Reactions of 5-methylsulfinyl-1-(4-nitrophenyl)tetrazole with N-nucleophiles

Full text of DOI:10.1007/s11178-005-0356-y

Russian Journal of Organic Chemistry, Vol. 41, No. 9, 2005, pp. 1399–1401. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 9, 2005,
pp. 1427–1429.
Original Russian Text Copyright © 2005 by Egorova, Artamonova, Hrabalek, Koldobskii.
SHORT
COMMUNICATIONS
Dedicated to Full Member of the Russian Academy of Sciences
N.S. Zefirov on His 70th Anniversary
Reactions of 5-Methylsulfinyl-1-(4-nitrophenyl)tetrazole
with N-Nucleophiles
N. G. Egorova1, T. V. Artamonova1, A. Hrabalek2, and G. I. Koldobskii1
1 St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 190013 Russia
e-mail: koldobsk@tu.spb.ru
2 Charles University in Prague, Faculty of Pharmacy, Heyrovskeho 1203, 50005 Hradec Kralove, Chech Republic
e-mail: hrabalek@faf.cuni.cz
Received April 2, 2005
Wide application of tetrazoles in the synthesis of
new medical agents for various purposes [1–7] stimu-
lated extensive search for simple and effective proce-
dures for functionalization of these compounds. While
continuing our studies on 1-aryltetrazole-5-thiones as
readily accessible synthons for the preparation of func-
tionally substituted tetrazoles, we examined the re-
activity of 5-methylsulfinyl-1-(4-nitrophenyl)tetrazole
with respect to various nitrogen-centered nucleophiles.
Initial 5-methylsulfinyl-1-(4-nitrophenyl)tetrazole (I)
was synthesized by oxidation of 5-methylsulfanyl-1-
(4-nitrophenyl)tetrazole with 35% hydrogen peroxide
in acetic acid at 70°C (Scheme 1). Under these condi-
tions, compound I was formed in almost quantitative
yield. The rate of oxidation considerably increases
under microwave irradiation, while the yield of tetra-
zole I remains almost unchanged.
sponding nucleophile as reaction medium. The re-
actions of I with imidazole and benzimidazole were
carried out in acetonitrile.
Scheme 2.
4-O2NC6H4
Ht
NaOH
N
N
N
N
HtH
IIa–IIc
I
4-O2NC6H4
Ht
NEt3, MeCN
N
N
N
N
IIIa, IIIb
II, Ht = 1-pyrrolidinyl (a), piperidino (b), morpholino (c);
III, Ht = 1-imidazolyl (a), 1-benzimidazolyl (b).
We examined chemical properties of some products
thus obtained and found that the benzimidazole frag-
ment in compound IIIb is replaced by the action of
oxygen-centered nucleophiles under mild conditions
(Scheme 3).
Scheme 1.
O
4-O2NC6H4
SMe
4-O2NC6H4
S
Me
H2O2, AcOH
N
N
N
N
N
N
N
N
To conclude, it should be noted that 5-methyl-
sulfinyl-1-(4-nitrophenyl)tetrazole is more reactive
I
Scheme 3.
4-O2NC6H4
We found that 5-methylsulfinyl-1-(4-nitrophenyl)-
tetrazole (I) reacts with pyrrolidine, piperidine, mor-
pholine, imidazole, and benzimidazole to give the
corresponding 5-substituted tetrazoles in high yield
(Scheme 2). The reactions with pyrrolidine, piperidine,
and morpholine were performed at room temperature
in the presence of sodium hydroxide using the corre-
OR
N
NaOH
N
IIIb
+
ROH
+
N
N
N
H
N
IVa–IVc
R = H (a), Me (b), Et (c).
1070-4280/05/4109-1399 © 2005 Pleiades Publishing, Inc.

EGOROVA et al.
1400
toward N-nucleophiles than 5-methylsulfonyl-1-(4-
nitrophenyl)tetrazole [8].
1412, 1422, 1452, 1499, 1520, 1541, 1596, 1612,
1755, 2848, 2861, 2926, 2947, 2980, 3089, 3119.
1H NMR spectrum, δ, ppm: 1.66 s (6H, CH2), 3.22 s
(4H, CH2), 7.90–7.94 d (2H, Harom), 8.40–8.45 d
(2H, Harom).
5-Methylsulfinyl-1-(4-nitrophenyl)tetrazole (I).
a. To a solution of 2.3 g (10 mmol) of 5-methylsul-
fanyl-1-(4-nitrophenyl)tetrazole [9] in 25 ml of glacial
acetic acid we added at 20°C 4 ml of 35% hydrogen
peroxide. The mixture was stirred for 5 h at 70°C,
cooled to 18°C, and diluted with 100 ml of ice water,
and the precipitate was filtered off, washed with water
(3×20 ml), and dried in air. Yield 2.34 g (95%),
mp 155–156°C (from ethanol–acetonitrile, 2:1). IR
spectrum, ν, cm–1: 954, 1010, 1060, 1103, 1118, 1164,
1231, 1270, 1299, 1313, 1326, 1339, 1380, 1416,
1499, 1527, 1539, 1596, 1618, 2300, 2870, 2931,
5-Morpholino-1-(4-nitrophenyl)tetrazole (IIc).
Yield 70%, mp 198–200°C (from ethanol–DMF, 3:1)
[10]. IR spectrum, ν, cm–1: 936, 988, 1010, 1049,
1071, 1079, 1106, 1116, 1174, 1253, 1274, 1294, 1314,
1336, 1352, 1366, 1378, 1427, 1453, 1500, 1530, 1566,
1600, 1615, 2857, 2899, 2931, 2973, 3010, 3055, 3073,
1
3087, 3119. H NMR spectrum, δ, ppm: 3.25 t (4H,
OCH2), 3.75 t (4H, NCH2), 7.92 d (2H, Harom), 8.42 d
(2H, Harom).
1
3009, 3046, 3081, 3122. H NMR spectrum, δ, ppm:
5-(1-Imidazolyl)-1-(4-nitrophenyl)tetrazole
(IIIa). To a solution of 0.5 g (2 mmol) of tetrazole I
in 10 ml of acetonitrile we added 0.14 g (2 mmol) of
imidazole and 0.22 g (2.2 mmol) of triethylamine. The
mixture was stirred for 7 h at 50°C, diluted with 30 ml
of ice water, and acidified with concentrated hydro-
chloric acid to pH 1. The precipitate was filtered off,
washed with water (2×5 ml), and dried in air. Yield
0.35 g (67%), mp 158–159°C (from acetonitrile). IR
spectrum, ν, cm–1: 951, 991, 1016, 1033, 1053, 1087,
1106, 1170, 1246, 1256, 1288, 1307, 1348, 1377, 1452,
1500, 1525, 1540, 1574, 1596, 1614, 3092, 3119, 3156.
1H NMR spectrum, δ, ppm: 7.16 s (1H, 4-H), 7.38 s
(1H, 5-H), 8.02 s (1H, 2-H), 7.81–7.86 d (2H, Harom),
8.44–8.48 d (2H, Harom). Found, %: C 46.69; H 2.72;
N 38.13. C10H7N7O2. Calculated, %: C 46.77; H 2.71;
N 38.22.
3.70 s (3H, CH3), 8.04–8.68 d (2H, Harom), 8.47–8.52 d
(2H, Harom). Found, %: C 37.74; H 2.70; N 27.70.
C8H7N5O3S. Calculated, %: C 37.94; H 2.77; N 27.67.
b. A heat-resistant reactor was charged with a solu-
tion of 2.3 g (10 mmol) of 5-methylsulfanyl-1-(4-nitro-
phenyl)tetrazole in 25 ml of glacial acetic acid, 4 ml of
35% hydrogen peroxide was added at 20°C, and the
mixture was stirred for 1 h at 70°C under microwave
irradiation (65 W) and was treated as described above
in a. Yield 2.25 g (91%), mp 155–156°C.
1-(4-Nitrophenyl)-5-(1-pyrrolidinyl)tetrazole
(IIa). To a solution of 0.5 g (2 mmol) of tetrazole I in
10 ml of pyrrolidine we added 0.08 g (2 mmol) of
sodium hydroxide. The mixture was stirred for 15 min
at room temperature, diluted with 50 ml of ice water,
and acidified with concentrated hydrochloric acid to
pH 1. The precipitate was filtered off, washed with
water (2×5 ml), and dried in air. Yield 0.42 g (82%),
mp 145–146°C (from ethanol). IR spectrum, ν, cm–1:
956, 1010, 1043, 1078, 1100, 1108, 1137, 1236, 1249,
1287, 1315, 1348, 1429, 1460, 1498, 1528, 1593,
1603, 2876, 2930, 2956, 2982, 3049, 3068, 3093,
Tetrazole IIIb was synthesized in a similar way
(reaction time 1 h at 20°C).
5-(1-Benzimidazolyl)-1-(4-nitrophenyl)tetrazole
(IIIb). Yield 83%, mp 183–184°C (from acetonitrile).
IR spectrum, ν, cm–1: 941, 969, 989, 1009, 1090, 1110,
1118, 1126, 1152, 1182, 1188, 1195, 1249, 1276, 1282,
1293, 1315, 1350, 1379, 1423, 1437, 1451, 1482, 1499,
1
3117. H NMR spectrum, δ, ppm: 1.88–1.98 m (4H,
CH2), 3.28–3.53 m (4H, CH2), 7.68–7.73 d (2H, Harom),
8.38–8.42 d (2H, Harom). Found, %: C 50.75; H 4.51;
N 32.33. C11H12N6O2. Calculated, %: C 50.77; H 4.61;
N 32.31.
1
1525, 1568, 1596, 1614, 3071, 3083. H NMR spec-
trum, δ, ppm: 7.35–7.82 m (4H, Harom), 8.20 s (1H,
NH), 7.87–7.91 d (2H, Harom), 8.40–8.45 d (2H, Harom).
Found, %: C 54.79; H 3.10; N 32.00. C14H9N7O2. Cal-
culated, %: C 54.72; H 2.93; N 31.92.
Tetrazoles IIb and IIc were synthesized in a similar
way (in the synthesis of compound IIc, the mixture
was stirred for 2 h).
1-(4-Nitrophenyl)tetrazol-5-one (IVa). To a sus-
pension of 0.2 g (0.65 mmol) of tetrazole IIIa in 10 ml
of water we added 0.03 g (0.65 mmol) of sodium
hydroxide. The mixture was stirred for 2 h at room
temperature, diluted with 30 ml of ice water, and
acidified with concentrated hydrochloric acid to pH 1.
1-(4-Nitrophenyl)-5-piperidinotetrazole (IIb).
Yield 78%, mp 89–90°C (from methanol) [10]. IR
spectrum, ν, cm–1: 909, 956, 982, 1007, 1019, 1035,
1066, 1108, 1120, 1149, 1261, 1286, 1331, 1346, 1382,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005

REACTIONS OF 5-METHYLSULFINYL-1-(4-NITROPHENYL)TETRAZOLE
1401
The precipitate was filtered off, washed with water
(2 × 5 ml), and dried in air. Yield 0.13 g (98%),
mp 216–217°C (from ethanol–water, 3:1) [9]. IR spec-
trum, ν, cm–1: 959, 1030, 1054, 1112, 1149, 1305,
1336, 1373, 1502, 1513, 1595, 1632, 1738, 3085, 3120,
3216. H NMR spectrum, δ, ppm: 8.02 d (2H, Harom),
8.50 d (2H, Harom), 14.85 s (1H, NH).
solutions in DMSO-d6. Microwave-assisted reactions
were performed in a Milestone P/N 44072 reactor
(230 V, 50 Hz). The purity of the products was checked
by TLC on Silufol plates using ethyl acetate–carbon
tetrachloride (2:3) as eluent.
1
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 05-03-32366).
5-Methoxy-1-(4-nitrophenyl)tetrazole (IVb). To
a solution of 0.35 g (1.15 mmol) of tetrazole IIIb in
10 ml of methanol we added 0.045 g (1.15 mmol) of
sodium hydroxide. The mixture was stirred for 15–
20 min at 20°C and diluted with 50 ml of ice water,
and the precipitate was filtered off and dried in air.
Yield 0.16 g (65%), mp 167–168°C (from ethanol–
acetonitrile, 3:1) [9]. IR spectrum, ν, cm–1: 962, 1000,
1039, 1092, 1109, 1132, 1190, 1291, 1313, 1338, 1353,
1411, 1442, 1503, 1514, 1525, 1577, 1584, 1595,
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005