The reactions of methylhydrazine and hydrazine hydrate with chlorinated pyridazines and pyridazones were studied.The reactivity of hydrazine and methylhydrazine toward aliphatic and aromatic compounds has been well studied [1,2]. However, data on reactions of hydrazine and methylhydrazine with heterocycles and, in particular, with pyridazines are scarce. The interest in the chemistry of hydrazine is determined by its diverse applications in science and technology. In particular, hydrazine derivatives are widely used in medicine as physiologically active compounds exhibiting antitubercular, anticancer, radiation-protective, and other effects; in agriculture, as plant growth regulators and stimulants, as insecticides, fungicides, and hebricides; and in industry, for preparing synthetic fibers, films, and coatings [3,4].In this study we examined the reactions of hydrazine hydrate and methylhydrazine with some chlorinated pyridazines and pyridazones.In the pyridazine series, available substrates for nucleophilic substitution are 4,5-dichloro-6-pyridazone I, 1-methyl-4, 5-dichloro-6-pyridazone II, 3, 4, 5-trichloropyridazine III, 3,6-dichloropyridazine IV, and 3-methyl-6-chloropyridazine V [538]: Q 8 ? C 9 9 O N N Q R S Cl Cl Q S Cl Cl 9 Cl 6 N N 9 Cl 6 N N 9 R I, II III IV, V Q 8 ? C 9 9 O N N Q R S Cl Cl Q S Cl Cl 9 Cl 6 N N 9 Cl 6 N N 9 R I, II III IV, V where R = H (I), Me (II, V), Cl (IV).It is known that pyridazone I reacts with ammonia [9], alkylamines [10], and hydrazine [11] selectively with chlorine substitution at the 4-position of the pyridazine ring. This is due to the activating effect of the keto group on the 4-position in I [10,12]. However, it has been reported [13,14] that the reaction of I with ammonia yields a mixture of 4-amino-5-chloro-6-pyridazone VI and 5-amino-4-chloro-6-pyridazone VII.Our experiments showed that pyridazone I reacts with methylhydrazine in 2-propanol strictly specifically to give 4-(1-methylhydrazino)-5-chloro-6-pyridazone VIII in 95% yield. In methylation of VIII with dimethyl sulfate in methanol in the presence of sodium, the reaction occurs selectively at the 1-position of the pyridazine ring, giving 1-methyl-4-(1-methylhydrazino)-5-chloro-6-pyridazone IX in 37% yield.It is known [11] that the reaction of I with 95% hydrazine in methanol yields exclusively 4-hydrazino-5-chloro-6-pyridazone X. Its structure was determined by hydrogenation (Pd/C) and independent synthesis of the dechlorination products. However, under the experimental conditions, the reaction of I with 100% hydrazine hydrate in ethanol yields a mixture of pyridazone X and 5-hydrazino-4-chloro-6-pyridazone XI in 29 and 48% yields, respectively, which is confirmed by the 1 H NMR and TLC data, and also by depression of the melting point, observed on mixing X and XI.Then we performed methylation of X with dimethyl sulfate. The reaction was performed in the system 10% aqueous NaOH solution3CHCl 3 in the presence of Et 4 NI. The reaction occurs selectively at the N 1 atom of the hydrazine moiety, yielding pyridazon...

Acetylation of 5-aryltetrazoles, 5-(5-methyl-2-furyl)tetrazole, and 5-(1,5-dimethyl-2-pyrrolyl)tetrazole with chloroacetyl chloride was studied.1,3,4-Oxadiazoles are key fragments of various drugs, from antiviral agents to antidepressants; they are used as organic scintillators and are components of specialty polymerizing formulations, etc.[1].The goal of this study is the development of a onepot procedure for preparing 5-aryl-2-chloromethyl-1,3,4-oxadiazoles and previously unknown 2-chloromethyl-5-(5-methyl-2-furyl)-and 2-chloromethyl-5-(1,5-dimethyl-2-pyrrolyl)-1,3,4-oxadiazoles from appropriate tetrazole derivatives. These 1,3,4-oxadiazoles are of interest as biologically active substances and reagents for further fine organic synthesis. Similarly to other 1,3,4-oxadiazoles [2], they can be involved in the peptide synthesis by the subsequent reactions with amino acids.2,5-Disubstituted 1,3,4-oxadiazoles of various structures can be prepared by several procedures. The starting compounds can be carboxylic acids and hydrazine; they are converted into diacylhydrazides via several intermediates. The cyclodehydration of diacylhydrazides under the action of POCl 3 yields 1,3,4-oxadiazoles; these compounds can also be prepared by cyclodehydration of diaroylhydrazines and diacylhydrazines under the action of various dehydrating agents (organic acid anhydrides, PCl 5 , H 2 SO 4 [235]).A procedure developed in [6] for preparing 2,5-diaryl-1,3,4-diazoles by the reactions of tetrazoles with benzoyl chlorides in o-xylene or toluene on heating was applied here to the synthesis of 2-chloromethyl-5-aryl-, 2-chloromethyl-5-(5-methyl-2-furyl)-, and 2-chloromethyl-5-(1,5-dimethyl-2-pyrrolyl)-1,3,4-oxadiazoles from tetrazoles and chloroacetyl chloride.Tetrazoles are prepared starting from aromatic and heterocyclic nitriles [7]. Their azidation with NaN 3 is performed in the presence of NH 4 Cl in DMF at 110 3 120oC. Following the procedures from [8310], we prepared 5-phenyltetrazole I, 5-(2-chlorophenyl)tetrazole II, 5-(2-nitrophenyl)tetrazole III, 5-(2-ethoxyphenyl)tetrazole IV, 5-(3-methylphenyl)tetrazole V, 5-(2,4-dimethoxyphenyl)tetrazole VI, 5-(3,4,5-trimethoxyphenyl)tetrazole VII, and also previously unknown 5-(1,5-dimethyl-2-pyrrolyl)tetrazole VIII and 5-(5-methyl-2-furyl)tetrazole IX. The reaction conditions, yields, melting points, and analytical data for

The reactions of 1,1-dimethylhydrazine, methylhydrazine, and hydrazine hydrate with 5-aryl-2-chloromethyl-1,3,4-oxadiazoles were studied. The structures and compositions of the final products were confirmed by 1 H NMR spectroscopy and elemental analysis.Hydrazine and its derivatives attract great interest of researchers [1] owing to wide use of these compounds in medicine (antitubercular, antitumor, and other drugs), agriculture (plant growth regulators and stimulants), and industry (production of synthetic fibers, films, coatings, etc.) [235]. 5-Aryl-2-chloromethyl-1,3,4-oxadiazoles, aromatic five-membered heterocycles, are key fragments of various drugs (antiviral agents, antidepressants, etc.) [6]. At the same time, introduction of a hydrazine fragment may enhance their biological activity.Our goal was synthesis of previously unknown 5-aryl-2-hydrazinomethyl-1,3,4-oxadiazoles, 5-aryl-2-(1-methylhydrazino)methyl-1,3,4-oxadiazoles, and 5-aryl-2-(1,1-dimethylhydrazinio)methyl-1,3,4-oxadiazole chlorides, which are of interest as potentially bioactive substances and agents for further fine organic synthesis. Accessible 1,3,4-oxadiazole substrates for nucleophilic substitution of chlorine by hydrazine, methylhydrazine, and 1,1-dimethylhydrazine fragments are 2-chloromethyl-5-phenyl-1,3,4-oxadiazole I, 2-chloromethyl-5-(2,4-dimethoxyphenyl)-1,3,4-oxadiazole II, 2-chloromethyl-5-(2-chlorophenyl)-1,3,4-oxadiazole III, and 2-chloromethyl-5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazole IV [739]: 4 e e i cc L T R d CH Cl 2 R R R 3 R 4 O N N , 2 1 I3IV 4 e e i cc L T R d CH Cl 2 R R R 3 R 4 O N N , 2 1 I3IVwhere R 1 = R 2 = R 3 = R 4 = H (I); R 2 = R 4 = H, R 1 = R 3 = MeO (II); R 1 = Cl, R 2 = R 3 = R 4 = H (III); R 2 = R 3 = R 4 = MeO, R 1 = H (IV). It is known that 5-aryl-2-chloromethyl-1,3,4-oxadiazoles react with amines and methylmercaptoacetyl derivatives selectively with the replacement of Cl in the 2-chloromethyl group [8,9].We found that compounds I!IV react with hydrazine hydrate in 2-propanol at 553 65oC strictly selectively to give 2-hydrazinomethyl-5-phenyl-1,3,4-oxadiazole V, 2-hydrazinomethyl-5-(2,4-dimethoxyphenyl)-1,3,4-oxadiazole VI, 2-hydrazinomethyl-5-(2-chlorophenyl)-1,3,4-oxadiazole VII, and 2-hydrazinomethyl-5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazole VIII in 67, 23, 25, and 75% yields, respectively.