Ammonium formate carbonyl compound reduction

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. 

The Leuckart-Wallach reaction is the oldest method of reductive amination of carbonyl compounds. It makes use of formamide, formic acid or ammonium formate at high temperature. The final product is a formamide derivative, which can be converted to an amine by reduction or hydrolysis. The method has been applied to the preparation of 1,2-diamines with a norbornane framework, which are interesting rigid analogues of 1,2-diaminocyclohexanes. As a matter of fact, starting from N-acetyl-2-oxo-l-norbornylamine 222, the diamide 223 was obtained with excellent diastereoselectivity and then converted to the M-methyl-N -ethyl derivative 224 by reduction with borane [ 104] (Scheme 34). On the other hand, when the reac-... 

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-... 

The Leuckart reductive animation of carbonyl compounds with ammonium formate or formamide was found to benefit strongly, when the reaction was carried out under solvent free conditions with microwave irradiation. Yields of N-alkylated formamides of up to 97% were produced in reaction times of about 30 min, as compared to thermal... 

Clemmensen-type reduction.1 Aromatic ketones can be reduced to the corresponding methylene compounds with ammonium formate on transfer hydrogenation in acetic acid catalyzed by 10% Pd/C. The reduction is usually complete in 10-30 minutes at 110°. Halo and nitro substituents can be reduced under these conditions, and a,p-unsaturated carbonyl groups are reduced to saturated carbonyl groups. 

Reduction The stable Ni(0) complex is a useful catalyst for reduction of carbonyl compounds (to alcohols), sulfonyl azides (to sulfonamides), imines and nitro compounds (to amines) with ammonium formate. 

Several modifications of this reduction involve formates and are effective for reduction of various functional groups. A mixture of formic acid and ethyl magnesium bromide was used to reduce decanal to decanol in 70% yield. Decanal was also reduced to decanol in 69% yield by using sodium formate in N-methyl-2-pyrrolidinone as a solvent. Functional groups other than carbonyl derivatives can be reduced under relatively mild conditions with formate derivatives. Ammonium formate, in the presence of palladium on carhon was used to reduce an azide to a primary amine.Aliphatic nitro compounds are also converted to an amine with this reagent. l°... 

Reductive amination of an aldehyde or ketone with ammonia or a primary amine can sometimes be problematic, as the product amine can undergo further reductive amination with the starting carbonyl compound. One method that promotes selective formation of primary amines uses the rhodium(lll) complex [RhCp Cl2]2 as a catalyst and ammonium formate (HCOONH4), which acts as the source of the ammonia and the hydride (7.87). ... 

An additional methodology for the selective reduction of unsaturated acyclic and cyclic carbonyl compounds is composed of refluxing for 15-45 minutes a mixture of limonene and the enone substrate in the presence of 10% Pd/C. For example, the reduction of /3-octalone afforded the cis isomer in 83% selectivity, which is comparable to the results obtained with hydrogen (Scheme 3 and 5) and ammonium formate (Scheme 19). The high yields and selectivity as well as the no need for an acid or basic medium makes this method very convenient. 

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]. 

Ketonic carbonyl groups are commonly encountered in steroids and their reduction is facile, even in the absence of an alcohol. The lithium-ammonia reduction of androsta-l,4-diene-3,17-dione affords androst-4-ene-3,17-dione in 20% yield but concurrent reduction of the C-17 ketone results in formation of testosterone in 40% yield, even though the reduction is performed rapidly at —40 to —60° and excess lithium is destroyed with solid ammonium chloride. Similar reduction of the C-17 carbonyl group has been observed in other compounds. In the presence of an alcohol, a ketone is complete-... 

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