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.

Sulfonyl hydrazides

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. When derived from ketones, these hydrazones participate in the Shapiro reaction^[2] and the Eschenmoser–Tanabe fragmentation.^[3][4]

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

Acyl hydrazides

An example of an acylhydrazine. This compound has been called acetylhydrazide, acetohydrazide, or acetic acid hydrazide.^[6]

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}

Use

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.

See also

• hydrazide imide - tautomeric form of amidrazone