Hydrazones are a class of
organic compounds with the structure . They are related to
ketone
In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...
s and
aldehydes by the replacement of the oxygen =O with the =
functional group. They are formed usually by the action of
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 toxic unless handled in solution as, for example, hydrazine ...
on ketones or aldehydes.
Synthesis
Hydrazine, organohydrazines, and 1,1-diorganohydrazines react with aldehydes and ketones to give hydrazones.
:
Phenylhydrazine reacts with reducing sugars to form hydrazones known as
osazone
Osazones are a class of carbohydrate derivatives found in organic chemistry formed when Reducing sugar, reducing sugars are reacted with excess of phenylhydrazine at boiling temperatures.
Formation
Osazone formation was developed by Emil Fisch ...
s, which was developed by German chemist
Emil Fischer as a test to differentiate monosaccharides.
Uses
Hydrazones are the basis for various analyses of ketones and aldehydes. For example,
dinitrophenylhydrazine
2,4-Dinitrophenylhydrazine (2,4-DNPH or DNPH) is the organic compound C6H3(NO2)2NHNH2. DNPH is a red to orange solid. It is a substituted hydrazine. The solid is relatively sensitive to shock and friction. For this reason DNPH is usually handled a ...
coated onto a
silica sorbent is the basis of an
adsorption cartridge. The hydrazones are then eluted and analyzed by
HPLC
High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pa ...
using a
UV detector.
The compound
carbonyl cyanide-''p''-trifluoromethoxyphenylhydrazone (abbreviated as FCCP) is used to
uncouple ATP
ATP may refer to:
Companies and organizations
* Association of Tennis Professionals, men's professional tennis governing body
* American Technical Publishers, employee-owned publishing company
* ', a Danish pension
* Armenia Tree Project, non ...
synthesis and
reduction of
oxygen in
oxidative phosphorylation
Oxidative phosphorylation (UK , US ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine tri ...
in
molecular biology.
Hydrazones are the basis of bioconjugation strategies.
Hydrazone-based coupling methods are used in medical biotechnology to couple drugs to targeted antibodies (see
ADC
ADC may refer to:
Science and medicine
* ADC (gene), a human gene
* AIDS dementia complex, neurological disorder associated with HIV and AIDS
* Allyl diglycol carbonate or CR-39, a polymer
* Antibody-drug conjugate, a type of anticancer treatment ...
), e.g. antibodies against a certain type of cancer cell. The hydrazone-based bond is stable at neutral pH (in the blood), but is rapidly destroyed in the acidic environment of lysosomes of the cell. The drug is thereby released in the cell, where it exerts its function.
Reactions
Hydrazones are susceptible to hydrolysis:
:
Alkyl hydrazones are 10
2- to 10
3-fold more sensitive to hydrolysis than analogous
oximes.
When derived from hydrazine itself, hydrazones condense with a second equivalent of a carbonyl to give
azines:
:
Hydrazones are intermediates in the
Wolff–Kishner reduction.
Hydrazones are reactants in
hydrazone iodination Hydrazone iodination is an organic reaction in which a hydrazone is converted into a vinyl iodide by reaction of iodine and a non-nucleophilic base such as DBU. First published by Derek Barton in 1962 the reaction is sometimes referred to as the Bar ...
, 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 discov ...
, and the
Bamford-Stevens reaction to
vinyl compounds. Hydrazones can also be synthesized by the
Japp–Klingemann reaction
The Japp–Klingemann reaction is a chemical reaction used to synthesize hydrazones from β-keto-acids (or β-keto-esters) and aryl diazonium salts. The reaction is named after the chemists Francis Robert Japp and Felix Klingemann.
:
The hydrazo ...
via β-keto-acids or β-keto-esters and aryl diazonium salts. Hydrazones are converted to
azines when used in the preparation of 3,5-disubstituted 1''H''-
pyrazoles, a reaction also well known using
hydrazine hydrate. With a transition metal catalyst, hydrazones can serve as organometallic reagent surrogates to react with various electrophiles.
:
''N'',''N''-dialkylhydrazones
In ''N'',''N''-dialkylhydrazones the C=N bond can be hydrolysed, oxidised and reduced, the N–N bond can be reduced to the free amine. The carbon atom of the C=N bond can react with organometallic nucleophiles. The alpha-hydrogen atom is more acidic by 10
orders of magnitude compared to the ketone and therefore more nucleophilic. Deprotonation with for instance
LDA LDA may refer to:
Aviation
*Localizer type directional aid, an instrument approach to an airport
*Landing distance available, the length of runway that is available for the ground run of an airplane landing
Law
*Legal document assistant, a non-la ...
gives an azaenolate which can be alkylated by alkyl halides. The hydrazines SAMP and RAMP function as
chiral auxiliary.
:
Gallery
File:Benzophenone hydrazone-structure.png, Benzophenone hydrazone, an illustrative hydrazone
File:Carbonyl cyanide m-chlorophenyl hydrazone.svg, Carbonyl cyanide ''m''-chlorophenyl hydrazone
File:Gyromitrin.svg, Gyromitrin
Gyromitrin is a toxin and carcinogen present in several members of the fungal genus ''Gyromitra'', like '' G. esculenta''. Its formula is . It is unstable and is easily hydrolyzed to the toxic compound monomethylhydrazine . Monomethylhydrazin ...
(Acetaldehyde methylformylhydrazone), a toxin
File:Dihydralazine structure.svg, Dihydralazine
Dihydralazine is a prescription drugDihydralazine - Uses, Side Effects, Substitutes, Composition And More. (n.d.). Lybrate. Retrieved July 10, 2021, from https://www.lybrate.com/medicine/dihydralazine with antihypertensive properties. It function ...
, an antihypertensive drug
File:NERYOZ.png, X-ray structure of DNP-derived hydrazone of benzophenone. Selected parameters: C=N, 128 pm; N-N, 138 pm, N-N-C(Ar), 119 pm
See also
*
Azo compound
*
Imine
*
Nitrosamine
In organic chemistry, nitrosamines (or more formally ''N''-Nitrosamines) are organic compounds with the chemical structure , where R is usually an alkyl group. They feature a nitroso group () bonded to a deprotonated amine. Most nitrosamines are ...
*
Hydrogenation of carbon–nitrogen double bonds In chemistry, the hydrogenation of carbon–nitrogen double bonds is the addition of the elements of dihydrogen (H2) across a carbon–nitrogen double bond, forming amines or amine derivatives. Although a variety of general methods have been develop ...
References
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Functional groups