Acetylation of alcohols catalyzed by dodeca-tungsto(molybdo)phosphoric acid

Article abstract of DOI:10.1007/s00706-006-0507-z

Acetylation of primary, secondary, and tertiary alcohols was carried out in some refluxing alkyl acetates and in two carboxylic acids with the participation of catalytic amounts of H₃PW₁₂O ₄₀, H₃PMo₁₂O₄₀, and H ₁₄P₅W₃₀O₁₁₀ with good yields and high stereo(regio)specificity under mild reaction condition. H ₃PW₁₂O₄₀ and H₃PMo ₁₂O₄₀ have also shown excellent reactivity in the formylation of 1-butanol with ethyl formate at room temperature and in short reaction times. Heteropolyacid catalysts could be separated after a simple work up and reused for several times. Springer-Verlag 2006.

Full text of DOI:10.1007/s00706-006-0507-z

Monatshefte f€ur Chemie 137, 1063–1069 (2006)
DOI 10.1007/s00706-006-0507-z
Acetylation of Alcohols Catalyzed
by Dodeca-tungsto(molybdo)phosphoric acid
Reza Tayebee1;ꢀ and Mohammad H. Alizadeh2
1
Department of Chemistry, Sabzevar University, Sabzevar, Iran
2
Department of Chemistry, Ferdowsi University, Mashhad, Iran
Received December 13, 2005; accepted (revised) February 1, 2006
Published online August 3, 2006 # Springer-Verlag 2006
Summary. Acetylation of primary, secondary, and tertiary alcohols was carried out in some refluxing
alkyl acetates and in two carboxylic acids with the participation of catalytic amounts of H3PW12O40,
H3PMo12O40, and H14P5W30O110 with good yields and high stereo(regio)specificity under mild reac-
tion condition. H3PW12O40 and H3PMo12O40 have also shown excellent reactivity in the formylation of
1-butanol with ethyl formate at room temperature and in short reaction times. Heteropolyacid catalysts
could be separated after a simple work up and reused for several times.
Keywords. Acetylation; Formylation; Heteropolyacid; Catalytic; Alcohol.
Introduction
The acetylation of hydroxyl groups is one of the most frequently used transforma-
tions in organic chemistry for the synthesis of valuable industrial and pharmaceu-
tical compounds, especially in the construction of polyfunctional molecules such as
nucleosides, carbohydrates, steroids, and natural products [1]. Therefore the pro-
tection of this functional group is of prime importance while carrying out reactions
sensitive to such functionality in a multifunctional substrate [1–3]. Among the
various protecting groups used for the hydroxyl function, acetyl is the most com-
mon group in view of its easy introduction, being stable to the acidic reaction
conditions, and also easily removable by mild alkaline hydrolysis [4–6]. Acetyl
chloride and acetic anhydride are generally used as acetylating agents in the pre-
sence of tributylphosphine or pyridine derivatives [7–9]. Lewis acid catalysts such
as Sc(OTf )3 [9], TMSOTf [10], Cu(OTf )2 [11], TaCl4 [12], In(OTf )3 [13], CoCl2
[14], and yttria-zirconia based Lewis acids have also been reported to be efficient
catalysts for acetylation of alcohols [15].
Homogeneouscatalysis with usingheteropolyoxometalateshas beenwidely devel-
oped in a broad range of organic synthesis and environmentally benign catalysis
ꢀ
Corresponding author. E-mail: Rtayebee@sttu.ac.ir

1064
R. Tayebee and M. H. Alizadeh
Scheme 1
during the past few decades. Good yields, high selectivity, economically conve-
nience, ease of work up, high stability and high catalytic activity of heteropolyacids
have motivated increasing potential for homogeneous catalysis in organic synthe-
sis, biomedical transformations, and environmentally benign catalysis [16–18].
Keggin-type heteropolyacids with the general formula of H8-x[XM12O40], where
X, x, and M are, respectively, the hetero-atom (e.g. P5þ or Si4þ), its oxidation state,
and the addenda atom (usually Mo6þ or W6þ), are the most common for industrial
catalysis such as oxidation of olefins, alkanes, alcohols, amines, and bond-breaking
of Sn–C [19–26].
Now, we wish to introduce the results of acetylation of some primary, secondary,
and tertiary alcohols with some alkyl acetates under reflux conditions catalyzed by
some Keggin-type heteropolyacids (Scheme 1). Since heteropolyacids are harmless
to the environment with respect to corrosiveness, safety, quantity of waste, and
separability, they are promising solid acid catalysts to replace environmentally
harmful liquid acid catalysts such as H2SO4 and other conventional solid acids
such as SiO2–Al2O3, H3PO4–SiO2, and zeolites [27–29].
Results and Discussion
Acetylation of some alcohols was studied in refluxing ethyl acetate mediated by
catalytic amounts of different acidic and anionic heteropolyoxometalates under mild
reaction conditions (Table 1) [30]. In a control experiment without any catalyst, no
acetylation was observed over the same or prolonged reaction time. Meanwhile,
phenols, thiols, and aromatic amines are unaffected under these reaction conditions.
Among the inspected catalysts, Mo-based heteropolyacid, H3PMo12O40, was the
most efficacious catalyst in the acetylation of 1-butanol and led to 92% of 1b within
2 h. Whereas, 85% of 1-butyl acetate was obtained in the presence of H3PW12O40 at
the same time. The Preyssler H14P5W30O110 has also revealed good catalytic activity
in the acetylation of 1-butanol. It provided 79% of 1-butyl acetate after 2 h. Although
H3PMo12O40 was a potent catalyst in the acetylation of 1a, its tetra-n-butyl ammo-
nium salt, (TBA)3PMo12O40, was almost inactive. Other W- and Mo-based catalysts,
such as Na6P2Mo18O62, K6P2W18O62, (TBA)7PW11O39, and Na3PW9Mo3O40 have
revealed the least catalytic activity in the acetylation of 1-butanol.

Acetylation of Alcohols
1065
Table 1. Acetylation of alcohols with ethyl acetate catalyzed by some heteropolyacidsa
Substrate
Catalyst
Time=h
Product
Yield=%
H3C(CH2)3OH (1a)
H3PW12O40
H3PMo12O40
H14P5W30O110
H3PMo12O40
H3PMo12O40
H3PMo12O40
Na3PW12O40
H14P5W30O110
H3PW12O40
H3PMo12O40
H3PMo12O40
H3PMo12O40
H3PMo12O40
H3PMo12O40
H14P5W30O110
H3PW12O40
Na3PW12O40
H3PMo12O40
H3PMo12O40
Na3PW12O40
H3PW12O40
H3PMo12O40
H3PW12O40
H3PMo12O40
H3PMo12O40
H3PMo12O40
H3PMo12O40
H3PMo12O40
2
2
2
2
2
2
2
2
2
2
2
2
2
1
1
1
1
1
2
6
2
2
6
6
2
2
6
6
H3C(CH2)3OAc (1b)
85
92
79
77
80
83
30
68
34
7
1a
1b
1a
H3C(CH2)2OH (1c)
H3C(CH2)5OH (1e)
H3C(CH2)6OH (1g)
1g
1b
H3C(CH2)2OAc (1d)
H3C(CH2)5OAc (1f)
H3C(CH2)6OAc (1h)
1h
C6H5CH2OH (1i)
1i
C6H5CH2OAc (1j)
1j
1i
1j
3-NO2–C6H4CH2OAc
4-Cl–C6H4CH2OAc
4-NO2–C6H4CH2OAc
(CH3)3COAc (1l)
1l
3-NO2–C6H4CH2OH
4-Cl–C6H4CH2OH
4-NO2–C6H4CH2OH
(CH3)3COH (1k)
1k
39
45
33
46
60
62
41
52
17
11
24
26
55
55
65
75
0
1k
1l
1k
1l
Adamantanol
(CH3)2CHOH (1m)
1m
Adamantanyl acetate
(CH3)2CHOAc (1n)
1n
1m
1n
(ꢁ)-Menthol
Cyclohexanol (1o)
1o
(ꢁ)-Menthyl acetate
Cyclohexyl acetate (1p)
1p
SH(CH2)4OH (1q)
4-OH–C6H4(CH2)2OH (1s)
C6H5NH2
SH(CH2)4OAc (1r)
4-OH–C6H4(CH2)2OAc (1t)
C6H5NHOAc
C6H5OAc
C6H5OH
0
a
Alcohol (2 mmol) was added to a solution of heteropolyacid (0.009 mmol) in ethyl acetate (4 cm3,
40 mmol) and the reaction mixture was allowed to stir at 65–70ꢂC for the required time; mol ratio of
catalyst:alcohol:ethyl acetate was 1:222:4444; progress of the reaction was followed by withdrawing
aliquots directly from the reaction mixture for GLC or TLC analysis; isolated yields were based on the
starting materials; all products were characterized by comparison of their spectral and physical data
with those of known samples
In order to extend the scope of this acetylation method, some linear, secondary,
and tertiary alcohols were exposed to the acetylation reactions catalyzed by
dodeca-tungsto(molybdo)phosphoricacids in refluxing ethyl acetate. In the acet-
ylation of linear alcohols, 1-propanol (1c), 1-butanol (1a), 1-hexanol (1e), and
1-heptanol (1g) were examined; among them 1-butanol has led to the highest yield.
The Preyssler H14P5W30O110 and Keggin H3PMo12O40 behaved alike in the acet-
ylation of benzyl alcohol (1i), whereas H3PW12O40 was obviously less effective
than the two above mentioned catalysts. These three catalysts have provided benzyl
acetate (1j) with 68, 70 and 34% yields, respectively, under the same reaction
t
conditions after 2 h. Butanol (1k) and 1-adamantanol, as tertiary alcohols, have
resulted in 46 and 52% of their corresponding acetates, respectively, catalyzed by

1066
R. Tayebee and M. H. Alizadeh
H3PMo12O40 after 1 h [31]. Isopropanol (1m) led to 17% of 1n with the mediation
of H3PMo12O40 after 2 h. Whereas cyclohexanol (1o) produced 55% of 1p with the
two above mentioned catalysts after 6 h. Cyclohexanol and isopropanol were
obviously less reactive than the other alcohols in the acetylation system. They have
provided <30% yields with H3PMo12O40 and H3PW12O40 after 3 h. To explore
stereoselectivity and regioselectivity of the acetylation method, catalytic acetyla-
tions of (ꢁ)-menthol, 2-mercaptoethanol (1q), and (ꢀ-hydroxyphenylethanol (1s)
were examined in ethyl acetate in the presence of H3PMo12O40. (ꢁ)-Menthol
afforded 26% of (ꢁ)-menthyl acetate; whereas 1q and 1s led to acetylation of only
the hydroxyl groups with 65 and 75% yields, respectively. Therefore, thiol and
phenol groups of 1q and 1s were unaffected under these reaction conditions. These
findings have confirmed stereo(regio)specificity of this acetylation procedure
among other present and useful methodologies.
To explore effects of phenyl substituents on the acetylation of benzyl alcohols,
ꢀ-chloro- and ꢀ-nitrobenzyl alcohols were exposed to the acetylation reactions with
ethyl acetate catalyzed by H3PMo12O40. Results have shown that chloro- and nitro-
substituents reduce efficacy of the acetylation. ꢀ-Chloro- and ꢀ-nitrobenzyl alco-
hols were converted to their corresponding acetates with 45 and 33% yields,
respectively, after 2 h. Whereas 70% yield was obtained with benzyl alcohol. Note-
worthy, chloro- and nitro-groups were unaffected under these reaction conditions.
Eventually, different reactivity patterns in the acetylation reactions may partly be
explained considering acid strength of catalyst and oxidation potential of the metal
center in catalyst.
Esterification of alcohols with carboxylic acids is among the fundamental and
routinely used functional transformations in organic chemistry. Traditionally, it is
performed using mineral or sulfonic acids as catalysts in the presence of excess of
either the alcohol or carboxylic acid to shift the equilibrium to the product side.
Table 2. Acylation of 1-butanol with some acylating agents catalyzed by heteropolyacidsa
Acetylating agent
Catalyst
Time=h
Yield=%
Ethyl acetate (2a)
H3PMo12O40
H3PMo12O40
H3PMo12O40
H3PMo12O40
H3PW12O40
H3PW12O40
H3PW12O40
H3PMo12O40
H14P5W30O110
H3PMo12O40
2
90b
100b
20d
95c
95c
91c
87b
85b
43b
75b
Acetic acid (2b)
1
Propionic acid (2c)
1
Ethyl formate (2d)
2d
15 min (rt)
5 min (reflux)
2d
15 min (rt)
Methyl acetate (2e)
2
2
1
2
2e
2e
Phenyl acetate
a
n-Butanol (0.18 cm3, 2 mmol) was added to a solution of heteropolyacid (0.009 mmol) in acylating
agent (40 mmol) and the reaction mixture was allowed to stir at 65–70ꢂC for the required time; mol
ratio of catalyst:alcohol:acetylating agent was 1:222:4444; progress of the reaction was followed by
withdrawing aliquots directly from the reaction mixture for GLC or TLC analysis; isolated yields were
based on the starting materials; bn-butyl acetate was formed; cn-butyl formate was produced; dn-butyl
propionate was formed

Acetylation of Alcohols
1067
The use of strong mineral acids, however, leads to waste streams posing environ-
mental problems for industrial processes. It is found that our catalytic system is
capable of efficient acetylation in carboxylic acids as in alkyl acetates. According
to the data in Table 2, acetic acid (2b) was more reactive than ethyl acetate (2a) in
the acylation of 1-butanol in the presence of H3PMo12O40. However, 2-chloropro-
pionic acid (2c) was clearly less reactive than ethyl acetate. The former produced
complete conversion after 1 h, whereas the substituted propionic acid led to 20%
yield at the same time.
Formylation is also an important transformation in organic synthesis. Although
various formylating reagents have been reported, there are still serious limitations
for the preparation of formates because of drastic reaction conditions, using
uncommon reagents, and formation of undesirable or toxic by-products [32–34].
Instability of the anhydride and acid chloride of formic acid led us to examine
formylation of 1-butanol by ethyl formate in this catalytic system. The results
introduced in Table 2 have demonstrated effective formylation of 1-butanol with
ethyl formate (2d). Formylation of 1-butanol could be driven to completion (>90%
yield) within 15 min.
In conclusion, an eco-friendly, clean, and cheap catalytic acetylation method
under mild reaction conditions using the simplest heteropolyacids has been devel-
oped for acetylation of a variety of primary, secondary, and tertiary alcohols in
good yields. Simple procedure, easy work up, regenerable catalyst, and high
stereo(regio)specificity, are other advantages of the acetylation method introduced
here.
Experimental
Materials and Instrumentation
Alkyl acetates, alcohols, and other solvents were commercially available, and their purity was mon-
itored by gas chromatography. All products were characterized by comparing their spectral and physical
data with those of known samples. Purity of the substances and progress of the reactions were monitored
by TLC on silica gel or by gas chromatography. GLC analyses were performed on a Shimadzu GC-17A
instrument equipped with a flame ionization detector using 25mꢃ0.25mm CPB(5–20) capillary
columns. H3PW12O40 and H3PMo12O40 were prepared according to the literature [35, 36] or were
purchased commercially. The heteropolyoxometalates Na3PW12O40 and H14[P5W30O110] were pre-
pared and characterized according to literature procedures as follows [37–39].
Synthesis of Na3PW12O40 ꢄ 7H2O
Na2WO4 ꢄ 2H2O (10 g, 30 mmol) was slowly added to 20cm3 distilled water and the mixture was
warmed to 60ꢂC with stirring. Then, H3PO4 85% (1cm3, 15mmol,) and HCl (8cm3, 100 mmol) were
added and the resulting mixture was stirred for 1 h. The white afforded precipitate was washed with
water and was recrystallized twice from hot water.
Preparation of Preyssler’s Anion K12.5Na1.5[NaP5W30O110] and it’s acidic form, H14[P5W30O110
]
The potassium salt was prepared following Alizadeh’s method [39], or a slight variation thereof.
ortho-Phosphoric acid 90% (75 cm3, 1.2 mol) was slowly added to 50 cm3 aqueous solution of
Na2WO4 ꢄ 2H2O (99 g, 0.3 mol) at 45ꢂC and the resulting mixture was refluxed for 5 h. Then, the ob-
tained solution was diluted by 15 cm3 water. Thereafter, powdered KCl (22.5 g, 0.32 mol) was slowly
added to the vigorously stirred above solution during 35 min at rt. The pale green impure precipitate

1068
R. Tayebee and M. H. Alizadeh
was filtered off and was washed with CH3COOK (0.1M). The white needle-like crystals of potassium
salt of the Preyssler’s anion were recrystallized from hot water.
The free acid was prepared by passage of a solution of 11.4g potassium salt in 20cm3 water
through a column (50ꢃ1 cm) of Dowex 50WX8 in the Hþ form. Evaporation of the elute to dryness in
vacuum resulted in H14[P5W30O110].
General Procedure for Acetylation of 1-Butanol with Ethyl Acetate Catalyzed by H3PMo12O40
To a stirred solution of H3PMo12O40 (0.03 g, 0.009 mmol) in ethyl acetate (4cm3, 40mmol), was added
1-butanol (0.18 cm3, 2 mmol) and the reaction mixture was allowed to stir at 65–70ꢂC for the required
time. Progress of the reaction was followed by aliquots withdrawn directly from the reaction mixture,
analyzed by gas chromatography using internal standard or by TLC using ethyl acetate hexane (1=5)
mixture as eluent. After completion of the reaction, ethyl acetate was removed under reduced pressure
and ether was added. Evaporation of the organic solution was followed by column chromatography on
a short pad of silica gel using petroleum ether as eluent to afford 1-butyl acetate as a liquid. The residue
on silica gel was washed with a mixture of water ethanol (1=1) to dissolve the catalyst. Thereafter, the
catalyst could be separated and reused several times after vacuum drying. However, the catalyst
activity was gradually declining in successive runs. The yield of 1-butyl acetate produced from the
reaction of 1-butanol with ethyl acetate promoted by the recovered H3PMo12O40 for three times
remained 90–92% and after six times was 75–78% under the reaction conditions described here.
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