Hydrazone
Encyclopedia
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
s with the structure R1R2C=NNH2. They are related to ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
s and aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
s by the replacement of the oxygen with the NNH2 functional group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
. They are formed usually by the action of hydrazine
Hydrazine
Hydrazine is an inorganic compound with the formula N2H4. It is a colourless flammable liquid with an ammonia-like odor. Hydrazine is highly toxic and dangerously unstable unless handled in solution. Approximately 260,000 tons are manufactured annually...
on ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
s or aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
s.
Uses
The formation of aromatic hydrazone derivatives is used to measure the concentration of low molecular weight aldehydeAldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
s and ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
s, e.g. in gas streams. For example, dinitrophenylhydrazine coated onto a silica sorbent
Sorbent
A sorbent is a material used to absorb liquids or gases. Examples include:*A material similar to molecular sieve material. It has a large internal surface area and good thermal conductivity. It is typically supplied in pellets of 1 mm to 2 mm diameter and roughly 5 mm length or as...
is the basis of an adsorption
Adsorption
Adsorption is the adhesion of atoms, ions, biomolecules or molecules of gas, liquid, or dissolved solids to a surface. This process creates a film of the adsorbate on the surface of the adsorbent. It differs from absorption, in which a fluid permeates or is dissolved by a liquid or solid...
cartridge. The hydrazones are then eluted and analyzed by HPLC
High-performance liquid chromatography
High-performance liquid chromatography , HPLC, is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.HPLC typically utilizes different types of stationary...
using a UV
Ultraviolet
Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...
detector.
The compound carbonyl cyanide-p-trifluoromethoxyphenylhydrazone
Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone
Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone is an ionophore that is a mobile ion carrier. It referred to as an uncoupling agent because it disrupts ATP synthesis by transporting hydrogen ions through a cell membrane before they can be used to provide the energy for oxidative...
(abbreviated as FCCP) is used to uncouple
Uncoupling protein
An uncoupling protein is a mitochondrial inner membrane protein that can dissipate the proton gradient before it can be used to provide the energy for oxidative phosphorylation.There are five types known in mammals:* UCP1, also known as thermogenin* UCP2...
ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
synthesis
ATP synthase
right|thumb|300px|Molecular model of ATP synthase by X-ray diffraction methodATP synthase is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate . ATP is the most commonly used "energy currency" of cells from most organisms...
and reduction of oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
in oxidative phosphorylation
Oxidative phosphorylation
Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate . Although the many forms of life on earth use a range of different nutrients, almost all aerobic organisms carry out oxidative phosphorylation to produce ATP,...
in molecular biology
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
. Phenylhydrazine reacts with glucose to form an osazone
Osazone
Osazones are a class of carbohydrate derivatives found in organic chemistry formed when sugars are reacted with phenylhydrazine . The famous German chemist Emil Fischer developed and used the reaction to identify sugars whose stereochemistry differed by only one chiral carbon...
.
Hydrazone-based coupling methods are used in medical biotechnology to couple drugs to targeted antibodies (see ADC
Antibody-drug conjugate
Antibody-drug conjugates are a new type of targeted therapy, used for example for cancer. They consist of an antibody linked to a payload drug . Hence, they are a type of immunoconjugate and often an immunotoxin.The antibody causes the ADC to bind to the target cancer cells...
), 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 reactants in hydrazone iodinationHydrazone 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 D. H. R...
, the Shapiro reaction
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 strong base. The reaction was discovered by Robert H. Shapiro in 1975...
and the Bamford-Stevens reaction
Bamford-Stevens reaction
The Bamford–Stevens reaction is a chemical reaction whereby treatment of tosylhydrazones with strong base gives alkenes. It is named for the British chemist William Randall Bamford and the Scottish chemist Thomas Stevens Stevens...
to vinyl
Vinyl
A vinyl compound is any organic compound that contains a vinyl group ,which are derivatives of ethene, CH2=CH2, with one hydrogen atom replaced with some other group...
compounds. A hydrazone is an intermediate in the Wolff–Kishner reduction. Another method to synthesis a hydrazone is the Japp–Klingemann reaction (from β-keto-acids or β-keto-esters and aryl diazonium salts)
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 if the C=N bond can react with organometallic nucleophiles. The alpha-hydrogen atom is more acidic by 10 orders of magnitudeOrder of magnitude
An order of magnitude is the class of scale or magnitude of any amount, where each class contains values of a fixed ratio to the class preceding it. In its most common usage, the amount being scaled is 10 and the scale is the exponent being applied to this amount...
compared to the ketone and therefore more nucleophilic. Deprotonation with for instance LDA
Lithium diisopropylamide
Lithium diisopropylamide is the chemical compound with the formula [2CH]2NLi. Generally abbreviated LDA, it is a strong base used in organic chemistry for the deprotonation of weakly acidic compounds. The reagent has been widely accepted because it is soluble in non-polar organic solvents and it...
gives an azaenolate which can be alkylated by alkyl halides, a reaction pioneered by E.J. Corey and Dieter Enders
Dieter Enders
Dieter Enders is an organic chemist who has done work developing asymmetric synthesis, in particular using modified prolines as asymmetric auxiliaries. The most widely appled of his chiral auxiliaries are the complementary SAMP and RAMP auxialliaries, which allow for asymmetric alpha-alkylation of...
in 1978. In asymmetric synthesis SAMP and RAMP are two chiral hydrazines that act as chiral auxiliary
Chiral auxiliary
A chiral auxiliary is a chemical compound or unit that is temporarily incorporated into an organic synthesis so that it can be carried out asymmetrically with the selective formation of one of two enantiomers...
with a chiral hydrazone intermediate.