DE2711956A1 - Unsatd. carbodiimide cpds. used in prepn. of pharmaceuticals - prepd. by reacting isothiocyanate cpds. with amine(s) and desulphurising resulting thiourea - Google Patents

Abstract

New unsatd. carbodiimides are of formula R1-N=C=N-R2 (I) (where R1 and R2 and each an opt. unsatd. (cyclo)aliphatic residue, either of which may contain a hetero atom, provided that >=1 or R1 and R2 is an olefinically unsatd. aliphatic residue). (I) are useful as intermediates for plastics and pharmaceuticals. They undergo the usual addition reactions of carbodiimides (e.g. qith water to give ureas, with alcohols or phenols to give trisubstd. isoureas, with H2S to give thioureas, with acids to give N-acyl-ureas, or with malonic acid to give barbituric acid derivs), the addition prod. carrying >=1 unsatd. residue. (I) may also be (co)polymerised via the olefinic unsaturation. Specific (I) include N-methallyl-N'-tert-butyl-carbodiimide. In an example, this is prepd. by reacting methallyl isothiocyanate with tert-butylamine in petroleum ether and desulphurising the resulting N-methallyl-N'-tertbuytyl-thiourea with a soln. of Cl2 in aq. NaOH.

Description

Unsaturated carbodiimides

The invention relates to carbodiimides which have at least one unsaturated Rest have the general formula R1-N = C = N-R2 in which R1 and R2 are the same or can be different, a linear or branched aliphatic, saturated or unsaturated radical or cycloaliphatic radical, optionally also heteroatom may contain, represent, where at least one of these radicals is an aliphatic, represents olefinically unsaturated radical.

The radicals R1 and R2 preferably represent radicals with up to 12 carbon atoms represent, very particularly preferably those with up to 6 carbon atoms. Among the preferred any heteroatoms which may be present, particularly nitrogen should be emphasized.

Preferred unsaturated radicals are the allyl and methallyl radicals.

Examples of such carbodiimides are: The unsaturated carbodiimides of the general formula given above are prepared either by reacting an unsaturated aliphatic mustard oil with a saturated amine or by reacting an unsaturated aliphatic amine with a saturated mustard oil or by reacting an unsaturated aliphatic amine with an unsaturated aliphatic mustard oil in an inert solvent Temperatures from 0OC to 1000C and subsequent desulfurization in a manner known per se, for example with the aid of a hypochlorite solution and / or mercury oxide.

This method is a further subject of this invention.

The intermediate thioureas are produced by reacting the amines with the mustard oil, the latter being obtained by treating the corresponding crude danide derivatives with, for example, zinc chloride. (E. Schmidt, W. Striewsky, M. Seefelder, F. Hitzler, Ann. 568, 192 (1950)), e.g. The mustard oil thus obtained is reacted with the amine in an inert solvent, preferably petroleum ether, at temperatures between + 50 ° C. and 50 ° C., preferably at room temperature. If you want to produce carbodiimides with a single unsaturated radical, it has been found that it does not matter whether you start from an unsaturated amine or from an unsaturated mustard oil. That is, one can react an unsaturated amine with a saturated mustard oil or an unsaturated mustard oil with a saturated amine. It is of course also possible to produce a carbodiimide from an unsaturated amine and an unsaturated mustard oil, which carbodiimide then has two identical or different unsaturated radicals. It was surprising that the formation of the carbodiimides of the general formula given above proceeds smoothly and with good yield and that side reactions do not occur.

The following unsaturated mustard oils are preferably: Methallyl mustard oil, Allyl mustard oil. Allylamine is preferably used as the unsaturated amine. Suitable Saturated mustard oils are e.g .: tert-butyl mustard oil, butyl mustard oil, acetyl mustard oil, cyclohexyl mustard oil. Examples of saturated amines are: butylamine, propylamine, octylamine, Tert-butylamine, 3- (dimethylamino) propylamine, 3- (diethylamino) propylamine, cyclohexylamine, 4- (dimethylamino) cyclohexylamine, 4- (diethylamino) cyclohexylamine, 2- (dimethylamino) ethylamine.

For desulfurization of the thioureas obtained in a known manner For example, yellow mercury oxide is used.

You work in inert solvents, such as petroleum ether or Benzene at temperatures up to 1000C. After cooling, it is filtered off. The desired Compound is initially produced as a crude product by distilling off the solvent isolated, then purified e.g. by distillation. The unsaturated carbodiimides are obtained in high yields, 70 to 90% as colorless liquids or as oils.

Those taken up in inert solvents, preferably methylene chloride Thioureas can also use an aqueous one by another procedure Sodium hypochlorite solution. Here you work at temperatures between OOC and + 200C, preferably + 50C and 100C. After distilling off of The desired compound remains in the organic solvent. The desulfurization the thioureas is preferably carried out by the latter method.

With the new carbodiimides, the known inclusion reactions can be carried out to the double bond system of the carbodiimide grouping, e.g. with Water, urea, isoureas trisubstituted with alcohols and phenols, with Hydrogen sulfide thioureas, with acids, e.g. acetic acid, N-acylureas arise which, depending on the starting substance, carry at least one unsaturated residue. The conversion of these carbodiimides with malonic acid leads to barbituric acid derivatives, which have at least one unsaturated radical. About the olefinically unsaturated Group, the carbodiimides of the present invention can be (co) polymerized.

Unsaturated carbodiimides of the formula given are therefore new intermediates for the manufacture of plastics and pharmaceuticals.

In the examples below, parts by weight are related to parts by volume how grams to milliliters, unless otherwise noted.

Example 1 a) Metal mustard oil In 2000 parts by volume of water were 1415 Parts by weight of ammonium thiocyanate and 358 parts by weight of zinc chloride are submitted. One left in 1484 Parts by weight of methallyl chloride mixed with 450 parts by volume of water are added dropwise. It was stirred at room temperature for 7 hours. In the separating funnel was the aqueous Phase separated, the mustard oil was extracted three times with water. After drying The methallyl mustard oil was distilled over calcium chloride.

Yield: 1445 parts by weight (78%) boiling point: 65 ° c / 100 - Analysis: C H N S %%%% Calc .: 53.0 6.1 12.3 28.3 found: 52.2 6.2 12.2 28.3 28.1 b) M-> sethallyl-S -Tert. N-Methallyl-N'-tert-butyl-thiourea There were 226 parts by weight of methallyl mustard oil submitted in 500 parts by volume of petroleum ether. 146 parts by weight were left at 5 to 10 ° C Add tert-butylanine in 300 parts by volume of petroleum ether. The mixture was subsequently stirred for 2 hours. After separation in a separating funnel, the residues of petroleum ether were removed by distillation deducted.

Yield: 350 Gev. -Parts (94%) Analysis: C H N S%%%% Calc .: 58.1 9.6 15.1 17.2 Found: 57.9 9.4 14.9 17.5 c) N-methallyl-N'-tert-butyl-carbodiimide At 0 ° C., 142 parts by weight of chlorine were dissolved in a solution of 240 parts by weight of sodium hydroxide introduced in 2000 parts by volume of water. This solution was left with stirring at OOC a solution of 93 parts by weight of the thiourea prepared according to b) in 300 parts by volume Add methylene chloride dropwise within 2 to 3 hours. It was then bend Stirred at 100 ° C. for 3 hours. The methylene chloride layer was then separated, the aqueous phase was extracted three times with 100 parts by volume of methylene chloride each time and the combined methylene chloride extracts dried over magnesium sulfate. Under Adding 10 parts by weight of dried yellow mercury oxide became the carbodiimide distilled into a template cooled with ice.

Yield: 67 parts by weight (88%) boiling point: 67 ° C / 12 mm analysis C H N%% % Calc .: 71.0 10.5 18.4 found: 70.9 10.6 18.6 Example 2 a) Tert-butyl mustard oil 1550 Parts by weight of tert-butylrhodanide were in the presence for 10 hours at room temperature stirred by 47 parts by weight of zinc chloride. It was then distilled in vacuo.

Yield: 1040 parts by weight (70%) boiling point: 40 to 450 ° C./18 mm Analysis: C H N S%%%% Calc .: 52.2 7.8 12.2 27.8 Found: 52.3 8.1 12.3 27.5 52.1 8.2 12.2 27.7 b) N-tert-butyl-N'-allylthiourea 230 parts by weight of tert-butyl mustard oil were added in 500 parts by volume of petroleum ether. At 5 to 100 ° C., 114 parts by weight were allylamine added dropwise. The mixture was left at this temperature for 2 hours, then for 5 hours at room temperature stir. The layers were separated. After concentration in vacuo, the thiourea became obtained as a colorless liquid.

Yield: 310 parts by weight (90 96) Analysis: C H N S%% 8% calc .: 55.7 9.3 16.2 18.6 Found: 55.4 9.0 16.1 18.2 55.4 9.2 16.0 18.4 c) N-tert -butyl-N'-allylcarbodiimide In a solution of 240 parts by weight of sodium hydroxide in 2000 parts by volume of water were initiated at OOC 142 parts by weight of chlorine. At OOC, a solution of 172 parts by weight was found of the thiourea prepared according to b) was added dropwise to 500 parts by volume of methylene chloride. The mixture was subsequently stirred at 100 ° C. for 3 hours. The two layers were in the separatory funnel separated, the aqueous phase was three times with 200 parts by volume of methylene chloride shaken out. The methylene chloride phases were combined and dried over calcium chloride dried.

After the solvent had been distilled off, the desired one was obtained Compound as a colorless liquid. Yield: 120 parts by weight (87%) Analysis: C H N%%% Calc .: 69.6 10.1 20.3 Found: 69.7 10.3 20.6 69.3 20.3 Example 3 a) N-Methallyl-N'-Allylthiourea 639 parts by weight of the methallyl mustard oil prepared according to Example 1 a) were in 1500 Parts by volume of petroleum ether submitted. A solution of 320 parts by weight of allylamine in 500 parts by volume of petroleum ether were added dropwise at 5-10 ° C.

The reaction is exothermic. It was left at 100 ° C. for 2 hours, then stir for another 2 hours at room temperature.

It was filtered off with suction and dried.

Yield: 895 parts by weight (93%) boiling point: 44-45 ° C.

Analysis: C H N S%%%% Calc .: 56.4 8.2 16.5 18.9 Found: 55.9 8.1 16.3 18.4 56.3 16.2 18.7 b) N-Methallyl-N-Allylcarbodiimide In a solution of 240 Parts by weight of sodium hydroxide in 2000 parts by volume of water became 140 parts by weight of chlorine initiated at OOC. At this temperature a solution of 340 Parts by weight of the thiourea prepared according to a) in 500 parts by volume of methylene chloride added dropwise. The mixture was subsequently stirred at 100 ° C. for 3 hours. The layers were in a separatory funnel severed. The aqueous phase was extracted three times with methylene chloride, the methylene chloride phases were combined and then over calcium chloride dried. After adding 10 g of mercury oxide, the solvent was distilled off; the carbodiimide was obtained as a residue.

Yield: 240 parts by weight (87%) Analysis: C H N%%% calc .: 70.6 8.8 20.6 Found: 70.4 8.9 20.4 70.2 8.6 20.5 Example 4 a) Allyl mustard oil 1320 parts by weight Allylihodanide was left in the presence of 500 parts by weight of zinc chloride for 24 hours stir at room temperature. This was followed by a water pump vacuum in an ice-cooled Original distilled off.

Yield: 1202 parts by weight (91%) boiling point: 500C / 15 mm b) N-allyl-N-allylthiourea At 5-100 ° C., a solution of 342 parts by weight of allylamine in 500 parts by volume was left Petroleum ether in a solution of 601 parts by weight of the allyl mustard oil prepared according to a) in 1500 vol. Add parts of petroleum ether. The reaction is exothermic.

It was left at 100 ° C. for 2 hours, then for 5 hours Stir at room temperature. After separating the layers in a separating funnel, the Remainder of petroleum ether stripped off in vacuo, the thiourea was in one yield of 850 parts by weight (85%) obtained.

Analysis: C H N S%%%% calc .: 53.7 7.7 17.9 20.5 found: 53.7 8.2 17.9 20.7 53.9 20.7 c) N-allyl-N'-allylcarbodiimide in a solution of 240 parts by weight Sodium hydroxide in 2000 parts by volume of water, 141 parts by weight of chlorine were passed in at OOC. A solution of 312 parts by weight of that prepared according to b) was left at this temperature Add dropwise thiourea in 500 parts by volume of methylene chloride. After stirring for 3 hours at 10 ° C the layers were separated. The aqueous phase was washed three times with methylene chloride shaken out; the methylene phases were combined and dried over calcium chloride. The mixture was then distilled with the addition of 10 parts by weight of mercury oxide.

Yield: 210 parts by weight (84.5%) boiling point: 56 ° C./10 mm Analysis: C, H N %%% Calc .: 68.9 8.2 22.9 found: 68.5 8.3 22.4

Claims (2)

Claims: 1. Unsaturated carbodiimides of the general formula R1-N = C = N-R2 in which R1 and R2 *, which can be the same or different, are linear or branched aliphatic, saturated or unsaturated radical or cycloaliphatic Radical, which may optionally contain heteroatom, represent, where at least one of these radicals is an aliphatic olefinically unsaturated radical. 2. Process for the preparation of unsaturated carbodiimides according to Claim 1, characterized in that one mustard oil with an amine, wherein at least one of the reactants has an olefinically unsaturated aliphatic radical an inert solvent, and then in a known manner desulfurized.