686 Venugopala
Asian J. Chem.
TABLE-1
PRELIMINARY SCREENING OF REACTION CONDITIONS FOR THE SYNTHESIS OF REPRESENTATIVE
COMPOUND 4-[3,5-BIS(TRIFLUOROMETHYL)PHENYL]-2-PHENYLOXAZOLE (3c)
Reaction time (min)
Yieldc
Entry
Reflux methoda
Microwave methodb
Reflux method
83
Microwave method
97
120
10
3c
aTo a solution of 1-[3,5-bis(trifluoromethyl)phenyl]-2-bromoethan-1-one (1) (0.5 mmol) in absolute ethanol (10 mL) was added benzamide (0.5
mmol) and refluxed for 120 min by monitoring reaction progress on the thin layer chromatography.
bTo a solution of 1-[3,5-bis(trifluoromethyl)phenyl]-2-bromoethan-1-one (1) (0.5 mmol) in absolute ethanol (10 mL) was added benzamide (0.5
mmol) and the resulting reaction mixture was exposed to microwaves for 10 min. The reaction progress was monitored on the thin layer
chromatography by withdrawing samples at every 2 min from reaction vessel.
cYields after purification by recrystallization method using ethanol as suitable solvent.
TABLE-2
PHYSICO-CHEMICAL CONSTANTS OF 4-[3,5-BIS(TRIFLUOROMETHYL)PHENYL)-2-SUBSTITUTED OXAZOLES (3a-i)
Compd. No.
m.f.
C13H7NOF6
C12H7NO2F6
C17H9NOF6
C18H12N2O2F6
C17H7NOCl2F6
C17H10N2OF6
C17H10N2OF6
C17H9N2OClF6
C16H9N3OF6
Molar mass
307.04
311.00
357.00
402.00
424.00
372.00
372.00
406.00
373.00
R
Reaction time (min)
Yield (%)a,b
m.p. (°C)
133-134
112-113
167-168
183-184
141-142
211-212
208-209
214-215
198-199
c Log Pc
4.4486
2.6866
5.8226
5.0245
6.7514
4.7756
4.7756
5.6523
4.3538
CH2=CH2
CH2-OH
C6H5
10
10
10
10
10
10
10
10
10
93
89
97
91
98
90
86
92
94
3a
3b
3c
3d
3e
3f
3g
3h
3i
3-NH2, 4-OCH3 C6H5
2,6-diCl-C6H5
3-NH2 C6H5
4-NH2 C6H5
2-NH2, 5-Cl C6H5
2-NH2 Pyridyl
aAll of the products were characterized by spectral and physical data; bYields after purification by recrystallization method using ethanol as solvent;
cc Log P was calculated using ChemDraw Professional 16
(400 MHz, DMSO-d6): δ = 150.61, 140.11, 133.63, 132.60,
132.52, 131.89, 131.90, 129.81, 129.80, 124.72, 124.71,
123.12, 63.01; LC-MS: m/z = 312 (M+1);Anal. calcd. (%) for
C12H7NO2F6; C, 46.32; H, 2.27; N, 4.50; Found (%): C, 46.33;
H, 2.26; N, 4.54.
4-[3,5-Bis(trifluoromethyl)phenyl]-2-phenyloxazole
(3c): FT-IR (KBr, νmax, cm–1): 2982, 1600, 1505, 1474, 1221;
1H NMR (400 MHz, DMSO-d6): δ = 8.32 (s, 1H), 7.63-8.18
(m, 8H); 13C NMR (400 MHz, DMSO-d6): δ = 159.39, 140.11,
139.92, 133.60, 131.80, 131.79, 130.63, 129.81, 129.80,
129.20, 128.71, 128.11, 127.51, 127.50, 124.71, 124.70; LC-
MS: m/z = 358 (M+1); Anal. calcd. (%) for C17H9NOF6; C,
57.15; H, 2.54; N, 3.92; Found (%): C, 57.13; H, 2.55; N,
3.93.
5-(4-[3,5-Bis(trifluoromethyl)phenyl]oxazol-2-yl)-2-
methoxyaniline (3d): FT-IR (KBr, νmax, cm–1): 2988, 1622,
1504, 1466, 1219; 1H NMR (400 MHz, DMSO-d6): δ = 8.09-
8.33 (m, 3H), 6.89-7.68 (m, 4H), 5.29 (s, 2H), 3.79 (s, 3H);
13C NMR (400 MHz, DMSO-d6): δ = 159.33, 147.43, 140.19,
139.92, 136.8, 133.6, 131.81, 131.80, 129.82, 129.81, 124.71,
124.70, 123.16, 119.21, 115.67, 115.27, 105.9, 55.82; LC-
MS: m/z = 403 (M+1); Anal. calcd. (%) for C18H12N2O2F6; C,
53.74; H, 3.01; N, 6.96; Found (%): C, 53.75; H, 2.98; N,
6.95.
4-[3,5-Bis(trifluoromethyl)phenyl]-2-(2,6-dichloro-
phenyl)oxazole (3e): FT-IR (KBr, νmax, cm–1): 2966, 1608,
1503, 1457, 1223; 1H NMR (400 MHz, DMSO-d6): δ = 8.09-
8.33 (m, 3H), 7.49-7.69 (m, 4H); 13C NMR (400 MHz, DMSO-
d6): δ = 159.33, 140.1, 139.98, 137.39, 133.6, 133.60, 131.81,
131.80, 130.57, 129.81, 129.80, 128.11, 127.42, 124.71, 124.7;
LC-MS: m/z = 425 (M+1);Anal. calcd. (%) for C17H7Cl2NOF6;
C, 47.92; H, 1.66; N, 3.29; Found (%): C, 47.93; H, 1.67; N,
3.29.
3-(4-[3,5-Bis(trifluoromethyl)phenyl]oxazol-2-yl)-
aniline (3f): FT-IR (KBr, νmax, cm–1): 2976, 1615, 1511, 1481,
1214; 1H NMR (400 MHz, DMSO-d6): δ = 8.08-8.33 (m, 3H),
7.69, (s, 1H), 6.74-7.51 (m, 4H), 4.62 (s, 2H); 13C NMR (400
MHz, DMSO-d6): δ = 159.35, 148.90, 140.12, 139.95, 133.67,
131.81, 131.80, 130.13,129.80, 127.71, 126.90, 124.70, 123.11,
118.79, 117.56, 114.22; LC-MS: m/z = 373 (M+1);Anal. calcd.
(%) for C17H10N2OF6; C, 54.85; H, 2.71; N, 7.53; Found (%):
C, 54.84; H, 2.72; N, 7.54.
4-(4-[3,5-Bis(trifluoromethyl)phenyl)oxazol-2-yl)-
aniline (3g): FT-IR (KBr, νmax, cm–1): 2977, 1611, 1521, 1479,
1224; 1H NMR (400 MHz, DMSO-d6): δ = 8.08-8.33 (m, 3H),
7.69 (s, 1H), 6.59-7.61 (m, 4H), 5.34 (s, 2H); 13C NMR (400
MHz, DMSO-d6): ν = 159.36, 145.67, 140.10, 133.60, 132.10,
131.81, 131.80, 129.85, 128.39, 124.71, 124.70, 120.60, 115.12;
LC-MS: m/z = 373 (M+1); Anal. calcd. (%) for C17H10N2OF6;
C, 54.85; H, 2.71; N, 7.53; Found (%): C, 54.86; H, 2.70; N,
7.57.
2-(4-[3,5-Bis(trifluoromethyl)phenyl)oxazol-2-yl)-4-
chloroaniline (3h): FT-IR (KBr, νmax, cm–1): 2981, 1605, 1518,
1
1481, 1207; H NMR (400 MHz, DMSO-d6): δ = 8.08-8.33
(m, 3H), 7.69 (s, 1H), 6.93-7.82 (m, 3H), 5.79 (s, 2H); 13C NMR
(400 MHz, DMSO-d6): δ = 159.33, 143.37, 140.10, 139.90,
133.62, 131.81, 131.80, 129.81, 129.80, 129.63, 128.87,
128.32, 124.71, 124.70, 124.56, 123.10, 118.20; LC-MS: m/z
= 407 (M+1); Anal. calcd. (%) for C17H9N2OF6Cl; C, 50.20;
H, 2.23; N, 6.89; Found (%): C, 50.22; H, 2.24; N, 6.90.
6-(4-[3,5-Bis(trifluoromethyl)phenyl)oxazol-2-
yl)pyridin-2-amine (3i): FT-IR (KBr, νmax, cm–1): 2958, 1609,
1511, 1451, 1214; 1H NMR (400 MHz, DMSO-d6): δ = 8.08-
8.33 (m, 3H), 7.69 (s, 1H), 6.73-7.50 (m, 3H), 6.32 (s, 2H);
13C NMR (400 MHz, DMSO-d6): δ = 159.11, 157.30, 156.68,
140.1, 139.96, 139.57, 133.60, 131.81, 131.80, 129.81, 129.80,