6
POKHODYLO ET AL.
Method
B
(starting from 5). 1 mmol of the
NMR (400 MHz, DMSO-d6), δ, ppm: 6.17 (s, 2H, CH2),
7.35 (t, J = 7.1 Hz, 1H, Н4Ph,), 7.45 (t, J = 7.1 Hz, 2H,
Н3,5Ph), 7.76-8.00 (m, 6H, НAr), 8.78 (s, 1H, Htriaz). LCMS
(m/z): 382, 384 [M++1]. Found, %: C 53,21; H 3,04; N
18,50. C17H12BrN5O. Calculated, %: C 53,42; H 3,16;
N 18,32.
corresponding azide, 5, and 0.11 mL (1 mmol) of alkyne,
2, were dissolved in 5 mL of tert-butanol. Water was
added dropwise, to the solution, till the formation of the
emulsion, after 0.4 mL (2.8 mmol) of triethylamine and
0.05 g of CuI were added. The mixture was stirred at
room temperature for 12 hours, 15 mL of water and 5 mL
of concentrated ammonia solution were added. The reac-
tion product was extracted with methylene chloride
(3 × 10 mL), the extract was dried with Na2SO4 and evap-
orated. If necessary, solid was recrystallized from
ethanol.
3-Phenyl-5-[(4-phenyl-1H-1,2,3-triazol-1-yl)methyl]-
1,2,4-oxadiazole (4f). Yield: Method А (0.24 g, 78%),
Method B (0.25 g, 84%), mp 135ꢀС-136ꢀС; 1H NMR
(500 MHz, DMSO-d6), δ, ppm: 6.30 (d, J = 2.0 Hz, 2H,
СН2), 7.34-7.40 (m, 1H, НAr), 7.45-7.52 (m, 2H, НAr),
7.54-7.63 (m, 3H, НAr), 7.88-7.93 (m, 2H, НAr), 7.97-8.03
(m, 2H, НAr), 8.82 (d, J = 2.0 Hz, 1H, Нtriaz). LCMS
(m/z): 304 [M++1]. Found, %: C 67.53; H 4.16; N 23.27.
C17H13N5O. Calculated, %: C 67.32; H 4.32; N 23.09.
5-([4-Phenyl-1H-1,2,3-triazol-1-yl]methyl)-3-(o-tolyl)-
1,2,4-oxadiazole (4g). Yield Method A (0.25 g, 78%), mp
104ꢀС-105ꢀС; 1H NMR (400 MHz, DMSO-d6), δ, ppm:
8.80 (s, 1H, Htriaz), 7.79-7.98 (m, 3H, НAr), 7.27-7.57 (m,
6H, НAr), 6.28 (s, 2H, CH2), 2.53 (s, 3H, CH3). LCMS
(m/z): 318 [M++1]. Found, %: C 67.89; H 4.95; N 20.21.
C18H15N5O. Calculated, %: C 68.13; H 4.76; N 22.07.
3-(4-Chlorophenyl)-5-((4-phenyl-1H-1,2,3-triazol-1-yl)
methyl)-1,2,4-oxadiazole (4h). Yield: Method А (0.27 g,
81%), Method B (0.29 g, 86%), mp 135ꢀС-136ꢀС; 1H
NMR (400 MHz, DMSO-d6), δ, ppm: 8.79 (s, 1H, Htriaz),
7.99 (d, J = 7.8 Hz, 2H, Н2,6Ar), 7.89 (d, J = 6.9 Hz, 2H,
Н2,6Ph), 7.63 (d, J = 7.8 Hz, 2H, Н3,5Ar,), 7.46 (t, J = 6.9 Hz,
2H, Н3,5Ph), 7.35 (t, J = 6.9 Hz, 1H, Н4Ph), 6.28 (s, 2H,
CH2). LCMS (m/z): 338 [M++1]. Found, %: C 60.30; H
3.46; N 20.58. C17H12ClN5O. Calculated, %: C 60.45; H
3.58; N 20.73.
2-Phenyl-5-([4-phenyl-1H-1,2,3-triazol-1-yl]
methyl)-1,3,4-oxadiazole (4a). Yield: Method А (0.22 g,
73%); Method B (0.26 g, 87%); mp 117ꢀС-118ꢀС; 1H
NMR (500 MHz, DMSO-d6), δ, ppm: 6.17 (s, 2H, CH2),
7.35 (t, J = 7.2 Hz, 1H, Н4Ph), 7.45 (t, J = 7.2 Hz, 2H,
Н3,5Ph), 7.54-7.71 (m, 3H, НPh), 7.88 (d, J = 7.2 Hz, 2H,
Н2,6Ph), 7.99 (d, J = 7.2 Hz, 2H, Н2,6Ph), 8.79 (s,1H, Нtriaz).
LCMS (m/z): 304 [M++1]. Found, %: C 67,07; H 4,15; N
23,26. C17H13N5O. Calculated, %: C 67,32; H 4,32;
N 23,09.
2-([4-Phenyl-1H-1,2,3-triazol-1-yl]methyl)-5-(m-
tolyl)-1,3,4-oxadiazole (4b). Yield: Method A (0.23 g,
72%); mp 166ꢀС-167ꢀС; H NMR (400 MHz, DMSO-d6),
1
δ, ppm: 2.39 (s, 3H, CH3), 6.16 (s, 2H, CH2), 7.35 (t,
J = 7.1 Hz, 1H, Н4Ph), 7.39-7.52 (m, 4H, НAr), 7.74-7.83
(m, 2H, НAr), 7.88 (d, 2H, J = 7.3 Hz, Н2,6Ph), 8.78 (s, 1H,
Htriaz). LCMS (m/z): 318 [M++1]. Found, %: C 67,86; H
4,93; N 21,90. C18H15N5O. Calculated, %: C 68,13; H 4,76;
N 22,07.
2-(4-Chlorophenyl)-5-([4-phenyl-1H-1,2,3-triazol-1-yl]
methyl)-1,3,4-oxadiazole (4c). Yield: Мethod А (0.26 g,
77%); Method B (0.30 g, 89%), mp 100ꢀС-101ꢀС; 1H
NMR (400 MHz, DMSO-d6), δ, ppm: 6.17 (s, 2H, CH2),
7.35 (t, J = 7.1 Hz, 1H, Н4Ph), 7.46 (t, J = 7.4 Hz, 2H,
Н3,5Ph), 7.68 (d, J 8.3 Hz, 2H, Н3,5Ar), 7.87 (d, J = 7.3 Hz,
2H, Н2,6Ph), 8.00 (d, J 8.3 Hz, 2H, Н2,6Ar), 8.78 (s, 1H,
Htriaz). LCMS (m/z): 338 [M++1]. Found, %: C 60,67;
H 3,44; N 20,57. C17H12ClN5O. Calculated, %: C 60,45;
H 3,58; N 20,73.
2-({1-[(3-Phenyl-1,2,4-oxadiazol-5-yl)methyl]-1H-
1,2,3-triazol-4-yl}methoxy)benzaldehyde
(4i).
Yield:
Method B (0.31 g, 87%); mp 158ꢀС-159ꢀС; 1H NMR
(500 MHz, DMSO-d6), δ, ppm: 5.45 (s, 2H, СН2), 6.27 (s,
2H, СН2), 7.14 (t, J = 7.4 Hz, 1H, НAr), 7.49 (d, J = 8.4 Hz,
1H, НAr), 7.59 (t, J = 7.3 Hz, 2H, НAr), 7.62 (d, J = 7.1 Hz
1H, НAr), 7.69-7.75 (m, 2H, НAr), 7.98 (d, J = 7.1 Hz, 2H,
НAr), 8.58 (s, 1H, Htriaz), 10.39 (s, 1H, СНО). LCMS
(m/z): 362 [M++1]. Found, %: C 63.36; H 4.04; N 19.55.
C19H15N5O3. Calculated, %: C 63.15; H 4.18; N 19.38.
General procedure for synthesis of (5-aryl-1,-
3,4-oxadiazol-2-yl)methylamines 6. A solution of 0.01 mol
of azide, 5, in 7 mL of ether and 7 mL of ethyl acetate
was added to 10 mL of 5% HCl (prepared with 0.14 mL of
HCl conc. and water) and triphenylphosphine of 2.5 g
(0.01 mol) was added in 5 portions during 1 hour, and
then the mixture was stirred for 24 hours at room tem-
perature. The organic layer was separated, and the aque-
ous layer was washed twice with methylene chloride
(2 × 15 mL). The aqueous phase was made basic with a
20% sodium hydroxide solution and then the amine 6 is
2-(2-Bromophenyl)-5-([4-phenyl-1H-1,2,3-triazol-1-yl]
methyl)-1,3,4-oxadiazole (4d). Yield: Method А (0.28 g,
74%); Method B (0.32 g, 83%), mp 135ꢀС-136ꢀС; 1H
NMR (400 MHz, DMSO-d6), δ, ppm: 6.20 (s, 2H, CH2),
7.35 (t, J = 7.4 Hz, 1H, Н4Ph), 7.46 (t, J = 7.4 Hz, 2H,
Н3,5Ph), 7.52-7.66 (m, 2H, НAr), 7.81-7.95 (m, 4H,
Н
Ar + Н2,6Ph), 8.78 (s, 1H, Htriaz). LCMS (m/z): 382, 384
[M++1]. Found, %:
53,63; 3,28; 18,46.
C17H12BrN5O. Calculated, %: C 53,42; H 3,16; N 18,32.
2-(4-Bromophenyl)-5-([4-phenyl-1H-1,2,3-triazol-1-yl]
methyl)-1,3,4-oxadiazole (4e). Yield: Method А (0.28 g,
75%), Method B (0.33 g, 88%), mp 169ꢀС-170ꢀС; 1H
C
H
N