High yielding methyl esterification catalyzed by indium(III) chloride

Article abstract of DOI:10.1248/cpb.54.918

The carboxylic acids are efficiently converted into the methyl esters in methanol using indium(III) chloride as the catalyst. This method is applicable for aromatic and aliphatic carboxyl moieties as well as amino acids in high yields.

Full text of DOI:10.1248/cpb.54.918

9
18
Notes
Chem. Pharm. Bull. 54(6) 918—919 (2006)
Vol. 54, No. 6
High Yielding Methyl Esterification Catalyzed by Indium(III) Chloride
Tomoko MINENO* and Hisao KANSUI
Laboratory of Organic Chemistry, Faculty of Pharmaceutical Sciences, Sojo University; 4–22–1 Ikeda, Kumamoto
8
60–0082, Japan. Received February 6, 2006; accepted March 10, 2006; published online March 17, 2006
The carboxylic acids are efficiently converted into the methyl esters in methanol using indium(III) chloride
as the catalyst. This method is applicable for aromatic and aliphatic carboxyl moieties as well as amino acids in
high yields.
Key words indium(III) chloride; carboxylic acid; methyl ester
1)
Methyl esterificaion of the carboxylic acids is the most tions, which generates diazomethane in situ. However, due
fundamental reaction, and there is a variety of methods avail- to the carcinogenic property a safer alternative, (trimethylsi-
2
—5)
able. Among the conventional procedures, the most common lyl)diazomethane,
is often preferred. Methyl esters can
6,7)
is the use of N-methyl-N-nitrosourea under basic condi- also be formed by the reactions
in MeOH/H SO or
2 4
a)
Table 1. Methyl Esterification Catalyzed by Indium(III) Chloride
Time
h)
Yield
(%)
Entry
1
Substrate
Product
Catalyst
InCl3
Temp.
reflux
(
18
83
92
2
3
4
5
InCl3
InCl3
InCl3
InCl3
reflux
reflux
reflux
reflux
40
40
12
8
b)
85
82
85
6
InCl3
reflux
20
98
7
8
InCl3
InCl3
reflux
reflux
40
48
96
83
c)
9
InCl3
reflux
48
83
1
1
1
0
1
2
InCl3
InCl3
InCl3
reflux
reflux
48
96
21
93
61
91
d)
r.t.
d)
1
1
1
3
4
5
InCl3
InCl3
r.t.
10
20
21
86
73
98
d)
r.t.
InCl ·4H O
reflux
3
2
a) All reactions were performed in MeOH using either 0.2 eq of indium(III) chloride or indium(III) chloride tetrahydrate as the catalyst. b) Side product of methyl 4-
methoxymethyl)benzoate was also formed in 12% yield. c) Since the starting substrate is a dicarboxylate, 0.4 eq of indium(III) chloride was used. d) The reaction was carried
(
out employing sonication at room temperature.
∗
To whom correspondence should be addressed. e-mail: tmineno@ph.sojo-u.ac.jp
© 2006 Pharmaceutical Society of Japan

June 2006
919
MeOH/TMS–Cl, and Me C(OMe) /HCl is utilized for amino (77.0 ppm) as an internal standard. High resolution mass spectra were meas-
2
2
8)
ured on JEOL AccuTOF LC-plus JMS-T100LP. All commercially available
chemicals were used without purification.
General Experimental Procedure In a typical experimental procedure,
the substrate of the carboxylic acid (1 mmol) was dissolved in methanol
acids. These procedures still have the drawbacks of toxicity
and incompatibility with the sensitive functional groups.
There has been a recent report about direct condensation of
carboxylic acids with alcohols using catalysts derived from (10 ml) and indium(III) chloride (0.2 mmol, 44 mg) was added to the solu-
9
)
tion at room temperature. The mixture was heated at reflux and monitored
for completion by TLC. The solvent was removed by rotary evaporation
under vacuum, and water (20 ml) was pored to the residue. This solution was
extracted with ethyl acetate (3ꢀ15 ml), washed with brine (30 ml), and dried
over Na SO . After evaporation of the organic solvent, column chromatogra-
the group 4 transition elements.
We previously reported a promising method for tetrahy-
dropyranylation/depyranylation of alcohols using indium(III)
triflate. Unlike MeOH/TMS–Cl condition that generate
10)
2
4
HCl in situ, indium(III) chloride, which is known to serve as phy on silica gel was applied to obtain the methyl ester, which was then con-
1
1)
firmed by the spectral data. Products of entries 1—4, 6, 10, 12, 13, and 15
could be compared with the commercially available sources, and the product
of entries 8, 9, and 11 was identical with those of the previously reported
an efficient and mild Lewis acid, would not serve as a pro-
ton source. During the course of our continuing study on in-
dium based chemistry, the methyl esterification of an array of
carboxylic acids was found to proceed in methanol with the
12—14)
spectroscopic data.
3-(2,4,6-Triisopropylphenylsulfonyloxy)phenylacetic Acid Methyl
1
catalytic amount of indium(III) chloride. Thus, a solution of Ester H-NMR (500 MHz, CDCl
): d: 7.24 (dd, 1H, Jꢁ8.6, 8.1 Hz), 7.20
3
(
s, 2H), 7.16 (d, 1H, Jꢁ7.5 Hz), 6.96 (s, 1H), 6.90 (d, 1H, Jꢁ8.0 Hz), 4.06
carboxylic acid in methanol was treated with indium(III)
chloride (0.2 eq) at reflux or the sonication condition at room
temperature to give a good yield of the corresponding methyl
ester.
(
1
sep, 2H, Jꢁ6.9 Hz), 3.65 (s, 3H) 3.55 (s, 2H), 2.93 (sep, 1H, Jꢁ6.9 Hz),
.27 (d, 6H, Jꢁ6.9 Hz), 1.18 (d, 12H, Jꢁ6.9 Hz); C-NMR (125 MHz,
13
CDCl ): d: 171.09, 154.26, 151.22, 149.50, 135.77, 129.63, 129.59, 127.91,
3
123.85, 123.43, 121.11, 52.11, 40.72, 34.25, 29.76, 24.54, 23.53; HR-MS
ꢂ
ꢂ
To evaluate the general applicability of this transforma- (ESI ): [MꢂNa] Calcd for C24
H O S 455.1868, Found 455.1893.
32 5
1
N-9-Fluorenylmethoxycarbonylglycine Methyl Ester H-NMR
tion, various compounds having diverse substituents or pro-
tecting groups were subjected to the methyl esterifying reac-
tions. The reaction conditions were mild, not containing inor-
ganic acids, and gave the corresponding methyl esters in ex-
cellent yields (Table 1). It worked not only for aliphatic car-
boxylic acids but also for aromatic ones (entries 3, 4). Pro-
tecting groups such as the 2,4,6-triisopropylbenzenesulfonoyl
group (entry 5) and the 9-fluorenylmethoxycarbonyl (Fmoc)
group (entries 7, 8) are stable to these reaction conditions.
The substrates bearing the olefin units were able to be con-
verted to the desired methyl eaters, including a C-7 long
aliphatic carboxylate (entry 6) and a,b-unsaturated carboxy-
lates (entries 9, 10). The reaction with ketopinic acid re-
quired 96 h to complete and ended up with 61% yield, pre-
sumably due to the steric hindrance (entry 11). A couple of
esterification employing sonication was attempted, and we
revealed that the reaction could proceed at room temperature,
shortening the reaction time in half (entries 12—14). We also
revealed that it was possible to carry out the esterification in
the presence of the water molecules, using the catalytic
amount of indium(III) chloride tetrahydrate instead of in-
dium(III) chloride, without affecting the completion of the
esterification (entry 15).
(
500 MHz, CDCl ): d 7.77 (d, 2H, Jꢁ7.4 Hz), 7.61 (d, 2H, Jꢁ7.5 Hz), 7.40
3
(t, 2H, Jꢁ7.5 Hz), 7.32 (dt, 2H, Jꢁ7.5, 1.2 Hz), 5.36 (br s, 1H), 4.42 (d, 2H,
Jꢁ7.5 Hz), 4.24 (t, 1H, Jꢁ7.5 Hz), 4.00 (d, 2H, Jꢁ5.8 Hz), 3.76 (s, 3H);
1
3
C-NMR (125 MHz, CDCl ): d 170.44, 156.23, 143.73, 141.23, 127.68,
3
ꢂ
1
27.02, 125.03, 119.94, 67.13, 52.35, 47.02, 42.58; HR-MS (ESI ):
ꢂ
[MꢂNa] Calcd for C H NO 334.1055, Found 334.1048.
1
8
17
4
Acknowledgement The authors thank Professor Mitchell A. Avery
(University of Mississippi) for his generous support.
References
1)
Hecht S. M., Kozarich J. W., Tetrahedron Lett., 14, 1397—1400
1973).
(
2)
Hashimoto N., Aoyama T., Shioiri T., Chem. Pharm. Bull., 29, 1475—
1478 (1981).
3) Hirai Y., Aida T., Inoue S., J. Am. Chem. Soc., 111, 3062—3063
1989).
Shioiri T., Aoyama T., Mori S., Org. Synth. Collect., VIII, 612—615
1993).
(
4
)
)
(
5
Fields S. C., Dent W. H., III, Green F. R., III, Tromiczak E. G., Tetra-
hedron Lett., 37, 1967—1970 (1996).
6) Danishefsky S., Hirama M., Gombatz K., Harayama T., Berman E.,
Schuda P., J. Am. Chem. Soc., 100, 6536—6538 (1978).
7)
8)
9)
Brook M. A., Chan T. H., Synthesis, 1983, 201—203 (1983).
Rachele J. R., J. Org. Chem., 28, 2898 (1963).
Ishihara K., Ohara S., Yamamoto H., Science, 290, 1140—1142
(2000).
1
1
1
0) Mineno T., Tetrahedron Lett., 43, 7975—7978 (2002).
1) Babu S. A., Synlett, 2002, 531—532 (2002).
2) Hayashida O., Sebo L., Rebek J., Jr., J. Org. Chem., 67, 8291—8298
In conclusion, the indium(III) chloride-catalyzed esterifi-
cation described here is a high yielding method and can
serve as an alternative to the previously known procedures.
(
2002).
3) Cotton F. A., Donahue J. P., Murillo C. A., J. Am. Chem. Soc., 125,
436—5450 (2003).
4) Ishizuka T., Kimura K., Ishibuchi S., Kunieda T., Chem. Pharm. Bull.,
8, 1717—1719 (1990).
1
1
Experimental
5
General Methods NMR spectra were recorded on a JEOL JNM-ECA-
5
00. The chemical shifts (d) are reported in parts per million (ppm) and J
3
1
1
3
values in Hz, using CDCl for H-NMR (7.26 ppm) and C-NMR
3