Molecules 2019, 24, 1996
12 of 18
Starting materials 1a
–
d,
1f
–
s, 1al
–
ar were obtained from Alfa Asear and were used as supplied
without additional purification. Other starting materials were synthesised, with spectra provided in
the supplementary information.
6-Chlorobenzo[1,3]thiazole (2d): Eluent: hexane/ethyl acetate (100:1)
1H-NMR (400 MHz, CDCl3)
8.98 (s, 1H), 8.05 (d, J = 8.7 Hz, 1H), 7.95 (d, J = 2.1 Hz, 1H), 7.49 (dd,
J = 8.7, 2.1 Hz, 1H). 13C-NMR (101 MHz, CDCl3)
154.51 (CH), 151.72 (C), 135.06 (C), 131.95 (C), 127.34
(CH), 124.46 (CH), 121.66 (CH). ASAP-MS (MeCN) Rt = 0.50 min [M + H]+ = 170.0.
→(4:1) yellow crystals, 68% yield.
δ
δ
3-(1-Methylethyl)benzoic acid (2e): Eluent: hexane/ethyl acetate (100:1) (4:1). Yellow needles, 96% yield.
1H-NMR (400 MHz, CDCl3)
8.00 (d, J = 1.8 Hz, 1H), 7.95 (dt, J = 7.6, 1.4 Hz, 1H), 7.48 (d, J = 1.3 Hz,
1H), 7.40 (t, J = 1.3 Hz, 1H), 2.99 (p, J = 7.3 Hz, 1H), 1.29 (d, J = 7.3 Hz, 6H). 13C-NMR (101 MHz,
→
δ
CDCl3) δ 172.87 (C), 149.44 (C), 132.29 (CH), 129.46 (C), 128.63 (CH), 128.34 (CH), 127.93 (CH), 34.16
(CH), 24.01 (CH3). LC-MS (MeCN) Rt = 2.25 min [M
found 163.0754, (∆ = −3.1 ppm).
−
H]− = 163.2. HRMS C10H11O2 calc. 163.0759,
1
Methyl thiophene-3-carboxylate (2r): Eluent: hexane/ethyl acetate (100:1)
→
(10:1). H-NMR (400 MHz,
CDCl3)
δ 8.12 (dd, J = 3.0, 1.2 Hz, 1H), 7.54 (dd, J = 5.1, 1.2 Hz, 1H), 7.41–7.28 (m, 1H), 3.95–3.85
(m, 3H). 13C-NMR (101 MHz, CDCl3)
δ 161.28, 133.50, 132.70, 127.88, 126.04, 51.84. LC-MS (MeOH)
Rt = 0.87 min [M + H]+ = 143.1.
Benzo[1,3]thiazole (2s): Eluent: hexane/ethyl acetate (100:1) (10:1). Brown, volatile oil, 99% yield.
→
1H-NMR (400 MHz, CDCl3)
δ = 9.00 (s, 1H), 8.35 (d, J = 8.2 Hz, 1H), 7.95 (d, J = 8.2 Hz, 1H), 7.51
(t, J = 7.7 Hz, 1H), 7.42 (t, J = 7.7 Hz, 1H). GC-MS M+ 135.1.
5-(2-Bromophenyl)-1,3,4-thiadiazol-2-amine (1t): Starting material 1t was prepared following the procedure
1
of Mullick et al. [19] and isolated as a white solid in 85% yield. H-NMR (400 MHz, CDCl3)
δ 8.01 (dd,
J = 7.8, 1.7 Hz, 1H), 7.70 (dd, J = 7.9, 1.3 Hz, 1H), 7.43 (td, J = 7.6, 1.3 Hz, 1H), 7.37–7.29 (m, 1H), 6.06 (br.
s, 2H). 1H-NMR (400 MHz, DMSO-d6)
7.87 (dd, J = 7.8, 1.8 Hz, 1H), 7.75 (dd, J = 7.8, 1.2 Hz, 1H),
7.53–7.41 (m, 3H), 7.37 (td, J = 7.8, 1.8 Hz, 1H). 13C-NMR (101 MHz, DMSO-d6)
170.47 (C), 153.62 (C),
134.17, 131.66,
δ
δ
134.17 (C), 132.07 (C), 131.65 (C), 128.53 (C), 121.38 (C). 13C-NMR (101 MHz, DMSO-d6)
δ
131.64, 128.53. LC-MS (MeCN) Rt = 1.69 min [M + H]+ = 258.2. HRMS C8H6N3S79Br calc. 255.9544,
found 255.9551, (∆ = 2.7 ppm).
2-(2-Bromophenyl)-1,3,4-thiadiazole (2t): Eluent: hexane/ethyl acetate (95:5)
→
(4:1). Brown oil, 67% yield.
1H-NMR (400 MHz, CDCl3)
δ 9.25 (s, 1H), 8.14 (d, J = 7.8 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.46
(t, J = 7.6 Hz, 1H), 7.36 (t, J = 7.5 Hz, 1H). 13C-NMR (101 MHz, CDCl3)
δ 165.25 (C), 152.87 (CH), 134.12
(CH), 132.21 (CH), 132.01 (CH), 130.67 (C), 128.03 (CH), 122.71 (C).
4-(4-Cyano-1H-pyrazol-1-yl)-benzoic acid (2u): [20] Starting material 1u was prepared following the
procedure of Smith et al. [21]. The product was obtained via recrystallization from methanol. Purple
1
powder, 70% yield. H-NMR (400 MHz, DMSO-d6)
δ
13.19 (s, 1H), 9.46 (s, 1H), 8.43 (s, 1H), 8.10 (d,
143.56 (CH), 138.89 (C),
J = 8.8 Hz, 2H), 8.00 (d, J = 8.8 Hz, 2H). 13C-NMR (101 MHz, DMSO-d6)
δ
134.24 (CH), 130.34 (CH), 118.24 (CH), 113.65 (C), 93.07 (C), 51.03 (CH). LC-MS (MeCN) Rt = 1.67 min
[M − H]– = 212.2. HRMS C11H6N3O2 calc. 212.0460, found 212.0456, (∆ = −1.9 ppm).
1-(4-Fluorophenyl)-1H-pyrazole-4-carbonitrile (2v): [22,23] Starting material 1v was prepared following
the procedure of Smith et al. [21]. The product was obtained via recrystallization from ethanol and
1
water. Brown crystals, 77% yield. H-NMR (400 MHz, DMSO-d6)
δ
9.28 (s, 1H), 8.33 (s, 1H), 8.00–7.73
(m, 2H), 7.52–7.16 (m, 2H). 13C-NMR (101 MHz, DMSO-d6)
δ161.62 (C, d, J = 245.8 Hz), 143.96 (CH),
135.47 (C, d, J = 3.0 Hz), 134.75 (CH), 122.01 (CH, d, J = 9.0 Hz), 116.93 (CH, d, J = 23.8 Hz), 113.97 (C),
93.59 (C). 19F NMR (376 MHz, DMSO-d6) δ −114.22. GC-MS (MeCN) Rt = 0.30 min M+ = 187.1. HRMS
C10H7N3F calc. 188.0624, found 188.0615, (∆ = −4.8 ppm).