Simple and efficient method for acetylation of alcohols, phenols, amines, and thiols using anhydrous NiCl2 under solvent-free conditions

Article abstract of DOI:10.1080/00397910902906529

Solvent-free acetylation of alcohols, phenols, amines, and thiols with acetic anhydride (Ac₂O) in the presence of 0.1mol% (13mg) anhydrous NiCl₂, an inexpensive and easily available catalyst, is described. Excellent yields, short reaction time, and mild reaction conditions are important features of this method.

Full text of DOI:10.1080/00397910902906529

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Simple and Efficient Method
for Acetylation of Alcohols,
Phenols, Amines, and Thiols
Using Anhydrous NiCl2 Under
Solvent-Free Conditions
Gangadhar Meshram a & Vishvanath D. Patil a
a Department of Chemistry , University of Mumbai ,
Mumbai, India
Published online: 12 Nov 2009.
To cite this article: Gangadhar Meshram & Vishvanath D. Patil (2009) Simple and
Efficient Method for Acetylation of Alcohols, Phenols, Amines, and Thiols Using
Anhydrous NiCl2 Under Solvent-Free Conditions, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 39:24,
4384-4395, DOI: 10.1080/00397910902906529
To link to this article: http://dx.doi.org/10.1080/00397910902906529
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Synthetic Communications1, 39: 4384–4395, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902906529
Simple and Efficient Method for Acetylation
of Alcohols, Phenols, Amines, and Thiols Using
Anhydrous NiCl2 Under Solvent-Free Conditions
Gangadhar Meshram and Vishvanath D. Patil
Department of Chemistry, University of Mumbai, Mumbai, India
Abstract: Solvent-free acetylation of alcohols, phenols, amines, and thiols with
acetic anhydride (Ac2O) in the presence of 0.1 mol% (13 mg) anhydrous NiCl2,
an inexpensive and easily available catalyst, is described. Excellent yields, short
reaction time, and mild reaction conditions are important features of this method.
Keywords: Acetic anhydride, acetylation, anhydrous NiCl2, solvent-free
INTRODUCTION
The development of simple, efficient, environmentally benign and
economically viable chemical processes and methodologies for widely
used organic compounds is in great demand. Acetylation reactions have
received considerable attention in organic synthesis because they result in
various useful organic compounds. They are widely used as perfumes,
cosmetics, flavors, food additives, plastisizers, and polymers. Acetylation
of phenols represents a versatile strategy for protection and is frequently
achieved with acetic anhydride.[1] Various catalysts developed for acetyla-
[3]
[4]
tion include metal triflates.[2] HBF4=SiO2
and HClO4=SiO2
as
acetylation catalysts require special efforts to prepare. The commercially
available aqueous HBF4 and aqueous HClO4 induce side reactions with
acid-sensitive substrates. Other catalysts such as ionic liquids,[5] InCl3,[6]
Received November 14, 2008.
Address correspondence to Gangadhar Meshram, Department of Chemistry,
University of Mumbai, Vidyanagari, Santacruz (E), Mumbai, India. E-mail:
vdp148@yahoo.com
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Simple and Efficient Acetylation
4385
chlorates,[7] yttria-zirconia,[8] CoCl2,[9] nafion-H,[10] clays,[11] TaCl5,[12]
Bu3P,[13] zeolites[14] require longer reaction time, stringent reaction condi-
tions,[15] and dimethylaminopyridine (DMAP).[16] Consequently, there is
opportunity to further develop mild conditions, increased variation of the
components, and better yields.
RESULTS AND DISCUSSION
A wide variety of compounds that were acetylated in this protocol are pri-
mary, allylic, benzylic, hindered, and unhindered secondary and sterically
hindered tertiary alcohols, amines, phenols, and thiols. The results are
summarized in Table 1. The primary and secondary alcohols were acety-
lated under solvent-free conditions at room temperature with excellent
yields (Table 1, entries 1–12). Interestingly, hindered tertiary alcohols such
as triphenyl methanol and 1-methyl cyclohexanol were also converted to
the corresponding acetates at room temperature in good yields (Table 1,
entries 13 and 14). Dihydroxy aromatic and aliphatic compounds
afforded the corresponding diacetates in excellent yields (Table 1, entries
15–18). The comparison of the results (Table 1, entries 20 and 21) indicates
that acetylation of substrates bearing an NO2 group adjacent to the phe-
nolic OH required longer times the steric hinderance offered by the group
with less yield. Anhydrous NiCl2 because of exhibited excellent catalytic
activity in the acetylation of amines and thiols under the same reaction
conditions with considerable yields (Table 1, entries 24–30).
CONCLUSIONS
In conclusion, this article describes a method in which anhydrous NiCl2 is
a highly efficient catalyst for the acetylation of alcohols, amines, phenols,
and thiols. The advantages include the low cost, ease of catalyst handling,
requirement of very small amounts of catalyst (0.1 mol%, 13 mg) and
Ac2O, mild reaction conditions, room temperature, excellent yield, short
reaction time, and no undesirable side products. The solvent-free condi-
tion employed in the present method should make it environmentally
friendly and useful for industrial applications.
EXPERIMENTAL
Typical Experimental Procedure
A mixture of aliphatic, aromatic compounds containing alcohols, amines,
phenols, or thiols (2 mmol), 3–4 mmol acetic anhydride (Ac2O), and

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G. Meshram and V. D. Patil
0.1 mol% (13 mg) anhydrous NiCl2 was stirred magnetically at room
temperature, and the progress of the reaction was monitored by
thin-layer chromatography (TLC). The reaction mixture was diluted with
water (30 ml) and extracted with chloroform (3 ꢀ 30 ml). The combined
chloroform extracts were washed successively with 10% sodium bicarbo-
nate and water, dried with Na2SO4, and concentrated under reduced
pressure. In all the cases, the product obtained after the usual workup
gave satisfactory spectral data.
Characterization Data for Products
Bezyl Acetate (1b)
IR (KBr): 700, 720, 1215, 1371, 1493, 1594, 1724, 1765, 3040, 3070 cmꢁ1
.
H1 NMR (300 MHz, CDCl2): d ¼ 7.0 (s, 5H, Ar-H); 1.8 (s, 3H, COCH3);
4.7 (s, 2H, CH2). Anal. calcd. for C9H10O2: C, 71.98; H, 6.71. Found: C,
71.95; H, 6.70.
1,5-Pentane Diacetate (15b)
IR (KBr): 900, 995, 1260, 1350, 1735, 1765, 2945, 3020 cmꢁ1. H1 NMR
(300 MHz, CDCl2): d ¼ 2.2 (s, 6H, 2 ꢀ COCH3); 4.7 (t, 4H, 2 ꢀ H2); 1.4
(m, 2H, CH2); 1.65 (m, 4H, 2 ꢀ CH2). Anal. calcd. for C9H16O4: C,
57.43; H, 8.56. Found: C, 57.42; H, 8.55.
Phenyl Acetate (19b)
IR (neat): 760, 1264, 1369, 1494, 1595, 1745, 2926, 3060 cmꢁ1. H1 NMR:
d ¼ 7.05 (s, 5H, Ar-H); 2.1 (s, 3H, COCH3). Anal. calcd. for C8H8O2: C,
70.57; H, 5.92. Found: C, 70.56; H, 5.88.
2-Nitro Benzyl Acetate (20b)
IR (KBr): 733, 1215, 1351, 1493, 1605, 1727, 1762, 3035 cmꢁ1. H1 NMR
(300 MHz, CDCl2): d ¼ 2.1 (s, 3H, COCH3); 4.7 (s, 2H, CH2); 7.2 (m, 4H,
Ar-H). Anal. calcd. for C9H9O4N: C, 55.38; H, 4.64; N, 7.17. Found: C,
55.38; H, 4.61; N, 7.15.
1-Naphthyl Acetate (22b)
IR (KBr): 685, 720, 750, 825, 925, 1197, 1264, 1369, 1494, 1600, 1745,
2926 cmꢁ1. H1 NMR (300 MHz, CDCl2): d ¼ 7.05 (m, 7H, Ar-H); 2.1

Simple and Efficient Acetylation
4393
(s, 3H, COCH3). Anal. calcd. for C12H10O2: C, 77.40; H, 5.41. Found: C,
77.40; H, 5.39.
Acetanilide (26b)
IR (KBr): 555, 1022, 1275, 1523, 1620, 1695, 1710, 3030, 3180 cmꢁ1
.
H1 NMR (300 MHz, CDCl2): d ¼ 3.3 (s, 3H, CH3), 6.5 (m, 5H, Ar-H),
7.2 (s, NH). Anal. calcd. for C8H9ON: C, 71.08; H, 6.71; N, 10.36.
Found: C, 71.07; H, 6.66; N, 10.33.
N,N-Diethyl Ethanamide (28b)
IR (KBr): 855, 915, 1010, 1125, 1410, 1750, 2947, 3025 cmꢁ1. H1 NMR
(300 MHz, CDCl2): d ¼ 0.9 (t, 6H, 2 ꢀ CH3); 1.4 (q, 4H, 2 ꢀ CH2); 2.5
(s, 3H, COCH3). Anal. calcd. for C6H13ON: C, 62.57; H, 11.37; N,
12.16. Found: C, 62.56; H, 11.36; N, 12.15.
Benzene Thio-acetate (29b)
IR (KBr): 697, 754, 1454, 1492, 1600, 1670, 1756, 1825, 1985, 2920,
3025 cmꢁ1. H1 NMR (300 MHz, CDCl2): d ¼ 7.01 (m, 5H, Ar-H), 3.3
(s, 3H, COCH3). Anal. calcd. for C8H8OS: C, 63.12; H, 5.29; S, 21.06.
Found: C, 63.11; H, 5.29; S, 21.01.
ACKNOWLEDGMENT
The authors acknowledge the partial support of this work by Prof. B. P.
Bandgar, Vice Chancellor, University of Solapur, India.
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