NL8006697A - METHOD FOR PREPARING NEW HYDRAZINE DERIVATIVES. - Google Patents

Description

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Method for preparing new hydrazine derivatives.

The invention relates to new hydrazine derivatives, which are valuable intermediates for the preparation of quinoxaline-1,4-dioxides, in particular 3-substituted (quinoxalinyl-2-methylene) -carbazate-N, N -dioxides, which compounds have antibacterial and veterinary properties. The preparation of such 3-substituted- (quinoxalinylmethylene) -1 4 carbazate-N, N -dioxides is described in Dutch patent application 77.05938, which was filed on May 31, 1977.

Continuous efforts in the synthetic field to find new compounds, which are active against bacteria and protozoa and also have a growth-promoting effect in pigs and poultry, have led over the years to the development of all kinds of prototype compounds, including many analogues of quinoxaline-1,4-dioxides: J. Chem. Soc., 2052 (1956); 15 Helv. Chim. Acta., 2% 95 (1946); Tetrahydron Letters, 3253 (1965); J. Org. Chem., 21 * 4067 (1966); Agnew. Chem. Internat. Edit., 8, 596 (1969); O.S. 3,679,679, 3,728,345, 3,753,987, 3,763,162, 3,767.

657, 3,803,145, 3,818,007, 3,433,971, 3,371,090 and Belgian Patent Specification 721,728.

A process for the preparation of 3-substituted- (quinoxalinyl-2-methylene) -carbazate-N *, N4-dioxides is described in U.S. Pat. No. 3,389,326, wherein a 2-dihalomethylquinoxaline derivative is reacted with hydroxyl amine or a suitable hydrazine carbonic acid ester in the presence of a primary or secondary amine and water.

The already mentioned Dutch patent application 77.05938 relates to a process for preparing a quinoxaline carbazate 1,4-dioxide of the formula 1, wherein R is hydrogen, alkyl of 1-6 carbon atoms, hydroxyalkyl of 1-6 carbon-30 atoms, alkanoyl with 2-7 carbon atoms, benzoyl or a group C0NR ^ R2, wherein R ^ and R2 each independently represent hydrogen, alkyl of 1-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, or amino-8006697 2 len alkyl of 1-6 carbon atoms /, by reacting a 2-halomethyl-quinoxaline-N *, N4-dioxide of the formula 2, wherein R has the above meaning and X represents chlorine or bromine, in a solvent inert under the reaction conditions. 2 equivalents of alkali carbonate and 1-2 equivalents of hydrazine of the formula 3, wherein R "represents a group CF ^ SO ^, CF ^ C ^ SC ^, CH ^ SO ^ or CH-, C" ELSO "and then recover the carbazate .

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The compounds of the formula I, in which R has a different meaning, hydrogen, alkyl of 1-6 carbon atoms or CONHCH2, are new.

Thus, Dutch patent application 77.05938 also provides a carbazate of the formula 1 ', wherein R' represents hydroxy-alkyl of 1-6 carbon atoms, alkanoyl of 2-7 carbon atoms, benzoyl or CONRjRj, wherein R 1 and R 1 independently of one another. 15 represent hydrogen, alkyl of 1-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, or aminoalkyl of 1-6 carbon atoms, provided that when R 1 or R 1 represents methyl, the other is not hydrogen.

According to the method of Dutch patent application 77.05938, a 2-halomethylquinoxaline-N, N-dioxide in a solvent inert under the reaction conditions in the presence of an alkali carbonate, for example anhydrous potassium carbonate, is reacted with an alkyl or arylsulfonyl substituted hydrazine, for example N-methoxycarbonyl-N * -trifylh, ydrazine, which can be represented by the attached reaction scheme A.

The 2-halomethylquinoxalines used as intermediates in the above process can be prepared by the general methods described in U.S. Pat. No. 3,753,987, J. Chem. Soc., 2052 (1956) and Chemistry of Heterocyclic Compounds, 940 (1967). The halogen can be chlorine or bromine. Preferred intermediates are the 2-bromomethylquinoxaline compounds. These compounds are prepared from the 2-methylquinoxaline-1,4-dioxides according to the methods described in J. Chem. Soc., 322 (1943); U.S. Pat. Nos. 3,474,097, 3,553,208, 3,660,398 and British Patent 1,215,815.

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Two of the hydrazine compounds of the formula III used as intermediates, namely N-methoxycarbonyl-N'-triphylhydrazine and N-methoxycarbonyl-N'-tresylhydrazine, are new compounds which can be prepared according to the general method them, described in J. Org. Chem., 40, 3450 (1975).

Thus, the invention relates to a process for preparing a hydrazine of the formula 3, wherein R "represents a group CF 3 SO 2 or CF 3 CH 2 SC> 2, whereby methyl carbazate is reacted with the corresponding anhydride or sulfonyl halide.

For example, according to the present invention, one can prepare N-methoxycarbonyl-N'-triphylhydrazine by adding a solution of triflic anhydride in methylene chloride dropwise to a methylene chloride solution, containing an equimolar amount of methyl carbazate and a small molar excess, at -78 ° C. contains triethylamine. The resulting mixture is allowed to warm to room temperature and stirred for 16 hours. The mixture is concentrated under vacuum at room temperature and the residue is then extracted with several portions of ether. The ether extract 20 is concentrated under vacuum at room temperature to a waxy solid which is used directly in the next reaction without further purification. Optionally, destruction of triethylamine and the use of 2 equivalents of methyl carbazate yield the crystalline product.

The following examples illustrate the preparation of the novel intermediates of the invention.

Example I

N-Methoxycarbonyl-N'-triphylhydrazine.

35.4 mmol of triflic anhydride in 40 ml of methylene chloride were added dropwise with stirring at -78 ° C to a solution of 35.5 mmol of methyl carbazate and 38.9 mmol of triethylamine in 200 ml of methylene chloride. The resulting mixture was allowed to warm to room temperature and stirred for 16 hours. The mixture was concentrated at room temperature under vacuum and 100 ml of the residue extracted with refluxing ether of 100 ml. The combined ether extract was concentrated under vacuum at room temperature to 5.26 g of waxy solid, about 67%. The nmr spectrum of the crude product was consistent with the expected product contaminated with the triethylamine salt of triflic acid. The crude material was used directly for further reactions without further purification.

336 mmol of methyl carbazate in 20 min. Was added to a solution of 178 mmol of triflic anhydride in 2000 ml of methylene chloride under stirring under a nitrogen atmosphere at -78 ° C. The resulting solution was allowed to warm to room temperature and stirred for 20 hours. The resulting thick white suspension was concentrated under vacuum at room temperature to a white solid. This substance was triturated with 450 grams of diethyl ether and recovered as the trimethyl carbazate of triflic acid. The diethyl ether filtrate was concentrated under vacuum at room temperature to a white solid which was triturated with hexane, recovered, washed with hexane and dried to yield the product as a white crystalline solid. Yield 84%, sn $> t. 107-109 ° C. Analysis:

Calculated for C 16 H 21 O F S: C 16.21; H 2.25; N 12.61; 3 5 4 2 3

Found: C 16.24; H 2.20; N 12.68.

Example II

N-Methoxycarbonyl-N-tresylhydrazine.

The procedure of Example I can be repeated using tresyl chloride instead of triflic anhydride to give the title compound.

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Claims (3)

1. Process for the preparation of a hydrazine, characterized in that a compound of the formula 3 in which R "represents a group CF 2 SO 4 or CF 2 Cl 2 SO 4 is prepared by reacting methyl carbazate with the corresponding anhydride or sulfonyl halide. 2. Process according to claim 1, characterized in that methyl carbazate in a suitable solvent is reacted with triflic anhydride at a reduced temperature, Process according to claim 1, characterized in that methyl carbazate is reacted with tresyl chloride in a suitable solvent at a reduced temperature. 15 8 00 6 69 7