1200
LETTER
Facile Acetylation of Alcohols, Ethers and Ketals with Catalytic FeCl3 in
AcOH#
G. V. M. Sharma*, A. K. Mahalingam, M. Nagarajan, A. Ilangovan, Palakodety Radhakrishna
Discovery Laboratory, Organic Chemistry Division III, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax +91-040-7173387/7173757; E-mail: esmvee@iict.ap.nic.in
Received 7 June 1999
Abstract: A simple and efficient protocol for the conversion of al-
cohols, ethers and ketals to acetates using catalytic FeCl3(5mol%)
in AcOH, or AcOH (3eq) in CH2Cl2 in very high yield is reported.
A variety of other acids such as CF3CO2H, HCO2H, CH2=CHCO2H,
CH3CH2CO2H, CH3(CH2)2CO2H have also been utilised for the
acylation of alcohols successfully.
Key words: esterification, acetylation, catalyst
Scheme 2
Generally primary alcohols underwent very fast acetyla-
tion, but in case of entries 6,7 and 8, longer reaction times
were required. This aspect could be partly attributed to bi-
dentate complexation of the catalyst. The secondary alco-
hols both in allylic, propargylic as well as steroid and
terpenoid substrates required longer reaction timings. In
the present reagent system, the tertiary alcohols (entries 8
and 14), were found unreacted. Under the similar reaction
conditions the acylation of decanol was also effected with
a variety of acids such as trifluoroacetic acid, formic acid,
acrylic acid, propionic acid and butyric acid (Table 1, en-
try 15) in good yields.
Functional group protection and deprotection is important
in synthetic organic chemistry.1 Amongst protecting
groups for alcohols, the esters are the most important with
acetate being the simplest and easiest of all. Acetylation2
is most commonly performed using3,4 reagents such as
Ac2O or AcCl in the presence of base, procedures which
are not environmentally friendly. The use of HOAc/min-
eral acid for acetylation suffers from the problem of re-
versibility. Later modifications involving the use of Lewis
acids5-10 in combination with Ac2O is inherently wasteful
since half of the every acid anhydride molecule is lost as
a carboxylic acid and the use of HOAc (as solvent)-lan-
thanide triflates11-13 whilst efficient, is expensive. Herein,
we report efficient FeCl3 (5mol%) catalysed conversion of
alcohols, ethers and ketals, by using either HOAc as sol-
vent or CH2Cl2-AcOH (3 equiv) into acetates (Scheme 1)
in very high yields.
We have extended this method to the one pot conversion
of ethers and ketals to acetates (Table 2). Compounds hav-
ing acid sensitive groups such as THP, TBS and TPS
ethers as well as ketal (entries 1, 2 and 3) underwent
deprotection with concomitant acetylation in the presence
of 0.3 equiv of FeCl3 in AcOH in 84-96% yields. In the
case of entry 3, with 0.3 equiv FeCl3, debenzylation was
not observed as reported.15
After the above general study, next it was aimed at the use
of equimolar quantity of AcOH for acetylation which not
only is cost effective but also simplifies the work up pro-
cedure. Accordingly, 4-phenyl butanol (entry 1, 1.0
mmol) in CH2Cl2 (5 mL) containing HOAc (3 equiv)-
FeCl3 (0.3 equiv) was efficiently converted into acetate in
90% yield over a period of 6h. Under the modified reac-
tion conditions, the acetylation was smooth and good
yielding, however duration of reaction was found to be
longer. The results of this study are summerised in Table
3.
Scheme 1
Initially, 4-phenyl butanol (entry 1, 1.0 mmol) in AcOH (5
mL) was treated with different mol% of FeCl3(commer-
cial) and 5 mol% was found to be optimal, giving (at room
temperature) the acetate14 in >95% yield in 1h. Having es-
tablished the reaction conditions, a wide variety of alco-
hols as shown in Table-I were subjected to acetylation to
give the desired acetates in 81-99% yield. The plausible
role of the FeCl3 may be the activation of acyl moiety by
coordination, triggering the acylation process with con-
comitant regeneration of FeCl3, followed by the loss of
water (Scheme 2).
Thus, in conclusion the present protocol offers a) mild re-
action conditions using cheaper catalyst such as FeCl3 (5
mol%)-AcOH for the efficient conversion of a wide vari-
ety of alcohols to acetates, b) acylation with other acids
such as trifluoroacetic acid, formic acid, acrylic acid,
propionic acid and butyric acid in good yields under the
Synlett 1999, No. 8, 1200–1202 ISSN 0936-5214 © Thieme Stuttgart · New York