Hydrazide

Hydrazides in organic chemistry are a class of organic compounds with the formula R−NR¹−NR²R³ where R is acyl (R'−C(=O)−), sulfonyl (R'−S(=O)₂−), phosphoryl ((R'−)₂P(=O)−), phosphonyl ((R'−O−)₂P(=O)−), etc. and R¹, R², R³ and R' are any groups (typically hydrogen or organyl).¹ Unlike hydrazine and alkylhydrazines, hydrazides are nonbasic owing to the inductive influence of the acyl, sulfonyl, or phosphoryl substituent.

A common sulfonyl hydrazide is p-toluenesulfonyl hydrazide, a white air-stable solid. They are also widely used as organic reagents.

Toluenesulfonyl hydrazide is used to generate toluenesulfonyl hydrazones. Derived from ketones, these hydrazones participate in the Shapiro reaction² and the Eschenmoser–Tanabe fragmentation.³⁴

2,4,6-Triisopropylbenzenesulfonylhydrazide is a useful source of diimide.⁵

Acylhydrazines are derivatives of carboxylic acids, although they are typically prepared by the reaction of esters with hydrazine.⁷

Transamidation is possible but requires long-duration heat, and acyl moieties rarely migrate off another hydrazide.^{8: 527, 543} An exception are the chloral hydrazones, which deacylate easily.^8: 570

Alternatively, bromine oxidizes aldehydic hydrazones to a hydrazidoyl bromide, which then hydrolyzes to an acyl hydrazide.^{8: 525–526}

Lithium aluminum hydride reduces acylhydrazides to the hydrazine only if the hydrazide lacks a labile proton.^{8: 550–552}

An applied example is a synthesis of sunitinib begins by mixing 5-fluoroisatin slowly into hydrazine hydrate.⁹ After 4 hours at 110 °C, the indole ring structure has been broken into (2-amino-5-fluoro-phenyl)-acetic acid hydrazide with reduction of the ketone at the 3-position. Subsequent annelation in strong acid creates the 1,3-dihydro-2-oxo indole structure required for the drug.