Syntheses based on 3,4-dimethyl-2-thioxothiazoline-5-carboxylic acid hydrazide and azide

Abstract

Treatment of 3,4-dimethyl-2-thioxothiazoline-5-carboxylic acid hydrazide with NH 4 SCN and PhCONCSgave the corresponding thiosemicarbazides, arylsulfochlorides yielded the arylsulfonylhydrazides, and diazotization conditions gave the corresponding azide. The interactions of the latter with different nucleophiles have been studied and a series of novel carbamic acid, urea, and semicarbazide derivatives containing a thiazoline fragment have been prepared.In continuation of our search for a novel series of biologically active substances based on the previously reported 3,4-dimethyl-2-thioxothiazoline-5-carboxylic acid hydrazide (1) [1] we now report the preparation of its arylsulfonyl and thiocarbamoyl derivatives 2a-e and 3, 4 respectively as well as the azide product of its diazotization 5. Compounds 2a-e are related in structure to known sulfonylamides [2] or thiourea derivatives [3] and hence attract particular interest as potential medicinal agents and pesticides. The azide 5, being a thiazolineisocyanate donor under Curtius reaction conditions can serve as a valuable starting compound for the development of novel routes to functionalize a thiazoline system and this has been demonstrated in a series of examples.When treated with arylsulfochlorides in pyridine medium at 20°C the hydrazide 1 gave high yields (80-90%) of the arylsulfonylhydrazides 2a-e and when refluxed with ammonium thiocyanate in ethanol or with benzoylisothiocyanate in dioxane the thiosemicarbazide 3 (yield 61%) or benzoylthiosemicarbazide 4 (yield 78%) respectively (Scheme 1).A single unsuccessful attempt to carry out the reaction of thiazolecarboxylic acid hydrazides to the corresponding azide has been reported in the literature. In [3] it was shown that 2-substituted 5-phenylthiazolecarboxylic acid hydrazides in excess acetic acid and the presence of NaNO 2 underwent a more extensive reaction and, in place of the expected azides, gave the N,N'-bis(2-substituted-5-phenyl)thiazolylureas.Despite this data we have found in our work that hydrazide 1 readily forms the azide 5 when treated with an equimolar amount of HNO 2 in aqueous medium in 91% yield. The reactions of the azide with various nucleophiles have been studied. It was found that, at 100-120°C in absolute toluene, the azide indicated underwent a Curtius rearrangement reaction to the corresponding isocyanate which reacts with alcohols, amines, and hydrazides to form novel derivatives of carbamic acid 6a-g, urea 7a-k, and semicarbazide 8a-d containing a thiazoline fragment.

Synthesis of 3,4‐Dialkyl‐5‐(1‐oxo‐ethyl)‐3H‐thiazole‐2‐thiones Derivatives and Their Pesticidal Activity

“…The latter with substituted hidrazines, ureas and thioureas were formed corresponding hydrazones (3,4), ureayl-imino and thioureayl-imino derivatives (5,6). The interaction of ketones 1,2 with hydroxylamine hydrochloride in alkaline solution lead to 1-(3-alkyl-4-methyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone oximes (7,8) formation. When obtained oximes were reacted with dimethyl sulfate, chloro-acetic acid methyl ester, phenyl isocyanate and various azinyl-trimethylammonium chlorides, corresponding O-substituted derivatives (9-12) were obtained.…”

“…In 1 H NMR spectra of oximes (7,8) and some of their derivatives (9,10a), two groups of absorptions corresponding to E-isomers and Z-isomers appeared. The E/Z-isomers ratio depended on steric factor.…”

“…The E/Z-isomers ratio depended on steric factor. In unsubstituted oximes (7,8), these isomers were in molar ratio of 1:1. When the hydrogen atom was replaced by methyl group (9,10a), the amount of E-isomer was increased (Z/E = 1:7).…”

“…The compound was obtained as white crystals; mp 208-210 C, yield: 1.62 g (80%). 1 1-(3-Ethyl-4-methyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone oxime (8).…”

“…Among them, there are known herbicides (mefenacet, thiazopir, metabenzthiazuron, fenthiaprop, benazolin, benzthiazuron), fungicides (ethaboxam, thiabendazole, fluthianil, thiadifluor, thifluzamide, metsulfovax, isotianil, octhilinone), insecticides (clothianidin, thiamethoxam, tazimcarb, thiacloprid, imidaclothiz, thiapronil), acaricides (flubenzimine, hexythiazox) and others. At the same time, the search for new pesticides is continuing among the new series of thiazole derivatives [1][2][3][4][5][6][7][8][9], in particular hydrazones, oximes and their ethers with fungicidal [10,11], herbicidal [12,13] and insecticidal [14] activities. The purpose of the present research was the synthesis of thiazole derivatives on the basis of 1-(3-alkyl-4-methyl-2-thioxo-2,3-dihydro-thiazol-5yl)-ethanones and study of their pesticidal activity.…”