Quarternary polycyclic polyammonium salts and process for...

Details Quarternary polycyclic polyammonium salts and process for... Quarternary polycyclic polyammonium salts and process for...

1999-03-04

2001-06-26

Rotman, Alan L. (Department: 1625)

Organic compounds -- part of the class 532-570 series

Organic compounds

Unsubstituted hydrocarbyl chain between the ring and the -c-...

C544S343000

Reexamination Certificate

active

06252066

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to specific quaternary polycyclic polyammonium salts having a basic structure of the general formula (1)
in which k, l, m and n independently of one another are numbers from 2 to 4 and R
1
and R
2
independently of one another are a substituted or unsubstituted alkyl, cycloalkyl or aryl radical and X and Y are an anion. These compounds serve as starting materials for the preparation of cyclic or bridged polyamine compounds; e.g. for syntheses of pharmacologically active substances, of ligands for catalytically active metal complexes, of host compounds for supramolecular structures and of proton sponges; moreover, these compounds often have unusual redox properties.
DESCRIPTION OF THE RELATED ART
Thus G. Weisman, M. Rogers, E. Wong, J. Jasinksi and E. Paight in J. Am. Chem. Soc. 112 (1990), 8605-8605 describe the preparation of the bridged ligand II by reduction of cis-4,11-dimethyl-4,7,11,14-tetraazaperhydro-pyrenium diiodide (I) by means of sodium borohydride.
II complexes Li
+
ions with unusually high selectivity and proves to be a proton sponge having unusual properties.
In the literature, only a few examples of quaternary polycyclic polyammonium salts having a basic structure of the general formula (1) are known, diiodides and dibromides being described exclusively.
These known diiodides and dibromides, however, are as a rule unsuitable for handling on the industrial scale. In addition to ecological aspects, it is especially disadvantageous that in many reactions (oxidations and reductions) of ammonium salts the presence of halide ions such as iodide or bromide proves to be troublesome; the result is often unsatisfactory yields and the formation of undesirable by-products.
This invention is thus based on the object of finding quaternary polycyclic polyammonium salts having a basic structure of the general formula (1) which can be handled on the industrial scale.
Surprisingly, it has been found that quaternary polycyclic polyammonium salts having a basic structure of the general formula (1) as the methylsulfate or sulfate salt are not afflicted with these disadvantages, and that these compounds can moreover be employed with excellent yield in subsequent reactions, especially reductions with sodium borohydride.
In the literature, only a few methods for the preparation of quatenary polycyclic polyammonium salts having a basic structure of the general formula (1) are described, these were also only worked out for the synthesis of small amounts for scientific purposes.
The reaction of cis-perhydro-3a,5a,8a,10a-tetraazapyrene with 15 equivalents of methyl iodide in acetonitrile was described by G. Weisman, M. Rogers, E. Wong, J. Jasinksi and E. Paight in J. Am. Chem. Soc. 112 (1990), 8604-8605; after a reaction time of 72 hours cis-3a,8a-dimethyl-5a,10a-diaza-3a,8a-diazoniaperhydropyrenium diiodide is obtained here in 80% yield.
In addition to the use of the toxic acetonitrile as a solvent, the long reaction time of 72 hours is problematical, despite the use of a several-fold excess of the alkylating agent methyl iodide.
The corresponding diquaternization of the trans isomer was reported by T. Okawara, H. Takaishi, Y. Okamoto, T. Yamasaki and M. Furukawa in Heterocycles 41 (1995), 1023-1033. After treatment of trans-perhydro3a,5a,8a,10a-tetraazapyrene with 10 equivalents of methyl iodide in chloroform as a solvent at 60° C. in a bomb tube for 12 hours, trans-3a,8a-dimethyl-5a,10a-diaza-3a,8a-diazoniaperhydropyrenium diiodide is obtained in a yield of 67%. Here too, the period of 12 hours necessary for the reaction is not satisfactory when using a five-fold excess of alkylating agent and a reaction temperature of 60° C.
A number of diquaternizations with benzyl bromide as an alkylating agent were investigated by G. Weisman, E. Wong, D. Hill, M. Rogers, D. Reed and J. Calabrese in Chem. Commun. 1996, 947-948. Accordingly, the reaction of cis-perhydro-3a,5a,8a,10a-tetraazaopyrene with excess benzyl bromide in acetonitrile at room temperature affords cis-3a,8a-dibenzyl-5a,10a-diaza-3a,8a-diazoniaperhydropyrenium dibromide in 78-99% yield after a reaction time of 3 to 21 days.
These known processes for the preparation of the desired quaternary polycyclic polyammonium salts having a basic structure of the general formula (1) have a number of disadvantages: the yields achievable are in some cases only 67%, toxic acetonitrile or chloroform is employed as a solvent, and, with regard to environmental protection, questionable organic bromine and iodine compounds are employed as alkylating agents. A large excess of these reagents is moreover used, which makes the isolation of the desired products difficult. Consistently long reaction times of 12 hours at 60° C. up to 21 days at room temperature are moreover necessary, so that these methods are unsuitable for the preparation of industrial amounts of these quaternary polycyclic polyammonium salts.
SUMMARY OF THE INVENTION
This invention is therefore additionally based on the object of finding a simple process for the synthesis of quaternary polycyclic polyammonium salts having a basic structure of the general formula (1). In addition, the process according to the invention should be suitable for the preparation of industrial amounts and should avoid solvents which are questionable from the toxicological point of view; the resulting products should moreover be obtained in high yield with minimum amounts of waste.
Surprisingly, it has been found that when not organic bromine or iodine compounds, but other substances suitable for the transfer of alkyl groups, in particular dialkyl sulfates and esters of organic sulfonic acids, are used as alkylating agents, extremely short reaction times are sufficient for the synthesis of quaternary polycyclic polyammonium salts having a basic structure of the general formula (1).
The invention relates to quaternary polycyclic polyammonium salts of the general formula (2)
in which
A
1
, A
2
, A
3
and A
4
independently of one another are either
a C
2
- to C
4
-alkylene radical which can be substituted by one or more groups P and/or Q, where
P is a C
1
- to a C
30
-alkyl or cycloalkyl group which can be substituted by one or more groups Q, and
Q is a group COR, in which R is a hydroxyl group, a C
1
- to C
5
-alkoxy group or C
6
- to C
14
-aryloxy group or a substituted or unsubstituted amino group,
a C
6
- to C
14
-aryl group which can be substituted by one or more C
1
- to C
30
-alkyl, cycloalkyl or aryl groups, C
1
- to C
5
-alkoxy or C
6
- to C
14
-aryloxy groups, substituted or unsubstituted amino groups, halogen atoms, cyano groups, sulfo groups, carboxyl groups or
groups of the formula —(CH
2
)
r
—COOH, —(CH
2
)
r
—SO
3
H, —(CH
2
)
r
—PO
3
H
2
, —(CH
2
)
r
OH, where r is an integer from 0 to 4 and the acid groups mentioned can also be present in salt form,
an aromatic heterocycle which contains nitrogen, oxygen and/or sulfur atoms and can be substituted by one or more C
1
- to C
30
-alkyl, cycloalkyl or aryl groups, C
1
- to C
5
-alkoxy groups or C
6
- to C
14
-aryloxy groups, substituted or unsubstituted amino groups, halogen atoms, cyano groups, sulfo groups, carboxyl groups or groups of the formula —(CH
2
)
r
—COOH, —(CH
2
)
r
—SO
3
H, —(CH
2
)
r
—PO
3
H
2
, —(CH
2
)
r
OH, where r is an integer from 0 to 4 and the acid groups mentioned can also be present in salt form,
a substituted or unsubstituted amino group,
a hydroxyl group,
a C
1
- to C
30
-alkyl or cycloalkyl group,
a C
1
- to C
30
-alkoxy or C
6
- to C
14
-aryloxy group,
a halogen atom,
a cyano, sulfo or carboxyl group,
a group of the formula —(CH
2
)
r
—COOH, —(CH
2
)
r
—SO
3
H, —(CH
2
)
r
—PO
3
H
2
, —(CH
2
)
r
OH, where r is an integer from 0 to 4 and the acid groups mentioned can also be present in salt form;
or A
1
, A
2
, A
3
and A
4
are a group —(CH
2
)
s
—E—(CH
2
)
t
—, in which E is a C
6
- to C
14
-arylene radical which can be substituted by groups P and/or Q, where the groups P and Q have the abovementioned meaning and s and t independently of one another can assume the value

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