Leuckart reaction synthesis

Knoevenagel reaction Knorr pyrrole synthesis. Kolbe>Schmitt reaction Leuckart reaction Mannich reaction... 

Dear readers please take notice Not once has the flask left the stirplate since the formamide and P2P reaction started up to the last point where MDA freebase was liberated. That s pretty damn convenient. Technically, the Leuckart reaction can continue as a one pot synthesis from the last part of P2P cleanup right up to final product. 

In the Leuckart thiophenol synthesis, the reaction of xanthates with dia2onium compounds may be violent. The reaction can be controlled. 

The Leuckart synthesis has been applied successfully in the thiophene series, iV,A -Dimethyl thenylamine and A, A -diethyl thenylamine were obtained from 2-thiophenealdehyde and the appropriate for-mamide. Seven -(2-thienyl)- -arylethylamine hydrochlorides have been prepared from the corresponding ketones in about 40-60% yields and, finally, A -methyl-1-(3-thienyl)-2-propylamine was obtained in 48% yield in the Leuckart reaction from 3-thienylace-tone, methylamine, and formic acid. ... 

Knoevenagel reaction Knorr p3rrrole synthesis. Kolbe-Schmitt reaction Leuckart reaction Mannich reaction Mccrwein-Ponndorf-Verley reduction Michael reaction Oppenauer oxidation... 

A major variation is the use of formic acid or one of its derivatives as the reductant (the Leuckart reaction). In the synthesis of 1-phenylethylamine (Expt 5.197), ammonium formate is heated with aceptophenone while the water formed in the reaction is carefully removed by fractional distillation to give the required amine as its N-formyl derivative, (l-phenylethyl)formamide. This is then hydrolysed with acid to yield the primary amine. The procedure has been satisfactorily applied to many aliphatic-aromatic, alicyclic and aliphatic-heterocyclic ketones, some aromatic ketones and aldehydes, and to some aliphatic aldehydes and ketones boiling at about 100 °C or higher. 

The first reported synthesis of MDMA was from safrole by converting it to its bromo derivative followed by reaction with meth-ylamine (Biniecki et al., 1960). Bailey et al. describe the synthesis of MDMA from 3,4-methylenedioxyphenylacetone using a Leuckart reaction with N-methylformamide and hydrolysis of the N-formyl derivative (Bailey et al., 1975). A third synthesis for MDMA described in the literature starts with peperonal which is reacted with nitroethane, ammonium acetate, and acetic acid to form a nitrostyrene derivative that is reduced to the ketone and then reacted with methylamine to form MDMA (Rabjohns, 1963). Using the method of Borch et al., MDMA can be synthesized by the reductive amination of the appropriate ketone in the presence of sodium cyanoborohydride (Borch et al., 1971). The MDMA syntheses used in clandestine laboratories are analogous. 

Similarly, the use of the microwave to accelerate the Leuckart reaction has been employed in the synthesis of pyrimidines20 and the stereoselective synthesis of endo-tropanamine.21... 

In the other synthesis 75), the Leuckart reaction on y-ketosuberic acid gave 3-(6-oxopiperidyl)propionic acid which on heating yielded LII. Lithium aluminum hydride reduction of LII gave S-coniceine (L). 

The original synthesis discovered by Leuckart was the reductive alkylation of benzaldehyde to form benzylamine using formamide or ammonium formate as the reducing agent. This was later extended by Wallach and by the Eschweiler-Glarke procedure . The scope of the Leuckart reaction has been reviewed by Moore Apart from the special case of formaldehyde, the reaction is most focile with aromatic aldehydes and water-insoluble ketones. Aliphatic... 

Until the last 10-20 years, domestic clandestine methamphetamine laboratories employed P2P, a common and versatile solvent with many legitimate uses. It and related compounds have also potent smells that can betray the location of a clandestine facility. The most common P2P synthesis is based on the Leuckart reaction, in which nucleophilic nitrogen attacks a carbonyl carbon, forming an intermediate that is reduced to methamphetamine or amphetamine... 

The Ferrario reaction generates phenoxathiins from diphenyl ethers (eq 19). The rearrangement of acyloxy aromatic systems is known as the Fries rearrangement (eq 20). Aryl aldehydes are produced by the Gatterman aldehyde synthesis (eq 21 The initial step of the Haworth phenanthrene synthesis makes use of a Friedel-Crafts acylation. The acylation of phenolic compounds is called the Houben-Hoesch reaction (eq 22). The Leuckart amide synthesis generates aryl amides from isocyanates (eq 23). ... 

The synthesis of amines by the in-situ reductive amination of ketones is termed the Leuckart-Wallach reaction. Recently, an asymmetric transfer hydrogenation version of this reaction has been realized [85]. Whilst many catalysts tested give significant amounts of the alcohol, a few produced almost quantitative levels of the chiral amine, in high enantiomeric excess. 

The synthesis of pyrrolizidine developed by LukeS and Sorm31 and by Micheel and Flitsch32 starts with furylacrylic acid (56) which is converted by the Markwald reaction into y-ketopimelic acid (57). The carbonyl group in 57 is replaced by an amino group via the oxime or by the Leuckart-Wallach reaction this substitution results immediately in the formation of the lactam 58, which can be converted by heat into 3,5-dioxopyrrolizidine (59). The latter compound yields pyrrolizidine... 

Among monoamines, both enantiomers of 1-phenylethylamine and their derivatives play a prominent role. They are commercially available, but can also be prepared by resolution of the racemate, obtainable by Leuckart- Wallach reaction of acetophenone1, with malic acid2 or, more conveniently, with tartaric acid in methanol3. They are used as chiral additives for the addition of zinc alkyls to aldehydes in Section D. 1.3.1.4., as copper complexes for the synthesis of biaryls in Section B.2., as lithium salts for enantioselective deprotonation in Section C., and as imines in Sections D.1.1.1.3.1., D.1.1.1,4.. D.1.4.4., D.1.5.2., D.1.5.8., D. 1.6.1.2.1., D.2.3.I., and D.8. A general procedure for the synthesis of imines from carbonyl compounds and primary amines, with many examples of both chiral carbonyl compounds and chiral amines is given in reference 4. 

Leuckart-like reactions have been noted for the co-phosphinoylalkanals 304 and related compounds In these reactions, and also for those with analogous ketones the carbonyl reactant is subjected to reductive amination with ammonia (as ammonium acetate) or amines and NaBH3CN in MeOH at pH 7-7.5 the process is very sensitive to steric hindrance and probably proceeds via an enaminophonate intermediate. The sequence is illustrated (Scheme 38) by a direct synthesis of racemic phosphinothricin, but the involvement of the optically active 1,2-azaphospholidine 118 led to an optically active product ". ... 

Ionic liquids derived from the alkaloid ephedrine or (S)-valinol have been readily obtained on a kilogram scale in a three-step synthesis a Leuckart-Wallach reaction followed by alkylation with Me2 SO4 and ion exchange in aqueous solution (Scheme... 

Studies have reported that the Leuckart-Wallach reaction is effective for the synthesis of chiral amines, with some very important contributions by Kadyrov and Riermeier, who employed a Ru(II)/BINAP derivative to excellent effect, yielding... 

Novel Application of the Leuckart-Wallach Reaction for the Synthesis of a Tetrahydro-1,4-benzodiazepin-5-one Library (Type V)... 

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