Information about Reductive Amination
Reductive amination is a chemical reaction which involves the conversion of a carbonyl group to an amine. The carbonyl group is most commonly a ketone or an aldehyde.
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 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 reaction depicted below is an example of an asymmetric reductive amination of an aryl ketone and an aniline.[1][2]
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.
)
Reductive amination
Reaction mechanism
In organic synthesis
In this organic reaction, the amine first reacts with the carbonyl group, in a reversible manner, to form the imine accompanied by the loss of one molecule of water by alkylimino-de-oxo-bisubstitution. 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.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 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.
Scope
In industry many primary amines for example triethylamine, Hunig's base or cyclopentylamine, are formed directly from ketones with a gasmixture of ammonia and hydrogen and a suitable catalyst .The reaction depicted below is an example of an asymmetric reductive amination of an aryl ketone and an aniline.[1][2]
)
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.
Biochemistry
A step in the biosynthesis of many α-amino acids is the reductive amination of an α-ketoacid. 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.[3] The sequence from keto-acid to amino acid can be summarized as follows:- HO2CC(O)R → HO2CC(=NCH-X)R → HO2CCH(N=CH-X)R → HO2CCH(NH2)R
External links
- Current methods for reductive amination
- Industrial Reductive amination at BASF
References
1. ^ 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)
2. ^ 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.
3. ^ Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISNB 1-57259-153-6.
2. ^ 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.
3. ^ Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISNB 1-57259-153-6.
See also
chemical reaction is a process that results in the interconversion of chemical substances.[1] The substance or substances initially involved in a chemical reaction are called reactants.
..... Click the link for more information.
..... Click the link for more information.
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.g.
..... Click the link for more information.
The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex (a metal carbonyl, e.g.
..... Click the link for more information.
Amines are organic compounds and a type of functional group that contain nitrogen as the key atom. Structurally amines resemble ammonia, wherein one or more hydrogen atoms are replaced by organic substituents such as alkyl and aryl groups.
..... Click the link for more information.
..... Click the link for more information.
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.
..... Click the link for more information.
..... Click the link for more information.
aldehyde is an organic compound containing a terminal carbonyl group. This functional group, which consists of a carbon atom which is bonded to a hydrogen atom and double-bonded to an oxygen atom (chemical formula O=CH-), is called the aldehyde group.
..... Click the link for more information.
..... Click the link for more information.
Organic reactions are chemical reactions involving organic compounds.[1] The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions and redox reactions.
..... Click the link for more information.
..... Click the link for more information.
The concept of a reversible reaction was intoduced by Berthollet (1803) after he had observed the formation of sodium carbonate crystals at the edge of a salt lake.[1]
..... Click the link for more information.
- 2NaCl + CaCO3 → Na2CO3 + CaCl2
..... Click the link for more information.
An imine is a functional group or chemical compound containing a carbon-nitrogen double bond. Due to their diverse reactivity, imines are common substrates in a wide variety of transformations.
..... Click the link for more information.
..... Click the link for more information.
Alkylimino-de-oxo-bisubstitution in organic chemistry is the organic reaction of carbonyl compounds with amines to imines [1]. The reaction name is based on the IUPAC Nomenclature for Transformations.
..... Click the link for more information.
..... Click the link for more information.
An imine is a functional group or chemical compound containing a carbon-nitrogen double bond. Due to their diverse reactivity, imines are common substrates in a wide variety of transformations.
..... Click the link for more information.
..... Click the link for more information.
Sodium borohydride, also known as sodium tetrahydroborate, has the chemical formula NaBH4. This white solid, usually encountered as a powder, is a specialty reducing agent used in the manufacture of pharmaceuticals and other organic and inorganic compounds.
..... Click the link for more information.
..... Click the link for more information.
Sodium cyanoborohydride (NaBH3(CN)) is a chemical compound.
Conditions/substances to avoid are: heat, flame, ignition sources, water, moist air, strong acids and strong oxidizers.
Strong acids on sodium cyanoborohydride release cyanide.
..... Click the link for more information.
Conditions/substances to avoid are: heat, flame, ignition sources, water, moist air, strong acids and strong oxidizers.
Strong acids on sodium cyanoborohydride release cyanide.
..... Click the link for more information.
Sodium borohydride, also known as sodium tetrahydroborate, has the chemical formula NaBH4. This white solid, usually encountered as a powder, is a specialty reducing agent used in the manufacture of pharmaceuticals and other organic and inorganic compounds.
..... Click the link for more information.
..... Click the link for more information.
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.
..... Click the link for more information.
..... Click the link for more information.
The Leuckart reaction is the chemical reaction of ammonium salts of formic acid with aldehydes (or ketones) to form amines by reductive amination. [1]
In addition to ammonia, primary and secondary amines are also successful.
..... Click the link for more information.
In addition to ammonia, primary and secondary amines are also successful.
..... Click the link for more information.
The Mannich reaction is an organic reaction and consists of a amino alkylation of an acidic proton placed next to a carbonyl functional group with formaldehyde and ammonia or any primary or secondary amine.
..... Click the link for more information.
..... Click the link for more information.
The Petasis reaction is the chemical reaction of an amine, aldehyde, and vinyl- or aryl-boronic acid to form substituted amines.[1] [2] [3]
..... Click the link for more information.
..... Click the link for more information.
Triethylamine is the chemical compound with the formula N(CH2CH3)3, commonly abbreviated Et3N. It is a commonly enountered in organic synthesis probably because it is the simplest symmetrically trisubstituted amine, i.e.
..... Click the link for more information.
..... Click the link for more information.
N,N-Diisopropylethylamine, or Hünig's base, DIPEA or DIEA, is an organic compound and an amine. It is used in organic chemistry as a base. Because the nitrogen atom is shielded by the two isopropyl groups and an ethyl group only a proton is small enough to easily fit.
..... Click the link for more information.
..... Click the link for more information.
Ammonia is a compound with the formula NH3. It is normally encountered as a gas with a characteristic pungent odor. Ammonia contributes significantly to the nutritional needs of the planet as a precursor to foodstuffs and fertilizers.
..... Click the link for more information.
..... Click the link for more information.
1, −1
(amphoteric oxide)
Electronegativity 2.20 (Pauling scale) More
Atomic radius 25 pm
Atomic radius (calc.) 53 pm
Covalent radius 37 pm
Van der Waals radius 120 pm
Miscellaneous
Thermal conductivity (300 K) 180.
..... Click the link for more information.
(amphoteric oxide)
Electronegativity 2.20 (Pauling scale) More
Atomic radius 25 pm
Atomic radius (calc.) 53 pm
Covalent radius 37 pm
Van der Waals radius 120 pm
Miscellaneous
Thermal conductivity (300 K) 180.
..... Click the link for more information.
Asymmetric synthesis, also called chiral synthesis, enantioselective synthesis or stereoselective synthesis, is organic synthesis which introduces one or more new and desired elements of chirality.
..... Click the link for more information.
..... Click the link for more information.
Aniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. It is the simplest and one of the most imporant aromatic amines, being used as a precursor to more complex chemicals.
..... Click the link for more information.
..... Click the link for more information.
In kinetic resolution two enantiomers show different reaction rates in a chemical reaction thereby creating an excess of the less reactive enantiomer [1]. This excess goes through a maximum and disappears on full completion of the reaction.
..... Click the link for more information.
..... Click the link for more information.
An enamine is an unsaturated compound derived by the reaction of an aldehyde or ketone with a secondary amine followed by loss of H2O.
The word "enamine" is apparently derived from the prefix en-, used as the suffix of alkene, and the root amine.
..... Click the link for more information.
The word "enamine" is apparently derived from the prefix en-, used as the suffix of alkene, and the root amine.
..... Click the link for more information.
amino acid is a molecule that contains both amine and carboxyl functional groups. In biochemistry, this term refers to alpha-amino acids with the general formula H2NCHRCOOH, where R is an organic substituent.
..... Click the link for more information.
..... Click the link for more information.
Pyridoxal-phosphate (PLP, pyridoxal-5'-phosphate) is a coenzyme of many enzymatic reactions. It is the active form of vitamin B 6 which comprises three natural organic compounds, pyridoxal, pyridoxamine and pyridoxine.
..... Click the link for more information.
..... Click the link for more information.
Glutamic acid or glutamate (abbreviated as Glu or E; Glx or Z represents either glutamic acid or glutamine), is the protonated form of glutamate (the anion). Glutamate is one of the 20 proteinogenic amino acids.
..... Click the link for more information.
..... Click the link for more information.
Journal of the American Chemical Society (usually abbreviated as J. Am. Chem. Soc., or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society.
..... Click the link for more information.
..... Click the link for more information.
digital object identifier (or DOI) is a permanent identifier given to a document, which is not related to its current location. A typical use of a DOI is to give a scientific paper or article a unique identifying number that can be used by anyone to locate details of the paper, and
..... Click the link for more information.
..... Click the link for more information.
This article is copied from an article on Wikipedia.org - the free encyclopedia created and edited by online user community. The text was not checked or edited by anyone on our staff. Although the vast majority of the wikipedia encyclopedia articles provide accurate and timely information please do not assume the accuracy of any particular article. This article is distributed under the terms of GNU Free Documentation License.
Herod_Archelaus
