Open Journal of Synthesis Theory and Applications, 2012, 1, 31-35
http://dx.doi.org/10.4236/ojsta.2012.13006 Published Online October 2012 (http://www.SciRP.org/journal/ojsta)
Highly Efficient Cobalt (II) Catalyzed O-Acylation of
Alcohols and Phenols under Solvent-Free Conditions
Shafeek A. R. Mulla*, Suleman M. Inamdar, Mohsinkhan Y. Pathan, Santosh S. Chavan
Chemical Engineering and Process Development Division, National Chemical Laboratory, Pune, India
Received August 6, 2012; revised September 12, 2012; accepted September 28, 2012
Solvent free, highly efficient method has been developed using ecofriendly, heterogeneous reusable cobalt chloride
catalyst at ambient reaction conditions for the O-acylation of various alcohols and phenols with acetyl chloride in ex-
cellent yield in a short reaction time. The catalyst is recycled several times without loss of catalytic activity.
Keywords: Acetylation, Alcohol, Phenol, Acetyl Chloride, Cobalt (II) Chloride
An esterification is a key and fundamental step to protect
hydroxyl group during functional transformation in vari-
ous organic synthesis [1-3]. However, protection and de-
protection of hydroxyl functional group of alcohols and
phenols being not only prime importance in pharmaceu-
tical industries but also in the polymers, cosmetics, per-
fumes, plasticizers to achieve excellent yield to potential
targeted synthetic compounds. Owing the importance of
protection of hydroxyl function al group du ring th e multi-
steps organic synthesis, the various methods for the pro-
tection of hydroxyl group of alcohols and phenols using
varieties of reagent and catalysts such as HgCl2 ,
Montmorillonite , TMS-Cl , TaCl5-SiO2 , ZnCl2
, ZnO [9-10], Ru-catalyst , Mg(ClO4) , SmI2
, CeCl3 , perchlorates , P2O5/Al2O3 ,
CoCl2 [17-18], ZrCl4 , NH2SO3H , solid sup-
ported HBF4-SiO2 , lipase enzyme , Al(OTf)3
, In(OTf)3 , Bi(OTf)3 , polymer supported
Gd(OTf)3 , Ce(OTf)3 , Ag(OTf)3 , molecular
Iodine , nitro benzeneboronic acid , NiCl2 ,
La(NO3).6H2O , DCC , Co(II)salen-complex
, Melamine trisulfonic acid (MTSA) , ionic liq-
uid [36-39], ZnAl2O4 , have been reported, however,
the most common acetylating reagents used are acetyl
chloride, acetic acid, acetic anhydride or any other protic
However, all the above methods are badly suffer from
one/or other limitations and drawbacks such as drastic
reaction conditions, long reaction time, high temperature,
use of moisture sensitive, toxic, expensive reagents and
catalysts. In addition these limitations, the catalysts are
non-recoverable besides the formation of toxic side pro-
duct and poor yield for th e desired product in presen ce of
Therefore, considering all th e above facts, still there is
a need and demand to develop a solvent free, greener
and an economical protocol and catalysts for protection
of hydroxyl of alcohols and phenols by esterification.
Therefore, herein we wish to report a solvent-free, a
cheap, mild, rapid and efficient protocol for the O-acyla-
tion of alcohols and phenols with acetyl chloride over
cobalt (II) chloride catalyst at room temperature (Schemes
R-OH 1 mol% CoCl2
AcCl (1. 2 eq uiv)
R= P h, Allyl, Benzyl, Nap hthyl, Alip hatic, etc.
Scheme 1. Cobalt (II) chloride catalyzed O-acylation of alco-
hols and phenols.
2. Experimental Section
All chemicals and reagents were procured from suppliers
and used without further purification. The products were
analyzed by a 5765 NUCON Gas Chromatograph with
FID detector using stainless steel column 4 m length x
1/8 inch O.D. x 2 mm I.D., packed with 10% SE-30 on
Chromosorb-W with mesh size 80-100 and also charac-
terized using 1H NMR, 13C NMR spectra. The NMR
spectrums of product were obtained using Bruker AC-
200 MHz spectrometer with TMS as the internal stan-
opyright © 2012 SciRes. OJSTA
S. A. R. MULLA ET AL.
2.1 General Experimental Procedure for
O-Acetylation of Alcohols and Phenols
The alcohol or phenol (5 mmol) in acetyl chloride (6
mmol) was taken in 50 ml round bottom flask. To this
reaction mixture 1mol% cobalt (II) chloride catalyst was
added and then mixture was stirred at room temperature
under solvent free conditions. The influence of acylating
agents was investigated using phenol, 4-methyl phenol
and chloroethanol as substrate. The completion of the
reactions was monitored by GC. After the completion of
reaction, the mixture was diluted with ethyl acetate (25
ml) and the catalyst was recovered by filtration. The fil-
trate was washed with NaHCO3 and then with water,
dried over anhydrous Na2SO4. The dry filtrate was con-
centrated under vacuum to obtain the p ure produ ct.
3. Results and Discussion
Acylation of phenol (5 mmol) was studied with acetyl
chloride (6 mmol) in presence of 1 mol% cobalt (II) chlo-
ride catalyst under solvent free condition at room tem-
perature to afford phenyl acetate in 99% yield in 20 sec-
onds. However, the acetylation reaction of phenol was
inefficient in absence of cobalt (II) chloride. After the
successful acetylation of phenol with excellent yield to
phenyl ester, the influence of acylating agents was invest
tigated using phenol, 4-methyl phenol and chloroethanol
as substrate and results are summarized in Table 1. The
influence of the acylating agent’s study (entries 1 - 3,
Table 1) reveals that reactivity of acetyl chloride is ex
tremely higher than that of acetic anhydride and acetic
acid over the cobalt (II) chloride catalyst under solvent
free conditions at room temperature.
The results on influence of acylating agents promoted
us to evaluate the scope of this methodology for different
types of primary, secondary, benzylic, allylic, cyclic al-
cohols and phenols using acetyl chloride as acylating
agent (Scheme 1).
A number of substituted phenols and alcohols such as
4-tert-butyl phenol, 2- tert-butyl, 4-methyl phenol, p-
cresol, o-cresol, m-cresol, 2-hydroxy benzaldehyde, 1-
naphthol and 2-naphthol (entries 2 - 9, Table 2) and bu-
tanol; hexanol; heptanol; 1, 8-octandiol; chloro ethanol;
Lauryl alcohol and 2-butanol (entries 1 - 7, Table 3),
secondary alcohols (entries 8 - 9, Table 3), allylic alco-
hol (entry 10, Table 3) and benzylic alcohols (entry 11 -
12, Table 3) were acetylated respectively, in good to
excellent yield without any difficulties.
The results (Tables 2 and 3) on the acetylation of alco
hols and phenols reveal that the good to excellent yield
up to 99% was achieved in very short reaction time
Table 1. Influence of acylating agents on various substratea.
(s) AcCl Ac2OAcOH
3 Cl OH Cl OAc 10
aReaction conditio ns: The s ubstrat e (5 mmol) , acetyl ating agent ( 6 mmol), 1
mol% CoCl2, room temperature; bGC yield. NR: No Reaction.
Table 2. Cobalt (II) chloride catalyzed acetylation o f phenols
with acetyl chloridea.
EntrySubstrate (R) Product Time (s)Yieldb
aReaction conditions: The substrate (5 mmol), CH3COCl (6 mmol/OH
group), 1 mol% CoCl2, room temperature; bGC yield; cwithout CoCl2 cata-
Copyright © 2012 SciRes. OJSTA
S. A. R. MULLA ET AL. 33
Table 3. Cobalt (II) chloride catalyzed acetylation of alco-
hols with acetyl chloridea.
Entry Substrate (R) Product Time
1 OH OAc 10 95
2 OH OAc 10 99
3 OH OAc 15 98
4 OH OH OAc
AcO 15 99
5 Cl OH Cl OAc 10 99
6 OH OAc 15 99
OH Me OAc
9 OH OH
10 OH OAc 10 82
aReaction conditions: The substrate (5 mmol), CH3COCl (6 mmol/OH group),
1mol % CoCl2, room temperature; bGC yield.
(10 - 50 seconds). Further, the result indicates that the
cobalt (II) chloride catalyst shows remarkably high cata-
lytic activity and efficiency not only with primary alco-
hols and phenols but also with sterically hindered secon-
dary, benzylic, allylic, cyclic alcohols and phenols under
mild and solvent free reaction conditions at room tem-
perature. The catalytic activity and / or recyclability study
of 1 mol% cobalt (II) chloride catalyst was performed for
the acetylation of phenol (Scheme 2, Table 4).
The catalyst was recovered quantitatively four times
by simple filtration of the reaction mixture and subse-
quently washed with ethyl acetate and water. The recov-
ered cobalt (II) chloride catalyst was reused four times
(Run 2-5, Table 4) for the acetylation of phenol with
acetyl chloride to give the phenyl acetate in 98% - 99%
yield, which is almost comparable with fresh catalyst
(Run 1, Table 4). This result clearly shows that the recy-
cled cobalt (II) chloride gives excellent yield without loss
of catalytic activity.
As shown in the Scheme 3, the plausible reaction
mechanism and/ or catalytic cycle for the acetylation of
alcohols and phenols using acetyl chloride as acylating
agents over the cob alt (II) chloride under the solvent free
AcCl (1.2 equiv)
1 mol% Rec.CoCl 2
Scheme 2. Recyclability study of cobalt (II) chloride catalyst
for acetylati on of phenols with ac etyl chloride.
Table 4. Recyclability study of cobalt (II) chloride for acety -
lation of phenol with acetyl chloridea.
No. of Run Time (s) Yield (%)
Run 1 (Fresh catalyst)20 99
Run 2 20 99
Run 3 25 98
Run 4 25 99
Run 5 30 99
aReaction conditions: phenol (5 mmol) CH3COCl (6 m mol) 1 mol% of Co Cl2
at room temperature Catalyst recovery = 97% ± 2%; bGC yield.
R= Ph, Allyl, Benzyl, Naphthyl, Aliphatic, etc.
Scheme 3. The proposed catalytic cycle for the acetylation
reaction over CoCl2 catalyst.
condition at room temperature is not clear so far, how-
ever, the results obtained in the present study shed some
light on these aspects.
The carbonyl group of acetyl chloride is known to co-
ordinating on Lewis acid sites of the CoCl2 catalyst sur-
face via intermediate (2) to activate itself being reactive
electrophile. The activation of carbonyl group of acetyl
chloride encourage the attack by the oxygen of alcohols
and/or phenols as an nucleophile and subsequently stabi-
lization intermediate (3) and release of leaving group
followed by formation of the corresponding acetate (4)
by the loss of hydrochloric acid (5).
In conclusion, cobalt (II) chloride is an efficient, versatile,
ecofriendly, inexpensive, nontoxic, reusable heterogene-
ous and green catalyst for the acetylation of alcohols and
phenols using acetyl chloride as acetylating reagent. The
following features make this methodology attractive: 1)
Copyright © 2012 SciRes. OJSTA
S. A. R. MULLA ET AL.
its simplicity, clean, efficient, rapid and mild reactions
conditions; 2) the protocol is very general and it works
well with variety o f alcohols and phenols affording good
to excellent yields; 3) the reaction carried out at room
temperature in absence of the organic solvent; 4) the
relative reactivity of acylating agents over the cobalt (II)
chloride catalyst were found to be higher in the order:
acetyl chloride > acetic anhydride > acetic acid; 5) the
recovered and reused catalyst without further purifica
tions gave 98% - 99% yield without loss of catalytic ac-
SMI, MYP and SSC thanks to CSIR New Delhi for a
SRF and JRF, respectively. The authors also th ank to Dr.
V. V. Ranade, Chair, CE-PD for their encouragement
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