SYNTHESIS OF 2,5-DISUBSTITUTED 1,3,4-OXADIAZOLES AND THEIR PRECURSORS

Full text of DOI:10.1135/cccc19941892

1892
Jedlovska, Gavlakova:
SYNTHESIS OF 2,5-DISUBSTITUTED 1,3,4-OXADIAZOLES
AND THEIR PRECURSORS
Eva JEDLOVSKA and Edita GAVLAKOVA
Department of Organic Chemistry,
Slovak Technical University, 812 37 Bratislava, The Slovak Republic
Received November 13, 1992
Accepted May 16, 1994
The characteristic feature of many commercial agrochemicals and drugs is the 5-nitro-
2-furyl or 2,5-dimethyl-3-furyl building block1,2. Within the scope of our research
aimed at utilization of dipolar cycloaddition reactions to prepare new compounds with
potential biological and phytoeffectorial activity, we report on the synthesis of some
substituted hydrazones I and their intramolecular cycloaddition to 2,5-disubstituted
1
1,3,4-oxadiazoles II. The basic IR, H NMR as well as mass spectral data of final
products are presented.
EXPERIMENTAL
The melting points are uncorrected, the IR spectra (ν, cm−1) were taken with Philips analytical PU
9800 FTIR spectrometer in KBr pellets, the 1H NMR spectra (δ, ppm; J, Hz) of hexadeuterio-
dimethyl sulfoxide solutions containing tetramethylsilane as an internal standard were recorded on
Tesla BS 487 C spectrometer (80 MHz). Mass spectra (m/z, rel.%) were recorded on AEI spec-
trometer MS 902 S with direct inlet and ionizing energy of 70 eV, capture current 100 µA and the
temperature of ionizing chamber 80 – 215 °C. Starting substituted 5-aryl-2-furancarbaldehydes were
prepared according to refs3–5, the requisite 2-furoyl- and 2,5-dimethyl-3-furoylhydrazides according
to ref.6.
Substituted Hydrazones I. General Procedure
The mixture of respective aldehyde (0.01 mol) and corresponding hydrazide of furancarboxylic acid
(0.01 mol) dissolved in ethanol (50 – 80 ml) was refluxed for 1 – 4 h (monitoring by TLC, ref.7).
After cooling to room temperature the separated solid was crystallized from ethanol or dioxane to
afford pure product. The characteristic data of prepared hydrazones are summarized in Table I.
2,5-Disubstituted Oxadiazoles II. General Procedure
Method A: To stirred suspension of hydrazone I (3 mmol) in dichloromethane (100 ml) was added
lead tetraacetate (1.77 g, 3 mmol) at room temperature and the reaction mixture was kept under re-
flux for several hours (monitoring by TLC). After the undissolved materials were filtered off, the
solvent was removed under reduced pressure. The residue was recrystallized from suitable solvent, or
purified on silica gel (chloroform).
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New Compounds
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Method B: A mixture of respective hydrazone I (7 mmol) and NiO2 (2.6 g) in chloroform (175 ml)
was refluxed for 6 h. After inorganic materials were filtered off, the solvent was removed under re-
duced pressure and the crude product was purified in the manner described in Method A.
2-Phenyl-5-(2-furyl)-1,3,4-oxadiazole (IIa)
Yield 47% (method A), m.p. 96 – 98 °C. For C12H8N2O2 (212.2) calculated: 67.91% C, 3.80% H,
1
13.20% N; found: 67.58% C, 3.61% H, 13.07% N. H NMR spectrum: 6.22 dd, 1 H, J = 1.8 (H-4);
7.23 d, 1 H, J = 3.5 (H-3); 7.57 – 7.48 m, 3 H (H arom.). Mass spectrum: 212 (M+, 100), 156 (16),
128 (46), 105 (67), 102 (31), 95 (46), 77 (48), 51 (16). IR spectrum: 1 632 (C=N).
2-(5-Nitro-2-furyl)-5-(2-furyl)-1,3,4-oxadiazole (IIb)
Yield 82% (method A), 86% (method B), m.p. 258 – 260 °C. For C10H5N3O5 (247.1) calculated:
1
48.60% C, 2.04% H, 17.00% N; found: 48.94% C, 2.40% H, 17.14% N. H NMR spectrum: 6.81 dd,
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Jedlovska, Gavlakova:
TABLE I
Characteristic data of prepared compounds I
Calculated/Found
% H
Formula
(M.w.)
M.p., °C
Yield, %
Compound
ν(C=O), cm−1
% C
% N
Ia
Ib
Ic
Id
Ie
If
C12H10N2O2
(214.2)
232 – 234
70
67.28
67.51
4.70
4.52
13.08
13.25
1 671
1 665
1 664
1 658
1 656
1 670
1 672
1 655
1 670
1 668
1 656
1 664
1 658
1 660
1 663
1 660
1 668
C10H7N3O5
(249.2)
233 – 235
95
48.19
47.91
2.83
3.02
16.86
16.55
C16H11N3O5
(325.3)
252 – 254
80
59.07
59.28
3.40
3.24
12.91
12.95
C16H11ClN2O3
(314.7)
201 – 203
70
61.06
61.20
3.52
3.82
8.90
8.77
C16H11BrN2O3
(359.1)
135 – 137
70
53.51
53.30
3.08
3.42
7.80
7.63
C17H14N2O4
(310.3)
227 – 229
58
65.79
65.54
4.54
4.75
9.02
9.18
Ig
Ih
Ii
C16H11N3O5
(325.3)
91 – 93
82
59.07
59.38
3.40
3.62
12.91
12.94
C12H9N3O4
(259.2)
268 – 269
86
55.60
55.78
3.50
3.21
16.21
16.40
C14H13N3O4
(287.2)
201 – 207
68
56.19
56.41
4.56
4.22
14.63
14.50
Ij
C15H16N2O2
(256.3)
241 – 243
62
70.28
70.52
6.29
6.47
10.93
11.08
Ik
Il
C15H13ClN2O2
(276.7)
207 – 209
63
60.76
60.18
4.70
4.67
10.12
9.81
C12H12N2O3
(232.2)
234 – 236
65
62.06
62.34
5.21
5.47
12.06
12.16
Im
In
Io
Ip
Ir
C18H15BrN2O3
(387.2)
204 – 206
55
55.83
55.97
3.90
3.99
7.23
7.16
C18H15ClN2O3
(342.8)
178 – 180
61
63.06
63.35
4.41
4.63
8.17
8.29
C18H15N3O5
(353.3)
214 – 215
80
61.88
61.92
4.27
4.49
11.89
11.63
C13H12N2O2
(228.2)
168 – 169
89
68.40
68.14
5.30
5.45
12.27
12.41
C12H9ClN2O2
(248.8)
197 – 199
87
57.91
58.10
3.64
3.92
11.26
11.35
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New Compounds
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1 H, J = 1.6 (H-4); 7.44 d, 1 H, J = 3.4 (H-3); 7.67 d, 1 H, J = 4.0 (H-3′); 7.86 d, 1 H (H-4′); 8.05 d,
1 H (H-5). IR spectrum: 1 632 (C=N), 1 545 (NO2)as, 1 358 (NO2)s.
2-[5-(4-Chlorophenyl)-2-furyl]-5-(2-furyl)-1,3,4-oxadiazole (IId)
Yield 65% (method A), 74% (method B), m.p. 208 °C. For C16H9ClN2O3 (312.7) calculated: 61.45% C,
1
2.90% H, 8.96% N; found: 61.13% C, 3.06% H, 9.10% N. H NMR spectrum: 6.84 dd, 1 H, J = 1.8
(H-4); 7.35 d, 1 H, J = 3.6 (H-3); 7.45 d, 1 H (H-4′); 7.54 d, 1 H (H-3′); 7.61 d, 2 H, J = 8.3 (H arom.);
7.90 d, 2 H (H arom.); 8.10 d, 1 H, J = 3.0 (H-5). Mass spectrum: 312 (M+, 100), 207 (14), 205 (44),
202 (11), 149 (28), 95 (39), 53 (23), 39 (11). IR spectrum: 1 626 (C=N).
2-[5-(4-Bromophenyl)-2-furyl]-5-(2-furyl)-1,3,4-oxadiazole (IIe)
Yield 45% (method A), 67% (method B), m.p. 188 – 190 °C. For C16H9BrN2O3 (357.1) calculated:
1
53.80% C, 2.54% H, 7.84% N; found: 53.41% C, 2.83% H, 7.41% N. H NMR spectrum: 6.81 dd, 1 H,
J = 2.1 (H-4); 7.27 d, 1 H, J = 3.6 (H-3′); 7.37 d, 1 H (H-3); 7.45 d, 1 H (H-4′); 7.75 d, 2 H, J = 8.3
(H arom.); 7.81 d, 2 H (H arom.); 7.96 d, 1 H, J = 2.9 (H-5). Mass spectrum: 357 (M+, 100), 249
(50), 195 (33), 165 (27), 104 (30), 95 (60), 53 (43). IR spectrum: 1 626 (C=N).
2-[5-(2-Nitrophenyl)-2-furyl]-5−(2-furyl)-1,3,4-oxadiazole (IIg)
Yield 76% (method A), m.p. 145 – 147 °C. For C16H9N3O5 (323.2) calculated: 59.44% C, 2.80% H,
12.99% N; found: 59.12% C, 2.45% N.1H NMR spectrum: 6.78 dd, 1 H, J = 2.1 (H-4); 7.07 d, 1 H,
J = 3.7 (H-3′); 7.34 d, 1 H, J = 3.52 (H-3); 7.47 d, 1 H, J = 3.5 (H-4′); 7.83 d, 1 H, J = 3.9 (H-5);
8.05 – 7.7 m, 4 H (H arom.). IR spectrum: 1 612 (C=N), 1 535 (NO2)as, 1 361 (NO2)s.
2-(4-Nitrophenyl)-5-(2-furyl)-1,3,4-oxadiazole (IIh)
Yield 60% (method A), m.p. 228 – 230 °C. For C12H7N3O4 (257.2) calculated: 56.03% C, 2.74% H,
1
16.33% N; found: 56.43% C, 3.10% H, 16.48% N. H NMR spectrum: 6.79 dd, 1 H, J = 2.0 (H-4);
7.42 d, 1 H, J = 3.5 (H-3); 8.02 d, 1 H, J = 3.2 (H-5); 8.29 d, 2 H, J = 9.04 (H arom.); 8.44 d, 2 H
(H arom.). Mass spectrum: 257 (M+, 100), 150 (26), 95 (92). IR spectrum: 1 642 (C=N), 1 555
(NO2)as, 1 356 (NO2)s.
2-(4-Chlorophenyl)-5-(2,5-dimethyl-3-furyl)-1,3,4-oxadiazole (IIk)
Yield 52% (method A), m.p. 177 – 182 °C. For C14H11ClN2O2 (247.7) calculated: 61.20% C, 4.03% H,
10.20% N; found: 61.42% C, 3.86% H, 10.05% N. 1H NMR spectrum: 1.64 s, 6 H (2 × CH3); 6.40 s, 1 H
(H-4); 7.45 d, 2 H, J = 8.3 (H arom.); 7.88 d, 2 H (H arom.). IR spectrum: 1 630 (C=N).
2-(4-Tolyl)-5-(2-furyl)-1,3,4-oxadiazole (IIp)
Yield 68% (method A), m.p. 135 – 136 °C. For C13H10N2O2 (226.2) calculated: 69.01% C, 4.45% H,
12.38% N; found: 68.93% C, 4.09% H, 12.20% N. 1H NMR spectrum: 2.44 s, 3 H (CH3); 6.77 dd,
1 H, J = 2.0 (H-4); 7.35 d, 1 H, J = 3.6 (H-3); 7.43 d, 2 H, J = 8.64 (H arom.); 7.94 d, 1 H, J = 3.0
(H-5); 8.01 d, 2 H (H arom.). IR spectrum: 1 633 (C=N).
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Jedlovska, Gavlakova:
2-(4-Chlorophenyl)-5-(2-furyl)-1,3,4-oxadiazole (IIr)
Yield 72% (method A), m.p. 132 – 133 °C. For C12H7ClN2O2 (246.6) calculated: 58.44% C, 2.86% H,
1
11.36% N; found: 58.73% C, 2.61% H, 11.14% N. H NMR spectrum: 6.79 dd, 1 H, J = 2.1 (H-4);
7.38 d, 1 H, J = 3.5 (H-3); 7.65 d, 2 H, J = 8.8 (H arom.); 7.94 d, 1 H, J = 3.5 (H-5); 8.13 d, 2 H
(H arom.). IR spectrum: 1 635 (C=N).
This study was supported by Grant Agency of Slovak Ministry of Education (Grant No. 1/140/92).
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