Hydrogen acetamide

Peroxide-Ketazine Process. Elf Atochem in France operates a process patented by Produits Chimiques Ugine Kuhhnaim (PCUK). Hydrogen peroxide (qv), rather than chlorine or hypochlorite, is used to oxidize ammonia. The reaction is carried out in the presence of methyl ethyl ketone (MEK) at atmospheric pressure and 50°C. The ratio of H202 MEK NH2 used is 1 2 4. Hydrogen peroxide is activated by acetamide and disodium hydrogen phosphate (117). Eigure 6 is a simplified flow sheet of this process. The overall reaction results in the formation of methyl ethyl ketazine [5921-54-0] (39) and water ... 

The mechanism of this reaction involves an activation of the ammonia and hydrogen peroxide because these compounds do not themselves react (118—121). It appears that acetamide functions as an oxygen transfer agent, possibly as the iminoperacetic acid (41) which then oxidizes the transient Schiff base formed between MEK and ammonia (40) to give the oxaziridine (42), with regeneration of acetamide ... 

With hydrogen sulfide at 500—600°C, monochlorotoluenes form the corresponding thiophenol derivatives (30). In the presence of palladium catalysts and carbon monoxide, monochlorotoluenes undergo carbonylation at 150—300°C and 0.1—20 MPa (1—200 atm) to give carboxyHc acids (31). Oxidative coupling of -chlorotoluene to form 4,4 -dimethylbiphenyl can be achieved in the presence of an organonickel catalyst, generated in situ, and zinc in dipolar aprotic solvents such as dimethyl acetamide (32,33). An example is shown in equation 4. 

Catalytic hydrogenation of the nitrile function of cyanohydrins can give amines. As in the case of ordinary nitriles, catalytic reduction of cyanohydrins can yield a mixture of primary, secondary, and tertiary amines. Addition of acid or acetic anhydride to the reaction medium minimizes formation of secondary or tertiary amines through formation of the amine salt or acetamide derivative of the primary amine. 

Kostic el al. discovered that Pd11 complexes, when attached to tryptophan residues, can rapidly cleave peptides in acetone solutions to which a stoichiometric amount of water is added, for hydrolysis.436 The indole tautomer in which a hydrogen has moved from the nitrogen to C(3) is named indolenine. Its palladium(II) complexes that are coordinated via the nitrogen atom have been characterized by X-ray crystallography and spectroscopic methods.451 Binuclear dimeric complexes between palladium(II) and indole-3-acetate involve cyclopalladation.452 Bidentate coordination to palladium(II) through the N(l) and the C(2) atoms occurs in binuclear complexes.453 Reactions of palladium(II) complexes with indole-3-acetamide and its derivatives produced new complexes of unusual structure. Various NMR, UV, IR, and mass spectral analyses have revealed bidentate coordination via the indole carbon C(3) and the amide oxygen.437... 

Cieplak, P., Caldwell, J. W., Kollman, P. A., Molecular mechanical models for organic and biological systems going beyond the atom centered two body additive approximation aqueous solution free energies of methanol and IV-methyl acetamide, nucleic acid base, and amide hydrogen bonding and chloroform/water partition coefficients of the nucleic acid bases, J. Comput. Chem. 2001, 22, 1048-1057... 

Borohydride reduction of NiCl2 in dimethylformamide or dimethyl-acetamide leads to very active catalysts, thought to be homogeneous, for hydrogenation of monoolefins, unsaturated fats, cyclic dienes to monoenes, and saturated aldehydes and ketones (165, 538, 539). Cobaltous chloride systems have also been used (540). 

Figure 5.64 Hydrogen-bonded and fully protonated acetamide complexes, showing the optimized pseudo-civ conformer for each species.

Alkyl enamides, such as N-(1 -tert-bulyl-viriyl)-acelamide 88 and N-(l-adaman-tyl-vinyl)-acetamide 89, can also be hydrogenated in high enantioselectivity (>99% ee) and activity (TON 5000 TOF >625 h ) with Rh-Me-DuPhos [19]. Remarkably, these bulky alkyl enamides are reduced with the opposite sense of induction, a phenomenon also observed when the bisphospholane Di Square P 63 was applied [87 b]. A computational modeling study by Landis and Feldgus suggested that the reduction of a-alkyl and a-arylenamides involves different coordination pathways [93, 158]. 

Two of the worst outliers were N,N-dimethylformamide and N,N-dimethyl-acetamide. For both of these, solubility in water was greatly underestimated. This may illustrate a situation in which conformation does assume importance. In the gas phase structures used to compute the surface properties, the nitrogens are planar. There is reason to believe, however, that interaction with water molecules will cause the nitrogens to become pyramidal,48 since that produces more localized lone pairs that better attract water hydrogens. Thus, analysis involving planar nitrogens would not indicate the true strength of the interaction. 

Aside from the N-compounds listed above, a number of low-molecular-weight N compounds were also identified. [17] These included ammonia, hydrogen cyanide, dinitrogen (N2), nitric oxide (NO), methylamine, nitrous oxide (N20), formamide, acetamide, and N, N-dimethylmethanamine. 

Scheme 17 y-Acetamidation of ketones via a ketone radical cation and a [l,5]-hydrogen shift. 

With ketones, a remote regioselective acetamidation is found. This result is mechanistically in accordance with the oxidation of the oxygen atom of the carbonyl group to a radical cation that abstracts a hydrogen from a remote CH bond. The generated radical is then oxidized to a cation, that reacts with acetonitrile to get the acetamide (Fig. 3) [15],... 

Scheme 6.12 Asymmetric hydrogenation of cinnamic acid acetamidates.

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