Oxidative methyl esterification of primary alcohols with iodine-mediated poly[4-(diacetoxyiodo)styrene]

Article abstract of DOI:10.1002/jccs.200700160

An operationally simple oxidative methyl esterification of primary alcohols in good yields using an iodine-mediated poly[4-(diacetoxyiodo)styrene] in methanol at room temperature is described. The polymeric reagent can be regenerated and reused as an environmentally benign reagent.

Full text of DOI:10.1002/jccs.200700160

Journal of the Chinese Chemical Society, 2007, 54, 1119-1122
1119
Communication
Oxidative Methyl Esterification of Primary Alcohols with Iodine-Mediated
Poly[4-(diacetoxyiodo)styrene]
Xiao-Ling Liu (
), Shu-Ying Lin (
), Shou-Ri Sheng* (
),
Mei-Hong Wei (
College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330027, P. R. China
) and Bin Gong (
)
An operationally simple oxidative methyl esterification of primary alcohols in good yields using an
iodine-mediated poly[4-(diacetoxyiodo)styrene] in methanol at room temperature is described. The poly-
meric reagent can be regenerated and reused as an environmentally benign reagent.
Keywords: Oxidation; Alcohol; Carboxylic acid methyl ester; Poly[4-(diacetoxyiodo)styrene];
Iodine.
It is well known that the transformation of a carbox-
ylic acid into an ester is one of the most important reactions
in organic synthesis.1 The oxidation of alcohols to carbonyl
compounds is a fundamental organic transformation, and
numerous methods utilizing various reagents have been re-
ported.2 One of the most useful and efficient approaches is
the direct oxidative transformation of alcohols to the corre-
sponding esters in one step. Many methods have been de-
veloped for this direct transformation, among which the
oxidation of primary alcohols to esters using hypervalent
iodine(III) reagents such as PhI(OAc)2 (DIB),3 etc. is an
important procedure. Hypervalent iodine(III) reagents have
now been widely used in organic synthesis due to their mild
reaction conditions, high selectivity and low toxicity.4,5 De-
spite the simple experimental operation and low toxicity
with DIB, it has a major shortcoming: the iodobenzene
formed is difficult to separate from the product and is hard
to reuse. Polymer supported trivalent iodine reagents could
solve the problem. After the reaction, the poly(4-iodosty-
rene) formed could be easily removed from the reaction
mixture just by filtration and reused. Recently, Kita et al6
reported the oxidation of primary alcohols to the corre-
sponding carboxylic acid esters with poly[4-(diacetoxy-
iodo)styrene](PSDIB)/KBr in methanol. As a part of our
study on environmentally friendly organic synthesis with
polymeric hypervalent iodine,7 we here would like to re-
port another operationally simple and environmentally be-
nign oxidation of primary alcohols to the corresponding
carboxylic acid esters in methanol, using an iodine-mediated
PSDIB system at room temperature as shown in Scheme I.
Scheme I
I(OAc)2
RCH2OH
RCOOMe
+
I
I2, CH3OH, rt
1
2
PSDIB was prepared from commercial polystyrene
(MW = 45,000) according to a literature method.8 With the
PSDIB in hand, we have selected the model oxidation reac-
tion of benzyl alcohol (1.0 mmol) and PSDIB (2.0 mmol)
with molecular iodine in methanol (10 mL) with stirring in
an open vessel for a given time in Table 1 at room tempera-
ture to examine this process. Seen from Table 1, the oxida-
tive conversion did not proceed at all without iodine (Entry
1). The reaction with 0.1 equiv of iodine was rather slow
(entry 2), and the reaction with 0.5 equiv of iodine was the
most effective for conversion of benzyl alcohol (1a) to the
corresponding methyl ester (2a) in 92% yield (entry 3). Ad-
ditionally, we found that other alcohols such as ethanol,
1-propanol, and 2-propanol also provide their correspond-
ing esters in moderate to good yields, although oxidation in
t-butyl alcohol furnished benzoic acid as the sole product
(entries 5-8). Having succeeded with methyl benzoate (2a)
formation, we then further investigated the direct oxidative
* Corresponding author. E-mail: shengsr@jxnu.edu.cn

1120 J. Chin. Chem. Soc., Vol. 54, No. 5, 2007
Liu et al.
Table 1. Oxidation of primary alcohols to the corresponding esters in methanol using
PSDIB/I2
Entry
Substrate (1)
Time (h)
Product (2)
Yield (%) a
1
C6H5CH2OH (1a)
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
4
4
4
(2a) b
0
2
C6H5CH2OH (1a)
(2a) c
55
92
89
82
75
70
88
84
86
85
84
88
90
86
88
90
91
3
C6H5CH2OH (1a)
(2a) d
(2a) e
PhCOOEt f
n-PrOCOPh g
i-PrOCOPh h
PhCOOH i
(2b)
4
C6H5CH2OH (1a)
5
C6H5CH2OH (1a)
6
C6H5CH2OH (1a)
7
C6H5CH2OH (1a)
8
C6H5CH2OH (1a)
9
4-CH3C6H4CH2OH (1b)
4-CH3OC6H4CH2OH (1c)
4-ClC6H4CH2OH (1d)
3,4-(MeO)2C6H3CH2OH (1e)
4-NO2C6H4CH2OH (1f)
(E)-C6H5CH=CHCH2OH (1g)
Phenylpropiolic alcohol (1h)
C6H5CH2CH2OH (1i)
Cyclohexylcarbinol (1j)
CH3(CH2)5CH2OH (1k)
10
11
12
13
14
15
16
17
18
(2c)
(2d)
(2e)
(2f)
(2g)
(2h)
(2i)
(2j)
(2k)
a Isolated yield; b Without iodine; c I2 (0.1 equiv); d I2 (0.5 equiv); e By applying PSDIB
recycled 4 times; f EtOH was used in place of methanol; g n-PrOH was used in place of
methanol; h i-PrOH was used in place of methanol; i t-BuOH was used in place of methanol.
methyl esterification of other primary alcohols. As antici-
pated, various primary alcohols (1a-1k) were converted
smoothly to their corresponding carboxylic acid methyl es-
ters (2a-2k) with good yields and in short reaction times
(4-5 h) under similar experimental conditions. It should be
noted that both substituted benzylic alcohols either with
electron releasing or withdrawing substituents (entries 9-
13) and primary aliphatic alcohol (entries 16-18) afforded
their corresponding methyl esters in equally good yields.
Interestingly, olefinic and alkynyl alcohols such as cinna-
myl alcohol (entry 14) and phenylpropiolic alcohol (entry
15) were also oxidized efficiently without any observable
reaction at the carbon-carbon double and triple bond func-
tionality. After the reaction with PSDIB, the formed poly-
(4-iodostyrene) was nearly quantitatively recovered by
simple filtration with an addition of water. The recovered
poly(4-iodostyrene) was again oxidized with peracetic
acid, prepared from the reaction of hydrogen peroxide and
acetic anhydride to afford PSDIB. To show the reactivity of
the regenerated polymeric reagent, the conversion of ben-
zyl alcohol (1a) to methyl benzoate (2a) was repeated four
times using the same batch of regenerated PSDIB after
each reaction. As seen from Table 1 (entry 4), the yield of
2a remained almost the same as when the first prepared
PSDIB was used, which showed that the PSDIB has good
recyclable reactivity for this conversion. The possible mech-
anism of the formation of carboxylic acid methyl esters 2 is
shown in Scheme II.
Scheme II
PhI(OAc)2
PhI
+
2 CH3COOI
+
I2
CH3COOI
AcOH
AcOH
RCH2OH
I2
+
+
CH3COOI
RCH2OI
RCHO
CH3COOI
AcOH
CH3COOI
AcOH
I
H
OH
O
C
+
+
I2
RCHO
MeOH
RCOOMe
C
R
OMe
H
R
OMe

Synthesis of Carboxylic Acid Methyl Ester
J. Chin. Chem. Soc., Vol. 54, No. 5, 2007 1121
In summary, we have developed a simple and effi-
cient procedure for the direct oxidation of primary alcohols
into methyl esters using poly[4-(diacetoxy)iodo]styrene in
combination with molecular iodine. This one-step reaction
is facile, high yielding and uses only readily available start-
ing materials; moreover, the polymeric reagent can be re-
generated and reused as an environmentally benign re-
agent.
2H), 7.15 (d, J = 8.7 Hz, 2H), 3.84 (s, 3H), 2.34 (s, 3H); IR
(neat) nmax 1727 cm-1.
Methyl p-methoxybenzoate (2c)9: Colorless solid;
mp 48-49 oC (lit. mp 49-51 oC); 1H NMR d 7.87 (d, J = 8.7
Hz, 2H), 7.12 (d, J = 8.7 Hz, 2H), 3.85 (s, 3H), 3.75 (s, 3H);
IR (neat) nmax 1725 cm-1.
Methyl p-chlorobenzoate (2d)9: Colorless solid; mp
43-44 oC (lit. mp 42-44 oC); 1H NMR d 7.95 (d, J = 8.8 Hz,
2H), 7.35 (d, J = 8.8 Hz, 2H), 3.80 (s, 3H); IR (neat) nmax
1718 cm-1.
EXPERIMENTAL SECTION
Methyl 3,4-dimethoxybenzoate (2e)9: Colorless
solid; mp 60-61 oC (lit. mp 59-62 oC); 1H NMR d 7.83 (d, J
= 8.7 Hz, 1H), 7.32 (s, 1H), 7.14 (d, J = 8.7 Hz, 1H), 3.83 (s,
3H), 3.75 (s, 3H), 3.73 (s, 3H); IR (neat) nmax 1726 cm-1.
Methyl p-nitrobenzoate (2f)9: Pale yellow solid; mp
91-92 oC (lit. mp 90-92 oC); 1H NMR d 8.25 (d, J = 8.8 Hz,
2H), 7.65 (d, J = 8.8 Hz, 2H), 3.90 (s, 3H); IR (neat) nmax
1735, 1528 cm-1.
Methyl trans-cinnamate (2g)9: Colorless solid; mp
36-37 oC (lit. mp 36-38 oC); 1H NMR d 7.57 (d, J = 15.8 Hz,
1H), 7.11-6.90 (m, 3H), 7.10 (d, J = 15.8 Hz, 1H),
6.82-6.71 (m, 2H), 3.80 (s, 3H); IR (neat) nmax 1720, 1635
cm-1.
Polystyrene (average MW = 45,000), all primary al-
cohols except MeOH, EtOH, n-PrOH, i-PrOH and t-BuOH
were purchased from Aldrich and used directly without fur-
1
ther purification. Melting points were uncorrected; H
NMR spectra were recorded on a Bruker Avance 400 MHz
spectrometer using CDCl3 as the solvent and with TMS as
internal standard; IR spectra were determined on a Perkin-
Elmer SP One FT-IR spectrophotometer. Poly[4-(diacet-
oxy)iodo]styrene containing 1.85 mmol/g of functional
group by elemental analysis was prepared according to the
reported method.8
Methyl 3-phenylpropynoate (2h)10: Oil, 1H NMR d
7.60-7.45 (m, 2H), 7.31-7.22 (m, 3H), 3.81 (s, 3H); IR
(neat) nmax 2110, 1721 cm-1.
General procedure for the synthesis of carboxylic
acid methyl esters 2
1
To a stirred solution of primary alcohol 1a (1.0 mmol),
iodine (0.5 mmol) in methanol (10 mL) was added PSDIB
(2.0 mmol, 1.08 g), and the mixture was stirred at room
temperature in an open vessel for the times mentioned in
Table 1. After the reaction, the mixture was quenched with
water (30 mL) and filtered to remove the polymer species,
which was then washed with ether (3 × 5 mL). The filtrate
was extracted with ether (2 × 15 mL), washed with water
and dried with magnesium sulfate. The solvent was evapo-
rated under reduced pressure and the residue was purified
by column chromatography on silica gel using ethyl ace-
tate/hexane (10/1) as eluent to give pure products 2a-2k.
Methyl 2-phenylethanoate (2i)11: Oil, H NMR d
7.35-7.27 (m, 5H), 3.71 (s, 3H), 3.62 (s, 2H); IR (neat) nmax
1730 cm-1.
Methyl cyclohexylmethanoate (2j)11: Oil, 1H NMR
d 3.61 (s, 3H), 2.26-2.23 (m, 1H), 1.86-1.82 (m, 2H),
1.71-1.64 (m, 2H), 1.60-1.57 (m, 1H), 1.41-1.30 (m, 2H),
1.26-1.17 (m, 3H); IR (neat) nmax 1741 cm-1.
1
Methyl n-heptylate (2k)9: Oil, H NMR d 3.62 (s,
3H), 2.26 (t, J = 7.5 Hz, 2H), 1.60-1.53 (m, 2H), 1.26-1.22
(m, 6H), 0.85 (t, J = 7.1 Hz, 3H); IR (neat) nmax 1743 cm-1.
1
All these esters were characterized by H NMR and IR
ACKNOWLEDGEMENTS
spectral analysis and by comparison with authentic com-
pounds.
We gratefully acknowledge financial support from
the National Natural Science Foundation of China (No.
20562005) and NSF of Jiangxi Province (No. 0620021).
Methyl benzoate (2a)9: Oil; 1H NMR d 8.01-7.93 (m,
2H), 7.51-7.40 (m, 3H), 3.90 (s, 3H); IR (neat) nmax 1725
cm-1.
Methyl p-methylbenzoate (2b)9: Colorless solid; mp
35-36 oC (lit. mp 33-36 oC); 1H NMR d 7.89 (d, J = 8.7 Hz,
Received February 6, 2007.

1122 J. Chin. Chem. Soc., Vol. 54, No. 5, 2007
Liu et al.
Huang, H.-Y.; Hou, R.-S.; Wang, H.-M.; Chen, L.-C. J.
Chin. Chem. Soc. 2004, 51, 1377. (c) Huang, H.-Y.; Wang,
H.-M.; Hou, R.-S.; Chen, L.-C. J. Chin. Chem. Soc. 2004,
51, 1025. (d) Chen, J.-M.; Huang, X. Synlett 2004, 552. (e)
Chen, J.-M.; Huang, X. Synthesis 2004, 1577. (f) McQuaid,
K. M.; Pettus, T. R. R. Synlett 2004, 2403. (g) Justik, M. W.;
Koser, G. F. Tetrahedron Lett. 2004, 45, 6159. (h) Tashino,
Y.; Togo, H. Synlett 2004, 2010. (i) Karade, N. N.; Tiwari,
G. B.; Huple, D. B. Synlett 2005, 2039. (j) Hossain, M. D.;
Kitamura, T. Synthesis 2005, 1932.
REFERENCES
1. (a) Mitsunobu, O. Synthesis 1981, 1. (b) Ogliaruso, M. A.;
Wolfe, J. F. Synthesis of Carboxylic Acids, Esters and Their
Derivatives; Patai, S.; Pappoport, Z., Eds.; John Wiley &
Sons, Inc.: New York, 1991. (c) Hughes, D. L. Org. React.
1992, 42, 335. (d) Sutherland, I. O. Comprehensive Organic
Chemistry; Barton, D. H. R.; Ollis, W. D., Eds.; Pergamon
Press: Oxford, 1997; Vol. 6, p 871.
2. (a) Larock, R. C. In Comprehensive Organic Transforma-
tions; 2nd Eds.; Wiley-VCH: New York, 1991; p 1197. (b)
Muzart, J. Chem. Rev. 1992, 92, 113.
6. Tohma, H.; Maegawa, T.; Kita, Y. Synlett 2003, 723.
7. Huang, Z.-Z.; Sheng, S.-R.; Liu, X.-L.; Lin, S.-Y.; Huang,
R.-S. J. Chin. Chem. Soc. 2006, 53, 991.
3. Karade, N. N.; Tiwari, G. B.; Huple, D. B. Synlett 2005,
2039.
8. Abe, S.; Sakuratani, K.; Togo, H. J. Org. Chem. 2001, 66,
6174.
4. For recent reviews, see: (a) Stang, P. J.; Zhdankin, V. V.
Chem. Rev. 1996, 96, 1123. (b) Kitamura, T.; Fujiwara, Y.
Org. Prep. Org. Proc. Int. 1997, 29, 411.
9. Catalog handbook of fine chemicals, Aldrich Chemical Co.
2003-2004.
10. Benghiat, I.; Becker, E. I. J. Org. Chem. 1958, 23, 885.
11. Chen, M.-Y.; Lee, A. S.-Y. J. Chin. Chem. Soc. 2003, 50,
103.
5. For several recent examples on hypervalent iodine reagents
in organic synthesis, see: (a) Kang, I.-J.; Wang, H.-M.; Lin,
M.-L.; Chen, L.-C. J. Chin. Chem. Soc. 2002, 49, 1031. (b)