ketone

Ketone group

In organic chemistry, a ketone (pronounced /ˈkiːtoʊn/ KEE-toan) (less often referred to as an alkanone) is a type of compound that contains a carbonyl group (C=O) bonded to two other carbon atoms in the form:

R₁(CO)R₂

Neither of the substituents R₁ and R₂ may be equal to hydrogen (H).^[1] Where either R group is a hydrogen atom, the compound is known as an aldehyde.

A carbonyl carbon bonded to two carbon atoms distinguishes ketones from carboxylic acids, aldehydes, esters, amides, and other oxygen-containing compounds. The double-bond of the carbonyl group distinguishes ketones from alcohols and ethers. The simplest ketone is acetone, CH₃-CO-CH₃ (systematically named propanone^[2]).

The carbon atom adjacent to a carbonyl group is called the α-carbon. Hydrogens attached to this carbon are called α-hydrogens. In the presence of an acid catalyst the ketone is subjected to so-called keto-enol tautomerism. The reaction with a strong base gives the corresponding enolate. A diketone is a compound containing two ketone groups.

Nomenclature

Acetone, the simplest ketone

In general, ketones are named using IUPAC nomenclature by changing the suffix -e of the parent alkane to -one. For common ketones, some traditional names such as acetone and benzophenone predominate, and these are considered retained IUPAC names ^[3], although some introductory chemistry texts use names such as propanone.

Oxo is the formal IUPAC nomenclature for a ketone functional group. However, other prefixes are also used by various books and journals. For some common chemicals (mainly in biochemistry), keto or oxo is the term used to describe the ketone (also known as alkanone) functional group. Oxo also refers to a single oxygen atom coordinated to a transition metal (a metal oxo).

Structure and properties

Keto-enol tautomerism. 1 is the keto form; 2 is the enol.

The ketone carbon is sp² hybridized. Ketones are trigonal planar about the ketone carbon, with bond angles distorted from an ideal 120°. The carbonyl group is polar, making ketones polar compounds. The carbonyl groups interact with water by hydrogen bonding, and ketones are soluble in water. It is a hydrogen-bond acceptor, but not a hydrogen-bond donor, and cannot hydrogen-bond to itself. This makes ketones more volatile than alcohols and carboxylic acids of similar molecular weight.

Ketones undergo keto-enol tautomerization; the tautomer is an enol. Tautomerization may be catalyzed by both acids and bases. Ketones are more stable than the enol. This allows ketones to be prepared by synthesizing the corresponding enols from alkynes.

The α-hydrogen of a ketone is far more acidic (pKa ≈ 20) than the hydrogen of a regular alkane (pKa ≈ 50). This is due to 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 or catalytic base.

Characterization

Ketones and aldehydes will display a significant peak in infrared spectroscopy, at around 1700 cm⁻¹ (slightly higher or lower, depending on the chemical environment).

While ¹H NMR is generally not useful for revealing the presence of a ketone, ¹³C NMR spectra exhibit (typically relatively weak) signals somewhat downfield of 200 ppm depending on structure. Since aldehydes resonate at similar chemical shifts, multiple different NMR experiments are required to definitively distinguish aldehydes and ketones spectrometrically.

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. In particular, methyl ketones give positive results for the iodoform test.

Synthesis

Many methods exist for the preparation of ketones in the laboratory or on industrial scale, including:

• Ketones can be created by oxidation of secondary alcohols, as in the oxidation of propan-2-ol to acetone: H₃C-CH(OH)-CH₃ → H₃C-CO-CH₃.

Classically, such reactions required a strong oxidant such as potassium permanganate or a Cr(VI) compound. In modern organic synthesis, much milder conditions such as use of the Dess-Martin periodinane or the Moffatt-Swern oxidation are commonly employed.

• Ketones can be prepared by geminal halide hydrolysis.
• Alkynes can be turned into enols through a hydration reaction in the presence of an acid and HgSO₄, and subsequent enol-keto tautomerization gives a ketone. This always produces a ketone, even with a terminal alkyne, and disiamylborane is needed to get an aldehyde from an alkyne
• Aromatic ketones can be prepared in the Friedel-Crafts acylation, the related Houben-Hoesch reaction and the Fries rearrangement.
• Ozonolysis, and related dihydroxylation/oxidative sequences, cleave alkenes to give aldehydes and/or ketones, depending on alkene substitution pattern.
• In the Kornblum–DeLaMare rearrangement ketones are prepared from peroxides and base.
• In the Ruzicka cyclization, cyclic ketones are prepared from dicarboxylic acids.
• In the Nef reaction, ketones form by hydrolysis of salts of secondary nitro compounds.
• In the Fukuyama coupling, ketones form from a thioester and an organozinc compound.
• Ketones can be prepared by the reaction of an 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.

Reactions

Ketones engage in many organic reactions:

• Nucleophilic addition. The reaction of a ketone with a nucleophile gives a tetrahedral carbonyl addition compound.
  • the reaction with the anion of a terminal alkyne gives a hydroxyalkyne
  • the reaction with ammonia or a primary amine gives an imine + water
  • the reaction with secondary amine gives an enamine + water
  • the reaction with a Grignard reagent gives a magnesium alkoxide and after aqueous workup a tertiary alcohol
  • the reaction with an organolithium reagent also gives a tertiary alcohol
  • the reaction with an alcohol, an acid or base gives a hemiketal + water and further reaction with an alcohol gives the ketal + water. This is a carbonyl-protecting reaction.
  • reaction of RCOR' with sodium amide results in cleavage with formation of the amide RCONH2 and the alkane R'H, a reaction called the Haller-Bauer reaction (1909) ^[4]
• Electrophilic addition, reaction with an electrophile gives a resonance stabilized cation.
• the reaction with phosphonium ylides in the Wittig reaction gives alkenes
• reaction with water gives geminal diols
• reaction with thiols gives a thioacetal
• reaction with hydrazine or derivatives of hydrazine gives hydrazones
• reaction with a metal hydride gives a metal alkoxide salt and then with water an alcohol
• reaction of an enol with halogens to form α-haloketone
• a reaction at an α-carbon is the reaction of a ketone with heavy water to give a deuterated ketone-d.
• fragmentation in photochemical Norrish reaction
• reaction with halogens and base of methyl ketones in the Haloform reaction
• reaction of 1,4-aminodiketones to oxazoles by dehydration in the Robinson-Gabriel synthesis
• reaction of aryl alkyl ketones with sulfur and an amine to amides in the Willgerodt reaction

Biochemistry

Acetone, acetoacetate and beta-hydroxybutyrate are ketones (or ketone bodies) generated from carbohydrates, fatty acids and amino acids in humans and most vertebrates. 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. Acetoacetate and beta-hydroxybutyrate are an important fuel for many tissues, especially during fasting and starvation. The brain, in particular, relies heavily on ketone bodies as a substrate for lipid synthesis and for energy during times of reduced food intake. At the NIH, Dr. Richard Veech refers to ketones as "magic" in their ability to increase metabolic efficiency, while decreasing production of free radicals, the damaging byproducts of normal metabolism. His work has shown that ketone bodies may treat neurological diseases such as Alzheimer's and Parkinson's disease,^[5] and the heart and brain operate 25% more efficiently using ketones as a source of energy.^[6] Research has also shown ketones play a role in reducing epileptic seizures with the so-called high-fat, near-zero carbohydrate Ketogenic Diet. [1]

Applications

Ketones are often used in perfumes and paints to stabilize the other ingredients so that they don't degrade as quickly over time. Other uses are as solvents and intermediates in chemical industry. Examples of ketones are acetone, acetophenone, and methyl ethyl ketone.

References

1. ^ International Union of Pure and Applied Chemistry. "ketones". Compendium of Chemical Terminology Internet edition.
2. ^ The position of the carbonyl group is usually denoted by a number; in propanone there can only be one position. While propanone or propan-2-one is how the molecule should be named according to systematic nomenclature, the name "acetone" is retained in official IUPAC nomenclature
3. ^ List of retained IUPAC names retained IUPAC names Link
4. ^ Haller-Bauer Reaction
5. ^ Y. Kashiwaya, T. Takeshima, N. Mori, K. Nakashima, K. Clarke and R. L. Veech (2000). "D-beta -Hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease". PNAS 97 (10): 5440–5444. doi:10.1073/pnas.97.10.5440. PMID 10805800. 
6. ^ Y. Kashiwaya, K. Sato, N. Tsuchiya, S. Thomas, D. A. Fell, R. L. Veech and J. V. Passonneau (1994). "Control of glucose utilization in working perfused rat heart". J. Biol. Chem. 269 (41): 25502–25514. PMID 7929251. http://www.jbc.org/cgi/content/abstract/269/41/25502.