Modification of the Gewald methodology for the synthesis of 3-amino-2-( 1 H-1 , 2 , 3-benzotriazol-1-yl ) substituted benzofurans , benzothiophenes and 1 H-indoles

Treatment of 1-chloromethylbenzotriazole (4) with salicylonitrile (5a), thiosalicylonitrile (5b), ethyl N-(2-cyanophenyl)carbamate (5c), and N-(2-cyanophenyl)methane-sulfonamide (5d) provided the corresponding intermediates 3. Cyclization of compounds 3a-3c with LDA gave 2(1H-benzo[d][1,2,3]triazol-1-yl)benzofuran-3-amine (2a), 2-(1H-benzo[d][1,2,3]triazol-1yl)benzo[b]thiophen-3-amine (2b), and ethyl 3-amino-2-(1H-benzo[d][1,2,3]triazol-1-yl)-1Hindole-1-carboxylate (2c), respectively. Attempts to accomplish elimination of the benzotriazole nitrogen under both thermal and photolytic conditions failed.


Results and Discussion
Easily available 1-chloromethyl-1H-benzotriazole 4 treated with the corresponding 2-substituted benzonitriles 5 provided good yields of compounds 3a-d (Scheme 4).Starting benzonitriles 5 were either commercially available (salicylonitrile) or were prepared by known methods.Transformation of nitriles 3 into amino derivatives 2 under mild conditions was unsuccessful.On the other hand, acceptable to good yields (55-80 %) of compounds 2a-c were obtained using LDA in THF (Scheme 5).However, compound 3d under the same conditions gave a rather complex mixture.The formed compounds 2a-c are yellow light-sensitive solids which darken on light.

Scheme 5
We have studied both thermal and photochemical behavior of these compounds.Heating of these compounds in boiling DMF or in various high-boiling solvents (quinoline, diphenylether, xylenes) at 200 °C, as well as in orthophosphoric or polyphosphoric acid led to complex mixtures.Similar results were obtained by photochemical treatment in various solvents (acetonitrile, methanol).
Therefore we decided to evaluate the influence of the free amino group on this behavior.For this purpose, we prepared acetyl derivative 6a and diacetyl derivative 6b.Treatment of amino derivative 2a with acetic anhydride provided good yields of 6b.Compound 6a was prepared by acylation of 2a with one equivalent of acetyl chloride in the presence of triethylamine.However, the compounds were either resistant to any reaction or provided also inseparable mixtures.
Benzotriazole chemistry advanced by the Katritzky group 7 has proved its wide scope and further applications could be expected in the future.In spite of the failed cyclization, we believe that the heteroaryl substituted benzotriazoles 2 or similar compounds available by this methodology could be useful in some other transformations.Therefore the present paper could be of interest for the methodology of the synthesis of this type of compounds.

Experimental Section
General Procedures.Melting points were measured on a Kofler block and are uncorrected.NMR spectra were measured on a Bruker 250 DPX spectrometer (250.13MHz for 1 H, 62.89 MHz for 13 C).Reference for 1 H δ (TMS) = 0.00ppm, for 13 C δ (CDCl3) = 77.0ppm.Chemical shifts are given in ppm (δ-scale), coupling constants (J) in Hz.IR spectra (KBr) were recorded on a Unicam SP 2006 and Perkin-Elmer FT-IR System Spectrum BX spectrometers, wavenumbers are given in cm -1 .UV spectra were measured on a Shimadzu UV-260 spectrometer in ethanol and wavelengths are given in nm.Flash chromatography was done on silica gel 60 (230-400 mesh) and preparative TLC on pre-coated PLC plates (silica gel 60) from EM Science.Spectroquality acetonitrile or methanol (Merck) was used without further purification in all photochemical experiments.A Hanovia merury lamp was used as the light source in a photochemical reactor with double-walled quartz immersion well.The following starting compounds were prepared by the previously published methods: thiosalicylonitrile (5b), 3a ethyl N-(2-cyanophenyl)carbamate (5c), 11 and N-(2cyanophenyl)methanesulfonamide (5d). 12