J. Chil. Chem. Soc., 55, Nº 1 (2010)
178.2, 149.9, 138.6, 141.3, 136.5, 129, 127.8, 126.5, 20.6; m/z (ES-MS) 173.0,
Mol. Formula C9H7N3O, Mol. Wt.: 173.2, Calculated C, 62.42; H, 4.04; N,
24.27, found C, 62.12; H, 4.00; N, 23.86 .
2-amino-5-(2,4-dichloro)phenyl-1,3,4-oxadiazole (1l) Pale yellow
0
needles, m. p. 89-91 C; IR cm-1 3360, 3045, 1608 (C=N-N=C), 1267, 1069
(C-O-C), 775, 655, 600; H1 NMR (400 MHz, CDCl3) 7.75 (s, 2H, NH2), 6.94-
7.04 (m, J= 2.6 and 5.6 Hz, 3H); C13 NMR (75 MHz, CDCl3) 164.5, 157,
143, 135, 133.5, 131.7, 128.7, 128.5; m/z (ES-MS) 229.7, Mol. Formula
C8H N OCl2, Mol. Wt.: 230.0, Calculated C, 41.92; H, 2.18; N, 18.34; Cl,
30.556, 3found C, 41.25; H, 2.03; N, 18.17; Cl, 30.27.
2-amino-5-(3-benzoyloxy)phenyl-1,3,4-oxadiazole (1b) Pale yellow
0
needles, m. p. 72-74 C; IR cm-1 3350, 3045, 1755, 1617 (C=N-N=C), 1269,
1065 (C-O-C), 910, 860; H1 NMR (400 MHz, CDCl3) 7.75 (s, 2H, NH2), 7.25-
7.69 (m, J= 2.6 and 5.6 Hz, 9H); C13 NMR (75 MHz, CDCl3) 172, 149.5, 137.1,
136.3, 132.9, 131.3, 130.2, 128.7, 128.1, 128.0, 127.8; m/z (ES-MS) 264.8,
Mol. Formula C15H11N O , Mol. Wt.: 265.3, Calculated C, 67.92; H, 4.14; N,
15.84, found C, 67.45; 3H,24.03; N, 15.44.
2-amino-5-(2,3-difluoro)phenyl-1,3,4-oxadiazole (1m) Dark brownish
0
needles, m. p. 80-82 C; IR cm-1 3360, 3050, 1611 (C=N-N=C), 1269, 1064
(C-O-C), 935, 765; H1 NMR (400 MHz, CDCl3) 7.75 (s, 2H, NH2), 6.94-
7.04 (m, J= 2.6 and 5.6 Hz, 4H); C13 NMR (75 MHz, CDCl3) 164.5, 162.5,
142.5, 140.6, 122.2, 111.0, 109.7, 100.1; m/z (ES-MS) 196.6, Mol. Formula
C8H5N3F O, Mol. Wt.: 197.1, Calculated C, 48.73; H, 2.53; N, 21.31; F, 19.28,
found C,248.12; H, 2.45; N, 21.18; F, 19.03.
2-amino-5-(5-bromo-4-hydroxy)phenyl-1,3,4-oxadiazole (1c) Black
0
needles, m. p. 85-87 C; IR cm-1 3440, 3360, 3045, 1604 (C=N-N=C), 1267,
1070 (C-O-C), 980, 890, 755, 655; H1 NMR (400 MHz, CDCl3) 7.75 (s, 2H,
NH2), 7.25-7.69 (m, J= 2.6 and 5.6 Hz, 4H), 6.09 (s, 1H, OH); C13 NMR (75
MHz, CDCl3) 158.9, 147.2, 141.2, 136.4, 134.2, 129.7, 123.9, 123.7; m/z (ES-
MS) 265.2, Mol. Formula C10H8N3OBr, Mol. Wt.: 266.1, Calculated C, 45.11;
H, 3.02; N, 15.79; Br, 30.07, found C, 44.85; H, 2.75; N, 15.39; Br, 29.65.
2-amino-5-(3-(4-tert-butyl phenoxy)phenyl-1,3,4-oxadiazole (1d)
2-amino-5-(2,6-difluoro)phenyl-1,3,4-oxadiazole (1n) Dark brownish
0
needles, m. p. 82-83 C; IR cm-1 3360, 3055, 1601 (C=N-N=C), 1273, 1068
(C-O-C), 950, 790; H1 NMR (400 MHz, CDCl3) 7.75 (s, 2H, NH2), 6.94-
7.04 (m, J= 2.6 and 5.6 Hz, 4H); C13 NMR (75 MHz, CDCl ) 165, 162.7,
142.5, 141.0, 122.2, 111.5, 109.7, 100.2; m/z (ES-MS) 196.4, 3Mol. Formula
C8H5N3F O, Mol. Wt.: 197.1, Calculated C, 48.73; H, 2.53; N, 21.31; F, 19.28,
found C,248.20; H, 2.35; N, 21.10; F, 19.05.
0
Yellow needles, m. p. 85-87 C; IR cm-1 3444, 3360, 2860, 1608 (C=N-
N=C), 1270, 1265, 1072 (C-O-C), 1130, 749.5; H1 NMR (400 MHz, CDCl3)
7.75 (s, 2H, NH ), 6.52-7.14 (m, J= 2.6 and 5.6 Hz, 8H), 1.3 (s, 9H, CH3); C13
NMR (75 MHz,2CDCl3) 172.4, 167, 147.5, 140.2, 138.9, 137.5, 132.6, 128.5,
128.2, 128.1, 128.4, 122.8, 118.6, 114.6, 42.1, 20.6; m/z (ES-MS) 308.1, Mol.
Formula C18H19N3O2, Mol. Wt.: 308.5, Calculated C, 69.90; H, 6.14; N, 13.59,
found C, 69.12; H, 5.88; N, 13.36.
Biological Activity
All the title compounds were tested for their antimicrobial activity by
adopting the experimental method of Benson32. Whatman No.1 filter paper
discs of 6 mm diameter, placed in a Petri dish, were autoclaved. The test
compounds in measured quantities (1.0 mg, 0.5 mg) were dissolved in 5 mL of
dimethylformamide to produce 200 ppm and 100 ppm solutions, respectively.
The filter paper discs were allowed to dry and the amount of the substance
per disc was taken as 500 and 250 µg. The bacterial (24 h) and fungal (48 h)
cultures from the slants were diluted with sterile water and mixed thoroughly
to prepare a clear homogeneous suspension. These suspensions were uniformly
spread on solidified agar (nutrient and potato dextrose agar) medium. The filter
paper discs prepared from dimethylformamide medium were carefully placed
over the spreaded cultures and incubated at 37 0C for 24 h for bacteria and at
28-30 0C for 48 h for fungi. Paper discs treated with dimethylformamide alone
served as control. After the incubation period the plates were examined for
inhibition zones. The diameters of inhibition zones (including the diameter of
the disc) were measured. All determinations were made in triplicate for each of
the compounds and the average value was taken.
2-amino-5-(4-carboxy)phenyl-1,3,4-oxadiazole (1e) Brown needles, m.
0
p. 87-89 C; IR cm-1 3360, 3300, 3060, 1715, 1612 (C=N-N=C), 1280, 1275,
1065 (C-O-C), 962; H1 NMR (400 MHz, CDCl3) 7.75 (s, 2H, NH2), 6.52-7.24
(m, J= 2.6 and 5.6 Hz, 4H); C13 NMR (75 MHz, CDCl3) 172.6, 144.9, 141.5,
141.2, 129.9, 129.5, 129.3; m/z (ES-MS) 204.6, Mol. Formula C H7N O , Mol.
Wt.: 205.2, Calculated C, 52.68; H, 3.41; N, 20.48, found C, 591.82;3H3, 3.22;
N, 20.00.
2-amino-5-(10-chloro)anthryl-1,3,4-oxadiazole (1f) Brown needles, m.
p. 93-95 0C; IR cm-1 3330, 3030, 1670, 1607 (C=N-N=C), 1267, 1068 (C-O-C),
780; H1 NMR (400 MHz, CDCl3) 7.75 (s, 2H, NH2), 7.25-7.69 (m, J= 2.6 and
5.6 Hz, 8H); C13 NMR (75 MHz, CDCl3) 172.4, 149.5, 139.2, 131.5, 128.3,
125.3; m/z (ES-MS) 295.0, Mol. Formula C16H N OCl, Mol. Wt.: 295.7,
Calculated C, 64.95; H, 3.38; N, 14.20; Cl, 12.00, 1f0ou3nd C, 64.12; H, 3.11; N,
14.05; Cl, 11.66.
2-amino-5-(5-chloro-2-nitro)phenyl-1,3,4-oxadiazole
(1g)
Dark
yellowish needles, m. p. 71-73 C; IR cm-1 3341, 3035, 1614 (C=N-N=C),
1580, 1273, 1071 (C-O-C), 860, 735; H1 NMR (400 MHz, CDCl3) 7.75 (s,
2H, NH2), 7.25-7.69 (m, J= 2.6 and 5.6 Hz, 3H); C13 NMR (75 MHz, CDCl3)
172.3, 148.3, 147.1, 146.8, 140.8, 136.8, 130.4, 121.2; m/z (ES-MS) 239.7,
Mol. Formula C8H5N4O Cl, Mol. Wt.: 240.6, Calculated C, 39.90; H, 2.07; N,
23.27; Cl, 14.75, found C3 , 39.45; H, 1.95; N, 22.95; Cl, 14.52.
RESULTS AND DISCUSSION
0
The organic synthesis involving electrochemical techniques under
suitable solvents and electrolytes are the basic requirements. The solution
phase methods, while successful, were deemed not readily amenable to
high throughout synthesis, and thus did not meet our needs. Considering the
importance of 1,3,4-oxadiazoles and methods of preparation, 2-amino-5-
substituted-1,3,4-oxadiazoles were synthesized by electrooxidative cyclization
of semicarbazone as an environmentally benign synthetic method in which
aforementioned troublesome were removed and minimized. The electroorganic
synthesis of 1,3,4-oxadiazole derivatives 1 is electrochemical cyclization by
electrooxidation of semicarbazone 4. The electrochemical oxidation has
various merits. The electrooxidation does not require oxidizing reagents and
can be performed at room temperature. Electricity provides chemical processes
with special attributes, such as enhanced reaction rate, higher yield of pure
products, better selectivity and several ecofriendly advantages.
2-amino-5-(5-chloro-2-hydroxy)phenyl-1,3,4-oxadiazole (1h) Yellow
0
needles, m. p. 78-80 C; IR cm-1 3440, 3261, 3045, 1611 (C=N-N=C), 1276,
1073 (C-O-C), 1050, 760; H1 NMR (400 MHz, CDCl3) 7.75 (s, 2H, NH2),
6.46-7.70 (m, J= 2.6 and 5.6 Hz, 3H), 6.09 (s, 1H, OH); C13 NMR (75 MHz,
CDCl3) 171.9, 166.2, 151.3, 128.7, 128.5, 128, 116.8; m/z (ES-MS) 211.2,
Mol. Formula C10H8N3OCl, Mol. Wt.: 211.6, Calculated C, 56.71; H, 3.78; N,
19.84; Cl, 16.77, found C, 55.82; H, 3.48; N, 19.65; Cl, 16.55.
2-amino-5-(4-cyano)phenyl-1,3,4-oxadiazole (4i) Yellow crystals, m. p.
69-71 0C; IR cm-1 3330, 3060, 2230, 1620 (C=N-N=C), 1265, 1064 (C-O-C),
960; H1 NMR (400 MHz, CDCl3) 7.75 (s, 2H, NH2), 6.54-7.52 (m, J= 2.6 and
5.6 Hz, 4H); C13 NMR (75 MHz, CDCl ) 171.9, 166.1, 145.8, 132.5, 128.6,
128.5, 125, 111; m/z (ES-MS) 185.4, Mol3. Formula C9H N O, Mol. Wt.: 186.2,
Calculated C, 58.06; H, 3.22; N, 30.10, found C, 57.55;6H4, 3.10; N, 29.76.
2-amino-5-(3,5-dibromo-2-hydroxy)phenyl-1,3,4-oxadiazole (1j) Black
This electrochemical cyclization gives the oxadiazoles (Scheme1). Acetic
acid was used as a solvent and lithium perchlorate as an electrolyte.
0
needles, m. p. 88-89 C; IR cm-1 3440, 3360, 3045, 1610 (C=N-N=C), 1266,
1071 (C-O-C), 980, 890, 755, 655; H1 NMR (400 MHz, CDCl3) 7.75 (s, 2H,
NH2), 7.25-7.69 (m, J= 2.6 and 5.6 Hz, 2H), 6.09 (s, 1H, OH); C13 NMR (75
MHz, CDCl3) 158.9, 147.5, 141.6, 136.2, 134.2, 129.9, 124, 123.7; m/z (ES-
MS) 344.3, Mol. Formula C H7N OBr2, Mol. Wt.: 344.9, Calculated C, 34.78;
H, 2.02; N, 12.17; Br, 46.371,0foun3d C, 34.10; H, 1.88; N, 12.03; Br, 46.11.
2-amino-5-(3,5-di-tert-butyl-4-hydroxy)phenyl-1,3,4-oxadiazole (1k)
0
Brownish crystals, m. p. 83-85 C; IR cm-1 3444, 3360, 2860, 1605 (C=N-
N=C), 1273, 1063 (C-O-C), 1130, 749.5; H1 NMR (400 MHz, CDCl3) 7.75
(s, 2H, NH2), 6.52-7.14 (m, J= 2.6 and 5.6 Hz, 3H), 1.3 (s, 18H, CH ); C13
NMR (75 MHz, CDCl3) 172.4, 167, 147.5, 137.5, 132.6, 128.5, 140.2, 3138.9,
42.1, 20.6; m/z (ES-MS) 288.6, Mol. Formula C H23N3O2, Mol. Wt.: 289.4,
Calculated C, 66.43; H, 7.95; N, 14.53, found C, 6156.88; H, 7.56; N, 14.36.
127