DE896651C - Process for the preparation of thiocarbhydrazine compounds - Google Patents

Description

Process for the preparation of thiocarbhydrazine compounds The invention relates to the production of new thiocarbhydrazine compounds. So far described Hydrazine compounds have proven to be ineffective or, in certain cases, weak effective against tuberculosis but proven too toxic to be therapeutic for _ Use to be suitable.

Surprisingly, it has been found that certain thiocarbhydrazine compounds have good activity in experimental tuberculosis and that they also have a have favorable toxicity. They are therefore suitable to be used as chemotherapeutic agents to become.

The new compounds to be obtained according to the invention have the general formula wherein R1 is a benzyl or cyclohexyl radical, R2 is either hydrogen or another bond to R3 and R3 is either a CHC, H5 radical, CO - C, 11, radical, CO - CH. radical, CS - O - CH , - CH, radical, CS - O - C, 11,1 radical, C, H "radical or i denote hydrogen atom. In the last two cases, R1 is a cyclohexyl radical.

These compounds, which are effective against tuberculosis, can be prepared according to the invention by using hydrazine compounds of the general formula or salts or functional derivatives thereof, with a xanthic R, 0 CSSH, their salts or known reactive derivatives thereof, or DAB Xanthogenhydrazide of the general formula R10-CS-NH-NH2 or salts or functional derivatives thereof with per se known reactive derivatives thereof implemented by R3.

For example, xanthogen hydrazides are combined with carbonyl compounds (e.g. a Aldehyde, an acid halide or a carbonylthioglycolic acid) or with a Xanthogenic acid, its salts or reactive derivatives implemented. Substituted Hydrazines with a free N H2 group can react with xanthogenic acids or their salts or. reactive derivatives are converted, and the same applies to hydrazine or its hydrate and its salts.

If R2 is hydrogen and R3 is the radical R10 C S, the compounds by simultaneous introduction of two identical oxythiocarbonyl residues in hydrazine, their salts or reactive derivatives are produced.

The following examples serve to illustrate the invention.

Example 1 18 g of sodium are boiled in 500 cc of dry cyclohexanol until solution has occurred. After cooling, the cake thus formed is ground and then suspended in 2 liters of ether and boiled for 15 minutes, after which 64 g of carbon disulfide are added. The mixture is then further boiled for 45 minutes and extracted with 1 liter of water. The extract is reacted with 40 g of hydrazine hydrate at room temperature and thereby precipitated cyclohexyloxythiocarbonyl hydrazine, which is obtained after recrystallization from benzene petroleum ether in a yield of 95 g with a melting point of 76 to 77 °.

Instead of using hydrazine hydrate, one of its salts can also be used will. In this case, the latter is neutralized in a suitable manner with caustic alkali. Example 2 For 1.8 g of benzyloxythiocarbonyl hydrazine in 5 cc of ethyl alcohol (95%) i, i g of benzaldehyde are added to 5 cc of ethyl alcohol. This will keep it at room temperature Benzaldehyde-Benzyloxythiocarbonylhydrazone precipitated in the form of narrow crystal prisms, which, after recrystallization from benzene, has a melting point of 124 to 24.5 ° to have.

EXAMPLE 3 To 0.3 moles of benzylxanthogenoacetic acid in 150 cc of ethyl alcohol (950 /,) the equivalent amount of 5N caustic alkali together with 0.14 mol of hydrazine hydrate admitted. After standing for 3 hours at room temperature, prismatic crystals appear of N1, N2-di-benzyloxythiocarbonylhydrazine with a melting point of 118 to 19.5 ° fail.

Example 4 To 4 g of benzoylthioglycolic acid in 2o ccm in caustic alkali are 3.5 9 cyclohexyloxythiocarbonyl- hydrazinin 2o cc ethyl alcohol (95 ° / 0) added. Here- gradually becomes Nl-benzoyl-N2-cyclohexyloxy- thiocarbonylhydrazine in prismatic crystals with a melting point of 12o.5 to r22.5 °. Example 5 To 18 g of cyclohexyloxythiocarbonylhydrazine in 6o cc of ethyl alcohol (95%) become 9.7 cc of vinegar acid anhydride added. This means that in short time Nl-acetyl-N2-cyclohexyloxythiocarbonyl- hydrazine in the form of prismatic crystals with a Melting point of 138 to 14o ° precipitated. In a corresponding manner, Nl-benzoyl-N2-cyclo- hexyloxythiocarbonylhydrazine obtained when e.g. B. Benzoyl chloride used instead of acetic anhydride will. In an analogous manner, the following connections can applications are made: Benzaldehyde-cyclohexyloxythiocarbonylhydrazine, C, H "O-CS-NH-N-CH-C, Hs; N "-Cyclohexyloxythiocarbonyl-N2-acetyl-hydrazine, C &H110CS-NH-NH-CO-CH3; Nl-Benzyloxythiocarbonyl-N2-acetyl-hydrazine, C, H, CH20-CS-NH-NH-CO-CH3; NI-Cyclohexyloxythiocarbonyl-N2-benzoyl-hydrazine, C, H "O-CS-NH-NH-CO-C @ H5; Nl-benzyloxythiocarbonyl-N2-benzoyl-hydrazine, C, H, CH2O-CS-NH-NH-CO-C @ HS; Nl-Cyclohexyloxythiocarbonyl-N2-phenyl-hydrazine, C, H110-CS-NH-NH-C @ Hs; Nl-Benzyloxythiocarbonyl-N2-cyclohexyloxythio- carbonyl hydrazine, CgH5CH20-CS-NH-NH-CS-0-C, H11; N1, N2-Di-cyclohexyloxythiocarbonyl-hydrazine, C, H110-CS-NH-NH-CS-0-C, H11.

Claims (3)

PATENT CLAIMS: i. Process for the preparation of thiocarbhydrazine compounds of the general formula wherein R, benzyl or cyclohexyl, R2 is either hydrogen 'or another bond to R3 and R3 is either CH C6 Hb, C 0 - CO 115, C 0 - C H3, CS - O - CH2C6Hb, CS - 0 - C6H ", C , HS or hydrogen, in which last two cases R1 is a cyclohexyl radical, characterized in that hydrazine compounds of the general formula or salts or functional derivatives thereof with a xanthogenic acid R1 OCSS H, its' salts or known reactive derivatives thereof or that xanthogen hydrazides of the general formula Rlp - CS - NH - N H2 or salts or functional derivatives thereof with known reactive Derivatives of R3 are implemented. 2. The method according to claim i, characterized in that Compounds which contain the radical R1 0 - C S - N H - N - with carbonyl compounds or xanthogenic acids or their salts or reactive derivatives reacted will. 3. The method according to claim i, characterized in that, if R2 is hydrogen and R3 is the radical R10 - C S, hydrazine or hydrazine hydrate or its salt with 2 molecules of a xanthogenic acid or its salts or reactive derivatives is treated with the introduction of two identical oxythiocarbonyl residues.