Convenient Synthesis of 5-Arylidene-2-imino-4-thiazolidinone Derivatives Using Microwave Irradiation

Abstract

A concise approach for the preparation of 5-arylidene-2-imino-4-thiazolidinone derivatives is described. Structurally diverse amines, isothiocyanates, aldehydes, and chloroacetyl chloride were combined under microwave irradiation to afford new 5-arylidene-2-imino-4-thiazolidinone derivatives. The one-pot synthesis involves the in situ formation of a thiourea followed by reaction with chloroacetyl chloride and an aldehyde to generate the target compounds.

Key words

5-arylidene-2-imino-4-thiazolidinone - thiourea - microwave irradiation - multicomponent reaction - Knoevenagel condensation

• References and Notes

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• 25 Optimized Procedure for the Synthesis of 5-Arylidene-2-aryliminothiazolidin-4-ones In a 10 mL reaction vial, the amine (0.5 mmol) was added to a solution of isothiocyanate (0.5 mmol) in absolute EtOH (1 mL). The formation of the thiourea was achieved either at r.t. or by irradiating the reaction mixture for the duration indicated for each compound at a maximum power of 90 W and 120 °C. Anhydrous NaOAc (61.5 mg, 1.5 equiv), chloroacetyl chloride (59.7 μL, 1.5 equiv), and aldehyde (1 equiv) were added successively. The reaction mixture was then irradiated for 20 min at a maximum power of 30 W and 120 °C. The precipitate was filtered and dissolved in CH₂Cl_2. The organic phase was washed with H₂O and brine, dried over Na₂SO₄, and concentrated in vacuo. Either crystallization from EtOH or purification by flash chromatography afforded the corresponding 5-arylidene-2-aryliminothiazolidin-4-ones.
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• 29 Selected Analytical Data Compound 1: pale yellow solid (106 mg, 45%); mp 143–145 °C. ¹H NMR (250 MHz, CDCl₃): δ = 3.81 (s, 3 H, CH₃), 3.84 (s, 3 H, CH₃), 3.88 (s, 3 H, CH₃), 4.60 (s, 2 H, CH₂), 5.04 (s, 2 H, CH₂), 6.84 (d, 2 H, J = 6.2 Hz, ArH), 6.91 (d, 2 H, J = 6.5 Hz, ArH), 7.00 (d, 2 H, J = 6.5 Hz, ArH), 7.26 (d, 2 H, J = 6.2 Hz, ArH), 7.47 (d, 2 H, J = 6.5 Hz, ArH), 7.51 (d, 2 H, J = 6.5 Hz, ArH), 7.73 (s, 1 H, C=CH). ¹³C NMR (63 MHz, CDCl₃): δ = 45.5, 55.2, 55.3, 55.4, 55.8, 113.7 (2 C), 113.8 (2 C), 114.5 (2 C), 118.8, 126.6, 128.6 (2 C), 128.8, 130.0, 130.5 (2 C), 131.3, 131.8 (2 C), 149.0, 158.6, 159.2, 160.7, 166.9. IR: ν = 2951, 2829, 1697, 1644, 1615, 1599, 1509, 1468, 1443, 1426, 1380, 1338, 1297, 1249, 1173, 1163, 1117, 1106, 1032 cm^–1. ESI-HRMS: m/z calcd for C₂₇H₂₇N₂O₄S [M + H]⁺: 475.1692; found: 475.1707. Compound 2: yellow solid (134 mg, 55%); mp 169–170 °C. ¹H NMR (250 MHz, CDCl₃): δ = 2.54 (s, 3 H, CH₃), 3.81 (s, 3 H, CH₃), 3.84 (s, 3 H, CH₃), 4.61 (s, 2 H, CH₂), 5.05 (s, 2 H, CH₂), 6.84 (d, 2 H, J = 6.5 Hz, ArH), 6.91 (d, 2 H, J = 6.5 Hz, ArH), 7.25–7.33 (m, 4 H, ArH), 7.47 (d, 2 H, J = 8.0 Hz, ArH), 7.71 (s, 1 H, C=CH). ¹³C NMR (63 MHz, DMSO-d ₆): δ = 16.5, 47.1, 56.7, 56.8, 57.2, 115.1 (2 C), 115.3 (2 C), 121.8, 127.4 (2 C), 130.0 (2 C), 130.1, 131.0, 131.7 (2 C), 131.8, 131.9 (2 C), 132.5, 143.0, 150.2, 160.1, 160.6, 168.1. IR: ν = 2840, 1698, 1646, 1610, 1585, 1513, 1497, 1467, 1423, 1403, 1380, 1331, 1295, 1248, 1171, 1162, 1092, 1072, 1041, 1030 cm^–1. ESI-HRMS: m/z calcd for C₂₇H₂₇N₂O₃S₂ [M + H]⁺: 491.1463; found: 491.1440. Compound 13: yellow solid (130 mg, 51%); mp 141–143 °C. ¹H NMR (250 MHz, CDCl₃): δ = 3.81 (s, 3 H, OCH₃), 3.84 (s, 3 H, OCH₃), 4.66 (s, 2 H, C=NCH₂), 5.05 (s, 2 H, NCH₂), 6.84–6.94 (m, 6 H, ArH), 7.29–7.55 (m, 8 H, ArH and C=CH), 7.78 (d, 2 H, J = 6.8 Hz, ArH). ¹³C NMR (63 MHz, CDCl₃): δ = 45.5, 55.2, 55.3, 55.5, 108.3, 113.7 (2 C), 113.8 (2 C), 116.2, 118.3, 119.0, 124.3 (2 C), 128.5, 128.7 (2 C), 128.9 (2 C), 129.0, 129.6, 130.3, 130.4 (2 C), 131.4, 149.7, 156.9, 158.7, 159.1, 166.4. IR: ν = 2924, 2851, 1728, 1697, 1678, 1647, 1608, 1510, 1439, 1415, 1379, 1328, 1289, 1244, 1163, 1110, 1088, 1029 cm^–1. ESI-HRMS: m/z calcd for C₃₀H₂₇N₂O₄S [M + H]⁺: 511.1685; found: 511.1694. Compound 21: yellow solid (52 mg, 29%); mp 68 °C. ¹H NMR (250 MHz, CDCl₃): δ = 0.94–1.01 (m, 6 H, 2 × CH₃), 1.34–1.49 (m, 4 H, 2 × CH₂), 1.63–1.74 (m, 4 H, 2 × CH₂), 2.54 (s, 3 H, SCH₃), 3.42 (t, 2 H, J = 6.8 Hz, C=NCH₂), 3.87 (t, 2 H, J = 7.2 Hz, NCH₂), 7.30 (d, 2 H, J = 8.5 Hz, H_ar), 7.47 (d, 2 H, J = 8.5 Hz, H_ar), 7.66 (s, 1 H, C=CH). ¹³C NMR (63 MHz, CDCl₃): δ = 13.7, 13.9, 15.1, 20.0, 20.5, 29.5, 32.8, 42.8, 52.9, 120.9, 126.0 (2 C), 128.6, 130.2 (2 C), 130.6, 141.1, 147.3, 166.9. IR: ν = 2952, 2851, 2817, 1706, 1641, 1602, 1586, 1490, 1429, 1381, 1295, 1261, 1198, 1116, 1090, 1009 cm^–1. ESI-HRMS: m/z calcd for C₁₉H₂₇N₂OS₂ [M + H]⁺: 363.1559; found: 363.1559