4.1. Chemistry

All starting materials, chemicals, and solvents were purchased from commercial suppliers (Sigma-Aldrich, St. Louis, MI, USA; FluoroChem, Hadfield, UK; Carlo Erba, Cornaredo, Italy) and used as received. Anhydrous solvents were utilized without further drying. Aluminum-backed Silica Gel 60 plates (0.2 mm; Merck, Darmstadt, Germany) were used for analytical thin-layer chromatography (TLC), to follow the course of the reactions. Microwave-assisted reactions were carried out with a Biotage^® Initiator Classic (Biotage, Uppsala, Sweden). Silica gel 60 (40–63 μm; Merck) was used for the purification of intermediates and final compounds, through flash column chromatography. Melting points were determined in open capillary tubes with a Stuart SMP30 Melting Point Apparatus (Cole-Parmer Stuart, Stone, UK). All tested compounds were characterized by means of mono- and bi-dimensional NMR techniques, FT-IR, and ESI-MS. ¹H and ¹³C NMR spectra were acquired at ambient temperature with a Varian Oxford 300 MHz instrument (Varian, Palo Alto, CA, USA) or a Bruker Avance 300 MHz instrument (Bruker, Billerica, MA, USA), operating at 300 MHz for ¹H and 75 MHz for ¹³C. Chemical shifts are expressed in ppm (δ), while J-couplings are given in Hertz. The full decoupling mode was employed for ¹³C spectra when the relaxation times of the carbons did not allow for a sufficient resolution using the APT sequence. The 2D-NOESY sequence was employed to unambiguously assign the hydrogen signals, when appropriate. HMBC and HSQC analyses were performed to aid the assignment of ¹³C NMR signals, when necessary. ATR-FT-IR spectra were acquired with a Perkin Elmer Spectrum One FT-IR (Perkin Elmer, Waltham, MA, USA), equipped with a Perkin Elmer Universal ATR sampling accessory consisting of a diamond crystal. Analyses were performed in a spectral region between 4000 and 650 cm⁻¹ and analyzed by transmittance technique with 28 scansions and 4 cm⁻¹ resolution. MS analyses were carried out with a Thermo Fisher (Waltham, MA, USA) LCQ Fleet system, equipped with an ESI electrospray ionization source and an Ion Trap mass analyzer; ionization: ESI positive or ESI negative; capillary temperature: 250 °C; source voltage: 5.50 kV; source current: 4.00 μA; multipole 1 and 2 offset: −5.50 V and −7.50 V, respectively; intermultipole lens voltage: −16.00 V; trap DC offset voltage: −10.00 V. The purity of the tested compounds was assessed by means of elemental analysis using a EuroVector EA 3000 CHNS-O analyzer (EuroVector, Pavia, Italy). All experimental values are within ± 0.40% of the theoretical predictions, indicating a ≥ 95% purity.

All synthetic procedures are reported in the Supplementary Materials (SM).

5-(3-Cyanophenyl)thiophene-2-carboxylic acid (1a). The compound was synthesized by a specific procedure, reported in SM. Aspect: white solid. Mp: 207 °C. TLC (DCM-MeOH 9:1): R_f = 0.20. The following analytical data are referred to the sodium salt. ¹H NMR (300 MHz, DMSO-d₆) δ 8.09 (t, J = 1.7 Hz, 1H, H₆), 7.91 (ddd, J = 7.9, 2.0, 1.2 Hz, 1H, H₈), 7.70 (dt, J = 7.7, 1.4 Hz, 1H, H₁₀), 7.57 (t, J = 7.8 Hz, 1H, H₉), 7.48 (d, J = 3.7 Hz, 1H, H₃), 7.21 (d, J = 3.7 Hz, 1H, H₄) ppm. ¹³C NMR (75 MHz, DMSO-d₆) δ 164.80 (COO⁻), 149.77 (C₂), 141.67 (C₅), 136.20 (C_5’), 131.04 (C₈), 130.74 (C₉), 130.17 (C₁₀), 128.71 (C₆, C₃), 125.45 (C₄), 119.01 (CN), 112.70 (C₇) ppm. FT-IR (ATR) ν = 2235, 1578, 1537, 1450, 1397, 1335, 811, 789, 767, 682, 675 cm⁻¹. Anal. calcd. for C₁₂H₆NNaO₂S: C, 57.37; H, 2.41; N, 5.58; S, 12.76. Found: C, 57.48; H, 2.45; N, 5.61; S, 12.83.

5-(4-Nitrophenyl)thiophene-2-carboxylic acid (1b). The compound was obtained according to Procedure A (SM). Starting compound: methyl 5-(4-nitrophenyl)thiophene-2-carboxylate. Yield: 98%. Aspect: yellow solid. Mp: 189 °C. TLC (DCM-MeOH 9:1): R_f = 0.20. The following analytical data are referred to the sodium salt. ¹H NMR (300 MHz, DMSO-d₆) δ 8.21 (d, J = 9.0 Hz, 2H, H_7,7’), 7.97 (d, J = 9.0 Hz, 2H, H_6,6’), 7.57 (d, J = 3.7 Hz, 1H, H₃), 7.22 (d, J = 3.7 Hz, 1H, H₄) ppm. ¹³C NMR (75 MHz, DMSO-d₆) δ 164.05 (COO⁻), 152.14 (C₂), 146.32 (C₈), 141.46 (C₅), 141.24 (C_5’), 128.78 (C₃), 126.96 (C₄), 126.15 (C_7,7’), 124.86 (C_6,6’) ppm. FT-IR (KBr) ν = 3435, 2920, 2550, 1927, 1664, 1622, 1514, 1450, 1365, 995, 833, 704 cm⁻¹. ESI-MS (m/z) calcd for C₁₁H₆NNaO₄S 270.99, found 204.71 [M-CO₂Na]⁻. Anal. calcd. for C₁₁H₆NNaO₄S: C, 48.71; H, 2.23; N, 5.16; S, 11.82. Found: C, 48.75; H, 2.27; N, 5.14; S, 11.71.

Sodium 5-(3-cyanophenyl)thiazole-2-carboxylate (2a). The compound was obtained according to Procedure B (SM). Starting compound: ethyl 5-(3-cyanophenyl)thiazole-2-carboxylate. Yield: 86%. Aspect: white solid. Mp: >300 °C (dec.). ¹H NMR (300 MHz, DMSO-d₆) δ 8.20 (s, 1H, H₄), 8.19 (t, J = 1.4 Hz, 1H, H₆), 7.95 (ddd, J = 7.9, 1.9, 1.2, Hz, 1H, H₁₀), 7.77 (dt, J = 7.7, 1.2, H₈), 7.60 (dt, J = 7.9, 0.5 Hz, 1H, H₉) ppm. ¹³C NMR (75 MHz, DMSO-d₆) δ 173.60 (C₂), 161.61 (COO⁻), 140.73 (C₄), 138.39 (C₅), 133.51 (C_5’), 131.81 (C₈), 131.51 (C₁₀), 130.85 (C₉), 129.86 (C₆), 118.85 (CN), 112.81 (C₇) ppm. FT-IR (ATR) ν = 3354, 2235, 1663, 1641, 1578, 1440, 1407, 1366, 1110, 866, 806, 796 cm⁻¹. Anal. calcd. for C₁₁H₅N₂NaO₂S: C, 52.38; H, 2.00; N, 11.11; S, 12.71. Found: C, 52.51; H, 2.02; N, 11.09; S, 12.75.

Sodium 5-(4-nitrophenyl)thiazole-2-carboxylate (2b). The compound was obtained according to Procedure A (SM). Starting compound: ethyl 5-(4-nitrophenyl)thiazole-2-carboxylate. Yield: 85%. Aspect: dark green solid. Mp: >300 °C (dec.). ¹H NMR (300 MHz, DMSO-d₆) δ 8.29 (s, 1H, H₄), 8.23 (d, J = 6.0 Hz, 2H, H_7,7’), 7.93 (d, J = 6.0 Hz, 2H, H_6,6’) ppm. ¹³C NMR (75 MHz, DMSO-d₆) δ 174.68 (C₂), 161.40 (COO⁻), 146.99 (C₈), 141.97 (C₄), 138.75 (C_5’), 138.37 (C₅), 127.62 (C_7,7’), 124.86 (C_6,6’) ppm. FT-IR (ATR) ν = 3648, 3297, 3100, 2963, 1675, 1645, 1621, 1595, 1514, 1424, 1408, 1365, 1343, 1108, 847 cm⁻¹. ESI-MS (m/z) calcd for C₁₀H₅N₂NaO₄S 272.21, found 205.78 [M-CO₂Na]⁻. Anal. calcd. for C₁₀H₅N₂NaO₄S: C, 44.12; H, 1.85; N, 10.29; S, 11.78. Found: C, 44.31; H, 1.87; N, 10.34; S, 11.67.

Sodium 5-(3-cyanophenyl)oxazole-2-carboxylate (3a). The compound was obtained according to Procedure B (SM). Starting compound: ethyl 5-(3-cyanophenyl)oxazole-2-carboxylate. Yield: 89%. Aspect: grey solid. Mp: >300 °C (dec.). ¹H NMR (300 MHz, DMSO-d₆) δ 8.17 (t, J = 1.6 Hz, H₆), 7.99 (dt, J = 8.0, 1.6 Hz, 1H, H₁₀), 7.74 (dt, J = 8.0, 1.6 Hz, 1H, H₈), 7.66 (t, J = 8.0 Hz, H₉) ppm. ¹³C NMR (75 MHz, DMSO-d₆) δ 161.87 (COO⁻), 157.88 (C₂), 148.06 (C₅), 131.96 (C₉), 130.85 (C₈), 129.69 (C_5’), 128.69 (C₁₀), 127.90 (C₆₎, 125.07 (C₄), 118.78 (CN), 112.74 (C₇) ppm. FT-IR (ATR) ν = 3522, 3383, 2234, 1650, 1616, 1520, 1422, 1389, 1318, 1273, 1216, 965, 825, 817, 795 cm⁻¹. ESI-MS (m/z) calcd. for C₁₁H₅N₂NaO₃ 236.16, found 169.67 [M-CO₂Na]⁻. Anal. calcd. for C₁₁H₅N₂NaO₃: C, 55.94; H, 2.13; N, 11.86. Found: C, 56.03; H, 2.15; N, 11.93.

Sodium 5-(4-nitrophenyl)oxazole-2-carboxylate (3b). The compound was obtained according to Procedure B (SM). Starting compound: ethyl 5-(4-nitrophenyl)oxazole-2-carboxylate. Yield: 80%. Aspect: pale yellow solid. Mp: >300 °C (dec.). ¹H NMR (300 MHz, DMSO-d₆) δ 8.30 (d, J = 8.9 Hz, 2H, H_7,7’), 7.96 (d, J = 6.0 Hz, 2H, H_6,6’), 7.87 (s, 1H, H₄) ppm. ¹³C APT NMR (75 MHz, DMSO-d₆) δ 162.28 (COO⁻), 157.95 (C₂), 148.37 (C₅), 147.06 (C₈), 134.32 (C_5’), 126.99 (C₄), 125.31 (C_7,7’), 124.92 (C_6,6’) ppm. FT-IR (ATR) ν = 3436, 2964, 1645, 1607, 1512, 1388, 1346, 1261, 1108, 854, 818 cm⁻¹. ESI-MS (m/z) calcd. for C₁₀H₅N₂NaO₅ 256.15, found 189.94 [M-CO₂Na]⁻. Anal. calcd. for C₁₀H₅N₂NaO₅: C, 46.89; H, 1.97; N, 10.94. Found: C, 46.59; H, 1.98; N, 10.92.

5-(3-Cyanophenyl)-1H-imidazole-2-carboxylic acid (4a). The compound was synthesized through a specific procedure, reported in SM. Aspect: white solid. Mp: 165 °C. TLC (DCM-MeOH 7:3): R_f = 0.42. ¹H NMR (300 MHz, DMSO-d₆) δ 12.0-9.0 (broad s exch. D₂O, 2H, NH₂⁺), 8.25 (s, 1H, H₆), 8.16 (d, J = 7.8 Hz, 1H, H₈), 7.99 (s, 1H, H₄), 7.68 (d, J = 7.8 Hz, 1H, H₁₀), 7.58 (t, J = 7.8 Hz, 1H, H₉) ppm. The compound degrades in solution at room temperature, during the acquisition of the ¹³C NMR spectrum. FT-IR (ATR) ν = 3205, 2228, 1666, 1601, 1514, 1473, 1426, 1403, 1334, 1130, 1089, 811, 780, 680 cm⁻¹. ESI-MS (m/z) calcd. for C₁₁H₇N₃O₂ 213.19, found 212.42 [M-H]⁻. Anal. calcd. for C₁₁H₇N₃O₂: C, 61.97; H, 3.31; N, 19.71. Found: C, 62.03; H, 3.35; N, 19.82.

5-(4-Nitrophenyl)-1H-imidazole-2-carboxylic acid (4b). The compound was obtained according to Procedure C (SM). Starting compound: ethyl 5-(4-nitrophenyl)-1H-imidazole-2-carboxylate. Yield: 66%. Aspect: red solid. Mp: 137 °C. TLC (DCM-MeOH 7:3): R_f = 0.40. The following analytical data are referred to the sodium salt. ¹H NMR (300 MHz, DMSO-d₆) δ 8.15-8.09 (m, 4H, H_6,6’, H_7,7’), 7.76 (s, 1H, H₄) ppm. ¹³C NMR (75 MHz, DMSO-d₆) δ 162.09 (COO⁻), 149.48 (C₂), 145.46 (C₈), 142.17 (C₅), 137.58 (C_5’), 125.45 (C_7,7’), 124.19 (C_6,6’), 117.67 (C₄) ppm. FT-IR (ATR) ν = 3607, 3156, 1652, 1600, 1494, 1472, 1415, 1342, 1135, 1112, 992, 849, 751 cm⁻¹. ESI-MS (m/z) calcd for C₁₀H₇N₃O₄ 233.18, found 232.32 [M-H]⁻. Anal. calcd. for C₁₀H₆N₃NaO₄: C, 47.07; H, 2.37; N, 16.47. Found: C, 47.31; H, 2.39; N, 16.36.

5-(3-Cyanophenyl)-1,3,4-oxadiazole-2-carboxylic acid (5a). The compound was obtained according to Procedure D (SM). Starting compound: ethyl 5-(3-cyanophenyl)-1,3,4-oxadiazole-2-carboxylate. Yield: quantitative. Aspect: white solid. Mp: 222 °C (dec.). TLC (DCM-MeOH 7:3): R_f = 0.42. The following analytical data are referred to the sodium salt. ¹H NMR (300 MHz, DMSO-d₆) δ 8.35 (t, J = 1.8 Hz, 1H, H₆), 8.28 (dt, J = 8.0, 1.4 Hz, 1H, H₈), 8.06 (dt, J = 7.8, 1.4 Hz, 1H, H₁₀), 7.79 (dt, J = 7.9, 0.7 Hz, 1H, H₉) ppm. The compound degrades in solution at room temperature, during the acquisition of the ¹³C NMR spectrum. FT-IR (ATR) ν = 3543, 3384, 2232, 1651, 1614, 1549, 1400, 1343, 1228, 1183, 1086, 812, 807, 679 cm⁻¹. Anal. calcd. for C₁₀H₄N₃NaO₃: C, 50.65; H, 1.70; N, 17.72. Found: C, 50.71; H, 1.81; N, 17.87.

5-(4-Nitrophenyl)-1,3,4-oxadiazole-2-carboxylic acid (5b). The compound was obtained according to Procedure D (SM). Starting compound: ethyl 5-(4-nitrophenyl)-1,3,4-oxadiazole-2-carboxylate. Yield: quantitative. Aspect: pale yellow solid. Mp: 220 °C (dec.). TLC (DCM-MeOH 7:3): R_f = 0.44. ¹H NMR (300 MHz, DMSO-d₆) δ 13.7 (broad s exch. D₂O, 1H, COOH), 8.30 (d, J = 8.9 Hz, 2H, H_7,7’), 8.15 (d, J = 8.9 Hz, 2H, H_6,6’) ppm. ¹³C NMR (75 MHz, DMSO-d₆) δ 166.24 (COOH), 150.51 (C₅), 136.98 (C_5’), 131.14 (C_7,7’), 124.15 (C_6,6’) ppm. FT-IR (ATR) ν = 2962, 2924, 2853, 1691, 1603, 1520, 1258, 1080, 1013, 789 cm⁻¹. Anal. calcd. for C₉H₅N₃O₅: C, 45.97; H, 2.14; N, 17.87. Found: C, 46.02; H, 2.17; N, 17.96.

1-(3-Cyanophenyl)-1H-1,2,3-triazole-4-carboxylic acid (6a). The compound was synthesized through a specific procedure, reported in SM. Aspect: white solid. TLC (DCM-MeOH 9:1): R_f = 0.14. ¹H NMR (300 MHz, DMSO-d₆) δ 8.90 (s, 1H, H₁), 8.44 (t, J = 2.0 Hz, 1H, H₆), 8.30 (ddd, J = 1.2, 2.0, 8.1 Hz, 1H, H₈), 7.91 (dt, J = 1.2, 8.1 Hz, 1H, H₁₀), 7.77 (t, J = 8.1 Hz, 1H, H₉) ppm. ¹³C NMR (75 MHz, DMSO-d₆) δ 177.11 (C₂), 163.73 (COOH), 137.81 (C_5’), 132.35 (C₈), 131.66 (C₉), 124.99 (C₁₀), 124.28 (C₆), 123.68 (C₁), 118.30 (CN), 113.25 (C₇) ppm. FT-IR (ATR) ν = 3389, 3091, 2235, 1589, 1557, 1536, 1403, 1343, 1312, 1021, 794 cm⁻¹. Anal. calcd. for C₁₀H₆N₄O₂: C, 56.08; H, 2.82; N, 26.16. Found: C, 56.27; H, 2.91; N, 26.35.

1-(4-Nitrophenyl)-1H-1,2,3-triazole-4-carboxylic acid (6b). The compound was obtained according to Procedure A (SM). Starting compound: ethyl 1-(4-nitrophenyl)-1H-1,2,3-triazole-4-carboxylate. Yield: 91%. Aspect: white solid. Mp: 175 °C. TLC (DCM-MeOH 8:2): R_f = 0.12. ¹H NMR (300 MHz, DMSO-d₆) δ 13.4 (broad s exch. D₂O, 1 H, COOH), 9.59 (s, 1H, H₁), 8.46 (d, J = 7.0 Hz, 2H, H_7,7’), 8.30 (d, J = 7.0 Hz, 2H, H_6,6’) ppm. ¹³C NMR (75 MHz, DMSO-d₆) δ 161.73 (COOH), 147.60 (C₈), 141.69 (C₂), 140.96 (C_5’), 128.02 (C₁), 125.90 (C_7,7’), 121.72 (C_6,6’) ppm. FT-IR (ATR) ν = 3249, 3142, 3102, 3061, 2962, 2913, 2866, 1729, 1704, 1596, 1516, 1342, 1268, 1219, 1151, 1032, 982, 869, 854 cm⁻¹. ESI-MS (m/z) calcd for C₉H₆N₄O₄ 234.17, found 161.30 [M-CO₂-N₂]⁻. Anal. calcd. for C₉H₆N₄O₄: C, 46.16; H, 2.58; N, 23.93. Found: C, 46.25; H, 2.60; N, 23.97.

5-(3-Cyano-5-(trifluoromethyl)phenyl)furan-2-carboxylic acid (IV). The compound was synthesized according to a previously published procedure [13]. Yield: 70%. Aspect: white solid. Mp: 210 °C. TLC (DCM-MeOH 7:3): R_f = 0.33. ¹H NMR (300 MHz, DMSO-d₆) δ 13.59-13.10 (broad s. exch. D₂O, 1H, COOH), 8.62-8.57 (m, 1H, H₇), 8.41-8.33 (m, 2H, H₁₁, H₉), 7.52 (d, J = 3.7 Hz, 1H, H₄), 7.38 (d, J = 3.7 Hz, 1H, H₃) ppm. ¹³C APT NMR (75 MHz, DMSO-d₆) δ 159.45 (COOH), 152.84 (C₅), 146.18 (C₂), 132.17 (C₇), 132.17-131.78-131.34-130.90 (q, C₁₀), 131.99 (C₆), 129.14 (C₉), 128.80-125.19-121.56-117.94 (q, CF₃), 125.09 (C₁₁), 120.09 (C₃), 117.53 (CN), 114.28 (C₈), 111.74 (C₄) ppm. FT-IR (ATR): ν = 3130, 3082, 2960, 2917, 2849, 2237, 1688, 1578, 1519, 1455, 1438, 1410, 1344, 1274, 1256, 1163, 1133, 1114, 1085, 1032, 900 cm⁻¹. ESI-MS (m/z) calcd for C₁₃H₆F₃NO₃ 281.03, found 280.14 [M-H]⁻. Anal. calcd. for C₁₃H₆F₃NO₃: C, 55.53; H, 2.15; N, 4.98. Found: C, 55.47; H, 2.19; N, 5.01.

5-(3,5-Bis(trifluoromethyl)phenyl)furan-2-carboxylic acid (V). The compound was synthesized according to a previously published procedure [13]. Yield: 91%. Aspect: white solid. Mp: 168 °C. TLC (DCM-MeOH 7:3): R_f = 0.39. ¹H NMR (300 MHz, DMSO-d₆) δ 13.65-13.20 (broad s. exch. D₂O, 1H, COOH), 8.41-8.36 (m, 2H, H₇, H₁₁), 8.12-8.07 (m, 1H, H₉), 7.59 (d, J = 3.7 Hz, 1H, H₃), 7.38 (d, J = 3.7 Hz, 1H, H₄) ppm. ¹³C APT NMR (75 MHz, DMSO-d₆) δ 159.48 (COOH), 153.19 (C₅), 146.03 (C₂), 132.34-131.90-131.46-131.03 (q, C₈), 132.00 (C₆), 128.98-125.36-121.74-118.12 (q, CF₃), 125.00 (C₁₁), 122.14 (C₉), 120.14 (C₃), 111.73 (C₄) ppm. FT-IR (ATR): ν = 2960, 2925, 2855, 1689, 1621, 1591, 1526, 1455, 1420, 1366, 1278, 1161, 1124, 1081, 1027, 896 cm⁻¹. ESI-MS (m/z) calcd for C₁₃H₆F₆O₆ 324.18, found 323.16 [M-H]⁻. Anal. calcd. for C₁₃H₆F₆O₃: C, 48.17; H, 1.87. Found: C, 48.02; H, 1.91.

5-(3-cyano-5-fluorophenyl)furan-2-carboxylic acid (VI). The compound was synthesized according to a previously published procedure [13]. Yield: quantitative. Aspect: white solid. Mp: 247 °C. TLC (DCM-MeOH 7:3): R_f = 0.26. ¹H NMR (300 MHz, DMSO-d₆) δ 13.38 (broad s exch D₂O, 1H, COOH), 8.14 (t, J = 1.6, 1H, H₇), 7.96 (dd, J = 7.8, 1.6 Hz, 1H, H₁₁), 7.88 (dd, J = 6.0, 1.6 Hz, 1H, H₉), 7.43 (d, J = 3.7 Hz, 1H, H₄), 7.37 (d, J = 3.7 Hz, 1H, H₃) ppm. ¹³C APT NMR (75 MHz, DMSO-d₆) δ 164.18-160.91 (d, CF), 159.53 (COOH), 153.20-153.16 (d, C₅), 145.89 (C₂), 133.05-132.93 (d, C₆) 124.92-124.87 (d, C₇), 120.19 (C₃), 119.75-119.41 (d, C₁₁), 117.72-117.68 (d, CN), 116.57-116.25 (d, C₉), 114.46-114.32 (d, C₈), 111.43 (C₄) ppm. FT-IR (ATR): ν = 3113, 2916, 2849, 2663, 2575, 2231, 1675, 1594, 1519, 1435, 1308, 1214, 1173, 1028, 866, 809, 760 cm⁻¹. ESI-MS (m/z) calcd for C₁₂H₆FNO₃ 231.18, found 230.50 [M-H]⁻. Anal. calcd. for C₁₂H₆F NO₃: C, 62.34; H, 2.62. Found: C, 62.53; H, 2.51.

5-(3-Cyano-5-methoxyphenyl)furan-2-carboxylic acid (VII). The compound was synthesized according to a previously published procedure [13]. Yield: 80%. Aspect: white solid. Mp: 226 °C. TLC (DCM-MeOH 7:3): R_f = 0.46. ¹H NMR (300 MHz, DMSO-d₆) δ 13.42-13.19 (broad s. exch. D₂O, 1H, COOH), 7.82 (t, J = 1.4 Hz, 1H, H₇), 7.59 (dd, J = 2.5, 1.5 Hz, 1H, H₁₁), 7.45 (dd, J = 2.5, 1.3 Hz, 1H, H₉), 7.35 (d, J = 3.7 Hz, 1H, H₃), 7.33 (d, J = 3.7 Hz, 1H, H₄), 3.87 (s, 3H, CH₃) ppm. ¹³C NMR (75 MHz, DMSO-d₆) δ 160.43 (C₁₀) 159.61 (COOH), 154.2 (C₅), 145.46 (C₂), 132.08 (C₆), 120.73 (C₃), 120.20 (C₇), 118.66 (CN), 117.65 (C₉), 115.02 (C₁₁), 113.72 (C₈), 110.60 (C₄), 56.49 (CH₃) ppm. FT-IR (ATR): ν = 3116, 3086, 2926, 2574, 2229, 1693, 1608, 1594, 1572, 1515, 1461, 1427, 1305, 1215, 1167, 1033, 960 cm⁻¹. ESI-MS (m/z) calcd for C₁₃H₉O₄ 243.05, found 242.28 [M-H]⁻. Anal. calcd. for C₁₃H₉F₃O₄: C, 54.56; H, 3.17. Found: C, 54.71; H, 3.23.

5-(3-cyano-5-methylphenyl)furan-2-carboxylic acid (VIII). The compound was synthesized according to a previously published procedure [13]. Yield: 90%. Aspect: white solid. Mp: 238 °C. TLC (DCM-MeOH 7:3): R_f = 0.31 ¹H NMR (300 MHz, DMSO-d₆) δ 13.20 (broad s exch D₂O, 1H, COOH), 8.08-8.02 (m, 1H, H₇), 7.93-7.88 (m, 1H, H₁₁), 7.67-7.62 (m, 1H, H₉), 7.33 (d, J = 3.6 Hz, 1H, H₃), 7.28 (d, J = 3.6 Hz, 1H, H₄), 2.39 (s, 3H, CH₃) ppm. ¹³C NMR (75 MHz, DMSO-d₆) δ 159.56 (COOH), 154.49 (C₂), 145.39 (C₅), 140.84 (C₁₀), 132.82 (C₉), 130.66 (C₆), 129.51 (C₁₁), 125.61 (C₇), 120.13 (C₃), 118.82 (CN), 112.64 (C₈), 110.06 (C₄), 20.89 (CH₃) ppm. FT-IR (ATR): ν = 3119, 2926, 2849, 2692, 2579, 2228, 1726, 1682, 1584, 1520, 1422, 1299, 1169, 1029, 858, 810, 760 cm⁻¹. ESI-MS (m/z) calcd for C₁₃H₉NO₃ 227.063, found 226.35 [M-H]⁻. Anal. calcd. for C₁₃H₉ NO₃: C, 68.72; H, 3.99. Found: C, 68.93; H, 4.01.

5-(3-cyano-5-hydroxyphenyl)furan-2-carboxylic acid (IX). The compound was synthesized according to a previously published procedure [13]. Yield: 95%. Aspect: white solid. Mp: 280 °C (dec.). TLC (DCM-MeOH 7:3 and 3 drops of CH₃COOH): R_f = 0.44. ¹H NMR (300 MHz, DMSO-d₆) δ 13.22 (broad s exch. D₂O, 1H, COOH), 10.54 (broad s exch. D₂O, 1H, OH), 7.71 (t, J = 1.5, 1H, H₇), 7.48 (dd, J = 2.4, 1.5 Hz, 1H, H₁₁), 7.32 (d, J = 3.6 Hz, 1H, H₃), 7.26 (d, J = 3.6 Hz, 1H, H₄), 7.14 (dd, J = 2.4, 1.5, 1H, H₉) ppm. ¹³C APT NMR (75 MHz, DMSO-d₆) δ 159.50 (C₁₀), 158.90 (COOH), 154.42 (C₅), 145.27 (C₂), 132.09 (C₆), 120.10 (C₃), 119.32 (C₇), 118.93 (C₉), 118.74 (CN), 115.92 (C₁₁), 113.50 (C₈), 110.08 (C₄) ppm. FT-IR (ATR): ν = 3400, 3108, 2602, 2228, 1652, 1595, 1516, 1487, 1439, 1310, 1241, 1213, 1174, 1152, 1035, 963, 881, 816, 668 cm⁻¹. ESI-MS (m/z) calcd. for C₁₂H₇NO₄ 229.19, found 228.29 [M-H]⁻. Anal. calcd. for C₁₂H₇ NO₄: C, 62.89; H, 3.08. Found: C, 62.53; H, 3.05.