RCHH HARM
A P
Arch. Pharm. Chem. Life Sci. 2016, 349, 42–49
New Triazoles as Potent Antifungal Agents
Archiv der Pharmazie
1,2,3-triazole-H), 7.35–6.77 (7H, m, Ar-H), 5.98 (1H, s, OH),
4.69–4.49 (2H, dd, J ¼ 14.1 Hz, 1,2,4-triazole-CH2), 4.46–4.43
(2H, t, CH2CH2O), 4.40 (2H, s, ArCH2O), 3.72–3.69 (2H, t,
CH2CH2O), 3.38–3.10 (2H, dd, J ¼ 15.3 Hz, 1,2,3-triazole-CH2C-
(OH); 13C NMR (125 MHz, DMSO-d6, TMS): d 163.97, 161.66,
150.99, 145.32, 141.90, 141.45, 130.70, 130.63, 130.41, 126.90,
124.42, 123.57, 114.64, 114.24, 110.99, 104.39, 74.16, 71.37,
68.75, 57.29, 49.65, 34.98; ESI-MS (m/z): 459.2 (MþH); Anal.
calcd. for C22H21F3N6O2: C, 57.64; H, 4.62; N, 18.33. Found, C,
57.58; H, 4.69; N, 18.43.
141.07, 133.45, 130.60, 130.43, 127.84, 127.44, 126.27, 126.20,
126.10, 124.41, 110.99, 104.39, 74.16, 71.2, 68.76, 57.33,
49.63, 34.99; d ESI-MS (m/z): 475.2 (MþH); Anal. calcd. for
C22H21ClF2N6O2: C, 55.64; H, 4.46; N, 17.70. Found, C, 55.58;
H, 4.55; N, 17.61.
1-(1-(2-((4-Chlorobenzyl)oxy)ethyl)-1H-1,2,3-triazol-4-yl)-
2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-
ol (6f)
The product 6f was obtained as a white solid. Mp: 105.9–
106.6°C; 1H NMR (300 MHz, DMSO-d6, TMS): d 8.26 (1H, s, 1,2,4-
triazole-H), 7.74 (1H, s, 1,2,4-triazole-H), 7.58 (1H, s, 1,2,3-
triazole-H), 7.36–6.73 (7H, m, Ar-H), 5.97 (1H, s, OH), 4.68–4.48
(2H, dd, J ¼ 14.4 Hz, 1,2,4-triazole-CH2), 4.44–4.41 (2H, t,
CH2CH2O), 4.36 (2H, s, ArCH2O), 3.70–3.67 (2H, t, CH2CH2O),
3.39–3.10(2H,dd,J ¼ 15.0 Hz,1,2,3-triazole-CH2C(OH);13CNMR
(125 MHz, DMSO-d6, TMS): d 161.08, 158.28, 151.01, 145.34,
141.90, 137.48, 132.47, 130.42, 130.30, 129.61, 128.67, 126.17,
126.07, 124.40, 111.02, 104.76, 74.17, 71.35, 68.65, 57.33,
49.65, 35.00; ESI-MS (m/z): 475.1 (MþH); Anal. calcd. for
1-(1-(2-((4-Fluorobenzyl)oxy)ethyl)-1H-1,2,3-triazol-4-yl)-
2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-
ol (6c)
The product 6c was obtained as a white solid. Mp: 79.7–
81.1°C; 1H NMR (300 MHz, DMSO-d6, TMS): d 8.37 (1H, s, 1,2,4-
triazole-H), 7.74 (1H, s, 1,2,4-triazole-H), 7.61 (1H, s, 1,2,3-
triazole-H), 7.33–6.72 (7H, m, Ar-H), 6.24 (1H, s, OH), 4.71–4.55
(2H, dd, J ¼ 14.1 Hz, 1,2,4-triazole-CH2), 4.44–4.40 (2H, t,
CH2CH2O), 4.35 (2H, s, ArCH2O), 3.69–3.66 (2H, t, CH2CH2O),
3.40–3.11 (2H, dd, J ¼ 15.0 Hz, 1,2,3-triazole-CH2C(OH);
13C NMR (125 MHz, DMSO-d6, TMS): d 162.97, 161.04, 158.33,
150.94, 141.99, 134.62, 130.55, 130.51, 130.44, 130.03, 129.97,
124.40,115.55,115.38,110.93, 104.99, 74.16,71.46,68.53,57.20,
49.65, 34.97; ESI-MS (m/z): 459.2 (MþH); Anal. calcd. for
C22H21ClF2N6O2: C, 55.64; H, 4.46; N, 17.70. Found, C, 55.66;
H, 4.39; N, 17.80.
1-(1-(2-((2-Bromobenzyl)oxy)ethyl)-1H-1,2,3-triazol-4-yl)-
2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-
ol (6g)
C22H21F3N6O2: C, 57.64; H, 4.62; N, 18.33. Found, C, 57.49; H,
4.58; N, 18.40.
The product 6g was obtained as a white solid. Mp: 87.6–
89.2°C; 1H NMR (300 MHz, DMSO-d6, TMS): d 8.26 (1H, s, 1,2,4-
triazole-H), 7.74 (1H, s, 1,2,4-triazole-H), 7.58 (1H, s, 1,2,3-
triazole-H), 7.56–6.71 (7H, m, Ar-H), 5.96 (1H, s, OH), 4.68–4.48
(2H, dd, J ¼ 14.1 Hz, 1,2,4-triazole-CH2), 4.48–4.45 (2H, t,
CH2CH2O), 4.43 (2H, s, ArCH2O), 3.81–3.79 (2H, t, CH2CH2O),
3.38–3.10(2H,dd,J ¼ 15.0 Hz,1,2,3-triazole-CH2C(OH);13CNMR
(125 MHz, DMSO-d6, TMS): d 161.07, 158.28, 151.00, 145.33,
141.90, 137.40, 132.78, 130.72, 129.94, 129.64, 128.12, 126.41,
124.44, 122.49, 110.99, 107.05, 74.16, 71.76, 69.11, 57.30,
49.68, 35.01; ESI-MS (m/z): 519.3 (MþH); Anal. calcd. for
1-(1-(2-((2-Chlorobenzyl)oxy)ethyl)-1H-1,2,3-triazol-4-yl)-
2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-
ol (6d)
The product 6d was obtained as a white solid. Mp: 87.7–
88.6°C; 1H NMR (300 MHz, DMSO-d6, TMS): d 8.27 (1H, s, 1,2,4-
triazole-H), 7.75 (1H, s, 1,2,4-triazole-H), 7.61 (1H, s, 1,2,3-
triazole-H), 7.43–6.72 (7H, m, Ar-H), 5.97 (1H, s, OH), 4.69–4.49
(2H, dd, J ¼ 14.4 Hz, 1,2,4-triazole-CH2), 4.49–4.46 (4H, t,
ArCH2O, CH2CH2O), 3.80–3.77 (2H, t, CH2CH2O), 3.39–3.11
(2H, dd, J ¼ 14.7 Hz, 1,2,3-triazole-CH2C(OH); 13C NMR
(125 MHz, DMSO-d6, TMS): d 160.26, 158.29, 151.01, 145.35,
141.92, 135.84, 132.39, 130.54, 129.69, 129.60, 129.57, 127.58,
126.30, 124.43, 110.98, 105.72, 74.18, 69.52, 69.11, 57.32,
49.67, 35.02; ESI-MS (m/z): 475.1 (MþH); Anal. calcd. for
C
22H21BrF2N6O2: C, 50.88; H, 4.08; N, 16.18. Found, C, 50.77;
H, 4.13; N, 16.12.
1-(1-(2-((3-Bromobenzyl)oxy)ethyl)-1H-1,2,3-triazol-4-yl)-
2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-
ol (6h)
C
22H21ClF2N6O2: C, 55.64; H, 4.46; N, 17.70. Found, C, 55.72; H,
4.53; N, 17.68.
The product 6h was obtained as a white solid. Mp: 137.9–
139.4°C; 1H NMR (300 MHz, DMSO-d6, TMS): d 8.27 (1H, s, 1,2,4-
triazole-H), 7.75 (1H, s, 1,2,4-triazole-H), 7.60 (1H, s, 1,2,3-
triazole-H), 7.47–6.74 (7H, m, Ar-H), 5.97 (1H, s, OH), 4.69–4.49
(2H, dd, J ¼ 14.1Hz, 1,2,4-triazole-CH2), 4.46–4.43 (2H, t,
CH2CH2O), 4.38 (2H, s, ArCH2O), 3.72–3.69 (2H, t, CH2CH2O),
3.39–3.11(2H,dd,J ¼ 15.0 Hz,1,2,3-triazole-CH2C(OH);13CNMR
(125 MHz, DMSO-d6, TMS): d 160.51, 158.87, 151.01, 145.34,
141.91, 141.34, 130.91, 130.77, 130.37, 126.69, 126.24, 126.09,
124.41, 122.07, 111.00, 105.49, 74.18, 71.25, 68.77, 57.29,
49.63, 35.03; ESI-MS (m/z): 519.2 (MþH); Anal. calcd. for
1-(1-(2-((3-Chlorobenzyl)oxy)ethyl)-1H-1,2,3-triazol-4-yl)-
2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-
ol (6e)
The product 6e was obtained as a white solid. Mp: 139.7–
140.7°C; 1H NMR (300 MHz, DMSO-d6, TMS): d 8.24 (1H, s, 1,2,4-
triazole-H), 7.83 (1H, s, 1,2,4-triazole-H), 7.38 (1H, s, 1,2,3-
triazole-H), 7.40–6.66 (7H, m, Ar-H), 5.45 (1H, s, OH), 4.76–4.56
(2H, dd, J ¼ 14.1 Hz, 1,2,4-triazole-CH2), 4.51–4.45 (2H, t,
CH2CH2O), 4.39 (2H, s, ArCH2O), 3.76–3.73 (2H, t, CH2CH2O),
3.51–3.14(2H,dd,J ¼ 15.0 Hz,1,2,3-triazole-CH2C(OH);13CNMR
(125 MHz, DMSO-d6, TMS): d 161.23, 158.49, 151.37, 141.91,
C
22H21BrF2N6O2: C, 50.88; H, 4.08; N, 16.18. Found, C, 50.80;
H, 4.15; N, 16.11.
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