SHORT PAPER
Synthesis of Monosubstituted Succinic Acids from tert-Butylsuccinate
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Table 3 Yields and Properties of 2-Substituted Succinic Anhydrides 5a-g
R
Yield Mp (°C)
(%)
Molecular Formula
HRMS Calc./Found
1H NMR (DMSO-d6), d, J (Hz)
13C NMR (DMSO-d6), d
5a
Et
96
Oil
C6H8O3
128.125/128.046
3.20-3.03 (m, 2 H), 2.78-2.60 (m, 1 H),
2.10-1.90 (m, 1 H), 1.88-1.67 (m, 1 H),
1.05 (t, 3 H, J = 6.2)
173.9, 170.6, 42.3, 33.9, 24.5,
11.3
5b
5c
i-Pr
87
96
Oil
C7H10O3
142.152/142.063
3.23-2.90 (m, 2 H), 2.85-2.65 (m, 1 H),
2.45-2.20 (br s, 1 H), 1.23-0.90 (m, 6 H)
173.3, 170.8, 47.2, 31.1, 29.6,
20.1, 18.4
n-Bu
42-43
C8H12O3
156.179/156.078
3.25-3.05 (m, 2 H), 2.80-2.50 (m, 1 H),
2.12-1.91 (m, 1 H), 1.75-1.52 (m, 1 H),
1.50-1.22 (m, 4 H), 0.99 (t, 3 H, J = 7.5)
174.3, 170.8, 41.2, 30.9, 29.1,
24.0, 22.5, 14.4
5d
5e
5f
Allyl
Bn
85
95
84
Oil
C7H8O3
140.136/140.047
5.90-5.65 (m, 1 H), 5.35-5.28 (m, 2 H),
3.40-3.20 (m, 1 H), 3.19-3.00 (m, 1 H),
2.83-2.40 (m, 3 H)
173.6, 170.5, 132.4, 120.4,
40.5, 34.9, 33.5
91-92
60-61
65-66
C11H10O3
190.195/190.063
7.48-7.10 (m, 5 H), 3.59-3.35 (m, 1 H),
3.32-3.15 (m, 1 H), 3.10-2.82 (m, 2 H),
2.80-2.60 (m, 1 H)
173.5, 169.9, 136.2, 129.6,
129.3, 128.0, 42.5, 36.3, 33.4
Octyl
C12H20O3
212.285/212.140
3.19-3.02 (m, 2 H), 2.75-2.59 (m, 1 H),
2.05-1.85 (m, 1 H), 1.72-1.54 (m, 1 H),
1.45-1.15 (br s, 12 H), 0.88 (t, 3 H, J = 7.3)
174.0, 170.5, 41.1, 34.5, 32.2,
31.4, 29.6, 29.5, 29.4, 27.0,
23.0, 14.5
5g
Cyclo- 91
C5H9
C9H12O3
168.189/168.045
3.25-2.95 (m, 2 H), 2.95-2.60 (m, 1 H),
2.39-2.15 (m, 1 H), 2.10-1.45 (m, 6 H),
1.45-1.10 (m, 2 H)
173.5, 170.9, 44.9, 41.4, 33.1,
30.6, 29.7, 25.5, 25.2
added dropwise. The reaction was allowed to warm to r.t. and stirred
for 24 h. The reaction was quenched with H2O (3 mL) and concen-
trated. The residue was partitioned between EtOAc (30 mL) and
cold 1 M HCl (20 mL). The organic layer was dried (MgSO4),
filtered, concentrated, and chromatographed (25% EtOAc in
hexanes) to afford products 3a-g as colorless oils (Table 1).
(4) Marcq, V.; Mirand, C.; Emonard, H.; Hornebeck, W.
Heterocycles 1999, 51, 1079.
(5) Laghmich, A.; Ladriere, L.; Malaisse-Lagae, F.; Dannacher,
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Bioorg. Med. Chem. Lett. 1999, 9, 2263.
2-Alkylsuccinic Acid 4a-g; General Procedure
Trifluoroacetic acid (3.6 mL, 47.2 mmol) was added to a solution of
2-alkyl tert-butylsuccinate 3a-g (1.5 mmol) in CH2Cl2 (20 mL).
The mixture was stirred at r.t. for 24 h and was then concentrated
and chromatographed (50% EtOAc in hexanes) to produce the diac-
id (4a-g) in good yields as white crystals (Table 2).
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(9) Minami, N.; Kuwajima, I. Tetrahedron Lett. 1977, 1423.
(10) Petragnani, N.; Yonashiro, M. Synthesis 1980, 710.
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C. J. Chem. Soc., Perkin Trans. 1 1989, 1162.
(12) Fadel, A.; Salaun, J. Tetrahedron Lett. 1988, 29, 6257.
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(14) Eck, R.; Simon, H. Tetrahedron 1994, 50, 13631.
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1972.
2-Alkylsuccinic Anhydride 5a-g; General Procedure
A mixture of 2-alkylsuccinic acid 4a-g (2 mmol) and acetyl chlo-
ride (0.9 mL, 12.3 mmol) was refluxed for 3 h. The solution was
concentrated to give the desired anhydride 5a-g (Table 3).
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1983, 2629.
(17) Guzzo, P. R.; Miller, M. J. J. Org. Chem. 1994, 59, 4862.
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(20) Shao, L.; Miyata, S.; Muramatsu, H.; Kawano, H.; Ishii, Y.;
Saburi, M.; Uchida, Y. J. Chem. Soc., Perkin Trans. 1 1990,
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Acknowledgement
We gratefully acknowledge support of our research from the Natio-
nal Institute on Drug Abuse at the National Institutes of Health (1
RO3 DA12706-01). K. A. I. would like to thank the Egyptian Cul-
tural and Educational Bureau for a fellowship. We would also like
to thank Kristjan M. Arason for his help.
(21) Kim, D. H.; Chung, S. Tetrahedron: Asymmetry 1999, 10,
3769.
References
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Article Identifier:
1437-210X,E;2000,0,10,1369,1371,ftx,en;M05200SS.pdf
Synthesis 2000, No. 10, 1369–1371 ISSN 0039-7881 © Thieme Stuttgart · New York