A mild and efficient method for the methoxymethylation and acetylation of alcohols promoted by benzyltriphenylphosphonium tribromide

Article abstract of DOI:10.1016/j.cclet.2010.04.031

A mild and efficient method for the conversion of alcohols to their corresponding methoxymethyl ethers and acetates using benzyltriphenylphosphonium tribromide (BTPTB) as catalyst is described. All reactions were performed under completely heterogeneous reaction conditions in good to high yields.

Full text of DOI:10.1016/j.cclet.2010.04.031

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Chinese Chemical Letters 21 (2010) 1187–1190
www.elsevier.com/locate/cclet
A mild and efficient method for the methoxymethylation and
acetylation of alcohols promoted by benzyltriphenylphosphonium
tribromide
b
a,b
Farhad Shirini a, , Gholam Hossein Imanzadeh , Seyyed Ali Reza Mousazadeh ,
*
Iraj Mohammadpoor-Baltork c, Masoumeh Abedin a
a Department of Chemistry, College of Science, University of Guilan, Rasht 41335, Iran
b Department of Chemistry, College of Science, University of Mohaghegh-Ardabili, Ardabil, Iran
c Department of Chemistry, College of Science, Isfahan University, Isfahan, Iran
Received 24 February 2010
Abstract
A mild and efficient method for the conversion of alcohols to their corresponding methoxymethyl ethers and acetates using
benzyltriphenylphosphonium tribromide (BTPTB) as catalyst is described. All reactions were performed under completely
heterogeneous reaction conditions in good to high yields.
# 2010 Farhad Shirini. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Benzyltriphenylphosphonium tribromide; Alcohols; Methoxymethylation; Acetylation; Heterogeneous reaction conditions
Methoxymethyl ethers, as important and stable derivatives of alcohols, are frequently prepared by the alkylation
of alcohols with excess amounts of chloromethylether (CME) in alkaline solution [1]. In spite of the applicability
of this method, the potent carcinogenic properties of CME [2], is considered as an important reason to encourage
organic chemists to use formaldehyde dimethoxy acetal (FDMA), as an inexpensive and commercially available
reagent, instead of this reagent. Even though handling of FDMA is easy and use of this reagent needs no special
precautions, the low methoxymethylating power is the main drawback for the application of FDMA. To improve
the methoxymethylating power of FDMA, a variety of catalysts have been reported of them scandium
trifluoromethane sulfonate [3], bismuth triflate [4], phenylsulfonic acid functionalized mesoporous silica [5], silica
sulfuric acid [6], Al(HSO4)3 [7], P2O5 [8], p-toluenesulfonic acid [9], expensive graphite [10], Nafion-H [11],
MoO2(acac)2 [12] and FeCl3 dispersed on molecular sieves 3A [13] are examples. Although these methods are an
improvement, most of them suffer from disadvantages such as long reaction times, harsh reaction conditions, use
of toxic or expensive reagents, tedious work-up and un-applicability in the methoxymethylation of tertiary
alcohols.
* Corresponding author.
E-mail address: shirini@guilan.ac.ir (F. Shirini).
1001-8417/$ – see front matter # 2010 Farhad Shirini. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.04.031

[(Scheme_1)TD$FIG]
1188
F. Shirini et al. / Chinese Chemical Letters 21 (2010) 1187–1190
Scheme 1.
1. Experimental
Chemicals were purchased from Merck, Fluka, and Aldrich Chemical Companies. Products were separated and
identified by the comparison of their mp, IR, NMR, and bp with those reported for the authentic samples, and also by
Table 1
Methoxymethylation and acetylation of alcohols catalyzed by BTPTBa,b,c,d
.
Entry
Product
Time (min)
Yield (%)
1
2
4-ClC6H4CH2OMOM
2-BrC6H4CH2OMOM
3,4-Cl2C6H3CH2OMOM
4-Me2CHC6H4CH2OMOM
4-Me3CC6H4CH2OMOM
PhCH(OMOM)CH3
17
23
25
13
25
45
90
23
10
35
96
92
95
90
95
92
80
95
90
90
3
4
5
6
7
Ph2CH(OMOM)
8
PhCH2CH2OMOM
9
PhCH2CH2CH2OMOM
PhCH(Me)CH2OMOM
10
11
12
55
92
[DT$INLE]
25
90
[DT$INLE]
13
14
40
40
95
92
[DT$INLE]
[DT$INLE]
15
16
17
18
19
20
21
22
23
24
25
4-ClC6H4CH2OMOM
4-ClC6H4CH2OAc
2-ClC6H4CH2OAc
2,4-Cl2C6H3CH2OAc
2-MeC6H4CH2OAc
4-Me2CHC6H4CH2OAc
4-NO2C6H4CH2OAc
2-NO2C6H4CH2OAc
C6H5CH(OAc)Me
60
10
12
8
0e
90
90
85
92
85
90
85
85
85
90
7
7
25
55
15
8
PhCH2CH2CH2OAc
PhCH(Me)CH2OAc
8
26
13
87
[DT$INLE]
27
18
90
[DT$INLE]
28
29
30
2-Adamantanyl acetate
PhCH2C(OAc)Me2
5
60
15
85
60
92
1-Adamantanyl acetate
a
NMR spectroscopy.
b
c
d
e
Isolated yields.
Methoxymethylation was performed in the presence of 0.1 mmol of BTPTB.
Acetylation was performed in the presence of 0.05 mmol of BTPTB.
Reaction was performed in the absence of BTPTB.

[(Scheme_2)TD$FIG]
F. Shirini et al. / Chinese Chemical Letters 21 (2010) 1187–1190
1189
Scheme 2.
regeneration of the corresponding alcohols. All yields refer to the isolated products. 1H NMR spectra were recorded on
JNM-EX 90A or Bruker-DRX MH2 NMR spectrometers.
1.1. General procedure
A mixture of the substrate (1 mmol), Ac2O (2 mmol, 0.21 g) and/or FDMA (3 mmol, 0.228 g) and BTPTB
[0.05 mmol, 0.03 g (used for acetylation) or 0.1 mmol, 0.06 g (used for methoxymethylation)] was stirred in refluxing
CHCl3 (3 mL). The progress of the reaction was monitored by TLC. After completion of the reaction, the solvent was
evaporated, and Et2O (5 mL) was added. The mixture was filtered and the solid residue was washed with Et2O (5 mL).
The filtrate was washed with saturated solution of NaHCO3 and H2O and dried over MgSO4. Evaporation of the
solvent followed by column chromatography on silica gel gave the corresponding acetates and/or methoxymethyl
ethers in good to high yields.
2. Results and discussion
Recently, benzyltriphenylphosphonium tribromide (BTPTB) has been prepared and used as an efficient catalyst in
different types of reactions [14–18]. On the basis of these studies and in continuation of our ongoing research program
on the development of new methods for functional group transformations [19–23], herein, we wish to report the
applicability of BTPTB in the promotion of the methoxymethylation and acetylation of alcohols with FDMA and
Ac2O, respectively. All reactions were performed in CHCl3 at reflux temperature and under completely heterogeneous
reaction conditions in excellent yields (Scheme 1 and Table 1).
As shown in Table 1, different types of alcohols, including primary, benzylic, hindered and unhindered secondary
and hindered tertiary ones are efficiently converted to their corresponding methoxymethyl ethers and acetates under
the selected conditions. It is important to note that the progress of the reaction is so depends to the presence of BTPTB
in the reaction mixture, which the reaction did not proceed in the absence of this reagent even after prolonged heating
(Table 1, entry15). Also, by-products resulting from the bromination of the starting materials were not observed during
the course of the reaction.
In 1987, Kajigaeshi reported that organic ammonium tribromides such as benzyltrimethylammonium tribromide
generate HBr and MeOBr in methanol [24]. On the basis of this and obtained results, the mechanism which is shown in
Scheme 2, is selected as the most plausible one for the methoxymethylation and acetylation of alcohols catalyzed by
BTPTB.
Table 2
Comparison of some of the results obtained by our method (1) with some of those reported by Sc(OTf)3 (2) [3], Bi(OTf)3 (3) [4], Al(HSO4)3 (4) [7],
N,N-dichloro-4-methylbenzenesulphonimide (5) [25], and 3-nitrobenzeneboronic acid (6) [26].
Entry
Product
Time (h)/yield (%)
1
2
3
4
5
6
1
2
PhCH(OMOM)Me
0.75/92
0.42/90
–
2/95
4/85
3/88
–
–
–
–
7/80
17.5/85
[TD$INLINE]
3
0.67/92
7/77
–
8.5/75
–
–
[TD$INLINE]
4
5
4-NO2C6H4CH2OAc
0.42/90
0.25/92
–
–
–
–
–
–
48/97
13/97
12/94
16/89
[TD$INLINE]

1190
F. Shirini et al. / Chinese Chemical Letters 21 (2010) 1187–1190
To illustrate the efficiency of the proposed method, Table 2 compares some of the results with some of those
reported in the literature [3,4,7,25,26].
In conclusion, we developed an efficient and high yielding method for the methoxymethylation and acetylation of
alcohols. Relatively short reaction times, high efficiency, heterogeneous reaction conditions, and easy work-up are
among the other advantages of this method, which make this procedure a useful and attractive addition to the available
methods.
Acknowledgment
We are thankful to the University of Guilan and Mohaghegh-Ardabili University Research Councils for the partial
support of this work.
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