Reductive amination (also known as reductive alkylation) is a chemical reaction which 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. For other uses, see Chemical reaction (disambiguation). ... 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. The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex (a metal carbonyl, e. ... The general structure of an amine Amines are organic compounds and a type of functional group that contain nitrogen as the key atom. ... The general structure of an imine An imine is a functional group or chemical compound containing a carbon-nitrogen double bond. ... Ketone group A ketone (pronounced as key tone) is either the functional group characterized by a carbonyl group (O=C) linked to two other carbon atoms or a chemical compound that contains this functional group. ... An aldehyde. ...

Reaction mechanism

In organic synthesis

In this organic reaction, the amine first reacts with the carbonyl group to form a hydroxylamine species, which subsequently loses one molecule of water in a reversible manner by alkylimino-de-oxo-bisubstitution, to form the imine. The equilibrium between aldehyde/ketone and imine can be shifted toward imine formation by removal of the formed water through physical or chemical means. This intermediate imine can then be isolated and reduced with a suitable reducing agent (e.g. sodium borohydride). This is indirect reductive amination. Organic reactions are chemical reactions involving organic compounds. ... Hydroxylamine is a reactive chemical with formula NH2OH. It can be considered a hybrid of ammonia and water due to parallels it shares with each. ... A reversible reaction is a chemical reaction that may proceed in both the forward and reverse directions. ... Alkylimino-de-oxo-bisubstitution in organic chemistry is the organic reaction of carbonyl compounds with amines to imines . ... The general structure of an imine An imine is a functional group or chemical compound containing a carbon-nitrogen double bond. ... The general structure of an imine An imine is a functional group or chemical compound containing a carbon-nitrogen double bond. ... Sodium borohydride, also known as sodium tetrahydroborate, has the chemical formula NaBH4. ...

However, it is also possible to carry out the same reaction all in one pot, with the imine formation and reduction occurring concurrently. This is known as direct reductive amination and is carried out with reducing agents that are more reactive toward imines than ketones, such as sodium cyanoborohydride (NaBH₃CN) or sodium triacetoxyborohydride (NaBH(OCOCH₃)₃). This reaction has in recent years been performed in an aqueous environment casting doubt on the necessity of forming the imine.^[1] This is because the loss of the water molecule is thermodynamically disfavoured by the presence of a large amount of water in its environment, as seen in the work of Turner et al.^[2] This therefore, suggests that in some cases the reaction proceeds via direct reduction of the hydroxylamine species.^[3] Sodium cyanoborohydride (NaBH3(CN) is a chemical compound. ...

This reaction is related to the Eschweiler-Clarke reaction in which amines are methylated to tertiary amines, the Leuckart-Wallach reaction with formic acid and to other amine alkylation methods as the Mannich reaction and the Petasis reaction. The Eschweiler-Clarke reaction (also called the Eschweiler-Clarke methylation) is a chemical reaction whereby a primary (or secondary) amine is methylated using excess formic acid and formaldehyde. ... The Leuckart reaction is the chemical reaction of ammonium salts of formic acid with aldehydes (or ketones) to form amines by reductive amination. ... The Mannich reaction is a chemical reaction in organic chemistry and is a amino alkylation of an acidic proton placed next to a carbonyl functional group with formaldehyde and ammonia or any primary or secondary amine. ... The Petasis reaction is the chemical reaction of an amine, aldehyde, and vinyl- or aryl-boronic acid to form substituted amines. ...

Scope

A classic named reaction is the Mignonac Reaction (1921) ^[4] involving reaction of a ketone with ammonia over a nickel catalyst for example in a synthesis of alpha-phenylethylamine ^[5] starting from acetophenone. This page aims to list well-known chemical reactions, name reactions, name reagents, and name rules to stimulate the creation of Wikipedia articles. ... Ketone group A ketone (pronounced as key tone) is either the functional group characterized by a carbonyl group (O=C) linked to two other carbon atoms or a chemical compound that contains this functional group. ... For other uses, see Ammonia (disambiguation). ... For other uses, see Nickel (disambiguation). ... Acetophenone is a crystalline ketone that is used as a solvent for cellulose ethers and esters in the manufacture of alcohol-soluble resins. ...

In industry, tertiary amines such as triethylamine and Hunig's base, are formed directly from ketones with a gasmixture of ammonia and hydrogen and a suitable catalyst . Triethylamine is the chemical compound with the formula N(CH2CH3)3, commonly abbreviated Et3N. It is a commonly encountered in organic synthesis probably because it is the simplest symmetrically trisubstituted amine, i. ... For other uses, see Ammonia (disambiguation). ... This article is about the chemistry of hydrogen. ...

The reaction depicted below is an example of an asymmetric reductive amination of an aryl ketone and an aniline.^[6][7] The two optical isomers of bromochlorofluoromethane Chiral synthesis also called asymmetric synthesis or enantioselective synthesis is organic synthesis which preserves or introduces a desired chirality. ... Aniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. ...

The formation of only one enantiomer from the racemic reactant is attributed to dynamic kinetic resolution because both enantiomers in the racemic imine intermediate interconvert through their common enamine. An enamine is an unsaturated compound derived by the reaction of an aldehyde or ketone with a secondary amine followed by loss of H2O. Form Categories: Functional groups | Stub ...

Biochemistry

A step in the biosynthesis of many α-amino acids is the reductive amination of an α-ketoacid, usually by a transaminase enzyme. The process is catalyzed by pyridoxal phosphate and the ammonia source is glutamate. The initial step entails formation of an imine, but the hydride equivalents are supplied by a reduced pyridine to give an aldimine, which hydrolyzes to the amine.^[8] The sequence from keto-acid to amino acid can be summarized as follows: This article is about the class of chemicals. ... Pyridoxal-phosphate (PLP, pyridoxal-5-phosphate) is a cofactor of many enzymatic reactions. ... Glutamate is the anion of glutamic acid. ...

HO₂CC(O)R → HO₂CC(=NCH₂-X)R → HO₂CCH(N=CH-X)R → HO₂CCH(NH₂)R

External links

• Current methods for reductive amination
• Industrial Reductive amination at BASF

References

1. ^ Shinya Sato, Takeshi Sakamoto, Etsuko Miyazawa and Yasuo Kikugawa, One-Pot Reductive Amination of Aldehydes and Ketones with $alpha$-Picoline Borane in Methanol, in Water, and in Neat Conditions, Tetrahedron, 7899-7906, 60, 2004
2. ^ Colin J. Dunsmore, Reuben Carr, Toni Fleming and Nicholas J. Turner, A Chemo-Enzymatic Route to Enantiomerically Pure Cyclic Tertiary Amines, J Am Chem Soc, 2224-2225, 128(7), 2006
3. ^ V. A. Tarasevich and N. G. Kozloz, Reductive Amination of Oxygen-Containing Organic Compounds, Russian Chemical Reviews, 68(1), 55-72, 1999
4. ^ Nouvelle méthodegénérale de préparation des amines à partir des aldéhydes ou des cétones. M. Georges Mignonac, Compt. rend., 172, 223 (1921).
5. ^ Organic Syntheses, Coll. Vol. 3, p.717 (1955); Vol. 23, p.68 (1943). http://www.orgsynth.org/orgsyn/pdfs/CV3P0717.pdf
6. ^ Catalytic Asymmetric Reductive Amination of Aldehydes via Dynamic Kinetic Resolution Sebastian Hoffmann, Marcello Nicoletti, and Benjamin List J. Am. Chem. Soc. 2006, 128(40), 13074 - 13075. (doi:10.1021/ja065404r)
7. ^ In this reaction the reducing agent is an Hantzsch ester and the chiral catalyst a hydrogen phosphate of the BINAP family. Molecular sieves remove formed water. The enantiomeric ratio is 99:1.
8. ^ Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISNB 1-57259-153-6.

Organic Syntheses is a scientific journal that Since 1921 has provided the chemistry community with annual collections of detailed and checked procedures for the organic synthesis of organic compounds. ... The Journal of the American Chemical Society (usually abbreviated as , or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A reducing agent (also called a reductant or reducer) is the element or a compound in a redox (reduction-oxidation) reaction (see electrochemistry) that reduces another species. ... This page meets Wikipedias criteria for speedy deletion. ... (S)- and (R)-BINAP Ball and stick model of BINAP viewed as above In organic chemistry, BINAP, an acronym used for 2,2-bis(diphenylphosphino)-1,1-binaphthyl, is an important chiral ligand widely used in asymmetric synthesis. ... A molecular sieve is a material containing tiny pores of a precise and uniform size that is used as an adsorbent for gases and liquids. ...

See also

• Forster-Decker method