Leuckart reaction

Leuckart reaction The conversion of ketones and aromatic aldehyde,s to primary amines by reaction with ammonium methanoale at a high temperature. 

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. 

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. 

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

The Leuckart reaction was originally conceived using a chemical called ammonium formate (HCOONH4) which is very similar to formamide (HCONH2) [30]. It is pretty much believed that this molecule donates its ammonium part to the P2P and then the formate part turns into formic acid (HCOOH) which then acts to reduce the intermediate into its stable formyl derivative (don t ask). 

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. 

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. 

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... 

Well, that s about as rounded an education on Leuckart reactions as Strike can give. Strike feels that after reading all of those similar, repetitious steps, one can start to get a good feel for where a product is at any given moment. Stuff like what happens to MDA when it s mixed with acid or base, or what happens to ketones (P2P) under the same circumstances. One can see now that it is possible to not only isolate safrole and P2Ps chemically but that the same can be true for the final MDA or meth freebase oil. Repeated washings with acid or base and solvent can effectively clean up a compound to an almost presentable state without the use of vacuum distillation, it can happen, one only needs have confidence in the chemistry. 

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 ... 

Preparation of Amines. Amines are prepared by heating aUphatic, aromatic, or cycHc ketones with ammonium formate, formamide, or an A/-substituted ammonium formate at 165—190°C (Leuckart reaction). For example, cx-methylbenzylamine is prepared by the reaction of acetophenone with ammonium formate. 

The Leuckart reaction uses formic acid as reducing agent. Reductive alkylation using formaldehyde, hydrogen, and catalyst, usually nickel, is used commercially to prepare methylated amines. These tertiary amines are used to prepare quaternary ammonium salts. 

Another interesting fact to be noted is that the bicyclic enamine (87) and its pyrrolidine analogue failed to undergo reduction with 98% formic acid, whereas the pyrrolidine enamine of 2-bicyclo[2.2.1]hepten-5-carboxalde-hyde (94), which exists largely in the transoid form (49), was readily reduced to (95). However, the saturated amine-substituted norbornane can be obtained directly from norbornanone under the more vigorous conditions of the Leuckart reaction (49a). 

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. ... 

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

Diphenylisoinclole (29) can be prepared by a modified Leuckart reaction of o-dibenzoylbenzene (46), using an ammonium salt of formic acid the process is essentially a reductive alkylation of ammonia, accompanied by cyclization, and leads to 29 in 44% yield with ammonium formate, and 47 in 28% yield with methylammonium formate. 1,3-Diphenylisoindole. (29) can also be obtained in good yield by the reaction of 46 with 1,1-dimethylhydrazine. ... 

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. 

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

Bimolecular formate decomposition HC02" + H20 <-> C02 + OH + H2 Leuckart reaction 6... 

Leuckart reaction, 2 522 Leuco compounds, 9 329 Leuco dye system, 79 349 Leucomycins, 75 288-2891... 

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 A -methyl derivative (32) was obtained from 31 via a Leuckart reaction and isolated as its hydrochloride 32 is also formed in the Hoffmann-Lbflfterreaction(photolysisinsulfuricacid)ofthei r-chloramine (33), since after separation of secondary amines and addition of methyl iodide a 10% yield of the methiodide (34) was obtained. The secondary amine (31) was also converted to its A-acyl and JV -nitroso derivatives (35-37) and (38), respectively, by conventional procedures. Free-radical chlorination of 37 gave the ca o-2-chloro derivative (39) and... 

Reductive alkylation can also be accomplished by heating carbonyl compounds at 150-250° with 4-5 mol of ammonium formate, formamide, or formates or formamides prepared by heating primary on secondary amines with formic acid at 180-190° (Leuckart reaction) [322]. An excess of85-90% formic acid is frequently used. Formyl derivatives of primary or secondary amines are sometimes obtained as products and have to be hydrolyzed to the corres-... 

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