Anhydrides, cyclic, reaction with hydrazine

There is one useful case of the second disconnection. Maleic anhydride 180 has to have a Z alkene because of its cyclic structure. Reaction with hydrazine gives a diamide 181 that prefers to exist as 182 and is known as maleic hydrazide . 

Aryltellnrinyl acetates, generated as previously described from the corresponding tellurinic anhydrides and acetic acid, add to hydroxy olefins, giving tellurinylated cyclic ethers. The reaction is performed in refluxing acetic acid or in chloroform in the presence of BFj EtjO. Owing to their hygroscopicity and intractable nature, the products are reduced with hydrazine hydrate, and isolated as tellurides (as for the aminotellurinylation reactions). 

Reaction of phthalic anhydride (70-1) with the ylide from ethyl triphenylphos-phoniumacetate leads to the condensation product (70-2), which in effect consists of a cyclic enol anhydride. Treatment of this product with hydrazine leads to the hydrazone-hydrazide (70-3). Alkylation of the anion from removal of the hydrazide proton with the substituted benzyl bromide (70-4) affords the alkylation product (70-5). Saponification then leads to the aldose reductase inhibitor ponalrestat (70-6) [79]. 

The conditions for the condensation of cyclic anhydrides 493 with hydrazines in acetic acid to give the substituted pyridazinediones 494 were varied, depending on both the reactants, from 1 h by stirring at room temperature to 24 h at solvent reflux. The yields were 45-85% and in some cases no products were obtained. However, under MWI the reaction times can be reduced to 2-6 min leading to the expected derivatives in good to excellent yields (72-88%) (Scheme 96) (96TL4145). 

Mazalova ZI, Lopyrev VA, Sokolov SV, Ryazanova RM (1975) Reactions of hydrazides of perfluoro acids. VI. Reaction of cyclic anhydrides of perfluoro acids with hydrazine and hydrazides of perfluoro adds. Zh Oig Khim 11 62-67... 

The saturated analogs, e.g., succinic anhydride or succinic esters, behave differently and only in few cases were pyridazines obtained. The reaction between succinic anhydride and various amounts of hydrazine hydrate has been studied under different reaction conditions, but always uncyclized products were formed. One of these is a polymeric hydrazide which, when treated with benzenesulfonyl chloride, yielded the monobenzenesulfonyl derivative of cyclic succinhydrazide (30, R = PhS02) along with a compound formulated as bicyclic disuccinhydrazide (152, Section IV,H, 4), but later shown to be 153. Authentic cyclic succinhydrazide (30, R = H) was obtained upon reducing maleic hydrazide with aluminum amalgam. Previous claims that 30 (R = H) may be obtained from succinic acid or A-aminosuccinimide proved to be incorrect. 

The structure of the osazone derived from dehydroascorbic acid remains in dispute. Recently (Vol. 13, p. 95) it was described as the phenylhydrazine-phenylazo-structure (34), but it is now claimed that the bis(hydrazone) formula (35) fits the n.m.r. and u.v. data more satisfactorily. The structure of the bi-cyclic oxidation product of (35) has been shown to be a 3,6-anhydride (36) by n.m.r. and m.s. A n.m.r. study of the formation of dehydroascorbic acid hydrazones revealed that the two 2-phenylhydrazides (37) were formed initially and subsequently underwent dehydration to give the two rotationally isomeric 2-phenyIhydrazones. Reaction of 6-bromo-6-deoxy-isoascorbic acid (D-ery thro) with phenyl hydrazine afforded the cyclized bis(hydrazone) (38). Treatment of D-threo-ascorbic acid bis(phenylhydrazone) with caustic soda afforded the cyclized product (39). The corresponding D-erythro- and L-threo-isomers were also prepared and the side-chains have been modified in various ways. 

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