A green method for selective acetylation of primary alcohols using ethyl acetate and solid potassium carbonate

Article abstract of DOI:10.3184/174751911X13155057300536

A simple and selective acetylation of primary alcohols in the presence of other reactive functionalities such as secondary alcohol, phenol, acetonide and amine is described using mild ethyl acetate as the acetyl-transfer agent and solid potassium carbonate as the catalyst.

Full text of DOI:10.3184/174751911X13155057300536

536 RESEARCH PAPER
SEPTEMBER, 536–539
JOURNAL OF CHEMICAL RESEARCH 2011
A green method for selective acetylation of primary alcohols using ethyl
acetate and solid potassium carbonate
N. Malleshaa, S. Prahlada Raob, R. Suhasa and D. Channe Gowdaa*
aDepartment of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore-570 006, India
bR&D Centre, CJEX Biochem, 7&8, 2nd cross, Muniswamappa layout, Hosur Road, Bommanahalli, Bangalore-560068, India
A simple and selective acetylation of primary alcohols in the presence of other reactive functionalities such as sec-
ondary alcohol, phenol, acetonide and amine is described using mild ethyl acetate as the acetyl-transfer agent and
solid potassium carbonate as the catalyst.
Keywords: transesterification, selective acetylation, ethyl acetate, K2CO3, green chemistry
Esterification is one of the fundamental reactions in organic
chemistry.1 There are several methods available to carry out
this reaction. In the methods where stoichiometric quantities
of the components, namely the alcohol and acid are used, the
acid is activated as an acyl halide, acyl cyanide, anhydride
or ketene.2,3 While this approach is advantageous in terms of
the quantities, the problem lies with the moisture-sensitive,
corrosive and hazardous nature of the acid derivatives. A green
replacement for the acid component is required. Alternatively,
one of the components can be used in excess and these meth-
ods include Fischer esterification4 and transesterification.5 The
latter method has received a lot of attention of late. Different
catalysts and different acyl transfer agents are being studied to
make this method more efficient and selective.6–13 While acidic
catalysts affect functional groups like acetals, strong basic
catalysts pose problems such as β-elimination and other side
reactions, especially if high nucleophilicity is associated with
basicity. In either case, the catalyst in insoluble solid form
offers advantages of easy work-up and minimal generation of
waste.
With the available and widely used catalysts (acidic and
basic), chemoselectivity has been an issue, necessitating sepa-
ration and purification steps. While trying to acylate a primary
hydroxyl group, other functional groups like a secondary alco-
hol, phenol and amine would come into competition. Although
there are methods in which ethyl acetate is used as the acetyl
transfer agent, the promoting agents are either highly basic and
hazardous such as sodium hydride14 or protic/Lewis acidic
conditions15 are used. Neutral alumina16 has been used for the
conversion of primary hydroxyalkylphenols to acetoxyalkyl-
phenols, but this method also transformed primary arylamines
to corresponding acetamides and hence these methods are not
compatible with some functional groups.
esters in good yield and in short time. Next we tried the method
on cis butene-1,4-diol (entry 3) and butyne-1,4-diol (entry 4).
Here also the reactions proceeded smoothly and in good
yields.
As a test of selectivity we tried the methodology on a wide
range of compounds (entries 5–17) which underwent smooth
O-acetylation under the given conditions and in all cases only
the primary hydroxyls were esterified leaving the other hydrox-
yls intact. We were expecting some products corresponding
to the acetylated secondary hydroxyl, at least, by way of acetyl
migration. However, that was not the case.
To test the chemoselectivity, dithiothreitol (entry 18), 2-
hydroxybenzyl alcohol (entry 19) and 3-aminobenzyl alcohol
(entry 20) were subjected to the reaction conditions. Here also
only primary selectivity was the feature. The other functional-
ities, viz: phenolic –OH and primary amine functionalities did
not react.
As a special case with a possibility of β-elimination, we
tried 9-fluorenylmethanol (entry 21), which underwent smooth
esterification without any elimination reaction. Resorcinol
(entry 22), triphenylmethanol (entry 23), benzylamine (entry
24), cyclohexylmethanamine (entry 25) and octylamine (entry
26) did not react under these reaction conditions. When
the reaction was carried out using catalytic amount of conc.
H2SO4 and ethyl acetate at 40 °C as described by Pi-Hui Liang15
et al., the acetonides (entries 7–9) were not stable and were
hydrolysed.
Surprisingly, replacing potassium carbonate by organic
bases like tributylamine, pyridine and also Dowex 550 resin
failed to bring about any satisfactory result as tested on xylose
monoacetonide (9) keeping all other parameters identical
(Table 2).
In summary, the reported method is highly chemoselective
for acetylating primary alcohols in the presence of secondary
alcoholic, phenolic acetonide and amine functionalities.
The method employs easily available, inexpensive potassium
carbonate in solid form as catalyst and ethyl acetate as both
the acetyl-transfer agent and solvent, which offers advantages
of easy work-up with minimal waste generation. The reaction
does not involve sensitive/toxic/hazardous reagents and are
generally very clean, good yielding without any side
products.
Here we report a simple, selective and efficient transesterifi-
cation method for preparing the acetate esters of primary alco-
hols using ethyl acetate as the acetyl-transfer agent as well as
solvent and solid potassium carbonate as the catalyst under
basic heterogeneous conditions (Scheme 1 and Table 1).
Results and discussion
Simple primary alcohols such as 1-heptanol (entry 1) and
benzyl alcohol (entry 2) resulted in the corresponding acetate
Experimental
A mixture of alcohol (10 mmol), ethyl acetate (10 mL) and anhydrous
potassium carbonate (10 mmol) was placed in a round bottom flask
and refluxed until completion of the reaction (monitored by TLC).
The reaction mass was cooled, filtered and the solvent was removed
in vacuo to dryness. The residue was dissolved in minimum amount
of methylene dichloride and passed a through plug of silica column
eluting with tert-butyl ether to isolate the product.
Scheme 1 Selective acetylation of alcohols.
1
The structure of the products was confirmed by b.p., m.p. and H
and 13C NMR spectra (provided in the supplementary data). In multi-
functional systems, the position of the acetyl group was ascertained by
* Correspondent: E-mail: dchannegowda@yahoo.co.in

JOURNAL OF CHEMICAL RESEARCH 2011 537
Table 1 Acetylation of alcohols using ethyl acetate and solid potassium carbonate
Entry no.
1.
Substrate
Product
Time /h
1
Yield /%a
85
2.
3.
4.
1
90
79
80
1.5
1
5.
6.
2
2
78
78
7.
8.
2
80
75
4*
9.
2
1
90
88
10.
11.
12.
1.5
76
79
1

538 JOURNAL OF CHEMICAL RESEARCH 2011
Table 1 Continued
Entry no.
Substrate
Product
Time /h
1
Yield /%a
70
13.
14.
15.
1
1
67
85
16.
17.
1
1
88
86
18.
1.5
79
19.
20.
2
1
85
90
21.
22.
23.
24.
1
91
Nil
Nil
Nil
No reaction
No reaction
No reaction
4hr
5hr
4hr
25.
26.
No reaction
No reaction
4hr
4hr
Nil
Nil
a Yield refers to isolated product.
*Reaction mass was warmed to 40 °C for 4h.

JOURNAL OF CHEMICAL RESEARCH 2011 539
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