Formamides from amines

Typical is the formation of formamides from amines. The authors are aware of no work in this area since the last review. 

Scheme 1 Production of formamides from amines and CO2 in SCCO2-IL.

Cuprous chloride Formamides from amines with carbon monoxide... 

Cuprous chloride CuCl Formamides from amines NH -> NCHO with carbon monoxide s. 26, 282 with hydrogen selenide-triethylamine instead of CuCl as catalyst cf. K. Kondo, N. Sonoda, and H. Sakurai, Chem. Commun. 7975, 853 ... 

Hydrogen chloride Formamides from amines s. 5,274 suppl. 32... 

Preparation of formamides from COz and a non-tertiary amine by homogeneous hydrogenation has been well studied and is extremely efficient (Eq. (12)). Essentially complete conversions and complete selectivity can be obtained (Table 17.3). This process seems more likely to be industrialized than the syntheses of formic acid or formate esters by C02 hydrogenation. The selectivity is excellent, in contrast to the case for alkyl formates, because the amine base which would stabilize the formic acid is used up in the synthesis of the formamide consequently little or no formic acid contaminates the product. The only byproducts that are likely to crop up in industrial application are the methylamines by overreduction of the formamide. This has been observed [96], but not with such high conversion that it could constitute a synthetic route to methylamines. 

Acid Amides can be produced by acylating ammonia with esters, acid anhydrides, or the acids themselves (above 100 °C) an important product is formamide from methyl formate. Alternatively acid amides can be synthesized by reacting acid halides with ammonia. Catalytic hydrogenation converts the acid amides to primary amines. Ammonia and aldehydes or ketones are the basis for different stable products. With formaldehyde hexamethylenetetramine (urotropine) is obtained with acetaldehyde, ammono acetaldehyde with benzaldehyde, hydrobenzamide with ethylene and propylene oxides, aqueous ammonia reacts to form ethanol- or propanolamine. 

Three types of product can be obtained from the reaction of amines with carbon monoxide, depending on the catalyst. (1) Both primary and secondary amines react with CO in the presence of various catalysts [e.g., Cu(CN)2, Me3N-H2Se, rhodium or ruthenium complexes] to give V-substituted and V,A-disubstituted formamides, respectively. Primary aromatic amines react with ammonium formate to give the formamide. Tertiary amines react with CO and a palladium catalyst to give an amide. (2) Symmetrically substituted ureas can be prepared by treatment of a primary amine (or ammonia) with CO " in the presence of selenium or... 

Because RuCl2(PMe3)4 is soluble in supercritical carbon dioxide, it catalyzes the formation of formate or formamide from carbon dioxide, hydrogen, and alcohol or amine under supercritical conditions with a maximum 370 000 ton- These reactions may lead to a breakthrough in CO activation [140]. 

S. (S)-N,II-Dimethyl-S -(l-tez t-butoxy-3-methyl-2-butyl)formamldine (2). In a 500-mL, round-bottomed flask 26 g (140 mmol) of the formamide from Part A is dissolved in 100 ml of ethanol and 200 mL of a 50% aqueous potassium hydroxide solution is added. The mixture is heated at reflux overnight upon cooling, the reaction separates into colorless aqueous and organic layers. The two layers are extracted three times with 100 mL of ether and the combined organic layers are washed with 100 mL of brine. After the solution is dried over anhydrous potassium carbonate and filtered, the ether and ethanol are carefully removed under aspirator vacuum at ambient temperature. The crude amine is treated with 25 g (210 mmol) of N,N-dimethylformamide dimethyl acetal (Note 8) and the reaction mixture is heated under argon at 40°C for 1 hr. The solution is concentrated under reduced pressure and the crude product is distilled bulb-to-bulb (0.05 mm, 55-65°C) to give 25.7-27 g (86-91.5%) of (S)-N,N-dimethyl-N -(l-tert-butoxy-3-methyl-2-butyl)formamidine (2) as a colorless liquid (Note 9). 

While entry 5 (CYPHOS IL 163) may be considered a borderline ionic, to date, of all the phosphonium-based ILs, it has received the most attention. Garayt et al. have patented a process to fluorinate aromatics [20]. Previously, Knifton, lin et al. have published and patented an enormous number of petrochemical applications using entry 5 as the solvent-alcohols from syngas [21-29], synthesis of acetaldehyde and acetic acid from syngas [40-45], synthesis of esters from syngas [46, 47], and synthesis of formamides and amines [48, 49],... 

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. 

In a more convenient and more environmentally friendly protocol, unsymmetrical N,N -disubstituted ureas, including stericaDy hindered ones, can be synthesized (76-93% yield) from N-aryl-substituted formamides and amines in the presence of catalytic amounts of Ru(PPh3)3 (substrate/catalyst ratio 20 1) [736]. A catalytic cycle involving the formation of an isocyanatedihydride intermediate is postulated. 

For M = Ru, formamides and amines were the principal products. Substitution of Fe3(CO)i2 for Ru3(CO)i2 results in the formation of carbamate esters (ArNHCOOMe) as the major products, with ureas as the main by-products. Without the metal carbonyl, nitroarenes are recovered imchanged from the reaction mixture. An imido-alcoxycarbonyl complex was suggested as an intermediate in the reaction and the difference between iron and ruthenium was proposed to be due to the different facility of this intermediate to undergo protonation and reductive elimination to give carbamate, or insertion of CO into the M-N bond, followed by hydrogenation, affording formamide (Scheme 13) ... 

Table 3.5. Preparation of secondary formamides from secondary amines...

Reactions of carbenes other than cyclopropanation can also be performed, and recent examples include the ring expansion of five-ring heterocycles, such as the indoles (18), to their six-membered counterparts (19), and the production of formamides from secondary amines (Scheme 7), both with dichlorocarbene. The latter method is of interest because of its relation to the catalysis of dichlorocarbene generation by tertiary amines in two-phase systems. Recent work indicates that such catalysis is possible because the carbene, after generation at the phase boundary, is transferred into the organic phase (to undergo reaction) in the form of the N-ylid adduct (20). 

Formamides from tert. amines—Oxidative opening of N-heterocycles s. 13, 228 s. a. Soc. 1960, 3559... 

Haynes, R Slaugh, L.H. Kohnle, J.F. Formamides from Carbon Dioxide, Amines and Hydrogen in the Presence of Metal Complexes.Tefra/jerfron Lett. 1970,11, 365-368. 

Chromium trioxide I pyridine Formamides from tert. amines... 

The desired pyridylamine was obtained in 69 % overall yield by monomethylation of 2-(aminomethyl)pyridine following a literature procedure (Scheme 4.14). First amine 4.48 was converted into formamide 4.49, through reaction with the in situ prepared mixed anhydride of acetic acid and formic acid. Reduction of 4.49 with borane dimethyl sulfide complex produced diamine 4.50. This compound could be used successfully in the Mannich reaction with 4.39, affording crude 4.51 in 92 % yield (Scheme 4.15). Analogous to 4.44, 4.51 also coordinates to copper(II) in water, as indicated by a shift of the UV-absorption maximum from 296 nm to 308 nm. 

Other fairly recent commercial products, poly(vinyl amine) and poly(vinyl amine vinyl alcohol), have addressed the need for primary amines and their selective reactivity. Prior efforts to synthesize poly(vinyl amine) have been limited because of the difficulty hydrolyzing the intermediate polymers. The current product is prepared from /V-ethenylformamide (20) formed from the reaction of acetaldehyde and formamide. The vinyl amide is polymerized with a free-radical initiator, then hydrolyzed (eq. 7). 

Pyrido[4,3-rf]pyrimidin-4(3/7)-oiie (138) was prepared from either ethyl 4-aminonicotinate or from 4-aminomcotinamide by fusion with formamide. A parallel to the pyrido[3,2-d]pyrimidines (cf. Section II,B, la) was demonstrated in the conversion of 2-methyl-pyrido[4,3-d][l,3]oxa7in-4-ones (139, Ri = Me) into the corresponding pyrido[4,3-d]pyrimidin-4(377)-ones (142) on treatment with a number of amines.There were certain limitations to the method in this series, however, and the intermediate diamides (140) were more conveniently prepared from the appropriate 4-amidonicotinate (141) and. .Ri... 

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