CS200219B2 - Method of producing novel derivatives of hydrazine - Google Patents

Description

The invention relates to a process for the preparation of novel hydrazine derivatives which are useful as starting materials for the preparation of quinoxaline-1,4-dioxides, in particular the N ¹ , N -dioxides of 3-substituted- (2-quinoxalinylmethylene) carbazates. These latter compounds are antibacterially active and have additional properties useful in veterinary medicine. Preparation of N ¹ * N-substituted-dioxide 3 .- (2-quinoxalinylmethylene) carbazate and is described in our related chráněifc Czechoslovak Pat. No. 200,218.

The constant effort to prepare novel compounds effective against bacteria and protozoa and acting as growth promoters in pigs and poultry has over the years led to the development of a number of organic compounds, including numerous quinoxaline-1,4-dioxide analogs, see J. Chem. Soc., 2052 (1956); Helv. Chim. Acta., 29, 95 (1946); Tetrahedron Letters, 3,253 (1965); J. Org. Chem. 31.

067 (1966); Angew. Chem. Dormitory. Edit., 8, 596 (1969); U.S. Pat.

679 679, 3,728,345, 3,753,987, 3,763,162, 3,767,657, 3,803,145, 3,818,007, 3,433,871,

No. 371,090 and Belgian Patent No. 721,728.

A process for preparing N ¹ ^ Ν-dioxide-substituted 3 .- (2-quinoxalinylmethylene) carbazate is disclosed in U.S. Pat. No. 3,389,326, according to which 2-bis (halo) methylchinoxalinový derivative is reacted with hydroxylamine or with an appropriate a carbonic acid ester of hydrazine in the presence of a primary or secondary amine and water.

Our co-pending Czechoslovak patent specification No. 200 218 describes a process for the preparation of 1,4-dioxides of c.hinoxaline carbazates of formula I,

ch-nnhcooch ₃ (I) wherein

R is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 hydroxyalkyl, C 2 -C 7 alkanoyl, benzoyl or CONHCH 3;

Characterized in that the 2-halomethyl-quinoxaline N, N-dioxide of the formula II is used

(II)

CH / in which

R is as defined above and

X is chlorine or bromine, reacted with 1 to 2 equivalents of an alkali metal carbonate and 1 to 2 equivalents of a hydrazine of formula III,

RNHNHCOOCH ₃ (III) wherein

R is CF ^SOj, CF ^CHgSOSO, CH ^SO SO or CH ^C CH HSO SO, in an inert solvent at a temperature of from 75 to 85 ° C. ζ

Using N-methoxycarbonyl-N'-triphylhydrazine as the starting material of formula (III), the reaction scheme described and protected in our above-cited related Czechoslovak patent specification can be described by the following reaction scheme:

CF I ³ so,

I ² K, CO,

NH 2 3

AND

NH

AND

COOCH ₃

O t

Italy (11)

o t

R

CH = NNHCO ₂ CH ₃ + ^CF 3 ^SO 2 ^K

O (O

The starting 2-halomethylehinoxalines II used in the above process can be prepared according to the general methods described in U.S. Patent 3,753,987 to J. Chem. Soc., 2052 (1956) and Chamistry of Heterocyclic Compounds, 940 (1967). The halogen X may be chlorine or bromine. Preferred starting materials are the corresponding 2-bromomethylquinoxaline derivatives. These compounds are prepared from 1,4-dioxides of 2-methylchlnozalin according to the procedures described in J. Chem. Soc., 322 (1943), U.S. Patent Nos. 3,474,097, 3,553,208 and 3,660,398, and British Patent Specification No. 1,215,815.

The starting hydrazine derivatives of the above formula III, i.e., N-methoxycarbonyl-N'-triphenylhydrazine, N-methoxycarbonyl-N'-tresylhydrazine, N-methoxycarbonyl-N'-methanesulfonylhydrazine and N-methoxycarbonyl-N'-tosylhydrazine are new. substances which can be prepared by the general procedure described in J. Org. Chem., 40, 3450 (1975).

The present invention provides a process for the preparation of the novel hydrazine derivatives of formula III,

ITNHNHCOOCH.J (III) wherein

R is CF ^SOj, CFyJHgSOg, CH ^SO SO or CH ^C CH ^SOj, characterized in that the methylcarbazate is reacted with the corresponding sulfonic anhydride or halide containing the radical R.

For example, in accordance with the invention, N-methoxycarbonyl-N'-triphylhydrazine is prepared by dropping a solution of trifluoromethanesulfonic anhydride in methylene chloride at -78 ° C to a methylene chloride solution containing an equimolar amount of methyl carbazate and a small molar excess of triethylamine. The resulting mixture was allowed to warm to room temperature, stirred for about 16 hours, then concentrated at room temperature in vacuo and the residue extracted several times with ether. The ether extracts are concentrated in vacuo at room temperature to a waxy solid residue, which is usually used directly without further purification for the next reaction described in the above-cited related Czechoslovak patent specification. Alternatively, triethylamine is not used, but the reaction is carried out using 2 equivalents of methyl carbazate. In this way, a crystalline product is obtained.

The invention is illustrated by the following non-limiting examples.

He did

N-Methoxycarbonyl-N'-triphenylhydrazine

To a solution of 35.5 mol of methyl carbazate and 38.9 mmol of triethylamine in 200 ml of methylene chloride at -78 ° C was added dropwise with stirring 35.4 mmol of trifluoromethanesulfonic anhydride in 40 ml of methylene chloride. The resulting mixture was allowed to warm to room temperature, stirred for 16 hours, then concentrated in vacuo at room temperature and the residue was extracted three times with 100 ml of boiling ether each time. The combined ether extracts were concentrated in vacuo at room temperature. 5.26 g (ca. 67%) of a waxy solid residue are obtained. The NMR spectrum of the crude product obtained corresponds to the desired product contaminated with triethylammonium salt of trifluoromethanesulfonic acid. This crude material is directly used for the next reaction without further purification.

To a solution of trifluoromethanesulfonic anhydride (178 mmol) in methylene chloride (2000 mL) was added methyl carbazate (336 mmol) under stirring at -78 ° C over 20 minutes. The resulting solution was allowed to warm to room temperature and stirred for 20 hours. The resulting thick white suspension was concentrated in vacuo at room temperature.

The solid white residue was triturated with 450 ml of diethyl ether and then filtered off. Trifluoromethanesulfonic acid salt of methyl carbazate is obtained. The diethyl ether filtrate was concentrated under vacuum at room temperature. The white solid was triturated with hexane and filtered, washed with hexane and dried to give the desired product in 84% yield as white crystals, mp 107-109 ° C.

H, 2.25; N, 12.61. Found: C, 16.21;

Found: C 16.24%, H 2.20%, N 12.68%.

Example 2

N-Methoxycarbonyl-N'-trisylhydrazine

The title compound was prepared in a manner analogous to Example 1 except that tresyl chloride was used in place of trifluoromethanesulfonic anhydride.

Example 3

N-Methoxycarbonyl-N'-methanesulfonylhydrazine

To a solution of methanesulfonyl chloride (0.02 mol) and methyl carbazate (0.02 mol) in chloroform (30 ml) was added pyridine (0.02 mol) with stirring. The resulting solution was heated to reflux for about 4 hours and then stirred at room temperature overnight. The reaction mixture was concentrated in vacuo at room temperature, the white oily residue was dissolved in ethyl acetate and the solution was concentrated. 4.86 g of a white solid are obtained, which is chromatographed on a column of 300 g of silica gel, eluting with chloroform / methanol (98: 2). 2.5 g (74%) of pure product are obtained in the form of a white solid, melting at 108-109 ° C.

H, 4.80%; N, 16.67%. Found: C, 22.13%; H, 4.89%; N, 16.78%.

Example 4

N-Methoxycarbonyl-N'-tosylhydrazine

To a solution of 0.3 mole of p-toluenesulfonyl chloride and 0.3 mole of methyl carbazate in 500 ml of chloroform was added 0.3 mol of pyridine with stirring. The resulting solution was heated to reflux for about 3 hours, then stirred at room temperature overnight. The reaction mixture was poured into 300 ml of 1N hydrochloric acid with stirring and then diluted with 900 ml of water. The resulting suspension is filtered and the residue on the filter is dried. 52.8 g (72%) of the desired product are obtained in the form of white crystals, melting at 149-150 ° C.

Claims (5)

SUBJECT OF THE INVENTION A process for the preparation of novel hydrazine derivatives of the general formula III RNHNHCOOCH ₃ (III) wherein R is CF ^SOj, CK ^CH ^SOj, CH ^SO SO or CH ^CgHHSO SO, characterized in that the methyl carbazate is reacted with the corresponding sulfonylanhydride or sulfonyl halide containing a residue R. 2. The process of claim 1, wherein the methyl carbazate is reacted with trifluoromethanesulfonic anhydride in a suitable solvent at a temperature of about 78 ° C. 5 2002.9 3. The process of claim 1 wherein the methyl carbazate is reacted with tresyl chloride in a suitable solvent at -78 ° C. 4. The process of claim 4 wherein the methyl carbazate is reacted with methanesulfonyl chloride or p-toluenesulfonyl chloride at room temperature. 5. The process of claim 1 wherein the methyl carbazate is reacted with methanesulfonyl chloride or p-toluenesulfonyl chloride at reflux temperature.