2-Methoxyphenyl isocyanate: a
chemoselective multitasking
reagent for an amine protection/
deprotection sequence
Meenakshi R L
I M.Sc. Chemistry
School of Chemical and Biotechnology
SASTRA University
Authors and Affiliation
▪ Anand Babu Velappan ▪ a Department of Chemistry,
a SCBT, SASTRA Deemed
University, Tamilnadu
▪ Subhashini Kogatam a 613401, India. E-mail:
joydebnath@scbt.sastra.ed
u
▪ Dhrubajyoti Datta b
▪ b Department of Chemistry,
▪ Rakshantha Srithar a Indian Institute of Science
Education and Research
▪ Gunasekaran Pune, Maharashtra 411008,
Nanjappan c India
▪ Joy Debnath *a ▪ c CeNTAB, SCBT, SASTRA
Deemed University,
Tamilnadu 613401, India
Article History
▪ Publication: Royal Society of Chemistry
▪ Journal: Organic Chemistry Frontiers
▪ Volume: 6, Page: 2360-2364
▪ Received: 23 February 2019
Accepted on: 16 April 2019
▪ DOI: 10.1039/c9qo00293frsc.li/frontiers-organic
▪ Citation: Org. Chem. Front., 2019, 6, 2360
▪ Impact factor: 4.6
Abstract
• Organic amines, in general, are protected through
carbamate bond mediated capping.
• The chemically stable urea linkage is suitably
employed for protection/ deprotection of amino
groups.
Abstract
• The stability of the urea linkage under acidic,
alkaline and aqueous conditions is an additional
advantage for such a protecting group.
• The chemoselective nature of 2-methoxyphenyl
isocyanate enables its use as a new class of
protecting groups which can regenerate free
amines after a convenient deprotection step.
Formation of Urea Bond
Demethylation
Demethylation
Regeneration
Regeneration
Stability
▪ The comparative inherent stability of the urea linkage
over the conventional linkages (carbonate, carbamate,
ester, amide, ether, silyl and alkyl linkages) at three
different pH values (0.5, 7.5 and 13) at room temperature
was assessed.
Stability
Chemoselectivity
▪ In all these three cases
we observe the formation
of only urea bonds which
is presumably because of
the higher nucleophilicity
of the amine.
Conclusion
▪ This protecting group can be selectively used for aromatic
amines (except heteroaromatics), and primary and
secondary aliphatic amines even in the presence of
hydroxyl, carboxylic and thiol functionalities.
▪ All three steps involved in the protection/deprotection
sequences are high yielding and pro- ducts can easily be
purified (>90% purity) by simple filtration or workup.
▪ The robust nature of this protecting group regarding its
stability (95–100%) under acidic, neutral and alkaline
conditions is attributed to the urea bond rather than the
conventional protecting groups.
Notes and References
1 M. Schelhaas and H. Waldmann, Angew. Chem., Int. Ed.,
1996, 35, 2056–2083.
2 A. Isidro-Llobet, M. Alvarez and F. Albericio, Chem. Rev.,
2009, 109, 2455–2504.
3 (a) P. Lloyd-Williams, F. Albericio and E. Giralt, Chemical
Approaches to the Synthesis of Peptides and Proteins, CRC
Press, Boca Raton, FL, 1997; (b) A. F. Abdel-Magid, K. G.
Carson, B. D. Harris, C. A. Maryanoff and R. D. Shah, J. Org.
Chem., 1996, 61, 3849–3862; (c) N. Yamazaki and C.
Kibayashi, J. Am. Chem. Soc., 1989, 111, 1396–1408.
Thank you
