Transamidation

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Transamidation is a chemical reaction in which an amide reacts with an amine to generate a new amide:

RC(O)NR'2 + HNR"2 → RC(O)NR"2 + HNR'2

The reaction is rarely employed, but it could prove relevant to peptide synthesis.[1]

Amides are characteristically inert, but the amino substituents can be exchanged in the presence of Lewis acid and organometallic catalysts.[2] Primary amides (RC(O)NH2) are more amenable to this reaction.

Ureas

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In contrast to the reluctance of amides as substrates, urea is more susceptible to this exchange process. Transamidation is practiced, sometimes even on an industrial scale, to prepare a variety of N-substituted ureas:[3]

(H2N)2CO + R2NH → (R2N)(H2N)CO + NH3
(R2N)(H2N)CO + R2NH → (R2N)2CO + NH3

Methylurea, precursor to theobromine, is produced from methylamine and urea. Phenylurea is produced similarly but from anilinium chloride:[4]

(H2N)2CO + [C6H5NH3]Cl → (C6H5(H)N)(H2N)CO + NH4Cl

Hydrazine derivatives of urea are often produced by transamidation-like reactions. These products include carbohydrazide, semicarbazide, and biurea.

Further reading

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References

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