Ammonia, reactions with carbodiimides

Reaction of the carbodiimide derived from the aza-Wittig reaction with ammonia generates the gaunidine, which under basic conditions, attacks the nitrile moiety in a nucleophilic manner. 

Reactions with Ammonia, Amines, Amine Derivatives and Azides. Ammonia, primary and secondary amines react with carbodiimides to give guanidine derivatives. For example, firom primary amines the guanidine derivative 559 is obtained. 

Phenyl isocyanate was used differently by Taylor and Patel (91JHC1857), who synthesized 2-anilinothieno[2,3-d]pyrimidine 76 by the sequence of reactions 48 — 74 — 75 — 76. This synthesis involves (i) adding the o-aminocarbonitrile 48 (R2 = R3 = H) to a mixture of triphenylphosphine and bromine at 0°C to give iminophosphorane 74, (ii) an aza-Wittig reaction on the iminophosphorane with phenyl isocyanate to yield carbodiimide 75, and (iii) cyclization of the latter with ammonia. 

The Lessen reaction of peptide carboxylic acids has teen investigated in order to determine the carboxy terminal amino acid residue of peptides." The procedure first involves the formation of 0-pivaloylhydroxamic acids (187) by condensation of peptide carboxylic acids (184) with 0-pivaloylhy-droxylamine (185) using a water soluble carbodimide, l-ethyl-3-(3-dimethylaminopropyl)carbodiimide (186). The Lossen rearrangement of (187) occurs at pH 8.5 and 50 C to give a mixture of isocyanates (188) and their reaction products, which, on acidic hydrolysis, afford the aldehydes (189), ammonia and amino acids, as shown in Scheme 30." Identification of aldehydes determines the C-terminal amino acids of the original peptides. 

Trimerization of nitriles, isocyanates, isothiocyanates, imidates, and carbodiimides all lead to symmetrical 2,4,6-trisubstituted 1,3,5-triazines (see Section 6.12.9.5). The use of lanthanide trifluoromethanesulfonate and ammonia as cocatalysts is claimed as a big improvement. The trisaminal of 2,4,6-triformyl-l,3,5-triazine is also useful for further derivatization to unusual structures (see Section 6.12.7.1). Treatment of a 1 1 pyridine/conc. ammonia solution of an aromatic aldehyde with excess Fremy s salt is another development. Separation of the amide coproduct was claimed to be easy. The synthesis fails with aliphatic aldehydes (see Section 6.12.9.5.4). Aminolysis of 2,4,6-triaryl-1,3,5-oxadiazinium salts gives symmetrical 1,3,5-triazines but the reactions are limited in that electron-withdrawing groups in the aromatic rings lead to instability and difficulty in separation of products (see Section 6.12.10.4). 

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