Chemistry:Hydrazide
Hydrazides in organic chemistry are a class of organic compounds with the formula R–NR1
–NR2
R3
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
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
- ↑ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "Hydrazides". doi:10.1351/goldbook.H02879
- ↑ Shapiro, Robert H. (1976). "Alkenes from Tosylhydrazones". Org. React. 23 (3): 405–507. doi:10.1002/0471264180.or023.03. ISBN 0471264180.
- ↑ Schreiber, J.; Felix, D.; Eschenmoser, A.; Winter, M.; Gautschi, F.; Schulte-Elte, K. H.; Sundt, E.; Ohloff, G. et al. (1967). "Die Synthese von Acetylen-carbonyl-Verbindungen durch Fragmentierung von α,β-Epoxy-ketonen mit p-Toluolsulfonylhydrazin. Vorläufige Mitteilung" (in German). Helv. Chim. Acta 50 (7): 2101–2108. doi:10.1002/hlca.19670500747.
- ↑ 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.
- ↑ 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.
- ↑ "ChemicalBook:2-(4-ethylphenoxy)acetylhydrazide". http://www.chemicalbook.com/ChemicalProductProperty_EN.aspx?CBNumber=CB0727806. Retrieved 24 May 2023.
- ↑ Schirmann, Jean-Pierre; Bourdauducq, Paul (2001). "Ullmann's Encyclopedia of Industrial Chemistry". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a13_177.
- ↑ 8.0 8.1 8.2 8.3 Paulsen, Hans; Stoye, Dieter (1970). "The chemistry of hydrazides". in Zabicky, Jacob. The Chemistry of Amides. The Chemistry of Functional Groups. London: Interscience (Wiley). pp. 515–600. doi:10.1002/9780470771235. ISBN 0-471-98049-8.
- ↑ "US patent 6573293". http://www.patentlens.net/patentlens/structured.cgi?patnum=US_6573293#show.
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