U.S. patent application number 09/880126 was filed with the patent office on 2002-01-03 for calixarenes and their use for sequestration of metals.
This patent application is currently assigned to Secretary of State for Defence in her Britannic Majesty's Government of the United Kingdom. Invention is credited to Beer, Paul D., Drew, Michael G., Kan, Mark J., Nicholson, Graeme P., Williams, Gareth.
Application Number | 20020002290 09/880126 |
Document ID | / |
Family ID | 46256841 |
Filed Date | 2002-01-03 |
United States Patent
Application |
20020002290 |
Kind Code |
A1 |
Nicholson, Graeme P. ; et
al. |
January 3, 2002 |
Calixarenes and their use for sequestration of metals
Abstract
1 Disclosed are "acid-amide" calixarenes of formula (I) wherein:
L is [--CH.sub.2--] or [--O--CH.sub.2--O--] and may be the same or
different between each aryl group; R.sub.5 is H, halogen, or
C.sub.1-C.sub.10 aliphatic hydrocarbyl group, C.sub.6-C.sub.20 aryl
group, C.sub.6-C.sub.20 hydrocarbyaryl group, any of which may
optionally be substituted by one or more halo or oxo groups or
interrupted by one or more oxo groups, and R.sup.5 may be the same
or different on each aryl group: R.sup.1 comprises an optionally
protected carboxy group: two groups out of R.sup.2, R.sup.3, and
R.sup.4 are H; the one group out of R.sup.2, R.sup.3, and R.sup.4
not being H comprises an amide group. The amide group may be linked
to a second calixarene to form a dimer. Also disclosed are methods
of use of such calixarenes for the purposes of metal sequestration,
especially of lanthanides and actinides. Also disclosed are
calixarene dimer derivatives of the calixarenes of the invention.
Also disclosed are processes for preparing the calixarenes and
dimers.
Inventors: |
Nicholson, Graeme P.;
(Reading, GB) ; Kan, Mark J.; (Reading, GB)
; Williams, Gareth; (Reading, GB) ; Drew, Michael
G.; (Reading, GB) ; Beer, Paul D.; (Oxford,
GB) |
Correspondence
Address: |
NIXON & VANDERHYE P.C.
8th Floor
1100 North Glebe Road
Arlington
VA
22201-4714
US
|
Assignee: |
Secretary of State for Defence in
her Britannic Majesty's Government of the United Kingdom
|
Family ID: |
46256841 |
Appl. No.: |
09/880126 |
Filed: |
June 14, 2001 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
09880126 |
Jun 14, 2001 |
|
|
|
09460237 |
Dec 13, 1999 |
|
|
|
6297395 |
|
|
|
|
09460237 |
Dec 13, 1999 |
|
|
|
09068148 |
Oct 14, 1998 |
|
|
|
Current U.S.
Class: |
549/348 ;
562/466; 562/471; 562/473 |
Current CPC
Class: |
C07C 235/20 20130101;
G01N 27/3335 20130101; C22B 3/304 20210501; C07C 2603/92 20170501;
C07C 235/24 20130101; Y02P 10/20 20151101; C07D 273/00 20130101;
C07C 327/42 20130101 |
Class at
Publication: |
549/348 ;
562/466; 562/471; 562/473 |
International
Class: |
C07C 062/06; C07C
062/30; C07C 062/12; C07C 065/105; C07C 065/24; C07D 323/00 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 4, 1996 |
GB |
PCTGB9602687 |
Nov 10, 1995 |
GB |
9523119.7 |
Claims
1. Calixarenes of the formula (I) 12wherein: L is [--CH.sub.2--] or
[--O--CH.sub.2--O--] and may be the same or different between each
aryl group. R.sup.5 is H, halogen, or C.sub.1-C.sub.10 aliphatic
hydrocarbyl group, C.sub.6-C.sub.20 aryl group, C.sub.6-C.sub.20
hydrocarbylaryl group, any of which may optionally be substituted
by one or more halo or oxo groups or interrupted by one or more oxo
groups, and R.sup.5 may be the same of different on each aryl
group. R.sup.1 comprises a carboxy group which may or may not be
protonated or protected. two groups out of R.sup.2, R.sup.3, and
R.sup.4 are H the one group out of R.sup.2, R.sup.3, and R.sup.4
not being H comprises an amide group.
2. Calixarenes as claimed in claim 1 wherein R.sup.2 and R.sup.4
are H and R.sup.3 comprises amide group.
3. Calixarenes as claimed in claim 1 or claim 2 wherein L is
[--CH.sub.2--] between each of the aryl groups.
4. Calixarenes as claimed in any one of claims 1 to 3 wherein
R.sup.5 is tertiary butyl.
5. Calixarenes as claimed in any one of claims 1 to 4 wherein the
carboxy group R.sup.1 conforms to the general formula (A): (A)
[--X--COOR.sup.10]wherein X is a C.sub.1, a C.sub.2 or a C.sub.3
carbon chain being a part of an aliphatic hydrocarbyl group, aryl
group or hydrocarbylaryl group, any of which may optionally be
substituted by one or more halo, oxo or nitro groups; and R.sup.10
is H or a protecting group being a salt or an Ester derivative.
6. Calixarenes as claimed in claim 5 wherein R.sup.10 is H and the
aliphatic hydrocarbyl group, aryl group or hydrocarbylaryl group of
formula (A) are substituted by one or more groups which cause a
reduction in the pKa of the carboxylic acid group with respect to
the unsubstituted molecule.
7. Calixarenes as claimed in claim 5 wherein R.sup.1 is of the
general formula (B): (B)
[(C.R.sup.6.R.sup.7).sub.n--COOR.sup.10]wherein n is 1, 2 or 3 and
R.sup.6 and R.sup.7 are H or halogen and can be the same or
different on each carbon.
8. Calixarenes as claimed in claim 5 wherein R.sup.1 is of the
general formula (C): 13wherein n is 0 or 1 and R.sup.6 and R.sup.7
are H or halogen and can be the same or different on each carbon
and wherein the phenyl ring of the benzoic acid group may be
optionally substituted by one or more halo, oxo or nitro
groups.
9. Calixarenes as claimed in claim 8 wherein R.sup.10 is H and the
phenyl ring of the benzoic acid of formula (C) is substituted by
one or more groups which cause a reduction in the pKa of the
carboxy group with respect to the unsubstituted molecule.
10. Calixarenes as claimed in any one of claims 5 to 9 wherein n is
1 and R.sup.6 and R.sup.7 are both H.
11. Calixarenes as claimed in any one of the preceding claims
wherein the amide group R.sup.2, R.sup.3, or R.sup.4 of formula (I)
is of the general formula (D): 14wherein n is 1, 2 or 3 and R.sup.6
and R.sup.7 are H, halogen, or C.sub.1-C.sub.10 aliphatic
hydrocarbyl group, and can be the same or different on each carbon,
and wherein R.sup.8 and R.sup.9, which may be the same or
different, are H or C.sub.1-C.sub.10 aliphatic hydrocarbyl group
which may be substituted by one or more halo groups, or may be a
cycloaliphatic ring formed by R.sup.8 and R.sup.9 together, or may
be conjugated to a second calixarene.
12. A calixarene of the formula (II) as described herein.
13. Calixarenes of the general formulae (I) or (II) wherein some or
all of phenyl groups of the calixarene ring are further
peripherally substituted.
14. A method of sequestering metals comprising contacting the
metals with a calixarene as claimed in any one of the preceding
claims.
15. A method as claimed in claim 14 wherein the method is carried
out at a pH of between 2 and 11.
16. A method as claimed in claim 14 or 15 wherein the pH at which
the method is carried is buffered.
17. A method as claimed in claim 16 wherein the buffer used is
citrate.
18. A method as claimed in any one of claims 14 to 17 comprising
the following steps: (i) dissolving the calixarene in an
hydrophobic organic solvent; (ii) mixing the organic solvent with
an aqueous phase containing metal ions; (iii) agitating the organic
solvent and aqueous phase together; (iv) recovering the metal from
the organic phase.
19. A method as claimed in any one of claims 14 to 18 wherein the
metal is selected from the list: a Lanthanide, U, Hg, Am, Pb, Sr,
Bi, Y.
20. A calixarene as claimed in any one of claims 1 to 13 further
characterised in that the calixarene is solid phase bound.
21. A process for preparing a calixarene as claimed in any one of
claims 1 to 13 substantially as herein described with reference to
Example 12 and FIG. 15.
22. A calixarene dimer comprising a calixarene as claimed in claim
11 wherein one of the R.sup.8 and R.sup.9 groups is conjugated to a
second calixarene.
23. A dimer as claimed in claim 22 comprising two calixarenes as
claimed in claim 11 wherein the R.sup.8 or R.sup.9 group of one
calixarene is conjugated to the R.sup.8 or R.sup.9 of the other
calixarene, optionally through a spacer group R.sup.11, the
optional spacer group R.sup.11 being C, C.sub.6 aliphatic
hydrocarbyl group, C.sub.6-C.sub.10 aryl group, C.sub.6-C.sub.16
hydrocarbylaryl group any of which may optionally be substituted by
one or more halo or oxo groups or interrupted by one or more oxo
groups.
24. A dimer as claimed in claim 23 wherein there is a 1, 2, 3 or 4
atom chain between the Nitrogen atoms of the two amide groups.
25. A process for preparing a dimer as claimed in any one of claims
22 to 24 comprising the use of a diamine to conjugate two
calixarene molecules.
26. A process for preparing a dimer as claimed in claim 25
substantially as herein described with reference to Example 15.
27. Calixarenes of a formula (I) 15wherein: L is [--CH.sub.2--] or
[--O--CH.sub.2--O--] and is the same or different between each aryl
group; R.sup.5 is H, halogen, or is a C.sub.1-C.sub.10 aliphatic
hydrocarbyl group, C.sub.6-C.sub.20 aryl group, or a
C.sub.6-C.sub.20 hydrocarbylaryl group, any of which is optionally
substituted by one or more halo or oxo groups or is interrupted by
one or more oxo groups, and R.sup.5 is the same or different on
each aryl group; R.sup.1 is a carboxy group which is or is not
protonated or protected; two groups out of R.sup.2, R.sup.3 and
R.sup.4 are H; and the one group out of R.sup.2, R.sup.3 and
R.sup.4 which is not H is an amide group.
28. Calixarenes as claimed in claim 27 wherein R.sup.2 and R.sup.4
are H and R.sup.3 is an amide group.
29. Calixarenes as claimed in claim 27 wherein L is [--CH.sub.2--]
between each of the aryl groups.
30. Calixarenes as claimed in claim 27 wherein R.sup.5 is a
tertiary butyl.
31. Calixarenes as claimed in claim 27 wherein the carboxy group
R.sup.1 is of the general formula (A): (A)
[--X--COOR.sup.10]wherein X is a C.sub.1, a C.sub.2 or a C.sub.3
carbon chain which is a part of an aliphatic hydrocarbyl group,
aryl group or hydrocarbylaryl group, any of which is optionally
substituted by one or more halo, oxo or nitro groups; and R.sup.10
is H or a salt or an ester protecting group.
32. Calixarenes as claimed in claim 31 wherein R.sup.10 is H and
the aliphatic hydrocarbyl group, aryl group or hydrocarbylaryl
group of formula (A) is substituted by one or more groups which
cause a reduction in the pKa of the carboxylic acid group with
respect to an unsubstituted molecule.
33. Calixarenes as claimed in claim 31 wherein R.sup.1 is of the
general formula (B): (B)
[--(C.R.sup.6.R.sup.7).sub.n--COOR.sup.10]wherein n is 1, 2 or 3
and R.sup.6 and R.sup.7 are H or halogen and are the same or
different on each carbon.
34. Calixarenes as claimed in claim 31 wherein R.sup.1 is of the
formula (C): 16wherein n is 0 or 1 and R.sup.6 and R.sup.7 are H or
halogen and are the same or different on each carbon and wherein
the phenyl ring of the benzoic acid group is optionally substituted
by one or more halo, oxo or nitro groups.
35. Calixarenes as claimed in claim 34 wherein R.sup.10 is H and
the phenyl ring of the benzoic acid of formula (C) is substituted
by one or more groups which cause a reduction in the pKa of the
carboxy group with respect to an unsubstituted molecule.
36. Calixarenes as claimed in claim 31 wherein n is 1 and R.sup.6
and R.sup.7 are both H.
37. Calixarenes as claimed in claim 27 wherein the amide group
R.sup.2, R.sup.3, or R.sup.4 of formula (I) is of the formula (D):
17wherein n is 1, 2 or 3 and R6 and R.sup.7 are H, halogen, or a
C.sub.1-C.sub.10 aliphatic hydrocarbyl group, and are the same or
different on each carbon, and wherein R.sup.8 and R.sup.9, which is
the same or different, are H or a C.sub.1-C.sub.10 aliphatic
hydrocarbyl group which is substituted by one or more halo groups,
or is a cycloaliphatic ring formed by R.sup.8 and R.sup.9 together,
or is conjugated to a second calixarene.
38. A calixarene of formula (II) 18
39. Calixarenes of the formulae (I) or (II) as claimed in claim 27
or 38 wherein at least one of the phenyl groups of the calixarene
ring are further peripherally substituted.
40. A method of sequestering metals comprising contacting metals
with a calixarene as claimed in claim 27.
41. The method as claimed in claim 40 wherein the method is carried
out at a pH of between 2 and 11.
42. The method as claimed in claim 40 wherein the pH at which the
method is carried out is buffered.
43. The method as claimed in claim 42 wherein the buffer is
citrate.
44. A method of sequestering metals comprising the steps of: (i)
dissolving a calixarene of claim 27 in an hydrophobic organic
solvent; (ii) mixing the organic solvent with an aqueous phase
containing metal ions; (iii) agitating the organic solvent and
aqueous phase together; and (iv) recovering the metal from the
organic phase.
45. The method as claimed in claim 40 or 44 wherein the metal is
selected from a Lanthanide, U, Hg, Am, Pb, Sr, Bi and Y.
46. The calixarene as claimed in claim 27 wherein the calixarene is
solid phase bound.
47. The process for preparing a calixarene of claim 27 comprising
the sequential steps of: (i) bis-esterifying a calix[4]arene; (ii)
deprotecting a first ester group to form a first acid group; (iii)
chlorinating the first acid group to form an acyl chloride; (iv)
substituting the chlorine group in the acyl chloride with a diamine
moiety; and (v) deprotecting a second ester group to form an acid
moiety.
48. A calixarene dimer comprising a calixarene as claimed in claim
37 wherein one of the R.sup.8 and R.sup.9 groups is conjugated to a
second calixarene.
49. The dimer as claimed in claim 48 comprising two calixarenes
wherein the R.sup.8 or R.sup.9 group of one calixarene is
conjugated to the R.sup.8 or R.sup.9 group of the other calixarene,
optionally through a spacer group R.sup.11, the optional spacer
group R.sup.11 being a C.sub.1-C.sub.6 aliphatic hydrocarbyl group,
or a C.sub.6-C.sub.10 aryl group, C.sub.6-C.sub.16 hydrocarbylaryl
group any of which is optionally substituted by one or more halo or
oxo groups or is interrupted by one or more oxo groups.
50. The dimer as claimed in claim 49 wherein there is a 1, 2, 3 or
4 atom chain between the nitrogen atoms of the two amide
groups.
51. The process for preparing a dimer as claimed in claim 48
comprising reacting 2 equivalents of a calixarene bearing an acyl
chloride substituent with 1 equivalent of diamine.
52. Calixarenes of a formula (IV) 19wherein: L is [--CH.sub.2--] or
[--O--CH.sub.2--O--] and is the same or different between each aryl
group; R.sup.5 is halogen, or is a C.sub.1-C.sub.10 aliphatic
hydrocarbyl group, C.sub.6-C.sub.20 aryl group, or a
C.sub.6-C.sub.20 hydrocarbylaryl group, any of which is optionally
substituted by one or more halo or oxo or is interrupted by one or
more oxo groups, and R.sup.5 is the same or different on each aryl
group; R.sup.1 is a carboxy group which is or is not protonated or
protected; two groups out of R.sup.2, R.sup.3 and R.sup.4 are H;
and the one group out of R.sup.2, R.sup.3 and R.sup.4 which is not
H is a thioamide group.
53. Calixarenes as claimed in claim 52 wherein: R.sup.2 and R.sup.4
are H; R.sup.5 is the same on each aryl group and is a tertiary
butyl; L is [--CH.sub.2--]; R.sup.1 is 20R.sup.3 is
54. Calixarenes as claimed in claim 52 wherein: R.sup.2 and R.sup.4
are H; R.sup.5 is the same on each aryl group and is a tertiary
butyl; L is [--CH.sub.2--]; R.sup.1 is 21R.sup.3 is
55. A method of sequestering metals comprising contacting metals
with a calixarene as claimed in claim 52.
56. A method of sequestering metals comprising the steps of: (i)
dissolving a calixarene of claim 52 in an hydrophobic organic
solvent; (ii) mixing the organic solvent with an aqueous phase
containing metal ions; (iii) agitating the organic solvent and
aqueous phase together; and (iv) recovering the metal from the
organic phase.
57. A process for preparing a calixarene of claim 52 comprising the
sequential steps of: (i) bis-esterification of a calix[4]arene;
(ii) deprotection of the first ester group to form a first acid
group; (iii) chlorination of the first acid group to form an acyl
chloride; (iv) substitution of the chlorine group with a diamine
moiety to form an amide group; and (v) substitution of the oxygen
group in the amide moiety with a sulphur group to form a thioamide
moiety.
58. The method according to claim 57 for preparing a calixarene of
claim 52 comprising a subsequent step of deprotecting the second
ester group to form a second acid group.
59. A process for preparing a calixarene of claim 27 comprising the
sequential steps of: (i) bis-esterifying a calix[4]arene; (ii)
deprotecting a first ester group to form a first acid group; (iii)
chlorinating the first acid group to form an acyl chloride; and
(iv) substituting the chlorine group in the acyl chloride with a
diamine moiety.
Description
[0001] The present invention relates to novel calixarenes, methods
of their preparation, and uses thereof, in particular for the
sequestration of metals.
[0002] European Patent Publication No. 0 432 989 describes a number
of calixarene and oxacalixarene derivatives as having metal
sequestering properties, and reviews some of the prior art in this
field.
[0003] In a first aspect of the present invention there is
disclosed calixarenes of the formula (I). The term calixarenes as
used hereinafter is intended to embrace also oxacalixarenes, 2
[0004] wherein:
[0005] L is [--CH.sub.2--] or [--O--CH.sub.2--O--] and may be the
same or different between each aryl group.
[0006] R.sup.5 is H, halogen, or C.sub.1-C.sub.10 aliphatic
hydrocarbyl group, C.sub.6-C.sub.20 aryl group, C.sub.6-C.sub.20
hydrocarbylaryl group, any of which may optionally be substituted
by one or more halo or oxo groups or interrupted by one or more oxo
groups, and R.sup.5 may be the same or different on each aryl
group.
[0007] R.sup.1 comprises a carboxy group [--COO.sup.-] which may or
may not be protonated or protected. Suitable protecting derivatives
include salts and ester derivatives of the carboxylic acid.
[0008] two groups out of R.sup.2, R.sup.3, and R.sup.4 are H
[0009] the one group out of R.sup.2, R.sup.3, and R.sup.4 not being
H comprises an amide group.
[0010] The combination of `acid` (or protected acid) and `amide` in
the calixarenes of the present invention is not found in the
calixarenes of the prior art; this combination leads to unexpected
and desirable metal sequestering properties (particularly for
lanthanide and actinide cations) as will be further discussed
below.
[0011] Preferably:
[0012] R.sup.2 and R.sup.4 are H and R.sup.3 comprises the amide
group; L is [--CH.sub.2--] -- between each of the aryl groups;
[0013] R.sup.5 is tertiary alkyl, especially butyl.
[0014] Preferably the carboxy group R.sup.1 conforms to the general
formula (A):
(A) [--X--COOR.sup.10]
[0015] wherein X is a C.sub.1, a C.sub.2 or a C.sub.3 carbon chain
being a part of an aliphatic hydrocarbyl group, aryl group or
hydrocarbylaryl group, any of which may optionally be substituted
by one or more halo, oxo or nitro groups.
[0016] R.sup.10 is H or a protecting group being a salt or an Ester
derivative. Salts include metal salts e.g. alkali (such as Li) or
alkali earth metals, or ammonium or substituted ammonium
derivatives. The choice of salt should be made such as to prevent
the cation interfering with the operation of the calixarene in
practice. Ester groups may be formed with C.sub.1-C.sub.10
aliphatic alkyl alcohols. C.sub.6-C.sub.20 aryl alcohols,
C.sub.6-C.sub.20 hydrocarbylaryl alcohols, any of which may
optionally be substituted by one or more halo, nitro, or oxo groups
or interrupted by one or more oxo groups. Examples include benzyl,
p-methoxybenzyl, benzoylmethyl, p-nitrobenzyl, methyl, ethyl,
butyl, t-butyl etc.
[0017] More preferably R.sup.1 is of the general formula (B):
(B) [--(C.R.sup.6.R.sup.7).sub.n--COOR.sup.10]
[0018] wherein n is 1, 2 or 3 and R.sup.6 and R.sup.7 are H or
halogen and can be the same or different on each carbon.
[0019] Alternatively a may be of the general formula (C): 3
[0020] wherein n is 0 or 1 and R.sup.6 and R.sup.7 are H or halogen
and can be the same or different on each carbon and wherein the
phenyl ring of the benzoic acid group may be optionally substituted
by one or more halo, oxo or nitro groups.
[0021] In each case it is preferable that n is 1 and R.sup.6,
R.sup.7 and R.sup.10 are all H.
[0022] In unprotected acid embodiments, preferably the aliphatic
hydrocarbyl group, aryl group or hydrocarbylaryl group of X in
formula (A) are substituted by one or more groups which cause a
reduction in the pKa of the carboxy group with respect to the
unsubstituted molecule e.g. nitro.
[0023] For instance the phenyl ring of the benzoic acid of formula
(C) is preferably substituted by one or more groups which cause a
reduction in the pKa of the carboxy group with respect to the
unsubstituted molecule e.g. nitro.
[0024] Preferably the amide group R.sup.2, R.sup.3, or R.sup.4 of
formula (I) is of the general formula (D): 4
[0025] wherein n is 1, 2 or 3 and R.sup.6 and R.sup.7 are H,
halogen, or C.sub.1-C.sub.10 aliphatic hydrocarbyl group, and can
be the same or different on each carbon, and wherein R.sup.8 and
R.sup.9, which may be the same or different, are H or
C.sub.1-C.sub.10 aliphatic hydrocarbyl group (optionally halo
substituted) including a cycloaliphatic ring formed by R.sup.8 and
R.sup.9 together.
[0026] In certain embodiments of the invention, as described in
more detail below, R.sup.8 or R.sup.9 may form a bridge to between
a calixarene of the present invention and a further calixarene in
order to produce a dimer.
[0027] Most preferably, the calixarene is of the formula (II):
5
[0028]
(5,11,17,23-tetra-tert-butyl-25-[hydroxycarbomylmethoxy]-27-[(N-die-
thylamino) carbomylmethoxy]-26-28-dihydroxy-calix[4]arene.)
[0029] This compound ("acid-amide") has been found to be useful for
the extraction of both divalent and trivalent metal ions such as
Pb, Sr, Hg, Bi and Y; in particular Lanthanides (e.g. La) and
Actinides (e.g. U).
[0030] Also embraced by the present invention are calixarenes of
the general formulae (I) and (II) but wherein some or all of phenyl
groups of the calixarene ring are further peripherally substituted
in such a way as not to compromise the advantageous combination of
the carboxy and amide groups which form the central core of the
present invention. Possible substituents include halogen, nitro,
C.sub.1-C.sub.10 aliphatic hydrocarbyl group, C.sub.6-C.sub.20 aryl
group, or C.sub.6-C.sub.10 hydrocarbylaryl group, any of which may
optionally be substituted by one or more halo or oxo groups or
interrupted by one or more oxo groups. Indeed certain substituents
(e.g. nitro) may be desirable in as much as they reduce the pKa
values of the two hydroxy groups of the calixarene ring, thereby
modifying the metal-chelating properties of the compound.
[0031] In a second aspect of the present invention there is
disclosed a method of sequestering metals comprising contacting the
metals with a calixarene as described above.
[0032] Preferably the calixarene is used to complex metals at a pH
of 2-6, (most preferably pH 3-6) since at higher pHs there is an
increased risk of the target metal precipitating. For instance,
precipitation of Lanthanides occurs at fairly low pH (7.5 for La,
6.4 for Lu).
[0033] If required, additional complexing agents (such as are well
known to the skilled person) may be used to prevent precipitation
of target metals. This allows the use of the calixarene at higher
pHs, which will advantageously reduce protonation of the carboxy
and hydroxy groups. The use of such additional complexing agents
can thus raise the useful working pH range of the calixarene to the
point at which the metal-calixarene complex itself precipitates
e.g. around pH 11.
[0034] The use of higher pHs (e.g. pH 7 to 10, preferably pH 9) may
be particularly advantageous for increasing the concentration of
negative charge in calixarenes having protected acid groups or in
calixarene-dimers, which may otherwise be reduced by the protecting
group or steric effects respectively.
[0035] If desired the environmental pH may be adjusted using
conventional methods of the art. For instance if it is desired to
raise the pH, then LiOH may be added. If desired, the pH may be
buffered by using an appropriate buffer such as are well known to
those skilled in this art e.g. citrate.
[0036] In all cases the lower pH limit of useful operation will be
dependent on the pea of each chelating group in the calixarene,
since that will dictate whether each (unprotected) carboxy or
hydroxy group will be protonated at any given pH. It may therefore
be desirable for each group to have a low pKa e.g. when treating
acidic waste streams for which the pH cannot be readily adjusted.
The pKa of the protonated carboxy and the amide group of the
calixarene of formula (II) is less than 3.
[0037] Preferably the calixarene is dissolved in a hydrophobic
organic solvent (e.g. dichloromethane) and this is mixed with an
aqueous phase containing metal ions (e.g. in equal volumes).
[0038] The phases are then stirred or otherwise agitated, typically
for around 1 hour, followed by a 2 hour separation time.
[0039] Preferably the calixarene is present in excess over the
metal target e.g. 25-fold, or 250-fold. The excess required for
useful extraction will depend on the nature of the metal target
e.g. size, charge etc.
[0040] Preferably the metal target is U, Hg, Am, Pb, Sr, Bi, or Y
for instance in methods of environmental clean up. Alternatively
the metal could be an actinide such as Am or another
lanthanide.
[0041] The calixarenes described above are such that the metal
complexes formed with the target ion may be overall neutral without
the necessity for additional counter-anions. A further advantage is
that the calixarenes can be highly selective, thereby preventing
unwanted metal ions complexing all available sites.
[0042] A still further advantage of the methods of the current
invention is that the extracted metal ions can be recovered
following sequestration into the hydrophobic phase simply by
contacting that phase with a relatively small (with respect to the
original metal-containing sample) volume of acid (e.g. 1M) thereby
causing the pH to drop and the metal to become decomplexed and
enter the acid aqueous phase. The calixarene can then be reused
simply by evaporation of the solvent.
[0043] Alternatively, the extracted metal ions can be recovered
following extraction simply by evaporating the solvent to leave the
metal-calixarene complex.
[0044] Thus in preferred forms, e.g. using the `acid-amide` above,
the extraction methods of the present invention are both selective
and efficient and do not require additional ions to operate. The
nature of the extraction can be readily optimised by adjustment of
the pH.
[0045] In a third aspect of the invention there is disclosed a
solid phase-bound calixarene of the type described above e.g.
polymer bound. For instance the calixarene may be physisorbed and
immobilised onto polystyrene divinyl benzene beads. Immobilisation
of the calixarene on a solid phase support may assist in the
extraction methods of the invention. The preparation of such bound
calixarenes would present no undue burden to those skilled in the
art, in the light of the present disclosure in conjunction with the
methods, or methods analogous to the methods, described by Harris
et al. in U.S. Pat. Nos. 4,642,362 or 4,699,966, or Parker in U.S.
Pat. No. 4,447,585 or Tetrahedron 36 461-510 (1980), or in European
Patent Publication No. 0 217 656.
[0046] In a fourth aspect of the invention there is disclosed a
process for preparing the calixarenes described above.
Intermediates for use in the process form a fifth aspect of the
invention.
[0047] In a sixth aspect of the invention there is disclosed a
calixarene dimer comprising two calixarenes of formula (I) wherein
the amide group of each is of the general formula (D) above, and
wherein the R.sup.8 or R.sup.9 group of one calixarene is
conjugated to the R.sup.8 or R.sup.9 of the other calixarene,
optionally through a spacer group R.sup.11, as shown schematically
in formula (III): 6
[0048] The optional spacer group R.sup.11 may be C.sub.1-C.sub.6
aliphatic hydrocarbyl group, C.sub.6-C.sub.10 aryl group,
C.sub.6-C.sub.16 hydrocarbylaryl group, any of which may optionally
be substituted by one or more halo or oxo groups or interrupted by
one or more oxo groups. In the absence of a spacer group the
R.sup.8 or R.sup.9 group of one calixarene is conjugated directly
to the R.sup.8 or R.sup.9 group of the other. In any case it is
preferable that there is only 1, 2, 3 or 4 bridging atoms
(preferably carbon atoms) between the Nitrogen atoms of the two
amide groups. Most preferably there is 2 or 3 bridging carbon
atoms. As described in more detail below, this spacing between the
calixarenes may help to pre-stress the dimer into a particular
stable, low-energy, chelating conformation, and thereby enhancing
the specificity for target metals with respect to calixarene
monomers. groups or interrupted by one or more oxo groups. In the
absence of a spacer group the R.sup.8 or R.sup.9 group of one
calixarene is conjugated directly to the R.sup.8 or R.sup.9 group
of the other. In any case it is preferable that thee is only 1, 2,
3 or 4 bridging atoms (preferably carbon atoms) between the
Nitrogen atoms of the two amide groups. Most preferably there is 2
or 3 bridging carbon atoms. As described in more detail below, this
spacing between the calixarenes may help to pre-stress the dimer
into a particular stable, low-energy, chelating conformation, and
thereby enhancing the specificity for target metals with respect to
calixarene monomers.
[0049] In a further aspect of the invention there is disclosed a
calixarene of formula (IV): 7
[0050] wherein:
[0051] L is [--CH.sub.2--] or [--O--CH.sub.2--O--] and is the same
or different between each aryl group;
[0052] R.sup.5 is halogen, or is a C.sub.1-C.sub.10 aliphatic
hydrocarbyl group, C.sub.6-C.sub.20 aryl group or a
C.sub.6-C.sub.20 hydrocarbylaryl group, any of which is optionally
substituted by one or more halo or oxo or is interrupted by one or
more oxo groups, and R.sup.5 is the same or different on each aryl
group;
[0053] R.sup.1 is a carboxy group which is or is not protonated or
protected; two groups out of R.sup.2, R.sup.3 and R.sup.4are H;
and
[0054] the one group out of R.sup.2, R.sup.3 and R.sup.4 which is
not H is a thioamide group.
[0055] In a preferred embodiment R.sup.2 and R.sup.4 are H, R.sup.5
is the same on each aryl group and is a tertiary butyl, L is
[--CH.sub.2--]. R.sup.1 is 8
[0056] and R.sup.3 is 9
[0057] Alternatively, R.sup.2 and R.sup.4 are H, R.sup.5 is the
same on each aryl group and is a tertiary butyl, L is
[--CH.sub.2--], R.sup.1 is 10
[0058] and R.sup.3 is 11
[0059] In another embodiment of the invention there is disclosed a
method for preparing the calixarenes of formula (IV) above.
[0060] Furthermore, there is described a method for the
sequestration of metals comprising contacting the metals with a
calixarene of formula (IV) as described above.
[0061] The compounds, methods and processes of the present
invention will now be described, by way of illustration only,
through reference to the following Figures and Examples. Other
embodiments falling within the scope of the invention will occur to
those skilled in the art in the light of these.
FIGURES
[0062] FIG. 1 shows the acid-amide of the present invention.
[0063] FIG. 2 shows the efficiency of extraction of Lqa(III) by
acid-amide as a function of concentration ratio of the two.
[0064] FIG. 3 shows the efficiency of extraction of La(III) by
acid-amide as a function of the present of various anions (citrate,
acetate, picrate).
[0065] FIG. 4 shows the efficiency of extraction of La (III) by
acid-amide as a function of concentration of buffer (citrate).
[0066] FIG. 5 shows the efficiency of competitive extraction of
different Lanthanide(III) cations by acid-amide in the presence of
buffer (citrate).
[0067] FIG. 6 shows the efficiency of extraction of various metals
by acid-amide in the presence of buffer (citrate).
[0068] FIG. 7 shows the efficiency of extraction of various metals
by acid-amide in the absence of buffer.
[0069] FIG. 8 shows the structure of an acid-amide/Ln(III) complex,
as determined by X-ray crystallography.
[0070] FIG. 9 shows the structure of an acid-amide/Lu(III) complex,
as determined by X-ray crystallography.
[0071] FIG. 10 shows a calixarene dimer (designated 13b) according
to the present invention.
[0072] FIG. 11 shows a calixarene dimer (designated 11b) according
to the present invention, having an aryl spacer group between the
Nitrogen atoms of the two amide groups.
[0073] FIG. 12 shows a calixarene dimer (designated 10) according
to the present invention wherein the carboxy groups of the
calixarenes have been protected by esterification with benzyl
alcohol. The Nitrogen atoms of the two amide groups are linked via
a 2-C ethyl bridge. The tertiary group of the Nitrogens (designated
R.sup.9) is methyl in each case.
[0074] FIG. 13 shows a calixarene dimer (designated 11) according
to the present invention wherein the carboxy groups of the
calixarenes have been protected by esterification with benzyl
alcohol. The Nitrogen atoms of the two amide groups are linked via
a 2-C ethyl bridge. The tertiary group of the Nitrogens (designated
R.sup.9) is hydrogen in each case.
[0075] FIG. 14 shows a calixarene dimer (designated 11a) according
to the present invention, wherein the carboxy groups of the
calixarenes have been protected by as an ethyl ester. The Nitrogen
atoms of the two amide groups are linked via a 3-C aromatic bridge.
The tertiary group of the Nitrogens is hydrogen in each case.
[0076] FIG. 15 shows a synthetic scheme for the acid-amide
(954)
[0077] FIG. 16 shows a synthetic scheme for the azacrown-acid
calix[4]arenes A957 and A959.
[0078] FIG. 17 shows a synthetic route for the ester-thioamide A960
and the acid-thioamide A961.
[0079] FIG. 18 shows the variation in % extraction of Cadmium (Cd)
ions with the molar ratio of Calixarene:Cd for acid-amide A954,
ester-thioamide A960 and acid-thioamide A961 at pH=9.4.
EXAMPLES
EXAMPLE 1
[0080] The pH changes associated with the combination of various of
the agents used in the later examples was first measured in order
to better interpret the findings. The standard extraction of
dichloromethane and aqueous phase in equal volumes with 1 hour
stirring plus 2 hours separation was employed. The La(III) was used
at a concentration of 0.4 mM, and the other agents were used in a
ratio of 1:3:24 for La(III):citrate:acid-amide. The results,
measured to +/-0.1 pH units, are shown in Table 1.
1TABLE 1 Solution pH before pH after type extraction extraction (no
agents) 5.6 5.5 acid-amide 5.6 5.6 La (III) 5.6 4.9 acid-amide La
(III) 5.6 4.0 Citrate 6.0 6.1 Citrate acid-amide 6.0 6.1 Citrate La
(III) 6.0 6.0 Citrate acid-amide 6.0 6.1 La (III)
EXAMPLE 2
[0081] The efficiency of extraction of La(ill) by acid-amide as a
function of the concentration ratio of the two was measured at an
initial pH of 5.8 (FIG. 2). The pH was not maintained at this level
during the experiment. A result of 90% extraction was achieved
using a large (250.times.) excess of acid-amide. It is postulated
that this large excess was required because of a drop in pH during
the course of the experiment (see Example 1) which led to reduced
deprotonation of the three ionizable groups. In a similar
experiment using UC.sub.2.sup.2+only a 25.times. excess was
required, possibly because as a divalant cation it can still be
efficiently bound when the three ionizable groups of the acid-amide
are partially protonated.
EXAMPLE 3
[0082] The effect of various anions on the efficiency of extraction
is shown in FIG. 3. Citrate was found to be the best, probably
because of its buffering ability. In order to demonstrate that
citrate is not itself involved in the actual extraction or
complexation of La(III), LiOH was titrated into the mixture to
retain pH 6 instead of using a citrate buffer. The level of
extraction obtained (90% La(III)) was similar to that achieved with
citrate, indicating that citrate is not actually required to
achieve efficient acid-amide extraction. The postulated
non-coordination of the La(III) by citrate when acid-amide is
present indicates a high formation constant (i.e. tight binding)
for the La(III)/acid-amide complex.
EXAMPLE 4
[0083] The optimum amount of citrate required for La(III)
extraction was assessed (FIG. 4). The results indicate that a
3.times.excess over La(III) is suitable.
EXAMPLE 5
[0084] The efficiency of competitive extraction of various members
of the Lanthanide series is shown in FIG. 5. The efficiency appears
to drop off across the series, probably as a result of the change
in the size of the metal cations. The results with Lanthanides
indicate that it is likely certain actinides such as Am(III) will
also be efficiently extracted.
EXAMPLE 6
[0085] The efficiency of extraction of various metals by acid-amide
in the presence of citrate was measured, the results being shown in
FIG. 6. The results indicate high selectivity within the broad
range of elements assessed. The extraction of La, U, Hg, Sr, Eu,
Tm, Lu, Bi, and Pb is especially efficient, particularly as
compared with the alkali and the smaller alkali-earth metals, and
various other transition metals.
EXAMPLE 7
[0086] FIG. 7 shows the efficiency of extraction of various metals
by acid-amide in the absence of buffer. As can be seen, efficiency
is reduced as compared with FIG. 6 (with buffer).
EXAMPLE 8
[0087] Single crystals of some metal/acid-amide complexes (Sm, Eu,
Lu) were grown and analysed using X-ray crystallography. Results
indicate that the intermediate Lanthanides (Sm, Eu) prefer to form
a neutral dimer structure of 2 acid-amide molecules binding 2 metal
ions (see FIG. 8 which shows an acid-amide/Ln(III) complex, wherein
La=Sm or Eu). The complex is a dimer in the solid state. The
acid-amide takes up the cone conformation. The Sm cations are 8
coordinate, being bound to the deprotonated phenolic oxygen atoms,
the ethereal oxygen atoms, the amide oxygen and one of the carboxyl
oxygens. The remaining two coordination sites are made up from a
methanol oxygen and a carboxyl oxygen from the second calixarene
hence forming a bridge between the two calixarenes.
[0088] Molecular modelling suggested that all the larger
Lanthanides would form isomorphic structures and that only the
smaller Lanthanides (Gd-Lu) would form discrete monomeric
complexes. Lu (smallest Lanthanide) forms a structure with 1
acid-amide and 1 metal ion which requires a counter anion for
charge neutrality. FIG. 9 shows an acid-amide/Lu(III) complex with
NO.sub.3 as the counter ion. The Lu cation is shown to be seven
coordinate, bound to the two phenolate oxygens, the two ethereal
oxygens, the amide oxygen, one carboxylate oxygen and a water
molecule.
[0089] These structures may help to account for the specificity
demonstrated in Examples 5 and 6.
EXAMPLE 9
[0090] Metal/acid-amide complexes were further investigated by
extracting the complexes from the hydrophobic phase and determining
the metal:acid-amide ratio. For La, Lu and U at pH 6 the M:L ratio
was 1:1. This confirms the solid-state ratios determined for the
larger lanthanides and Lu by X-ray crystallography in Example 8
(which were 2:2 and 1:1 respectively). No X-ray data was obtained
for U.
EXAMPLE 10
[0091] Acid-amide dimers and esters thereof were prepared based on
the acid-amide calixarenes of the present invention, as described
in more derail in Example 15 below. Some of these are shown FIGS.
10 to 14.
[0092] Compound 13b (FIG. 10) was prepared in order to mimic the
calixarene/Lanthanide complex of FIG. 8. The dimer did not complex
La.sup.+3 at pH 6, a more alkaline pH (i.e. pH 9) being required to
quantitatively extract La. This is possibly because steric
hindrance may reduce La's ability to compete with protons for
oxygen coordination sites at low pHs. Metal:Ligand ratios in the
solvent extracted complex were determined to be 0.54 i.e. for every
2 La:dimer. This suggests that all six ionizable --OH groups are
dissociated forming a complex similar to that in FIG. 8. La, in the
presence of Lu and U, at pH 9 is preferentially extracted.
[0093] By contrast, U is quantitatively extracted at pH 6 (unlike
La). The Metal:Ligand ratio at pH 6 was approximately 1:1
suggesting a different complex is forming to that formed by La at
higher pH.
[0094] Compound 11b (FIG. 11) was prepared in order to optimise the
bridging group between the calixarenes for U extraction. The
meta-di-phenylamine linkage restricts the two calixarene halves
such that the carboxyl groups are close to each other. This is the
predicted conformation in the metal complex, unlike the
conformation in free solution, wherein it is predicted that steric
effects will mean that the halves are diametrically opposed around
the bridging group. The compound extracted U much more efficiently
at pH 9 than pH 6 (80% rather than 20%). This is in contrast to
Compound 13b above. The more alkaline operating conditions of 11b
may be more applicable to some clean up applications.
[0095] In Compound 10 (FIG. 12) the carboxy group of the
calixarenes has been protected with benzyl alcohol. No U extraction
occurred at pH 6 (as with Compound 13b). Compound 11 (FIG. 13) is
similar to compound 10 but was generated using a different diamine.
Again no extraction of U occurred at pH 6. Significant extraction
of U and Hg occurred at pH 9 notwithstanding the presence of the
protecting group. This implies that a deprotonated carboxy group is
not necessary for complexing U or Hg, but that the phenolic groups
(deprotonated at high pH) are crucial to extraction. Compound 11a
is protected with as an ethyl ester, and has the di-phenylamine
linkage of compound 13b. Again no U extraction occurred at pH
6.
[0096] It is clear that the pH dependent specificity of the dimeric
compounds above give them utility in the selective extraction of
different metals.
EXAMPLE 11
[0097] The acid-amide was physisorbed and immobilised onto
polystyrene divinyl benzene beads in an inert diluent. Solutions
containing U were passed through a chromatography column containing
the beads at various different pHs at a flow rate of approximately
2 mls/min. A control experiment was carried out with blank beads.
The results are shown Table 2. As can be seen, above pH 2
extraction of U occurred, reaching 100% at pH 3. The kinetics were
fast enough to absorb the U from the relatively fast moving mobile
phase.
2 TABLE 2 Extraction Efficiency Acid-amide pH resin Blank 1 2 10 2
37 34 3 100 20 4 100 21 6 93 21 9 34 0
EXAMPLE 12
[0098] Synthesis of acid-amide (designated A954 below).
[0099] Synthetic Scheme
[0100] A954 was synthesised using the route shown in FIG. 15. The
bis-ester(A955) was synthesised following the literature method of
Collins et al (1991) J. Chem Soc., Perkin Trans., 1, 3137. Reaction
of p-tert-Butylcalix[4]arene with 2 equivalents of ethyl
bromoacetate in acetone with potassium carbonate (as base) gave the
bis-ester in good yield. This was mono-deprotected using 1
equivalent of potassium hydroxide in ethanol. Although the product
contained traces of both bis-ester and bis-acid as impurity, it was
used without further purification and the impurities removed in
subsequent steps. Overnight reflux with thionyl chloride in
dichloromethane gave the acyl chloride which was reacted
immediately with excess diethylamine(in dichloromethane with
triethylamine present) to give the calixarene amide-ester (A953) in
72% overall yield. Finally, deprotection of the ester group using
potassium hydroxide in ethanol gave the desired acid-amide
(A954).
[0101] Detailed Synthesis
[0102] NMR data was compiled after each step, but is shown only for
the final product.
[0103] A955: p-tert-Butylcalix[4]arene (10 g, 0.015 mol) and
anhydrous potassium carbonate (4.68 g, 0.34 mol) were slurried in
dry acetone (distilled from CaSO.sub.4) for 2 hours.
Ethylbromoacetate (5.15 g, 0.031 mol) was added, and the mixture
stirred under nitrogen for three days. It was then filtered, the
solvent distilled off and the residue dried under vacuum. It was
then slurried with cold ethanol to form a white powder and
collected by filtration. This solid was washed with a further
quantity of cold ethanol and dried under vacuum. Yield 8.97 g (73
%)
[0104] 951: bis-ester A955 (8.0 g, 9.76 mmol) was slurried in
ethanol (600 ml). Potassium hydroxide (85% AR, 0.55 g, 9.76 mmol)
added and the mixture heated to reflux for 1-2 hours. On cooling
the ethanol was reduced in volume (to 50-100 ml) and 1M HCl added
to precipitate the product. This was collected by filtration and
washed with water(50 ml). The product was dried under vacuum.
[0105] Yield 6.95 g (90%) (Found: C, 73.84; H, 7.42; required C,
75.72; H. 7.62%);
[0106] A953: acid-ester 951 (5.0 g, 6.31 mmol) was refluxed
overnight with thionyl chloride (3.5 ml) in dry dichloromethane
(100 ml). The solvent was then removed by distillation and the oily
yellow residue dried under vacuum. Additions of dichloromethane
(4-5 ml) were necessary to help azeotrope off the last traces of
thionyl chloride. When dry, the product was a glassy off-white
solid. The acyl chloride ester was then dissolved in dry
dichloromethane (50 ml). To this solution was added dropwise, a
solution containing dry diethylamine (dried over KOH) (0.98 ml,
9.45 mmol) and dry triethylamine (dried over CaH.sub.2 ) (0.87 ml,
6.31 mmol) in dry dichloromethane (50 ml) over 30 minutes. After
stirring overnight at room temperature, the solution was
transferred to a dropping funnel and washed with 1M HCl (50 ml) and
then water (50 ml). It was then dried over MgSO4, filtered and the
solvent removed in vacua. The crude product was purified by column
chromatography on silica (Kieselgehl) using
dichloromethane/methanol(98:2) eluent.
[0107] Yield 3.86 g (72%) (Found: C, 74.83; H, 8.13; N 2.12.
required C,74.87, H, 8.72, N 1.61%)
[0108] 954: amide-ester, A953, (2.20 g, 2.48 mmol) was dissolved in
ethanol(150 ml) and potassium hydroxide (0.28 g, 4.96 mmol) added.
The resulting solution was then refluxed for 2 hours. After cooling
to room temperature, the volume of the solution was reduced to ca.
25 ml by rotary evaporation. Addition of 1M HCl gave a white
precipitate which was collected by filtration and washed with
water. It was then dissolved in dichloromethane (30 ml). washed
with 1M HCl (30 ml) water (30 ml) and then dried over MgSO4. The
solvent was removed in vacuo to give a foamy white solid. It was
converted to a powder by dissolving in a minimum of dichloromethane
and adding hexane (30-40 ml)-evaporation to dryness gave a white
solid. Yield 2.06 g (97%) (Found: C, 75.24; H, 8.77; N 1.97.
required C, 75.33, H,8.51, N 1.69%).
[0109] NMR data (300 MHz, CDCl3) 1.07 (9H, s, --Bu) 1.11 (9H, s,
--Bu), 1.25 (18H, s, --Bu), 1.25 (3H, t, --CH.sub.3), 3.38 (2H, d,
Ar--CH.sub.2--Ar), 3.38 (2H, q, --NCH.sub.2--), 3.42 (2H, d,
J=13.02, Ar--CH.sub.2--Ar), 3.55 (2H, q, --NCH.sub.2--), 4.22 (2H,
d, J=13.0 Hz, Ar--CH.sub.2--Ar), 4.30 (2H, d, J=13.3 Hz,
Ar--CH.sub.2--Ar), 4.64 (2H, s, --OCH.sub.2CO--), 4.78 (2 a, s,
--OCH.sub.2CO--), 6.93 (2H, s, Ar), 6.99 (2H, s, Ar), 7.03 (2H, d,
Ar), 7.06 (2H, d, Ar), 8.90 (2H, br s, --OH); (75.42 MHz, CDCl3)
13.02, 14.36, 31.12, 31.68, 32.17, 32.35, 33.91, 34.05, 34.16,
40.78, 41.20, 72.44, 73.29, 125.24, 125.55, 126.10, 127.21, 128.29,
132.71, 132.94, 142.32, 147.49, 148.51, 149.76, 150.11, 150.21,
166.71, 170.44; FAB m.s., m/z 864 (M+2 Na.sup.+--H., 18%), 842
(M+Na.sup.+, 100), 820 (M+10).
[0110] It should be noted that the synthesis of other calixarenes
falling within the claims of the present application may be readily
achieved by the skilled person in the light of the disclosure of
the present document, particularly in combination with the common
general knowledge of the skilled person, as evidenced for example
by the teaching and references of EP 0 432 989.
[0111] 954/Metal Complex Synthesis
[0112] To prepare Ln(NO.sub.3).sub.3 .nDMSO, n=3,4 Ln.sub.2O.sub.5
was dissolved in a minimum of nitric acid (fast exothermic process
for large Ln, slow process for small Ln). To the resulting solution
was added a 5-6 fold excess of dimethyl sulphoxide. Ethanol and
then diethyl ether were then added to precipitate the product.
Occasionally, when the product oiled out, it was necessary to
decant the mother liquor, add more ethanol/diethyl ether and then
scratch with a glass rod. The product was then collected by
filtration, redissolved in DMSO and precipitated with
ethanol/ether. The final product was collected by filtration and
dried under vacuum. All DMSO solvates gave elemental analyses in
accordance with their proposed structures.
[0113] A simpler method involved the use of Ln(NO.sub.3).sub.3
penta and hexahydrates instead of the oxide. In this case the salt
was twice dissolved in DMSO and precipitated with ethanol and
diethyl ether.
[0114] The calixarene acid-amide A954 (0.0189 g, 0.023 mmol) was
dissolved in 1 ml DMF. To this solution was added
Ln(NO.sub.3).sub.3 .nDMSO (n=3 or 4, 0.025 mmol) also in 1 ml DMF.
After the further addition of 30 microliters of triethylamine
(excess), the solution was immediately filtered and left to stand.
As mentioned earlier, the larger lanthanides precipitated quite
quickly from solution whereas the smaller ones took considerably
longer. The precipitated complex was then collected by filtration
and washed with a minimum of cold ethanol (ca. 0.5 ml) and dried
under vacuum. Attempts were made to recrystallise these complexes
from dichloromethane/ethanol. This typically involved dissolving
the complex in dichloromethane (1.5 ml) and then adding ethanol (1
ml). After filtering, the solution was left to slowly
evaporate.
[0115] For the larger lanthanides (La-Eu), the complex precipitated
fairly quickly from solution, and was then recrystallised from
dichloromethane/ethanol. In case of the Eu and Sm complexes,
crystals suitable for X-ray crystallographic analysis were
isolated.
[0116] Precipitated from DMF/NEt:Sm complex of A954; Found: C,
64.0; H, 7.2; N 3.3. required C, 64.3, H, 7.5, N 3.7%.
[0117] Eu complex of A954; Found: C, 63.9; H, 7.1; N 3.4. required
C, 64.2, H, 7.5, N 3.7%.
[0118] Recrystallised from ethanol/dichloromethane:
[0119] Eu complex of A954; Found: C, 65.6;H, 7.5; N 2.8. required
C, 65.6, H, 7.9, N 2.6%,
[0120] The smaller lanthanide complexes (Lu) less readily
precipitated from DMF solution than the larger ones described
above, instead crystallising out only after a period of weeks.
EXAMPLE 13
[0121] Synthesis of azacrown-acid calix[4]arenes
[0122] In attempt to form discrete monomeric complexes across the
Lanthanide series, the azacrown-acid calix[4]arenes A957 and A959
(FIG. 16) were prepared with the idea that the extra O-donor sites
present would more easily satisfy the normal 8-10 coordination
sphere of the larger Lanthanides.
[0123] The synthetic scheme used in the synthesis of the simpler
acid-amide (A354) was also applied in the synthesis of the
azacrownacidcalix[4]arenes, FIG. 15. For the final deprotection
step, in order to eliminate the possibility of isolating
alkali-metal complexes of the product, potassium hydroxide was used
as base in the deprotection of the N-aza-15-crown-5 ligand and
sodium hydroxide in the case of the N-aza-18-crown-6 ligand.
[0124] Isolation of Complexes
[0125] Preliminary work was also begun on the isolation of the
Lanthanide complexes of these ligands, the majority of this
involving theN-aza-15-crown-5 analogue only. The same methods were
applied as for the simpler acid-amide (A954) and, in general, the
same observations made. Again the larger La cations formed
complexes which readily precipitated from DMF solution. Attempts at
recrystallisation of these complexes from dichloromethane/ethanol
again yielded X-ray crystallographic quality crystals of the Sm
complex. Disappointingly, however, the anticipated monomeric
complex was not formed. Instead, a similar dimeric structure was
adopted with the aza-crown folding away and not coordinating to
Sm.
EXAMPLE 14
[0126] U.V. Spectra
[0127] The observed maxima for the 954 acid-amide are listed in
Table 3 together with the corresponding values for selected
complexes. The extinction values given are approximate only. Given
that the sample sizes measured were only about 1 mg, weighing
errors could easily account for apparent differences in absorption
between related species.
EXAMPLE 15
[0128] Synthesis of acid-amide dimer. The dimers of Example 10 were
prepared by methods analogous to those above. In the case of 11a,
compound A952 (FIG. 15) was prepared as described above. Two
molecules of A952 were dimerised with m-phenylenediamine in
dichloromethane and triethylamine. The yield was 68%. Compound 11b
was prepared from 11a by regenerating the carboxy group with
potassium hydroxide in ethanol. The yield was 90%. The other dimers
were prepared using different diamines (e.g.
1,2-di-(methylamino)ethane for 11 and 13b). Other protecting groups
can be added either as alcohols to the deprotected acid group, or
incorporated into the precursor e.g. by substituting the
ethylbromoacetate used to prepare A955 in Example 12 with a
bromylated benzyl ester. The diamine synthetic route is flexible in
that a wide variety of spacer groups may be introduced between the
calixarene halves, allowing factors such as chain length,
coordination etc. to be assessed.
3 TABLE 3 Wavelength Maxima Compound/complex (nm) cm.sup.-1M.sup.-1
954 228 36000 282 9500 954/La 228 50000 260 (sh) 15000 307 9400
954/Sm 228 46000 260 (sh) 13000 307 9600 954/Eu 228 48000 260 (sh)
15000 306 9700
EXAMPLE 16
[0129] Synthesis of the Ester-Thioamide A960
[0130] A960 was synthesised using the route shown in FIG. 17. The
precursor A953 was prepared by the route shown in FIG. 15 and
Example 12. Lawesson's reagent (0.49 g, 1.2 mmol) was added to a
solution of ester-amide A953 (1.0 g, 1. 1 7 mmol) in toluene (20
cm3) and the mixture was heated at 80.degree. C. for 4 hr. After
cooling to room temperature, the toluene was removed under reduced
pressure to give a yellow oil. This oil was dissolved in
acetonitrile (15 cm.sup.3) and filtered through an alumina pad.
Dropwise addition of water to the filtrate afforded a yellow
precipitate, which was removed by filtration and recrystallised
from dichloromethane-ethanol to afford A960 as yellow prismatic
crystals (0.95 g, 94%). The structure of this compound was
confirmed by NMR, mass spectrometry and X-ray crystallography.
EXAMPLE 17
[0131] Synthesis of the Acid-Thioamide A961
[0132] A961 was synthesised using the route shown in FIG. 17. The
ester-thioamide A960 was synthesized by the route shown in FIG. 17
and Example 16. Potassium hydroxide (0.036 g, 0.65 mmol) was added
to a solution of ester-thioamide A960) (0.5 g, 0.58 mmol) in
ethanol (25 cm.sup.3) and the solution heated under reflux for I
hr. The ethanol was reduced in volume to approximately 5 cm.sup.3
and 1M HCl added to precipitate A961 as a pale yellow powder which
was recrystallised from dichloromethanehexane (0.41 g, 85%). The
structure of this compound was confirmed by NMR and mass
spectrometry.
EXAMPLE 18
[0133] FIG. 18 shows the ability of the calixarenes A954, A960 and
A961 to extract cadmium ions at pH 9.4. Equal volumes of aqueous
cadmium cyanide solution (pH 9.4, [Cd.sup.2+=0.238 mMolar) and a
solution of a calixarene in dichloromethane were mixed for 15
minutes by stirring. The aqueous and organic phases were then
allowed to separate for about 30 minutes. The aqueous layer (Aq1)
was then removed and the organic layer was washed with a nitric
acid blank (pH 9.4). The aqueous and organic layers were allowed to
separate for about 30 minutes, and the aqueous layer was then
removed (Aq2). Aq1 contained the cadmium ions that had not been
extracted by the calixarenes, whereas Aq2 contained the cadmium
ions that had been extracted by the calixarenes (and subsequently
liberated by acidification of the organic layer). Aq1 and Aq2 were
made up to known volumes. ICP AES (inductively coupled plasma
atomic emission spectroscopy) was then used to determine the
concentration of cadmium ions in the solutions. These figures can
readily be used to determine the percentage extraction of cadmium
for a given ratio of concentration of calixarene:cadmium.
[0134] FIG. 18 indicates that both the acid-thioamide A961 and the
ester-thioamide A960 are capable of extracting cadmium ions from
solution. The order of efficiency of extraction is acid-thioamide,
A961>acid-amide, A954>ester-thioamide, A960. The order can be
explained by the fact that both A961 and A954 have a proton that
can be readily lost from the acid substituent. The resulting anion
will attract and retain cadmium ions more effectively than the
(usually uncharged) ester group. The acid-thioamide (A961) forms
complexes with cadmium more readily than the acid-amide (A954)
because the S atom in A961 is a "softer" atom than the 0 atom in
A954, and is thus more polarisable and thus is more likely to form
a complex with a Cd.sup.2+ ion, which is itself a "soft" ion.
* * * * *