DEA0021223MA - - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

Registration date: September 28, 1954 Bekanintgiemmacht on September 20, 1956

GERMAN PATENT OFFICE

PATENT APPLICATION

CLASS 12p GROUP 9 INTERNAT. CLASS C07d

A 21223 IVb / 12 p

Dr. phil. nat. habil. Herbert Arnold and Dr. rer. nat. Dietrich Vogelsang, Bielefeld

have been named as inventors

Asta-Werke Aktiengesellschaft Chemical Factory, Brackwede (Westphalia)

Process for the preparation of bis [imidazyl- (2)] disulfide and its derivatives

It is known that mercaptans can be used in the sense of hydrogen-removing agents subsequent equation (i) into corresponding disulfides can convict:

2-R-SH

R — S — S — R W

The dehydrating agents used here include hydrogen peroxide, potassium permanganate, Nitric acid, oxygen, elemental iodine, sulfuryl chloride or phosphorus pentachloride use.

While C-substituted 2-mercaptoimidazoles, for example 2-mercapto-4,5-diphenylimidazole (I), can easily be converted oxidatively to corresponding disulfides according to scheme (1) (see Beilstein's handbook, vol. 23, p. 447) ); run corresponding reactions with free 2-mercapto-imidazole and its N-substitution products, z. B. 2-mercapto-i-methyl-imidazole (II, R = CH ₃ ), very unsatisfactory and usually give, depending on the nature of the dehydrogenating agent, oxygen or halogen-containing products. In no case could the desired form IV disulfide be captured. That may be with the sensitivity of the unsubstituted and the. N-substituted bis [imidazyl- (2)] - disulfide compared to the

609 619/387

A 21223 IVb / 12 p

agents used or the reaction conditions.

C ₆ H ₅ -C -NH.

: c-SH

C ₆ H ₅ -C

-N "
R.

CH-N

CH-N ^:

—SH

It has now been found that bis [imidazyl (2)] disulfide and its on nitrogen or Carbon can produce derivatives substituted by alkyl or aryl radicals in that the corresponding 2-mercapto-imidazoles with solutions of phosgene in organic solvents, such as dioxane or benzene. Compounds of type I, i.e. C-substituted derivatives des 2-mercapto-imidazole, can, as mentioned above, by the usual oxidizing agents be converted into disulfide, but leads to the implementation of the mercapto group by means of them Phosgene to the disulfide in considerably better yields.

Here, as has been proven perfectly, the one to be reproduced by the following formulas takes place Process from:

CR'-N

C-SH + COCl ₂

CR'-N '

(2)

+ 2 HCl

-CO

CR'-N

CR'-N '

c — s — s — c:

(IV)

.N-CR '

¹ N-CR '

+ 2 HCl

R '= H, C ₆ H ₅ , R = H, CH ₃ , C ₆ H ₃

The intermediate dithiocidal acid ester (III, R = H, R '= R) formed by phosgene acylation of 2 molecules of 2-mercapto-imidazole (II, R = H) is very unstable and decomposes into bis [imidazyl- (2)] disulphide, since the hydrochloric acid released is obtained as dihydrochloride (IV, R = H, R '= H). In this hitherto unknown way, among other things, both from 2-mercaptoimidazole (II, R = H) and from its N-methyl group N-phenyl- (II, R = CH ₃ and C ₆ H ₅ ) and C-phenyl- derivatives (I) the corresponding disulfides (IV, R '= H, R = H, CH ₃ , C ₆ H ₅ or R' = C ₆ H ₅ , R = H) can be obtained with excellent yields.

These compounds find use as intermediates and drugs with antithyroid Effectiveness.

Examples

i. N-methyl-irnidazolyldisulnd. 250 ecm of dry benzene are saturated with phosgene at 0 °. In this solution is added at once with stirring 50 g of N-methyl-2-mercapto-imidazole, and then the temperature is allowed gradually to 70 ⁰ to rise. The mass puffs up and turns yellow, then collapses and is then stirred for several hours at 70 to 100 °. After the reaction product has been filtered off with suction and washed with acetone, it is dissolved in water and the solution is adjusted to be weakly alkaline while cooling with 2N ammonium hydroxide. The base dissolved in the aqueous phase is isolated by extraction with chloroform. After the chloroform extract has dried, the solvent is carefully removed in vacuo and the yellow crystals that remain are recrystallized from ethyl acetate. Yield: 80% of theory. Melting point: 127 to 128 ⁰ .

2. N-phenyl-imidazolyl-disulfide. 100 g of N-phenyl-2-mercapto-imidazole are introduced into a saturated solution of phosgene in 500 ecm of dioxane with stirring and cooling. It is allowed to increase the temperature to 30 ^0th After standing for an hour, the reaction product is filtered off with suction, washed with acetone, then dissolved in water and the aqueous solution is neutralized with 2-N ammonium hydroxide. The precipitated yellow base is filtered, washed with ethyl acetate and recrystallized from a mixture of ethyl acetate and chloroform. Yield: 78% of theory. Melting point: 158 to 160 °.

3. Imidazolyl disulfide. 300 g of 2-mercapto-imidazole is heated in an autoclave together with a solution of excess phosgene in dioxane for 2 hours at 110 to 150 ^0th After the autoclave has cooled, the precipitate formed is filtered off with suction, washed with acetone and taken up in water. The solution is neutralized with 2N NaOH and the brown precipitate that forms is filtered off with suction. Recrystallization from methanol gives yellow crystals with a melting point of 155 ^° . Yield: 85% of theory.

619/387

A 21223 IVb / 12 p

4. 4,5-Diphenyl-imidazole disulfide. 30 g of 4,5-D1-phenyl-2-mercapto-imidazole are introduced into 300 ecm of dioxane which is saturated with phosgene. When heated, everything dissolves with a green color. It then increases with stirring, the temperature to 90 ^0, cooled and centrifuged from the precipitated precipitate is then washed with sodium carbonate solution, and recrystallized from alcohol. Melting point: 250 ⁰ . Yield: 80% of theory.

Claims (1)

PATENT CLAIM: Process for the preparation of bis- [imidazyl- (2)] - disulnd and its derivatives which are substituted on the nitrogen or carbon by alkyl or aryl radicals, characterized in that that corresponding 2-mercaptoimidazoles with solutions of phosgene in an organic solvent, preferably benzene or dioxane. © 609 619/387 .9-. 56