Leuckart synthesis

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. ... 

Furfuryl dimethyl amine is first produced. This may conveniently be accomplished by employing the Leuckart synthesis known to those skilled in the art, which involves the use of an aldehyde or a ketone, and formate of ammonia or an amine, or corresponding formamide derived by dehydration of formate of ammonia or an amine. 

Figure 2.8 Exemplar impurities found in amphetamine produced by using the Leuckart 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. 

LEUCKART Thiophenot Synthesis Formation of Ihiophenols from diazonium salts and xanthates... 

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

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... 

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. 

Various accounts report the synthesis of heterocyclic androstane derivatives. 17)8-Acetoxy-4-oxa-androst-2-ene (215) has been prepared in three steps from the hemiacetal (214). Since various 4-aza-steroids exhibit antimicrobial activity, several new 4-aza-androstanes have been prepared. The reduction of ring a enamine lactams, such as 4-aza-androst-5-ene-3,17-dione (216a), under conditions of the Leuckart-Wallace reductive amination, provided 17/ -(iV-methyl-... 

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