Preparation of 1,5-functionally disubstituted tetrazoles

Full text of DOI:10.1023/B:RUJO.0000013150.17227.7e

Russian Journal of Organic Chemistry, Vol. 39, No. 11, 2003, pp. 1679 1680. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 11, 2003,
pp. 1747 1748.
Original Russian Text Copyright
2003 Smirnova, Kovaleva, Artamonova, Koreneva, Koldobskii.
SHORT
COMMUNICATIONS
Preparation of 1,5-Functionally Disubstituted Tetrazoles
G. G. Smirnova, O. P. Kovaleva, T. V. Artamonova, A. P. Koreneva, and G. I. Koldobskii
St. Petersburg State Technological Institute, St. Petersburg, 198013 Russia
Received June 10, 2003
The extensive application of tetrazoles to the syn-
thesis of pharmaceuticals of high efficiency [1, 2]
significantly stimulated the search for new and easy
methods for preparation of functionally substituted
tetrazoles.
It should be added to the above that the treatment
of tetrazoles Ia, b with a mixture of hydrobromic and
acetic acids cleanly provided hydrolysis product 1-(4-
nitrobenzyl)-4,5-dihydro-1H-tetrazol-5-one.
We established that replacement of methyl- and
phenylsulfonyl groups in 5-mesyl-1-(4-nitrobenzyl)-
and
1-(4-nitrobenzyl)-5-phenylsulfonyltetrazoles
effected by O-nucleophiles may be considered among
methods of this sort.
1- and 2-(Nitrobenzyl)-5-phenylmercaptotetr-
azoles. To a solution of 2.3 mmol of 5-phenyl-
mercaptotetrazole in 10 ml of 10% water solution of
NaOH was added 0.1 mmol of tetrabutylammonium
bromide and 20 mmol of 4-nitrobenzyl bromide in
45 ml of chloroform. The reaction mixture was stir-
red for 10 h at 18 20 C, the organic layer was
separated, washed with 10% water solution of NaOH
(20 ml), then with water (2 20 ml), and dried with
magnesium sulfate. The solvent was removed in a
vacuum, the solid residue was subjected to column
chromatography on silica gel. eluent toluene chloro-
form, 1: 1.
For instance, reactions of the mentioned substrates
with methanol, ethanol, and also with phenol in the
presence of sodium hydroxide afforded the cor-
responding 5-alkoxy(phenoxy) tetrazoles in high
yields. The reaction occurs under mild conditions in
solution in the corresponding alcohol or in aceto-
nitrile at the use of phenol as nucleophile.
1-(4-Nitrobenzyl)-5-phenylmercaptotetrazole.
Yield 3.23 g (57%), mp 116 118 C (from toluene).
1
IR spectrum, cm : 930, 965, 1020, 1100, 1110,
1190, 1210, 1250, 1290, 1360, 1390, 1450, 1485,
1
1530, 1615, 2865, 2940, 3090, 3130. H NMR spec-
trum, , ppm: 5.80 s (2H, CH2), 7.27 7.42 m (7H
arom), 8.15 d (2H arom). Found, %: C 53.70; H3.55;
N 22.38. C14H11N5O2S. Calculated, %: C 53.67;
H 3.51; N 22.36.
I, R = Me (a), Ph (b); II, R = Me (a), Et (b), Ph (c).
Interestingly, the preparative nucleophilic substitu-
tion of methylsulfonyl and phenylsulfonyl groups in
tetrazoles Ia, b proceeded with almost the same rate.
1-(4-Nitrobenzyl)-5-phenylmercaptotetrazole.
Yield 2.34 g (34%), mp 91 92 C (from ethanol). IR
1
spectrum, cm : 885, 1020, 1055, 1140, 1180, 1275,
This fact suggests that the reaction occurs along
the SNAr mechanism. The same conclusion made
Demko and Sharpless in the study of substitution of
the phenylsulfonyl group in 1-benzyl-5-phenylsul-
fonyltetrazole by thiophenol [3].
1305, 1315, 1350, 1395, 1450, 1485, 1535, 1620,
1
2865, 2930, 3095, 3120. H NMR spectrum, , ppm:
6.05 s (2H), 7.32 7.56 m (5H arom), 7.60 d (2H,
C6H4), 8.20 d (2H, C6H4). Found, %: C 53.80;
1070-4280/03/3911-1679$25.00 2003 MAIK Nauka/Interperiodica

1680
SMIRNOVA et al.
H 3.41; N 22.48. C14H11N5O2S. Calculated, %:
C 53.67; H 3.51; N 22.36.
was filtered off and dried in air. Yield 0.32 g (78%),
mp 119 C (from ethanol). IR spectrum, cm : 930,
1
970, 985, 1000, 1010, 1030, 1075, 1110, 1130,
1165, 1190, 1210, 1255, 1295, 1320, 1355, 1435,
1490, 1530, 1560, 1600, 1620, 2870, 2935, 3070,
1-(4-Nitrobenzyl)-5-phenylsulfonyltetrazole (Ib).
A mixture of 4 mmol of 1-(4-nitrobenzyl)-5-phenyl-
mercaptotetrazole, 0.4 mmol of tetrabutylammonium
bromide, 15 ml of 10% acetic acid, and 15 ml of
chloroform was stirred to homogenization, and then
8 mmol of potassium permanganate was added. The
reaction mixture was stirred for 10 h at 20 C, then
5 ml of ethanol was added, the manganese(IV) oxide
was filtered off, washed with boiling chloroform
(3 15 ml), and the organic layer was separated,
washed with water (15 ml), and dried over magnes-
ium sulfate. The solvent was removed in a vacuum.
Yield 1.34 g (97%), mp 100 102 C (from ethanol).
1
3095, 3140. H NMR spectrum, , ppm: 5.70 s (2H,
CH2), 7.30 7.60 m (5H, C6H5), 7.70 d (2H, C6H4),
8.30 d (2H, C6H4). Found, %: C 56.69; H 3.85;
N 23.64. C14H11N5O3. Calculated, %: C 56.57;
H 3.70; N 23.57.
1-(4-Nitrobenzyl)-4,5-dihydro-1H-tetrazol-5-one
(III). A solution of 1.8 mmol of compound Ia in a
mixture of 10 ml of HBr and 10 ml of AcOH was
stirred for 5 h at 120 C, on cooling to 10 C 50 ml of
water was added, the separated precipitate was filter-
ed off and dried in air. Yield 0.30 g (74%), mp174 C
(from a mixture petroleum ether ethyl acetate, 1: 1).
1
IR spectrum, cm : 860, 940, 1090, 1120, 1160,
1200, 1360, 1455, 1540, 1620, 2870, 2935, 3100.
1H NMR spectrum, , ppm: 6.12 s (2H, CH2), 7.50
8.25 m (9H arom). Found, %: C 48.75; H 3.07;
N 20.20. C14H11N5O4S. Calculated, %: C 48.69;
H 3.19; N 20.29.
1
IR spectrum, cm : 870, 940, 1010, 1080, 1115,
1150, 1195, 1295, 1310, 1350, 1370, 1430, 1505,
1535, 1620, 1705, 1720, 2870, 2940, 3090, 3200.
1H NMR spectrum, , ppm: 5.30 s (2H, CH2),
7.50 d (2H, C6H4), 8.25 d (2H, C6H4), 13.70 s (1H,
NH). Found, %: C 43.52; H 3.17; N 31.56.
C8H7N5O3. Calculated, %: C 43.44; H 3.17; N 31.67.
5-Methoxy-1-(4-nitrobenzyl)tetrazole
(IIa).
A solution of 1.8 mmol of compound Ia and 2.2 mmol
of NaOH in 15 ml of methanol were stirred for 2 h at
18 20 C, then 20 ml of water was added, and the
mixture was cooled to 5 10 C. The separated pre-
cipitate was filtered off, washed with water (15 ml),
and dried in air. Yield 0.33 g (81%), mp 108 109 C
Characteristics of tetrazoles IIa c and III prepared
from Ia, b were identical.
5-Mesyl-1-(4-nitrobenzyl)tetrazole
(Ia)
was
prepared by procedure from [4].
1
(from 50% ethanol). IR spectrum, cm : 980, 1015,
1110, 1130, 1190, 1260, 1310, 1350, 1430, 1485,
1530, 1595, 2870, 2980, 3020, 3095, 3140. H NMR
IR spectra were recorded on spectrometer UR-20
from samples pelletized with KBr. H NMR spectra
1
1
spectrum, , ppm: 4.20 s (3H, CH3), 5.50 s (2H,
CH2), 7.50 7.57 d (2H, C6H4). Found, %: C 45.91;
H3.77; N29.88. C9H9N5O3. Calculated, %: C 45.96;
H 3.83; N 29.79.
were registered on spectrometer Bruker AC-200 from
solutions in DMSO-d6. For column chromatography
was used a sorbent Silicagel L 100/200.
The study was carried out under financial support
from a grant of the President of Russian Federation
for young scientists MK-1685.2003.03
Tetrasole IIb was prepared in a similar way.
1-(4-Nitrobenzyl)-5-ethoxytetrazole (IIb). Yield
77%, mp 109 C (from 50% ethanol). IR spectrum,
cm : 905, 935, 970, 990, 1030, 1105, 1120, 1165,
1
REFERENCES
1185, 1210, 1255, 1305, 1350, 1400, 1435, 1450,
1480, 1540, 1600, 2870, 2935, 3000, 3080, 3130.
1H NMR spectrum, , ppm: 1.30 s (3H, CH3),
4.50 m (2H, CH2), 5.50 s (2H, CH2Ar), 7.50 d (2H,
C6H4), 8.25 d (2H, C6H4). Found, %: C 48.10;
H 4.38; N 28.07. C10H11N5O3. Calculated, %:
C 48.19; H 4.42; N 28.11.
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1-(4-Nitrobenzyl)-5-phenoxytetrazole (IIc).
A solution of 1.4 mmol of 5-mesyl-1-(4-nitrobenzyl)-
tetrazole (Ia), 1.9 mmol of phenol, 1.9 mmol of
NaOH in 15 ml of acetonitrile was stirred for 1.5 h
at 20 C, water was added, the separated precipitate
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003