Leuckart reaction ammonium formate

P-2-P using the Leuckart reaction Ammonium formate Formic acid... 

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 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). 

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. 

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. ... 

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-... 

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... 

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... 

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 Leuckart Reaction. When high boiling carbonyl compounds are heated with formamide or ammonium formate the corresponding amino derivative is often obtained.20 This reaction is usually called the Leuckart reaction.200 One possible mechanism for it is the following ... 

Diphenylisoindole can be conveniently prepared from o-dibenzoyl benzene, for example, by treatment with ammonium formate (Leuckart reaction).5,33 The same type of reaction is observed when the aryl diketone... 

Other ways to do this reaction would be to use what the dudes did in the old days ammonium formate [25]. This way uses 60g of ammonium formate, no formic acid, and a distillation setup. Another combination that works equally well is 1 1 formic acid and ammonia in place of formamide. It is also perfectly fine to remove the water under the distillation setup, then replace it with a reflux condenser and conduct the reaction under reflux for the 5 hours [10]. In fact, reflux is a good way to do any of these Leuckart reactions. 

In 1885, R. Leuckart reported that the reaction of ammonia and primary or secondary amines with ketones (and aldehydes) was possible with ammonium formate, to produce the corresponding primary, secondary, or tertiary amine.1 This reaction became known as the Leuckart reaction. In 1891, Wallach reported that the use of excess formic acid led to an improvement in yield, and that the reaction could be carried out at lower temperatures.2 The Leuckart-Wallach reaction was bom. Wallach went on to apply this reaction to a wide variety of carbonyl compounds, including alicyclic and terpenoid ketones.5... 

In 1931, Ingersoll et al. noted that formamide could act as an Intermediate, and consequently ammonium formate could be replaced with formamide in the Leuckart reaction,12 and in 1968, Bach carried out Leuckart-Wallach reactions on cyclic aliphatic ketones with dimethylformamide in high yields, and with reaction times of only 8-16 h.13... 

Kitamua et al. have identified a useful catalyst for the Leuckart-Wallach reaction that can be used to form primary amines at lower temperatures, and in a higher yield than the standard conditions.14 The reaction uses 0.5 mol% [RhCp Cl2]2 and a 1 5 substrate ammonium formate ratio. 

Optically active amines can also be generated directly from ketones with ammonium formate in a catalytic version of the Leuckart-Wallach reaction (Equation 15.89). The imine is derived from the ammonia generated from the ammonium formate, and the reducing equivalent is derived from the formate. In the presence of the [Ru(BINAP)Cl2]2 catalyst, the amine and formamide were formed as the major products. After hydrolysis of the formamide, the amine was isolated in high yield and ee. 

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... 

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]. 

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