A fast and convenient procedure for the acetylation of alcohols

Article abstract of DOI:10.1081/SCC-200043272

Treatment of different steroidal and aliphatic alcohols with BF₃ · OEt₂ and acetic anhydride for 5 seconds produced complete acetylation in high to quantitative yields.

Full text of DOI:10.1081/SCC-200043272

This article was downloaded by: [Rutgers University]
On: 13 April 2015, At: 18:39
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T
3JH, UK
Synthetic Communications:
An International Journal
for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
A Fast and Convenient
Procedure for the Acetylation
of Alcohols
Roxana Martinez‐Pascual a , Omar Viñas‐Bravo a ,
Socorro Meza‐Reyes a , Martín. A. Iglesias‐Arteaga
a & Jesús Sandoval‐Ramírez a
a Facultad de Ciencias Químicas , Benemérita
Universidad Autónoma de Puebla, Ciudad
Universitaria , C.P. 72570, Puebla, Pue. México
Published online: 10 Jan 2011.
To cite this article: Roxana Martinez‐Pascual , Omar Viñas‐Bravo , Socorro
Meza‐Reyes , Martín. A. Iglesias‐Arteaga & Jesús Sandoval‐Ramírez (2004) A Fast and
Convenient Procedure for the Acetylation of Alcohols, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry,
34:24, 4591-4596, DOI: 10.1081/SCC-200043272
To link to this article: http://dx.doi.org/10.1081/SCC-200043272
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all
the information (the “Content”) contained in the publications on our
platform. However, Taylor & Francis, our agents, and our licensors
make no representations or warranties whatsoever as to the accuracy,
completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of

the authors, and are not the views of or endorsed by Taylor & Francis.
The accuracy of the Content should not be relied upon and should be
independently verified with primary sources of information. Taylor and
Francis shall not be liable for any losses, actions, claims, proceedings,
demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in
relation to or arising out of the use of the Content.
This article may be used for research, teaching, and private study
purposes. Any substantial or systematic reproduction, redistribution,
reselling, loan, sub-licensing, systematic supply, or distribution in any form
to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 24, pp. 4591–4596, 2004
A Fast and Convenient Procedure for the
Acetylation of Alcohols
Roxana Martinez-Pascual, Omar Vin˜as-Bravo,
´
´ ´
and Jesus Sandoval-Ramırez
Socorro Meza-Reyes, Martın. A. Iglesias-Arteaga,
*
´ ´ ´
Facultad de Ciencias Quımicas, Benemerita Universidad Autonoma de
´
Puebla, Ciudad Universitaria, Puebla, Pue. Mexico
ABSTRACT
.
Treatment of different steroidal and aliphatic alcohols with BF3 OEt2 and
acetic anhydride for 5 seconds produced complete acetylation in high to
quantitative yields.
.
Key Words: O-Acetylation; BF3 OEt2.
Acetylation of alcohols is the most common procedure for the protection
of the hydroxyl group. Although a wide variety of procedures are known,[1]
new methodologies are always desirable. Acetylation of tertiary alcohols
*
´
´ ´
Correspondence: Jesus Sandoval-Ramırez, Facultad de Ciencias Quımicas,
´ ´
Benemerita Universidad Autonoma de Puebla, Ciudad Universitaria, C.P. 72570
´
Puebla, Pue. Mexico; E-mail: jsandova@siu.buap.
4591
DOI: 10.1081/SCC-200043272
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

4592
Martinez-Pascual et al.
is particularly important, due to the fact that this functionality is prone
to elimination or to carbocationic rearrangement when drastic conditions
are employed. For example, attempts to acetylate the 3b,6b-diacetoxy-
5a-cholestan-5-ol (Fig. 1) led to the rearranged product instead of
acetylation.[2]
During our recent studies on the reactivity of the spiroketal side chain
[3,4]
.
of different steroidal sapogenins through BF3 OEt2 and acetic anhydride,
we found that in addition to the reaction involving the spiroketal moiety,
free hydroxyl groups were also acetylated in quantitative yields (Fig. 2).
Owing to this observation, we decided to explore this reaction as an
alternative procedure for the acetylation of different alicyclic and aliphatic
alcohols.
Treatment of solutions or suspensions of different alcohols in methylene
chloride (Table 1, entries a–d) or ethyl acetate (Table 1, entries e–g) with
.
BF3 OEt2 and acetic anhydride for 5 seconds resulted in acetylation of all
hydroxyl groups (Eq. 1). The acetylation reactions were run, with similar
results, using 2 mmol of substrate, but can be scaled up to 20 mmol. Using
these conditions, even tertiary hydroxyl groups were acetylated (see
Table 1, entry d).
Table 1 shows the results of the acetylation of steroidal and nonsteroidal
1
alcohols. Although H and 13C NMR indicated that the crude products were
pure enough for synthetic purposes, chromatographic purifications using
silica gel were carried out to eliminate the yellowish coloring developed
during the reactions.
Figure 1. Formation of an abeo-cholestane.

Fast and Convenient Acetylation of Alcohols
4593
Figure 2. Acetolysis of steroidal sapogenins.
EXPERIMENTAL
NMR spectra were registered in CDCl3 on a Varian Mercury spectrometer
at 400 MHz for 1H or 100 MHz for 13C. Chemical shifts are expressed in ppm
downfield from TMS. Melting points were obtained on a Mel-Temp apparatus
and were not corrected.
Table 1. Starting materials and products of acetylation.
Entry
a
Starting alcohol (1)
Product (2)
Yielda
85%
b
c
91%
75%
d
85%
e
f
100%
100%
100%
g
aYields (mol%) are given after chromatographic purification.

4594
Martinez-Pascual et al.
General Procedure for the Acetylation of Alcohols
To a solution or suspension of alcohols 1a–g (2 mmol, in all experiments)
in 5 mL of either CH2Cl2 (Entries a–d) or AcOEt (Entries e–g), Ac2O
.
(1 mL) and BF3 OEt2 (0.5 mL) were added in this order. The mixture was
stirred for 5 seconds, poured into ice/water, stirred for 15 min, and extracted
with selected solvents (2 Â 10 mL). The organic layer was washed with water
(3 Â 15 mL), 10% aqueous NaHCO3 (3 Â 15 mL) and water (3 Â 15 mL),
dried (anh. Na2SO4), and evaporated to afford the desired acetylated
product 2a–h.
1
Cholesteryl acetate, 2a. M.p 113–1158C. Lit[5] 114–1158C. H NMR: 5.4
(1H, m, H-6), 4.6 (1H, m, H-3), 2.03 (3H, s, CH3-AcO), 1.02 (3H, s, CH3-
19), 0.91 (3H, d, J20–21 ¼ 6.2 Hz, CH3-21), 0.86 (3H, d, J25–26 ¼ 6.6 Hz,
CH3-26), 0.86 (3H, d, J25–27 ¼ 6.6 Hz, CH3-27). 13C NMR: 37.06 (C-1),
27.86 (C-2), 73.95 (C-3), 38.18 (C-4), 139.45 (C-5), 122.51 (C-6), 31.93
(C-7), 31.98 (C-8), 50.06 (C-9), 36.65 (C-10), 21.14 (C-11), 39.58 (C-12),
42.36 (C-13), 57.70 (C-14), 24.38 (C-15), 28.33 (C-16), 56.14 (C-17), 11.98
(C-18), 19.42 (C-19), 35.88 (C-20), 18.83 (C-21), 36.26 (C-22), 23.95
(C-23), 39.79 (C-24), 28.10 (C-25), 22.94 (C-26), 22.69 (C-27), 170.25
(CH3COO), 21.55 (CH3COO).
5a-Cholestanyl acetate, 2b. M.p 108–1098C. Lit[5] 110–1118C. 1H NMR: 4.7
(1H, m, H-3), 2.02 (3H, s, CH3-AcO), 0.89 (3H, d, J20–21 ¼ 6.6 Hz, CH3-21),
0.85 (3H, d, J25–26 ¼ 6.6 Hz, CH3-26), 0.83 (3H, d, J25–27 ¼ 6.6 Hz, CH3-27).
13C NMR: 36.80 (C-1), 27.54 (C-2), 73.72 (C-3), 34.08 (C-4), 44.67 (C-5),
28.68 (C-6), 32.07 (C-7), 35.86 (C-8), 54.21 (C-9), 35.86 (C-10), 21.29 (C-11),
40.01 (C-12), 42.62 (C-13), 56.40 (C-14), 24.29 (C-15), 28.33 (C-16), 56.25
(C-17), 12.18 (C-18), 12.33 (C-19), 35.51 (C-20), 18.77 (C-21), 36.21 (C-22),
23.93 (C-23), 39.56 (C-24), 28.09 (C-25), 22.93 (C-26), 22.67 (C-27), 170.40
(CH3COO), 21.58 (CH3COO).
5a-Cholestan-3b,5,6b-triol triacetate, 2c. M.p 149–1518C. Lit[6] 149–
1
1508C. H NMR: 5.86 (1H, dd, J6e–7e ¼ 2.56, J6e–7a ¼ 2.94 Hz, H-6), 4.7
(1H, m, H-3), 2.81(1H, ddd, J4a–4e ¼ 13.56, J4e–3a ¼ 5.13, J4e–2e ¼ 1.8 Hz
H-4e), 2.07, 2.068, 2.0 (3H, s, 3CH3-AcO), 1.20 (3H, s, CH3-19), 0.91
(3H, d, J20–21 ¼ 6.6 Hz, CH3-21), 0.86 (3H, d, J25–26 ¼ 6.6 Hz, CH3-26),
0.85 (3H, d, J25–27 ¼ 6.6 Hz, CH3-27), 0.69 (3H, s, H-18). 13C NMR:
31.90 (C-1), 26.53 (C-2), 69.93 (C-3), 30.17 (C-4), 86.55 (C-5),
69.46 (C-6), 31.34 (C-7), 30.17 (C-8), 45.23 (C-9), 39.85 (C-10), 21.14
(C-11), 39.72 (C-12), 42.71 (C-13), 55.85 (C-14), 24.08 (C-15), 28.20
(C-16), 56.07 (C-17), 12.30 (C-18), 17.16 (C-19), 35.76 (C-20), 18.72

Fast and Convenient Acetylation of Alcohols
4595
(C-21), 36.14 (C-22), 23.79 (C-23), 39.51 (C-24), 28.04 (C-25), 22.61 (C-26),
22.87 (C-27), 169.93, 169.22, 169.07 (CH3COO), 22.23, 21.34, 21.33
(CH3COO).
3b, 19-Diacetoxypreg-5-en-20-one, 2d. M.p 101–1038C. Lit[5] 104–1058C.
1H NMR: 5.6 (1H, m, H-6), 4.6 (1H, m, H-3), 4.49 (1H, d, J ¼ 12 Hz H-19),
3.96(1H, d, J ¼ 12 Hz H-19), 2.13 (3H, s, H-21), 2.04, 2.03 (3H, s, CH3-AcO),
0.650 (3H, s, H-18). 13C NMR: 33.49 (C-1), 27.88 (C-2), 73.16 (C-3), 38.09
(C-4), 134.32 (C-5), 126.34 (C-6), 31.23 (C-7), 32.89 (C-8), 49.93 (C-9),
39.73 (C-10), 21.71 (C-11), 38.91 (C-12), 44.03 (C-13), 57.31 (C-14), 24.45
(C-15), 22.84 (C-16), 63.51 (C-17), 13.39 (C-18), 64.32 (C-19), 209.039
(C-20), 31.57 (C-21), 170.40, 170.28 (2CH3COO), 21.46, 21.15 (2CH3COO).
Heptyl acetate, 2e. B.p. 184–1858C/580 mmHg, Lit.[7] 1938C/760 mm Hg,
1H NMR: 4.05 (2H, t, J1–2 ¼ 6.4 Hz, H-1), 2.04 (3H, s, CH3-AcO), 1.67
(2H, q, J ¼ 6.4 Hz, H-2), 1.0 (8H, m, H-3,6), 0.89 (3H, t, J ¼ 7.2 Hz, H-7).
13C NMR: 64.55 (C-1), 31.71 (C-2), 28.92 (C-3), 28.60 (C-4), 25.89 (C-5),
22.59 (C-6), 14.08 (C-7), 170.89 (CH3COO), 21.00 (CH3COO).
(+)-1,3-Butanediol diacetate, 2f. B.p.102–1038C/26 mm Hg, Lit.[8]
92–948C/13 mm Hg. 1H NMR: 5.0 (1H, m, H-3), 4.11 (2H, t, J1–
¼ 5.9 Hz, H-1), 2.05, 2.04 (3H, s, 2CH3-AcO), 1.88 (2H, m, H-2),
2
1.26 (3H, d, J4–3 ¼ 6.2 Hz, H-4). 13C NMR: 60.67 (C-1), 34.66 (C-2),
67.69 (C-3), 20.04 (C-4), 170.62, 170.18 (2CH3COO), 21.21, 20.88
(2CH3COO).
2-Phenylethanol
acetate,
2g.
B.p.109–1118C/26 mmHg,
Lit.[8]
1
118–1208C/13 mmHg. H NMR: 7.32–7.20 (5H, aromatics), 4.27 (2H, t,
J1–2 ¼ 7.2 Hz, H-2), 2.93 (2H, t, J2–1 ¼ 7.2 Hz, H-1), 2.03 (3H, s, CH3-
AcO). 13C NMR: 35.10 (C-1), 64.89 (C-2), 137.56, 128.69, 128.30, 126.37
(aromatics), 170.74 (CH3COO), 21.03 (CH3COO).
.
In summary, the mixture BF3 OEt2/acetic anhydride constitutes a useful
alternative for the fast acetylation of alcohols in high yields.
ACKNOWLEDGEMENTS
We are indebted to CONACyT, Mexico, for financial support via grant
35235-E and the scholarships granted to R.M.P and O.V.B.

4596
Martinez-Pascual et al.
REFERENCES
1. (a) Greene, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis,
3rd Ed.; John Wiley and Sons: New York, 1999; (b) McOmie, J.F.W.
Protective Groups in Organic Chemistry; Plenum Press: New York,
1973; (c) Kocienski, J.K. Protecting Groups, Corrected Ed.; Georg
Thieme Verlag: Stuttgart, 2000; (d) Das, B.; Venkataiah, B.;
Madhusudhan, P. Selective acetylation of aliphatic hydroxyl group in
the presence of phenolic hydroxyl groups using silica gel supported
BF3 catalyst. Synth. Commun. 2002, 32, 249; (e) Breton, G.W. Selective
monoacetylation of unsymmetrical diols catalyzed by silica gel-supported
sodium hydrogen sulfate. J. Org. Chem. 1997, 62, 8952 and references
therein; (f) Gao, H.; Dias, J.R. Selective protection of hydroxyl
groups of cholic acid and derivatives. A review. Org. Prep. Proc. Int.
1999, 31, 145.
2. Fieser, L.; Fieser, M. Steroids; Reinhold: San Francisco, 1959;
325–327, and references therein.
´
3. Sandoval-Ramırez, J.; Castro-Mendez, A.; Meza-Reyes, S.; Reyes-
Vazquez, S.; Santillan, R.; Farfan, N. Preparation of 22,26-epoxy-
cholest-22-ene steroids. Novel transformation of the side chain in
sapogenins. Tetrahedron Lett. 1999, 40, 5143.
´
4. Sandoval-Ramırez, J.; Meza-Reyes, S.; del Rio, R.E.; Hernandez-
Linares, G.; Suarez-Rojas, A.; Rincon, S.; Farfan, N.; Santillan, R.L.
Regioselective cleavage of rings E and F in sarsasapogenin. Steroids
2003, 68, 199.
5. Hill, R.A.; Makin, H.L.J.; Kirk, D.N.; Murphy, G.M., Eds., Dictionary of
Steroids; Chapman and Hall: London, 1991.
6. Tarlton, E.J.; Fieser, M.; Fieser, L. J. Am. Chem. Soc. 1953, 75, 4433.
7. Lide, D.R., Ed.. Handbook of Chemistry and Physics, 77th Ed.; C.R.C:
Boca Raton, 1996.
8. Pollock, J.R.A.; Stevens, R., Eds.. Dictionary of Organic Compounds,
4th Ed.; Eyre & Spottiswoode Publ.: London, 1965.
Received in the USA August 24, 2004