By the Leuckart reaction

Acetophenone similarly gives an oxime, CHjCCgHjlCtNOH, of m.p. 59° owing to its lower m.p. and its greater solubility in most liquids, it is not as suitable as the phenylhydrazone for characterising the ketone. Its chief use is for the preparation of 1-phenyl-ethylamine, CHjCCgHslCHNHj, which can be readily obtained by the reduction of the oxime or by the Leuckart reaction (p. 223), and which can then be resolved by d-tartaric acid and /-malic acid into optically active forms. The optically active amine is frequently used in turn for the resolution of racemic acids. 

To make MDMA from the formyl intermediate obtained by the Leuckart reaction the chemist is going to have to distill it to get the clean-yellow oil first. That black crap one gets from the formamide... 

N-Methyl-l,2-diphenylethylamine has been prepared in 8% yield by the Leuckart reaction from desoxybenzoin and methyl-ammonium formate 8 and by the present method.9... 

Methylation of Primary and Secondary Fatty Amines. This is done by the Leuckart reaction (1,30) or reductive methjiation... 

A-Formylamines can be prepared by the Leuckart reaction, a reductive amination of carbonyl compounds by reaction with formamide and formic acid. Evidence for an unprecedented intramolecular transamidation in the mechanism of enantioselective Leuckart reaction of 2-norbornanone with a (l-norbornyl)acetamide is presented. ... 

The reaction of formic acid or a variety of formic acid derivatives, such as formate salts and formamides, with ammonia or a variety of amines, as well as various amine derivatives and salts such as ammonium formate salts, and carbonyl compounds, results in the reductive alkylation of the amine in which the entering alkyl group is derived from the carbonyl compound. This reaction is known as the Leuckart reaction [30]. By proper selection of reagents, primary, secondary, and tertiary amines may be prepared. In general this reaction is carried out at elevated temperatures without further solvents. More recent work indicates that magnesium chloride and ammonium sulfate are particularly useful catalysts in the preparation of tertiary amines by the Leuckart reaction [31]. 

Aldehydes and ketones may be converted into the corresponding primary amines by reduction of their oximes or hydrazones (p. 93). A method of more limited application, known as the Leuckart Reaction, consists of heating the carbonyl compound with ammonium formate, whereby the formyLamino derivative is formed, and can be readily hydrolysed by acids to the amine. Thus acetophenone gives the i-phenylethylformamide, which without isolation can be hydrolysed to i-phenylethylamine. 

By utilizing the improvements stated above in any combination preferable to the chemist, convenience will be enhanced and yield will jump from around 20% to that of 50%. Not bad, but there is one more oddball form of the Leuckart reaction that was devised specifically for X production and produces a yield of 70% This little procedure [32] has been around for 40 years and has, until recently, failed to be reported as a superior Leuckart conversion method by underground sources. This sort of thing really frustrates Strike. 

METHOD 5 Contributed by Osmium [53], The paper reads (at least to Strike) that this reduction method can work to reduce the formyl intermediate made in the Leuckart reaction directly into MDMA instead of needing to hydrolyze to MDA with HCi (don t ask). For this reaction one substitutes an equimolar amount of p-Nitropropene for the 3,4-dimethoxybenzylcyanide in the representative experimental below ... 

The previous sections have dealt with stable C=N-I- functionality in aromatic rings as simple salts. Another class of iminium salt reactions can be found where the iminium salt is only an intermediate. The purpose of this section is to point out these reactions even though they do not show any striking differences in their reactivity from stable iminium salts. Such intermediates arise from a-chloroamines (133-135), isomerization of oxazolidines (136), reduction of a-aminoketones by the Clemmensen method (137-139), reductive alkylation by the Leuckart-Wallach (140-141) or Clarke-Eschweiler reaction (142), mercuric acetate oxidation of amines (46,93), and in reactions such as ketene with enamines (143). 

Aliphatic tertiary amines have been prepared by the desulfurization of thenyl-dialkylamines obtained from the Leuckart reaction with 2-... 

Pr)4, " borohydride-exchange resin,and formic acid. When the last is used, the process is called the Wallach reaction. Conjugated aldehydes are converted to alkenyl-amines with the amine/silica gel followed by reduction with zinc borohydride.In the particular case where primary or secondary amines are reductively methylated with formaldehyde and formic acid, the method is called the Esch-weiler-Clarke procedure. It is possible to use ammonium (or amine) salts of formic acid, " or formamides, as a substitute for the Wallach conditions. This method is called the Leuckart reaction,and in this case the products obtained are often the N-formyl derivatives of the amines instead of the free amines. Primary and secondary amines can be iV-ethylated (e.g., ArNHR ArNREt) by treatment with NaBH4 in acetic acid. Aldehydes react with aniline in the presence of Mont-morillonite KIO clay and microwaves to give the amine. Formaldehyde with formic acid converts secondary amines to the N-methyl derivative with microwave irradiation. 

Conditions for the optimization of the Leuckart reaction have been established. Thus heating a mixture of acetophenone, formamide and water for 6 h at 205 °C, followed by the addition of 6M hydrochloric acid, gave a 86% yield of 1-phenylethylamine (equation 55a)165. 

Eschweiler-Clarke modification org chem A modification of the Leuckart reaction, involving reductive alkylation of ammonia or amines (except tertiary amines) by formaldehyde and formic acid. esh,vTl-3r klark. mad-o-fo ka-shon ... 

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. 

Alkyl groups may be introduced into ammonia, a primary amine, or a secondary amine by means of an aldehyde or ketone in the presence of a reducing agent, such as molecular hydrogen and a catalyst, active metals and acids, or formic acid or one of its derivatives. When the reducing agent is formic acid or a derivative, the reaction is known as the Leuckart reaction and is discussed elsewhere (method 432). An excellent review of the preparation of amines by reductive alkylation has been presented. This article includes a discussion of the scope and utility of the reaction, a selection of experimental conditions, illustrative preparations, and a tabulation of primary, secondary, and tertiary amines prepared thereby. ... 

The methylation of amines by formic acid and formaldehyde 23 is evidently a special case of the Leuckart reaction. 

As an example of all lation, methylation by the Eschweiler-Clarke modification of the Leuckart reaction was adopted. The methylation of the cyclic amines was carried out without difficulty by only refluxing the mixture of the amine, 37% formalin and 95% formic acid. 

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