Transamidation and related reactions

The NH2 group of carboxamides, particularly if unsubstituted, can be exchanged for residues from other amines, hydrazines, etc. Thus A-formyl-amines are often obtained quite smoothly by heating the amine with form-amide in a vacuum at as low as 70°.1144 Higher carboxamides react analogously at temperatures of 150-200°.1145 Transamidation occurs more readily if the carboxamide is melted with the amine hydrochloride 692,1146 and diacyl-amides, including cyclic dicarboximides such as succinimide and phthalimide are more reactive than simple carboxamides.1147 

Transamidation has often been used also as a convenient method of converting urea into N- or N,N -substituted ureas and hydrazides. The amine and urea are melted together1150 or heated together for some time in glacial acetic acid.1151 The reaction temperature and the proportions of the reactants determine whether the monosubstituted or symmetrically disubstituted urea is produced, but mixtures of the two are frequently formed. Amide hydrochlorides can also be used, being boiled with the urea in aqueous solution a well-known example is the conversion of urea into methylurea by 3 hours boiling with methylamine hydrochloride, which is a step in the preparation of 1-methyl-l-nitrosourea.1152 

Conversion of urea into phenyl- and 1,3-diphenyl-urea by aqueous aniline hydrochloride solution is described in Organic Syntheses1153. 

Very good yields are almost always obtained by starting with nitro-urea.1154-1157 In these cases the N02NH group is exchanged almost exclusively, so that this method is especially suitable for preparation of monosubstituted ureas and is in many cases superior even to the route from isocyanates.1155 

Ethylurea 1158 Ethylamine (44 g) is dissolved in a mixture of water (200 ml) and ice (100 g) in a 2-1 flask, nitrourea (104 g) is added, and the whole is heated on a water-bath until lively evolution of nitrogen begins. The reaction is moderated by ice-cooling, but the mixture is eventually heated to the boiling point to complete the transformation. After evaporation in a vacuum ethylurea crystallizes the mixture is cooled to 0° and the product (55 g m.p. 90-92°) is filtered off and washed with ice-water. A second crop (15.7 g m.p. 89-92°) is obtained by evaporating the mother-liquor and washings and, when dissolved in anhydrous ethanol and precipitated with ether, the residue affords a third crop (7-8 g). The total yield is 90 % (78 g). 

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