61.8% |
With sodium acetate; acetic acid; for 3h;Reflux; |
General procedure: [0268] Synthesis of Compounds 120 to 122, which are (Z)-5-(substituted benzylidene)-2-iminothiazolidin-4-one analogs, was performed as follows. In detail, in an acetic acid (4 mL/1 g sodium acetate) solvent, a mixture including a substituted benzaldhehyde (300 mg), <strong>[556-90-1]pseudothiohydantoin</strong> (1.1 eq.), and sodium acetate (3.0 eq.) was refluxed for 3 to 7 hours. Afier cooling, water was added thereto, and the produced precipitate was filtered, and in consideration of physical characteristics of the used starting materials, the resultant precipitate was washed with water and methylene chloride and/or ethyl acetate to obtain a solid target product. [0271] Orange solid; a reaction time of 3 hours; a yield of61.8%; a melting point of >300 C.; ?H NMR (500 MHz,DMSO-d5) oe 10.10 (s, 1H), 9.29 (brs, 1H), 9.04 (s, 1H), 7.49(s, 1H), 7.40 (d, 2H, J=9.0 Hz), 6.88 (d, 2H, J=8.5 Hz); ?3CNMR (100 MHz, DMSO-d5) oe 181.4, 176.1, 159.6, 132.1,130.2, 126.0, 125.5, 116.8; ERMS (ES) mlz 219 (M-H)-. |
61.8% |
With sodium acetate; acetic acid; for 3h;Reflux; |
General procedure: Synthesis of Compounds 120 to 122, which are (Z)-5-(substituted benzylidene)-2-iminothiazolidin-4-one analogs, was performed as follows. In detail, in an acetic acid (4 mL/1 g sodium acetate) solvent, a mixture including a substituted benzaldhehyde (300 mg), <strong>[556-90-1]pseudothiohydantoin</strong> (1.1 eq.), and sodium acetate (3.0 eq.) was refluxed for 3 to 7 hours. After cooling, water was added thereto, and the produced precipitate was filtered, and in consideration of physical characteristics of the used starting materials, the resultant precipitate was washed with water and methylene chloride and/or ethyl acetate to obtain a solid target product. |
61.8% |
With sodium acetate; acetic acid; for 3h;Reflux; |
General procedure: The desired compounds, (Z)-5-(substituted benzylidene)-2-iminothiazolidin-4-one analogues (1a- 1l) (Figure 1), were prepared by Knoevenagel condensation.With one exception, refluxing a solution of appropriate benzaldehydes and <strong>[556-90-1]pseudothiohydantoin</strong>in acetic acid in the presence of NaOAc produced (Z)-5-benzylidene-2-iminothiazolidin-4-ones as a single stereoisomer in yields of 41.4-94.1%. A Knoevenagel condensation between 2,4-dimethoxybenzaldehyde and <strong>[556-90-1]pseudothiohydantoin</strong> under the same conditions gave amixture of (E)- and (Z)-5-(2,4-dimethoxybenzylidene)-2-iminothiazolidin-4-ones. These compounds could not be easily separated by conventional silica gel column chromatography. Milder reaction conditions capable of accomplishing the Knoevenagel condensation were needed to synthesize only (Z)-stereoisomer. Interestingly,heating a solution of 2,4-dimethoxy benzaldehyde and <strong>[556-90-1]pseudothiohydantoin</strong> in ethanol:H2O (1:1) in the presence of 1.0 equiv. of piperidine as a base catalyst at 80 C afforded the corresponding (Z)-stereoisomer(1l) as a sole product. A suspension of an appropriate benzaldehyde (300 mg, 1.53-2.46 mmol), <strong>[556-90-1]pseudothiohydantoin</strong>(1.1 eq.), and sodium acetate (3.0 eq.) in acetic acid (1 mL/1 mmol of benzaldehyde) was refluxed for 3-7 h. The reaction mixture was cooled and water was added. The resulting precipitates were filtered, and washed with water and, if necessary, a small amount of methylene chloride or ethyl acetate, to produce (Z)-5-(substituted benzylidene)-2-iminothiazolidin-4-oneproducts (1a - 1k) in 41.4-94.1% yields. The resulting precipitates were filtered, and washed with water,ethyl acetate and methylene chloride to give (Z)-5-(2,4-dimethoxybenzylidene)-2-iminothiazolidin-4-one (1l) all final products were confirmed by 1H and 13C NMR spectroscopy and mass spectroscopy. (Z)-5-(4-Hydroxybenzylidene)-2-iminothiazolidin-4-one (1a, MHY762) Orange colored solid; reaction time, 3 h; yield, 61.8%; melting point, >300 C; 1H-NMR (500 MHz, DMSO-d6)delta 10.10 (s, 1H, OH), 9.29 (br s, 1H, NH), 9.04 (s, 1H,NH), 7.49 (s, 1H, vinylic H), 7.40 (d, 2H, J = 9.0 Hz,2?-H, 6?-H), 6.88 (d, 2H, J = 8.5 Hz, 3?-H, 5?-H); 13CNMR(100 MHz, DMSO-d6) delta 181.4 (C-4), 176.1 (C-2),159.6 (C-4?), 132.1 (C-2?, C-6?), 130.2 (benzylic C), 126.0(C-5), 125.5 (C-1?), 116.8 (C-3?, C-5?); LRMS (ESI-) m/z 219 (M-H)-. |