A new approach to the one-pot synthesis of 5-substituted 2-methyl-1,3,4-oxadiazoles from N-tributylstannyltetrazoles

Article abstract of DOI:10.1023/A:1015432432759

A new approach to the synthesis of 5-substituted 2-methyl-1,3,4-oxadiazoles was developed.

Full text of DOI:10.1023/A:1015432432759

Russian Chemical Bulletin, International Edition, Vol. 51, No. 2, pp. 357—358, February, 2002
357
A new approach to the oneꢀpot synthesis of
5ꢀsubstituted 2ꢀmethylꢀ1,3,4ꢀoxadiazoles from Nꢀtributylstannyltetrazoles

B. B. Semenov and Yu. I. Smushkevich
D. I. Mendeleyev Russian University of Chemical Technology,
9 Miusskaya pl., 125047 Moscow, Russian Federation.
Fax: +7 (095) 200 4204. Eꢀmail: semenovb@mail.ru; smu@muctr.edu.ru
A new approach to the synthesis of 5ꢀsubstituted 2ꢀmethylꢀ1,3,4ꢀoxadiazoles was deꢀ
veloped.
Key words: Nꢀtributylstannyltetrazoles, tributylstannyl azide, 5ꢀsubstituted 2ꢀmethylꢀ1,3,4ꢀ
oxadiazoles.
Earlier,1 the antiinflammatory activity of 5ꢀsubstituted
1,3,4ꢀoxadiazoles and the antiarrhythmia properties of
compounds containing a 1,3,4ꢀoxadiazole fragment2 were
studied. 1,3,4ꢀOxadiazoles are generally synthesized by
cyclization of 1,2ꢀdiacylated hydrazines. Later,3 a method
for the synthesis of 1,3,4ꢀoxadiazoles from tetrazoles has
been proposed. The use of this method is limited since it
involves difficultly accessible tetrazoles containing bulky
substituents. Recently,4 the latter have been obtained from
tributylstannyl azide. This method allows one to syntheꢀ
size sterically hindered tetrazoles.
We developed a new approach to the oneꢀpot syntheꢀ
sis of 5ꢀsubstituted 1,3,4ꢀoxadiazoles from the correspondꢀ
ing tributylstannyl tetrazoles, including sterically hinꢀ
dered ones. The reactions of the corresponding nitriles
1a—c with Bu3SnN3 prepared in situ from NaN3 and
Bu3SnCl gave 5ꢀphenylꢀ1ꢀ(tributylstannyl)tetrazole (2a),5
3ꢀ[1ꢀ(tributylstannyl)tetrazolꢀ5ꢀyl]ꢀ1Hꢀindole (2b), and
3ꢀ{(phenyl)[1ꢀ(tributylstannyl)tetrazolꢀ5ꢀyl]methyl}ꢀ1Hꢀ
indole (2c) (Scheme 1).
The reactions of compounds 2a—c with Ac2O for
9 h afforded 2ꢀmethylꢀ5ꢀphenylꢀ1,3,4ꢀoxadiazole (3a),
1ꢀacetylꢀ3ꢀ(5ꢀmethylꢀ1,3,4ꢀoxadiazolꢀ2ꢀyl)ꢀ1Hꢀindole
(3b), and 3ꢀ[(5ꢀmethylꢀ1,3,4ꢀoxadiazolꢀ2ꢀyl)(phenyl)meꢀ
thyl]ꢀ1Hꢀindole (3c) in 80, 57, and 53% yields, reꢀ
spectively.
Experimental
1
H NMR spectra* were recorded on a Bruker WMꢀ250 specꢀ
trometer with Me4Si as the internal standard. Mass spectra were
recorded on a Finnigan MAT SSQꢀ710 spectrometer (EI, ionizꢀ
ing voltage 70 eV). The course of the reaction was monitored by
TLC (Silufol UVꢀ254, EtOAc—CCl4 (1 : 4) as the eluent).
Benzonitrile, 3ꢀcyanoindole, and Bu3SnCl (Aldrich) and Ac2O,
oꢀxylene, and PriOH (reagent grade) were used.
(Indolꢀ3ꢀyl)phenylacetonitrile was prepared according to the
known procedure.6
5ꢀSubstituted 1ꢀ(tributylstannyl)tetrazoles 2a—c (general
procedure). A solution of NaN3 (0.02 mol) and Bu3SnCl
(0.02 mol) in 20 mL of oꢀxylene was refluxed for 5 h and cooled
to ∼20 °C. Nitrile 1a—c (0.0065 mol) was added, and the reacꢀ
tion mixture was refluxed for an additional 15 h. The hot soluꢀ
tion was filtered to separate inorganic salts, cooled to ∼20 °C,
and poured into cold light petroleum or hexane. The precipitate
that formed was filtered off and washed repeatedly with boiling
heptane. Compound 2a was isolated by flash chromatography in
EtOAc—CCl4 (1 : 4) and then in PriOH.
Scheme 1
5ꢀPhenylꢀ1ꢀ(tributylstannyl)tetrazole (2a). Yield 80%, m.p.
66—68 °C (cf. Ref. 5: m.p. 66—71 °C).
3ꢀ[1ꢀ(Tributylstannyl)tetrazolꢀ5ꢀyl]ꢀ1Hꢀindole (2b). Yield
60%, m.p. 148—150 °C. Found (%): C, 52.89; H, 6.87; N, 14.41.
C21H33N5Sn. Calculated (%): C, 53.19; H, 7.01; N, 14.77.
1H NMR (CD3CN), δ: 0.89 (t, 9 H, 3 Me, J = 7.2 Hz);
1.36—1.68 (m, 18 H, (CH2)9); 7.19 (m, 1 H, H(5)Ind); 7.24 (m,
* The H atoms in the indole fragment are marked with the Ind
subscript.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 334—335, February, 2002.
1066ꢀ5285/02/5102ꢀ357 $27.00 © 2002 Plenum Publishing Corporation

358
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 2, February, 2002
Semenov and Smushkevich
1 H, H(6)Ind); 7.51 (m, 1 H, H(7)Ind); 7.85 (d, 1 H, H(2)Ind
J = 2.8 Hz); 8.28 (m, 1 H, H(4)Ind); 9.60 (br.s, 1 H, NH). MS,
m/z (Irel (%)): 474 [M]+ (10).
,
8.25 (m, 2 H, H(4)Ind + H(2)Ind); 8.45 (m, 1 H, H(7)Ind). MS,
m/z (Irel (%)): 240 [M]+ (45), 199 [M – COCH3]+ (100).
3ꢀ[(5ꢀMethylꢀ1,3,4ꢀoxadiazolꢀ2ꢀyl)(phenyl)methyl]ꢀ1Hꢀinꢀ
dole (3c). Yield 53%, m.p. 185—186 °C (PriOH). Found (%):
C, 74.44; H, 5.12; N, 14.26. C18H15N3O. Calculated (%):
C, 74.72; H, 5.23; N, 14.52. 1H NMR (CD3CN), δ: 2.43 (s, 3 H,
Me); 5.94 (s, 1 H, CH); 6.99 (m, 1 H, H(5)Ind); 7.13 (m, 1 H,
H(6)Ind); 7.16 (d, 1 H, H(2)Ind, J = 2.6 Hz); 7.30—7.40 (m, 5 H,
Ph); 7.35 (m, 1 H, H(4)Ind); 7.42 (m, 1 H, H(7)Ind); 9.35
(br.s, 1 H, NH). MS, m/z (Irel (%)): 289 [M]+ (100), 206
[IndCHPh]+ (95).
3ꢀ{(Phenyl)[1ꢀ(tributylstannyl)tetrazolꢀ5ꢀyl]methyl}ꢀ1Hꢀinꢀ
dole (2c). Yield 60%, m.p. 199.5—200.5 °C (PriOH). Found (%):
C, 59.59; H, 6.97; N, 12.41. C28H39N5Sn. Calculated (%):
1
C, 59.39; H, 7.07; N, 12.56. H NMR (DMSOꢀd6), δ: 0.75 (m,
9 H, 3 Me); 1.26 (m, 12 H, 3 CH2CH2CH3); 1.51 (m, 6 H,
3 CH2(CH2)2CH3); 5.86 (s, 1 H, CH); 6.85 (m, 1 H, H(5)Ind);
7.01 (m, 1 H, H(6)Ind); 7.09 (m, 1 H, H(2)Ind); 7.12 (m, 1 H,
H(4)Ph); 7.22 (m, 2 H, H(3)Ph, H(5)Ph); 7.31 (m, 1 H, H(7)Ind);
7.37 (m, 1 H, H(4)Ind); 7.43 (m, 2 H, H(2)Ph, H(6)Ph); 10.82
(br.s, 1 H, NH). MS, m/z (Irel (%)): 563 [M]+ (15), 206
[IndCHPh]+ (100).
References
2,5ꢀDisubstituted 1,3,4ꢀoxadiazoles 3a—c (general proceꢀ
dure). Compounds 2a—c (0.0062 mol) were dissolved in 40 mL
of Ac2O and refluxed for 9 h. The acetic anhydride was removed
in a rotary evaporator, and the residue was washed repeatedly
with heptane and recrystallized from PriOH.
2ꢀMethylꢀ5ꢀphenylꢀ1,3,4ꢀoxadiazole (3a). Yield 80%, m.p.
65—68 °C (PriOH). Found (%): C, 74.42; H, 5.03; N, 14.22.
C9H8N2O. Calculated (%): C, 74.72; H, 5.23; N, 14.52.
1H NMR (CD3CN), δ: 2.55 (s, 3 H, Me); 7.60 and 8.01 (both m,
3 H + 2 H, Ph). MS, m/z (Irel (%)): 160 [M]+.
1ꢀAcetylꢀ3ꢀ(5ꢀmethylꢀ1,3,4ꢀoxadiazolꢀ2ꢀyl)ꢀ1Hꢀindole (3b).
Yield 57%, m.p. 176—178 °C (PriOH). Found (%): C, 69.74;
H, 4.82; N, 10.86. C14H12N2O2. Calculated (%): C, 69.99;
H, 5.03; N, 11.66. 1H NMR (CD3CN), δ: 2.57 (s, 3 H, Me);
2.68 (s, 3 H, Me); 7.43 (m, 1 H, H(5)Ind); 7.49 (m, 1 H, H(6)Ind);
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Received April 27, 2001;
in revised form June 28, 2001