Ketone
Encyclopedia
In organic chemistry
, a ketone (icon) is an organic compound
with the structure RC(=O)R', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group (C=O) bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology. Examples include many sugars and the industrial solvent acetone
.
According to the rules of IUPAC nomenclature
, ketones are named by changing the suffix -e of the parent alkane
to -one. For the most important ketones, however, traditional nonsystematic names are still generally used, for example acetone
and benzophenone
. These nonsystematic names are considered retained IUPAC names, although some introductory chemistry textbooks use names such as 2-propanone or propan-2-one instead of acetone, the simplest ketone (C
H
3-CO
-CH3). The position of the carbonyl group is usually denoted by a number.
Although used infrequently, "oxo" is the IUPAC nomenclature for a ketone functional group
. Other prefixes, however, are also used. For some common chemicals (mainly in biochemistry), "keto" or "oxo" is the term used to describe the ketone functional group
. The term "oxo" is used widely through chemistry. For example, it also refers to an oxygen atom bonded to a transition metal (a metal oxo).
s in that the carbonyl group (CO) is bonded to two carbons within a carbon skeleton. In aldehydes, the carbonyl is bonded to one carbon and one hydrogen and are located at the ends of carbon chains. Ketones are also distinct from other carbonyl-containing functional group
s, such as carboxylic acid
s, ester
s and amide
s.
The carbonyl group is polar as a consequence of the fact that the electronegativity of the oxygen center is greater than that for carbonyl carbon. Thus, ketones are nucleophilic at oxygen and electrophilic at carbon. Because the carbonyl group interacts with water by hydrogen bond
ing, ketones are typically more soluble in water than the related methylene compounds. Ketones are hydrogen-bond acceptors. Ketones are not usually hydrogen-bond donors and cannot hydrogen-bond to itself. Because of their inability to serve both as hydrogen-bond donors and acceptors, ketones tend not to "self-associate" and are more volatile than alcohol
s and carboxylic acid
s of comparable molecular weights. These factors relate to pervasiveness of ketones in perfumery and as solvents.
A ketone that has an α-hydrogen participates in a so-called keto-enol tautomerism
. The reaction with a strong base gives the corresponding enolate, often by deprotonation
of the enol.
(C6H5C(O)C6H5) are symmetrical ketones. Acetophenone
(C6H5C(O)CH3) is an unsymmetrical ketone. In the area of stereochemistry
, unsymmetrical ketones are known for being prochiral
.
. Acetylacetone
(pentane-2,4-dione) is virtually a misnomer (inappropriate name) because this species exists mainly as the monoenol CH3C(O)CH=C(OH)CH3. Its enolate is a common ligand in coordination chemistry.
, CH3C(O)CH=CH2, which is useful in Robinson annulation
reaction. Lest there be confusion, a ketone itself is a site of unsaturation; that is, it can be hydrogenated.
to the teens. Larger derivatives exist. Cyclohexanone, a symmetrical cyclic ketone, is an important intermediate in the production of nylon
. Isophorone
, derived from acetone, is an unsaturated, unsymmetrical ketone that is the precursor to other polymers. Muscone
, 3-methylpentadecanone, is an animal pheromone
.
. Tautomerization is catalyzed by both acids and bases. Usually, the keto form is more stable than the enol. This equilibrium allows ketones to be prepared via the hydration of alkyne
s.
≈ 20) than a regular alkane (pKa ≈ 50). This difference reflects resonance stabilization of the enolate ion that is formed through dissociation. The relative acidity of the α-hydrogen is important in the enolization reactions of ketones and other carbonyl compounds. The acidity of the α-hydrogen also allows ketones and other carbonyl compounds to undergo nucleophilic reactions at that position, with either stoichiometric and catalytic base.
near 1700 cm−1
. The exact position of the peak depends on the substituents.
Whereas 1H NMR
spectroscopy is, in general, not useful for establishing the presence of a ketone, 13C NMR
spectra exhibit signals somewhat downfield of 200 ppm depending on structure. Such signals are typically weak due to the absence of nuclear Overhauser effect
s. Since aldehydes resonate at similar chemical shift
s, multiple resonance experiments are employed to definitively distinguish aldehydes and ketones.
or with the Fehling's solution
. Methyl ketones give positive results for the iodoform test.
are produced annually by aerobic oxidation of cyclohexane
. Acetone is prepared by air-oxidation of cumene
.
For specialized or small scale organic synthetic
applications, ketones are often prepared by oxidation of secondary alcohols
:
Typical strong oxidants (source of "O" in the above reaction) include potassium permanganate
or a Cr(VI)
compound. Milder conditions make use of the Dess-Martin periodinane
or the Moffatt-Swern
methods.
Many other methods have been developed including:
s. The most important reactions follow from the susceptibility of the carbonyl carbon toward nucleophilic addition
and the tendency for the enolates to add to electrophiles.
Nucleophilic additions include in approximate order of their generality:
Electrophilic addition
, reaction with an electrophile
gives a resonance stabilized cation
occurs via the ketone ribulose-1,5-bisphosphate
. Many sugars are ketones, known collectively as ketose
s. The best known ketose is fructose
, which exists as a cyclic hemiketal, which masks the ketone functional group. Fatty acid synthesis
proceeds via ketones. Acetoacetate is an intermediate in the Kreb cycle which releases energy from sugars and carbohydrates.
In medicine, acetone
, acetoacetate, and beta-hydroxybutyrate
are collectively called ketone bodies
, generated from carbohydrate
s, fatty acid
s, and amino acid
s in most vertebrate
s, including humans. Ketones are elevated in blood
after fasting including a night of sleep, and in both blood and urine
in starvation
, hypoglycemia
due to causes other than hyperinsulinism
, various inborn errors of metabolism
, and ketoacidosis
(usually due to diabetes mellitus
). Although ketoacidosis is characteristic of decompensated or untreated type 1 diabetes, ketosis or even ketoacidosis can occur in type 2 diabetes
in some circumstances as well.
, methylethyl ketone, and cyclohexanone
. They are also common in biochemistry, but less so than in organic chemistry in general. The combustion of hydrocarbons is an uncontrolled oxidation process that gives ketones as well as many other types of compounds.
is a ketone). This characteristic is one reason for their popularity as solvents. Exceptions to this rule are the unsaturated ketones such as methyl vinyl ketone
with of 7 mg/kg (oral).
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
, a ketone (icon) is an organic compound
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...
with the structure RC(=O)R', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group (C=O) bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology. Examples include many sugars and the industrial solvent acetone
Acetone
Acetone is the organic compound with the formula 2CO, a colorless, mobile, flammable liquid, the simplest example of the ketones.Acetone is miscible with water and serves as an important solvent in its own right, typically as the solvent of choice for cleaning purposes in the laboratory...
.
Nomenclature and etymology
The word ketone derives its name from Aketon, an old German word for acetone.According to the rules of IUPAC nomenclature
IUPAC nomenclature
A chemical nomenclature is a set of rules to generate systematic names for chemical compounds. The nomenclature used most frequently worldwide is the one created and developed by the International Union of Pure and Applied Chemistry ....
, ketones are named by changing the suffix -e of the parent alkane
Alkane
Alkanes are chemical compounds that consist only of hydrogen and carbon atoms and are bonded exclusively by single bonds without any cycles...
to -one. For the most important ketones, however, traditional nonsystematic names are still generally used, for example acetone
Acetone
Acetone is the organic compound with the formula 2CO, a colorless, mobile, flammable liquid, the simplest example of the ketones.Acetone is miscible with water and serves as an important solvent in its own right, typically as the solvent of choice for cleaning purposes in the laboratory...
and benzophenone
Benzophenone
Benzophenone is the organic compound with the formula 2CO, generally abbreviated Ph2CO. Benzophenone is a widely used building block in organic chemistry, being the parent diarylketone.-Uses:...
. These nonsystematic names are considered retained IUPAC names, although some introductory chemistry textbooks use names such as 2-propanone or propan-2-one instead of acetone, the simplest ketone (C
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
H
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...
3-CO
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...
-CH3). The position of the carbonyl group is usually denoted by a number.
Although used infrequently, "oxo" is the IUPAC nomenclature for a ketone 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...
. Other prefixes, however, are also used. For some common chemicals (mainly in biochemistry), "keto" or "oxo" is the term used to describe the ketone 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...
. The term "oxo" is used widely through chemistry. For example, it also refers to an oxygen atom bonded to a transition metal (a metal oxo).
Structure and properties
The ketone carbon is often described as "sp2 hybridized," terminology that describes both their electronic and molecular structure. Ketones are trigonal planar about the ketonic carbon, with C-C-O and C-C-C bond angles of approximately 120°. Ketones differ from 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 in that the carbonyl group (CO) is bonded to two carbons within a carbon skeleton. In aldehydes, the carbonyl is bonded to one carbon and one hydrogen and are located at the ends of carbon chains. Ketones are also distinct from other carbonyl-containing 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...
s, such as carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
s, ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
s and amide
Amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
s.
The carbonyl group is polar as a consequence of the fact that the electronegativity of the oxygen center is greater than that for carbonyl carbon. Thus, ketones are nucleophilic at oxygen and electrophilic at carbon. Because the carbonyl group interacts with water by hydrogen bond
Hydrogen bond
A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...
ing, ketones are typically more soluble in water than the related methylene compounds. Ketones are hydrogen-bond acceptors. Ketones are not usually hydrogen-bond donors and cannot hydrogen-bond to itself. Because of their inability to serve both as hydrogen-bond donors and acceptors, ketones tend not to "self-associate" and are more volatile than alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
s and carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
s of comparable molecular weights. These factors relate to pervasiveness of ketones in perfumery and as solvents.
A ketone that has an α-hydrogen participates in a so-called keto-enol tautomerism
Keto-enol tautomerism
In organic chemistry, keto-enol tautomerism refers to a chemical equilibrium between a keto form and an enol . The enol and keto forms are said to be tautomers of each other...
. The reaction with a strong base gives the corresponding enolate, often by deprotonation
Deprotonation
Deprotonation is the removal of a proton from a molecule, forming the conjugate base.The relative ability of a molecule to give up a proton is measured by its pKa value. A low pKa value indicates that the compound is acidic and will easily give up its proton to a base...
of the enol.
Classes of ketones
Ketones are classified on the basis of their substituents. One broad classification subdivides ketones into symmetrical and unsymmetrical derivatives, depending on the equivalency of the two organic substituents attached to the carbonyl center. Acetone and benzophenoneBenzophenone
Benzophenone is the organic compound with the formula 2CO, generally abbreviated Ph2CO. Benzophenone is a widely used building block in organic chemistry, being the parent diarylketone.-Uses:...
(C6H5C(O)C6H5) are symmetrical ketones. Acetophenone
Acetophenone
Acetophenone is the organic compound with the formula C6H5CCH3. It is the simplest aromatic ketone. This colourless, viscous liquid is a precursor to useful resins and fragrances.-Production:Acetophenone can be obtained by a variety of methods...
(C6H5C(O)CH3) is an unsymmetrical ketone. In the area of stereochemistry
Stereochemistry
Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms within molecules. An important branch of stereochemistry is the study of chiral molecules....
, unsymmetrical ketones are known for being prochiral
Prochiral
In stereochemistry, prochiral molecules are those that can be converted from achiral to chiral in a single step.If two identical substituents are attached to a sp3-hybridized atom, the descriptors pro-R and pro-S are used to distinguish between the two...
.
Diketones
Many kinds of diketones are known, some with unusual properties. The simplest is biacetyl (CH3C(O)C(O)CH3), once used as butter-flavoring in popcornPopcorn
Popcorn, or popping corn, is corn which expands from the kernel and puffs up when heated. Corn is able to pop because, like sorghum, quinoa and millet, its kernels have a hard moisture-sealed hull and a dense starchy interior. This allows pressure to build inside the kernel until an explosive...
. Acetylacetone
Acetylacetone
Acetylacetone is an organic compound that famously exists in two tautomeric forms that rapidly interconvert. The less stable tautomer is a diketone formally named pentane-2,4-dione. The more common tautomer is the enol form. The pair of tautomers rapidly interconvert and are treated as a single...
(pentane-2,4-dione) is virtually a misnomer (inappropriate name) because this species exists mainly as the monoenol CH3C(O)CH=C(OH)CH3. Its enolate is a common ligand in coordination chemistry.
Unsaturated ketones
Ketones containing alkene and alkyne units are often called unsaturated ketones. The most widely used member of this class of compounds is methyl vinyl ketoneMethyl vinyl ketone
Methyl vinyl ketone is a reactive organic compound classified as an enone. It is a colorless, flammable, highly toxic liquid with a pungent odor...
, CH3C(O)CH=CH2, which is useful in Robinson annulation
Robinson annulation
The Robinson annulation is an organic reaction used to create a six-member ring α,β-unsaturated cyclic ketone, using a ketone and methyl vinyl ketone...
reaction. Lest there be confusion, a ketone itself is a site of unsaturation; that is, it can be hydrogenated.
Cyclic ketones
Many ketones are cyclic. The simplest class have the formula (CH2)nCO, where n varies from 3 for cyclopropanoneCyclopropanone
Cyclopropanone is an organic compound with molecular formula C3H4O consisting of a cyclopropane carbon framework with a ketone functional group. The parent compound is labile with melting point −90 °C and has been prepared by reaction of ketene with diazomethane at −145 °C...
to the teens. Larger derivatives exist. Cyclohexanone, a symmetrical cyclic ketone, is an important intermediate in the production of nylon
Nylon
Nylon is a generic designation for a family of synthetic polymers known generically as polyamides, first produced on February 28, 1935, by Wallace Carothers at DuPont's research facility at the DuPont Experimental Station...
. Isophorone
Isophorone
Isophorone is an α,β-Unsaturated cyclic ketone, a colorless to yellowish liquid with characteristic smell, that is used as a solvent and as an intermediate in organic synthesis...
, derived from acetone, is an unsaturated, unsymmetrical ketone that is the precursor to other polymers. Muscone
Muscone
Muscone is an organic compound that is the primary contributor to the odor of musk.The chemical structure of muscone was first elucidated by Lavoslav Ružička. It consists of a 15-membered ring ketone with one methyl substituent in the 3-position. It is an oily liquid that is found naturally as...
, 3-methylpentadecanone, is an animal pheromone
Pheromone
A pheromone is a secreted or excreted chemical factor that triggers a social response in members of the same species. Pheromones are chemicals capable of acting outside the body of the secreting individual to impact the behavior of the receiving individual...
.
Keto-enol tautomerization
Ketones that have at least one alpha-hydrogen, undergo keto-enol tautomerization; the tautomer is an enolEnol
Enols are alkenes with a hydroxyl group affixed to one of the carbon atoms composing the double bond. Alkenes with a hydroxyl group on both sides of the double bond are called enediols. Deprotonated anions of enols are called enolates...
. Tautomerization is catalyzed by both acids and bases. Usually, the keto form is more stable than the enol. This equilibrium allows ketones to be prepared via the hydration of alkyne
Alkyne
Alkynes are hydrocarbons that have a triple bond between two carbon atoms, with the formula CnH2n-2. Alkynes are traditionally known as acetylenes, although the name acetylene also refers specifically to C2H2, known formally as ethyne using IUPAC nomenclature...
s.
Acidity of ketones
Ketones are far more acidic (pKaAcid dissociation constant
An acid dissociation constant, Ka, is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction known as dissociation in the context of acid-base reactions...
≈ 20) than a regular alkane (pKa ≈ 50). This difference reflects resonance stabilization of the enolate ion that is formed through dissociation. The relative acidity of the α-hydrogen is important in the enolization reactions of ketones and other carbonyl compounds. The acidity of the α-hydrogen also allows ketones and other carbonyl compounds to undergo nucleophilic reactions at that position, with either stoichiometric and catalytic base.
Spectroscopy
Ketones and aldehydes absorb strongly in infra-red spectrumInfrared spectroscopy
Infrared spectroscopy is the spectroscopy that deals with the infrared region of the electromagnetic spectrum, that is light with a longer wavelength and lower frequency than visible light. It covers a range of techniques, mostly based on absorption spectroscopy. As with all spectroscopic...
near 1700 cm−1
Wavenumber
In the physical sciences, the wavenumber is a property of a wave, its spatial frequency, that is proportional to the reciprocal of the wavelength. It is also the magnitude of the wave vector...
. The exact position of the peak depends on the substituents.
Whereas 1H NMR
Proton NMR
Proton NMR is the application of nuclear magnetic resonance in NMR spectroscopy with respect to hydrogen-1 nuclei within the molecules of a substance, in order to determine the structure of its molecules. In samples where natural hydrogen is used, practically all of the hydrogen consists of the...
spectroscopy is, in general, not useful for establishing the presence of a ketone, 13C NMR
Carbon-13 NMR
Carbon-13 NMR is the application of nuclear magnetic resonance spectroscopy to carbon. It is analogous to proton NMR and allows the identification of carbon atoms in an organic molecule just as proton NMR identifies hydrogen atoms...
spectra exhibit signals somewhat downfield of 200 ppm depending on structure. Such signals are typically weak due to the absence of nuclear Overhauser effect
Nuclear Overhauser effect
The Nuclear Overhauser Effect is the transfer of nuclear spin polarization from one nuclear spin population to another via cross-relaxation. It is a common phenomenon observed by nuclear magnetic resonance spectroscopy. The theoretical basis for the NOE was described and experimentally verified...
s. Since aldehydes resonate at similar chemical shift
Chemical shift
In nuclear magnetic resonance spectroscopy, the chemical shift is the resonant frequency of a nucleus relative to a standard. Often the position and number of chemical shifts are diagnostic of the structure of a molecule...
s, multiple resonance experiments are employed to definitively distinguish aldehydes and ketones.
Qualitative organic tests
Ketones give positive results in Brady's test, the reaction with 2,4-dinitrophenylhydrazine to give the corresponding hydrazone. Ketones may be distinguished from aldehydes by giving a negative result with Tollens' reagentTollens' reagent
Tollens' reagent is a chemical reagent most commonly used to determine whether a known carbonyl-containing compound is an aldehyde or a ketone. It is usually ammoniacal silver nitrate, but can also be other mixtures, as long as aqueous diamminesilver complex is present...
or with the Fehling's solution
Fehling's solution
Fehling's solution is a chemical test used to differentiate between water-soluble aldehyde and ketone functional groups, and as a test for monosaccharides. The test was developed by German chemist Hermann von Fehling in 1849.-Laboratory preparation:...
. Methyl ketones give positive results for the iodoform test.
Synthesis
Many methods exist for the preparation of ketones in industrial scale, biology, and in academic laboratories. In industry, the most important method probably involves oxidation of hydrocarbons, often with air. For example, a billion kilograms of cyclohexanoneCyclohexanone
Cyclohexanone is the organic compound with the formula 5CO. The molecule consists of six-carbon cyclic molecule with a ketone functional group. This colorless oil has an odor reminiscent of peardrop sweets as well as acetone. Over time, samples assume a yellow color due to oxidation...
are produced annually by aerobic oxidation of cyclohexane
Cyclohexane
Cyclohexane is a cycloalkane with the molecular formula C6H12. Cyclohexane is used as a nonpolar solvent for the chemical industry, and also as a raw material for the industrial production of adipic acid and caprolactam, both of which being intermediates used in the production of nylon...
. Acetone is prepared by air-oxidation of cumene
Cumene process
The Cumene process is an industrial process for developing phenol and acetone from benzene and propylene. The term stems from cumene , the intermediate material during the process. It was invented by Heinrich Hock in 1944 and independently by R. Ūdris and P...
.
For specialized or small scale organic synthetic
Organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
applications, ketones are often prepared by oxidation of secondary alcohols
Alcohol oxidation
Alcohol oxidation is an important organic reaction. Primary alcohols can be oxidized either to aldehydes or to carboxylic acids , while the oxidation of secondary alcohols normally terminates at the ketone stage...
:
- R2CH(OH) + O → R2C=O + H2O
Typical strong oxidants (source of "O" in the above reaction) include potassium permanganate
Potassium permanganate
Potassium permanganate is an inorganic chemical compound with the formula KMnO4. It is a salt consisting of K+ and MnO4− ions. Formerly known as permanganate of potash or Condy's crystals, it is a strong oxidizing agent. It dissolves in water to give intensely purple solutions, the...
or a Cr(VI)
Chromium
Chromium is a chemical element which has the symbol Cr and atomic number 24. It is the first element in Group 6. It is a steely-gray, lustrous, hard metal that takes a high polish and has a high melting point. It is also odorless, tasteless, and malleable...
compound. Milder conditions make use of the Dess-Martin periodinane
Dess-Martin periodinane
Dess–Martin periodinane is a chemical reagent used to oxidize primary alcohols to aldehydes and secondary alcohols to ketones. This periodinane has several advantages over chromium- and DMSO-based oxidants that include milder conditions , shorter reaction times, higher yields, simplified workups,...
or the Moffatt-Swern
Swern oxidation
The Swern oxidation, named after Daniel Swern, is a chemical reaction whereby a primary or secondary alcohol is oxidized to an aldehyde or ketone using oxalyl chloride, dimethyl sulfoxide and an organic base, such as triethylamine...
methods.
Many other methods have been developed including:
- By geminal halide hydrolysisGeminal halide hydrolysisGeminal halide hydrolysis is an organic reaction. The reactants are a geminal dihalide and water or a hydroxide. The reaction product is a ketone or an aldehyde. The first part of the reaction mechanism consists of an ordinary nucleophilic aliphatic substitution to produce a gem-halohydrin...
. - By hydrationHydration reactionIn organic chemistry, a hydration reaction is a chemical reaction in which a hydroxyl group and a hydrogen cation are added to the two carbon atoms bonded together in the carbon-carbon double bond which makes up an alkene functional group. The reaction usually runs in a strong acidic, aqueous...
of alkyneAlkyneAlkynes are hydrocarbons that have a triple bond between two carbon atoms, with the formula CnH2n-2. Alkynes are traditionally known as acetylenes, although the name acetylene also refers specifically to C2H2, known formally as ethyne using IUPAC nomenclature...
s. Such processes occur via enolEnolEnols are alkenes with a hydroxyl group affixed to one of the carbon atoms composing the double bond. Alkenes with a hydroxyl group on both sides of the double bond are called enediols. Deprotonated anions of enols are called enolates...
s and require the presence of an acid and HgSO4Mercury(II) sulfateMercury sulfate, commonly called mercuric sulfate is the chemical compound Hg S O4. It is an odorless solid that forms white granules or crystalline powder...
. Subsequent enol-keto tautomerization gives a ketone. This reaction always produces a ketone, even with a terminal alkyne. - From Weinreb AmidesWeinreb ketone synthesisThe Weinreb ketone synthesis is a chemical reaction used in organic chemistry to make carbon–carbon bonds. It was discovered in 1981 by Steven M. Weinreb and Steven Nahm as a method to synthesize ketones...
using stoichiometric organometallic reagents. - Aromatic ketones can be prepared in the Friedel-Crafts acylation, the related Houben-Hoesch reaction and the Fries rearrangementFries rearrangementThe Fries rearrangement, named for the German chemist Karl Theophil Fries, is a rearrangement reaction of a phenyl ester to a hydroxy aryl ketone by catalysis of Lewis acids.It involves migration of an acyl group of phenyl ester to benzene ring.- Mechanism:...
. - OzonolysisOzonolysisOzonolysis is the cleavage of an alkene or alkyne with ozone to form organic compounds in which the multiple carbon–carbon bond has been replaced by a double bond to oxygen...
, and related dihydroxylation/oxidative sequences, cleave alkeneAlkeneIn organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...
s to give aldehydes and/or ketones, depending on alkene substitution pattern. - In the Kornblum–DeLaMare rearrangementKornblum–DeLaMare rearrangementThe Kornblum–DeLaMare rearrangement is a rearrangement reaction in organic chemistry in which a primary or secondary organic peroxide is converted to the corresponding ketone and alcohol under base catalysis...
ketones are prepared from peroxides and base. - In the Ruzicka cyclization, cyclic ketones are prepared from dicarboxylic acidDicarboxylic acidDicarboxylic acids are organic compounds that contain two carboxylic acid functional groups. In molecular formulae for dicarboxylic acids, these groups are often written as HOOC-R-COOH, where R may be an alkyl, alkenyl, alkynyl, or aryl group...
s. - In the Nef reactionNef reactionThe Nef reaction is an organic reaction describing the acid hydrolysis of a salt of a primary or secondary nitroalkane to an aldehyde or a ketone and nitrous oxide ....
, ketones form by hydrolysis of salts of secondary nitro compounds. - In the Fukuyama couplingFukuyama couplingThe Fukuyama coupling is a coupling reaction taking place between a thioester and an organozinc halide in the presence of a palladium catalyst. The reaction product is a ketone. This reaction was discovered by Tohru Fukuyama et al. in 1998...
, ketones form from a thioester and an organozinc compound. - By the reaction of an acid chloride with organocadmium compoundOrganocadmium compoundAn organocadmium compound is a organometallic compound containing a carbon to cadmium chemical bond. Organocadmium chemistry describes physical properties, synthesis, reactions and use of these compounds. Cadmium shares group 12 with zinc and mercury and their corresponding chemistries have much in...
s or organocopper compoundOrganocopper compoundOrganocopper compounds in organometallic chemistry contain carbon to copper chemical bonds. Organocopper chemistry is the science of organocopper compounds describing their physical properties, synthesis and reactions...
s. - The Dakin-West reactionDakin-West reactionThe Dakin–West reaction is a chemical reaction that transforms an amino-acid into a keto-amide using an acid anhydride and a base, typically pyridine. It is named for Henry Drysdale Dakin and Randolph West . Of special note, the keto-amide product is always racemic.With pyridine as a base and...
provides an efficient method for preparation of certain methyl ketones from carboxylic acids. - Ketones can also be prepared by the reaction of Grignard reagents with nitrileNitrileA nitrile is any organic compound that has a -C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, one example being super glue .Inorganic compounds containing the -C≡N group are not called...
s, followed by hydrolysis. - By decarboxylation of carboxylic anhydrideCarboxylic anhydride"Anhydride" redirects here. For inorganic acid anhydrides see acidic oxide.An acid anhydride is an organic compound that has two acyl groups bound to the same oxygen atom. Most commonly, the acyl groups are derived from the same carboxylic acid, the formula of the anhydride being 2O...
. - Ketones can be prepared from haloketones in reductive dehalogenation of halo ketonesReductive dehalogenation of halo ketonesReductive dehalogenations of halo ketones are organic reactions that result in the formation of ketones and functionalized derivatives of ketones from α-halo ketones in the presence of metallic reducing agents.-Introduction:...
.
Reactions
Ketones engage in many organic reactionOrganic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...
s. The most important reactions follow from the susceptibility of the carbonyl carbon toward nucleophilic addition
Nucleophilic addition
In organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a π bond is removed by the creation of two new covalent bonds by the addition of a nucleophile....
and the tendency for the enolates to add to electrophiles.
Nucleophilic additions include in approximate order of their generality:
- With water (hydration) gives geminal diolGeminal diolA geminal diol is any organic compound having two hydroxyl functional groups bound to the same carbon atom.The simplest geminal diol is methanediol CH4O2 or H2C2...
s, which are usually not formed in appreciable (or observable) amounts - With an acetylide to give the α-hydroxyalkyne
- With ammoniaAmmoniaAmmonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
or a primary amine gives an imineImineAn imine is a functional group or chemical compound containing a carbon–nitrogen double bond, with the nitrogen attached to a hydrogen atom or an organic group. If this group is not a hydrogen atom, then the compound is known as a Schiff base... - With secondary amine gives an enamineEnamineAn enamine is an unsaturated compound derived by the reaction of an aldehyde or ketone with a secondary amine followed by loss of H2O.The word "enamine" is derived from the affix en-, used as the suffix of alkene, and the root amine. This can be compared with enol, which is a functional group...
- With Grignard and organolithium reagentOrganolithium reagentAn organolithium reagent is an organometallic compound with a direct bond between a carbon and a lithium atom. As the electropositive nature of lithium puts most of the charge density of the bond on the carbon atom, effectively creating a carbanion, organolithium compounds are extremely powerful...
s to give, after aqueous workup, a tertiary alcohol - With an alcoholAlcoholIn chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
s or alkoxideAlkoxideAn alkoxide is the conjugate base of an alcohol and therefore consists of an organic group bonded to a negatively charged oxygen atom. They can be written as RO−, where R is the organic substituent. Alkoxides are strong bases and, when R is not bulky, good nucleophiles and good ligands...
s to gives the hemiketal or its conjugate base. With a diolDiolA diol or glycol is a chemical compound containing two hydroxyl groups A geminal diol has two hydroxyl groups bonded to the same atom...
to the ketal. This reaction is employed to protect ketones. - With sodium amideSodium amideSodium amide, commonly called sodamide, is the chemical compound with the formula NaNH2. This solid, which is dangerously reactive toward water, is white when pure, but commercial samples are typically gray due to the presence of small quantities of metallic iron from the manufacturing process...
resulting in C-C bond cleavage with formation of the amide RCONH2 and the alkane R'H, a reaction called the Haller-Bauer reaction.
Electrophilic addition
Electrophilic addition
In organic chemistry, an electrophilic addition reaction is an addition reaction where, in a chemical compound, a π bond is broken and two new σ bonds are formed...
, reaction with an electrophile
Electrophile
In general electrophiles are positively charged species that are attracted to an electron rich centre. In chemistry, an electrophile is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile...
gives a resonance stabilized cation
- With phosphonium ylides in the Wittig reactionWittig reactionThe Wittig reaction is a chemical reaction of an aldehyde or ketone with a triphenyl phosphonium ylide to give an alkene and triphenylphosphine oxide....
to give the alkeneAlkeneIn organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...
s - With thiolThiolIn organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...
s to give the thioacetalThioacetalThioacetals are the sulfur analogue of acetals. They are prepared in a similar way to acetals: by reacting a thiol with an aldehyde:Dithioacetals are prepared similarly to thioacetals, which are intermediates:... - With hydrazineHydrazineHydrazine 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...
or 1-disubstituted derivativesDerivative (chemistry)In chemistry, a derivative is a compound that is derived from a similar compound by some chemical or physical process. In the past it was also used to mean a compound that can be imagined to arise from another compound, if one atom is replaced with another atom or group of atoms, but modern...
of hydrazine to give hydrazoneHydrazoneHydrazones are a class of organic compounds with the structure R1R2C=NNH2. They are related to ketones and aldehydes by the replacement of the oxygen with the NNH2 functional group...
s. - With a metal hydride gives a metal alkoxide salt, hydrolysis of which gives the alcoholAlcoholIn chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
, an example of ketone reduction - With halogenHalogenThe halogens or halogen elements are a series of nonmetal elements from Group 17 IUPAC Style of the periodic table, comprising fluorine , chlorine , bromine , iodine , and astatine...
s to form α-haloketoneHaloketoneA haloketone in organic chemistry is a functional group consisting of a ketone group or more general a carbonyl group with a α-halogen substituent. The general structure is RR'CCR where R is an alkyl or aryl residue and X any one of the halogens...
, a reaction that proceeds via an enolEnolEnols are alkenes with a hydroxyl group affixed to one of the carbon atoms composing the double bond. Alkenes with a hydroxyl group on both sides of the double bond are called enediols. Deprotonated anions of enols are called enolates...
(see Haloform reactionHaloform reactionThe haloform reaction is a chemical reaction where a haloform is produced by the exhaustive halogenation of a methyl ketone in the presence of a base. R may be , alkyl or aryl...
) - With heavy waterHeavy waterHeavy water is water highly enriched in the hydrogen isotope deuterium; e.g., heavy water used in CANDU reactors is 99.75% enriched by hydrogen atom-fraction...
to give a α-deuterated ketone - Fragmentation in photochemical Norrish reactionNorrish reactionThe Norrish reaction in organic chemistry describes the photochemical reactions taking place with ketones and aldehydes. This type of reaction is subdivided in Norrish type I reactions and Norrish type II reactions...
- Reaction of 1,4-aminodiketones to oxazoles by dehydration in the Robinson-Gabriel synthesisRobinson-Gabriel synthesisThe Robinson-Gabriel synthesis is a chemical reaction that forms oxazoles by dehydration of 2-acylamino-ketones.Historically, the dehydration agent is concentrated sulfuric acid. Recently, phosphorus oxychloride is successful with this reaction also....
- In the case of aryl-alkyl ketones, with sulfur and an amine give amides in the Willgerodt reaction
- With hydroxylamineHydroxylamineHydroxylamine is an inorganic compound with the formula NH2OH. The pure material is a white, unstable crystalline, hygroscopic compound. However, hydroxylamine is almost always provided and used as an aqueous solution. It is used to prepare oximes, an important functional group. It is also an...
to produce oximeOximeAn oxime is a chemical compound belonging to the imines, with the general formula R1R2C=NOH, where R1 is an organic side chain and R2 may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime. O-substituted oximes form a closely related family of compounds...
s
Biochemistry
Ketones are pervasive in nature. The formation of organic compounds in photosynthesisPhotosynthesis
Photosynthesis is a chemical process that converts carbon dioxide into organic compounds, especially sugars, using the energy from sunlight. Photosynthesis occurs in plants, algae, and many species of bacteria, but not in archaea. Photosynthetic organisms are called photoautotrophs, since they can...
occurs via the ketone ribulose-1,5-bisphosphate
Ribulose-1,5-bisphosphate
Ribulose-1,5-bisphosphate is an organic substance that is involved in photosynthesis. The anion is a double phosphate ester of the ketose called ribulose. Salts of this species can be isolated, but its crucial biological function involves this colourless anion in solution...
. Many sugars are ketones, known collectively as ketose
Ketose
A ketose is a sugar containing one ketone group per molecule.With 3 carbon atoms, dihydroxyacetone is the simplest of all ketoses and is the only one having no optical activity. Ketoses can isomerize into an aldose when the carbonyl group is located at the end of the molecule...
s. The best known ketose is fructose
Fructose
Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...
, which exists as a cyclic hemiketal, which masks the ketone functional group. Fatty acid synthesis
Fatty acid synthesis
Fatty acid synthesis is the creation of fatty acids from acetyl-CoA and malonyl-CoA precursors through action of enzymes called fatty acid synthases...
proceeds via ketones. Acetoacetate is an intermediate in the Kreb cycle which releases energy from sugars and carbohydrates.
In medicine, acetone
Acetone
Acetone is the organic compound with the formula 2CO, a colorless, mobile, flammable liquid, the simplest example of the ketones.Acetone is miscible with water and serves as an important solvent in its own right, typically as the solvent of choice for cleaning purposes in the laboratory...
, acetoacetate, and beta-hydroxybutyrate
Beta-hydroxybutyrate
beta-Hydroxybutyric acid is a ketone body. It is a chiral compound having two enantiomers, D-3-hydroxybutyric acid and L-3-hydroxybutyric acid. Like the other ketone bodies , levels of beta-hydroxybutyrate are raised in ketosis...
are collectively called ketone bodies
Ketone bodies
Ketone bodies are three water-soluble compounds that are produced as by-products when fatty acids are broken down for energy in the liver and kidney. They are used as a source of energy in the heart and brain. In the brain, they are a vital source of energy during fasting...
, generated from carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
s, fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s, and amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s in most vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
s, including humans. Ketones are elevated in blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
after fasting including a night of sleep, and in both blood and urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
in starvation
Starvation
Starvation is a severe deficiency in caloric energy, nutrient and vitamin intake. It is the most extreme form of malnutrition. In humans, prolonged starvation can cause permanent organ damage and eventually, death...
, hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
due to causes other than hyperinsulinism
Hyperinsulinemic hypoglycemia
Hyperinsulinemic hypoglycemia describes the condition and effects of low blood glucose caused by excessive insulin. Hypoglycemia due to excess insulin is the most common type of serious hypoglycemia. It can be due to endogenous or injected insulin.-Causes:...
, various inborn errors of metabolism
Inborn error of metabolism
Inborn errors of metabolism comprise a large class of genetic diseases involving disorders of metabolism. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances into others...
, and ketoacidosis
Ketoacidosis
Ketoacidosis is a metabolic state associated with high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids. The two common ketones produced in humans are acetoacetic acid and β-hydroxybutyrate....
(usually due to diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
). Although ketoacidosis is characteristic of decompensated or untreated type 1 diabetes, ketosis or even ketoacidosis can occur in type 2 diabetes
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
in some circumstances as well.
Applications
Ketones are produced on massive scales in industry as solvents, polymer precursors, and pharmaceuticals. In terms of scale, the most important ketones are acetoneAcetone
Acetone is the organic compound with the formula 2CO, a colorless, mobile, flammable liquid, the simplest example of the ketones.Acetone is miscible with water and serves as an important solvent in its own right, typically as the solvent of choice for cleaning purposes in the laboratory...
, methylethyl ketone, and cyclohexanone
Cyclohexanone
Cyclohexanone is the organic compound with the formula 5CO. The molecule consists of six-carbon cyclic molecule with a ketone functional group. This colorless oil has an odor reminiscent of peardrop sweets as well as acetone. Over time, samples assume a yellow color due to oxidation...
. They are also common in biochemistry, but less so than in organic chemistry in general. The combustion of hydrocarbons is an uncontrolled oxidation process that gives ketones as well as many other types of compounds.
Toxicity
Although it is difficult to generalize on the toxicity of such a broad class of compounds, simple ketones are, in general, not highly toxic (for instance, the sugar fructoseFructose
Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...
is a ketone). This characteristic is one reason for their popularity as solvents. Exceptions to this rule are the unsaturated ketones such as methyl vinyl ketone
Methyl vinyl ketone
Methyl vinyl ketone is a reactive organic compound classified as an enone. It is a colorless, flammable, highly toxic liquid with a pungent odor...
with of 7 mg/kg (oral).