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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  • T. A. Dineen; M. A. Zajac; A. G. Myers (2006). "Efficient Transamidation of Primary Carboxamides by in situ Activation with N,N-Dialkylformamide Dimethyl Acetals". J. Am. Chem. Soc. 128 (50): 16406–16409. Bibcode:2006JAChS.12816406D. doi:10.1021/ja066728i. PMID 17165798.

References

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  1. ^ Pattabiraman, Vijaya R.; Bode, Jeffrey W. (2011). "Rethinking amide bond synthesis". Nature. 480 (7378): 471–479. Bibcode:2011Natur.480..471P. doi:10.1038/nature10702. PMID 22193101.
  2. ^ Emma L. Baker; Michael M. Yamano; Yujing Zhou; Sarah M. Anthony; Neil K. Garg (2016). "A two-step approach to achieve secondary amide transamidation enabled by nickel catalysis". Nature Communications. 7: 11554. Bibcode:2016NatCo...711554B. doi:10.1038/ncomms11554. PMC 4876455. PMID 27199089.
  3. ^ C. Nitschke; G. Scherr (2012). "Urea Derivatives". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.o27_o04. ISBN 978-3-527-30673-2.
  4. ^ "Arylureas II. Urea Method p-Ethoxyphenylurea". Org. Synth. 31: 11. 1951. doi:10.15227/orgsyn.031.0011.