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.

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

References

1. IUPAC , Compendium of Chemical Terminology , 5th ed. (the "Gold Book") (2025). Online version: (2006–) " Hydrazides ". doi : 10.1351/goldbook.H02879
2. Shapiro, Robert H. (1976). "Alkenes from Tosylhydrazones". Org. React. 23 (3): 405–507. doi:10.1002/0471264180.or023.03. ISBN   0471264180.
3. Schreiber, J.; Felix, D.; Eschenmoser, A.; Winter, M.; Gautschi, F.; Schulte-Elte, K. H.; Sundt, E.; Ohloff, G.; Kalovoda, J.; Kaufmann, H.; Wieland, P.; Anner, G. (1967). "Die Synthese von Acetylen-carbonyl-Verbindungen durch Fragmentierung von α,β-Epoxy-ketonen mit p-Toluolsulfonylhydrazin. Vorläufige Mitteilung". Helv. Chim. Acta (in German). 50 (7): 2101–2108. doi:10.1002/hlca.19670500747.
4. Tanabe, Masato; Crowe, David F.; Dehn, Robert L. (1967). "A novel fragmentation reaction of α,β-epoxyketones the synthesis of acetylenic ketones". Tetrahedron Lett. 8 (40): 3943–3946. doi:10.1016/S0040-4039(01)89757-4.
5. Chamberlin, A. Richard; Sheppeck, James E.; Somoza, Alvaro (2008). "2,4,6-Triisopropylbenzenesulfonylhydrazide". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rt259.pub2. ISBN   978-0471936237.
6. "ChemicalBook:2-(4-ethylphenoxy)acetylhydrazide" . Retrieved 24 May 2023.
7. Schirmann, Jean-Pierre; Bourdauducq, Paul (2001). "Hydrazine". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a13_177. ISBN   3527306730.
8. Paulsen, Hans; Stoye, Dieter (1970). "The chemistry of hydrazides". In Zabicky, Jacob (ed.). The Chemistry of Amides. The Chemistry of Functional Groups. London: Interscience (Wiley). pp. 515–600. doi:10.1002/9780470771235. ISBN   0-471-98049-8. LCCN   76-116520.
9. "US patent 6573293". Archived from the original on 2012-09-06.