxymethyl-6-methyl-1,10-undecadiene
(Compound 8)
[0101] To an argon purged 1000 mL 3-neck flask equipped with a stir
bar and condenser, 200 mL of dry diethyl ether and 12.0 g of the
crude carboxylic acid mixture (about 82% dialkenylated and 18%
monoalkenylated by GC analysis) from step 1 were added. Prior to
addition, the carboxylic acid mixture had been left under vacuum
for 12 hours to partially dry it. The solution was stirred for 5
minutes and cooled in an ice bath, before 140 mL of 1.0 M lithium
aluminum hydride (LAH) in diethyl ether (Aldrich) was added slowly,
in three portions, via syringe. Gas evolution was observed upon
addition of LAH. The reaction mixture was allowed to warm to room
temperature and stirred for approximately 20 hours.
[0102] After 20 hours, the mixture was slowly poured onto ice in a
1400 mL beaker. Vigorous evolution of gas was observed. Three
normal (3N) HCl was added slowly until the salts dissolved. About
450 mL of 3N HCl was required. The aqueous layer was extracted
three times with 100 mL of Et.sub.2O. The combined ether layers
were washed with two 100 mL portions of 3N HCl, once with 100 mL of
saturated aqueous sodium bicarbonate, and once with de-ionized
water. The organic layer was then dried over anhydrous magnesium
sulfate, gravity filtered, and evaporated under reduced
pressure.
[0103] The crude product was a strong smelling, viscous, clear oil,
obtained in 94.3% yield. The two-component, alcohol product mixture
was distilled at a pressure of 13 Pa. The monoalkenylated alcohol
boiled at 4143.degree. C., and the desired diene alcohol boiled at
84-85.degree. C. An isolated yield of 72.3% was obtained for the
diene alcohol, and its purity was confirmed by GC analysis.
[0104] The following spectral properties were observed: .sup.1H NMR
(CDCl.sub.3): .delta.0.84 (s, 3H), 1.19-1.35 (m, 9H), 2.03 (q, 4H),
3.35 (d, 2H), 4.93-5.05 (m, 4H), 5.75-5.86 (m, 2H); .sup.13C NMR
(CDCl.sub.3): 621.83, 22.81, 34.57, 35.84, 37.21, 69.64, 114.43,
138.90; EI/HRMS: [M].sup.+ calcd. for C.sub.13H.sub.24O: 196.1827,
found: 196.1829. Elemental analysis calcd. for C.sub.13H.sub.24O:
79.52 C, 12.33 H; found: 79.40 C, 12.36 H.
Step 3: Tosylation of the Alcohol. Synthesis and Characterization
of 6-Methyl-6-(p-toluenesulfonyl)methyl-1,10-undecadiene (Compound
9, FIG. 3)
[0105] To a flame dried, argon purged 500 mL 3-neck flask equipped
with a stir bar, were added 100 mL of dry CHCl.sub.3, via cannula,
and 7.72 g (39.3 mmol) of the alcohol (Compound 8, FIG. 3) from
step 2. After cooling the solution in an ice bath and stirring for
15 minutes, nine (9) mL (125 mmol) of dry pyridine was added via
syringe. The reaction mixture was stirred for 30 minutes, and then
toluenesulfonyl chloride was added in four 4 g portions
(approximately 84 mmol) over a 30 minute period. The reaction
mixture was allowed to warm to room temperature and stirred for 48
hours. The solution gradually became pale yellow.
[0106] The reaction mixture was poured over ice in a 1000 mL
beaker, and 200 mL of 3N HCl was added slowly, with stirring. The
mixture was placed in a separatory funnel and the CHCl.sub.3 layer
was drained. The aqueous layer was extracted twice more with a
total of 100 mL of CHCl.sub.3. The combined organic layers were
washed twice with 100 mL of saturated aqueous potassium carbonate
and twice with 100 mL of distilled water. The CHCl.sub.3 layer was
dried over magnesium sulfate, gravity filtered, and evaporated
under reduced pressure. A yield of 21.8 g of crude yellow material
was obtained. Analysis of the crude product using .sup.1H and
.sup.13C NMR showed the presence of toluenesulfonic acid. The crude
product was used in the next example without further
purification.
[0107] The following spectral properties were observed: .sup.1H NMR
(CDCl.sub.3): .delta.0.82 (s, 3H), 1.12-1.23 (m, 8H), 1.94 (q, 4H),
2.45 (s, 3H), 3.69 (s, 2H), 4.90-4.99 (m, 4H), 5.66-5.79 (m, 2H),
7.34 (d, 2H), 7.78 (d, 2H); .sup.13C NMR (CDCl.sub.3): 621.73,
22.42, 34.24, 35.70, 36.33, 114.60, 127.89, 129.77, 132.75, 138.51,
144.64. The toluenesulfonic acid impurity has .sup.1H NMR
(CDCl.sub.3) shifts at 2.49 (s, 3H), 7.41 (d, 2H), and 7.92 (d,
2H).
Step 4: Reduction of the Tosylate. Synthesis and Characterization
of 6,6-dimethyl-1,10-undecadiene (Compound 1, FIG. 3)
[0108] To a flame dried, argon purged 500 mL 3-neck flask equipped
with a condenser and stir bar, were added 80 mL of dry diethyl
ether and 20.7 g of the crude tosylate (Compound 9, FIG. 3) from
the previous step. The solution was chilled in an ice bath, and 175
mL of 1.0 M lithium aluminum hydride in Et.sub.2O was slowly added,
in four portions, via syringe. The reaction mixture immediately
turned cloudy white. The mixture was allowed to warm to room
temperature, and stirred for approximately 20 hours.
[0109] The reaction mixture was slowly poured over ice in a 1600 mL
beaker, with stirring. Deionized water was added until frothing
ceased. Then, 3N HCl was added until the white salt had completely
dissolved. The aqueous layer was extracted three times with 100 mL
of diethyl ether. The combined organic layers were washed twice
with 100 mL of saturated aqueous potassium carbonate, twice with 3N
HCl, twice more with 100 mL of saturated aqueous potassium
carbonate, and once with 100 mL of distilled water. The colorless
crude product was purified by flash column chromatography using
silica gel 60 as the stationary phase and 100% hexanes as the
mobile phase. Pure dimethyl diene (4.68 g) was obtained. The
two-step yield (tosylation followed by reduction) was 66%, and the
overall yield for all four steps was 27%. Before polymerization,
the dimethyl diene was distilled from CaH.sub.2 at 2.00 kPa into a
50 mL Schlenk flask, and stored under argon atmosphere. The boiling
point at 2.00 kPa was 80-81.5.degree. C.
[0110] The following spectral properties were observed: .sup.1H NMR
(CDCl.sub.3): .delta.0.83 (s, 6H), 1.13-1.21 (dt, 4H), 1.25-1.35
(m, 4H), 2.01 (q, 4H), 4.91-5.04 (m, 4H), 5.75-5.88 (m, 2H);
.sup.13C NMR (CDCl.sub.3): 623.45, 27.25, 32.57, 34.70, 41.43,
114.16, 139.19; EI/HRMS: [M].sup.+ calcd. for C.sub.13H.sub.24:
180.1878, found: 180.1877. Elemental analysis calcd. for
C.sub.13H.sub.24: 86.58 C, 13.42 H; found: 85.99 C, 13.26 H.
Example 2
Chain Transfer Agent Synthesis
[0111] The synthesis of 1,8-diacetoxy-4-octene was carried out by
the dimerization of acetic acid 4-pentenyl ester using the Grubbs'
benzylidene catalyst (FIG. 2). In an argon atmosphere dry box, 108
mg (0.131 mmol) of the Grubbs' benzylidene catalyst was added to a
100 mL round bottomed flask equipped with one dry ice/isopropanol
condenser and one water condenser, each with a hose connector with
a valve, and a magnetic stir bar. The apparatus was removed from
the dry box and attached to a Schlenk line through the dry
ice/isopropanol condenser. The flask was opened to argon after
purging the hose. An oil bubbler was attached to the water
condenser, but the valve was left closed. Then, 21.66 g (0.1690
mol) of acetic acid 4-pentenyl ester was added to the flask by
syringe, and the flask was placed in a 47.degree. C. oil bath. A
small amount of bubbling was observed in the purple solution. The
valve connected to the oil bubbler was opened to allow argon and
ethylene byproduct to flow out continuously. After 30 minutes, the
dry ice/isopropanol bath was filled, the bubbler valve was closed,
and the pressure was reduced to 9.3 kPa. The solution bubbled
vigorously as it degassed and then slowed to a constant rate. After
90 minutes at reduced pressure the bubbling had ceased and the
solution was a purplish-brown. The reaction vessel was opened to
air and left stirring overnight at 48.degree. C. The crude product
was 95% dimer (30% cis, 60% trans) by GC, and was now a black
solution. It was exposed to a reduced pressure of 40 Pa for one
hour to remove residual starting ester, and then the product was
distilled over CaH.sub.2 at 40 Pa (bp 111-113.degree. C.) and
stored in a Schlenk flask. The isolated product weighed 12.2 g,
with a yield of 63%.
Example 3
Telechelic Diol Polymer Synthesis
Step 1: ADMET Polymerization/Depolymerization of
6,6-dimethyl-1,10-undecadiene (Compound 1, FIG. 1) with
1,8-diacetoxy-4-octene as the chain transfer agent (CTA) (Compound
3, y=3, FIG. 1) Using the Grubbs' Imidazolium Catalyst to give the
unsaturated telechelic diacetate polymer (Compound 4, FIG. 1)
[0112] In an argon atmosphere dry box, 6.162 g (34.17 mmol) of the
dry, degassed gem-dimethyl diene monomer (1) was placed in a 100 mL
round bottom flask equipped with a large TEFLON magnetic stir bar.
About 63 mg (460:1 monomer to catalyst ratio) of the Grubbs'
imidazolium catalyst was added to the flask, and a valve adapter
was attached to the flask in the closed position. The reaction
vessel was removed from the glove box and immediately attached to a
Schlenk line, where the valve adapter was flame dried under vacuum.
The mixture was stirred slowly in a 46.degree. C. oil bath (only
about 1/3 of the liquid monomer level was immersed) and was opened
to the vacuum line for 1-2 seconds. Vacuum was applied every 5-15
minutes for 1-2 seconds to control the intensity of bubbling for
the next 12 hours. By then, the bubbling had slowed and the
orange-brown mixture had become viscous enough to leave open to the
vacuum line. After 10 minutes of full vacuum, the pressure was at 7
Pa, and the solution was bubbling steadily. After 4 hours the
bubbling had slowed and the mixture was more viscous, so the
temperature was increased to about 60.degree. C. Over the next 24
hours the pressure gradually decreased to 0.67 Pa and the bubbling
slowed. By that time the mixture was very viscous and difficult to
stir, so the diffusion pump was turned on to reduce the pressure
further (about 0.4 Pa). There was still an occasional bubble. After
another 42 hours of reaction, no bubbles were observed, so the
reaction vessel was sealed and taken into the dry box.
[0113] In the argon atmosphere dry box, 1.112 g (4.871 mmol, or 7:1
monomer to chain transfer agent ratio) of 1,8-diacetoxy-4-octene
was added to the reaction vessel. About 2 mL of dry, degassed
toluene was added and a condenser with two valve adapters was
attached (for argon in and out). The reaction vessel was removed
from the dry box and attached to a Schlenk line. The connector hose
was put under vacuum and backfilled with argon three times. To
dissolve the polymer and allow easy stirring, the mixture was
heated to 60.degree. C. and stirred with a large U-shaped magnet.
Once loosened, the stir bar spun freely. The reaction vessel was
then opened to the argon line and bubbler, and placed in a
60.degree. C. oil bath. No bubbles were observed in the
orange/brown solution. The solution gradually became less viscous
over 72 hours, at which time it was removed from the oil bath and
the reaction was quenched by exposure to air. Upon exposure to air
for several hours, the mixture turned from orange/brown to
black/brown. Finally, the solvent was removed under reduced
pressure (27 Pa) and 5.959 g of polymer (4) was obtained (95%
yield).
[0114] The .sup.1H NMR spectrum (run in CDCl.sub.3) showed that no
terminal olefinic resonances were observed at 4.9 ppm and 5.8 ppm,
indicating that the polymer is perfectly bifunctional within NMR
detection limits. Integration of the peaks indicates a number
average molecular weight of about 1340 grams per mole (7.3 repeat
units on average).
Step 2: Hydrogenation of the Unsaturated Telechelic Diacetate
Polymer (Compound 4, FIG. 1) to the Saturated Telechelic Diacetate
Polymer (Compound 5, FIG. 1)
[0115] Polymer 4 (5.96 g) was dissolved in approximately 200 mL of
toluene in the 450 mL glass liner for a Parr high pressure reactor.
About 1.0 g of 10% palladium on activated carbon was added and the
reactor was sealed. The reaction vessel was charged with 500 pounds
per square inch (psi) (34 atmospheres) of ultra high purity
hydrogen (grade 5), and the mixture was stirred at 100 revolutions
per minute (rpm) and heated to 80.degree. C. During the 5-day
reaction period the reactor had to be re-pressurized with hydrogen
several times.
[0116] After 5 days the mixture was allowed to cool to room
temperature and the pressure was released. The reaction mixture was
filtered through a short pad of silica gel (5.7 centimeter (cm) in
a 10 cm diameter column) using a ratio of 75:25 of toluene and
ethyl acetate as the mobile phase. This column removes both the
imidazolium Grubbs and Pd/C catalysts. About 6.28 g of the
saturated acetoxytelechelic polymer (Compound 5, FIG. 1) was
obtained after heating to 50.degree. C. under reduced pressure, but
.sup.1H NMR showed that a small quantity of toluene solvent
remained. Analysis of the integrals in the .sup.1H NMR spectrum
indicated a number average molecular weight of about 1300 grams per
mole (6.9 repeat units on average). This spectrum also showed that
the polymer was quantitatively hydrogenated within detection limits
(no olefin resonances were detected at 5.4 ppm).
Step 3: Hydrolysis of the Telechelic Diacetate Polymer (Compound 5,
FIG. 1) to the Target Telechelic Hydrocarbon Diol (Compound 6, FIG.
1)
[0117] Under an argon atmosphere, about 6.28 g of polymer (Compound
5, FIG. 1) was dissolved in 100 mL of dry diethyl ether in a 1000
mL round bottomed flask, equipped with a condenser and magnetic
stir bar. The solution was chilled in an ice bath and 140 mL (10
equivalents to acetate groups) of an ice chilled 0.7 M solution of
sodium methoxide in dry methanol was added (5.3 g NaOMe in 140 mL
of methanol). The mixture was stirred and allowed to warm to room
temperature overnight. When the stirring was stopped, the mixture
settled into two layers. A colorless liquid (the polymer) settled
on the bottom, and on top was a yellowish solution. The solvents
were removed using a rotary evaporator, and a yellowish polymer and
salt mixture remained. About 50 mL of diethyl ether was added and
the polymer partially dissolved. The polymer dissolved upon the
addition 50 mL of 1.0 M HCl with stirring. The organic layer was
colorless, while the aqueous layer was yellow. The mixture was
poured into a separatory funnel, along with two 10 mL washings of
1.0 M HCl and three 15 mL diethyl ether washings of the flask. The
separatory funnel was shaken and vented several times and the
aqueous layer was drained. The aqueous layer was basic to litmus
paper (pH 11+). The organic layer was saved and the aqueous layer
was washed twice with 50 mL of diethyl ether. The three organic
layers were combined and washed twice with 10 mL of 1.0 M HCl
(washings were pH 1) and once with 50 mL of deionized water. The
organic layer was then dried over MgSO.sub.4, filtered, and then
evaporated under reduced pressure, yielding a colorless viscous
liquid.
[0118] After drying on a vacuum line at 40.degree. C., the
telechelic gem-dimethyl diol (Compound 6, FIG. 1) weighed 5.2 g for
an overall percent yield of 87%. The .sup.1H NMR spectrum showed a
molecular weight of about 1200 grams per mole (6.9 repeat units on
average). The .sup.1H NMR spectrum also indicated that the end
groups of polymer 5 were quantitatively hydrolyzed and that the
hydroxytelechelic hydrocarbon polymer is perfectly difunctional
within detection limits. The characteristic acetate signals due to
the methyl group (2.05 ppm) and the methylene adjacent to the
acetate (4.05 ppm) were not present.
Example 4
Synthesis of a Polyurethane Containing a Soft Segment Featuring
Gem-Dimethyl Substituents
[0119] The soft segment dialcohol containing gem-dimethyl
substituents (Compound 6, FIG. 1) was transferred in dioxane
solvent to a 100 milliliter round bottom flask. After rotary
evaporation for 5 hours at 60.degree. C. under oil pump vacuum, the
flask containing the clear, colorless, viscous liquid diol (4.92 g,
0.0082 equivalents (as determined by proton NMR)) was transferred
to a nitrogen-purged glovebox. Then 0.13 g 1,4-butanediol (0.00286
equivalents) was added, followed by dilution with 60 g anhydrous
dioxane. Magnetic stirring of the flask contents under nitrogen was
initiated before adding 1.57 g (0.01251 equivalents) freshly
distilled, molten 4,4'-methylenebis(phenyl isocyanate).
[0120] The clear, colorless solution was stirred magnetically under
nitrogen. Heat was supplied with an electrically heated mantle.
Temperature was recorded using an immersed stainless steel
thermocouple and an electronic temperature controller. After the
temperature was stabilized at 67.degree. C., one drop (about 0.03
g) dibutyltin dilaurate catalyst was added. The exotherm of
reaction peaked at 71.degree. C. Temperature was then maintained at
70.degree. C. After 40 minutes, a drop of the flask contents was
evaporated on a KBR plate and infrared spectroscopy was used to
monitor the degree of reaction. Residual isocyanate was observed by
absorbance at 2272 cm.sup.-1. To complete reaction of all
isocyanate, 1,4-butane diol was added dropwise in two increments of
0.06 and 0.02 g. At that point, IR analysis indicated absence of
residual isocyanate. The calculated isocyanate/hydroxyl ratio based
on theoretical equivalent weights was 1.00/1.00.
[0121] To isolate the resultant polymer, one hundred milliliters
isopropyl alcohol was stirred in a one-liter Waring blender. The
warm (approximately 55.degree. C.) solution was poured into the
running blender over a period of 2-3 minutes. The polymer
precipitated as a discrete white powder. Additional isopropyl
alcohol was added and the stirring was continued for five minutes.
The precipitate was filtered using #41 "fast" WHATMAN paper filter
in a Buechner funnel connected to a water-aspirated four-liter
filter flask. The damp powder was transferred back to the Waring
blender and stirred with 500 milliliters of methanol for five
minutes. The filtration and stirring with methanol was repeated as
above. The solution was filtered a final time and the powder dried
in a 60.degree. C. vacuum oven at oil pump vacuum overnight.
[0122] The final product was 5.43 g of a fluffy white powder,
yielding 81.4% of the theoretical amount. The powder was molded
into a 0.254 mm (10 mil film in a heated press at 180.degree. C.
The film was clear, bubble free and did not adhere to itself.
Analytical data for the polymer is included in the Table below.
Example 5
Synthesis of an Epoxy Polymer
[0123] Six (6) grams of poly(1,1-dimethyl nonane)diamine of
molecular weight 1100 g/mol (amine equivalent weight (275 g/eq) is
combined with 2 grams of diethylene triamine (amine equivalent
weight 21 g/eq). The amine mixture is placed in a 60.degree. C.
oven for one hour and mixed occasionally until a clear solution is
formed. This mixture is added to 22 grams of EPON 815C epoxy resin,
a mixture of 89% w/w diglycidyletherbisphenol A and 11% w/w of
butyl glycidyl ether (epoxide equivalent weight 192 g/eq) that is
also preheated to 60.degree. C. The epoxy resin and amine mixture
are mixed with a spatula until a clear solution is formed. This
mixture is poured into a TEFLON-coated pan and cured in an oven at
100.degree. C. for four hours. A solid epoxy is formed from this
reaction.
Example 6
Synthesis of a Polyester-Poly(1,1-Dimethylnonane) Block
Copolymer
[0124] One gram of hydroxytelechelic diol 6 is placed in a dried
100 mL single-neck round-bottomed flask. To this flask is added 500
mg epsilon-caprolactone. The contents are warmed until well mixed.
The flask is then cooled to room temperature. One drop of stannous
octanoate is added to the mixture. A valved vacuum adapter is
connected to the flask, and the flask is then degassed by
application of vacuum. The valve is closed, and the flask is
removed to a vacuum oven. The flask is maintained at 140.degree. C.
under vacuum for twelve hours. The flask contents are next
dissolved in methylene chloride and then precipitated into cold
methanol to remove residual epsilon-caprolactone.
Example 7
Synthesis of 6-Acetoxymethyl-6-Methyl-1,10-Undecadiene
[0125] Into a 100 mL round-bottom flask equipped with a magnetic
spin bar and a glass stopper was added
6-hydroxymethyl-6-methyl-1,10-undecadiene (9.41g, 48 mmol), glacial
acetic acid (60.1g, 1.0 mol) and scandium (III) triflate (1.23g,
2.5 mmol). The mixture was stirred at ambient temperature for
approximately 10 minutes and a colorless solution was obtained. The
reaction mixture was stirred for an additional 24 hours at ambient
temperature. The reaction mixture was then transferred into a 500
mL separatory funnel and diluted with 100 mL of deionized water.
The solution was extracted with three 50 mL portions of methylene
chloride. The combined methylene chloride extracts were washed with
two 100 mL portions of deionized water, 100 mL of saturated sodium
bicarbonate, 100 mL of brine and finally dried over anhydrous
magnesium sulfate. The excess methylene chloride was removed with a
rotary evaporator to afford a light oil. The oil was distilled
under vacuum to afford 9.39g of
6-acetoxymethyl-6-methyl-1,10-undecadiene (bp=66 to 71.degree.
C./8.7 Pa). The FTIR, .sup.13C and .sup.1H nmr were consistent with
the proposed structure.
Example 8
Synthesis of 6-Methoxymethyl-6-Methyl-1,10-Undecadiene
[0126] Into a 500 mL 3-necked round-bottom flask equipped with a
thermometer, 125 mL pressure equalizing funnel, and a glass
stirring shaft with a TEFLON paddle attached to an air motor was
added 6-hydroxymethyl-6-methyl-1,10-undecadiene (49.1 g, 0.25 mol),
tetra-n-butylammonium iodide (0.5g) and 100 mL of hexane. To the
vigorously stirred solution (maximum rpm with the air motor) was
added 50% sodium hydroxide solution (52.0 g, 0.65 mol). The
two-phase reaction mixture was stirred vigorously for approximately
30 minutes and dimethyl sulfate (37.8 g, 0.30 mol) was added
dropwise to the reaction mixture over a 40 to 45 minute interval,
not allowing the temperature to exceed 45.degree. C. The reaction
mixture was stirred an additional three hours and 5 mL of 30%
ammonium hydroxide solution was added and stirring was continued
for 30 minutes.
[0127] Into the reaction flask was added 100 mL of deionized water
and the entire contents of the flask was transferred into a 500 mL
separatory funnel. The aqueous layer was separated and the hexane
layer was washed with 100 mL of deionized water and dried over
anhydrous sodium sulfate. The excess hexane was removed with a
rotary evaporator to afford a light oil.
[0128] Vacuum distillation of the oil afforded 19.3g of
6-methoxymethyl-6-methyl-1,10-undecadiene (bp=154-155.degree.
C./1.07 kPa). The FTIR, .sup.13C and .sup.1H nmr were consistent
with the proposed structure.
Example 9
Stability Testing
[0129] The oxidative stability of the polyurethane synthesized in
Example 4 was compared to that of three other polyurethanes. All
three of the polyurethanes used as comparisons contained
poly(tetramethyleneoxide) in the soft segment. The comparative
polyurethane of Example 10 had the same molar ratio of soft segment
diol, 1,4-butanediol, and 4,4'-methylenebis(phenyl isocyanate) as
found in the polyurethane of Example 4, permitting a direct
evaluation of the effect of substituting the
gem-dimethyl-containing diol of Example 3 for the
poly(tetramethyleneoxide) soft segment typically used in implanted
polyurethanes. The comparative polyurethane of Example 11 was
formulated using the same starting materials as in Example 10, but
their ratio was selected to have a durometer identical to that of
the polyurethane of Example 4, which was 90 on the Shore A scale.
This permits a comparison based on physical properties, rather than
formulation. The third comparison polyurethane was the commercially
available PELLETHANE-2363-80A polyurethane. The PELLETHANE
polyurethane is a standard of the medical industry for use in
long-term implant applications, such as pacemaker leads, and is
sold by the Dow Chemical Company, Midland, Mich. As noted in the
Table, below, the PELLETHANE polyurethane had significantly higher
molecular weight than the other polyurethanes, and also contained a
commercial antioxidant package. This higher molecular weight and
the antioxidant package would be expected to give the PELLETHANE
polyurethane an advantage in stability testing over the other
polyurethanes, which contained no antioxidants.
[0130] Polymer specimens were soaked in 1 M silver nitrate and 1 M
ferric chloride to test their oxidative stability. The polymers
were molded into 0.305 mm (12 mil) thick films and cut into test
specimens with a die according to ASTM D638-5. These test specimens
were then annealed at 60 for eight hours. Test specimens were
stored at 70.degree. C. for 8 weeks in each of these solutions. The
specimens were tested after rinsing with deionized water, drying to
a constant weight in a vacuum oven, and then allowing the moisture
level of the specimen to equilibrate to ambient laboratory
conditions. Tensile properties of the test specimens were
determined using an MTS Sintech 1/D tensile tester with
extensometer with a crosshead speed of 12.7 cm per minute using a
45.5 kg (100 pound) load cell. Retention of physical properties was
determined by comparison of the tensile properties of the test
specimens to the tensile properties of identical specimens stored
at ambient laboratory conditions. This comparison is reported for
various properties of interest as a percentage in the Table, below,
as "Percent Retention". In the Table, below, "UTS" stands for
ultimate tensile strength, "Elong." stands for elongation,
"Modulus" refers to Young's modulus, and "Disint." means that the
polymer specimen disintegrated under the test conditions. Also in
the Table, below, M.sub.w, refers to the weight-average molecular
weight, M.sub.n, refers to the number-average molecular weight.
Molecular weights are reported in kilodaltons (kD) and were
determined by gel permeation chromatography using polystyrene
standards. In the Table, below, PDI refers to the polydispersivity
index, which is defined as M.sub.w/M.sub.n. TABLE-US-00001 TABLE
Summary of polyurethane oxidation resistance testing. Polyurethane
Shore M.sub.w M.sub.n Test PERCENT RETENTION Formulation hardness
(kD) (kD) PDI Solution UTS Elong. Modulus Example 4 90A 60.2 43.0
1.76 AgNO.sub.3 88 92 94 FeCl.sub.3 79 84 115 Example 10 75A 74.4
43.0 1.72 AgNO.sub.3 17 16 254 FeCl.sub.3 Disint. Disint. Disint.
Example 11 90A 118.0 43.8 2.83 AgNO.sub.3 13 28 91 FeCl.sub.3
Disint. Disint. Disint. PELLETHANE 85A 154.0 75.6 2.05 AgNO.sub.3
13 66 56 FeCl.sub.3 63 104 56
[0131] It can be seen from the data presented in the Table, above,
that soaking the polyurethane of Example 4 in the silver nitrate
solution reduced its ultimate tensile strength to 88% of the
control value. In contrast, the other polyurethanes suffered a
significantly larger decrease in ultimate tensile strength, to 17%,
13%, and 13% of their control values for the polyurethanes of
Examples 10, 11, and PELLETHANE polyurethane, respectively. This
test demonstrated the superior oxidative resistance of the
polyurethane of Example 4 compared to the other polyurethanes. The
elongation of the polyurethane of Example 4 was also better
retained than was found for the comparison polyurethanes. The
Young's modulus of Example 4 after exposure to silver nitrate was
94% of the control value, while the polyurethane of Example 10 was
significantly increased to 254% of its control value. This increase
in modulus is not desirable in many medical device applications,
such as the insulation for cardiac pacemaker leads. The retention
of the Young's modulus of Example 11 was similar (but slightly less
than) that of Example 4. The Young's modulus of PELLETHANE fell to
56% of its control value. This loss of modulus is also undesirable
for medical device applications.
[0132] For the ferric chloride test solution, the results were even
more striking, in which the polyurethanes of Examples 10 and 11
disintegrated in the ferric chloride solution. While the
polyurethane of Example 4 retained 79% of its ultimate tensile
strength, the ultimate tensile strength of the PELLETHANE
polyurethane tested in ferric chloride fell to 63% of its control
value. The elongation of the polyurethane of Example 4 fell
slightly to 84% of its control value, while the elongation of the
PELLETHANE polyurethane increased slightly to 104% of its control
value. The modulus of the polyurethane of Example 4 exposed to
ferric chloride rose slightly to 115% of the control value, while
the modulus of the PELLETHANE polyurethane fell to 56% of its
control value.
[0133] Overall, this data demonstrates the superior oxidative
resistance of the polyurethane of Example 4 compared to that of
polyurethanes formulated with poly(tetramethyleneoxide) soft
segments. The polyurethane of Example 4 had better retention of
ultimate tensile strength than any of the other polyurethanes, and
also had retention of elongation and of Young's modulus that was
better than or similar to that of the other polyurethanes.
Example 10
Synthesis of a Comparative Polyurethane with a
Poly(Tetramethyleneoxide) Soft Segment
[0134] To a dry 100-mL round-bottomed flask equipped with a
magnetic stirring bar was added 5.60 g of POLYMEG-1000, 0.20 g
1,4-butanediol, and anhydrous dioxane. A heating mantle was used to
heat the reaction. The amount of dioxane used was calculated to
give a final composition of 15% solids. Molten, freshly distilled
4,4'-methylenebis(phenyl isocyanate) (2.19 g) was added to the
stirred solution and heating was initiated. The temperature was
stabilized at 61.degree. C. A small drop (approximately 0.003 g) of
dibutyltin dilaurate was then added. The reaction mixture
exothermed to 66.degree. C. about two minutes after the addition.
The reaction mixture was stirred for an additional 2.5 hours. At
this time, 0.06 g 1,4-butanediol was added. After 35 minutes, the
IR band due to isocyanate had reduced considerably and stabilized
in size. The reaction mixture was cooled to room temperature and
the polymer was precipitated by pouring the cooled reaction mixture
into stirred isopropanol in a Waring blender. The resulting slurry
was then vacuum filtered using a Buechner funnel with a paper
filter. The precipitated polymer particles were returned to the
blender and stirred with methanol. The polymer was again filtered
and washed with methanol, and then filtered a final time. The
polymer particles were dried overnight in a 50.degree. C. vacuum
oven at full oil pump vacuum, at which time the polymer weight was
checked. There was no further weight loss from the sample upon
further treatment in the vacuum oven. The yield of polymer was
77.9%. The polymer was molded into a 0.254 mm thick film, which was
clear and free of bubbles. The molded film was tacky. This film was
then submitted to the protocol described in Example 9.
Example 11
Synthesis of a Comparative Polyurethane with a
Poly(Tetramethyleneoxide) Soft Segment
[0135] To a dry 100-mL round-bottomed flask equipped with a
magnetic stirring bar was added 5.61 g of POLYMEG-1000 and
anhydrous dioxane. A heating mantle was used to heat the reaction.
The amount of dioxane used was calculated to give a final
composition of 15% solids. Molten, freshly distilled
4,4'-methylenebis(phenyl isocyanate) (2.93 g) was added to the
stirred solution and heating was initiated. The temperature was
stabilized at 70.degree. C., at which time the solution was clear
and of low viscosity. A small drop (approximately 0.003 g) of
dibutyltin dilaurate was then added. The reaction mixture
exothermed to 78.degree. C. about two minutes after the addition.
The reaction mixture was stirred for an additional three hours.
Infrared analysis of the polymer residue created by evaporating a
drop of the reaction mixture on a KBr plate showed the presence of
a prominent band due to isocyanate. At this time, 0.42 g
1,4-butanediol was added. The reaction mixture exothermed to
74.degree. C. over about five minutes. After 40 minutes, the IR
band due to isocyanate had reduced considerably and stabilized. An
additional 0.13 g of 1,4-butanediol was added, which again caused
an exotherm to 74.degree. C. over about five minutes. The solution
was now much higher in viscosity. Forty five minutes after the
final addition, the reaction mixture was cooled to room
temperature. The polymer was precipitated by pouring the cooled
reaction mixture into stirred isopropanol in a Waring blender. The
resulting slurry was then vacuum filtered using a Buechner funnel
with a paper filter. The precipitate polymer particles were
returned to the blender and stirred with methanol. The polymer was
again filtered and washed with methanol, and then filtered a final
time. The polymer particles were dried overnight in a 50.degree. C.
vacuum oven at full oil pump vacuum. There was no further weight
loss from the sample due to evaporating solvent. The polymer was
molded into a 0.254 mm film, which was clear and free of bubbles.
This film was then submitted to the protocol described in Example
9.
Example 12
Synthesis of a Hydroxytelechelic Copolymer Based on the
Gem-Dimethyl Monomer and 1,9-Decadiene
Step 1: ADMET Copolymerization of gem-Dimethyl Monomer and
1,9-Decadiene
[0136] A sample of 1,9-decadiene was purified by distillation using
a spinning band column. The fraction that distilled at
53.0-53.8.degree. C. at 1.33 kPa was used. Inside an argon
atmosphere glovebox, 30.57 g (0.17 mol) gem-dimethyl monomer
(synthesized as in Example 1) and 23.49 g (0.17 mol) distilled
1,9-decadiene were magnetically stirred in an oven-dried 500 mL
single-neck round-bottomed flask. To this mixture 0.65 g Grubbs'
imidazolium catalyst was added and the flask was connected to a
vacuum line through a port in the glovebox. A vacuum controller was
used to maintain the pressure at 5.2 kPa, to prevent 1,9-decadiene
from evaporating before polymerization occurred. The solution
bubbled rapidly. The temperature within the glovebox was 33.degree.
C. After 1.5 hours, full vacuum was applied to the flask, and the
pressure dropped to 670 Pa. The solution continued to bubble
rapidly. After 18 hours of reaction time, the pressure was 33 Pa,
the glovebox temperature was 37.degree. C. and large bubbles were
still forming. When the pressure decreased to 20 Pa, a diffusion
pump was opened to the system to further reduce the pressure. After
24 hours of reaction time, the pressure was 13 Pa and many bubbles
were still forming. After 90 hours reaction time, the solution was
very viscous and difficult to stir. The pressure had decreased to 4
Pa and large bubbles were generated. After 5 days (120 hours) of
reaction time, a heating mantle, thermocouple and temperature
controller were used to increase the reaction temperature to
55.degree. C., and the stir rate was also increased, due to the
reduction in viscosity upon heating. The pressure changed from 4 Pa
to 7 Pa and an increase in the rate of bubble production was
observed. On the sixth day of the reaction (144 hours), the
solution was very viscous and difficult to stir. The temperature
was increased to 70.degree. C. and held at this temperature for
eighteen hours. At that time the reaction was terminated and the
flask was removed from the glovebox. The solution was dark brown in
color and extremely viscous. The solution was diluted in hexanes
and transferred to a one-liter round-bottomed flask. Approximately
800 mL hexanes were used in the dilution and transfer. AMBERLITE
IRC-718 ion exchange resin (54 grams) was added in batches of 10-20
grams over a course of three hours and slowly stirred. The solution
was still brown in color and the AMBERLITE resin was filtered from
the solution using a Buechner funnel and Whatman 40 filter paper.
Black particles collected on the filter paper and the solution
changed from dark brown to light brown. The collected AMBERLITE
resin was rinsed with additional hexanes. The solution was
transferred from the filter flask to a two-liter round-bottomed
flask. A second treatment of AMBERLITE resin was added (35g) and
within half an hour, the solution was yellow in color. The
AMBERLITE resin was then removed by filtration as before. The
copolymer solution was then eluted through a column of 3.25 cm
diameter containing 4 cm each silica gel and activated neutral
aluminum oxide. Additional hexanes were used to complete the
elution of the polymer (until no trace of polymer was visible when
a few drops of eluent were evaporated on a watchglass). The hexanes
were removed by rotary evaporation at reduced pressure, and the
clear, colorless, viscous product was transferred to a 500 mL
round-bottomed flask. The final weight of the collected copolymer
was 23.44 g (44 % yield). The copolymer was analyzed using FTIR and
NMR. The absorbances observed by FTIR were: 2954, 2852, 1470, 1438,
1384, 1364, 1311, 1240, 1081, 965, and 731 cm.sup.-1. The peaks
observed by proton NMR were: 5.95 (m), 5.3(m), 4.95(m), 1.9(m),
1.25(m), 1.15(m), 0.8 (d) ppm with CDCl.sub.3 as the reference. The
molecular weight of the polymer was estimated from the proton NMR
spectrum (based on the integrals of the internal double bond peak
at 5.35 ppm and of the chain end double bond peak at 4.95 ppm) to
be 105,000 g/mol. The NMR analysis showed that most of the mass
loss was due to loss of 1,9-decadiene from the copolymer, which
presumably cyclized to form the moderately volatile cyclooctene and
evaporated from the polymerization reaction. The polymer was thus
preferentially enriched with units derived from the gem-dimethyl
monomer, which was estimated by NMR to comprise approximately 75%
of the copolymer composition.
Step 2: Synthesis of an Acetoxytelechelic Copolymer by ADMET
Depolymerization
[0137] In a 500 mL single-neck round-bottomed flask, 10.55 g of the
chain transfer agent 1,20-diacetoxyeicosa-10-ene (prepared
according to the procedure of Example 14) was magnetically stirred
into 23.44 g of the gem-dimethyl/1,9-decadiene copolymer
synthesized above. The flask was transferred to an argon atmosphere
glovebox, where 0.08 g Grubbs' imidazolium catalyst was added to
the flask. Vacuum was then applied to the flask and the contents
started to bubble rapidly. After a few minutes, the pressure
stabilized around 19 Pa. The solution was pink and viscous. The
temperature inside the glovebox was 38.degree. C. After 21 hours,
the solution was orange in color and appeared to be much less
viscous. The pressure had decreased to 7 Pa. The diffusion pump was
then opened to the system and the pressure decreased to 3 Pa. After
an additional 42 hours, the pressure had not changed and no more
bubbles were observed. The flask was taken out of the glovebox and
about 20 g AMBERLITE IRC-718 resin were added. The mixture was
stirred for one hour, at which point the color had lightened. The
AMBERLITE resin was filtered from the solution using a Buechner
funnel and Whatman 40 filter paper. The product was further
purified by passage through a column of 3.25 cm diameter containing
4 cm each silica gel and activated neutral aluminum oxide, with
hexanes used as the eluent. The hexanes were then removed by rotary
evaporation at reduced pressure. The final weight of the product
was 28.16 g (82% yield). The acetoxytelechelic copolymer was
characterized by FTIR and NMR. The absorbances observed by FTIR
were: 2860, 2854, 1744, 1467, 1437,1385, 1364, 1306, 1237, 1038,
966, 723, 633, and 605cm.sup.-1. The peaks observed in the proton
NMR spectrum were: 5.3(m), 4.0(t), 2.0(s), 1.94(m), 1.6(m), 1.2(m),
1.1(m), and 0.81 ppm with CDCl.sub.3 as the reference. No terminal
vinyl end groups were observed in the proton NMR region 5.9-6.0 or
4.9-5.0, indicating the polymer was completely terminated with
acetoxy groups.
Step 3: Deprotection of the Acetoxytelechelic Copolymer
[0138] A 50 weight percent NaOH solution was made by dissolving
22.9 g NaOH in 22.9 g water. This solution was added to a one-liter
round-bottomed flask containing the 28.16 g acetoxytelechelic
copolymer synthesized above. Next, 2.31 g of the phase transfer
catalyst ALIQUOT 336 was added to the flask. The solution was
magnetically stirred for eighteen hours. At that time, a small
amount of white precipitate was observed, and 200 mL hexanes were
added to make the solution homogeneous. After 20.5 hours, a heating
mantle and water condenser were attached to the flask and the
solution was heated to reflux. The deprotection reaction was
monitored by FTIR, with the endpoint determined by the
disappearance of the acetoxy peak at 1744 cm.sup.-1. After 2 hours
at reflux (22.5 hours total reaction time) the IR peak at 1744
cm.sup.-1 was gone. The two-phase solution was then transferred to
a 20-L separatory funnel. Saturated NaCl solution and chloroform
were added until the emulsion dissipated and the organic and
aqueous layers became clearly distinguishable. The aqueous phase
was drained from the funnel, and the remaining organic phase was
rinsed several times with deionized water, until the water used to
wash the organic phase was pH 7. The organic phase was transferred
to an Erlenmeyer flask and dried using anhydrous magnesium sulfate.
The magnesium sulfate was then filtered using a Buechner funnel
with Whatman 40 filter paper. The hexanes were removed by rotary
evaporation under reduced pressure. The result was 27.77 g of the
hydroxytelechelic copolymer. The copolymeric diol was a viscous,
pale yellow liquid. The polymer was characterized by FTIR and NMR
spectroscopy. The absorbances observed by FTIR were: 2958, 2872,
2858,1466, 1378, 1364, 966, and 724 cm.sup.-1. The peaks observed
in the proton NMR spectrum were: 5.3(m), 3.6 (t), 1.9(m), 1.27(m),
1.18(m), 1.1 3(m), and 0.81 ppm with CDCl.sub.3 as the
reference.
Step 4: Hydrogenation of the Hydroxytelechelic Copolymer
[0139] The copolymeric diol synthesized in the previous step was
dissolved in toluene to give a solution that was 9.7% solids. This
solution was placed in a Parr pressure reactor and hydrogenated for
ten days at 4.14 MPa and 60.degree. C. The catalyst used was 10%
palladium on activated carbon, one gram used for the first eight
days and an additional 0.13 g added for the last two days. The
catalyst was filtered from the reaction mixture. Analysis of the
resulting polymer using proton NMR showed a small residual peak in
the alkene region due to incomplete hydrogenation of the sample,
corresponding to about eight percent of the initial value.
Example 13
Synthesis of a Polyurethane Based on the Hydroxytelechelic Diol of
Example 12
[0140] The hydroxytelechelic diol of Example 12 was dissolved in
300 mL hexanes and a portion of the solution was passed through a
column of 3.25 cm diameter containing 4 cm silica gel, with
additional hexanes used as the eluent. The hexanes were removed
under reduced pressure using a rotary evaporator. The extremely
viscous, yellow diol was transferred to an oven-dried 250-mL 3-neck
round-bottomed flask using 100 mL hexanes in the transfer. The
3-neck flask was placed on a rotory evaporator, with care taken not
to submerge the joints. The hexanes were then removed under reduced
pressure. A total of 6.1 g of hydroxytelechelic diol remained in
the flask. The flask was then transferred to a nitrogen atmosphere
glovebox. A magnetic stirring bar and 87.3 g anhydrous dioxane were
added to the flask and the solution was magnetically stirred. From
a syringe with a 21 Gauge needle, 0.60 g 1,4-butanediol (BDO) was
added dropwise. The flask was then outfitted with an electric
heating mantle, thermocouple, temperature controller, and air
condenser. The diol mixture in anhydrous dioxane was heated and
stirred. The hydroxytelechelic diol dissolved when the temperature
reached 35.degree. C. The solution temperature was increased to
67.degree. C. and held at that temperature before the
4,4'-methylenebis(phenyl isocyanate) (MDI) was added. A total of
2.9 g MDI was weighed into a small plastic weighing boat and then
added to the dioxane solution. One drop of dibutyltin dilaurate
catalyst (0.0028g) was added from a syringe with a 26 Gauge needle.
The reaction was monitored by FTIR. A drop of the reaction solution
was spread on a single KBR plate and placed in a 60.degree. C.
vacuum oven under full vacuum for two minutes to remove the
dioxane. The isocyanate peak at 2275 cm.sup.-1 was initially very
strong. The temperature was held at 67.degree. C. for half an hour
and then increased to 70.degree. C. for the remainder of the
reaction. After one hour, there was no change in the FTIR spectrum.
Over the course of 3.5 hours, 0.384 g more BDO was added dropwise,
with one drop equal to 0.008 g on average, until the isocyanate
absorbance at 2275 cm.sup.-1 was very weak. The resulting
absorbances observed by FTIR were: 3328, 3123, 3039, 2926, 2853,
2278,1902, 1702, 1597, 1534, 1468, 1437, 1414, 1384, 1363, 1311,
1233, 1110, 1080, 1019, 968, 915, 849, 817, 772, 720, 663, 611, 509
cm.sup.-1. The polyurethane was precipitated from the dioxane
solution using acetone. Half of the polymer solution was poured
into a Waring blender containing 500 ml acetone. The polyurethane
formed a white, flaky precipitate. The precipitate was filtered
using a Buechner funnel with 41 WHATMAN filter paper. The procedure
was repeated with the other half of the batch. The two precipitate
batches were then combined in the blender with another 500 ml
acetone. The mixture was stirred in the blender to extract
additional dioxane, and the precipitate was again filtered as
described above. The polyurethane was transferred from the Buechner
funnel to a MYLAR weighing boat and stored in a vacuum oven at
60.degree. C. under full oil pump vacuum for eighteen hours. The
fluffy, white polymer weighed 5.6 g, a 57% yield.
[0141] The polyurethane was then pressed into a 0.25 mm thick film
in a heated press at 190.degree. C., producing a bubble-free film
that was yellow in color. ASTM D-638 Type 5 tensile strength test
samples were stamped out of the polyurethane sheet.
[0142] Tensile testing was performed following ASTM method D638-5
with ext. (rev. A) using six samples. The averaged results were:
Ultimate Tensile Strength=20.3 MPa; Percent Elongation at
Break=245%; Young's Modulus=27.3 MPa; Toughness=34.7 MPa; Stress at
Yield=6.66 MPa; Percent Strain at Yield=25.7%.
Example 14
Synthesis of 1,20-Diacetoxyeicosa-10-ene by Metathetic Dimerization
of 10-Undecen-1-Yl Acetate
[0143] A chromatography column with an outside diameter of 7.6
inches containing 15 cm activated neutral alumina was connected to
a twelve-liter single-neck round-bottomed flask using an adapter
with a vacuum adapter. The 10-undecen-1-yl acetate was purified by
passage through the column directly into the flask with vacuum
applied through the adapter. The flask was weighed to find that
4.82 kg had been transferred to it. The flask was placed in a
heating mantle on a magnetic stirring plate. A magnetic stir bar
was added to the flask, and a sparge tube attached to a ground
glass joint was fitted to it. The stirred monomer was sparged for
twenty hours, then 10.93 g of the Grubbs' benzylidene catalyst
(FIG. 2) was added to the flask and the neck quickly capped with a
20 cm Vigreux column connected to a vacuum line through an adapter.
The vacuum line comprised an oil pump and a diffusion pump. Vacuum
was immediately applied, and after 45 minutes, the pressure inside
the flask had dropped sufficiently that the diffusion pump could be
opened to the system, which reduced the pressure inside the flask
to 1.33 Pa, and further dropped to 0.67 Pa five hours after the
start of the reaction. Six hours after the catalyst was added, the
reaction started to solidify, and gentle heat was applied to keep
the reaction a stirrable slurry. An hour after heating was
initiated, the temperature measure by a thermocouple placed between
the flask and the mantle was 47.2.degree. C. The variac controlling
the heating mantle was turned down slightly at this point. The cold
trap in the vacuum line had to be emptied every few hours to remove
the condensed ethylene. Ten hours after the reaction was started,
the temperature was 38.degree. C., and after a further 15 hours,
was 41.5.degree. C. At this time, the variac was again turned down
slightly. The reaction mixture at this time was an intense
burgundy-colored liquid (except where mixture thrown against the
wall of the flask above the mantle had solidified) and the pressure
inside the flask was 0.4 Pa. By measuring the volume of liquid
ethylene collected, the reaction was estimated to be 75% complete
at this point. The reaction was continued for 7 days, with the
temperature measured between the flask and mantle maintained at
43-44.degree. C. At this point, the variac was turned up and the
temperature equilibrated at 55.7.degree. C. After 12 hours, the
variac was again turned up, and the temperature equilibrated at
63.5.degree. C. After twelve hours at this final temperature, the
reaction was terminated, the flask backfilled with nitrogen, and
ten grams of Irganox 1010 was added. The reaction mixture was
diluted 1:1 with hexanes and maintained under nitrogen. Then 480 g
of AMBERLITE IRC-718 ion exchange resin (washed with deionized
water and dried under vacuum) was added to the flask and an
air-driven mechanical stirrer was used to stir the reaction
overnight. The next day, a chromatography column 76 cm long and 7.6
cm in diameter was filled consecutively with 5 cm sand, 20 cm
activated neutral alumina, 5 cm AMBERLITE resin (ground in a ball
mill), and 5 cm sand. The column was attached to a three-neck
12-liter round-bottomed flask. Vacuum from a water aspirator was
attached to the flask through an adapter. The solution was pumped
into the column using a peristaltic pump. The filtered solution was
pale amber. The residue in the reaction flask was washed with
several portions of hexanes, which was also pumped into the column.
The column was further eluted with hexanes until no appreciable
product remained on the column. The solution was placed in a
freezer overnight, where it became a solid crystalline mass. After
standing at room temperature for 24 hours, there was a large lump
of white crystals in a pale amber solution. The liquid was pumped
from the flask and the white crystals were washed twice with a
liter of hexanes, with the liquid from these washings also pumped
from the flask. Then hexanes were added to the flask to give a
total volume of about eleven liters and the flask was heated to
dissolve the crystals. The resulting solution was much paler in
color than the initial hexanes solution. It was allowed to stand
overnight at room temperature, but no crystals precipitated. It was
then put in a freezer overnight, which resulted in a solid mass.
After standing at room temperature for about two hours, the massed
had thawed sufficiently that it could be filtered in two portions
using a paper filter in a large Buechner funnel. Each portion of
crystals was washed with 500 mL of room-temperature hexanes. The
crystals were placed in a PYREX dish and then placed under vacuum
overnight to remove the remaining hexanes. A total of 640 g of
white crystalline product was isolated (the remaining product of
the reaction was also isolated and reserved for other uses). The
product was recrystallized from hexanes before use. As expected,
twelve peaks were observed by .sup.13C NMR: 6171.3, 130.4, 64.7,
31.2, 29.7, 29.5, 29.4, 29.3, 29.1, 28.6, 25.9, 20.3 ppm. The peaks
observed by proton NMR were: 65.3 (t), 4.0 (t), 2.1 (s), 1.9 (m),
1.5 (m), 1.2 (m).
Example 15
Alternative Tosylation and Reduction to Produce
6,6-Dimethyl-1,10-Undecadiene
Step 1: Tosylation
[0144] Into an oven-dried nitrogen-purged one-liter 3-neck
round-bottomed flask equipped with a nitrogen inlet and a magnetic
stir bar was added 98.16 g of
6-hydroxymethyl-6-methyl-1,10-undecadiene and 300 mL chloroform.
The solution was cooled to 5-15.degree. C. with an ice bath and
48.5 mL pyridine (47.5 g) was added to the flask. The solution was
stirred for about five minutes and p-toluenesulfonyl chloride
(104.9 g) was added to the solution over a 15 minute interval. The
solution was allowed to warm to ambient temperature and was stirred
for about 72 hours. The light yellow reaction mixture was poured
onto approximately 1.5 kg crushed ice, followed by the addition of
800 mL of 3N HCl. The two-phase system was transferred to a 3 L
separatory funnel and the chloroform layer was isolated. The
aqueous layer was extracted with two 125 mL portions of chloroform.
The combined chloroform extracts were washed sequentially with two
100 mL portions of saturated aqueous potassium carbonate, two 250
mL portions of de-ionized water, and 100 mL of brine. The
chloroform solution was then dried over anhydrous magnesium
sulfate. The chloroform was removed using a rotary evaporator to
afford 165.95 g of a light yellow oil, which is 95% of the
theoretical yield. The crude product was used in the following step
with no further purification. Infrared analysis showed no bands due
to hydroxyl. Prominent IR bands were found at 2938, 1640, 1596,
1468, 1362, 1189, 1098, 965, 913, 845, 814, 668, 655, 573, 556, and
530 cm.sup.-1.
Step 2: Reduction
[0145] Into an oven-dried two-liter three-neck round-bottomed flask
equipped with a 500 mL pressure-equalizing addition funnel,
magnetic stir bar, thermometer, and a nitrogen inlet was added
140.8 g of the crude tosylate of Step 1 and 120 mL of THF. Into the
pressure-equalizing addition funnel was placed 600 mL of 1.0 M
lithium triethylborohydride in tetrahydrofuran (SUPER-HYDRIDE,
purchased from Aldrich). The tetrahydrofuran solution was added to
the over one hour. The temperature of the reaction mixture rose to
35-40.degree. C. during the addition. The reaction mixture was
refluxed for three hours and then cooled to 25-30.degree. C. using
an ice bath. Ten milliliters of de-ionized water was added to the
flask to destroy unreacted lithium triethylborohydride. The
organoborane was oxidized by adding 300 mL of 3N NaOH followed by
the dropwise addition of 30% hydrogen peroxide. This addition was
exothermic. The mixture was poured into a 3 L separatory funnel and
extracted with three 200 mL portions of hexane. The combined hexane
extracts were washed sequentially with two 100 mL portions of
de-ionized water and 150 mL of brine. The hexane solution was then
dried using anhydrous magnesium sulfate. The hexane was removed
from the product by distillation at atmospheric pressure to afford
a light yellow oil. The crude product was distilled under reduced
pressure. The main fraction distilled at 33-41.degree. C. at 30-34
Pa. The product was analyzed by IR, proton NMR and carbon NMR, and
found to be consistent with the desired product.
[0146] The complete disclosures of the patents, patent documents,
and publications cited herein are incorporated by reference in
their entirety as if each were individually incorporated. Various
modifications and alterations to this invention will become
apparent to those skilled in the art without departing from the
scope and spirit of this invention. It should be understood that
this invention is not intended to be unduly limited by the
illustrative embodiments and examples set forth herein and that
such examples and embodiments are presented by way of example only
with the scope of the invention intended to be limited only by the
claims set forth herein as follows.
* * * * *