Unusual Thermal Isomerization of 1-phenyl-3-(2-thienyl)-1,5,6,7-tetrahydro-4H-indazol-4-one under Gas Phase Conditions

GUILLERMO M. CHANS; MA. TERESA BAUMGARTNER; GLORIA I. YRANZO; ELIZABETH L. MOYANO

FLORIANOPOLIS

Conferencia; 10a Conferencia Latinoamericana de Físico-Química Orgánica; 2009

It is well established that 1,5,6,7-tetrahydro-4H-indazol-4-ones are of considerable importance, not only for their potential biological activity1 but also because of their value as synthons in organic reactions.2 Nevertheless, there is no bibliography about thermal reactivity in gas phase of these fused rings and only few studies of indazoles have been described.3 Here we present the thermal behavior of 1-phenyl-3-(2-thienyl)-1,5,6,7-tetrahydro-4H-indazol-4-one 1 under Flash Vacuum Pyrolysis conditions (FVP). Mechanistic insights of the reaction are also discussed. FVP of 1 was performed at 600-750ºC with contact time of 10-3 s and vacuum of 10 µtorr. The main reaction product was 2-phenyl-3-(2-thienyl)-2,5,6,7-tetrahydro-4H-indazol-4-one (2) (15% yield at 700°C) (Scheme 1). The product 2 has been obtained by conventional synthesis4 to verify the proposed structure. The characterization of main reaction products was performed using GC-MS, and NMR techniques (1H, 13C, COSY, HSQC, HMBC and ROESY). The formation of 2-phenylindazolone 2 could be rationalized by a N1N5 phenyl migration in the starting 1-phenylindazolone 1. This type of sigmatropic isomerization was also observed in the FVP reactions of trityl- and adamantylindazoles where the 1-R-indazole was the most stable isomer.5H-indazol-4-ones are of considerable importance, not only for their potential biological activity1 but also because of their value as synthons in organic reactions.2 Nevertheless, there is no bibliography about thermal reactivity in gas phase of these fused rings and only few studies of indazoles have been described.3 Here we present the thermal behavior of 1-phenyl-3-(2-thienyl)-1,5,6,7-tetrahydro-4H-indazol-4-one 1 under Flash Vacuum Pyrolysis conditions (FVP). Mechanistic insights of the reaction are also discussed. FVP of 1 was performed at 600-750ºC with contact time of 10-3 s and vacuum of 10 µtorr. The main reaction product was 2-phenyl-3-(2-thienyl)-2,5,6,7-tetrahydro-4H-indazol-4-one (2) (15% yield at 700°C) (Scheme 1). The product 2 has been obtained by conventional synthesis4 to verify the proposed structure. The characterization of main reaction products was performed using GC-MS, and NMR techniques (1H, 13C, COSY, HSQC, HMBC and ROESY). The formation of 2-phenylindazolone 2 could be rationalized by a N1N5 phenyl migration in the starting 1-phenylindazolone 1. This type of sigmatropic isomerization was also observed in the FVP reactions of trityl- and adamantylindazoles where the 1-R-indazole was the most stable isomer.51 but also because of their value as synthons in organic reactions.2 Nevertheless, there is no bibliography about thermal reactivity in gas phase of these fused rings and only few studies of indazoles have been described.3 Here we present the thermal behavior of 1-phenyl-3-(2-thienyl)-1,5,6,7-tetrahydro-4H-indazol-4-one 1 under Flash Vacuum Pyrolysis conditions (FVP). Mechanistic insights of the reaction are also discussed. FVP of 1 was performed at 600-750ºC with contact time of 10-3 s and vacuum of 10 µtorr. The main reaction product was 2-phenyl-3-(2-thienyl)-2,5,6,7-tetrahydro-4H-indazol-4-one (2) (15% yield at 700°C) (Scheme 1). The product 2 has been obtained by conventional synthesis4 to verify the proposed structure. The characterization of main reaction products was performed using GC-MS, and NMR techniques (1H, 13C, COSY, HSQC, HMBC and ROESY). The formation of 2-phenylindazolone 2 could be rationalized by a N1N5 phenyl migration in the starting 1-phenylindazolone 1. This type of sigmatropic isomerization was also observed in the FVP reactions of trityl- and adamantylindazoles where the 1-R-indazole was the most stable isomer.52 Nevertheless, there is no bibliography about thermal reactivity in gas phase of these fused rings and only few studies of indazoles have been described.3 Here we present the thermal behavior of 1-phenyl-3-(2-thienyl)-1,5,6,7-tetrahydro-4H-indazol-4-one 1 under Flash Vacuum Pyrolysis conditions (FVP). Mechanistic insights of the reaction are also discussed. FVP of 1 was performed at 600-750ºC with contact time of 10-3 s and vacuum of 10 µtorr. The main reaction product was 2-phenyl-3-(2-thienyl)-2,5,6,7-tetrahydro-4H-indazol-4-one (2) (15% yield at 700°C) (Scheme 1). The product 2 has been obtained by conventional synthesis4 to verify the proposed structure. The characterization of main reaction products was performed using GC-MS, and NMR techniques (1H, 13C, COSY, HSQC, HMBC and ROESY). The formation of 2-phenylindazolone 2 could be rationalized by a N1N5 phenyl migration in the starting 1-phenylindazolone 1. This type of sigmatropic isomerization was also observed in the FVP reactions of trityl- and adamantylindazoles where the 1-R-indazole was the most stable isomer.53 Here we present the thermal behavior of 1-phenyl-3-(2-thienyl)-1,5,6,7-tetrahydro-4H-indazol-4-one 1 under Flash Vacuum Pyrolysis conditions (FVP). Mechanistic insights of the reaction are also discussed. FVP of 1 was performed at 600-750ºC with contact time of 10-3 s and vacuum of 10 µtorr. The main reaction product was 2-phenyl-3-(2-thienyl)-2,5,6,7-tetrahydro-4H-indazol-4-one (2) (15% yield at 700°C) (Scheme 1). The product 2 has been obtained by conventional synthesis4 to verify the proposed structure. The characterization of main reaction products was performed using GC-MS, and NMR techniques (1H, 13C, COSY, HSQC, HMBC and ROESY). The formation of 2-phenylindazolone 2 could be rationalized by a N1N5 phenyl migration in the starting 1-phenylindazolone 1. This type of sigmatropic isomerization was also observed in the FVP reactions of trityl- and adamantylindazoles where the 1-R-indazole was the most stable isomer.5H-indazol-4-one 1 under Flash Vacuum Pyrolysis conditions (FVP). Mechanistic insights of the reaction are also discussed. FVP of 1 was performed at 600-750ºC with contact time of 10-3 s and vacuum of 10 µtorr. The main reaction product was 2-phenyl-3-(2-thienyl)-2,5,6,7-tetrahydro-4H-indazol-4-one (2) (15% yield at 700°C) (Scheme 1). The product 2 has been obtained by conventional synthesis4 to verify the proposed structure. The characterization of main reaction products was performed using GC-MS, and NMR techniques (1H, 13C, COSY, HSQC, HMBC and ROESY). The formation of 2-phenylindazolone 2 could be rationalized by a N1N5 phenyl migration in the starting 1-phenylindazolone 1. This type of sigmatropic isomerization was also observed in the FVP reactions of trityl- and adamantylindazoles where the 1-R-indazole was the most stable isomer.51 was performed at 600-750ºC with contact time of 10-3 s and vacuum of 10 µtorr. The main reaction product was 2-phenyl-3-(2-thienyl)-2,5,6,7-tetrahydro-4H-indazol-4-one (2) (15% yield at 700°C) (Scheme 1). The product 2 has been obtained by conventional synthesis4 to verify the proposed structure. The characterization of main reaction products was performed using GC-MS, and NMR techniques (1H, 13C, COSY, HSQC, HMBC and ROESY). The formation of 2-phenylindazolone 2 could be rationalized by a N1N5 phenyl migration in the starting 1-phenylindazolone 1. This type of sigmatropic isomerization was also observed in the FVP reactions of trityl- and adamantylindazoles where the 1-R-indazole was the most stable isomer.5H-indazol-4-one (2) (15% yield at 700°C) (Scheme 1). The product 2 has been obtained by conventional synthesis4 to verify the proposed structure. The characterization of main reaction products was performed using GC-MS, and NMR techniques (1H, 13C, COSY, HSQC, HMBC and ROESY). The formation of 2-phenylindazolone 2 could be rationalized by a N1N5 phenyl migration in the starting 1-phenylindazolone 1. This type of sigmatropic isomerization was also observed in the FVP reactions of trityl- and adamantylindazoles where the 1-R-indazole was the most stable isomer.5Scheme 1). The product 2 has been obtained by conventional synthesis4 to verify the proposed structure. The characterization of main reaction products was performed using GC-MS, and NMR techniques (1H, 13C, COSY, HSQC, HMBC and ROESY). The formation of 2-phenylindazolone 2 could be rationalized by a N1N5 phenyl migration in the starting 1-phenylindazolone 1. This type of sigmatropic isomerization was also observed in the FVP reactions of trityl- and adamantylindazoles where the 1-R-indazole was the most stable isomer.51H, 13C, COSY, HSQC, HMBC and ROESY). The formation of 2-phenylindazolone 2 could be rationalized by a N1N5 phenyl migration in the starting 1-phenylindazolone 1. This type of sigmatropic isomerization was also observed in the FVP reactions of trityl- and adamantylindazoles where the 1-R-indazole was the most stable isomer.52 could be rationalized by a N1N5 phenyl migration in the starting 1-phenylindazolone 1. This type of sigmatropic isomerization was also observed in the FVP reactions of trityl- and adamantylindazoles where the 1-R-indazole was the most stable isomer.51. This type of sigmatropic isomerization was also observed in the FVP reactions of trityl- and adamantylindazoles where the 1-R-indazole was the most stable isomer.55 Thus, our results indicated that the typical ring contraction of 1,2-azoles to form 1-azirine intermediates did not take place under FVP conditions since imidazole 3 was not detected. At higher temperatures isomerization reaction competes with other processes as homolytic cleavages, where thiophene, benzene, phenol, thiophene-2-carbonitrile and 1,5,6,7-tetrahydro-4H-indazol-4-one were identified as minority products.3 was not detected. At higher temperatures isomerization reaction competes with other processes as homolytic cleavages, where thiophene, benzene, phenol, thiophene-2-carbonitrile and 1,5,6,7-tetrahydro-4H-indazol-4-one were identified as minority products.H-indazol-4-one were identified as minority products.