Tetrahedron Letters
Microwave assisted synthesis of nitro phenols from the reaction of
phenols with urea nitrate under acid-free conditions
Sanny Verma a, Sangeeta Pandita b, Suman L. Jain a,
⇑
a Chemical Sciences Division, CSIR-Indian Institute of Petroleum, Mohkampur, Dehradun 248005, India
b Department of Chemistry, Zakir Husain Delhi College, University of Delhi, Delhi 110002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Urea nitrate was found to be an inexpensive, acid-free, and safe nitrating agent that provides mononitra-
tion of phenols and substituted phenols in excellent yields with exclusive ortho-selectivity under micro-
wave irradiation. Microwave assisted reactions reduced the reaction times substantially and enhanced
the product yields from good to excellent within shorter reaction times.
Received 17 October 2013
Revised 28 December 2013
Accepted 30 December 2013
Available online 8 January 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Microwave
Nitration
Phenol
Urea nitrate
Regioselectivity
Urea nitrate is an inexpensive, stable, and biodegradable organ-
ic compound which is mostly known as a nitrogenous fertilizer.1
Urea nitrate (UN) can easily be obtained from the reaction of urea
and nitric acid under cooling conditions.2 Prior literature reports
reveal the use of UN as a nitration agent for the nitration of aro-
matic compounds in the presence of an acid. In this context,
Majumdar and Kudav3 reported urea nitrate in sulfuric acid for
the dinitration of anisole and diphenyl ether and the mono (meta)
nitration of acetophenone and methyl benzoate. Nabar and Kudav4
used urea nitrate in polyphosphoric acid for the nitration of bro-
mobenzene, anisole, and acetophenone. In a later study, they de-
scribed the regioselective para-nitration of anilines using urea
nitrate in sulfuric acid.5 Almog et al.6 reported the use of urea ni-
trate as a nitrating agent for the regioselective nitration of aro-
matic compounds in the presence of sulfuric acid. However, to
the best of our knowledge there is no literature report on the use
of urea nitrate for the nitration of aromatic compounds under
acid-free conditions.
compounds, oxidized products due to the over-oxidation of the
substrate.9 In addition, the acid mixture (HNO3 and H2SO4) that
is used in direct methods of nitration of organic compounds has
proved to be hazardous, highly toxic, and corrosive.10 Furthermore,
several other nitrating agents or methods avoiding harsh reaction
conditions have been explored using peroxy nitrite,11 metal
nitrates,12 nitrogen oxides,13 and ionic liquid mediated14 or micro-
wave-assisted nitrations.15 The literature on aromatic nitration re-
veals a persistent quest for achieving higher regioselectivity in
orientations. There is, thus, a need to develop a mild, economical,
and environmentally benign method for the nitration of aromatic
compounds.
In the present Letter we report for the first time a simple, effi-
cient, and highly regioselective procedure for the nitration of phe-
nols to o-nitrophenols in moderate to high yields by using urea
nitrate as the nitrating agent under microwave irradiation condi-
tions (Scheme 1).
UN was prepared from urea and nitric acid according to the lit-
erature procedure.2 The FTIR of the as synthesized UN was found to
be consistent with the literature.16 The FTIR spectra of UN (Fig. 1)
Nitration of aromatic compounds is an important industrial
process which has widely been used in the manufacture of a wide
range of chemicals such as dyes, pharmaceuticals, agrochemicals,
and explosives.7 Conventional methods for the nitration of aro-
matic compounds utilize a mixture of nitric and sulfuric acids or
nitronium tetrafluoroborate.8 However these methods are associ-
ated with many drawbacks, such as, formation of undesired dinitro
OH
OH
UN (1 eq.)
NO2
R
R
MW, 80 o
C
CH3CN:H2O
(95:5; 5 ml)
⇑
Corresponding author. Tel.: +91 135 2525788 (O); fax: +91 135 2660202.
Scheme 1. Microwave assisted nitration of phenols using urea nitrate.
0040-4039/$ - see front matter Ó 2014 Elsevier Ltd. All rights reserved.