Hydrazides from heterocycles

Hydrazinolysis products obtained from oxazolones 528 are versatile synthetic intermediates and can be further elaborated to a variety of different heterocycles depending on the substituents and on the experimental conditions. For example, N-aminoimidazolones 529, isolated from reaction of 528 and hydrazine, have been acylated ° or condensed with carbonyl compounds to produce 530 and 531, respectively. On the other hand, ring-opening 528 with hydrazine affords a dehydroamino acid hydrazide 532. Condensation of 532 with aldehydes yields a hydrazone 533 that can be cyclized to an A -iminoimidazolone 534 (Scheme 7.168). ... 

The patents 9 47) filed by Richter and Hoebn in du Pont include many aromatic and heterocyclic condensed polymers for asymmetric reverse osmosis membranes, for example, the condensed polymers 4 from 3-arninobcnzhydrazide, 4-amino-benz-hydrazide (5), isophthaloyl chloride, and terephthaloyl chloride (6). The membranes were cast from polyamide solutions containing 0 3 % LiCl in dimethylacetamide,... 

The 1,2,4-triazine core is a synthetically important scaffold because it could be readily transformed into a range of different heterocyclic systems such as pyridines (Sect. 3.1) via intramolecular Diels-Alder reactions with acetylenes. 1,2,4-Triazines have been synthesized by the condensation of 1,2-diketones with acid hydrazides in the presence of NH4OH in acetic acid for up to 24 h at reflux temperature. Microwave dielectric heating in closed vessels allowed the reaction to be performed at 180 °C (60 °C above the boiling point of acetic acid). As a result, the reaction time was reduced to merely 5 minutes. Subsequently, a 48-membered library of 1,2,4-triazines was generated from diverse acyl hydrazides and a-diketones [139]. Two thirds of the desired heterocycles precipitated from the reaction mixture upon cooling with > 75% purity, while the remaining part of the library was purified by preparative LCMS (Scheme 56). 

Aromatic and heterocyclic aldehydes have been prepared from hydra-zides, via the arylsulfonyl derivative, in 50-65% and 20-40% yields, respectively the method fails in the aliphatic series. The hydrazide is treated with benzenesulfonyl chloride in pyridine, and the subsequent product is isolated by precipitation with water and decomf>osed by heating with sodium carbonate in ethylene glycol or glycerol at 160°. 

Reaction of aromatic or heterocyclic amines with formaldehyde and urea or phenylthioureas gave 2-(oxo)thioxohexahydro-l,3,5-triazines 90. Regioselective cyclization and isomerization of propargylthio-l,2,4-triazinones were achieved to give the fused heterocycles 91-93. Cyclization of isatin 3-thiosemicarbazones gave 94 which can be alkylated to 95 . The imidazotriazepines 96 were obtained from heating a mixture of hydrazide and ortho-ester. 

M-Acetylsaccharinyl acid derivatives 408, which are structurally related to COX-2 inhibitor celecoxib, were designed and synthesised [133] from M-saccharinyl acetate 407a, prepared via the reaction of ethyl bromoacetate with sodium saccharin by heating the reactants in DMF (see [133]). Its transformation into the corresponding hydrazide 407b and subsequent reaction with ethyl acetoacetate, /3-diketones and maleic anhydride, afforded the heterocyclic compounds 408 [134] (Scheme 97). 

There are examples of pyridazine formation from bicyclic heterocycles. 1-Substituted carboxyalkylpyridazines (83) are obtained by alkaline hydrolysis of the corresponding pyrazolo[l,2-a]pyridazines (82), obtainable from maleic hydrazide and chlorides of a,/(-unsaturated acids.198 1-Phenacy-... 

Aromatic acid hydrazides, semicarbazides, and thiosemicarbazides react with carbonimidoyl dichlorides with elimination of hydrogen chloride and formation of the corresponding heterocycles Thus, from... 

S. G. Kucukguzel, I. Kucukguzel, E. Tatar, S. RoUas, F. Sahin, M. GuUuce, E. De Clercq, and L. Kabasakal. Synthesis of some novel heterocyclic compounds derived from diflunisal hydrazide as potential anti-infective and antiinflammatory agents. Eur. J. Med. Chem., 42(7) 893-901, July 2007. 

---