Copper-catalyzed arylation of tetrazole-5-thiones upon convection heating and microwave activation conditions

Article abstract of DOI:10.1007/s10593-012-0996-0

The arylation of 1-phenyltetrazole-5-thione using a series of iodobenzene derivatives in the presence of cuprous chloride and a ligand such as ethylenediamine. It was shown that the use of microwave activation permitted shortening of the reaction time, increasing yields and simplification of the reaction products isolation.

Full text of DOI:10.1007/s10593-012-0996-0

Chemistry of Heterocyclic Compounds, Vol. 48, No. 2, May, 2012 (Russian Original Vol. 48, No. 2, February, 2012)
COPPER-CATALYZED ARYLATION OF TETRAZOLE-
5-THIONES UPON CONVECTION HEATING AND
MICROWAVE ACTIVATION CONDITIONS
U. N. Dmitrieva1, S. M. Ramsh1, Yu. E. Zevatskii1,
T. V. Artamonova1, and L. V. Myznikov1*
The arylation of 1-phenyltetrazole-5-thione using a series of iodobenzene derivatives in the presence of
cuprous chloride and a ligand such as ethylenediamine. It was shown that the use of microwave
activation permitted shortening of the reaction time, increasing yields and simplification of the reaction
products isolation.
Keywords: aryl iodide, cuprous chloride, ethylenediamine, tetrazole-5-thione, arylation, microwave
activation.
The most promising approach to the preparation of 1,5-disubstituted tetrazoles is functionalization of
the side chain of a suitable substrate. Until recently, the synthesis of 1-substituted 5-arylsulfanyltetrazoles was
carried out by the direct arylation of mercapto group with corresponding fluoro- or chlorodinitrobenzenes [1],
electrolytic reaction with dihydroxybenzenes [2], or the nucleophilic substitution of the functional group at the
tetrazole ring carbon atom by means of a corresponding thiol [3]. However, these and other methods suitable for
the preparation of 1-substituted 5-arylsulfanyltetrazoles are not general in scope or require complicated
multistep procedures.
Catalytic arylation of corresponding tetrazole-5-thiones is the most attractive method for preparation of
1-substituted 5-arylsulfanyltetrazoles. Thus, Niu et al. [4] have arylated 1-methyltetrazole-5-thione using
iodobenzene. This reaction was carried out in the presence of catalytic amounts of cuprous salts and
1,10-phenanthroline as a ligand at 120°C in DMF during 10 h.
ArI, CuCl, (CH2NH2)2·HCl, K2CO3
S
S
Ar
N
N
DMF
N
NH
N
N
N
N
1–5
1 Ar = 2,4,6-Me3C6H2; 2 Ar = 4-MeC6H4; 3 Ar = 4-MeOC6H4; 4 Ar = 4-O2NC6H4; 5 Ar = Ph
_______
*To whom correspondence should be addressed, e-mail: myznikov_lv@mail.ru.
1St. Petersburg State Technological Institute (Technical University), 26 Moskovskii Ave., Saint Petersburg
190013, Russia.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 377-379, February, 2012. Original
article submitted May 21, 2011.
0009-3122/12/4802-0355©2012 Springer Science+Business Media, Inc.
355

TABLE 1. Reaction Time and Yields in the Arylation Reaction Using
Convection Heating and under MWA Conditions
Com-
pound
Reaction
time, h
Yield using
convection heating, %
Yield under MWA
conditions, %
2.0
1.5
2.5
2.0
1.5
52
60
38
36
42
76
99
90
95
80
1
2
3
4
5
In a continuation of a study of methods for the preparation of functionally-substituted tetrazoles, we
have investigated the arylation of 1-phenyltetrazole-5-thione by aryl iodides in the presence of cuprous salts
with thermal heating and in microwave activation (MWA) conditions. We have found that the corresponding
S-aryltetrazoles 1-5 were formed upon the arylation using substituted aryl iodides in the presence of 20 mol%
CuCl and ethylenediamine as the ligand in DMF at 85°C.
Microwave activation has a great effect on the course of this reaction. The yields are 20-50% greater
than with convection heating at the same reaction time. The reaction times and yields are given in Table 1. The
amount of tar formation is markedly reduced using MWA so that isolation of the reaction products is much
more convenient.
The use of 1,10-phenanthroline as the ligand did not lead to a significant change in the reaction product
yields.
Thus, the arylation of 1-substituted tetrazole-5-thiones in the presence of cuprous salts under microwave
activation conditions can be seen today as the most convenient method for the preparation of 5-thioaryl-
tetrazoles.
TABLE 2. Spectral Characteristics of Compounds 1-5
Com-
pound
IR spectrum, ν, cm-1
1Н NMR spectrum, δ, ppm (J, Hz)
3430, 3057, 3025, 2966, 2919, 2903,
1596, 1499, 1460, 1436, 1413, 1388,
1300, 1274, 1237, 1175, 1090, 1074,
1017, 974, 848, 761, 688, 562
7.65-7.75 (5H, m, H Ph);
7.06 (2H, s, H-3,5 Ar); 2.30 (6H, s, 2,6-CH3);
2.27 (3H, s, 4-CH3)
1
3445, 3106, 3069, 3046, 3022, 1595,
1501, 1493, 1464, 1416, 1389, 1277,
1241, 1180, 1091, 1061, 1041, 1013,
811, 763, 696, 686, 536
7.50-7.75 (5H, m, H Ph);
7.44 (2H, d, J = 8.0, H Ar);
7.25 (2H, d, J = 8.0, H Ar); 2.32 (3H, s, CH3)
2
3
4
5
3432, 3017, 2976, 2934, 2829, 1589,
1571, 1492, 1456, 1419, 1408, 1389,
1288, 1254, 1241, 1175, 1087, 1075,
1023, 1007, 976, 826, 771, 690, 555
7.65-7.70 (5H, m, H Ph);
7.52 (2H, d, J = 8.8, H Ar);
7.01 (2H, d, J = 8.8, H Ar); 3.79 (3H, s, CH3)
3437, 3092, 3063, 1595, 1576, 1519,
1499, 1462, 1419, 1388, 1346, 1332,
1313, 1276, 1245, 1094, 1062, 1010,
981, 853, 758, 746, 694, 685, 560
8.22 (2H, d, J = 9.0, H Ar);
7.65-7.73 (7H, m, H Ar)
3440, 3067, 1593, 1500, 1474, 1462,
1440, 1413, 1401, 1390, 1277, 1241,
1090, 1073, 1058, 1013, 1000, 973,
759, 706, 696, 687, 555, 537
7.65-7.68 (5H, m, H 1-Ph);
7.53-7.55 (2H, m, H 5-Ph);
7.43-7.46 (3H, m, H 5-Ph)
356

TABLE 3. Physicochemical Characterictics of Compounds 1-5
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
Mp, С
С
Н
N
C16H16N4S
64.75
64.84
62.60
62.66
59.01
59.14
52.10
52.17
5.30
5.44
4.47
4.51
4.13
4.25
3.09
3.03
18.81
18.90
20.87
20.88
19.78
19.70
23.15
23.40
135-136
1
2
3
4
C14H12N4S
81-82
C14H12N4OS
C13H9N5O2S
87-88
140-141
C13H10N4S
61.34
61.40
3.93
3.96
22.02
22.03
129-130
5
EXPERIMENTAL
The IR spectra were recorded on a Shimadzu FTIR-8400S spectrometer using KBr pellets. The 1H NMR
spectra were recorded on a Bruker WM-400 spectrometer (400 MHz) in DMSO-d6. The elemental analysis was
carried out on a LECO CHNS-932 analyzer. The microwave-assisted reactions were carried out in a Milestone
MicroSynth reactor. The purity and identity of the samples obtained were monitored by thin-layer
chromatography on Silufol UV-254 plates.
1,3,5-Trimethyliodobenzene was prepared according to Liu et al. [5] and 1-phenyltetrazole-5-thione was
prepared according to Lieber and Ramachandran [6].
1-Phenyl-5-(phenylsulfanyl)-1H-tetrazole (5). K2CO3 (1.93 g, 14.0 mmol), cuprous chloride (0.11 g,
1.1 mmol), and ethylenediamine hydrochloride (0.15 g, 1.1 mmol) were added to a solution of 1-phenyl-
tetrazole-5-thione (1.00 g, 5.6 mmol) and iodobenzene (1.20 g, 5.9 mmol) in DMF (15 ml). The reaction
mixture was stirred for 2 h at 85°C under microwave activation conditions (100 W), cooled to 20°C, and poured
into water (50 ml). The precipitate formed was filtered off. Yield 1.15 g (80%).
The reaction of 1-phenyltetrazole-5-thione with iodobenzene upon convection heating was carried out
analogously. After pouring into water, the reaction product was extracted with ethyl acetate. The organic layer
was washed with water, dried over sodium sulfate, and evaporated. The residue was subjected to column
chromatography to give 0.60 g (42%) tetrazole 5.
Products 1-4 were synthesized analogously. The yields, melting points, spectral data, and elemental
analyses data for compounds 1-5 are given in Tables 2 and 3.
REFERENCES
1.
2.
3.
4.
5.
6.
M. A. Gol'tsberg and G. I. Koldobskii, Zh. Org. Khim., 32, 1238 (1996).
M. M. Khodaei, A. Alizadeh, and N. Pakravan, J. Org. Chem., 73, 2527 (2008).
Z. P. Demko and K. B. Sharpless, Angew. Chem., Int. Ed., 41, 2110 (2002).
L.-F. Niu, Y. Cai, C. Liang, X.-P. Hui, and P.-F. Xu, Tetrahedron, 67, 2878 (2011).
Q. Liu, Y. Lan, J. Liu, G. Li, Y.-D. Wu, and A. Lei, J. Am. Chem. Soc., 131, 10201 (2009).
E. Lieber and J. Ramachandran, Can. J. Chem., 37, 101 (1959).
357