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DIAZ AND GONZALEZ
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702
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General Procedure for the Synthesis of N,N -Methylenebisthiazolidines.
To a mixture of L-cysteine ester hydrochloride or (R)-thiazolidine-4-car-
boxylic ester hydrochloride or (S)-5,5-dimethylthiazolidine-4-carboxylic
ester hydrochloride (8 mmoL) and paraformaldehyde (twenty fold excess),
ꢀ
1
solution was stirred for 6 h at room temperature, the solvent was evaporated
5 mL of trifluoroacetic acid was added at 0 C with stirring. The resulting
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under reduced pressure at 45 C, and quenched with 50 mL of H O. The
2
crude solution was neutralized with NaHCO , filtered to eliminate poly-
3
meric formaldehyde and the transparent solution was extracted with ether
and dried. After filtration, the organic solvent was removed in vacuo afford-
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ing pure N,N -methylenebisthiazolidines.
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,1-Bis[(R)-4-methoxycarbonylthiazolidin-3-yl]methane 7. Yield: 0.95 g,
2
2
1
7
8% (oil). [a] D ¼ À129 (c ¼ 0.25, CHCl ). H NMR (CDCl /TMS): d 4.30
3
3
1
3
(
dd, J ¼ 7.2 and 3.2 Hz, 2H), 4.15 (m, 4H), 3.65 (s, 6H), 3,2–3.0 (m, 6H).
C
NMR (CDCl ): d 171.4 (C ¼ O), 73.1 (CH ), 67.1 (CH), 57.4 (CH ), 52.6
3
2
2
(
CH ), 32.6 (CH ). IR (NaCl): 2954, 1735, 1448, 1372, 1286, 1221, 1193,
3 2
À1
1
calcd. for C H N O S (306.39): C, 43.12%; H; 5.92%; N, 9.14%. Found:
079, 1031 cm . MS m/z (%): 306 (3), 160 (100), 132 (66), 59 (36). Anal.
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1
18
2
4 2
C, 43.40%; H; 5.78%; N, 9.38%.
,1-Bis[(R)-4-ethoxycarbonylthiazolidin-3-yl]methane 8. Yield: 1.15 g,
1
2
2
1
8
(
6% (oil). [a] D ¼ À134 (c ¼ 1, CHCl ). H NMR (CDCl /TMS): d 4.36
3
3
dd, J ¼ 7.8 and 3.6 Hz, 2H), 4.23 (m, 8H), 3.3–3.1 (m, 6H), 1.28 (t,
3 2
1
3
J ¼ 7.2 Hz, 6H). C NMR (CDCl ): d 170.8 (C ¼ O), 73.0 (CH ), 67.1
(
1
CH), 61.3 (CH ), 57.4 (CH ), 32.6 (CH ), 14.2 (CH ). IR (NaCl): 2951,
2 2 2 3
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739, 1436, 1287, 1221, 1203, 1176, 1079 cm . MS m/z (%): 334 (3), 174
(
100), 146 (25), 59 (53). Anal. calcd. for C H N O S (334.45): C, 46.69%;
13 22 2 4 2
H; 6.63%; N, 8.38%. Found: C, 46.89%; H; 6.40%; N, 8.57%.
,1-Bis[(R)-4-benzyloxycarbonylthiazolidin-3-yl]methane 9.
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Yield:
ꢀ
22
1
1
.37 g, 75% mp ¼ 80–81 C (EtOH). [a] D ¼ À66 (c ¼ 1, CHCl ). H NMR
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(
CDCl /TMS): d 7.4–7.2 (m, 10H), 5.11 (s, 4H), 4.39 (dd, J ¼ 7.4 and 3.4 Hz,
3
1
3
2
1
H), 4.28 (m, 4H), 3.4–3.0 (m, 6H). C NMR (CDCl ): d 170.6 (C ¼ O),
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35.3 (C), 128.6 (CH), 128.4 (CH), 128.1 (CH), 73.1 (CH ), 67.2 (CH), 67.0
2
(
CH ), 57.3 (CH ), 32.7 (CH ). IR (KBr): 2944, 1734, 1455, 1387, 1292, 1223,
2 2 2
192, 1067, 1009, 740 cm . MS m/z (%): 458 (3), 236 (21), 91 (100). Anal.
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1
calcd for C H N O S (458.59): C, 60.24%; H; 5.71%; N, 6.11%. Found:
2
3
26
2
4 2
C, 60.51%; H; 5.60%; N, 6.33%.
,1-Bis[(S)-4-ethoxycarbonyl-5,5-dimethylthiazolidin-3-yl]methane 10.
1
2
2
1
Yield: 1.14 g, 73% (oil). [a] D ¼ þ126 (c ¼ 0.25, CHCl ). H NMR
3
(
CDCl /TMS): d 4.48 (d, J ¼ 8.2 Hz, 2H), 4.40 (dd, J ¼ 5.8 and 3.6 Hz, 2H),
3
4
1
7
.20 (q, J ¼ 7.0 Hz, 4H), 4.08 (d, J ¼ 8.2 Hz, 2H), 3.65 (s, 2H), 1.60 (s, 6H),
1
3
.41 (s, 6H), 1.26 (t, J ¼ 7.0 Hz, 6H). C NMR (CDCl ): d 170.5 (C ¼ O),
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6.3 (CH), 73.2 (CH ), 60.7 (CH ), 54.8 (CH ), 53.1 (C), 31.2 (CH ), 26.8
2
2
2
3