U.S. patent application number 09/832579 was filed with the patent office on 2002-01-17 for methods of making cross-bridged macropolycycles.
This patent application is currently assigned to The Procter & Gamble Company. Invention is credited to Hiler, George Douglas II, Perkins, Christopher Mark.
Application Number | 20020007057 09/832579 |
Document ID | / |
Family ID | 21908062 |
Filed Date | 2002-01-17 |
United States Patent
Application |
20020007057 |
Kind Code |
A1 |
Hiler, George Douglas II ;
et al. |
January 17, 2002 |
Methods of making cross-bridged macropolycycles
Abstract
Improved synthesis of a macropolycycle, more particularly, of a
cross-bridged tetraazamacrocycle.
Inventors: |
Hiler, George Douglas II;
(Harrison, OH) ; Perkins, Christopher Mark;
(Cincinnati, OH) |
Correspondence
Address: |
THE PROCTER & GAMBLE COMPANY
PATENT DIVISION
IVORYDALE TECHNICAL CENTER - BOX 474
5299 SPRING GROVE AVENUE
CINCINNATI
OH
45217
US
|
Assignee: |
The Procter & Gamble
Company
|
Family ID: |
21908062 |
Appl. No.: |
09/832579 |
Filed: |
April 11, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09832579 |
Apr 11, 2001 |
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09380675 |
Sep 7, 1999 |
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6225464 |
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09380675 |
Sep 7, 1999 |
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PCT/IB98/00299 |
Mar 6, 1998 |
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60039920 |
Mar 7, 1997 |
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Current U.S.
Class: |
540/474 |
Current CPC
Class: |
C07D 487/08
20130101 |
Class at
Publication: |
540/474 |
International
Class: |
C07D 257/02 |
Claims
What is claimed is:
1. A method for preparing a cross-bridged macropolycycle comprising
a series of steps of derivatizing cyclam or a particular acyclic
tetraamine, wherein said series of steps is carried out using one
solvent system.
2. A method according to claim 1 wherein said solvent system is an
alcoholic solvent system.
3. A method according to claim 1 wherein said solvent system
comprises from about 60% to 100% of a C1-C4 alcohol or mixtures
thereof.
4. A method according to claim 1 wherein said solvent system is
ethanol or mixtures of ethanol with water.
5. A method according to claim 1 wherein said series of steps are
all carried out in one reaction vessel.
6. A method for preparing a cross-bridged macropolycycle comprising
a series of steps of derivatizing cyclam or a particular acyclic
tetraamine including a step of quaternizing an intermediate using a
quaternizing agent, wherein said step is carried out using less
than fifteen-fold of said quaternizing agent.
7. A method according to claim 6 wherein said step is carried out
using less than ten-fold of said quaternizing agent.
8. A method according to claim 6 wherein said step is carried out
using from five-fold to ten-fold of said quaternizing agent.
9. A method according to claim 8 wherein said quaternizing agent is
selected from the group consisting of methyl iodide, methyl
tosylate, and dimethyl sulfate.
10. A method for preparing a cross-bridged macropolycycle according
to claim 1 comprising a series of steps of derivatizing cyclam or a
particular acyclic tetraamine including a step of reducing a
diquaternized intermediate, wherein said step is carried out using
an amount less than fifteen-fold of reducing agent.
11. A method for preparing a cross-bridged macropolycycle
comprising a series of steps of derivatizing cyclam or a particular
acyclic tetraamine including a step of reducing a diquaternized
intermediate, wherein said step is carried out using an amount of
less than fifteen-fold of reducing agent.
12. A method according to claim 11 wherein said reducing agent is a
non-catalytic reducing agent.
13. A method according to claim 12 wherein said reducing agent is a
hydride compound.
14. A method according to claim 13 wherein said hydride compound is
a borohydride.
15. A method according to claim 14 wherein said borohydride
compound is selected from the group consisting of sodium
borohydride and potassium borohydride.
16. A method according to claim 15 wherein said borohydride
compound is potassium borohydride.
17. A method for preparing a cross-bridged macropolycycle, said
method comprising derivatizing cyclam or a particular acyclic
tetraamine by a series of steps including: quaternizing an
intermediate using a quaternizing agent, wherein said step is
carried out using less than fifteen-fold of said quaternizing
agent; and reducing a diquaternized intermediate, wherein said step
is carried out using an amount of less than fifteen-fold of
reducing agent; and wherein further said series of steps is carried
out using one solvent system.
18. A method according to claim 17, carried out in the absence of
any step of vacuum distilling an intermediate.
19. A method according to claim 17, carried out at or below
50.degree. C.
20. A method according to claim 17, wherein said quaternization and
reduction steps are carried out at the temperatures of from ambient
temperature to 50.degree. C.
21. A method according to claim 17 wherein all of said steps are
carried out at concentrations of the reactants of 7% or higher in
total of the sum of reactants plus solvent.
22. A method according to claim 17 wherein all of said steps are
carried out at concentrations of the reactants exceeding 15% in
total of the sum of reactants plus solvent.
23. A method according to claim 14 in which sodium ion is
substantially absent.
24. A method for producing a complex of Mn and a cross-bridged
macropolycyclic ligand, said method comprising reacting with
manganous chloride a cross-bridged macropolycycle.
25. A method for producing a complex of Mn and a cross-bridged
macropolycyclic ligand, said method comprising reacting a
cross-bridged macropolycycle with MnCl.sub.2 which has been
produced by an anhydrous reaction of manganese metal with a
chlorinating agent.
26. A method according to claim 24, conducted in a nonaqueous
solvent.
27. A method according to claim 25, conducted in a nonaqueous
solvent.
28. A method for preparing a transition metal complex of a
cross-bridged macropolycycle comprising a series of steps of (A)
forming a bisaminal from an acyclic amine; (B) forming a diquat
derivative of said bisaminal; (C) reducing said diquat derivative;
(D) separating reducing agent and solvent from the product of step
(C) in one or more operations; (E) removing residual hydride from
the product of (D); (F) isolating a cross-bridged
tetraazamacrocycle product of steps (A)-(E); and (G) reacting the
product of step (F) with a transition-metal, thereby forming a
transition-metal complex useful as a catalyst in detergent
compositions.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This is a continuation under 35 USC .sctn.120 of U.S.
application Ser. No. 09/380,675, filed Sep. 7, 1999 of which in
turn claims priority under 37 U.S.C. .sctn.371 to PCT International
Application Serial No. PCT/IB98/00299, filed Mar. 6, 1998 which
claims priority under 37 USC .sctn.119(e) to U.S. Provisional
Application Serial No. 60/039,920, filed Mar. 7, 1997).
TECHNICAL FIELD
[0002] The present invention is in the field of macrocycle
synthesis, more specifically, the synthesis of cross-bridged
macrocycles having utility as proton sponges or as ligands for
metal binding, especially for preparation of transition-metal
containing oxidation catalysts useful, for example, in laundry
detergents. The present invention is also directed to the synthesis
of Mn-containing complexes of cross-bridged macrocycles.
BACKGROUND OF THE INVENTION
[0003] Whereas macrocyclic chemistry, in general, is highly
developed, the art of manufacturing cross-bridged macrocycles is
new. Certain such macrocycles, such as cross-bridged derivatives of
cyclam, have only recently been synthesized in small amounts, and
commercial processes are not known. It would be highly desirable to
have such processes, since cross-bridged macrocycles have unique
advantages as proton sponges or when used as ligands in the
catalysis of bleaching.
[0004] Macrocycles have been made in numerous ways. See, for
example, "Heterocyclic compounds: Aza-crown macrocycles", J. S.
Bradshaw et. al., Wiley-Interscience, 1993, which also describes a
number of syntheses of such ligands. Though macrocycle synthesis is
well developed in general, synthesis of cross-bridged macrocycles
is not. Cross-bridged macrocycle synthesis is rare and difficult,
and involves multiple steps and unpleasant solvents (DMF,
acetonitrile, or the like).
[0005] Cross-bridging, i.e., bridging across nonadjacent nitrogens,
of a known macrocycle, cyclam (1,4,8,11-tetraazacyclotetradecane),
is known in limited context. It is, for example, described by
Weisman et al, J. Amer. Chem. Soc., (1990), 112(23), 8604-8605.
More particularly, Weisman et al., Chem. Commun., (1996), pp.
947-948, describe a range of assertedly new cross-bridged
tetraamine ligands which are bicyclo[6.6.2], [6.5.2], and [5.5.2]
systems, and their complexation to Cu(II) and Ni(II), demonstrating
that the ligands coordinate the metals in a cleft. Specific
complexes reported include those of the ligands 1.1: 1
[0006] in which A is hydrogen or benzyl and (a) m=n=1; or (b) m=1
and n=0; or (c) m=n=0, including a Cu(II)chloride complex of the
ligand having A=H and m=n=1; Cu(II) perchlorate complexes where A=H
and m=n=1 or m=n=0; a Cu(II)chloride complex of the ligand having
A=benzyl and m=n=0; and a Ni(II)bromide complex of the ligand
having A=H and m=n=1. This handful of complexes appears to be the
total of those known wherein the bridging is not across "adjacent"
nitrogens.
[0007] Weisman also provides a synthesis method for a cross-bridged
cyclam which uses three steps, two of which use acetonitrile as
solvent. These steps are (1) reaction of a parent macrocycle with
glyoxal to form a bisaminal and (2) quaternization of the bisaminal
with methyl iodide, to form a dimethylated bisaminal diiodide. A
further step, (3), reduction of the diquaternary intermediate
produced in the second step, is required to make the desired
product. This step uses ethanol as solvent. There is an apparent
requirement to conduct the synthesis at relatively high dilution,
which is commercially unattractive. Yields are borderline for
commercial utility (only 80% and 85% in the first and second steps,
respectively.) In view of the desirable properties of cross-bridged
macrocycles as ligands and the limitations of the existing method
of making such a macrocycle, there is a clear need and desire for
improvement in the synthesis of such cross-bridged macrocycles.
[0008] To summarize, current syntheses have one or more of the
following limitations: (a) they use relatively environmentally
undesirable solvents, such as acetonitrile; (b) they may
incorporate "high-dilution" steps, increasing solvent consumption;
(c) they require switching from one solvent to another in different
stages of manufacture; increasing cost and complexity further, and
(d) they are wasteful in calling for large excesses of materials
such as alkyl halides and/or reducing agents.
[0009] Accordingly, it would be highly desirable to improve the
synthesis of cross-bridged macrocycles, and in particular, methods
for making cross-bridged derivatives of cyclam, and to provide
methods for synthesizing Mn-containing complexes with cross-bridged
macrocyclic ligands. These and other improvements are secured
herein, as will be seen from the following disclosure.
BACKGROUND ART
[0010] See documents cited in the background. Also, Tabushi and
co-workers, cited in Bradshaw et al., supra, make use of ethanol as
a solvent for preparing a tetraazamacrocycle by dimerization.
However, the macrocycle is not cross-bridged and the method
described is not capable of forming a cross-bridged macrocycle.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 is a process outline presented for purposes of
orienting in the present process. In a preferred embodiment, the
present process has a series of essential steps, marked (A), (B),
and (C) in FIG. 1; these are single steps, they are marked in bold,
and they are conducted in sequence. The process may also contain
further operations, such as (D), (E) or (F), any one of which
operations may comprise one or more steps and which may be used to
work up the crude product of the essential process steps; the
product may then be sold or used for further conversions, for
example in one or more steps to make a useful transition-metal
bleach catalyst (G). The process desirably incorporates solvent
recycle from one or more of (A), (B), (C) and (when used), (D).
[0012] FIG. 2 is also a process outline for a preferred embodiment
of the invention. In this process, the bisaminal in step (A) is
formed from a relatively inexpensive acyclic amine. In step (B) the
bisaminal is converted to a specific diquaternary derivative. In
step (C) this is reduced. In step (D), reducing agent and solvent
are separated in one or more separation operations. In step (E),
which in general is optional but is preferred if there is any
appreciable amount of reducing agent left after step D, residual
hydride is removed. In step (F) the product, a cross-bridged
macrocycle suitable for forming transition metal complexes which
are useful bleach catalysts in detergents, is isolated. In step (G)
optionally including one or more purification steps on the final
product, transition metal complex of the cross-bridged macrocycle
is formed. (A)-(G) occur in the indicated sequence.
SUMMARY OF THE INVENTION
[0013] In one aspect, the present invention relates to a method for
preparing a cross-bridged macropolycycle, preferably a
cross-bridged tetraazamacrocycle, comprising a series of steps,
preferably three steps in sequence, of derivatizing cyclam or a
particular acyclic tetraamine, wherein said series of steps is
carried out using in common in each of said steps, substantially
one solvent system. Preferably, said solvent system is an alcoholic
solvent system; more preferably the solvent system comprises from
about 60% to 100% of a C1-C4 alcohol, such as methanol, ethanol,
n-propanol, 2-propanol, n-butanol, t-butanol, or mixtures thereof;
ethanol and 2-propanol are preferred. More generally, and in
preferred embodiments, mixtures of lower alcohol and, for example,
from about 0.1% to about 70% water, more typically from about 1% to
about 40% water, can also be useful and economic. In a highly
preferred embodiment, said solvent system is substantially ethanol
or mixtures thereof with water. The solvent system is preferably
completely free from acetonitrile. Accordingly, the invention
secures a "one-pot" method for making the cross-bridged macrocycle.
"One pot" methods in general are highly advantageous--they permit
reduced investment in manufacturing steps and equipment. Such an
advantage is secured by the present process, which is simple,
economic, and improved in terms of environmental acceptability.
[0014] The invention further relates to a method for preparing a
cross-bridged macropolycycle comprising a series of steps of
derivatizing cyclam or a particular acyclic tetraamine including a
step of quaternizing an intermediate using a quaternizing agent,
wherein said step is carried out using a minimized amount of said
quaternizing agent.
[0015] The invention further relates to a method for preparing a
cross-bridged macropolycycle comprising an alternate first step of
forming a bisaminal by (i) reacting a suitable acyclic tetraamine
with glyoxal to form a tricyclic macropolycycle and (ii) converting
the tricyclic compound to the bisaminal by reacting it with a
dihaloalkane, preferably and more generally a compound selected
from the group consisting of .alpha.,{overscore
(.omega.)}-dichloroalkanes, .alpha.,{overscore
(.omega.)}-dibromooalkanes, .alpha.,{overscore
(.omega.)}-diiodoalkanes, .alpha.,{overscore
(.omega.)}-ditosylalkanes and mixtures thereof, more preferably
.alpha.,{overscore (.omega.)}-dibromooalkanes or .alpha.,{overscore
(.omega.)}-ditosylalkane- s.
[0016] Preferably, the method of the invention has a second step
which is carried out using less than about fifteen-fold of said
quaternizing agent; typically, levels of about five-fold to about
10-fold of said quaternizing agent can be practiced. "Reagents"
herein are materials, such as the glyoxal of step A, the
quaternizing agent of step B, or the reducing agent of step C,
which are chemically reacted with a macrocycle. Ratios of reagents
herein, unless otherwise noted, are expressed on a molar basis;
thus the term "three-fold" with respect to an amount of reagent
over an amount of macrocycle means that the amount of reagent is
three times the number of moles of the macrocycle it is being used
to functionalize. A suitable quaternizing agent is methyl iodide,
but the present method contains the further improvement of
providing alternative, more environmentally attractive quaternizing
agents further illustrated hereinafter.
[0017] In another aspect, the present invention encompasses a
method for preparing a cross-bridged macropolycycle comprising a
series of steps of derivatizing cyclam or a particular acyclic
tetraamine including a step of reducing a diquaternized
intermediate, wherein said step is carried out using a minimized
amount of reducing agent. Preferably, said step is carried out
using an amount of less than about fifteen-fold of said reducing
agent. More typically, the reducing agent is from about 2.5- fold
to about 10-fold the amount of macrocycle, on a molar basis.
[0018] In general, any suitable reducing agent, both catalytic and
non-catalytic, may be used. For example, a tube reactor containing
materials for catalytic hydrogenation providing a locally high
concentration of reducing species can be used. Alternately, a
preferred group of reducing agents herein, especially for the
one-pot process, are non-catalytic reducing agents. For example
Zn/HCl is a well-known reducing agent having the advantage that it
can be used in water, and can be used herein. Preferred
non-catalytic reducing agents are hydride compounds; more preferred
are hydride compounds which can be used in wet (water-containing)
systems. Preferred hydride compounds are borohydride and borane.
Suitable borohydride compounds are selected from sodium borohydride
and potassium borohydride. Less preferably, lithium borohydride can
be used. When using borohydrides in methanol or ethanol herein, pH
may be adjusted using small amounts of alkali to limit wasteful
decomposition and release of hydrogen from the hydride. 2-propanol
and t-butanol have known advantages of producing less wasteful
hydrogen evolution than, say, methanol or ethanol.
[0019] The invention also encompasses a method in which sodium ion
is substantially absent. The terms "substantially absent" or
"substantially free" in connection with a material herein mean that
the material is not deliberately added, though adventitious amounts
are permissible. Surprisingly, sodium ion, though usable, has some
adverse effect on the method, so sodium ion, other than
adventitious amounts, are excluded in certain preferred
embodiments.
[0020] Although the invention overall is not so limited, in a
further aspect, the present invention relates to a method having
each of the foregoing steps, in sequence. As noted, the steps can
be carried out in "one pot" to secure the maximum advantages. Of
course, the practitioner may choose not to secure the maximum
benefits, for example if the different steps are carried out at
multiple manufacturing locations, or for other reasons, such as a
desire to use a specialized hydrogenation reactor in the third
step. In this instance, practitioners may still avail themselves of
the improvements in any one or two of the individual steps in any
one manufacturing location or facility.
[0021] In preferred embodiments, the invention further relates to
the method described hereinabove which is carried out in the
absence of any step of vacuum distilling an intermediate; and to a
method which is carried out at low temperatures, especially wherein
said quaternization and reduction steps are carried out at the low
temperatures of from about ambient temperature to about 50.degree.
C., more preferably lower than about 50.degree. C.
[0022] In preferred embodiments, all steps are carried out at
concentrations of the reactants of about 7% or higher, by weight in
total of the sum of reactants plus solvent; preferably, the
concentrations of the reactants exceeds about 15% in total of the
sum of reactants plus solvent. This permits the use of smaller and
less costly manufacturing plant and the use of lower, safer amounts
of flammable materials.
[0023] As will already be apparent, the invention secures numerous
advantages in relation to the manufacture of cross-bridged
macrocycles, as non-limitingly illustrated by cross-bridged cyclam
derivatives. Indeed the advantages of the present method make a
substantial difference to the possibility of commercially producing
cross-bridged macrocycles for the useful purposes outlined in the
background.
[0024] Finally, the present invention relates to a method for
producing a complex of Mn with a cross-bridged macrocyclic ligand.
Said method comprises preparing said complex, preferably under
strictly oxygen and hydroxyl-free (ideally completely anhydrous)
conditions by reaction of MnCl.sub.2 with a cross-bridged
macropolycycle.
[0025] All ratios, proportions and percentages are by weight unless
otherwise specifically indicated. An exception is yields. Yields
are given as percentages obtained of the amounts expected for
complete chemical reaction according to the equations given.
Percentage yields can, of course, be computed on either a weight or
a mole basis, given the designated reactions.
DETAILED DESCRIPTION OF THE INVENTION
[0026] In a preferred embodiment, the present invention involves a
process or method having three essential steps, (A), (B) and (C) as
shown in FIG. 1, optionally followed by additional steps. In one
such embodiment,
[0027] Step (A) is non-limitingly illustrated as follows: 2
[0028] The above step, the yield of which is from about 85% to
100%, typically near quantitative (100%), can be carried out using
ethanol as a solvent and a concentration of reactants of 7%. The
reagent, glyoxal, can be used pure or undiluted, or as a solution,
for example and aqueous solution. More generally, in this step, the
concentration of reactants by weight in the sum of all solvents
including water, if present, is in the range from about 7% to about
20%, or higher. Thus, cyclam is slurried at 7% in ethanol. The
slurry is stirred using any convenient stirring means, such as a
mechanically driven paddle stirrer. The above depicted co-reactant,
glyoxal, is dripped in, preferably keeping the temperature below
about 35.degree. C. More generally, the temperature can be in the
range from about 10.degree. C. to about 40.degree. C. After the
addition reaction is over, typically within one hour, more
generally in from about 10 min. to about 3 hours, it is found to be
quantitative by any suitable means, for example C-13 NMR. Step (A)
and all other steps herein can in general be conducted at
atmospheric pressure, or overpressures if desired. The term
"overpressures" herein means pressures greater than atmospheric.
Although preferred embodiments of the invention include those
conducted at atmospheric pressure, any step or steps can be
conducted at overpressures, for example to contain volatile
solvents or reagents above their normal boiling-points. The
cis-tetracycle (product of step (A)) is not isolated; rather it is
kept in the reaction solvent and the process proceeds to step
(B).
[0029] In another preferred embodiment, the cis-tetracycle is
prepared using the following scheme: 3
[0030] This alternate procedure is referred to as alternate Step
(A), comprising step A (i) and step A(ii) as shown. In more detail,
a suitable tetramine, N,N'-bis-(2-aminoethyl)-1,3-propanediamine,
is reacted with glyoxal, typically about 1-10 molar equivalents,
preferably from about 0.8 to about 1.5 molar equivalents, very
suitably 1 molar equivalent, in a solvent, ethanol being preferred,
at temperatures in the range from about 0 to 100.degree. C., more
preferably 0 to 25.degree. C., for a period of from about 1 min. to
about 7 days, preferably from about 15 min. to about 2 hours. The
intermediate product, a tricycle of the shown structure, can either
be isolated by distillation or can be further reacted to form the
cis-tetracycle without changing reactor. The conversion of the
tricycle to the cis-tetracycle can suitably be conducted using a
1,3-dihalopropane, typically 1,3-dibromopropane, or the ditosylate
of 1,3-propanediol can alternatively be used. Suitable solvents are
ethanol (ideal for one-pot purposes) or acetonitrile. A base is
used to prevent the tricyclic amine reactant from protonating as
the reaction continues. Suitable bases can vary widely and can
include potassium carbonate or organic bases which are resistant to
alkylation, such as di-isopropylethylamine (Koenig's base). The
amount of the base is typically from 1-10 equivalents, preferably
from about 2 equivalents to about 6 equivalents. The reaction
temperature is in the range from about 0 to 100.degree. C., more
preferably 0 to 30.degree. C., for a period of from about 15 min.
to about 7 days, preferably from about 30 min. to about 2 hours.
Depending on the base used, workup can vary. With potassium
carbonate, for example, the reaction mixture is filtered to remove
solid base and the filtrate is evaporated to yield the
cis-tetracycle as a solid. With an organic base, the solvent is
evaporated and the evaporate is distilled. Step (B) is
non-limitingly illustrated as follows: 4
[0031] After making the cis tetracycle (product of any variation of
step(A) ), this material is quaternized, as non-limitingly
illustrated using alkyl halide (CH.sub.3I) in the reaction scheme.
Such a step has a yield of about 80%, or higher. Yields of 80% can
typically be achieved. More generally, in this step, the
concentration of reactants by weight in the sum of all solvents
including water, if present, is in the range from about 7% to about
20%, or higher. In a preferred embodiment, from about 2.01 to about
14 equivalents, preferably from about 2.5 to about 8 equivalents,
for example 7 equivalents of methyl iodide are added to the
reaction solution and the reaction is stirred using any convenient
means, such as a mechanically driven stirrer (sparkless motor).
More generally, any one or more alkyl halides can be used, for
example a mixture of methyl iodide and 1-iodopropane. As will be
seen from the working examples hereinafter, by introducing a second
alkyl halide in addition to methyl iodide, step (B) is thereby
modified to allow access to additional macrocyclic compounds as
alternate products of the present process. The temperature is
maintained in the general range from about 10.degree. C. to about
38.degree. C., more preferably from about 15.degree. C. to about
30.degree. C. At the low end of these reaction temperatures, there
is a tendency for more monoquaternized intermediate (not shown in
the reaction sequence) to precipitate. At the high end of these
reaction temperatures, there is more tendency to form undesired
byproducts, such as a triquaternized derivative (also not shown in
the reaction sequence). Desirably, in view of byproduct formation
tendencies, mono-quat intermediate is precipitated; but in order to
maximize reaction rate, measures are taken to keep the particle
size small and the surface area of intermediate mono-quat as high
as possible. Vigorous stirring, small adjustments of the solvent
system, or compatible additives, for example inert water-soluble
nonsodium salts, can help. Illustrative of reaction time in step
(B) is a period of from about 0.5 hours to 72 hours. Typical
reaction times when not taking any special measures to accelerate
reaction are from about 24 hours to about 72 hours, for example
about 48 hours. The monoquat intermediate referred to supra usually
begins to separate from solution about 1 hour after addition of
methyl iodide. The reaction can desirably be monitored, for example
by C-13 NMR. When reaction to form diquat is complete the ethanol
can, if desired, be siphoned off (this is convenient, especially
for the one-pot variation of the present process). Solvents are
desirably recycled in this and all other steps where recycle is
possible. Recycle can be by any convenient means, for example by
means of conventional distillation apparatus. Solid product of step
(B) can be washed with ethanol, typically several times, to remove
excess methyl iodide. Step (B) can be conducted at atmospheric
pressure; however, any suitable overpressure may be quite desirable
when the quaternizing agent is low-boiling.
[0032] Other alkyl halides, such as chloromethane, or, more
generally, other quaternizing agents such as dimethyl sulfate or
methyltosylate, can be substituted in the above procedure. As
noted, faster reaction times occur when the mono-quat is
solubilized, but faster reaction times, for example using dimethyl
sulfate/water/ethanol, may increase tendency to form an undesired
tri-quat.
[0033] As noted, the desired product of this step, the di-quat
compound shown in the illustration, is derived from an
initially-formed and practically insoluble mono quat. Note that in
relative terms, the di-quat compound is even more insoluble than
the mono-quat. In order to accelerate the reaction, it might have
been thought desirable to solublize the mono-quat; however,
excessive solubilization of mono-quat intermediate, which, in turn,
may lead to undesirable solubilization of diquat, is avoided in
preferred embodiments of the present process, thereby limiting
formation of undesired, tri quat byproduct. 5
[0034] Step (C) is non-limitingly illustrated as follows:
[0035] Step (C) is a reduction step, having typical yield of 80% or
higher. The solids from the diquat reaction of step (B) are
dissolved in water and ethanol is added to make a 80% ethanol
solution; the final concentration of the diquat is 20% by weight in
the total of solvents (for example 81:19 ethanol:water by weight).
More generally, C1-C4 lower alcohol may be used in all of steps
(A), (B) and (C) and in step (C) a preferred solvent system
comprises from about 50% to about 95% lower alcohol and the balance
water. An excess, preferably from about 3 to about 10, for example,
6, equivalents of sodium borohydride are added slowly, with
stirring using any convenient means. For convenience, the
borohydride may, for example, by slurried in a portion of solvent
and added as the slurry, if it is desired to avoid solids-handling
and obtain excellent control of the addition. On addition of the
borohydride, the reaction becomes very exothermic. Temperature is
maintained in the range from about 0.degree. C. to about 80.degree.
C., more preferably from about 20.degree. C. to about 50.degree.,
using cooling means such as an ice bath if needed. Once all
borohydride is added, the reaction mixture is stirred, generally
from about 1.5-72 hours, typically up to ethanol reflux. Longer
reaction times at relatively lower temperatures are safest in this
step (C) and safety may be further enhanced by passage of an inert
gas, such as nitrogen, to flush out hydrogen, especially from the
reactor headspace. Suitable reducing agents herein include the
borohydrides, but preferably, non-sodium salt forms. Reaction is
optionally monitored by ion spray mass spec. This constitutes the
end of the basic process: it will be seen that all the above has
been accomplished using ethanol or equivalent lower alkanol
(preferably with some water) as the solvent. The crude product is
useful as an intermediate for further processing as illustrated
herein.
[0036] Steps (D)-(G)
[0037] As can be seen from FIG. 1 and further illustrated in FIG.
2, any of a range of alternative steps or combination of steps may
follow step (C). For example, once the step (C) reaction is
finished, a step identified as (E) in FIG. 1. can be used. In such
a step, the pH is adjusted to between 1 and 2 with 37% HCl (slow
addition of acid is required, reaction is very exothermic) and the
reaction solution is concentrated at reduced pressure to a thick
slurry. The thick slurry is then made basic (pH>14), for example
with 8M KOH. If desired, product can be extracted with toluene and
subjected to further purification, such as by distillation.
Preferred embodiments of the instant invention, however, include
those not having vacuum distillation as a requirement.
[0038] An alternative procedure for workup, (D) in FIG. 1, simply
involves evaporating to dryness the crude product of step (C); the
organic product is then separated from residual salts by extraction
with ethanol. Another alternative workup, (F), is illustrated by a
direct distillation of the desired product from the crude reaction
mixture. The product can then be used for conversion to useful
transition-metal complexes, especially the dichloro-Mn(II) complex,
which are effective bleach catalysts, preferably by the present
invention process by reaction with MnCl.sub.2.
[0039] In more detail, with reference to FIG. 2, a preferred workup
sequence comprises the steps of (D) (i) reducing agent removal, for
example by simple filtration, (D) (ii) solvent removal, for example
by evaporation, (E) residual hydride removal, for example by using
acid-treatment followed by base treatment as defined supra, and (F)
separation of the desired cross-bridged macrocycle, for example by
distillation. The product of step (F) is used in subsequent step
(G) to form a transition-metal complex, for example a complex of
manganese.
[0040] A preferred product of the present process (product of step
(C)), is 5,12-dimethyl-1,5,8,12-tetraaza-bicyclo[6.6.2]hexadecane.
This product is obtained when cyclam is used as the parent
macrocycle. However, the invention methods should not be taken as
limited to this particular material, as it is equally amenable to
the preparation of any one of a wide range of cross-bridged
macrocycles. For example, any one or more substituent moieties such
as alkyl or alkaryl moieties, may be present, covalently attached
to the parent macrocycle used in step (A). Moreover, other
macrocycles can be made by the process through the variation of
adding methyl halide along with another alkyl halide in step (B).
Thus, for example,
5-n-butyl-12-methyl-1,5,8,12-tetraaza-bicyclo[6.6.2]hexadeca- ne
can be prepared by the present process by use of a mixture of
1-iodobutane and methyl iodide, very preferably by consecutive
reaction first of an equivalent of iodobutane then an equivalent of
methyl iodide, in step (B). Similarly, the present process can be
used to prepare the cross-bridged macrocycle
5-benzyl-12-methyl-1,5,8,12-tetraaza-bicyclo[6.6- .2]hexadecane,
simply by use of the variation of adding methyl iodide and benzyl
bromide, instead of only methyl iodide, in step (B). All of these
cross-bridged macrocycles can thus be prepared using the desirable
features of the invention, for example their independence from use
of dimethylformamide or acetonitrile and their improved yields,
especially in step (A), all to great economic advantage.
[0041] In a preferred embodiment of the present invention, the
macrocyclic ligand is reacted directly with manganese as an
inorganic salt free of organic ligands such as pyridine, to form
useful transition-metal complexes. The source of manganese chloride
can include analytical and technical grades, and can be fully
anhydrous or only partly anhydrous. Manganese chloride is
commercially available from Chemetals Corp., Spectrum Bulk
Chemicals Corp., American International Chemical Inc., Barker
Industries Inc., and Mineral Research and Development Corp. As
noted in Kirk-Othmer's Encyclopedia, manganese chloride can be
prepared from the carbonate or oxide by dissolving it in
hydrochloric acid. Heavy-metal contamination can be removed by
precipitation through the addition of manganese carbonate which
increases the pH. Following filtration, the solution can be
concentrated and upon cooling, crystals of MnCl.sub.2.4H.sub.2O are
collected. If an anhydrous product is desired, dehydration in a
rotary dryer to a final temperature of 220.degree. C. is required.
Anhydrous manganese chloride can also be made by reaction of
manganese metal, carbonate or oxide, and dry hydrochloric acid.
Manganese chloride is manufactured by Chemetals Corp., using a
process in which manganese(II) oxide is leached with hydrochloric
acid. Manganese carbonate is added after completion of the initial
reaction to precipitate the heavy-metal impurities. Following
filtration of the impurities, the solution is concentrated and
cooled and the manganese chloride is isolated. Gradual heating in a
rotary dryer above 200.degree. C. gives anhydrous manganese
chloride. For top quality MnCl.sub.2.xH.sub.2O grades, the
starting-material is manganese metal or high purity MnO. To make
anhydrous MnCl.sub.2 directly, manganese metal or ferromanganese is
chlorinated at 700.degree. C. to 1000.degree. C. Any iron
trichloride initially present in the product is removed by
sublimation. For more detail on manganese chloride, see Kirk
Othmer's Encyclopedia of Chemical Technology, 4th Ed., Wiley, 1991,
"Manganese Compounds", pp 991 and following. It is an advantage of
the present invention to be able to proceed all the way from step
(A) to step (G) (see FIG. 1) without having to make an intermediate
complex of manganese with an organic ligand. Moreover, although
high-purity manganese chloride grades, especially those which are
totally anhydrous, work very well in the instant invention, it is a
further advantage to be able to use grades such as the 98%+ grade
and the 99% grade which are not totally anhydrous and are available
at substantially lower cost. On the other hand, for the most
exacting purity, it can be desirable and is equally encompassed
herein to use a manganese chloride which has been made by the
anhydrous route from the pure metal.
[0042] The macropolycyclic ligands herein (product of step (C)) can
be reacted with manganese chloride in any convenient manner. See
Examples 10 and 11, in each, see (b), Method (II). Any variation of
such non-limiting illustrations of the process for step (G) of the
instant invention are encompassed herein; for example, argon or
nitrogen and degassing procedures while they can be useful for best
results can be dispensed with, especially in larger-scale
commercial operation; likewise rotary evaporation and other
laboratory-scale procedures can readily be scaled up to
commercial-scale equipment. Any convenient organic solvent can be
used, for example acetonitrile, though other solvents are also
possible. Typically the step (G) conversion of macrocyclic ligand
to transition-metal complex is conducted at temperatures from about
ambient to about 100.degree. C., preferably from about 40.degree.
C. to about 80.degree. C.; and no water is deliberately added to
the solvent system. Pressures are typically atmospheric, though
higher pressures may be used if desired, for example to help
contain volatile solvents. 6
[0043] The present invention is further non-limitingly illustrated
by the following examples.
EXAMPLE 1
[0044] The method of the invention illustrated by steps (A)+(B)+(C)
as described in detail hereinabove is carried out using the
following parameters:
[0045] Step A Reagents: Parent macrocycle, MW 506.21, 10 moles
[0046] Step B reagents: Product of step A and Methyl Iodide
[0047] Step C reagents: Product of Step B and Sodium
Borohydride.
[0048] All steps are conducted in a single reaction vessel equipped
with a mechanical stirrer and means for gas inlet and outlet.
Purging of hydrogen is accomplished using nitrogren or argon.
1 Total Reagent Reagent (mole ratio concen- Press. Temp Time to
tration (atm.) (.degree. C.) (hrs.) macrocycle) (%) Solvent Step
(A) 1 30 1 1:1 7 Ethanol/ Water (97:3 vol.)* Step (B) 1 38 48 6:1 7
Solvent of Step A Step (C) 1 40 24 6:1 20% Ethanol/ Water (80:20
vol.)* Alternate 1 78 2 4:1 20% Ethanol/ Step Water (C) (80:20
vol.)* *Using known densities, these volume ratios, provided for
convenient handling of materials, can readily be converted to
weight ratios in accordance with preferred weight ratios cited
elsewhere herein.
EXAMPLE 2
[0049] The method of Example 1 is repeated, except that an equal
number of moles of dimethylsulfate replaces the methyl iodide.
EXAMPLE 3
[0050] The method of Example 1 is repeated, except that potassium
borohydride replaces sodium borohydride in equimolar amount.
EXAMPLE 4
[0051] The method of Example 1 is repeated, except that the solvent
system is ethanol-only in steps A and B.
EXAMPLE 5
[0052] The method of Example 1 is repeated, except that the solvent
system is substantially water.
EXAMPLE 6
[0053] The method of Example 1 is repeated, except that steps A and
B are carried out in the original reaction vessel while step C is
conducted in a second reaction vessel. The first reaction vessel is
then freed from the requirement to handle hydrogen evolution.
EXAMPLE 7
[0054] The method of Example 1 is repeated, except that the reagent
ratio to macrocycle is 1.1-fold, 3-fold and 3-fold in steps (A),
(B) and (C) respectively. (In the terms given in the Table of
Example 1, column 5 numbers are 1.1:1, 3:1 and 3:1). In another
variation, a mixture of methyl iodide and 1-iodobutane replaces the
methyl iodide of Example 1, demonstrating that the present process
can be used to prepare different kinds of cross-bridged
macrocycles.
EXAMPLE 8
[0055] Purification of the product of Example 1. (Conventional).
Aqueous phase crude product from Example 1 is extracted with 5
portions of toluene. The extracts are combined and evaporated. The
product is vacuum distilled at 100.degree. C., 0.1 mm Hg.
EXAMPLE 9
[0056] This example further illustrates the conversion of product
of Example 1, after purification, to a useful bleach catalyst by
the present invention process. 7
[0057] Reagents according to the present invention are in anhydrous
form. Product of Example 1 after conventional purification (for
example distillation) is slurried in a 10% solution of acetonitrile
and degassed with argon. Anhydrous MnCl.sub.2 (more economically,
98% or 99% grade) is then added and the reaction refluxed under
argon for 4 hours. Reaction can be monitored qualitatively by
color; pale blue being positive indication reaction is proceeding
normally--any ingress of air may cause darkening. The reaction
mixture is then filtered hot through a glass micro fiber filter
and, if desired, again through a 0.2 micron filter. Filtrate is
then concentrated at reduced pressure to dryness and the solids
suspended and washed 5X in 2 volumes of toluene and then filtered
and dried.
EXAMPLE 10
Synthesis of [Mn(Bcyclam)Cl.sub.2 ]
[0058] This example also further illustrates the conversion of
product of Example 1, after purification, to a useful bleach
catalyst. 8
[0059] (a) Method I.
[0060] The "Bcyclam",
(5,12-dimethyl-1,5,8,12-tetraaza-bicyclo[6.6.2]hexad- ecane) , is
the product of the process of the invention. Bcyclam (1.00 g., 3.93
mmol) is dissolved in dry CH.sub.3CN (35 mL, distilled from
CaH.sub.2). The solution is then evacuated at 15 mm until the
CH.sub.3CN begins to boil. The flask is then brought to atmospheric
pressure with Ar. This degassing procedure is repeated 4 times.
Mn(pyridine).sub.2Cl.su- b.2 (1.12 g., 3.93 mmol), synthesized
according to the literature procedure of H. T. Witteveen et al., J.
Inorg. Nucl. Chem. (1974), 36, 1535, is added under Ar. The cloudy
reaction solution slowly begins to darken. After stirring overnight
at room temperature, the reaction solution becomes dark brown with
suspended fine particulates. The reaction solution is filtered with
a 0.2.mu. filter. The filtrate is a light tan color. This filtrate
is evaporated to dryness using a rotoevaporator. After drying
overnight at 0.05 mm at room temperature, 1.35 g. off-white solid
product is collected, 90% yield.
[0061] Elemental Analysis: % Mn, 14.45; % C, 44.22; % H, 7.95;
theoretical for [Mn(Bcyclam)Cl.sub.2],
MnC.sub.14H.sub.30N.sub.4Cl.sub.2, MW=380.26. Found: % Mn, 14.98; %
C, 44.48; % H, 7.86; Ion Spray Mass Spectroscopy shows one major
peak at 354 mu corresponding to [Mn(Bcyclam)(formate)].su- p.+.
[0062] (b) Method II (Present Invention Process).
[0063] Freshly distilled Bcyclam (25.00 g., 0.0984 mol), which is
the product of the present process, is dissolved in dry CH.sub.3CN
(900 mL, distilled from CaH.sub.2). The solution is then evacuated
at 15 mm until the CH.sub.3CN begins to boil. The flask is then
brought to atmospheric pressure with Ar. This degassing procedure
is repeated 4 times. MnCl.sub.2 (11.25 g., 0.0894 mol) is added
under Ar. The cloudy reaction solution immediately darkens. After
stirring 4 hrs. under reflux, the reaction solution becomes dark
brown with suspended fine particulates. The reaction solution is,
if desired, filtered through a 0.2.mu. filter under dry conditions.
The filtrate is a light tan color. This filtrate is evaporated to
dryness using a rotoevaporator. The resulting tan solid is dried
overnight at 0.05 mm at room temperature. The solid is suspended in
toluene (100 mL) and heated to reflux. The toluene is decanted off
and the procedure is repeated with another 100 mL of toluene. The
balance of the toluene is removed using a rotoevaporator. After
drying overnight at 0.05 mm at room temperature, 31.75 g. of a
light blue solid product is collected, 93.5% yield.
[0064] Elemental Analysis: % Mn, 14.45; % C, 44.22; % H, 7.95; % N,
14.73; % Cl, 18.65; theoretical for [Mn(Bcyclam)Cl.sub.2],
MnC.sub.14H.sub.30N.sub.4Cl.sub.2, MW=380.26. Found: % Mn, 14.69; %
C, 44.69; % H, 7.99; % N, 14.78; % Cl, 18.90 (Karl Fischer Water,
0.68%). Ion Spray Mass Spectroscopy shows one major peak at 354 mu
corresponding to [Mn(Bcyclam)(formate)].sup.+.
EXAMPLE 11
Synthesis of [Mn(C.sub.4-Bcyclam)Cl.sub.2] where
C.sub.4-Bcyclam=5-n-butyl-
-12-methyl-1,5,8,12-tetraaza-bicyclo[6.6.2]hexadecane
[0065] 9
[0066] (a) C.sub.4-Bcyclam Synthesis 10
[0067] The following synthesis method is conventional and is
included for comparative purposes; however the product, (III) (see
hereinafter) is another macrocycle which can be manufactured by the
hereinabove-described process of the present invention, simply by
addition of an additional alkyl halide, 1-iodobutane, to step (B)
of the instant process. Tetracyclic adduct (I) can be made using
step (A) of the instant process, or, for comparison, can be
prepared by the literature method of H. Yamamoto and K. Maruoka, J.
Amer. Chem. Soc., (1981), 103, 4194. I (3.00 g., 13.5 mmol) is
dissolved in dry CH.sub.3CN (50 mL, distilled from CaH.sub.2).
1-Iodobutane (24.84 g., 135 mmol) is added to the stirred solution
under Ar. The solution is stirred at room temperature for 5 days.
4-Iodobutane (12.42 g., 67.5 mmol) is added and the solution is
stirred an additional 5 days at RT. Under these conditions, I is
fully mono-alkylated with 1-iodobutane as shown by .sup.13C-NMR.
Methyl iodide (26.5 g, 187 mmol) is added and the solution is
stirred at room temperature for an additional 5 days. The reaction
is filtered using Whatman #4 paper and vacuum filtration. A white
solid, II, is collected (6.05 g., 82%).
[0068] .sup.13C NMR (CDCl.sub.3) 16.3, 21.3, 21.6, 22.5, 25.8,
49.2, 49.4, 50.1, 51.4, 52.6, 53.9, 54.1, 62.3, 63.5, 67.9, 79.1,
79.2 ppm. Electro spray Mass Spec. (MH.sup.+/2, 147).
[0069] II (6.00 g., 11.0 mmol) is dissolved in 95% ethanol (500
mL). Sodium borohydride (11.0 g., 290 mmol) is added and the
reaction turns milky white. The reaction is stirred under Ar for
three days. Hydrochloric acid (100 mL, concentrated) is slowly
dripped into the reaction mixture over 1 hour. The reaction mixture
is evaporated to dryness using a rotoevaporator. The white residue
is dissolved in sodium hydroxide (500 mL, 1.00N). This solution is
extracted with toluene (2.times.150 mL). The toluene layers are
combined and dried with sodium sulfate. After removal of the sodium
sulfate using filtration, the toluene is evaporated to dryness
using a rotoevaporator. The resulting oil is dried at room
temperature under high vacuum (0.05 mm) overnight. A colorless oil
results 2.95 g., 90%. This oil (2.10 g.) is distilled using a short
path distillation apparatus (still head temperature 115 C. at 0.05
mm). Yield: 2.00 g. .sup.13C NMR (CDCl.sub.3) 14.0, 20.6, 27.2,
27.7, 30.5, 32.5, 51.2, 51.4, 54.1, 54.7, 55.1, 55.8, 56.1, 56.5,
57.9, 58.0, 59.9 ppm. Mass Spec. (MH.sup.+, 297).
[0070] (b) [Mn(C.sub.4-Bcyclam)Cl.sub.2] Synthesis (According to
the present invention)
[0071] C.sub.4-Bcyclam (2.00 g., 6.76 mmol) is slurried in dry
CH.sub.3CN (75 mL, distilled from CaH.sub.2). The solution is then
evacuated at 15 mm until the CH.sub.3CN begins to boil. The flask
is then brought to atmospheric pressure with Ar. This degassing
procedure is repeated 4 times. MnCl.sub.2 (0.81 g., 6.43 mmol) is
added under Ar. The tan, cloudy reaction solution immediately
darkens. After stirring 4 hrs. under reflux, the reaction solution
becomes dark brown with suspended fine particulates. The reaction
solution is filtered through a 0.2.mu. membrane filter under dry
conditions. The filtrate is a light tan color. This filtrate is
evaporated to dryness using a rotoevaporator. The resulting white
solid is suspended in toluene (50 mL) and heated to reflux. The
toluene is decanted off and the procedure is repeated with another
100 mL of toluene. The balance of the toluene is removed using a
rotoevaporator. After drying overnight at 0.05 mm, RT, 2.4 g. a
light blue solid (III) results, 88% yield. Ion Spray Mass
Spectroscopy shows one major peak at 396 mu corresponding to
[Mn(C.sub.4-Bcyclam)(formate)].- sup.+.
EXAMPLE 12
Synthesis of [Mn(Bz-Bcyclam)Cl.sub.2] where
Bz-Bcyclam=5-benzyl-12-methyl--
1,5,8,12-tetraaza-bicyclo[6.6.2]hexadecane
[0072] 11
[0073] (a) Bz-Bcyclam Synthesis
[0074] The macrocycle is synthesized similarly to the
C.sub.4-Bcyclam synthesis described above, except that benzyl
bromide is used in place of the 1-iodobutane in step (B) of the
instant process. .sup.13C NMR (CDCl.sub.3) 27.6, 28.4, 43.0, 52.1,
52.2, 54.4, 55.6, 56.4, 56.5, 56.9, 57.3, 57.8, 60.2, 60.3, 126.7,
128.0, 129.1, 141.0 ppm. Mass Spec. (MH.sup.+, 331).
[0075] (b) [Mn(Bz-Bcyclam)Cl.sub.2] Synthesis
[0076] This complex is made similarly to the
[Mn(C.sub.4-Bcyclam)Cl.sub.2] synthesis described above except that
Bz-Bcyclam is used in place of the C.sub.4-Bcyclam. Ion Spray Mass
Spectroscopy shows one major peak at 430 mu corresponding to
[Mn(Bz-Bcyclam)(formate)].sup.+.
EXAMPLE 13
Synthesis of [Mn(C.sub.8 -Bcyclam)Cl.sub.2] where
C.sub.8-Bcyclam=5-n-octy-
l-12-methyl-15,8,12-tetraaza-bicyclo[6.6.2]hexadecane
[0077] 12
[0078] (a) C.sub.8-Bcyclam Synthesis:
[0079] This ligand is synthesized similarly to the C.sub.4-Bcyclam
synthesis described above except that 1-iodooctane is used in place
of the 1-iodobutane. Mass Spec. (MH.sup.+, 353).
[0080] (b) [Mn(C.sub.8-Bcyclam)Cl.sub.2] Synthesis
[0081] This complex is made similarly to the
[Mn(C.sub.4-Bcyclam)Cl.sub.2] synthesis described above except that
C.sub.8-Bcyclam is used in place of the C.sub.4-Bcyclam.
[0082] Ion Spray Mass Spectroscopy shows one major peak at 452 mu
corresponding to [Mn(B.sub.8-Bcyclam)(formate)].sup.+.
EXAMPLE 14
Synthesis of [Mn(H.sub.2-Bcyclam)Cl.sub.2] where
H.sub.2-Bcyclam=1,5,8,12-- tetraaza-bicyclo[6.6.2]hexadecane
[0083] 13
[0084] The H.sub.2-Bcyclam is synthesized similarly to the
C.sub.4-Bcyclam synthesis described above except that benzyl
bromide is used in place of the 1-iodobutane and the methyl iodide.
The benzyl groups are removed by catalytic hydrogenation. Thus, the
resulting 5,12-dibenzyl-1,5,8,12-tetra-
aza-bicyclo[6.6.2]hexadecane and 10% Pd on charcoal is dissolved in
85% acetic acid. This solution is stirred 3 days at room
temperature under 1 atm. of hydrogen gas. The solution is filtered
though a 0.2 micron filter under vacuum. After evaporation of
solvent using a rotary evaporator, the product is obtained as a
colorless oil. Yield: 90.sup.+%.
[0085] The Mn complex is made similarly to the
[Mn(Bcyclam)Cl.sub.2] synthesis described hereinabove except that
the that H.sub.2-Bcyclam is used in place of the Bcyclam.
[0086] Elemental Analysis: % C, 40.92; % H, 7.44; % N, 15.91;
theoretical for [Mn(H.sub.2-Bcyclam)Cl.sub.2],
MnC.sub.12H.sub.26N.sub.4Cl.sub.2, MW=352.2. Found: % C, 41.00; %
H, 7.60; % N, 15.80. FAB+ Mass Spectroscopy shows one major peak at
317 mu corresponding to [Mn(H.sub.2-Bcyclam)Cl].sup.+ and another
minor peak at 352 mu corresponding to
[Mn(H.sub.2-Bcyclam)Cl.sub.2].sup.+.
EXAMPLE 15
Synthesis of [Fe(H.sub.2-Bcyclam)Cl.sub.2] where
H.sub.2-Bcyclam=1,5,8,12-- tetraaza-bicyclo[6.6.2]hexadecane
[0087] 14
[0088] The Fe complex is made similarly to the
[Mn(H.sub.2-Bcyclam)Cl.sub.- 2] synthesis described hereinabove
except that the that anhydrous FeCl.sub.2 is used in place of the
MnCl.sub.2.
[0089] Elemental Analysis: % C, 40.82; % H, 7.42; % N, 15.87;
theoretical for [Fe(H.sub.2-Bcyclam)Cl.sub.2],
FeC.sub.12H.sub.26N.sub.4Cl.sub.2, MW=353.1. Found: % C, 39.29; %
H, 7.49; % N, 15.00. FAB+Mass Spectroscopy shows one major peak at
318 mu corresponding to [Fe(H.sub.2-Bcyclam)Cl].s- up.+ and another
minor peak at 353 mu corresponding to
[Fe(H.sub.2-Bcyclam)Cl.sub.2].sup.+.
EXAMPLE 16
[0090] Synthesis of:
[0091]
Chloro-20-methyl-1,9,20,24,25-pentaaza-tetracyclo[7.7.7.1.sup.3,7.1-
.sup.11,15.]pentacosa-3,5,7(24),11,13,15(25)-hexaene manganese(II)
hexafluorophosphate, 7(b);
[0092] Trifluoromethanesulfono-20-methyl-1,9,20,24,25-pentaaza
tetracyclo[7.7.7.1.sup.3,7.1.sup.11,15.]pentacosa-3,5,7(24),11,13,15(25)--
hexaene manganese(II) trifluoromethanesulfonate, 7(c) and
Thiocyanato-20-methyl-1,9,20,24,25-pentaaza-tetracyclo[7.7.7.1.sup.3,7.1.-
sup.11,15.]pentacosa-3,5,7(24),11,13,15(25)-hexaene iron(II)
thiocyanate, 7(d)
[0093] (a) Synthesis of the ligand
[0094]
20-methyl-1,9,20,24,25-pentaaza-tetracyclo[7.7.7.1.sup.3,7.1.sup.11-
,15.]pentacosa-3,5,7(24),11,13,15(25)-hexaene
[0095] The ligand 7-methyl-3, 7, 11,
17-tetraazabicyclo[11.3.1.sup.17]hept- adeca-1(17), 13, 15-triene
is synthesized by the literature procedure of K. P. Balakrishnan et
al., J. Chem. Soc., Dalton Trans., 1990, 2965.
[0096] 7-methyl-3, 7, 11,
17-tetraazabicyclo[11.3.1.sup.17]heptadeca-1(17)- , 13, 15-triene
(1.49 g, 6 mmol) and O,O'-bis(methanesulfonate)-2,6-pyridi- ne
dimethanol (1.77 g, 6 mmol) are separately dissolved in
acetonitrile (60 ml). They are then added via a syringe pump (at a
rate of 1.2 ml/hour) to a suspension of anhydrous sodium carbonate
(53 g, 0.5 mmol) in acetonitrile (1380 ml). The temperature of the
reaction is maintained at 65.degree. C. throughout the total
reaction of 60 hours.
[0097] After cooling, the solvent is removed under reduced pressure
and the residue is dissolved in sodium hydroxide solution (200 ml,
4M). The product is then extracted with benzene (6 times 100 ml)
and the combined organic extracts are dried over anhydrous sodium
sulfate. After filtration the solvent is removed under reduced
pressure. The product is then dissolved in an
acetonitrile/triethylamine mixture (95:5) and is passed through a
column of neutral alumina (2.5.times.12 cm). Removal of the solvent
yields a white solid (0.93 g, 44%).
[0098] This product may be further purified by recrystallization
from an ethanol/diethylether mixture combined with cooling at
0.degree. C. overnight to yield a white crystalline solid.
[0099] Anal. Calcd. for C.sub.21H.sub.29N.sub.5: C, 71.75; H, 8.32;
N, 19.93. Found: C, 71.41; H, 8.00; N, 20.00. A mass spectrum
displays the expected molecular ion peak [for
C.sub.21H.sub.30N.sub.5].sup.+ at m/z=352. The .sup.1H NMR(400 MHz,
in CD.sub.3CN) spectrum exhibits peaks at .delta.=1.81 (m,4H); 2.19
(s, 3H); 2.56 (t, 4H); 3.52 (t,4H); 3.68 (AB, 4H), 4.13 (AB, 4H),
6.53 (d, 4H) and 7.07 (t, 2H). The .sup.13C NMR(75.6 MHz, in
CD.sub.3CN) spectrum shows eight peaks at .delta.=24.05, 58.52,
60.95, 62.94, 121.5, 137.44 and 159.33 ppm.
[0100] All metal complexation reactions are performed in an inert
atmosphere glovebox using distilled and degassed solvents.
[0101] (b) Complexation of the ligand L.sub.1 with bis(pyridine)
manganese (II) chloride
[0102] Bis(pyridine)manganese (II) chloride is synthesized
according to the literature procedure of H. T. Witteveen et al., J.
Inorg. Nucl. Chem., 1974, 36, 1535.
[0103] The ligand L.sub.1 (1.24 g, 3.5 mmol), triethylamine(0.35 g,
3.5 mmol) and sodium hexafluorophosphate (0.588 g, 3.5 mmol) are
dissolved in pyridine (12 ml). To this is added
bis(pyridine)manganese (II) chloride and the reaction is stirred
overnight. The reaction is then filtered to remove a white solid.
This solid is washed with acetonitrile until the washings are no
longer colored and then the combined organic filtrates are
evaporated under reduced pressure. The residue is dissolved in the
minimum amount of acetonitrile and allowed to evaporate overnight
to produce bright red crystals. Yield: 0.8 g (39%).
[0104] Anal. Calcd. for
C.sub.21H.sub.31N.sub.5Mn.sub.1Cl.sub.1P.sub.1F.su- b.6: C, 43.00;
H, 4.99 and N, 11.95. Found: C, 42.88; H, 4.80 and N 11.86. A mass
spectrum displays the expected molecular ion peak [for
C.sub.21H.sub.31N.sub.5Mn.sub.1Cl.sub.1] at m/z=441. The electronic
spectrum of a dilute solution in water exhibits two absorption
bands at 260 and 414 nm (.epsilon.=1.47.times.10.sup.3 and 773
M.sup.-1cm.sup.-1 respectively). The IR spectrum (KBr) of the
complex shows a band at 1600cm.sup.-1 (pyridine), and strong bands
at 840 and 558 cm.sup.-1 (PF.sub.6.sup.-).
[0105] (c) Complexation of the ligand with manganese (II)
trifluoromethanesulfonate
[0106] Manganese (II) trifluoromethanesulfonate is prepared by the
literature procedure of Bryan and Dabrowiak, Inorg. Chem., 1975,
14, 297.
[0107] Manganese (II) trifluoromethanesulfonate (0.883 g, 2.5 mmol)
is dissolved in acetonitrile (5 ml). This is added to a solution of
the ligand L.sub.1(0.878 g, 2.5 mmol) and triethylamine (0.25 g,
2.5 mmol) in acetonitrile (5 ml). This is then heated for two hours
before filtering and then after cooling removal of the solvent
under reduced pressure. The residue is dissolved in a minimum
amount of acetonitrile and left to evaporate slowly to yield orange
crystals. Yield 1.06 g (60%).
[0108] Anal. Calc. for
Mn.sub.1C.sub.23H.sub.29N.sub.5S.sub.2F.sub.6O.sub.- 6: C, 39.20;
H, 4.15 and N, 9.95. Found: C, 38.83; H, 4.35 and N, 10.10. The
mass spectrum displays the expected peak for
[Mn.sub.1C.sub.22H.sub.2- 9N.sub.5S.sub.1F.sub.3O.sub.3].sup.+ at
m/z=555. The electronic spectrum of a dilute solution in water
exhibits two absorption bands at 260 and 412 nm (.epsilon.=9733 and
607 M.sup.-1cm.sup.-1 respectively). The IR spectrum (KBr) of the
complex shows a band at 1600 cm.sup.-1 (pyridine) and 1260, 1160
and 1030cm.sup.-1(CF.sub.3SO.sub.3).
[0109] (d) Complexation of the ligand with iron (II)
trifluoromethanesulfonate
[0110] Iron (II) trifluoromethanesulfonate is prepared in situ by
the literature procedure Tait and Busch, Inorg. Synth., 1978,
XVIII, 7.
[0111] The ligand (0.833 g, 2.5 mmol) and triethylamine (0.505 g, 5
mmol) are dissolved in acetonitrile (5 ml). To this is added a
solution of hexakis(acetonitrile) iron (II)
trifluoromethanesulfonate (1.5 g, 2.5 mmol) in acetonitrile (5 ml)
to yield a dark red solution. Sodium thiocyanate (0.406 g, 5 mmol)
is then added and the reaction stirred for a further hour. The
solvent is then removed under reduced pressure and the resulting
solid is recrystallized from methanol to produce red microcrystals.
Yield: 0.65 g (50%).
[0112] Anal. Calc. for Fe.sub.1C.sub.23H.sub.29N.sub.7S.sub.2:C,
52.76; H, 5.59 and N, 18.74. Found: C 52.96; H, 5.53; N, 18.55. A
mass spectrum displays the expected molecular ion peak [for
Fe.sub.1C.sub.22H.sub.29N.s- ub.6S.sub.1].sup.+ at m/z=465. The
.sup.1H NMR (300 MHz, CD.sub.3CN) .delta.=1.70(AB,2H), 2.0 (AB,2H),
2.24 (s,3H), 2.39 (m,2H), 2.70 (m,4H), 3.68 (m,4H), 3.95 (m,4H),
4.2 (AB,2H), 7.09 (d,2H), 7.19 (d,2H), 7.52 (t,1H), 7.61 (d,1H).
The IR spectrum (KBr) of the spectrum shows peaks at 1608
cm.sup.-1(pyridine) and strong peaks at 2099 and
2037cm.sup.-1(SCN.sup.-).
[0113] The metal complexes can be used in detergents, for example
by adding about 0.05% of complex to a granular detergent containing
10% sodium perborate, to improve bleaching.
[0114] Purification of Catalyst
[0115] In general, the state of purity of the transition-metal
oxidation catalyst of Example 9 can vary, provided that any
impurities, such as byproducts of the synthesis, free ligand(s),
unreacted transition-metal salt precursors, colloidal organic or
inorganic particles, and the like, are not present in amounts which
substantially decrease the utility of the transition-metal
oxidation catalyst. It has been discovered to be desirable that the
transition-metal oxidation catalyst should be purified. This can be
done using any suitable means, such that the catalyst does not
excessively consume available oxygen (AvO). Excessive AvO
consumption is defined as including any instance of exponential
decrease in AvO levels of bleaching, oxidizing or catalyzing
solutions with time at 20-40.degree. C. Preferred transition-metal
oxidation catalysts, whether purified or not, when placed into
dilute aqueous buffered alkaline solution at a pH of about 9
(carbonate/bicarbonate buffer) at temperatures of about 40.degree.
C., have a relatively steady decrease in AvO levels with time; in
preferred cases, this rate of decrease is linear or approximately
linear. In the preferred embodiments, there is a rate of AvO
consumption at 40 deg C. given by a slope of a graph of % AvO vs.
time (in sec.) (hereinafter "AvO slope") of from about -0.0050 to
about -0.0500, more preferably -0.0100 to about -0.0200. Thus, a
preferred Mn(II) oxidation catalyst has an AvO slope of from about
-0.0140 to about -0.0182; in contrast, a somewhat less preferred
transition metal oxidation catalyst has an AvO slope of
-0.0286.
[0116] Preferred methods for determining AvO consumption in aqueous
solutions of transition metal oxidation catalysts herein include
the well-known iodometric method or its variants, such as methods
commonly applied for hydrogen peroxide. See, for example, Organic
Peroxides, Vol. 2., D. Swern (Ed.,), Wiley-Interscience, New York,
1971, for example the table at p. 585 and references therein
including P. D. Bartlett and R. Altscul, J. Amer. Chem. Soc., 67,
812 (1945) and W. E. Cass, J. Amer. Chem. Soc., 68, 1976 (1946).
Accelerators such as ammonium molybdate can be used. The general
procedure used herein is to prepare an aqueous solution of catalyst
and hydrogen peroxide in a mild alkaline buffer, for example
carbonate/bicarbonate at pH 9, and to monitor the consumption of
hydrogen peroxide by periodic removal of aliquots of the solution
which are "stopped" from further loss of hydrogen peroxide by
acidification using glacial acetic acid, preferably with chilling
(ice). These aliquots can then be analyzed by reaction with
potassium iodide, optionally but sometimes preferably using
ammonium molybdate (especially low-impurity molybdate, see for
example U.S. Pat. No. 4,596,701) to accelerate complete reaction,
followed by back-titratation using sodium thiosulfate. Other
variations of analytical procedure can be used, such as
thermometric procedures, potential buffer methods (Ishibashi et
al., Anal. Chim. Acta (1992), 261(1-2), 405-10) or photometric
procedures for determination of hydrogen peroxide (EP 485,000 A2,
May 13, 1992). Variations of methods permitting fractional
determinations, for example of peracetic acid and hydrogen
peroxide, in presence or absence of the instant transition-metal
oxidation catalysts are also useful; see, for example JP 92-303215,
Oct. 16, 1992.
[0117] In another embodiment of the present invention, there are
encompassed laundry and cleaning compositions incorporating
transition-metal oxidation catalysts which have been purified to
the extent of having a differential AvO loss reduction, relative to
the untreated catalyst, of at least about 10% (units here are
dimensionless since they represent the ratio of the AvO slope of
the treated transition-metal oxidation catalyst over the AvO slope
for the untreated transition metal oxidation catalyst--effectively
a ratio of AvO's). In other terms, the AvO slope is improved by
purification so as to bring it into the above-identified preferred
ranges.
[0118] In yet another embodiment of the instant invention, two
processes have been identified which are particularly effective in
improving the suitability of transition-metal oxidation catalysts,
as synthesized, for incorporation into laundry and cleaning
products or for other useful oxidation catalysis applications.
[0119] One such process is any process having a step of treating
the transition-metal oxidation catalyst, as prepared, by extracting
the transition-metal oxidation catalyst, in solid form, with an
aromatic hydrocarbon solvent; suitable solvents are
oxidation-stable under conditions of use and include benzene and
toluene, preferably toluene. Surprisingly, toluene extraction can
measurably improve the AvO slope (see disclosure hereinabove).
[0120] Another process which can be used to improve the AvO slope
of the transition metal oxidation catalyst is to filter a solution
thereof using any suitable filtration means for removing small or
colloidal particles. Such means include the use of fine-pore
filters; centrifugation; or coagulation of the colloidal
solids.
[0121] In more detail, a full procedure for purifying a
transition-metal oxidation catalyst herein can include:
[0122] (a) dissolving the transition-metal oxidation catalyst, as
prepared, in hot acetonitrile;
[0123] (b) filtering the resulting solution hot, e.g., at about
70.degree. C., through glass microfibers (for example glass
microfiber filter paper available from Whatman);
[0124] (c) if desired, filtering the solution of the first
filtration through a 0.2 micron membrane, (for example, a 0.2
micron filter commercially available from Millipore), or
centrifuging, whereby colloidal particles are removed;
[0125] (d) evaporating the solution of the second filtration to
dryness;
[0126] (e) washing the solids of step (d) with toluene, for example
five times using toluene in an amount which is double the volume of
the oxidation catalyst solids;
[0127] (f) drying the product of step (e).
[0128] Another procedure which can be used, in any convenient
combination with aromatic solvent washes and/or removal of fine
particles is recrystallization. Recrystallization, for example of
Mn(II) Bcyclam chloride transition-metal oxidation catalyst, can be
done from hot acetonitrile. Recrystallization can have its
disadvantages, for example it may on occasion be more costly.
* * * * *