September 2004
1139
6.50; N, 8.28. Found: C, 57.00; H, 6.49; N, 8.32.
one proton of CH2), 4.50 (1H, m, CH), 6.74 and 7.04 (each 1H, each m,
2-Amino-3-(thiophen-2-yl)propanoic Acid (1d): Compound 1d was ob- thiophene-3H and -4H), 8.04 (1H, br s, CHO), 8.44 (1H, br d, Jꢁ8 Hz, NH).
tained in 83% yield, mp 235—237 °C (lit.32) 243—245 °C). IR (single
bounce ATR): 1587 (COOꢀ) cmꢀ1
Anal. Calcd for C8H8BrNO3S: C, 34.53; H, 2.87; N, 5.03. Found: C, 34.27;
H, 2.93; N, 4.77.
.
2-Amino-3-(thiophen-3-yl)propanoic Acid (1e): Compound 1e was ob-
tained in 94% yield, mp 260—262 °C (lit.33) 265—267 °C). IR (single
Acknowledgments We thank the Health Science Promotion Foundation
of Kobe Gakuin University for partial financial support of this research,
bounce ATR): 1586 (COOꢀ) cmꢀ1
.
2-Amino-3-(5-methylthiophen-2-yl)propanoic Acid (1f): Compound 1f which was carried out as a part of a project at the High Technology Research
was obtained in 77% yield, mp 232—234 °C. IR (single bounce ATR): 1587
(COOꢀ) cmꢀ1. NMR (D2O) d: 2.45 (3H, s, CH3), 3.36 (1H, dd, Jꢁ7, 15 Hz,
one proton of CH2), 3.42 (1H, dd, Jꢁ5, 15 Hz, one proton of CH2), 3.97
(1H, dd, Jꢁ5, 7 Hz, CH), 6.74 (1H, d, Jꢁ2 Hz, thiophene-4H), 6.82 (1H, d,
Jꢁ3 Hz, thiphene-3H). Anal. Calcd for C8H11NO2S: C, 51.89; H, 5.94; N,
7.56. Found: C, 51.62; H, 5.89; N, 7.51.
Center.
References and Notes
1) Present address: Chemical Technology Department, Mongolian Uni-
versity of Sciences and Technology, Sukhbaatar district, Ulaanbaatar-
12, Mongolia.
2) ChemFiles 2001 Vol.1, No. 5, Unnatural Amino Acids, Sigma-Aldrich.
unnaturalaa_small.pdf], PSJ Web, 29 March, 2004.
2-Amino-3-(5-bromothiophen-2-yl)propanoic Acid (1g): Compound 1g
was obtained in 48% yield, mp 230—233 °C (dec.) [lit.34) 235—238 °C
(dec.)]. IR (single bounce ATR): 1586 (COOꢀ) cmꢀ1
.
3) ChemFiles 2002 Vol.2, No. 4, Unnatural Amino Acids II, Sigma-
General Procedure for the Preparation of 2-(Formylamino)-3-(het-
eroaryl)propanoic Acids (6) The procedure of Watanabe14) was employed
with some modifications. To a solution of 2-amino-3-(heteroaryl)propanoic
acid (16 mmol) in formic acid (5 ml), acetic anhydride (16.6 ml) was added
dropwise with ice-cooling. The reaction mixture was stirred for 1 h at room
temperature, diluted with water (16 ml) and concentrated in vacuo to give
the crude product (6), which was further purified by recrystallization.
2-Formylamino-3-(furan-2-yl)propanoic Acid (6a): Compound 6a was
given in 82% yield, mp 145—147 °C (from AcOEt) (lit.14) mp 144—
Aldrich.
Acids_IINP.pdf], PSJ Web, 29 March, 2004.
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Mar., 1990) [Chem. Abstr., 113, 115862b (1990)].
com/index.asp], PWJ Web. 29 March, 2004.
1
145 °C). IR (single bounce ATR): 3291 (NH), 1720 (CO) cmꢀ1. H-NMR
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(DMSO-d6) d: 2.98 (1H, dd, Jꢁ8, 15 Hz, one proton of CH2), 3.10 (1H, dd,
Jꢁ5, 15 Hz, one proton of CH2), 4.56 (1H, m, CH), 6.35, 6.55 and 7.52
(each 1H, each m, furan-4H, -3H and -5H), 8.01 (1H, br d, Jꢁ0.7 Hz, CHO),
8.37 (1H, br d, Jꢁ8 Hz, NH).
2-Formylamino-3-(furan-3-yl)propanoic Acid (6b): Compound 6b was
obtained in 51% yield, mp 144—146 °C. IR (single bounce ATR): 3248
1
(NH), 1736 (CO) cmꢀ1. H-NMR (DMSO-d6) d: 2.74 (1H, dd, Jꢁ8, 14 Hz,
one proton of CH2), 2.87 (1H, dd, Jꢁ4, 14 Hz, one proton of CH2), 4.46
(1H, m, CH), 6.40, 7.45 and 7.55 (each 1H, each m, furan-4H, -2H and
-5H), 8.01 (1H, br s, CHO), 8.34 (1H, br d, Jꢁ8 Hz, NH). Anal. Calcd for
C8H9NO4: C, 52.45, H, 4.91, N, 7.65. Found: C, 52.23, H, 4.84, N, 7.65.
2-Formylamino-3-(5-methylfuran-2-yl)propanoic Acid (6c): Compound
6c was obtained in 88% yield, mp 134—136 °C (from EtOH–water). IR (sin-
1
gle bounce ATR): 3327 (NH), 1722 (CO) cmꢀ1. H-NMR (DMSO-d6) d:
2.19 (3H, s, CH3), 2.91 (1H, dd, Jꢁ8, 15 Hz, one proton of CH2), 3.03 (1H,
dd, Jꢁ5, 15 Hz, one proton of CH2), 4.52 (1H, m, CH), 5.93 and 6.00 (each
1H, each d, Jꢁ6 Hz, furan-3H and -4H), 8.01 (1H, br s, CHO), 8.36 (1H,
br d, Jꢁ8 Hz, NH). Anal. Calcd for C9H11NO4: C, 54.82; H, 5.58; N, 7.10.
Found: C, 54.73; H, 5.54; N, 7.07.
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32) du Vigneaud V., McKennis H., Jr., Simmonds S., Dittmer K., Brown
G. B., J. Biol. Chem., 159, 385—394 (1945).
2-Formylamino-3-(thiophen-2-yl)propanoic Acid (6d): Compound 6d was
obtained in 80% yield, mp 171—147 °C (form EtOH–water), (lit.25) 173—
1
176 °C). IR (single bounce ATR): 3290 (NH), 1722 (CO) cmꢀ1. H-NMR
(DMSO-d6) d: 3.15 (1H, dd, Jꢁ8, 15 Hz, one proton of CH2), 3.38 (1H, dd,
Jꢁ4, 15 Hz, one proton of CH2), 4.52 (1H, m, CH), 6.89, 6.94 and 7.35
(each 1H, each m, thiophene-5H, -4H and -3H), 8.03 (1H, br d, Jꢁ0.7 Hz,
CHO), 8.41 (1H, br d, Jꢁ8, NH).
2-Formylamino-3-(thiophen-3-yl)propanoic Acid (6e): Compound 6e was
obtained in 95% yield, mp 151—153 °C (from EtOH–water). IR (single
1
bounce ATR): 3209 (NH), 1737 (CO) cmꢀ1. H-NMR (DMSO-d6) d: 2.93
(1H, dd, Jꢁ9, 14 Hz, one proton of CH2), 3.08 (1H, dd, Jꢁ5, 14 Hz, one pro-
ton of CH2), 4.51 (1H, m, CH), 6.99, 7.21 and 7.44 (each 1H, each m, thio-
phene-3H, -5H and -4H), 8.00 (1H, br d, Jꢁ0.7 Hz, CHO), 8.35 (1H, br d,
Jꢁ8 Hz, NH). Anal. Calcd for C8H9NO3S: C, 48.24; H, 4.52; N, 7.03.
Found: C, 48.16; H, 4.57; N, 7.02.
2-Formylamino-3-(5-methylthiophen-2-yl)propanoic Acid (6f): Com-
pound 6f was obtained in 63% yield, mp 173—175 °C (from EtOH–water).
IR (single bounce ATR): 3291 (NH), 1721 (CO) cmꢀ1. 1H-NMR (DMSO-d6)
d: 2.49 (3H, s, CH3), 3.05 (1H, dd, Jꢁ8, 15 Hz, one proton of CH2), 3.19
(1H, dd, Jꢁ4, 15 Hz, one proton of CH2), 4.52 (1H, m, CH), 6.60 and 6.65
(each 1H, each m, thiophene-3H and -4H), 8.02 (1H, br s, CHO), 8.36 (1H,
br d, Jꢁ8 Hz, NH). Anal. Calcd for C9H11NO3S: C, 50.70; H, 5.16; N, 6.57.
Found: C, 50.49; H, 5.13; N, 6.55.
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L., Day H. G., J. Am. Chem. Soc., 70, 2611 (1848).
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1201—1204 (1949).
3-(5-Bromothiophen-2-yl)-2-(formylamino)propanoic Acid (6g): Com-
pound 6g was obtained in 76% yield, mp 158—160 °C (from EtOH). IR
(single bounce ATR): 3273 (NH), 1720 (CO) cmꢀ1. 1H-NMR (DMSO-d6) d:
3.10 (1H, dd, Jꢁ8, 15 Hz, one proton of CH2), 3.26 (1H, dd, Jꢁ4, 15 Hz,