DE1618106A1 - Process for the preparation of N, N'-disubstituted thioureas - Google Patents

Description

BADISGHE AWILIE- & SODIL-I ¹ ASAIK AG

Our reference: O.Z. 24 745 WB / Hi Ludwigshafen am Rhein, March 7, 1967

Process for the preparation of U, N'-disubstituted thioureas

This invention relates to a process for the preparation of N, N ¹ -disubstituted thioureas by reacting methylene halides with elemental sulfur and primary amines.

From Houben-Weyl, Methods of Organic Chemistry, Volume 9, pages 884 ff. Is a series of processes for the preparation of HjN ^ -disubstituted Thioureas "known, e.g. by reacting amines with thiophosgene, thiocarbamic acid chlorides, thiocyanic acid, Mustard oils, acyl isothiocyanates, or carbon disulfide; Mustard oils and cyanamide or sulfamide can also be used "or derivatives of dithiocarbamic acid are used as starting materials will. All of these.Processes start from inaccessible or uneconomical raw materials; to some extent only can aromatic, but not aliphatic. disubstituted F, N'-thioureas, z. B. in the reaction of carbon disulfide with amines.

It has now been found that N, N-disubstituted thioureas the general formula

- 2 1 0 9 8 2 0/2 U 0

O.Z. , 24 745

HW-C-NH

in which the radicals R can be the same or different and each mean an aliphatic, araliphatic or cycloaliphatic radical ", advantageously obtained when methylene halides with elemental sulfur and primary amines of the general formula R - NH _n (II)" in which R are used Has meaning, implements.

Implementation for the pail of using methylene chloride and benzylamine is represented by the following equation:

CH ₀ -Gl ₀ + 2S + 4 NH

Il

HN - C - NH + H _n + 2 S NH Cl / \ ^2/5

CH ^ CH CH "

According to the method of the invention, compared to the aforementioned Method N, N'-disubstituted thioureas in good Yield from readily available starting materials in a simple and therefore economical manner.

Methylene halides and elemental sulfur are used as starting materials in any form of preparation and primary amines

- 3 -
109820 / 2U0

. - 3 - O.Z. 24 745

turns. The amines can be aliphatic ^ amines, preferably alkyl or alkenylamines with up to 10 carbon atoms, aralkylamines, preferably with up to 10 carbon atoms, or cycloalkylamines, preferably with up to 12 carbon atoms. she can be attached to the carbon atoms by further groups or atoms which are inert under the reaction conditions, e.g. B. Nitro, alkoxy, aroxy, alky! Mercapto, ary! Mercapto or alkylamino groups, be substituted «As a rule, the starting materials are used in roughly stoichiometric amounts; the But amines can also be used in excess, preferably when working without an organic solvent. You can also work with mixtures of amines, with one corresponding differently substituted thioureas obtained.

The reaction generally takes place at a temperature between 20 and 200 ^° C., preferably between 50 and 150 ^° C. The IT decomposition pressure results from the vapor pressure of the components. You can pressureless or under. Pressure work. Optionally, organic solvents inert under the reaction conditions, e.g. B. alkanols, such as ethyl alcohol, or aromatic hydrocarbons, such as benzene, are used.

The reaction can be carried out as follows: sulfur, primary Amine and optionally an inert organic solvent are mixed with thorough mixing, for. B. with the help of a Stirrer, heated to the aforementioned reaction temperature. Methylene halide is then added continuously or discontinuously in such an amount per unit of time to the reaction mixture,

- 4 -109820/2140

- 4 - O.Z. 24 745

that the aforementioned reaction temperature is kept constant. The mixture is then at its boiling point for as long kept with thorough mixing until no hydrogen sulfide development is observed more. The reaction mixture is then cooled, if necessary concentrated, and precipitated The amine salt and thiourea are filtered off. The amine salt is washed out of the parent material with water, the remaining thiourea is dried and removed from a suitable solvent, e.g. B. ethyl alcohol or ethyl acetate, recrystallized. From the Mitrat can be another part of thiourea, depending on your constitution of the thioureas or the reaction conditions, if appropriate also the total amount of thiourea, can be isolated. the Separation is then done by the usual methods, for. B. Evaporation of the mixture and recrystallization of the remaining Residue with the addition of activated charcoal from a suitable solvent ·.

The compounds which can be prepared by the process of the invention are valuable starting materials for the preparation of pharmaceuticals ic a.

The parts given in the following examples are parts by weight.

example 1

128 parts of sulfur and 792 parts of cyclohexylamine in 1000 parts of ethyl alcohol are used as solvents in a stirred apparatus

- 5 - 109820 / 2U0

- 5 - O.Z. 24 745

7O ⁰ C warmed. 170 parts of methylene chloride are then added to this mixture over the course of 2 hours. Babel, the mixture turns dark and hydrogen sulfide begins to evolve. The mixture is ^{then stirred for about 10 hours at 85 °} C., then cooled to room temperature and The filtrate is concentrated to half of its tolumen and filtered again. The combined miter residues are washed free of chlorine ions with water, dried and recrystallized from ethanol. 231 parts of Ή, Ή'- dicyclohexylthiourea with a melting point of 179-181 ° C. are obtained. ! the combined filtrates are concentrated completely and the residue in Essigester using recrystallized from activated carbon are ff further 106 parts, IT '- ^ cyclohexyl thiourea, melting, get 178-180 ⁰ C. total yield:.. 337 parts (equivalent to 71% of Theory).

Example 2

In a stirred apparatus 128 parts of sulfur and 856 parts of benzylamine are heated in 1000 parts of ethyl alcohol at 70 ⁰ C and in 2 hours, 170 parts of methylene chloride. The mixture is ^{stirred at 80 °} C. for a further 15 hours. The work-up is carried out in the same way as in Example 1.

There are 4H parts (corresponds to 81 $ of the theory) of NjU'-dibenzyl-

> thiourea of melting point 151 ° C. obtained.

109820/2 UO

- 6 - O.Z. 24 745

Example 5

In einer.Rührapparatur 64 parts of sulfur are heated in 500 parts of ethyl alcohol at 80 ⁰ C and then gleichzeitig507 cyclooctylamine parts and 85 parts of methylene chloride added gradually. The mixture is heated to boiling for a further 15 hours, until no more hydrogen sulfide evolution occurs. The mixture is then cooled and filtered. The filter residue is washed with water, dried and recrystallized from ethyl acetate. Oyclooctylamine can be recovered from the wash water by adding sodium hydroxide solution. The alcoholic filtrate is concentrated completely, unreacted cyclooctylamine is distilled off at a pressure of 2 torr and the residue that remains is recrystallized from ethyl acetate.

A total of 173 parts of N, N get ¹ -Dicyclooctylthioharnstoff mp. 174 C (equivalent to 59 i <> of theory).

Example 4

In a stirred apparatus 128 parts of sulfur and 792 parts Oyclohexylamin in 800 parts of benzene are heated to 80 ⁰ C and 170 parts of methylene chloride added gradually. The mixture is kept at the boiling temperature for 20 hours, then the evolution of hydrogen sulfide ceases, and the mixture is cooled and filtered. The filter material (cyclohexylamine hydrochloride) is filtered off with suction and washed with benzene.

- 7 - 109820 / 2U0

- 7 - OZ 24 745

The combined Benzolfiltrate be concentrated completely, and the remaining residue is recrystallized from ethyl alcohol with the addition of activated carbon, Es.werden 372 parts (corresponding to 78 io of theory)! Obtained U'-dicyclohexylthiourea Pp from 180 ⁰ C.

109820/2 UO

Claims (1)

- 8 - O. Z-. 24 745 Patent claim "ieioinr" loloiub Process for the preparation of N, K'-dLisubstituted thioureas the general formula S.
Hl-O-NH (I), f I R R in which the radicals R can be identical or different and each represent an aliphatic, araliphatic or cycloaliphatic radical, characterized in that methylene halides with elemental sulfur and primary amines of the general formula R-IH (II), in which R has the aforementioned meaning "implements. BADISOHE ANILIF- & SODA-FABRIK AG 109820 / 2U0