DE2701372A1 - Prepn. of cyclic amidine cpd. used as pharmaceutical intermediate - from carboxylate ester cpd. and di:amine cpd. without using catalyst - Google Patents

Abstract

Prepn. of cyclic amidines of formula (I): (where x = 0 or 1; each R is H alkyl, cycloalkyl, aryl or aralkyl, or 2 R groups can form an alkylene chain) comprises reacting an ester RCOOR' (where R' is alkyl, aralkyl, aryl or cycloalkyl) with a diamine H2N-CHR-(CHR)x-CHR-NHR at 120-250 degrees C. (I) are useful as textile auxiliaries, epoxy resin hardeners, catalysts for polyurethane foams, surfactants, antistatic agents, corrosion inhibitors, fungicides, bactericides, additives for foodstuffs and perfumes, and pharmaceutical intermediates. The process gives good yields (e.g. 54-92%) without the use of catalysts.

Description

Process for the preparation of cyclic amidines

In the literature there are various synthesis options for the preparation cyclic amidines described. So starting from 1,2-alkylenediamines and certain carbonyl compounds, as well as esters, at 320 - 650 ° C in the presence imidazoles optionally substituted by Cu - and / or Cr - containing catalysts produce. Furthermore, the production of imidazolines is described, which from Carboxylic acid esters and 1,2-diamines under the influence of acidic catalysts from Type of ion exchanger can be produced at 25 - 115 OC. The usage of ion exchange resins for this condensation, however, possesses a number of Disadvantages that an economic implementation in a technical process does not enable.

The task was therefore to develop a technical, if possible catalyst-free process for the production of cyclic amidines, such as tmidazole nen and tetrahydropyrimidines.

It has now been found, surprisingly, that cyclic amidines can also be produced industrially from such starting materials without catalysts if the process for the production of cyclic amidines of the general formula is used in which x 0 or 1 and R is an identical or different radical from the group consisting of hydrogen, alkyl, cycloalkyl, aryl or aralkyl and 2 R can also jointly be part of an alkylene chain, so that carboxylic acid esters of the general formula in which R has the above meaning and R 'can be an alkyl, aralkyl, aryl or cycloalkyl radical, with alkylenediamines of the general formula where x and R likewise have the above meaning at temperatures in the range from 120-250.degree. C., preferably 150-210.degree.

Suitable carboxylic acid esters of the general formula above leave from aliphatic, cycloaliphatic, aromatic and araliphatic monocarboxylic acids derive.

In the case of an alkyl radical, the radicals R and R 'can mean -alkyl radicals, such as methyl, ethyl, n- and i-propyl, n-, i- and tert-butyl, pentyl and hexyl. It however, higher alkyl radicals are also possible. In the case of an aryl radical, such with 6-10 carbon atoms can be used, such as phenyl, tolyl, xylyl and similar aralkyl have the meaning benzyl, 2-phenylethyl or the like. However, this owns Listed only by way of example.

Alkylenediamines which have primary and / or secondary amino groups in the 1,2- or 1,3-position are suitable for the reaction according to the present invention. Diamines of the type that can be used can be identified by the general formula describe in which x and R have previously described meaning. The alkyl radical can be a methyl, ethyl, butyl radical or the like. Suitable aryl radicals are: phenyl, tolyl, xylyl and the like. The aralkyl radical can have 7 or more carbon atoms. 2 R can also together be part of an alkylene chain and form a cycloaliphatic ring.

Particularly suitable diamines are: ethylenediamine, 1,2-diaminopropane, 1,2 or 2,3-diaminobutane, 1,2-diaminopentane, 1,2-diaminohexane, 1,2-diaminoheptane, 1,2-diaminooctane, 1,2-diaminononane, 1,2-diaminodecane; 2-cyclohexyl-, 2-cyclopentyl-, 2-benzyl-, 2-phenyl-, o-methoxyphenyl-, m-methoxyphenylp-methoxyphenyl-, 2,5-dimethylphenyl-, 2,6-dimethylphenyl-, 2,4-dimethylphenyl-, 2,3-dimethylphenyl-, 2-o-toluyl-, 2-m-toluyl-, 2-p-toluyl-, 2-o-ethylphenyl-, 2-m-ethylphenyl-, 2-p-ethylphenyl-1,2-ethylenediamine; 1,2-diphenylethylenediamine, 1,2-diamino-1-xylylpropane, 1-phenylpentylenediamine - 2,3, 1-phenylpentylenediamine-3, 4,1 -phenylnonylenediamine-3, 4; N-methylethylenediamine; N-cyclohexyl-, N-cyclopentyl-, N-benzyl-, N-phenyl-, N-o-methoxyphenyl-, N-m-methoxyphenyl-, N-p-methoxyphenyl-, N-2, 5-dimethylphenyl- N-2 N-2,6-dimethylphenyl-, N-2,4-dimethylphenyl-, N-2,3-dimethylphenyl-, N-o-toluyl-, N-m-toluyl-, N-p-toluyl-, N-o-ethylphenyl-, N-m-ethylphenyl-, N-p-ethylphenyl-1,2-ethylenediamine; N, 2-dicyclohexyl-, N, 2-dicyclopentyl-, N, 2-dibenzyl-, N, 2-diphenyl-, N, N, 2-di- (o-methoxyphenyl) -, N, 2-di- (m-methoxyphenyl) -, N, 2-di- (p-methoxyphenyl) -, N, 2-di- (2,5-dimethylphenyl) -, N, 2-di- (2,6-dimethylphenyl) -, N, 2-di- (2,4-dimethylphenyl) -, N, 2-di- (2,3-dimethylphenyl) -, N, 2-di- (o-toluyl) -, N, 2-di- (m-toluyl) -, N, 2- (p-toluyl) -, N, 2-di- (o-ethylphenyl) -, N, 2-di- (m-ethylphenyl) -, N, 2-di (p-ethylphenyl) -1,2-ethylenediamine or the like with adjacent amino groups, 1,3-diaminopropane, 1-amino-2-aminomethyl-3,3,5-trimethylcyclopentane, 1-amino-2-aminomethyl-3,5,5-trimethylcyclopentane or the like with amino groups separated by a further carbon atom.

The starting materials, the diamine and the carboxylic acid ester can be used in equimolar amounts are used. However, it has proven to be advantageous to use an excess of diamine. The most preferred range is one Diamine / ester ratio in the range of 3 - 6: 1. The use of a larger one A surplus is possible, but not advisable for economic reasons.

The reaction can normally use the above special solvent addition take place. When using solvents as the reaction medium, preference is given to those which are inert under the reaction conditions and also as an entrainer for removal of the resulting water of reaction can be used, e.g. higher-boiling aromatics, such as toluene, xylene, etc., and higher-boiling alcohols, such as pentanols, hexanols, etc.

The reaction of the diamines with the carboxylic acid ester can be both at Normal pressure or elevated pressure can be carried out, taking under elevated pressure this is understood to be up to 20 atm. The increased pressure is in most Cases of the intrinsic pressure of the system, which is the sum of the pressures of the output products and the end products (desired product + split off alcohol or phenol and Water). The application of pressure is particularly necessary when the Starting products are gaseous at the reaction temperatures.

When working under normal pressure, the sequence brings the Adding the starting materials has certain advantages, i.e. if the carboxylic acid ester is added to the Diamine is added. This sequence determines the proportion of the diacylation product of the diamine on the total acylation product is reduced. The monoacylation product is Intermediate product of the reaction, which then forms the cyclic with elimination of water Amidines condensed.

The diacylation can also be in the presence of a large Convert excess diamine into the cyclic amidine.

The method described above also has opposite Those processes for the preparation of imidazolines from 1,2-diamines and nitriles Advantage that substances (esters) can be used that do not have the toxicity of nitriles and that no cleavage product such as ammonia occurs. The procedure according to the present invention is therefore also more environmentally friendly, in addition, works it is catalyst-free and is characterized by its high reaction speed.

The imidazolines and tetrahydropyrimidines which can be prepared according to the invention and other cyclic amidines are used as textile coating auxiliaries, Epoxy resin hardeners, catalysts for polyurethane foams, surfactants, antistatic agents, anti-corrosive agents, fungicides, bactericides, additives for Food and fragrances and as intermediates in the manufacture of medicines.

The method according to the present invention is carried out by the following Examples illustrated: Example 1: 90 g of ethylenediamine were mixed with 120 g of methyl benzoate (Molar ratio 1.7: 1) mixed, slowly heated to reflux (approx. 120 ° C.) and refluxed for 4 h. Then the excess ethylenediamine separated off via a Vigreux column and the 2-phenylimidazoline formed in vacuo distilled off at 1 torr. The product passed over at a head temperature of 152.degree. The yield of 2-phenyl-imidazoline was 69 g = 54% of theory. Th. Based on ester.

Example 2: Ethylenediamine and methyl benzoate were in the molar ratio 4: 1 implemented together. The ester became boiling in 1 hour Diamine was added dropwise at 120 ° C. and the reaction mixture was refluxed for 4 h. After the excess alkylenediamine had been separated off, the 2-phenylimidazoline could be obtained Isolate in a yield of 69 days. The ethylene diamine can be recycled.

Example 3: 360 g of ethylenediamine were mixed with 480 g of methyl benzoate (Ratio 1.7: 1) stirred in a pressure reactor at 190 ° C. for 2.5 h. After completion The reaction was first of all the excess diamine distilled off via a column; then 2-phenylidazoline was allowed to dissolve in a vacuum at 152 ° C./1 Torr in 65 Separate% yield by distillation (344 g = 65 C 'of theory.

based on ester).

Example 4: Ethylenediamine and methyl benzoate were used oil ratio 4.5: 1 reacted with one another at 190 ° C under pressure for 2 h, so the 2-phenylimidazoline could be separated by distillation in a 92% yield; M.p. 98 ° C.

The ethylenediamine can be recycled.

Example 5: 312 g of an isomer mixture of 1-amino-2-aminomethyl-3,3,5-trimethylcyclopentane and 1-amino-2-aminomethyl-3,5,5-trimethylcyclopentane were mixed with 136 g of methyl benzoate, with stirring in one The reactor was heated to 190 ° C. and held at this temperature for 2 h. When the excess diamine had been distilled off, an isomer mixture of amidines containing compounds of the formula below could be isolated at 2 torr and 168 ° C. Yield: 212 g = 87%, based on ester.

They can be called 2,4-Diaza -3-phenyl-7,9,9-trimethyl-bicyclo-L4.3.01 -nonen (2) or 2,4-diaza-3-phenyl-7,7'9-trimethyl bicyclo [4.3.0] -nonen (2) will.

The product is viscous and viscous at room temperature. The Ill spectrum of the product obtained is shown in Appendix 1.

The C.lI.N analysis gave the following values:% C 79.13; theor. 79.34% H. 9.30; 9.09% N 11.75; 11.57 Example 6: 185 g of 1,3-dianlinopropane were added with 136 g of methyl benzoate reacted under pressure at 200 ° C. in the reactor. After 3 hours, the excess diamine was distilled off and the 2-phenyltetrahydropyrimidine isolated in 79% yield; Bp 165 ° C / 1 mm mp = 86-87 ° C.

Example 7: Methyl benzoate and 1,2-diaminopropane were im Ratio 1: 4 blurred together and 4 h at 195 ° C. under pressure for reaction brought. After separating off the excess, the 2-phenyl-4-methyl - imidazoline could be Isolate in a yield of 82% (mp = 69-71 ° C.; bp = 129 ° C./1 mm) Example 8: ethyl acetate and ethylenediamine were in a molar ratio of 1: 4 under pressure implemented at 170 0C. After 3 hours, the unreacted ethylenediamine was separated off and the 2-methylimidazoline is distilled over a Vigreux column at 110 ° C and 2 Torr. The yield was 83% of theory. Th. Based on ester.

The unreacted diamine can be recycled.

Example 9: Ethyl propionate and 1,2-diaminopropane in a molar ratio 1: 2 could be converted into the corresponding 2-ethyl-4-methyl within 3 h at 190 ° C h2, implement imidazoline. Yield 79%; Boiling point 121 ° C / 50 mm.

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Claims (4)

Claims: 1 5 process for the preparation of cyclic amidines of the general formula where x is 0 or 1 and R is an identical or different radical from the group consisting of hydrogen, alkyl, cycloalkyl, aryl or aralkyl, characterized in that one carboxylic acid ester of the general formula in which R has the above meaning and R 'is an alkyl, aralkyl, aryl or cycloalkyl radical, with alkylenediamines of the general formula where x and R have the above meaning and 2 R are also jointly part of an alkylene chain, at temperatures in the range from 120-250 ° C. 2. The method according to claim 1, d a d u r c h g e k e n n -z e i c h n e t that the reaction is carried out at elevated pressure. 2 = method according to claim 2, d u r c h g e n n n z e i c h n e t that the increased pressure is up to 20 atmospheres. 4. Reaction product from the isomer mixture of 1-amino-2-aminomethyl-3,3,5-trimethylcyc] opentane and 1-amino-2-aminomethyl-3,5,5-trimethylcyclopentane and methyl benzoate obtained by reaction at a temperature in the range of 120-250 ° C.