An Eco friendly and Simple Route to Synthesis of Acetanilide from Aniline

International Journal of Trend in Scientific Research and Development (IJTSRD)
Volume 6 Issue 2, January-February 2022 Available Online: www.ijtsrd.com e-ISSN: 2456 – 6470
@ IJTSRD | Unique Paper ID – IJTSRD49128 | Volume – 6 | Issue – 2 | Jan-Feb 2022 Page 131
An Eco-friendly and Simple Route to
Synthesis of Acetanilide from Aniline
Sharda Pasricha
Department of Chemistry, Sri Venkateswara College, University of Delhi, New Delhi, India
ABSTRACT
Magnesium sulphate-glacial acetic acid system has been found to be
a benign, eco-friendly and inexpensive catalyst for the synthesis of
acetanilide from aniline. The method is simple, fast, green, avoids
use of toxic acetic anhydride and involves catalysed reaction in line
with the green chemistry principles. The method can be easily
adopted at the undergraduate level and may find applications in the
industrial scale acetylation of primary and secondary amines.
KEYWORDS: Lewis acid catalyst, Magnesium Sulphate heptahydrate,
Acetylation, Undergraduate-Chemistry
How to cite this paper: Sharda Pasricha
"An Eco-friendly and Simple Route to
Synthesis of Acetanilide from Aniline"
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INTRODUCTION
Acetylation of primary and secondary amines,
alcohols and phenols is a simple nucleophilic acyl
substitution reaction, which is conventionally carried
out in the presence of an acidic[1] or basic[2]catalyst
(Figure 1).The reaction finds extensive use in
chemistry labs at undergraduate, post-graduate,
research and industrial scale for protection of amino
and hydroxy groups in a multistep synthesis of
polyfunctional compounds[3, 4]. Conventionally, the
acetylation reactions involve the use of acetyl
chloride oracetic anhydride as acetylating agents.
However, these reagents are corrosive and
lachrymatory respectively, and therefore not ideal[5]
for the acetylation reactions. Although a number of
reagents and catalysts have been proposed for this
reaction, there is a need for simple and efficient
method, given the importance of this reaction.
Wang et al. [6] carried out acetylation of primary
amines using glacial acetic acid. Acetylation reactions
employing acetic acid for acetylation are slow since
the carbonyl carbon in acetic acid is deactivated by
the +R effect of the hydroxyl group [Figure 2].If,
however, the electrophilicity of the carbonyl carbon
in acetic acid can be increased, by using a suitable
catalyst, the reaction may prove to be highly
beneficial, since acetic acid is cheap and will involve
only water as by-product. Acetylation with acetic acid
is therefore environmentally benign and has 100%
atom economy. Recently, Brahmachari et al. [5]
reported use of zinc acetate/metal oxide and glacial
acetic acid for N-acetylation of amines. Use of zinc
salts is however discouraged due to potential toxicity
of zinc. Several other reports of acetylation of amines,
alcohols and phenols with acetic anhydride or Lewis-
acid/acetic acid is known in literature [7-17]. These
methods are however costly or use toxic solvents or
generate toxic waste or require catalysts which are not
readily available. Thus, a mild, cheap, simple and
efficient method acetylation of amines is need of the
hour.
Alkaline earth metals like magnesium (Mg) are
abundant in earth. Using catalysts derived from
abundant resources is vital for sustainable chemistry.
Efficient reactions with Mg(II) based Lewis acid
catalysts could offer a cheap yet practical synthetic
route for acetylation of useful molecular skeletons.
IJTSRD49128

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Several examples of use of Mg(II) salts as Lewis acid
catalyst are known till date[18-21].
Therefore, it is worthwhile to explore the use of
magnesium salts as a viable reagent/catalyst in
acetylation reaction of aniline. The current method
reports the use of magnesium sulphate heptahydrate-
glacial acetic acid for a solvent-free, mild, cheap and
benign route for the synthesis of acetanilide for
aniline[Figure 3].
Figure 1: General route to acetylation of amines and phenols
Figure 2: Delocalization of carbonyl carbon through +R effect
Figure 3: Acetylation of aniline with glacial acetic acid using magnesium sulphate heptahydrate as
catalyst
Experimental
Amixture of magnesium sulphate heptahydrate (0.2 mmol), glacial acetic acid (3.0 mL) and aniline (1.0 mL, 10
mmol) was taken in a dry round-bottomed flask. 1-2 pumice stones were added and the reaction mixture was
refluxed on a wire gauze for suitable time. Upon completion of the reaction (TLC), the contents were diluted
with hot water (5.0 mL) and filtered hot. The filtrate was allowed to cool to room temperature and then cooled in
an ice-water bath(100 mL).The sample was filtered at suction pump, washed well with minimum amount of ice-
cold water, dried and weighed. A part of the crude sample was recrystallized from hot water. Melting point of
the recrystallized sample was found to be 114o
C.
Result and Discussion
A reaction of aniline (1.0 mL) with glacial acetic acid (3.0 mL) was carried out in the presence of magnesium
sulphate heptahydrate (30 mg) as catalyst. It was found that the reaction proceeded to completion in 90 minutes
to afford 80% yield of the desired product. No further increase in yield was observed on increasing the reaction

time. The yield was however found to decrease on reducing the reaction time[Table 1]. It was therefore
concluded that 90 minutes is the optimum reaction time. Next, the reaction was carried out with varying amounts
of magnesium sulphate heptahydrate (30, 40, 50------ 100 mg). It was found that the best yields(92%) was
obtained when 50 mg of magnesium sulphate heptahydrate was used as catalyst[Table 2]. No further increase in
yield of the desired product was obtained on increasing the amount of catalyst. The reaction in absence of
catalyst gave poor yields of the desired product (60%). This strongly indicates the role of Lewis acid catalyst in
catalysing the reaction [Figure 4].
O
O MgL
H
ArNH2
N O
O MgL
H
H
H
Ar
Intramolecular
Proton
Transfer
N O
O MgL
H
H
Ar
H
-MgL
-H2O
ArNHCOCH3
L= SO4
2-
Figure 4: Mechanism of Lewis acid catalysed acetylation of aniline
Table 1: Effect of reaction time on the acetylation reaction
Conditions: Aniline (1.0 mL), glacial acetic acid (3.0 mL), 118o
C, magnesium sulphate heptahydrate(30 mg),
Table 2: Effect of varying amounts of magnesium sulphate heptahydrateon the acetylation reaction
Conditions: aniline (1.0 mL), glacial acetic acid (3.0 mL), 118o
C, 90 min.
Conclusion
Magnesium sulphate heptahydrate-glacial acetic acid
system has proved to be a mild, cheap, simple, and
benign catalyst for the synthesis of acetanilide from
aniline. Lewis acid catalysis nucleophilic acyl
substitution reaction by increasing the electrophilicity
of the carbonyl group. The method may serve as a
sustainable, inexpensive and green route for the
acetylation of the primary amines.
References
[1] J. Iqbal and R. R. Srivastava, J. Org. Chem.,
1992, 57, 2001; K. Ishihara, M. Kubota, H.
Kurihara and H. Yamamoto, J. Am.Chem. Soc.,
117, 4413, 1995; J. Izumi, I. Shiina and T.
Mukaiyama, Chem. Lett., 141, 1995; A. G. M.
Barret and D. C. Braddock,Chem. Commun.,
351, 1997; R. Ballini, G. Bosica, S. Carloni,L.
Ciaralli, R. Maggi and G. Sartori, Tetrahedron
Lett., 39,6049, 1998.
[2] T. Nishiguchi, K. Kawamine and T. Ohtsuka, J.
Org. Chem., 57, 312, 1992; Y. Kita, H. Maeda,
K. Omori, T. Okuno and Y. Tamura,J. Chem.
Soc., Perkin Trans. 1, 2999, 1993; J. Otera,
Chem. Rev., 93, 1449, 1993; A. Loupy, A. Petit,
M. Ramdani, C. Yuanaeft, M. Majdoub, B.
Labiad and D. Villemin, Can. J. Chem., 71,90,
1993,; G. W. Breton, J. Org. Chem., 62, 8952,
1997; G. Hofle, V. Steglich and H.
Vorbruggen, Angew. Chem., Int. Ed. Engl., 17,
569, 1978.
S. No. Duration of reaction (minutes) Yield Percentage (%)
1 45 50
2 60 70
3. 75 77
4 90 80
S. No. Amount of Magnesium sulphate heptahydrate(mg) Yield Percentage (%)
1 30 80
2 40 85
3. 50 92
3. 70 92
4 100 92

[3] T. W. Green and P. G. M. Wuts, Protective
Groups in Organic Synthesis, 3rd edn, Wiley,
New York, 1999.
[4] L. Pearson, W.J. Roush, Handbook of reagents
for organic synthesis: activating agents and
protecting groups, John Wiley and Sons,
Chichester, UK, pp 9–16, 1999.
[5] G. Brahmachari, S. Laskar and S. Sarkar,Metal
acetate/metal oxide in acetic acid: an efficient
reagent for the chemoselective N-acetylation of
amines under green conditions, Journal of
Chemical Research, Volume 34, issue: 5, 288-
295, 2010,
https://doi.org/10.3184/030823410X127463059
05926.
[6] X. Wang, Qian Yang, F. Liu, Q.,
Microwave‐Assisted Synthesis of Amide
under Solvent‐free Conditions, Synthetic
Communications, 38:7, 1028-1035, 2008.
DOI: 10.1080/00397910701860372.
[7] S. Gowda, K.M. Lokanatha Rai Manganese
(III) acetate as catalyst for the direct acetylation
of alcohols with acetic acid, Journal of
Molecular Catalysis A: Chemical 217, 27–29,
2004.
[8] S.Jamwal, R.Dharela, R. Gupta, J.Ahn, G. S.
Chauhan, Synthesis of cross linked lipase
aggregates and their use in the synthesis of
aspirin, Chemical Engineering Research and
Design, Volume 97,159-164, 2015.
https://doi.org/10.1016/j.cherd.2014.09.010.
[9] R. Biswas, A. Mukherjee, Introducing the
Concept of Green Synthesis in the
Undergraduate Laboratory: Two-Step Synthesis
of 4-Bromoacetanilide from Aniline, J. Chem.
Educ. 94, 9, 1391–1394, 2017.
https://doi.org/10.1021/acs.jchemed.6b00749
[10] K. V. V. K. Mohan, N. Narender, S. J.
Kulkarni, Zeolite catalyzed acylation of
alcohols and amines with acetic acid under
microwave irradiation, ,Green Chem., 8, 368–
372, 2006. DOI: 10.1039/b600031b.
[11] N. Narender, P. Srinivasu, S. J. Kulkarni, K. V.
Raghavan, Synth. Commun., 30, 1887, 2000;
N. Narender, P. Srinivasu, S. J. Kulkarni and K.
V. Raghavan, Green Chem., 3, 104, 2000.
[12] R. Alleti, M. Perambuduru, S. Samantha and V.
Prakash Reddy, J. Mol. Catal. A, 226, 57, 2005.
[13] T. N. Parac-Vogt, K. Deleersnyder and K.
Binnemans, Eur. J. Org. Chem., 1810, 2005.
[14] S. Velusamy, S. Borpuzari and T.
Punniyamurthy, Tetrahedron, 2005, 61, 2011.
[15] R. Ghosh, S. Maiti and A. Chakraborty,
Tetrahedron Lett., 46, 147, 2005.
[16] C.Li, M.Wang, X.Lu, L. Zhang, J. Jiang, &L.
Zhang, ACS Sustainable Chemistry &
Engineering, 8(11), 4353-4361,2020.
[17] S. M. Rafiaei, A. Kim, &M. Shokouhimehr,
Nanoscience and Nanotechnology Letters, 6(4),
309-313, 2014.
[18] D. E. Raup, B. Cardinal-David, D. Holte, and
K.A. Scheidt, Cooperative Catalysis by
Carbenes and Lewis Acids in a Highly Stereo
selective Route to γ-Lactams, Nat Chem. Sep;
2(9),766–771,2010.
[19] K.C. Ashalu,N. Rao, MgSO4 catalyzed one-pot
multi-component reaction: Synthesis of
amidoalkylnaphthols. Journal of Chemical and
Pharmaceutical Research, Volume 5, Issue 2,
Pages 44-47, 2013.
[20] B. Karami, S. khodabakhshi, A facile synthesis
of phenazine and quinoxaline derivatives using
magnesium sulfate heptahydrate as a catalyst, J.
Serb. Chem. Soc. 76 (9) 1191–1198, 2011.
[21] D. Yang, L. Wang, D. Li, R. Wang, Magnesium
Catalysis in Asymmetric Synthesis,, Chem5,
1108–1166, May 9, 2019.

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