New method of 5-mercaptotetrazoles functionalization

Full text of DOI:10.1134/S1070428011110273

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 11, pp. 1786−1788. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © P.A. Aleshunin, D.V. Aleshunina, V.A. Ostrovskii, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 11, pp. 1743−1744.
SHORT
COMMUNICATIONS
New Method of 5-Mercaptotetrazoles Functionalization
P. A. Aleshunin, D. V. Aleshunina, and V. A. Ostrovskii
St. Petersburg State Technological Institute (Technical University), St. Petersburg, 190013 Russia
e-mail: apa-ti@mail.ru
Received February 23, 2011
DOI: 10.1134/S1070428011110273
Tetrazole derivatives containing a sulfur atom in the
position 5 of the ring are promising as biologically active
compounds and also as components of photomaterials
[1–4].At the same time the mercaptothiazoles are efficient
reagents in the schemes of the total synthesis of natural
substances [4].
We found that the arylation of 1-phenyl-5-mercapto-
tetrazole (I) with iodobenzene catalyzed by CuI
(10 mol%) in the presence of a ligand (2 equiv of
ethylenediamine) and a base (2 equiv of Cs2CO3), made
it possible to obtain 5-phenylsulfanyltetrazole (II) in
a high yield (see the scheme).
The developed method of the sysnthesis of
5-arylsulfanyl-tetrazoles can be used for the synthesis
of 5-(R-sulfanyl)tetrazoles (R = Vin, Ht). By the Сu-
catalyzed vinylation and hetarylation tetrazole I we
obtained sulfanyltetrazoles III and IV in the yields of
92 and 85% respectively (see the scheme).
Asignificant attention was paid to the development of
efficient synthetic procedures for 5-(R-sulfanyl)tetrazoles
(R = Alk, Bn) [1]. The traditional methods of prepara-
tion of these compounds are based on the alkylation of
5-mercaptotetrazoles with various electrophilic agents
[1, 2].
Note that in contrast to the method of direct arylation
of mercaptotetrazoles [5] the Cu-catalyzed arylation
allows the preparation also of the other 5-(R-sulfanyl)
tetrazoles with R = Vin and Ht, and also does not require
the use of rare reagents and additional equipment.
The preparation methods of 5-(R-sulfanyl)tetrazoles
(R =Ar) are poorly understood.Asynthesis was reported
of 5-arylsulfanyltetrazoles by the direct arylation of
5-mercaptotetrazoles by fluoro(chloro)nitrobenzenes
[5], by the reaction of 5-mercaptotetrazoles with phenols
under electrolysis conditions [6], and also by the reaction
of 5-tosyltetrazoles with thiophenols [7]. These methods
are not general for they make it possible to obtain 5-aryl-
sulfanyltetrazoles only with definite substituents (R =Ar).
Besides the necessity to use difficultly available reagents
and special equipment, long reaction time and relatively
low yield of target compounds reduce the efficiency of
the cited methods.
Synthesis of tetrazoles II–IV. General procedure.
A dispersion of 2.8 mmol of tetrazole I, 0.28 mmol
of CuI, 5.9 mmol of ethylenediamine, 5.9 mmol of
Cs2CO3,1 3.4 mmol of halide, and 2 ml of DMF was
stirred for 1 h (TLC monitoring of conversion) at 85°С in
an argon atmosphere. The reaction mixture was cooled
to 20°С and poured into 20 ml of water. The obtained
solution was extracted with ethyl acetate (2 × 8 ml).
The combine extract was washed with brine (2 × 8 ml),
dried with anhydrous Na2SO4, the solvent was removed
in a vacuum. The residue obtained was dispersed in
30 ml of hexane, and the dispersion was filtered. The
precipitate, sulfanyltetrazole II–IV, was dried in an air
flow.
Therefore the development of a general and efficient
method of the synthesis of 5-арилsulfanyltetrazoles is
an urgent problem.
At present one of the most promising methods of
synthesis and functionalization of aromatic thioethers
is their direct arylation with aryl halides catalyzed by
palladium and copper complexes [6].
1 The application of K2CO3 as base gave worse results.
1786

NEW METHOD OF 5-MERCAPTOTETRAZOLES FUNCTIONALIZATION
1787
Scheme.
Ph
S
Ph
N
PhI
N
N
N
II
Ph
HS
Ph
S
Ph
N
Br
Ph
N
i
N
N
N
N
N
III
N
I
Br
Ph
S
N
N
N
N
N
N
IV
i, CuI (10 mol%), H2N(CH2)2NH2 (2 equiv), Cs2CO3 (2 equiv), DMF, 85оС, under argon.
152.98 (С6H4N). Mass spectrum: m/z 256.41 [M + H]+.
Calculated M 255.3.
1-Phenyl-5-(phenylsulfanyl)tetrazole (II). Yield
0.67 g (94%), colorless crystals, mp 129–130°C,
Rf 0.3 (hexane–ethyl acetate, 7:3). 1Н NMR spectrum
(DMSO-d6), δ, ppm: 7.41–7.46 m (3Н, Ph, Ph–S),
7.53–7.56 m (2Н, Ph, Ph–S), 7.64–7.70 m (5Н, Ph, Ph–S).
13С NMR spectrum, δ, ppm: 125.16, 127.40 (Ph), 129.63
(Ph–S), 129.76 (Ph), 129.86 (Ph–S), 130.76 (Ph), 133.02
(PhS), 153.20 (CN4). Mass spectrum: m/z 255.37 [M +
H]+. Calculated M 254.31.
1Н, 13С NMR spectra were registered on a spectrometer
Bruker DPX-300 at operating frequencies 300.1 and
75.5 МHz respectively. The signals of the solvent
DMSO-d6 (δH, 2.50, δC 39.52 ppm) served as internal
references. Mass spectra were obtained on a liquid
chromato-mass spectrometer Thermo Scientific TSQ
Quantum Access MAX. The melting points were
measured on a PTP device at the heating rate of
1 deg min–1 in the range of the melting point. The
homogeneity of compounds obtained was checked by
TLC on Merck Kieselgel 60F245 plates, development
under UV irradiation (λ 254 nm).
1-Phenyl-5-(Е)-(styrylsulfanyl)tetrazole (III).
Yield 0.72 g(92%), colorless crystals, mp 92–93°C,
1
Rf 0.25 (hexane–ethyl acetate, 7 : 3). Н NMR spectrum
(DMSO-d6), δ, ppm: 7.07 d (1Н, Ph–СH=СH, J 15.67 Hz),
7.26–7.40 m (4Н, Ph, C6H4СH=СH), 7.49–7.51 m (2Н,
Ph, C6H4–СH=СH), 7.66–7.72 m (5Н, Ph–СH=СH,
Ph). 13С NMR spectrum, δ, ppm: 115.57 (Ph–СH=СH),
124.87 (Ph), 126.58 (C6H4–СH=СH), 128.66 (Ph),
128.81 (C6H4–СH=СH), 129.99 (Ph), 130.81, 132.94
(C6H4–СH=СH), 135.13 (Ph), 135.56 (Ph–СH=СH),
152.61 (CN4). Mass spectrum: m/z 281.39 [M + H]+.
Calculated M 280.34.
The characteristics of 1-phenyl-5-mercaptotetrazole
(I) were consistent with the published data [9].
ACKNOWLEDGMENTS
The study was carried out under the financial support
of the Russian Foundation for Basic Research (grants
nos. 10-03-00-700-а, 11-08-00757-а).
2-(1-Phenyltetrazol-5-yl)pyridine (IV). Yield 0.6 g
(85%), colorless crystals, mp 88–89оC, Rf 0.4 (hexane–
ethyl acetate, 7:3). 1Н NMR spectrum (DMSO-d6),
δ, ppm: 7.24 m (1Н, С6H4N), 7.45–7.75 m (7H, Ph,
С6H4N), 8.34 m (1Н, С6H4N). 13С NMR spectrum, δ,
ppm: 122.45, 123.47 (С6H4N), 125.23, 129.50, 130.67,
133.32 (Ph), 138.08 (С6H4N), 149.46 (CN4), 150.15,
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