In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing . Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone (where R and R' are methyl), with the formula . Many ketones are of great importance in biology and industry. Examples include many (), many , e.g., testosterone, and the solvent acetone.
Nomenclature and etymology
The word
ketone is derived from
Aketon, an old German word for
acetone.
[The word "ketone" was coined in 1848 by the German chemist Leopold Gmelin. See: Leopold Gmelin, ed., Handbuch der organischen Chemie: Organische Chemie im Allgemeinen … (Handbook of organic chemistry: Organic chemistry in general … ), 4th ed., (Heidelberg, (Germany): Karl Winter, 1848), volume 1, p. 40. From page 40: "Zu diesen Syndesmiden scheinen auch diejenigen Verbindungen zu gehören, die als Acetone im Allegemeinen (Ketone? ) bezeichnet werden." (To these syndesmides*, those compounds also seem to belong, which are designated as acetones in general ( ketones?).") *Note: Comptes rendus, 19 : 1089–1100; see especially p. 1097.]
According to the rules of IUPAC nomenclature, ketone names are derived by changing the suffix -ane of the parent alkane to -anone. Typically, the position of the carbonyl group is denoted by a number, but traditional nonsystematic names are still generally used for the most important ketones, for example acetone and benzophenone. These nonsystematic names are considered retained IUPAC names,[List of retained IUPAC names retained IUPAC names Link ] although some introductory chemistry textbooks use systematic names such as "2-propanone" or "propan-2-one" for the simplest ketone () instead of "acetone".
The derived names of ketones are obtained by writing separately the names of the two attached to the carbonyl group, followed by "ketone" as a separate word. Traditionally the names of the alkyl groups were written in order of increasing complexity, for example Butanone. However, according to the rules of IUPAC nomenclature, the alkyl groups are written alphabetically, for example Butanone. When the two alkyl groups are the same, the prefix "di-" is added before the name of alkyl group. The positions of other groups are indicated by Greek letters, the α-carbon being the atom adjacent to carbonyl group.
Although used infrequently, oxo is the IUPAC nomenclature for the oxo group (=O) and used as prefix when the ketone does not have the highest priority. Other prefixes, however, are also used. For some common chemicals (mainly in biochemistry), keto refer to the ketone functional group.
Structure and bonding
The ketone carbon is often described as sp
2 hybridized, a description that includes both their electronic and molecular structure. Ketones are
trigonal planar around the ketonic carbon, with C–C–O and C–C–C bond angles of approximately 120°. Ketones differ from
in that the carbonyl group (C=O) 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
, such as
,
and
.
The carbonyl group is polar molecule because the electronegativity of the oxygen is greater than that for carbon. Thus, ketones are nucleophilic at oxygen and electrophilic at carbon. Because the carbonyl group interacts with water by , 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 themselves. Because of their inability to serve both as hydrogen-bond donors and acceptors, ketones tend not to "self-associate" and are more volatile than alcohols and of comparable . These factors relate to the pervasiveness of ketones in perfumery and as solvents.
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
benzophenone () are symmetrical ketones.
Acetophenone is an unsymmetrical ketone.
Diketones
Many kinds of diketones are known, some with unusual properties. The simplest is
diacetyl , once used as butter-flavoring in
popcorn.
Acetylacetone (pentane-2,4-dione) is virtually a misnomer (inappropriate name) because this species exists mainly as the monoenol . Its enolate is a common ligand in coordination chemistry.
Unsaturated ketones
Ketones containing
alkene and
alkyne units are often called unsaturated ketones. A widely used member of this class of compounds is methyl vinyl ketone, , a α,β-unsaturated carbonyl compound.
Cyclic ketones
Many ketones are cyclic. The simplest class have the formula , where
n varies from 2 for
cyclopropanone () to the tens. Larger derivatives exist.
Cyclohexanone (), a symmetrical cyclic ketone, is an important intermediate in the production of
nylon.
Isophorone, derived from acetone, is an unsaturated, asymmetrical ketone that is the precursor to other
.
Muscone, 3-methylpentadecanone, is an animal
pheromone. Another cyclic ketone is
cyclobutanone, having the formula .
Characterization
An aldehyde differs from a ketone in that it has a hydrogen atom attached to its carbonyl group, making aldehydes easier to oxidize. Ketones do not have a hydrogen atom bonded to the carbonyl group, and are therefore more resistant to oxidation. They are
oxidized only by powerful
oxidizing agents which have the ability to
Bond cleavage carbon–carbon bonds.
Spectroscopy
Ketones (and aldehydes) absorb strongly in the infra-red spectrum near 1750
wavenumber, which is assigned to ν
C=O ("carbonyl stretching frequency"). The energy of the peak is lower for aryl and unsaturated ketones.
Whereas Proton NMR spectroscopy is generally 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 effects. Since aldehydes resonate at similar , 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' reagent or with Fehling's solution. Methyl ketones give positive results for the
iodoform test.
Ketones also give positive results when treated with
m-dinitrobenzene in presence of dilute sodium hydroxide to give violet coloration.
Synthesis
Many methods exist for the preparation of ketones in industrial scale and academic laboratories. Ketones are also produced in various ways by organisms; see the section on biochemistry below.
In industry, the most important method probably involves oxidation of hydrocarbons, often with air. For example, a billion kilograms of cyclohexanone are produced annually by aerobic oxidation of cyclohexane. Acetone is prepared by cumene process.
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
chromium compound. Milder conditions make use of the Dess–Martin periodinane or the
Swern oxidation methods.
Many other methods have been developed, examples include:
-
By geminal halide hydrolysis.
-
By hydration of .
-
From Weinreb amides using stoichiometric organometallic reagents.
-
Aromatic ketones can be prepared in the Friedel–Crafts acylation,
-
Ozonolysis, and related dihydroxylation/oxidative sequences, cleave to give aldehydes or ketones, depending on alkene substitution pattern.
-
From peroxides (Kornblum–DeLaMare rearrangement).
-
Cyclization of dicarboxylic acids (Ruzicka cyclization)
-
Hydrolysis of salts of secondary ( Nef reaction
-
Alkylation of thioester with organozinc compounds (Fukuyama coupling).
-
Alkylation of acid chloride with organocadmium compounds or organocopper compounds.
-
The Dakin–West reaction provides an efficient method for preparation of certain methyl ketones from carboxylic acids.
-
Ketones can be prepared by the reaction of Grignard reagents with , followed by hydrolysis.
-
By decarboxylation of carboxylic anhydride.
-
Ketones can be prepared from haloketones in reductive dehalogenation of halo ketones.
-
In ketonic decarboxylation symmetrical ketones are prepared from carboxylic acids.
-
Hydrolysis of unsaturated secondary amides,
-
Acid-catalysed rearrangement of 1,2-diols,
Reactions
Keto-enol tautomerization
Ketones that have at least one
alpha-hydrogen, undergo keto-enol tautomerization; the tautomer is an
enol. 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
.
Acid/base properties of ketones
bonds adjacent to the carbonyl in ketones are more acidic p''K''a ≈ 20) than the bonds in alkane (p''K''a ≈ 50). This difference reflects resonance stabilization of the [[enolate ion]] that is formed upon [[deprotonation]]. 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 react as nucleophiles at that position, with either [[stoichiometric]] and catalytic base. Using very strong bases like lithium diisopropylamide (LDA, p''K''a of conjugate acid ~36) under non-equilibrating conditions (–78 °C, 1.1 equiv LDA in THF, ketone added to base), the less-substituted ''kinetic'' ''enolate'' is generated selectively, while conditions that allow for equilibration (higher temperature, base added to ketone, using weak or insoluble bases, e.g., [[|sodium ethoxide]] in [[|ethanol]], or [[NaH|sodium hydride]]) provides the more-substituted ''thermodynamic enolate''.
Ketones are also weak bases, undergoing protonation on the carbonyl oxygen in the presence of Brønsted acids. Ketonium ions (i.e., protonated ketones) are strong acids, with p Ka values estimated to be somewhere between –5 and –7.
Nucleophilic additions
An important set of 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:
[
]
Oxidation
Ketones are cleaved by strong oxidizing agents and at elevated temperatures. Their oxidation involves carbon–carbon bond cleavage to afford a mixture of carboxylic acids having lesser number of carbon atoms than the parent ketone.
Other reactions
-
Electrophilic addition, reaction with an electrophile gives a resonance stabilized cation
-
With phosphonium ylides in the Wittig reaction to give the
-
With to give the thioacetal
-
With hydrazine or 1-disubstituted derivatives of hydrazine to give .
-
With a metal hydride gives a metal alkoxide salt, hydrolysis of which gives the alcohol, an example of ketone reduction
-
With to form an α-haloketone, a reaction that proceeds via an enol (see Haloform reaction)
-
With heavy water to give an α-deuterated ketone
-
Fragmentation in photochemical Norrish reaction
-
Reaction of 1,4-aminodiketones to oxazoles by dehydration in the Robinson–Gabriel synthesis
-
In the case of aryl–alkyl ketones, with sulfur and an amine give amides in the Willgerodt reaction
-
With hydroxylamine to produce
-
With reducing agents to form secondary alcohols
-
With to form in the Baeyer–Villiger oxidation
Biochemistry
Ketones do not appear in standard , nucleic acids, nor lipids. The formation of organic compounds in photosynthesis occurs via the ketone ribulose-1,5-bisphosphate. Many sugars are ketones, known collectively as . The best known ketose is fructose; it mostly exists as a cyclic hemiketal, which masks the ketone functional group. Fatty acid synthesis proceeds via ketones. Acetoacetate is an intermediate in the Krebs cycle which releases energy from sugars and carbohydrates.[Nelson, D. L.; Cox, M. M. (2000) Lehninger, Principles of Biochemistry. 3rd Ed. Worth Publishing: New York. .]
In medicine, acetone, acetoacetate, and beta-hydroxybutyrate are collectively called ketone bodies, generated from , , and in most , including humans. Ketone bodies are elevated in the blood (ketosis) after fasting, including a night of sleep; in both blood and urine in starvation; in hypoglycemia, due to causes other than hyperinsulinism; in various inborn errors of metabolism, and intentionally induced via a ketogenic diet, and in 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.
Applications
Ketones are produced on massive scales in industry as solvents, polymer precursors, and pharmaceuticals. In terms of scale, the most important ketones are acetone, methylethyl ketone, and cyclohexanone.
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. 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).
See also
External links
