Hydrazides in
organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic matter, organic materials, i.e., matter in its various forms that contain ...
are a class of
organic compound
Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...
s with the formula where R is
acyl
In chemistry, an acyl group is a moiety derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids. It contains a double-bonded oxygen atom and an organyl group () or hydrogen in the case of formyl grou ...
(),
sulfonyl
In organosulfur chemistry, a sulfonyl group is either a functional group found primarily in sulfones, or a substituent obtained from a sulfonic acid by the removal of the hydroxyl group, similarly to acyl groups.
Group
Sulfonyl groups can be w ...
(),
phosphoryl
A phosphoryl group is a trivalent group, consisting of a phosphorus atom (symbol P) and an oxygen atom (symbol O), where the three free valencies are on the phosphorus atom. While commonly depicted as possessing a double bond (P=O) the bonding i ...
(),
phosphonyl () and similar groups (
chalcogen
The chalcogens (ore forming) ( ) are the chemical elements in group 16 of the periodic table. This group is also known as the oxygen family. Group 16 consists of the elements oxygen (O), sulfur (S), selenium (Se), tellurium (Te), and the rad ...
analogs are included, for example
sulfur
Sulfur ( American spelling and the preferred IUPAC name) or sulphur ( Commonwealth spelling) is a chemical element; it has symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms ...
analogs called thiohydrazides),
[ (subscription required)] and R' are any groups (typically
hydrogen
Hydrogen is a chemical element; it has chemical symbol, symbol H and atomic number 1. It is the lightest and abundance of the chemical elements, most abundant chemical element in the universe, constituting about 75% of all baryon, normal matter ...
or
organyl
In organic and organometallic chemistry, an organyl group (commonly denoted by the letter " R") is an organic substituent with one (sometimes more) free valence electron(s) at a carbon atom.. The term is often used in chemical patent literatur ...
).
Unlike
hydrazine
Hydrazine is an inorganic compound with the chemical formula . It is a simple pnictogen hydride, and is a colourless flammable liquid with an ammonia-like odour. Hydrazine is highly hazardous unless handled in solution as, for example, hydraz ...
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
The Shapiro reaction or tosylhydrazone decomposition is an organic reaction in which a ketone or aldehyde is converted to an alkene through an intermediate hydrazone in the presence of 2 equivalents of organolithium reagent. The reaction was disco ...
and the
Eschenmoser–Tanabe fragmentation.
2,4,6-Triisopropylbenzenesulfonylhydrazide is a useful source of
diimide
Diimide, also called diazene or diimine, is a compound having the formula HN=NH. It exists as two geometric isomers, ''E'' (''trans'') and ''Z'' (''cis''). The term diazene is more common for organic derivatives of diimide. Thus, azobenzene is an ...
.
Acyl hydrazides
Acylhydrazines are
derivatives of
carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...
s, although they are typically prepared by the reaction of esters with hydrazine:
Use
An applied example is a synthesis of
sunitinib
Sunitinib, sold under the brand name Sutent, is an anti-cancer medication. It is a small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imat ...
begins by mixing 5-fluoro
isatin
Isatin, also known as tribulin, is an organic compound derived from indole with formula C8H5NO2. The compound was first obtained by Otto Linné Erdman and Auguste Laurent in 1840 as a product from the oxidation of indigo dye by nitric acid and ...
slowly into
hydrazine hydrate
Hydrazine is an inorganic compound with the chemical formula . It is a simple pnictogen hydride, and is a colourless flammable liquid with an ammonia-like odour. Hydrazine is highly hazardous unless handled in solution as, for example, hydraz ...
.
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
{{Authority control
Functional groups