A Novel Route to 1,2,3-Thiadiazole, 1,3,4-Thiadiazine, and 1,2,5-Triazepine Derivatives

Abstract

New convenient methods for the synthesis of 1,2,3-thiadiazole, 1,3,4-thiadiazine, and 1,2,5-triazepine derivatives are reported. In the heterocyclization process, the reactivity of 1-thia-4-aza-1,3-butadiene system of syn-2-phenylhydrazono-3-oxothiobutanoic acid anilides was exploited.The structure and chemistry of the 1,2,3-thiadiazole system have been under active investigation for years. 1-3 Its derivatives are useful in the treatment of hyperproliferative disorders including tumor growth and angiogenesis, and lymphoproliferative symptoms. 4 Moreover, derivatives of this system are applied in the treatment and/or prevention of morbid states mediated by oxytocin, including premature labour and dysmenorhea. 5 The 1,2,3-thiadiazole moiety is crucial for the antibacterial activity of new carbapenems 6 as well as for the efficacy of some pesticides. 7 The biological activity of 1,2,5-triazepines 8 has received less attention than the corresponding benzofused system.Recently, we have reported 9,10 the synthesis of 1,3-and 1,4-diazines which used the C-2 disubstituted thioanilides of 3-oxobutanoic acid 1 (X = S) 11 in heterocyclization reactions with various diamines. We have found that good leaving groups at C-2 of compound 1 offer an entry to formation of six-and seven-membered rings by treatment with binucleophiles. The reaction includes the initial nucleophilic attack of the nitrogen atoms of aliphatic 1,3-or 1,4-diamines on C-2 of compounds 1, followed by a novel sigmatropic rearrangement. On the other hand, the reactions of 1 with aliphatic 1,2-diamines lead to 1,4-diazines by ring expansion of the intermediate 1, 3-diazines. 12 In order to develop synthetic applications of thioanilides 1a-c in closing heterocyclic rings we have transformed them into phenylhydrazones 2a-c by treatment with phenylhydrazine (Scheme 1). The nucleophilic attack of the amino group of phenylhydrazine took place exclusively on the C-2 position of 2-anilino-2-methoxy-3-oxothiobutanoic acid anilides 1a-c.In contrast, the reaction of 2-anilino-2-methoxy-3-oxobutanoic acid anilide 3a (X = O), under similar conditions, exclusively provided osazone 4a (Scheme 1).Compounds 2a-c can appear in two isomeric forms corresponding to Z or E configuration of the 1-thia-4-aza-1,3-butadiene system. In solution, spectral data confirm the structure of the molecules of 2a-c as shown in Scheme 1 as the unique reaction product. X-ray analysis of 2a was carried out to prove the configuration in the solid state and precisely determine the molecular geometry. 14 A perspective view of molecule of 2a with the crystallographic atom numbering is presented in Figure 1. The central framework of the molecule, consisting of heteroatoms (S1, O1, N1-N3) and carbon atoms C1-C4, is quite flat. None of these atoms deviates from the least-squares plane passing through the heteroatoms by more than 0.1 Scheme 1Downloaded by: Chinese University of Hong Kong. Copyrighted material.

Multiplicity of Diverse Heterocycles from Polymer-Supported α-Acylamino Ketones

“…4 H -1,2,5-Triazepine derivatives were prepared from from α-amino hydrazones 43. Two reports described syntheses of 1,2,5-triazepin-3,6-diones44 and their 4-thioxo derivatives 45. Koenig et al46 attempted to synthesize 3-aryl-tetrahydro-1,2-diazepines by a reaction of aryl-δ-chlorobutyl ketones with unsubstituted and monosubstituted hydrazines.…”

Perhydropyrimidinylium and 1,3-diazepinylium salts as potential ionic liquids

“…Since reactions of anilides and pyridilides of some 3-oxoacids were one of the major aspects of our recent works, 22 we selected one of them as a reference reaction (Scheme 3). It has been shown 22 that reaction of pyridilide 15 with nitrosobenzene leads to formation of pyrido [1,2-a] [1,3,5]triazin-2-one 16 as the main product.…”

“…It has been shown 22 that reaction of pyridilide 15 with nitrosobenzene leads to formation of pyrido [1,2-a] [1,3,5]triazin-2-one 16 as the main product. Ionic liquid 10 was chosen as a medium for the reaction and reaction time was arbitrarily chosen as shorter than typical.…”

One-Pot Synthesis of 3,4-Dihydro-2H-pyrido[1,2-a][1,3,5]triazin-2-one Derivatives fromN-(2′-Pyridinyl)benzoylacetamide and Nitrosobenzenes

“…This results in forming corresponding carbodiimides 5a-c and 2¢-pyridinylisocyanate 6 (Scheme 2). (8) and N-(2¢-pyridinyl)benzoylthioacetamide (9) underwent oxidative cyclisation by the treatment with nitrosobenzene. Oxidative ring closure of 8 takes place between the nitrogen atom of the pyridine ring and the sulfur atom of the thioamide moiety forming a 1,2,4-thiadiazolo[2,3-a]pyridine derivative 10 with elimination of the acetyl fragment.…”

“…The structure of compound 10 was established on the basis of IR, 13 C NMR, 1 H NMR, and MS analyses and microanalyses. On the other hand N-(2¢-pyridinyl)benzoylthioacetamide (9) gave the known 1-phenyl-2-(2H-[1,2,4]thiadiazolo[2,3-a]pyridin-2-yliden)ethanone (11) 12a (Scheme 3). Such oxidation is a common way of obtaining [1,2,4]thiadiazolo[2,3-a]pyridine derivatives, 13a,b,c which constitute a new family of potassium channel openers, 13b and exhibit excellent endothelin receptor antagonistic activity.…”