Potassium fluoride assisted selective acetylation of alcohols with acetic acid

Article abstract of DOI:10.1081/SCC-200026245

Potassium fluoride promotes the acetylation of primary and secondary alcohols with acetic acid in excellent yield. Phenols are not affected under this reaction conditions. The groups like double bond, chloro, methoxy, benzyloxy, thiol, and nitro remain unaffected.

Full text of DOI:10.1081/SCC-200026245

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Potassium Fluoride Assisted
Selective Acetylation of
Alcohols with Acetic Acid
J. W. John Bosco a , B. Rama Raju a & Anil K.
Saikia a
a Department of Chemistry , Indian Institute of
Technology Guwahati , Guwahati, 781039, India
Published online: 12 Jan 2011.
To cite this article: J. W. John Bosco , B. Rama Raju & Anil K. Saikia (2004)
Potassium Fluoride Assisted Selective Acetylation of Alcohols with Acetic Acid,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 34:15, 2849-2855, DOI: 10.1081/SCC-200026245
To link to this article: http://dx.doi.org/10.1081/SCC-200026245
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 15, pp. 2849–2855, 2004
Potassium Fluoride Assisted Selective
Acetylation of Alcohols with Acetic Acid
*
J. W. John Bosco, B. Rama Raju, and Anil K. Saikia
Department of Chemistry, Indian Institute of Technology Guwahati,
Guwahati, India
ABSTRACT
Potassium fluoride promotes the acetylation of primary and secondary
alcohols with acetic acid in excellent yield. Phenols are not affected
under this reaction conditions. The groups like double bond, chloro,
methoxy, benzyloxy, thiol, and nitro remain unaffected.
Key Words: Potassium fluoride; Acetic acid; Acetylation; Alcohols.
INTRODUCTION
The acetylation of alcohols is an important and frequently used transform-
ation in organic synthesis.[1] The direct acetylation of alcohols with acetic acid
*
Correspondence: Anil K. Saikia, Department of Chemistry, Indian Institute of Tech-
nology Guwahati, Guwahati 781039, India; Fax: þ91-361-2690762; E-mail: asaikia@
iitg.ernet.in.
2849
DOI: 10.1081/SCC-200026245
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

2850
Bosco, Raju, and Saikia
is carried out in the presence of mineral acids or sulfonic acids. Generally, this
method is avoided because it is reversible in nature and the byproduct water
has to be removed by azeotropic distillation or addition of dehydrating
agent to drive the reaction forward direction. The main disadvantage of this
method is that acid sensitive groups are not tolerated.[2] Moreover, the use
of strong mineral acids leads to highly acidic waste streams posing an environ-
mental problem for industrial processes. These limitations make preferable the
use of more reactive derivatives of carboxylic acid, such as acid chloride[3] or
(mixed) anhydride,[4] in the presence of tributylphosphine[5] or pyridine
derivatives.[6] Recently, Lewis acid catalyst such as titanium(IV) chloride
tris(trifluoromethanesulfonate),[7] scandium(III), and lanthanide(III) triflates
have been reported as catalyst for the direct acetylation of alcohols with
acetic acid.[8] In a recent work, direct acylation of alcohols with carboxylic
acids using H2SO4 supported on silica is reported.[9] However, the use of
mineral acid, expensive transition metal catalyst and acetic anhydride makes
these methods unsuitable for routine work. More recently, Yamamoto[10] and
co-workers disclosed that HfCl4 could be used as a catalyst for the direct ester-
ification of carboxylic acids with alcohols. Although yield is high in this
method, it suffers from some inconvenience. As the system is sensitive to
water and thus rigorous dehydration by soxhlet extraction with molecular
sieve is indispensable.
Potassium fluoride has long been used as a useful reagent in organic
synthesis.[11] In this communication, some of the results obtained from the
acetylation of alcohols using easily available and cheap reagents KF and
AcOH have been disclosed (Sch. 1). Under the reaction condition, neither
elimination nor fluorinated products were observed. The use of acetic acid
rather than acetic anhydride or acetyl chloride is both economically and envir-
onmentally advantageous. The reaction is generalized through entries 1–18
(Table 1).
It was observed that primary and secondary alcohols can be acetylated
readily with a very high yield and neither fluorinated nor eliminated products
were identified. This is due to the fact that the hydrogen bonding between
fluoride ion and hydroxyl group of acetic acid reduces nucleophilicity and
basicity of the fluoride ion. In the case of tertiary alcohol, the reaction
becomes sluggish and takes longer time with the formation of elimination pro-
Scheme 1.

Acetylation of Alcohols with Acetic Acid
2851
Table 1. Direct acetylation of various alcohols with acetic acid in the presence of
potassium fluoride.
t
(hr)
Yielda
(%)
Entry
Substratea
Productb
1
2
1.5
3
98
97
3
4
1.5
3
98
97
5
6
7
3
3
7
96
98
95
8
5
97
9
7
7
98
94
10
11
12
5
4
98
97
13
14
15
3.5
3
99
92
0
9
16
7
94
(continued)

2852
Bosco, Raju, and Saikia
Table 1. Continued.
t
(hr)
Yielda
(%)
Entry
17
Substratea
Productb
9
9
34b
18
41b
aYields are isolated yields. The compounds were characterized by GC, H NMR, and
IR spectroscopy and by comparisons with the literature.
bOlefins are the byproduct.
1
ducts and the reaction ends up with a low yield (Table 1). However, phenols
are not affected and alcoholic group can be selectively acetylated. More
importantly, the hydroxyl group residing in chiral center could be acetylated
with retention of configuration (entry 7). The groups like double bond,
chloro, nitro, methoxy, benzyloxy, thiol, etc. remain unaffected. Moreover,
the reaction does not require any dry glassware and inert atmosphere. The
operation is quite simple, because the dehydrating systems like Dean–Stark
apparatus or agent like molecular sieve is not necessary. The purification
process is very simple, as both potassium fluoride and acetic acid are water-
soluble and final product does not require any tedious purification procedures.
CONCLUSION
In conclusion, we have developed a new, high yielding, and selective
methodology for the direct acetylation of primary and secondary alcohols
with acetic acid and potassium fluoride. The ease of use of potassium fluoride,
and low cost of both acetic acid and KF; and clean, easy work up of the
product mixture makes this protocol important for both industrial and
general purposes.
TYPICAL EXPERIMENTAL PROCEDURE
In a typical reaction benzyl alcohol (0.35 g, 3.1 mmol), KF (0.22 g,
3.8 mmol), and acetic acid (5 mL) were heated at 808C in a round bottom
flask. The reaction was monitored by TLC and GC. After completion
(1.5 hr) of the reaction, the reaction mixture was diluted with water (20 mL),

Acetylation of Alcohols with Acetic Acid
2853
and extracted with ethyl acetate (2 ꢀ 50 mL). The organic layer was washed
with aqueous NaHCO3 (30 mL) and brine (20 mL), dried (Na2SO4), and evap-
orated to dryness and finally passed through a short silica gel column to
1
give benzyl acetate (0.45 g, 98%); H NMR (60 MHz, CDCl3): d 2.0 (s, 3H,
–O–CO–CH3), 4.9 (s, 2H, –CH2–O–), 7.19 (m, 5H, aromatic); IR: 3026,
1741, 1228, 1029 cm21
.
p-Nitrobenzyl acetate (2b). 1H NMR (200 MHz, CDCl3): d 2.17 (s, 3H,
–O–CO–CH3), 5.20 (s, 3H, O-CH22 ), 7.52 (d, J ¼ 5.50 Hz, 2H, aromatic),
2H, 8.22 (d, J ¼ 5.62 Hz, 2H, aromatic); IR: 3098, 1741, 1516, 1347, 1244,
1055 cm21
.
p-Methoxybenzyl acetate (3b). 1H NMR (60 MHz, CDCl3): d 1.95
(s, 3H, –O–CO–CH3), 3.6 (s, 3H, O-CH3), 4.8 (s, 2H, –CH2–O–), 6.85
(m, 4H, aromatic); IR: 2950, 1736, 1516, 1245, 1173, 1040 cm21
.
p-Chlorobenzyl acetate (4b). 1H NMR (60 MHz, CDCl3): d 1.95 (s, 3H,
–O–CO–CH3), 4.8 (s, 2H, –CH2–O–), 7.0 (m, 4H, aromatic); IR: 2960, 1746,
1495, 1383, 1234, 1096, 1014 cm21
.
Cetyl acetate (5b). 1H NMR (300 MHz, CDCl3): d 0.88 (t, J ¼ 6.3 Hz,
3H, –CH3), 1.26 (m, 30H, –CH2–), 1.62 (m, 2H, –CH2–), 2.05 (s, 3H,
O–COCH3), 4.05 (t, J ¼ 6.90 Hz, 2H, –OCH2–); IR: 2924, 2853, 1747,
1465, 1373, 1240, 1040 cm21
.
Menthyl acetate (7b). 1H NMR (300 MHz, CDCl3):
d
0.77
(d, J ¼ 6.9 Hz, 3H, 2-CH3), 0.90 (d, J ¼ 7.2 Hz, 6H, 2-CH3), 1.00–1.90
(m, 9H, 3-CH–, 3-CH2–), 2.09 (s, 3H, –OCOCH3), 4.67 (dt, J ¼ 10.8 and
4.5 Hz, 1H, O–CH–); IR: 2955, 1741, 1244, 1029 cm21; [a]D25 279.428 (c
1.6 g/100 mL, CHCl3) [Lit.[12] [a]D20 280.58 (c 2 g/100 mL, CHCl3)].
Cholesteryl acetate (8b). 1H NMR (200 MHz, CDCl3): d 0.68 (s, 3H,
–CH3), 0.86 (d, J ¼ 4.4 Hz, 6H, 2-CH3), 0.91 (d, J ¼ 4.6 Hz, 3H, –CH3), 1.00
(s, 3H, –CH3), 1.20–1.80 (m, 26H, –CH2–, –CH–), 2.03 (s, 3H, O-COCH3),
2.30 (d, J ¼ 5.06 Hz, 2H, –CH2–), 4.60 (m, J ¼ 4, 1H, –O–CH–), 5.37
(m, 1H, –CH55C–); IR: 2955, 1741, 1470, 1372, 1255, 1045 cm21
.
Cyclododecyl acetate (9b). 1H NMR (300 MHz, CDCl3): d 1.25–1.54
(m, 18H, 9-CH2–), 1.71 (m, 4H, 2-CH2–), 2.04 (s, 3H, –OCOCH3), 5.0
(m,1H, –O–CH–); IR: 2934, 1741, 1475, 1239, 1024 cm21
.
1-Acetoxy-1,1-diphenyl-methane (10b). 1H NMR (300 MHz, CDCl3):
d 2.16 (s, 3H, O-CO-CH3), 6.88 (s, 1H, O–CH–), 7.31 (m, 10H, 2Ph); IR:
3042, 1741, 1377, 1239, 1025 cm21
.
Cinnamyl acetate (12b). 1H NMR (300 MHz, CDCl3): d 2.90 (s, 3H,
–O–COCH3), 4.72 (d, J ¼ 6.30 Hz, 2H, O–CH2–), 4.05 (dt, J ¼ 12.90 and
6.60 Hz, 2H, –CH–), 6.64 (d, J ¼ 15.90 Hz, –CH–), 7.31 (s, 5H, –Ph); IR:
2955, 1741, 1244, 1029 cm21
.
4-Benzyloxy pentyl acetate (13b). 1H NMR (300 MHz, CDCl3): d 1.42
(m, 2H, –CH2–), 1.62 (m, 4H, 2-CH2–), 2.04 (s, 3H, –O–COCH3), 3.47

2854
Bosco, Raju, and Saikia
(t, J ¼ 6.30 Hz, 2H, O–CH2–), 4.05 (t, J ¼ 6.60 Hz, 2H, O–CH2–), 4.50
(s, 2H, –CH2Ph), 7.30 (s, 5H, –Ph); 13C NMR (300 MHz, CDCl3): 171.2,
138.5, 128.3 (2C), 127.6 (2C), 127.5, 72.9, 70.1, 64.5, 29.12, 28.41, 22.67,
20.98; IR: 2930, 2853, 1737, 1240, 1096, 1061, 1030 cm21
.
2-Acetoxy ethane thiol (14b). 1H NMR (300 MHz, CDCl3): d 2.05
(s, 3H, O–CO–CH3), 2.75 (dt, J ¼ 9.00 and 6.00 Hz, 2H, S–CH2–), 4.19
(t, J ¼ 6.6 Hz, 2H, –CH2–); IR: 2542, 1741, 1377, 1239, 1025 cm21
.
4-Hydroxy benzyl acetate (15b). 1H NMR (400 MHz, CDCl3): d 2.09
(s, 3H, –O–CO–CH3), 5.03 (s, 2H, –CH2–O–), 5.43 (br, 1H, OH), 6.82
(d, J ¼ 8.80 Hz, 2H, aromatic), 7.25 (d, J ¼ 8.80 Hz, 2H, aromatic); IR:
3406, 2955, 1716, 1516, 1235, 1030 cm21
.
1-Ethyl-2-methyl-cyclohexyl acetate (16b). 1H NMR (200 MHz,
CDCl3): d 0.88 (m, 6H, 2-CH3), 1.25–1.41 (m, 11H, 1-CH–, 5-CH2–), 2.16
(s, 3H, –OCOCH3); IR: 2929, 1736, 1459, 1275, 1131, 1070 cm21
.
ACKNOWLEDGMENT
The authors are grateful to CSIR, New Delhi for financial support and
1
CDRI, Lucknow for providing H NMR spectra.
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Received in India April 15, 2004