Carbonyl group

In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a carbonyl group is often referred to as a carbonyl compound.

The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex (a metal carbonyl, e.g. nickel carbonyl).

The remainder of this article concerns itself with the organic chemistry definition of carbonyl, where carbon and oxygen share a double bond.

Ketone-general
A compound containing a carbonyl group (C=O)

Carbonyl compounds

A carbonyl group characterizes the following types of compounds:

Compound Aldehyde Ketone Carboxylic acid Carboxylate Ester Amide
Structure Aldehyde Ketone Carboxylic acid Ester Amide
General formula RCHO RCOR' RCOOH RCOOR' RCONR'R''
Compound Enone Acyl halide Acid anhydride Imide
Structure Enone Acyl chloride Acid anhydride Imide
General formula RC(O)C(R')CR''R''' RCOX (RCO)2O RC(O)N(R')C(O)R''

Note that the most specific labels are usually employed. For example, R(CO)O(CO)R' structures are known as acid anhydride rather than the more generic ester, even though the ester motif is present.

Carbon dioxide
Carbon dioxide

Other organic carbonyls are urea and the carbamates, the derivatives of acyl chlorides chloroformates and phosgene, carbonate esters, thioesters, lactones, lactams, hydroxamates, and isocyanates. Examples of inorganic carbonyl compounds are carbon dioxide and carbonyl sulfide.

A special group of carbonyl compounds are 1,3-dicarbonyl compounds that have acidic protons in the central methylene unit. Examples are Meldrum's acid, diethyl malonate and acetylacetone.

Reactivity

Carbonyl resonance chemistry

Because oxygen is more electronegative than carbon, carbonyl compounds often have resonance structures which affect their reactivity. This relative electronegativity draws electron density away from carbon, increasing the bond's polarity, therefore making carbon an electrophile (i.e. slightly positive). Carbon can then be attacked by nucleophiles (e.g. negatively charged ions, like the cyanide ion) or a negatively charged part of another molecule (e.g. the lone pair electrons of nitrogen in the ammonia molecule). During the reaction, the carbon-oxygen double bond is broken, and the carbonyl group may experience addition reactions. This reaction is known as addition-elimination (because a water molecule is often lost) or condensation.[1] The electronegative oxygen also can react with an electrophile; for example a proton in an acidic solution or with Lewis acids to form an oxocarbenium ion.

Carbonylgruppe
A carbonyl compound

The polarity of oxygen also makes the alpha hydrogens of carbonyl compounds much more acidic (roughly 1030 times more acidic) than typical sp3 C-H bonds, such as those in methane. For example, the pKa values of acetaldehyde and acetone are 16.7 and 19 respectively,[2] while the pKa value of methane is extrapolated to be approximately 50.[3] This is because a carbonyl is in tautomeric resonance with an enol. The deprotonation of the enol with a strong base produces an enolate, which is a powerful nucleophile and can alkylate electrophiles such as other carbonyls.

Amides are the most stable of the carbonyl couplings due to their high resonance stabilization between the nitrogen-carbon and carbon-oxygen bonds.

Carbonyl reduction

Carbonyl groups can be reduced by reaction with hydride reagents such as NaBH4 and LiAlH4, with baker's yeast, or by catalytic hydrogenation. Ketones give secondary alcohols while aldehydes, esters and carboxylic acids give primary alcohols.

Carbonyl alkylation

Carbonyls can be alkylated in nucleophilic addition reactions using organometallic compounds such as organolithium reagents, Grignard reagents, or acetylides. Carbonyls also may be alkylated by enolates as in aldol reactions. Carbonyls are also the prototypical groups with vinylogous reactivity (e.g. the Michael reaction where an unsaturated carbon in conjugation with the carbonyl is alkylated instead of the carbonyl itself).

Carbonyl chemoselectivity

In case of multiple carbonyl types in one molecule, one can expect the most electrophilic carbonyl carbon to react first. Acyl chlorides and carboxylic anhydrides react fastest, followed by aldehydes and ketones. Esters react much more slowly and amides are almost completely unreactive due to resonance of the amide nitrogen towards the carbonyl group. This reactivity difference allows chemoselectivity when a reactant contains multiple carbonyl groups. An instructive example is found in the last part of the total synthesis of monensin by Kishi in 1979:[4]

Monensin total synthesis Kishi 1979 JACS final stage aldol coupling

The left-hand reactant possesses two potential electrophilic sites: an aldehyde (indicated in blue) and an ester (indicated in green). Only the aldehyde, which is more electrophilic, will react with the enolate of the methyl ketone in the other part of the molecule. The methyl ester remains untouched. Of course, other effects can play a role in this selectivity process, including electronic effects, steric effects, and thermodynamic versus kinetic reaction control.

Carbonyl specialty reactions

Other important reactions include:

α,β-Unsaturated carbonyl compounds

Propenal
Acrolein, an α,β-unsaturated carbonyl compound.

α,β-Unsaturated carbonyl compounds are an important class of carbonyl compounds with the general structure (O=CR)−Cα=Cβ-R; for example enones and enals. In these compounds the carbonyl group is conjugated with an alkene (hence the adjective unsaturated), from which they derive special properties. Unlike the case for simple carbonyls, α,β-unsaturated carbonyl compounds are often attacked by nucleophiles at the β carbon. This pattern of reactivity is called vinylogous. Examples of unsaturated carbonyls are acrolein (propenal), mesityl oxide, acrylic acid, and maleic acid. Unsaturated carbonyls can be prepared in the laboratory in an aldol reaction and in the Perkin reaction.

The carbonyl group draws electrons away from the alkene, and the alkene group is, therefore, deactivated towards an electrophile, such as bromine or hydrochloric acid. As a general rule with asymmetric electrophiles, hydrogen attaches itself at the α-position in an electrophilic addition. On the other hand, these compounds are activated towards nucleophiles in nucleophilic conjugate addition.

Since α,β-unsaturated compounds are electrophiles, many α,β-unsaturated carbonyl compounds are toxic, mutagenic and carcinogenic. DNA can attack the β carbon and thus be alkylated. However, the endogenous scavenger compound glutathione naturally protects from toxic electrophiles in the body. Some drugs (amifostine, N-acetylcysteine) containing thiol groups may protect biomolecules from such harmful alkylation.

Spectroscopy

  • Infrared spectroscopy: the C=O double bond absorbs infrared light at wavenumbers between approximately 1600–1900 cm−1(5263 nm to 6250 nm). The exact location of the absorption is well understood with respect to the geometry of the molecule. This absorption is known as the "carbonyl stretch" when displayed on an infrared absorption spectrum.[5] In addition, the ultraviolet-visible spectra of propanone in water gives an absorption of carbonyl at 257 nm.[6]
  • Nuclear magnetic resonance: the C=O double-bond exhibits different resonances depending on surrounding atoms, generally a downfield shift. The 13C NMR of a carbonyl carbon is in the range of 160-220 ppm.

See also

References

  1. ^ "an introduction to aldehydes and ketones". www.chemguide.co.uk.
  2. ^ Ouellette, R.J. and Rawn, J.D. "Organic Chemistry" 1st Ed. Prentice-Hall, Inc., 1996: New Jersey. ISBN 0-02-390171-3
  3. ^ Claden, Johnathan; et al. Organic Chemistry. Oxford University Press. ISBN 978-0-19-850346-0.
  4. ^ Nicolaou, Kyriacos Costa; E. J. Sorensen (1996). Classics in Total Synthesis: Targets, Strategies, Methods. Wiley-VCH. pp. 230–232. ISBN 3-527-29231-4.
  5. ^ Mayo D.W., Miller F.A and Hannah R.W “Course Notes On The Interpretation of Infrared and Raman Spectra” 1st Ed. John Wiley & Sons Inc, 2004: New Jersey. ISBN 0-471-24823-1.
  6. ^ "Archived copy" (PDF). Archived from the original (PDF) on 2015-08-24. Retrieved 2015-07-11.CS1 maint: Archived copy as title (link)

Further reading

Acid catalysis

In acid catalysis and base catalysis, a chemical reaction is catalyzed by an acid or a base. By Brønsted–Lowry acid–base theory, the acid is the proton (hydrogen ion, H+) donor and the base is the proton acceptor. Typical reactions catalyzed by proton transfer are esterfications and aldol reactions. In these reactions, the conjugate acid of the carbonyl group is a better electrophile than the neutral carbonyl group itself. Depending on the chemical species that act as the acid or base, catalytic mechanisms can be classified as either specific catalysis and general catalysis. Many enzymes operate by specific catalysis.

Acyl halide

An acyl halide (also known as an acid halide) is a chemical compound derived from an oxoacid by replacing a hydroxyl group with a halide group.If the acid is a carboxylic acid, the compound contains a –COX functional group, which consists of a carbonyl group singly bonded to a halogen atom. The general formula for such an acyl halide can be written RCOX, where R may be, for example, an alkyl group, CO is the carbonyl group, and X represents the halide, such as chloride. Acyl chlorides are the most commonly encountered acyl halides, but acetyl iodide is the one produced (transiently) on the largest scale. Billions of kilograms are generated annually in the production of acetic acid.The hydroxyl group of a sulfonic acid may also be replaced by a halogen to produce the corresponding sulfonyl halide. In practical terms this is almost always chloride to give the sulfonyl chloride.

Aldehyde

An aldehyde is a compound containing a functional group with the structure −CHO, consisting of a carbonyl center (a carbon double-bonded to oxygen) with the carbon atom also bonded to hydrogen and to an R group, which is any generic alkyl or side chain. The group—without R—is the aldehyde group, also known as the formyl group. Aldehydes are common in organic chemistry, and many fragrances are aldehydes.

Aldose

An aldose is a monosaccharide (a simple sugar) with a carbon backbone chain with a carbonyl group on the endmost carbon atom, making it an aldehyde, and hydroxyl groups connected to all the other carbon atoms. Aldoses can be distinguished from ketoses, which have the carbonyl group away from the end of the molecule, and are therefore ketones.

Cyclopropenone

Cyclopropenone is an organic compound with molecular formula C3H2O consisting of a cyclopropene carbon framework with a ketone functional group. It is a colorless, volatile liquid that boils near room temperature. Neat cyclopropenone polymerizes upon standing at room temperature. The chemical properties of the compound are dominated by the strong polarization of the carbonyl group, which gives a partial positive charge with aromatic stabilization on the ring and a partial negative charge on oxygen. It is an aromatic compound.

Dihydroxybenzenes

Dihydroxybenzenes are organic chemical compounds in which two hydroxyl groups are substituted onto a benzene ring. These aromatic compounds are classed as phenols. There are three isomer: 1,2-dihydroxybenzene (the ortho isomer) is commonly known as catechol, 1,3-dihydroxybenzene (the meta isomer) is commonly known as resorcinol, and 1,4-dihydroxybenzene (the para isomer) is commonly known as hydroquinone.

All three of these compounds are colorless to white granular solids at room temperature and pressure, but upon exposure to oxygen they may darken. All three isomers have the chemical formula C6H6O2.

Similar to other phenols, the hydroxyl groups on the aromatic ring of a benzenediol are weakly acidic. Each benzenediol can lose an H+ from one of the hydroxyls to form a type of phenolate ion.

The Dakin oxidation is an organic redox reaction in which an ortho- or para-hydroxylated phenyl aldehyde or ketone reacts with hydrogen peroxide in base to form a benzenediol and a carboxylate. Overall, the carbonyl group is oxidized, and the hydrogen peroxide is reduced.

Double bond

A double bond in chemistry is a chemical bond between two chemical elements involving four bonding electrons instead of the usual two. The most common double bond occurs between two carbon atoms and can be found in alkenes. Many types of double bonds exist between two different elements. For example, in a carbonyl group with a carbon atom and an oxygen atom. Other common double bonds are found in azo compounds (N=N), imines (C=N) and sulfoxides (S=O). In skeletal formula the double bond is drawn as two parallel lines (=) between the two connected atoms; typographically, the equals sign is used for this. Double bonds were first introduced in chemical notation by Russian chemist Alexander Butlerov.Double bonds involving carbon are stronger than single bonds and are also shorter. The bond order is two. Double bonds are also electron-rich, which makes them potentially more reactive in the presence of a strong electron acceptor (as in addition reactions of the halogens).

Enol

Enols, or more formally, alkenols, are a type of reactive structure or intermediate in organic chemistry that is represented as an alkene (olefin) with a hydroxyl group attached to one end of the alkene double bond. The terms enol and alkenol are portmanteaus deriving from "-ene"/"alkene" and the "-ol" suffix indicating the hydroxyl group of alcohols, dropping the terminal "-e" of the first term. Generation of enols often involves removal of a hydrogen adjacent (α-) to the carbonyl group—i.e., deprotonation, its removal as a proton, H+. When this proton is not returned at the end of the stepwise process, the result is an anion termed an enolate (see images at right). The enolate structures shown are schematic; a more modern representation considers the molecular orbitals that are formed and occupied by electrons in the enolate. Similarly, generation of the enol often is accompanied by "trapping" or masking of the hydroxy group as an ether, such as a silyl enol ether.

Grignard reaction

The Grignard reaction (pronounced /ɡriɲar/) is an organometallic chemical reaction in which alkyl, vinyl, or aryl-magnesium halides (Grignard reagent) add to a carbonyl group in an aldehyde or ketone. This reaction is important for the formation of carbon–carbon bonds. The reaction of an organic halide with magnesium is not a Grignard reaction, but provides a Grignard reagent.

Grignard reactions and reagents were discovered by and are named after the French chemist François Auguste Victor Grignard (University of Nancy, France), who published it in 1900 and was awarded the 1912 Nobel Prize in Chemistry for this work.

Hemiacetal

A hemiacetal or a hemiketal is a compound that results from the addition of an alcohol to an aldehyde or a ketone, respectively. The Greek word hèmi, meaning half(semi), refers to the fact that a single alcohol has been added to the carbonyl group, in contrast to acetals or ketals, which are formed when a second alkoxy group has been added to the structure.

Ketone

In chemistry, a ketone is a functional group with the structure RC(=O)R', where R and R' can be a variety of carbon-containing substituents. Ketones and aldehydes are simple compounds that contain a carbonyl group (a carbon-oxygen double bond). They are considered "simple" because they do not have reactive groups like −OH or −Cl attached directly to the carbon atom in the carbonyl group, as in carboxylic acids containing −COOH. Many ketones are known and many are of great importance in industry and in biology. Examples include many sugars (ketoses) and the industrial solvent acetone, which is the smallest ketone.

Knoevenagel condensation

The Knoevenagel condensation (pronounced [ˈknøːvənaːɡl̩]) reaction is an organic reaction named after Emil Knoevenagel. It is a modification of the aldol condensation.A Knoevenagel condensation is a nucleophilic addition of an active hydrogen compound to a carbonyl group followed by a dehydration reaction in which a molecule of water is eliminated (hence condensation). The product is often an α,β-unsaturated ketone (a conjugated enone).

In this reaction the carbonyl group is an aldehyde or a ketone. The catalyst is usually a weakly basic amine. The active hydrogen component has the form

Z–CH2-Z or Z–CHR–Z for instance diethyl malonate, Meldrum's acid, ethyl acetoacetate or malonic acid, or cyanoacetic acid.

Z–CHR1R2 for instance nitromethane.where Z is an electron withdrawing functional group. Z must be powerful enough to facilitate deprotonation to the enolate ion even with a mild base. Using a strong base in this reaction would induce self-condensation of the aldehyde or ketone.

The Hantzsch pyridine synthesis, the Gewald reaction and the Feist–Benary furan synthesis all contain a Knoevenagel reaction step. The reaction also led to the discovery of CS gas.

Lomefloxacin

Lomefloxacin hydrochloride (sold under the following brand names in English-speaking countries Maxaquin, Okacyn, Uniquin) is a fluoroquinolone antibiotic used to treat bacterial infections including bronchitis and urinary tract infections. It is also used to prevent urinary tract infections prior to surgery. Lomefloxacin is associated with phototoxicity and central nervous system adverse effects.October 2008 the FDA added the following black box warning to the product insert for Maxaquin: "Lomefloxacin is unique in that it forms a magnesium chelate with itself. The chelate is formed between the 2-carbonyl group of two separate lomefloxacin molecules."

It was patented in 1983 and approved for medical use in 1989.

Mannoheptulose

Mannoheptulose is a heptose, a monosaccharide with seven carbon atoms, and a ketose, with the characteristic carbonyl group of the carbohydrate present on a secondary carbon (functioning as a ketone group). The sugar alcohol form of mannoheptulose is known as perseitol.

Osazone

Osazones are a class of carbohydrate derivatives found in organic chemistry formed when sugars are reacted with excess of phenylhydrazine.The famous German chemist Emil Fischer developed and used the reaction to identify sugars whose stereochemistry differed by only one chiral carbon. Glucosazone and fructosazone are identical.Osazones formation test involves the reaction of a reducing sugar (free carbonyl group) with excess of phenylhydrazine when kept at boiling temperature. All reducing sugars form osazones. Therefore, sucrose, for example, does not form osazone crystals because it is a non reducing sugar as it has no free carbonyl group.

The reaction involves formation of a pair of phenylhydrazone functionalities, concomitant with the oxidation of the hydroxymethyl group in alpha carbon (carbon atom adjacent to the carbonyl center).

The reaction can be used to identify monosaccharides. It involves two reactions. Firstly glucose with phenylhydrazine gives glucosephenylhydrazone by elimination of a water molecule from the functional group. The next step involves reaction of one equivalent of glucosephenylhydrazone with two equivalents of phenylhydrazine (excess). First phenylhydrazine is involved in oxidizing the alpha carbon to a carbonyl group, and the second phenylhydrazine involves in removal of one water molecule with the new-formed carbonyl group of that oxidized carbon and forming the similar carbon nitrogen bond. The alpha carbon is attacked here because it is more reactive than the others.

Osazones are highly coloured and crystalline compounds and can be easily detected. Each sugar has a characteristic crystal form of osazones.

Maltose forms petal-shaped crystals.

Lactose forms powder puff-shaped crystals.

Galactose forms rhombic-plate shaped crystals.

Glucose, fructose and mannose form broomstick or needle-shaped crystals.

Reductive amination

Reductive amination (also known as reductive alkylation) is a form of amination that involves the conversion of a carbonyl group to an amine via an intermediate imine. The carbonyl group is most commonly a ketone or an aldehyde. It is considered the most important way to make amines, and a majority of amines made in the pharmaceutical industry are made this way.

Regioselectivity

In chemistry, regioselectivity is the preference of one direction of chemical bond making or breaking over all other possible directions. It can often apply to which of many possible positions a reagent will affect, such as which proton a strong base will abstract from an organic molecule, or where on a substituted benzene ring a further substituent will add.

A specific example is a halohydrin formation reaction with 2-propenylbenzene:

Because of the preference for the formation of one product over another, the reaction is selective. This reaction is regioselective because it selectively generates one constitutional isomer rather than the other.

Various examples of regioselectivity have been formulated as rules for certain classes of compounds under certain conditions, many of which are named. Among the first introduced to chemistry students are Markovnikov's rule for the addition of protic acids to alkenes, and the Fürst-Plattner rule for the addition of nucleophiles to derivatives of cyclohexene, especially epoxide derivatives.Regioselectivity in ring-closure reactions is subject to Baldwin's rules. If there are two or more orientations that can be generated during a reaction, one of them is dominant (e.g., Markovnikov/anti-Markovnikov addition across a double bond)

Regioselectivity can also be applied to specific reactions such as addition to pi ligands.

Selectivity also occurs in carbene insertions, for example in the Baeyer-Villiger reaction. In this reaction, an oxygen is regioselectively inserted near an adjacent carbonyl group. In ketones, this insertion is directed toward the carbon which is more highly substituted (i.e. according to Markovnikov's rule). For example, in a study involving acetophenones, this oxygen was preferentially inserted between the carbonyl and the aromatic ring to give acetyl aromatic esters instead of methyl benzoates.

Transesterification

In organic chemistry, transesterification is the process of exchanging the organic group R″ of an ester with the organic group R′ of an alcohol. These reactions are often catalyzed by the addition of an acid or base catalyst. The reaction can also be accomplished with the help of enzymes (biocatalysts) particularly lipases (E.C.3.1.1.3).

Strong acids catalyse the reaction by donating a proton to the carbonyl group, thus making it a more potent electrophile, whereas bases catalyse the reaction by removing a proton from the alcohol, thus making it more nucleophilic. Esters with larger alkoxy groups can be made from methyl or ethyl esters in high purity by heating the mixture of ester, acid/base, and large alcohol and evaporating the small alcohol to drive equilibrium.

Triose

A triose is a monosaccharide, or simple sugar, containing three carbon atoms. There are only three possible trioses (including Dihydroxyacetone): L-Glyceraldehyde and D-Glyceraldehyde, the two enantiomers of glyceraldehyde, which are aldotrioses because the carbonyl group is at the end of the chain, and dihydroxyacetone, the only ketotriose, which is symmetrical and therefore has no enantiomers.Trioses are important in cellular respiration. During glycolysis, fructose-1,6-bisphosphate is broken down into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Lactic acid and pyruvic acid are later derived from these molecules.

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