Regioselective Reduction of 5-Substituted 2-Alkylidene-4-Oxothiazolidines by Metal Hydrides

Rade Marković; Marija Baranac; Milovan Stojanović

doi:10.1055/s-2004-820051

LETTER

Regioselective Reduction of 5-Substituted 2-Alkylidene-4-Oxothiazolidines by Metal Hydrides

Rade Marković*^a,b, Marija Baranac^a,b, Milovan Stojanović^b
^a Faculty of Chemistry, University of Belgrade, Studentski trg 16, P. O. Box 158, 11001 Belgrade, Serbia and Montenegro
^b Center for Chemistry ICTM, P. O. Box 473, 11000 Belgrade, Serbia and Montenegro
Fax: +381(11)636061; e-Mail: markovic@helix.chem.bg.ac.yu;

Abstract

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Abstract

Thiazolidine β-enamino derivatives possessing a 5-substituted acetate substituent were chemoselectively reduced to corresponding alcohols, or new condensed 2-alkylidenethiazolidines. The method is based on the resistance of an enaminone fragment to reduction by metal hydrides.

Key words

thiazolidine - reductions - hydrides - regioselectivity - ring closure

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References

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Typical Experimental Procedure: An appropriate 5-substituted-4-oxothiazolidine 1 (100 mg) dissolved in anhydrous EtOH (10 mL) was added dropwise at r.t. to the tenfold molar excess of NaBH₄ in EtOH (ca. 5 mL). When the hydrogen evolution had ceased the reaction mixture was heated under reflux with stirring for a period of time required (2-3 h) to complete the reaction (TLC). The reaction mixture was cooled, neutralized with NH₄Cl and extracted with EtOAc. The combined extracts, washed with brine and dried, were evaporated in vacuo. The residue was purified by column chromatography (SiO₂, toluene-EtOAc, 10:0 → 8:2) to afford a pure product 5.
Spectroscopic data for (Z)-[5-(2-Hydroxyethyl)-4-oxothiazolidin-2-ylidene]-1-phenylethanone (5a): Colorless solid; mp 158-159 °C. ¹H NMR (200 MHz, DMSO-d ₆): δ = 1.71-1.93 (m, 1 H, CH _AH_BCH_X), 2.14-2.30 (m, 1 H, CH_A H _BCH_X); 3.58 (m, 2 H, CH ₂OH), 4.09 (dd, J ₁ = 9.5 Hz, J ₂ = 4.2 Hz, 1 H, H_x), 4.82 (br s, 1 H, OH; signal disappears upon D₂O addition), 6.72 (s, 1 H, =CH), 7.47-7.62 (m, 3 H, p-Ph and m-Ph), 7.83 (dd, 1 H, J ₁ = 7.6 Hz, J ₂ = 1.6 Hz, o-Ph), 11.85 (br s, 1 H, NH; signal disappears upon D₂O addition). ¹³C NMR (50.3 MHz, DMSO-d ₆): δ = 35.7 (CH_AH_B), 44.1 (CH_X), 58.6 (CH₂OH), 94.5 (=CH), 127.2 (m-Ph), 129.0 (o-Ph), 132.4 (p-Ph), 138.5 (C₁-Ph), 161.2 (C=), 177.3 (CO_ring), 187.3 (CO_exo). IR (KBr): 3453, 3194, 3068, 2924, 1685, 1631, 1577, 1517, 1468, 1364, 1295, 1198 cm^-1. MS (EI): m/z (rel. intensity%) = 263 (100) [M⁺], 232 (86), 178 (8), 146 (20), 105 (80). UV (DMSO): l _max (e) = 335.0 (18000) nm. Anal. Calcd for C₁₃H₁₃NO₃S: C, 59.30; H, 4.98; N, 5.32; S, 12.18. Found: C, 59.03; H, 4.92; N, 5.33; S, 12.24.

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Strong intramolecular 1,5-interactions of nonbonded S and O within the SC=CC=O subunit with cis-configuration of C=C bond additionally stabilize the enaminone structure.

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Methylation of (Z)-5a led to alcohol 13f, which, in a one-pot sequence, comprising reduction followed by cyclization, was transformed into the identical bicylic thiazolidine 6f in moderate yield (Scheme [4] ).

(Z)-(N-Methyltetrahydrofuro[2,3-d]thiazol-2-ylidene)-1-phenylethanone (6f): Colorless solid; mp 121-122 °C. ¹H NMR (200 MHz, CDCl₃): δ = 2.12-2.43 (m, 2 H, CH _A H _BCH_XS), 3.10 (s, 1 H, NCH₃), 3.77-3.89 (m, 1 H, OCH_YCH _XS), 4.02 (t, 1 H, J = 8.0 Hz, OCH _QH_Z), 4.12 (t, 1 H, J = 7 Hz, OCH_Q H _Z), 5.67 (d, 1 H, J _XY = 6.6 Hz, OCH _YCH_XS), 6.08 (s, 1 H, =CH), 7.36-7.47 (m, 3 H, m-Ph, p-Ph), 7.90-7.95 (m, 2 H, o-Ph). ¹³C NMR (50.3 MHz, CDCl₃): δ = 33.7 (NCH₃), 35.2 (CH_AH_B), 44.6 (CH_X), 65.8 (CH₂O), 87.5 (=CH), 99.1 (CH_Y), 127.2 (o-Ph), 128.2 (m-Ph), 131.0 (p-Ph), 139.7 (C₁Ph), 165.7 (C=), 186.9 (CO). IR (KBr): 3530, 3412, 2974, 2939, 1602, 1571, 1525, 1433, 1355, 1264, 1213, 1028, 973, 727 cm^-1. MS (EI, 70 eV): m/z (rel. intensity) = 261 (57) [M⁺], 260 (100), 245 (34), 191 (20), 184 (42), 163 (32), 105 (97), 86 (39), 82 (58), 51 (26). UV (DMSO): l _max (e) = 337.9 (19 700) nm. Anal. Calcd for C₁₄H₁₅NO₂S: C, 64.34; H, 5.79; N, 5.36; S, 12.27. Found: C, 64.24; H, 5.82; N, 5.30; S, 12.59.

In all push-pull thiazolidines 1 and 6 high field ¹³C chemical shifts (85-96 ppm) for the acceptor-substituted C(α) atoms, and low field shifts (161-169 ppm) for the donor-substituted C(β) atoms are typical.

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