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Leuckart reaction
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Main page The Leuckart reaction is the chemical reaction that converts aldehydes or Leuckart reaction
ketones to amines by reductive amination in the presence of heat. [1][2] The Named after Rudolf Leuckart
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Featured content reaction, named after Rudolf Leuckart, proceeds via two mechanisms: one Reaction type Substitution reaction
Current events using ammonium formate and the other using formamide as the reducing Identifiers
Random article agent.[3] It requires high temperatures, usually between 120 and 130 °C, RSC ontology ID RXNO:0000101
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although under the presence of formamide, the temperature can be greater
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than 165 °C.[1] The reaction works best using ammonium formate and the general reaction can be seen below.
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What links here The ketone is converted to an amine via reductive amination using ammonium formate
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Permanent link 1 History
Page information 2 Mechanism
Wikidata item 3 Applications
Cite this page 4 See also
5 References
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The Leuckart reaction is named in honor of its developer, the German chemist Rudolf Leuckart (1854–1899). He
Languages discovered that heating benzaldehyde with formamide does not produce benzylidenediformamide as anticipated, but
Deutsch benzylamine.[4] In 1891, a colleague of Leuckart at the University of Göttingen, Otto Wallach, performed further
‫ﻓﺎرﺳﯽ‬ reactions using alicyclic and terpenoid ketones as well as aldehydes, demonstrating the general application.[4] Over the
Français course of the past century, chemists have discovered several methods to improve the yield of the reaction and carry it
Italiano
out under less strenuous conditions. Pollard and Young summarized various ways in which amines can be formed:
Bahasa Melayu
Nederlands using either formamide or ammonium formate, or both, or adding formic acid to formamide.[3] However, using just
日本語 ammonium formate as the reagent produces the best yields.[1][3] Using formamide produces low yields compared to
Polski ammonium formate but yields can be increased by using large amount of formamide, or using ammonium formate,
Русский ammonium sulfate, and magnesium chloride as catalysts.[5]
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Mechanism [edit]
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Ammonium formate as reagent:
 The mechanism depicts the conversion of ketone (or aldehyde) to an amine using
ammonium formate as a reagent.

Ammonium formate first dissociates into formic acid and ammonia. Ammonia then performs a nucleophilic attack on the
carbonyl carbon.[3] The oxygen deprotonates hydrogen from nitrogen to form a hydroxyl. The hydroxyl is protonated
using hydrogen from formic acid, which allows for water molecule to leave. This forms a carbocation, which is
resonance stabilized. The compound attacks hydrogen from the deprotonated formic acid from previous step, forming a
carbon dioxide and an amine.
Formamide as reagent:

The scheme depicts the mechanism for the Leuckart reaction using formamide as the
reducing agent.

Formamide first nucleophilically attacks the carbonyl carbon.[3] The oxygen is protonated by abstracting hydrogen from
 the nitrogen atom, subsequently forming a water molecule that leaves, forming N-formyl derivative, which is resonance
stabilized.[3] Water hydrolyzes formamide to give ammonium formate, which acts as a reducing agent and adds on to
the N-formyl derivative. Hydride shift occurs, resulting in loss of carbon dioxide. Ammonium ion is added forming an
imine and releasing ammonia. The imine goes through hydrolysis to form the amine, which is depicted in the scheme
below.

Hydrolysis of imine

Applications [edit]
A notable example of the Leuckart reaction is its use in the synthesis of tetrahydro-1,4 benzodiazepin-5-one, a
molecule that is part of the benzodiazepine family.[6] Many compounds in this family of molecules are central nervous
system suppressants and are associated with therapeutic uses and a variety of medications, such as antibiotics,
antiulcer, and anti-HIV agents.[6] Researchers were able to synthesize tetrahydro-1,4-benzodiazepin-5-ones with
excellent yields and purities by utilizing the Leuckart Reaction. Researchers performed the reaction via solid-phase
synthesis and used formic acid as the reducing agent.[6]

See also [edit]

Eschweiler–Clarke reaction

References [edit]
1. ^a b c Alexander, Elliot; Ruth Bowman Wildman (1948). "Studies on the Mechanism of the Leuckart Reaction". Journal of
the American Chemical Society. 70: 1187–1189. doi:10.1021/ja01183a091 .
2. ^ Ingersoll, A. W. (1937). "α-Phenylethylamine". Organic Syntheses. 17: 76. doi:10.15227/orgsyn.017.0076 .
3. ^ a b c d e f Pollard, C.B.; David C. Young (1951). "The Mechanism of the Leuckart Reaction". Journal of Organic
Chemistry. 16: 661–672. doi:10.1021/jo01145a001 .
4. ^ a b Crossley, Frank S.; Maurice L. Moore (1944). "Studies on the Leuckart Reaction". Journal of Organic Chemistry. 9
(6): 529–536. doi:10.1021/jo01188a006 .
5. ^ Webers, Vincent J.; William F. Bruce (1948). "The Leuckart Reaction: A study of the Mechanism". Journal of the
American Chemical Society. 70: 1422–1424. doi:10.1021/ja01184a038 .
6. ^ a b c Lee, Sung-Chan; Seung Bum Park (2007). "Novel application of Leuckart–Wallach reaction for synthesis of
tetrahydro-1,4-benzodiazepin-5-ones library" . Chemical Communications (36): 3714–3716. doi:10.1039/B709768A .
PMID 17851604 .

Categories: Substitution reactions Name reactions Organic redox reactions

This page was last edited on 2 November 2017, at 10:19.

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