Received: May 7, 2014 | Accepted: May 18, 2014 | Web Released: September 5, 2014
CL-140454
Reductive Acylation of Nitroarenes to Anilides by Sodium Sulfite in Carboxylic Acids
Mohammad Ghaffarzadeh* and Pegah Akhavan
Chemistry and Chemical Engineering Research Center of Iran, P. O. Box 14335-186, Tehran, Iran
(E-mail: mghaffarzadeh@ccerci.ac.ir)
A facile and efficient reductive acylation of aromatic nitro
compounds to corresponding anilides using a sodium sulfite-
carboxylic acid system for the first time has been reported.
The sodium sulfite reagent provides the colorless reductant in
combination with stoichiometric amounts of carboxylic acid and
enables the formation of anilides from nitroarenes without any
additives in good to excellent yields with high purities and
simple work-up. Furthermore, this protocol provides a novel and
complementary access to some industrially important chemicals
in kilogram scale under mild conditions.
investigation of reductive acylation reaction,16,17 herein, we
report an economical and highly efficient protocol for the
synthesis of anilide derivatives from aromatic nitro compounds
under mild operational conditions. In this context, we disclosed
the one-pot cascade reaction of aromatic nitro compounds with
sodium sulfite in carboxylic acid medium leading to direct
amidation, in which sodium sulfite plays a triple role acting as
the dehydrating agent and causing the subsequent reduction
and amide formation reactions. Furthermore, the sulfite salts are
inherently color reducing agents, especially for aniline and
amine impurities, the products obtained by this method were free
from colored impurities. In addition, another important result is
kinetic aspects of this reaction. In preparation of anilides from
nitroarenes by iron powder in carboxylic acid, the reduction
step is faster than acylation, so the formation and detection of
anilines every time in reaction medium are possible, while in our
method the aniline intermediate is not detectable at any time.
The formation of anilides from nitroarenes passes from aniline
intermediate certainly, we concluded that the reduction step
was slower than acylation, hence there did not accumulate any
aniline compounds during the reaction progress. It is important
to note that with aliphatic nitro compounds, we could not
obtain the desired amides and also with solid carboxylic acids
(especially with benzoic acids) even in the molten state or in the
suitable solvents (dimethyl sulfoxide and dimethylformamide)
we obtained very poor yields of benzanilides.
Initially, the model reaction of nitrobenzene with sodium
sulfite was examined under acidic conditions (Scheme 1). Based
on a stoichiometric point of view of the reductive acylation
reactions, we performed this reaction with molar ratio of 1:3:7 of
nitrobenzene:sodium sulfite:acetic acid, respectively in order to
optimize temperature and reaction times. The effects of reaction
temperature on the yields of anilides at different time intervals
were examined. No reactions occurred lower than 50 °C over the
course of 72 h. After careful examination, it was found that the
boiling point of the acetic acid was the best and optimum
temperature of the reaction and 40% of the desired product was
obtained for overnight heating. Although at higher temperatures
in pressurized vessel the yields were increased, to avoid of the
harsh reaction condition it was rejected. Encouraged by this
result we tried to optimize the reaction conditions by varying the
amount of sodium sulfite and acetic acid and the results are
summarized in Tables 1 and 2. The best result was obtained in
the molar ratio 1:3.5:8 of nitroarenes:sodium sulfite:carboxylic
acids respectively in the boiling acetic acid for 16 h.
Nowadays, diminishing the number of reaction steps to
facilitate the formation of specific products without any further
process is the ultimate goal of chemists.1 In this context,
designing of chemical processes with operational control with-
out further purification is the main challenge of chemical
engineers and applied chemists, and these factors make its
commercialization very easy and economic.
Anilide derivatives are key building blocks and intermedi-
ates in chemical industries.2 Consequently, a number of syn-
thetic methods for construction of this important unit have been
established in the literature. The standard procedure for the
formation of anilide derivatives is the amidation of carboxylic
acid derivatives with aniline at high temperature3 or in the
presence of catalysts and promoters.4 The reaction proceeds
in good to excellent yields for simple anilide derivatives, but
suffers from several disadvantages such as expensive reagents
and purification of the target.
Within the past decade, alternative strategies have been
developed for the synthesis of anilides from cheap and available
nitroarenes to overcome some of the above-mentioned draw-
backs. These methods include use of carbon monoxide in the
presence of group IV transition-metal complexes,5 molybdenum
hexacarbonyl,6 carbon monoxide, catalytic amount of platinum
complex, and a Lewis acid,7 methyl formate and triruthenium
dodecacarbonyl,8 indium in carboxylic acid and anhydride,9 car-
boxylic ester in the presence of samarium diiodide,10 samarium
in carboxylic acid and anhydride,11 sodium iodide and iron(III)
on montmorillonite,12 iodine and red phosphorus,13 and hydro-
genation on platinum nanowire.14 Expensive reagents and harsh
reaction conditions are drawbacks of these methods. Iron
powder in carboxylic acid is another example of direct reductive
acylation methods.15 Tedious work-up and formation of tar and
viscose material are disadvantages of this method. To overcome
to this problem, the reaction mixture is treated with inorganic
acid solutions (aqueous HCl). Under these conditions, some
amount of the product is hydrolyzed to corresponding anilines.
Furthermore, the work-up of the reaction is time consuming.
With the aim to develop a practical approach for the
synthesis of anilide derivatives without purification or isolation
of reaction intermediates and in the course of our continuing
O
NO2
HN
O
Na2SO3
+
OH
Scheme 1. Reductive acylation of aromatic nitro compounds.
© 2014 The Chemical Society of Japan | 1417