Facile conversion of alcohols to the corresponding 2,2,2-trifluoroethyl esters with molecular iodine and potassium carbonate in 2,2,2-trifluoroethanol

Article abstract of DOI:10.1055/s-2004-817789

A simple, effective, and high-yield procedure for the oxidative conversion of primary alcohols to the corresponding 2,2,2-trifluoroethyl esters, with molecular iodine and potassium carbonate in 2,2,2-trifluoroethanol, was studied.

Full text of DOI:10.1055/s-2004-817789

880
LETTER
Facile Conversion of Alcohols to the Corresponding 2,2,2-Trifluoroethyl
Esters with Molecular Iodine and Potassium Carbonate in 2,2,2-Trifluoro-
ethanol
F
acile Conversion
a
of
A
lcohol
o
s
to the Corre
s
sponding
h
2,2,2-Trifluo
i
roethyl
E
ster
M
s
ori,a Hideo Togo*a,b
a
Graduate School of Science and Technology, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba 263-8522, Japan
b
Department of Chemistry, Faculty of Science, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba 263-8522, Japan
E-mail: togo@faculty.chiba-u.jp
Received 15 January 2004
molecular iodine in such fluorinated alcoholic solvents
have not appeared, while the electrochemical conversion
of alcohols to the corresponding ketones or esters using
potassium iodide via the formation of iodonium ion spe-
cies generated by electroxidation was reported.9 Thus, we
tried the direct oxidative conversion of alcohols to the es-
ters with molecular iodine in the presence of potassium
carbonate. Table 1 shows the effect of a protic polar sol-
vent, i.e. t-butanol, ethanol, methanol, water, and 2,2,2-
trifluoroethanol in the oxidative conversion of p-methyl-
benzyl alcohol to the corresponding esters or acid (with
water), and it indicates 2,2,2-trifluoroethanol provides the
corresponding 2,2,2-trifluoroethyl ester in high yield (en-
try 8). Thus, less acidic solvents such as water, methanol,
ethanol, t-butanol give the ester or acid products in low
yields. Since it is known that pKa value of 2,2,2-trifluoro-
ethanol is ca. 12.4,10 the result suggests that the present
reaction is promoted by the acidic polar solvent. Thus,
2,2,2-trifluoroethanol activates molecular iodine as an
oxidant. Recently, it has been known that 2,2,2-trifluoro-
ethanol sometimes promotes the reactions; therefore, syn-
thetic use of 2,2,2-trifluoroethanol as a solvent is
interesting.11 For example, 2,2,2-trifluoroethanol acti-
vates hydrogen peroxide for the oxidation of thiols to di-
sulfides,11a epoxidation of olefins,11b–d Mn(III)/Cu(II)-
mediated oxidative radical cyclization of a-(methyl-
thio)acetamides,11e Et3N-induced b-cleavage reaction,11f
etc. The addition of a small amount of methanesulfonic
acid to the methanol or ethanol solvent was not effective.
The present reaction requires potassium carbonate as a
base (entry 6). Though 1,1,1,3,3,3-hexafluoro-2-propanol
(pKa 9.2) is more acidic than 2,2,2-trifluoroethanol, the
yield was much reduced due to the poor solubility of mo-
lecular iodine (entry 9). In the oxidation of alcohols in
2,2,2-trifluoroethanol with molecular iodine and potassi-
um carbonate, it was found that the solvent was not oxi-
dized at all by the NMR measurement of the reaction
mixture. Here, exactly, aldehyde is formed at first, and,
therefore, it can be obtained in high yields when the reac-
tion was carried out at room temperature. For example,
the treatment of p-methoxybenzyl alcohol, 2,4,6-trimeth-
ylbenzyl alcohol, and a-thienylmethanol with molecular
iodine (2.5 equiv) and potassium carbonate (2.5 equiv) in
2,2,2-trifluoroethanol at room temperature for 19 hours,
83 hours, and 70 hours provided the corresponding alde-
hydes in 99%, 85%, and 87% yields together with trace
Abstract: A simple, effective, and high-yield procedure for the
oxidative conversion of primary alcohols to the corresponding
2,2,2-trifluoroethyl esters, with molecular iodine and potassium
carbonate in 2,2,2-trifluoroethanol, was studied.
Key words: molecular iodine, oxidation, alcohol, aldehyde, 2,2,2-
trifluoroethyl ester
Oxidation of alcohols with less toxic reagents is very im-
portant in organic synthesis. Therefore, it has been inten-
sively studied and numerous reagents and methods have
been developed.1 Among them, oxidation with molecular
halogens and related reagents is attractive due to the sim-
ple operation and low cost. To date, oxidation of alcohols
to aldehydes or ketones with aqueous NaOCl,2 conversion
of aldehydes to the methyl esters in methanol by NaOCl
in the presence of HOAc,3 oxidation of alcohols to alde-
hydes or ketones with Cl2–pyridine, Cl2–dimethyl sulfide,
Cl2–dimethyl sulfoxide,4 oxidation of alcohols to alde-
hydes or ketones with Cl2–HMPT or Br2–HMPT5 have
been well studied. Conversion of aldehydes to the methyl
esters with NaOCl is effective; however, activated aro-
matic aldehydes gave lower yield of the esters because of
the ring chlorination.3 Molecular iodine is a mild, cheap
and easily available oxidizing reagent, and, moreover, it is
useful because of its solid form and is less toxic than
molecular bromine or chlorine. Previously, simple and
effective conversion of aldehydes to the corresponding
methyl esters, carboxylic acids,6a–6c and nitriles6d in the
presence of molecular iodine in methanol, in water/aceto-
nitrile, and in ammonia water, respectively, was reported.
Lieben iodoform reaction, which is the reaction of methyl
ketones with molecular iodine in aqueous basic solution,
is known for the detection of the methyl ketone group.7
Here, as a part of our basic study of molecular iodine for
organic synthesis,8 we would like to report a useful oxida-
tion of primary alcohols to the corresponding 2,2,2-tri-
fluoroethyl esters by a simple procedure using molecular
iodine and potassium carbonate in 2,2,2-trifluoroethanol.
To the best of our knowledge, reports on the direct oxida-
tive conversion of primary alcohols to the esters with
SYNLETT 2004, No. 5, pp 0880–0882
0
2.
0
4.
2
0
0
4
Advanced online publication: 24.02.2004
DOI: 10.1055/s-2004-817789; Art ID: U01404ST.pdf
© Georg Thieme Verlag Stuttgart · New York

LETTER
Facile Conversion of Alcohols to the Corresponding 2,2,2-Trifluoroethyl Esters
881
Table 2 Oxidative Conversion of Various Alcohols to Esters with
I2/K2CO3 in CF3CH2OH
amounts of the corresponding 2,2,2-trifluoroethyl esters,
respectively. Though TEMPO-mediated oxidation of al-
cohols to aldehydes with molecular iodine was reported
recently,12 aldehydes can be formed by the reaction of
alcohols with molecular iodine alone in 2,2,2-trifluoro-
ethanol. Once aldehydes are formed, their oxidative con-
version to 2,2,2-trifluoroethyl esters proceeds smoothly
via the hemiacetals, as shown in Scheme 1. Based on
these results, a variety of primary alcohols were directly
oxidized to the corresponding 2,2,2-trifluoroethyl esters
in good yields as shown in Table 2. Benzylic alcohols,
neopentyl-type alcohols, and other primary alcohols can
be oxidized to the corresponding 2,2,2-trifluoroethyl
esters. In benzylic alcohols, formation of the esters with
high yields requires 5 equivalents each of molecular
iodine and potassium carbonate, while in aliphatic prima-
ry alcohols, 3 equivalents each is required. The present
reaction is clean and the esters are obtained in quite good
yield from the simple primary alcohols.
I2 (5.0 equiv)
K2CO3 (5.0 equiv)
R
CO2CH2CF3
R
CH2OH
CF3CH2OH
50 °C
1
3
Entry
1
1
Time (h) Yield (%) of 3
m-O2NC6H4CH2OH
3,4-Cl2C6H3CH2OH
p-CF3C6H4CH2OH
p-ClC6H4CH2OH
1
2a
80
91
87
93
78
87
91
91
85
63
85
93
78
2
3
4
4
5a
5
5b
6
p-FC6H4CH2OH
C6H5CH2OH
8a
7
5a
8
p-CH3C6H4CH2OH
p-CH3OC6H4CH2OH
14a
24a
24b
24a
16
1
Table 1 Oxidative Conversion of p-Methylbenzylalcohol with
I2/K2CO3 in Alcohol
9
I
2, K2CO3
CH3
CH2OH
CH3
CHO
+
10
11
12
13
ROH
50 °C
2a
1a
2,5-(CH3)2C6H3CH2OH
CH3
CO2R
3,4,5-(CH3O)3C6H2CH2OH
3a
CH2OH
N
Entry I2/K2CO3 ROH
(mmol)
Time (h)
Yield (%)
14
14
95
CH2OH
1a
2a
87
10
4
3a
7a
1
2
3
4
5
6
7
8
9
5/5
5/5
5/5
5/5
3/3
5/0
5/5
5/5
5/5
(CH3)3COH
CH3CH2OH
CH3OH
19
14
24
21
18
18
14
18
14
0
90
30
0
15
16
24a
5b
67
0
66
53a
83
0
CH2OH
S
100
CH2OH
H2O
47
16
0
CF3CH2OH
CF3CH2OH
CF3CH2OH
CF3CH2OH
(CF3)2CHOH
0
17
18
19
14b
15b
9b
91
91
62
CH3
100
0
CH2OH
6
85
91
0
CH2OH
0
5
76
24
CH2OH
a Yield of p-toluic acid.
20
21
CH3(CH2)11CH2OH
48
4
50
80c
HOCH2
CH2OH
I
I2
R
CH
O
R
CH
H
O
R
CH2OH
-HI
-HI
a Half amount each of I2 and K2CO3 was added at first, and the rest
was added later.
CF3CH2OH
b Mmol ratio of I2/K2CO3 is 3.0/3.0.
c Diester was obtained.
OCH2CF3
OCH2CF3
OCH2CF3
CH
OH
I2
R
C
O
R
C
H
O
I
R
-HI
-HI
Scheme 1 Plausible reaction pathway
Synlett 2004, No. 5, 880–882 © Thieme Stuttgart · New York

882
N. Mori, H. Togo
LETTER
(4) (a) Corey, E. J.; Kim, C. U. J. Am. Chem. Soc. 1972, 94,
Typical Procedure for the Oxidative Conversion of Primary
Alcohols to Esters13
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To a solution of benzylalcohol (1 mmol) in CF3CH2OH (5 mL) were
added I2 (2.5 mmol) and K2CO3 (2.5 mmol) under an argon atmos-
phere. The mixture obtained was stirred for 2 h at 50 °C, then I2
(2.5 mmol) and K2CO3 (2.5 mmol) were added to the mixture again.
After 3 h at the same temperature, the mixture was quenched with
sat. aq Na2SO3 (3–5 mL) at 0 °C, and was extracted with Et2O three
times. The organic layer was washed with brine and dried over
Na2SO4 to provide 2,2,2-trifluoroethyl benzoate in 91% yield in an
almost pure state. If necessary, the product was purified by flash
column chromatography on silica gel (hexane:EtOAc = 4:1) to give
pure 2,2,2-trifluoroethyl benzoate as an oil. Bp 84–86 °C/19 mmHg
(lit.14 bp = 77 °C/13 mmHg). IR (NaCl): 1740, 1290, 1260, 1170,
1110 cm–1. 1H NMR (CDCl3, TMS): d = 4.70 (2 H, q, J = 8.4 Hz),
7.48 (2 H, t, J = 7.7 Hz), 7.62 (1 H, tt, J = 7.7 and 1.4 Hz), 8.09 (2
H, dt, J = 7.7 and 1.4 Hz). 19F NMR (CDCl3, CF3CO2H): d = 72.8
(J = 8.4 Hz).
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Acknowledgment
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microanalytical data.
Financial support from Forum on Iodine Utilization is gratefully
acknowledged.
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Synlett 2004, No. 5, 880–882 © Thieme Stuttgart · New York