Amines, Amine Derivatives, Congeners, and Acidic Additives

Amines, Amine Derivatives, Congeners, and Acidic Additives 

Ammonia and numerous primary and secondary amines have been subjected to HAM. Since amines display different basicities depending on the number and nature of the AT-substituents, the transformation of the starting amine to the product amine alters the pH value during the reaction [68]. Especially in aqueous solutions this feature may become important, and control of the pH is necessary [68]. The addition of substoichiometric or stoichiometric amounts of acids or the submission of corresponding ammonium salts (e.g., sulfates) can enhance the formation of the product amines as well as the desired regioselectivity [29, 69, 70]. Thus, the addition of a substoichiometric amount of HBF increased significantly the yield of the amine [48]. At high catalyst concentrations, also the addition of acetic acid could be of value, but this additive was less efficient than HBF [51]. Formic acid or sulfuric acid decelerated the transformation. 

Instead of arylamines, also nitro compounds as masked anilines have been scrutinized as potential substrates for hydroamidomethylation [73]. Under the same reaction conditions as with amines as substrates ([RhCl(COD)] 2, phosphine, CO/H2 = 7 14 bar), they have been cleanly reduced to the corresponding amines prior to HAM without affecting the final results. 

DMF has been suggested as a surrogate for dimethylamine taking into account that DMF can be decomposed into dimethylamine and CO in the presence of platinum metals [41]. 

Good -regioselectivities in HAM can be achieved in nonpolar solvents such as THF. Dichloroethane or DMF inhibits the reaction or may lead to polymerization. Seller and later Vogt observed that in THF, toluene, and methyl-ferf-butyl ether the hydrogenation of the in situ formed enamine is the rate-determining step of the whole reaction sequence [37, 38]. Sy using a mixture of nonpolar aromatic solvents and methanol, the rate of this reaction step could be increased. Noteworthy, acidic alcohols, such as phenol or trifluoroethanol, support the undesired aldol condensation [58]. Acetals, which may derive from the reaction of the intermediate aldehyde with methanol, have never been observed in HAM [75]. Moreover, such acetals do not react under these conditions. A mixture of methanol and a fluorinated alcohol (trifluoroethanol, hexafluoroisopropyl alcohol) inhibits 

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