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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. A chemical reaction is a process that always results in the interconversion of Chemical substances The substance or substances initially involved in a chemical reaction are called In Organic chemistry, a carbonyl group is a Functional group composed of a Carbon Atom double-bonded to an Oxygen Amines are Organic compounds and Functional groups that contain a basic Nitrogen Atom with a Lone pair. An imine is a Functional group or Chemical compound containing a Carbon – Nitrogen Double bond. The carbonyl group is most commonly a ketone or an aldehyde. 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 An aldehyde is an organic compound containing a terminal Carbonyl group.

Reductive amination

Contents

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. Organic reactions are Chemical reactions involving Organic compounds The basic Organic chemistry reaction types are Addition reactions Elimination Hydroxylamine is a reactive chemical with formula NH2OH It can be considered a hybrid of Ammonia and Water due to parallels it shares A reversible reaction is a Chemical reaction that results in an equilibrium mixture of Reactants and products. Alkylimino-de-oxo-bisubstitution in Organic chemistry is the Organic reaction of Carbonyl compounds with Amines to Imines. An imine is a Functional group or Chemical compound containing a Carbon – Nitrogen Double bond. 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. An imine is a Functional group or Chemical compound containing a Carbon – Nitrogen Double bond. g. sodium borohydride). Sodium borohydride, also known as sodium tetrahydroborate, has the Chemical formula Na[[boron B]] H 4 This is indirect reductive amination.

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). Sodium cyanoborohydride ( Na[[Boron B]] H3 ( C[[Nitrogen N]] is a Chemical compound. Sodium borohydride, also known as sodium tetrahydroborate, has the Chemical formula Na[[boron B]] H 4 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]

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 The Leuckart reaction is the Chemical reaction of ammonium salts of Formic acid with Aldehydes (or Ketones to form Amines by Reductive The Mannich reaction is an Organic reaction which consists of an amino alkylation of an acidic proton placed next to a Carbonyl Functional group The Petasis reaction is the Chemical reaction of an Amine, Aldehyde, and Vinyl - or Aryl - Boronic acid to form substituted

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. A name reaction is a Chemical reaction named after its discoverers or developers 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 Ammonia is a compound with the formula N[[hydrogen H3]] It is normally encountered as a Gas with a characteristic pungent Odor Nickel (ˈnɪkəl is a metallic Chemical element with the symbol Ni and Atomic number 28 Acetophenone is the Organic compound with the formula C6H5C(OCH3


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(CH2CH33 commonly abbreviated Et 3N NN-Diisopropylethylamine, or Hünig's base, DIPEA or DIEA is an Organic compound and an Amine. Ammonia is a compound with the formula N[[hydrogen H3]] It is normally encountered as a Gas with a characteristic pungent Odor Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1

The reaction depicted below is an example of an asymmetric reductive amination of an aryl ketone and an aniline. Asymmetric synthesis, also called chiral synthesis, enantioselective synthesis or stereoselective synthesis, is Organic synthesis which Aniline, phenylamine or aminobenzene is an Organic compound with the formula C6H7N [6][7]

Asymmetric Reductive Amination Hoffmann 2006

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. In kinetic resolution two Enantiomers show different Reaction rates in a Chemical reaction thereby creating an excess of the less reactive enantiomer. An enamine is an unsaturated compound derived by the reaction of an Aldehyde or Ketone with a Secondary amine followed by loss of H2O

Biochemistry

A step in the biosynthesis of many α-amino acids is the reductive amination of an α-ketoacid, usually by a transaminase enzyme. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this The process is catalyzed by pyridoxal phosphate and the ammonia source is glutamate. Pyridoxal-phosphate (PLP Pyridoxal -5'- Phosphate, P5P is a Prosthetic group of some Enzymes It is the active form of vitamin B6 Glutamic acid (abbreviated as Glu or E) is one of the 20 Alpha Amino acids It is not among the human Essential amino acids Its 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:

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

External links

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. Organic Syntheses is a Scientific journal that since 1921 has provided the Chemistry community with annual collections of detailed and checked procedures 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. The Journal of the American Chemical Society (usually abbreviated as J (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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. A reducing agent (also called a reductant or reducer) is the element or a compound in a Redox (reduction-oxidation reaction (see Electrochemistry The Hantzsch pyridine synthesis or Hantzsch dihydropyridine synthesis is a multi-component Organic reaction between an Aldehyde such A phosphate, an Inorganic chemical, is a salt of Phosphoric acid. BINAP is an Acronym for the Organophosphorus compound 22'-bis(diphenylphosphino-11'-binaphthyl Molecular sieves remove formed water. 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 Molecules The enantiomeric ratio is 99:1. Enantiomeric excess exists where one Enantiomer is present more than the other in a Chemical substance, and is defined as the absolute difference between the mole
  8. ^ Nelson, D. L. ; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISNB 1-57259-153-6.

See also

The Forster-Decker method is a series of Chemical reactions that transform a primary Amine ( 1) ultimately to a secondary amine ( 6)
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