Carbonylation formamide

Recently, the application of microwave conditions to reactions that normally proceed thermally, but with long reaction times, has led to a much-hastened procedure for the Leuckart-Wallach reaction. 9 Loupy et al. have carried out the reductive amination of various aromatic ketones using a 1 3 3 ratio of carbonyl formamide formic acid under microwave irradiation for 30 minutes to produce the corresponding amines in high yields.19 In comparative studies the authors report considerable improvements in yield with microwave use. 

Formic acid is currently produced iadustriaHy by three main processes (/) acidolysis of formate salts, which are ia turn by-products of other processes (2) as a coproduct with acetic acid ia the Hquid-phase oxidation of hydrocarbons or (3) carbonylation of methanol to methyl formate, followed either by direct hydrolysis of the ester or by the iatermediacy of formamide. 

The carbonylation of methanol [67-56-1] to methyl formate ia the presence of basic catalysts has been practiced iadustriaHy for many years. Ia older processes for formic acid utili2ing this reactioa, the methyl formate [107-31-3] reacts with ammonia to give formamide [75-12-7] which is hydroly2ed to formic acid ia the preseace of sulfuric acid ... 

Coproductioa of ammonium sulfate is a disadvantage of the formamide route, and it has largely been supplanted by processes based on the direct hydrolysis of methyl formate. If the methanol is recycled to the carbonylation step the stoichiometry corresponds to the production of formic acid by hydration of carbon monoxide, a reaction which is too thermodynamicaHy unfavorable to be carried out directly on an iadustrial scale. 

Examine the geometry of formamide. Is the CN bond shorter than expected for a normal single bond (in methylamine), and closer to that expected for a full double bond (in methyleneimine) Is the CO bond longer than that expected in a carbonyl compound (in formaldehyde), perhaps closer to that appropriate for a single bond (in methanol) Also, compare the electrostatic potential map for formamide with those of formaldehyde and methylamine. Is the CO bond in formamide more or less polar than that in formaldehyde Is the CN bond in formamide more or less polar than that in methylamine Draw whatever Lewis structures are needed to properly describe the geometry and charge distribution of formamide. 

In the authors opinion (81UK1252), the evidence for such a scheme is the isolation of formamide transamination products, dialkylformamides (in case of l-dialkylaminoalk-l-en-3-ynes). Examples of formamide transamination, e.g., by /3-amino-substituted carbonyl compounds, are known [58CB2832 60CB1402 60HC( 14)272],... 

A likely pathway is also that in which the key stage is the addition of the second formamide molecule to the carbonyl group of the intermediate 157 to form the amide 159. The latter, with loss of water, closes the dihydropyrimidine ring 160, which undergoes aromatization to 4-metylpyrimidine via 1,4-hydrogen shift and decarbonylation. 

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-... 

Gold(I) complexes of the type [AuCl(PPh3)ra] (n= 1, 2) or [Au(N03)(PPh3)] show an excellent performance towards oxidative addition carbonylation or aromatic amines to form corresponding carbamates, and also towards the carbonilation of aliphatic amines to produce either alkylureas or formamides.2552,2553 Cationic gold(I) compounds of the type [AuL]+ where L = phosphine, phosphite, or arsine are excellent catalysts for the addition of alcohols to alkynes.2554... 

The RAHB effect may be illustrated by the ubiquitous C=0- -H—N hydrogen bond of protein chemistry. As shown in Section 5.2.2, the simplest non-RAHB prototype for such bonding, the formaldehyde-ammonia complex (5.31c), has only a feeble H-bond (1.41 kcalmol-1). However, when the carbonyl and amine moieties are combined in the resonating amide group of, e.g., formamide, with strong contributions of covalent (I) and ionic (II) resonance structures,... 

Three alternative mechanisms have been mentioned in the literature. Reduction of C02 to CO followed by carbonylation of dimethylamine was ruled out by Haynes et al. [3] for RhCl(PPh3)3 because no carbonyl complexes were detected. Aminolysis of formate complexes (Eq. (14)) was proposed by Kudo et al. [69], but strong evidence has not been obtained. Finally, C02 is known to react with the amine to produce a carbamate salt (Eq. (15)), and it is possible that the pathway to the formamide is by hydrogenation of the carbamate rather than of the C02. 

Functional groups attached to the carbonyl group naturally alter the shape of the energy surface to some extent. Rode and Preuss 212> studied the interaction of Li+ with formamide. As a result of the amine substituent the mobility... 

In a dehydration reaction (Scheme 12.4), the IR band of the formamide carbonyl group at 1684 cm in (7) decreased and eventually converted to the isonitrile band at 2150 cm in (8) (Fig. 12.8). In a separate example (Scheme 12.5), the conversion of the IR band from the carbonate carbonyl group in (9) to the IR band of the carbamide carbonyl group in (10) can be monitored to assure the reaction completion (Fig. 12.9). Based on FTIR analysis, the reaction time course can be analyzed by integrating peak areas of the IR bands from the starting resin and the product. From the point of view of kinetics, the side reaction product formation can be excluded if the pseudo first order rates of the starting material consumption and the product formation are identical. 

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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