Hydrazones are a class of

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...

s 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 b ...

s and

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl gro ...

s by the replacement of the oxygen =O with the =

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the r ...

. 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. : Hydrazone General Synthesis

Phenylhydrazine reacts with reducing sugars to form hydrazones known as osazones, which was developed by German chemist

Emil Fischer Hermann Emil Louis Fischer (; 9 October 1852 – 15 July 1919) was a German chemist and 1902 recipient of the Nobel Prize in Chemistry. He discovered the Fischer esterification. He also developed the Fischer projection, a symbolic way of draw ...

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 ...

coated onto a

silica Silicon dioxide, also known as silica, is an oxide of silicon with the chemical formula , most commonly found in nature as quartz and in various living organisms. In many parts of the world, silica is the major constituent of sand. Silica is ...

sorbent A sorbent is a material used to absorb or adsorb liquids or gases. Examples include: *A material similar to molecular sieve material, which acts by adsorption (attracting molecules to its surface). It has a large internal surface area and good th ...

is the basis of an

adsorption Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or dissolved solid to a surface. This process creates a film of the ''adsorbate'' on the surface of the ''adsorbent''. This process differs from absorption, in which a ...

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 p ...

using a UV detector. The compound carbonyl cyanide-''p''-trifluoromethoxyphenylhydrazone (abbreviated as FCCP) is used to uncouple ATP synthesis and reduction of

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements ...

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 t ...

molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and phys ...

. Hydrazones are the basis of bioconjugation strategies. Hydrazone-based coupling methods are used in medical biotechnology to couple drugs to targeted antibodies (see ADC), 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 10²- to 10³-fold more sensitive to hydrolysis than analogous

oximes In organic chemistry, an oxime is a organic compound belonging to the imines, with the general formula , where R is an organic side-chain and R’ may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime. O-substitute ...

. When derived from hydrazine itself, hydrazones condense with a second equivalent of a carbonyl to give

azine Azines are a functional class of organic compounds with the connectivity RR'C=N-N=CRR'. These compounds are the product of the condensation of hydrazine with ketones and aldehydes, although in practice they are often made by alternative routes ...

s: : Hydrazones are intermediates in the

Wolff–Kishner reduction The Wolff–Kishner reduction is a reaction used in organic chemistry to convert carbonyl functionalities into methylene groups. In the context of complex molecule synthesis, it is most frequently employed to remove a carbonyl group after it has se ...

. 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 B ...

, 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 Vinyl may refer to: Chemistry * Polyvinyl chloride (PVC), a particular vinyl polymer * Vinyl cation, a type of carbocation * Vinyl group, a broad class of organic molecules in chemistry * Vinyl polymer, a group of polymers derived from 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

s when used in the preparation of 3,5-disubstituted 1''H''-

pyrazole Pyrazole is an organic compound with the formula C3H3N2H. It is a heterocycle characterized by a 5-membered ring of three carbon atoms and two adjacent nitrogen atoms, which are in ortho-substitution. Pyrazole is a weak base, with p''K''b 11.5 ( ...

s, a reaction also well known using

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 toxic unless handled in solution as, for example, hydrazine h ...

. With a transition metal catalyst, hydrazones can serve as organometallic reagent surrogates to react with various electrophiles. : Lasri condensation reaction

''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 An order of magnitude is an approximation of the logarithm of a value relative to some contextually understood reference value, usually 10, interpreted as the base of the logarithm and the representative of values of magnitude one. Logarithmic dis ...

compared to the ketone and therefore more nucleophilic. Deprotonation with for instance LDA gives an azaenolate which can be alkylated by alkyl halides. The hydrazines SAMP and RAMP function as

chiral auxiliary In stereochemistry, a chiral auxiliary is a stereogenic group or unit that is temporarily incorporated into an organic compound in order to control the stereochemical outcome of the synthesis. The chirality present in the auxiliary can bias the ...

. :

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 . Monomethylhydra ...

(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 Benzophenone is the organic compound with the formula (C6H5)2CO, generally abbreviated Ph2CO. It is a white solid that is soluble in organic solvents. Benzophenone is a widely used building block in organic chemistry, being the parent diarylket ...

. Selected parameters: C=N, 128 pm; N-N, 138 pm, N-N-C(Ar), 119 pm

References