Transamidation

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

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

• 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

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.