In fact, treatment of solutions of compounds 3a,b (prepared by the alkylation of 4-amino-3-mercapto-
triazole 1) with the ortho-nitrobenzyl bromides 2a,b [1] in DMF in the presence of the corresponding aldehydes
successively with methanolic KOH solution, hydrochloric acid, and zinc gives the target indoles 5a,b.
This method is an example of the synthesis of indoles based on a heterocyclic matrix. The 4-amino-
3-mercaptotriazole 1 acts as this matrix, which can be separated from the reaction mixture.
Despite the low yields, the advantage of this route is the availability of the starting materials and
simplicity of carrying out the reaction. The whole process can be realized in one pot starting with the
aminotriazole 1 with successive addition of all of the components. Further study of the factors influencing the
route of opening of the thiadiazine ring has allowed us to develop a novel method for the synthesis of the
2-arylindoles. These are of interest as antifungal, antimicrobial, antibacterial, and cytotoxic agents [3-7].
1H NMR spectra were recorded on a Bruker DPX 250 instrument (250 MHz) using CDCl3 with TMS as
internal standard. Mass spectra were taken on a Kratos MS-30 spectrometer by electron impact with ionization
intensity 70 eV and ionization chamber temperature 200ºC.
Synthesis of Indoles 5 (General Method). A mixture of compound 3 (50 mmol) and the corresponding
aldehyde (57 mmol) in DMF (10 ml) was treated with KOH in methanol solution (5 N, 2 ml) and stirred for 3 h
at room temperature. The reaction mixture on a water bath was treated dropwise with stirring with conc. HCl
(4 ml) and the stirring was continued for 30 min. Zinc powder (2.9 g) was carefully added portionwise, the
mixture obtained was stirred for 3 h at room temperature, and the zinc powder was removed by filtration. The
filtrate was treated with KOH solution (15%, 20 ml) and then extracted with benzene (2 x 30 ml). The benzene
layer was separated, concentrated, passed through a silica gel layer, evaporated to dryness in vacuo, and the
residue was recrystallized.
2-(5-Methyl-2-furanyl)-1H-indole (5a). Yield 0.35 g (35%) as beige crystals; mp 86-87ºC (a mixture
1
of petroleum ether and chloroform); (mp 85-86ºC [8]). H NMR spectrum, , ppm (J, Hz): 2.38 (3H, s, CH3);
6.07 (1H, d, J = 3.3, H Fur); 6.50 (1H, d, J = 3.3, H Fur); 6.67 (1H, s, H Ind); 7.06-7.19 (2H, m, H Ar); 7.33-
7.36 (1H, m, H Ar); 7.57-7.60 (1H, m, H Ar); 8.37 (1H, br. s, NH). Mass spectrum, m/z (Irel, %): 197 [M]+ (100),
168 (30), 154 (60), 127 (21), 115 (10), 98 (25), 89 (53), 84 (13), 77 (20), 63 (27), 51 (29), 43 (50).
2-(4-Chlorophenyl)-5,6-dimethoxy-1H-indole (5b). Yield 0.3 g (21%) as colorless crystals; mp
1
210-211ºC (CHCl3). H NMR spectrum, , ppm (J, Hz): 3.87 (3H, s, OCH3); 3.91 (3H, s, OCH3); 6.67 (1H, s,
H Ind); 6.84 (1H, s, H Ar); 7.04 (1H, s, H Ar); 7.34 (2H, d, AA'BB' system, J = 8.7, H Ar); 7.49 (2H, d, AA'BB'
system, J = 8.7, H Ar); 8.20 (1H, br. s, NH). Mass spectrum, m/z (Irel, %): 289/287 [M]+ (32/96), 274/272
(34/100), 246/244 (18/53), 227 (16), 216 (13), 210 (16), 209 (63), 201 (19), 166 (17), 161 (16), 151 (11), 144
(13), 143 (40), 91 (17), 63 (15), 59 (12), 43 (23). Found, %: C 66.92; H 5.01; N 4.78. C16H14ClNO2. Calculated,
%: C 66.79; H 4.90; N 4.87.
This work was carried out through realization of a Federal agency target program "Development of
University Science Schools (2009-2010)" (project No. 2.1.1/4628).
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