INTRODUCTION:

Indazole nucleus is one of the vital structural unit in many therapeutically active molecules and exhibit wide range of pharmacological activities^[1] like antimicrobial,^[2] anti-inflammatory,^[3]anti-tumor,^[4] anti-HIV protease inhibition,^[5] Nitric oxide synthesis inhibition.^[6] The diverse pharmacological properties of Indazole has lead to the development of various derivatives for therapeutic application.

Many synthetic methods have been developed to produce novel compounds of indazoles.^[7] Cyclization of various hydrazones in the presence of polyphosphoric acid,^[8] copper-catalyzed cyclization of 2-haloarylcarbonylic compounds,^[9] palladium-mediated cross-coupling reactions^[10]and cyclization of aryl hydrazones substituted with halo, nitro or mesylates^[11-12] are some of the methods for synthesis of indazoles. Microwave irradiation has been emerged as widely applied technique in organic synthesis.^[13] Microwave techniques offers alternative option to improve the drawbacks of conventional synthesis.

Many organic transformations have been improved by subjecting to Microwave irradiation.^[14] Microwave assisted synthesis of indazole derivatives includes Diels-Alder cycloaddition,^[15] one-pot two steps Cu-catalyzed intramolecular N-arylation of arylhydrazone^[16] and via nitrenes^[17]have been developed to obtain good yield of various indazole derivatives.

Conventional methods of synthesis suffer certain drawbacks like vigorous reaction conditions, low yield, purity issues and cost of chemicals. The reactions carried out by the microwave techniques are environment friendly and therapeutically useful drug molecules. Microwave can reduce the time required for formation of the compounds. In the present work microwave technique has been used to speed up the reaction optimization of indazoles.

Considering the significance of indazoles and limitations of the existing methods the need for the development of newer methodologies for synthesis of indazoles by use of microwave technology is strongly desirable.

EXPERIMENTAL:

General

IR spectra in KBr were recorded on a FTIR Spectrophotometer with Diffuse Reflectance Attachment (Varian 680). 1H-NMR spectra were obtained using Varian Mercury YH 300 Spectrometer (400 MHz) with CDCl3 as solvent. Chemical shifts were expressed in parts per million relative to TMS as internal standard. GC-MS were performed using (QP 5010) Shimadzu and elemental analyses were performed using a Heracus CHN-O-Rapid analyzer. The microwave used in this study was Ethosi Milestone with temperature control.

Procedure for the microwave assisted synthesis of indazoles:

To a solution of salicylaldehyde 1 (1 equiv) in ethanol (5 mL,) was added hydrazine hydrate (2 equiv). For the first step power level was kept at (350 W) for 8 min yielded hydrazone.^[18]The hydrazone was mixed with acidic ethanol and cool at room temperature, the mixture was kept at power level (420 W) for 10 min in presence of K2CO3. In process reaction was monitor by using TLC using Chloroform: Methanol (9.6:0.4) as solvents and synthesized product was recrystlized by ethanol with purification of residue by filtration through a pad of silica. (Scheme1) The synthesized products were characterized from melting points and spectral data.

Scheme 1

Table 1. Experimental data of synthesized substituted indazole derivatives.

Entry^a	Substitution				Microwave			Conventional
Entry^a	R¹	R²	R³	R⁴	Watt (W) 1^st/2^nd Step	Time (min) 1^st/2^nd Step	Yield^b(%)	Yield^b(%)
3a	H	H	H	-	350/420	10/10	80	70
3b	H	OCH₃	H	-	350/420	10/10	92	79
3c	H	H	OCH₃	-	350/420	10/12	91	80
3d	H	H	NO₂	-	350/420	10/12	86	75
3e	Br	H	Br	-	350/420	10/10	83	72
3f	OCH₃	H	Br	-	350/420	10/10	90	77
4a	H	H	H	H	350/420	10/10	94	74
4b	H	H	H	Br	350/420	10/10	86	75
4c	H	H	H	Cl	350/420	10/12	84	72
4d	H	OCH₃	H	H	350/420	10/12	91	79
4e	H	OCH₃	H	Br	350/420	10/15	85	78
4f	H	OCH₃	OCH₃	Cl	350/420	10/15	88	72
4g	H	H	OCH₃	H	350/420	10/12	86	70
4h	Ph	H	OCH₃	Br	350/420	10/10	94	76
4i	H	H	OCH₃	Cl	350/420	10/12	88	69
4j	H	H	NO₂	H	350/420	10/10	85	72
4k	Br	H	Br	H	350/420	10/12	91	77
4l	OC₂H₅	H	H	Br	350/420	10/12	86	71
4m	OC₂H₅	H	H	Cl	350/420	10/15	81	65

^aSynthesized compound were characterized by IR, ¹H NMR and elemental analysis. ^b Yields refer to the synthesized pure products.

RESULTS AND DISCUSSION:

In the present work, indazole has been synthesized by novel method developed in our earlier work involving cyclization of salicylaldehyde and hydrazine hydrates. The reaction of various substituted salicyaldehydes with hydrazine hydrate and phenyl hydrazine hydrate under different microwave conditions gave corresponding 1-H-indazole and 1-phenyl-1H-indazole derivatives. Microwave technique has been used to yield the novel indazoles in lesser time with good to excellent yield. The yields of the compounds synthesized by both methods are given in Table 1.

For the preparation of 3 and 4 microwaves irradiation was applied for the reaction of various substituted salicylaldehydes 1 with hydrazine hydrates / phenyl hydrazine hydrates in ethanol for 10 mins at 420 Watt. The method has been extended to a number of azoles. The method affords expected products 3 and 4 quantitatively and reaction time is very short. The method is advantageous over conventional method since the reaction rate is accelerated by many folds. The optimal temperature for azoles was 60-80^oC. The present method, in terms of yields, reaction time, temperature, ease of work-up and scale up is superior to the existing conventional method. A large group of novel substituted indazoles can be obtained in good yield by using the developed method. The compound have been characterized and identified as follows.

Spectral Characterization

4, 6-dibromo-1H-indazole, 3e

Dark brown, Solid, yield 83%; Rf = 0.55 m.p. 147-149 °C; IR [v, cm-1, KBr]: 3294 (N-H, cyclic), 3024 (C-H, aromatic), 1594 (N=CH-, cyclic), 688 (Ar-Br); 1H NMR [400 MHz, CDCl3]: δ 7.12 (1H, s, CH, aromatic), 7.32 (1H, s, CH, aromatic), 7.98 (1H, s, N=CH-, cyclic), 11.95 (1H, s, N-H, cyclic); GC-MS (70eV) m/z (%): 273 (M+ +1), 119, 92, 63; Anal. Calcd (%) for C7H4 Br2 N2: C, 30.47; H, 1.46; N, 10.15. Found: C, 30.51; H, 1.56; N, 10.19.

6-bromo-4-methoxy-1H-indazole, 3f

Dark yellow, Solid, yield 84%; Rf = 0.59 m.p. 142-144 °C; IR [v, cm-1, KBr]: 3226 (N-H, cyclic), 3046 (C-H, aromatic), 1595 (N=CH-, cyclic), 1247 (Ar-OCH3) 732 (Ar-Br); 1H NMR [400 MHz, CDCl3]: δ 3.88 (3H, s, CH3, methoxy), 6.85 (1H, s, CH, aromatic), 6.91 (1H, s, CH, aromatic), 7.74 (1H, s, N=CH-, cyclic), 11.23 (1H, s, N-H, cyclic); GC-MS (70eV) m/z (%): 225 (M+), 119, 92, 65; Anal. Calcd (%) for C8H7 Br N2O: C, 42.32; H, 3.11; N, 12.32. Found: C, 42.57; H, 3.56; N, 12.38.

1-(4-bromophenyl)-1H-indazole, 4b

Green, Solid, yield 81%; Rf = 0.49; m.p. 164-166 °C; IR [v, cm-1, KBr]: 3163 (C-H, aromatic), 1576 (N=CH-, cyclic), 595( Ar-Br); 1H NMR [400 MHz, CDCl3]: δ 6.62 (1H, t, J = 8.0 Hz, CH, aromatic),7.06 (1H, t, J = 7.6 Hz, CH, aromatic), 7.11 (1H, t, J = 7.6 Hz, CH, aromatic ), 7.22 (1H, t, J = 7.6 Hz, CH, aromatic), 7.51 (1H, d, J = 8.4 Hz, CH, aromatic), 7.68 (1H, d, J = 8.2 Hz, CH, aromatic), 7.98 (1H, s, N=CH-, cyclic); GC-MS (70eV) m/z (%): 171 (M+), 118, 91, 65; Anal. Calcd (%) for C13H9BrN2: C, 57.17; H, 3.32; N, 10.26. Found: C, 57.21; H, 3.41; N, 10.32.

1-(4-chlorophenyl)-1H-indazole, 4c

Buff brown,Solid, yield 83%; Rf = 0.51; m.p. 168-170 °C; IR [v, cm-1, KBr]: 3171 (C-H, aromatic), 1596 (N=CH-, cyclic), 611( Ar-Br); 1H NMR [400 MHz, CDCl3]: δ 6.58 (1H, t, J = 8.0 Hz, CH, aromatic),7.05 (1H, t, J = 7.8 Hz, CH, aromatic), 7.13 (1H, t, J = 7.6 Hz, CH, aromatic ), 7.18 (1H, t, J = 7.6 Hz, CH, aromatic), 7.53 (1H, d, J = 8.4 Hz, CH, aromatic), 7.66 (1H, d, J = 8.2 Hz, CH, aromatic), 8.01 (1H, s, N=CH-, cyclic); GC-MS (70eV) m/z (%): 228 (M+ + 1), 118, 92, 63; Anal. Calcd (%) for C13H9ClN2: C, 68.28; H, 3.97; N, 12.25. Found: C, 68.34; H, 3.91; N, 12.32.

5-methoxy-1-phenyl-1H-indazole, 4d

Brown, Solid, yield 81%; Rf = 0.59; m.p. 131-133 °C; IR [v, cm-1, KBr]: 3063 (C-H, aromatic), 2928 (methyl), 1569 (N=CH-, cyclic), 1358 (methyl, def) 1211 (Ar-OCH3); 1H NMR [400 MHz, CDCl3]: δ 3.81 (3H, s, methyl), 6.51 (1H, d, J = 8.8 Hz, CH, aromatic), 6.92 (5H, m, CH, aromatic ), 7.24 (1H, d, J = 8.0 Hz, CH, aromatic), 7.83 (1H, s, CH, aromatic), 8.58 (1H, s, N=CH-, cyclic); GC-MS (70eV) m/z (%): 224 (M+), 119, 92, 63; Anal. Calcd (%) for C14H12N2O: C, 74.98; H, 5.39; N, 12.49. Found: C, 74.92; H, 5.38; N, 12.54.

1-(4-bromophenyl)-5-methoxy-1H-indazole, 4e

Dark brown, Solid, yield 82%; Rf = 0.59; m.p. 146-148 °C; IR [v, cm-1, KBr]: 3058 (C-H, aromatic), 2974 (methyl), 1565 (N=CH-, cyclic), 1345 (methyl, def) 1206 (Ar-OCH3) 675 (Ar-Br); 1H NMR [400 MHz, CDCl3]: δ 3.89 (3H, s, methyl), 6.55 (1H, d, J = 8.8 Hz, CH, aromatic), 6.81 (1H, d, J = 8.2 Hz, CH, aromatic), 7.08 (1H, d, J = 8.2 Hz, CH, aromatic), 7.21 (1H, d, J = 8.0 Hz, CH, aromatic), 7.84 (1H, s, CH, aromatic), 8.60 (1H, s, N=CH-, cyclic); GC-MS (70eV) m/z (%): 302 (M+), 119, 92, 63; Anal. Calcd (%) for C14H11BrN2O: C, 55.47; H, 3.66; N, 9.24. Found: C, 55.51; H, 3.68; N, 9.31.

1-(4-chlorophenyl)-5-methoxy-1H-indazole, 4f

Brown, Solid, yield 77%; Rf = 0.59; m.p. 170-172 °C; IR [v, cm-1, KBr]: 3033 (C-H, aromatic), 2964 (methyl), 1585 (N=CH-, cyclic), 1348 (methyl, def) 1216 (Ar-OCH3) 732 (Ar-Cl); 1H NMR [400 MHz, CDCl3]: δ 3.79(3H, s, methyl), 6.59 (1H, d, J = 8.8 Hz, CH, aromatic), 6.83 (1H, d, J = 8.2 Hz, CH, aromatic), 7.11 (1H, d, J = 8.2 Hz, CH, aromatic), 7.23 (1H, d, J = 8.0 Hz, CH, aromatic), 7.89 (1H, s, CH, aromatic), 8.63(1H, s, N=CH-, cyclic); GC-MS (70eV) m/z (%): 258 (M+), 119, 91, 64; Anal. Calcd (%) for C14H11ClN2O: C, 65.00; H, 4.29; N, 10.83. Found: C, 65.12; H, 4.32; N, 10.72.

6-methoxy-1-phenyl-1H-indazole, 4g

Silver brown, Solid, yield 74%; Rf = 0.56 m.p. 132-133 °C; IR [v, cm-1, KBr]: 3063 (C-H, aromatic), 2972 (methyl), 1602 (N=CH-, cyclic), 1344 (methyl, def) 1212 (Ar-OCH3); 1H NMR [400 MHz, CDCl3]: δ 3.72 (3H, s, methyl), 6.81 (1H, d, J = 8.8 Hz, CH, aromatic), 6.86 (1H, s, CH, aromatic), 6.92 (5H, m, CH, aromatic ), 7.23 (1H,d, J = 8.8 Hz, CH, aromatic), 7.76 (1H, s, N=CH-, cyclic); GC-MS (70eV) m/z (%): 224 (M+), 119, 92, 63; Anal. Calcd (%) for C14H12N2O: C, 74.98; H, 5.39; N, 12.49. Found: C, 74.94; H, 5.36; N, 12.42.

1-(4-bromophenyl)-6-methoxy-1H-indazole, 4h

Blackish brown, Solid, yield 95%; Rf = 0.56 m.p. 137-139 °C; IR [v, cm-1, KBr]: 3046 (C-H, aromatic), 2934 (methyl), 1598 (N=CH-, cyclic), 1327 (methyl, def) 1201 (Ar-OCH3) 684 (Ar-Br); 1H NMR [400 MHz, CDCl3]: δ 3.93 (3H, s, methyl), 6.77 (1H, d, J = 8.8 Hz, CH, aromatic), 6.84 (1H, d, J = 8.8 Hz, CH, aromatic), 6.89 (1H, d, J = 8.8 Hz, CH, aromatic), 7.07 (1H, s, CH, aromatic), 7.14 (1H,d, J = 8.6 Hz, CH, aromatic), 7.76(1H, s, N=CH-, cyclic); GC-MS (70eV) m/z (%): 302 (M+), 119, 92, 63; Anal. Calcd (%) for C14H11BrN2O: C, 55.47; H, 3.66; N, 9.24. Found: C, 55.51; H, 3.68; N, 9.31.

1-(4-chlorophenyl)-6-methoxy-1H-indazole, 4i

Dark brown, Solid, yield 88%; Rf = 0.49 m.p. 141-143 °C; IR [v, cm-1, KBr]: 3036 (C-H, aromatic), 2929 (methyl), 1596 (N=CH-, cyclic), 1322 (methyl, def) 1208 (Ar-OCH3) 724 (Ar-Cl); 1H NMR [400 MHz, CDCl3]: δ 3.92 (3H, s, methyl), 6.81 (1H, d, J = 8.8 Hz, CH, aromatic), 6.85 (1H, d, J = 8.8 Hz, CH, aromatic), 6.91 (1H, d, J = 8.8 Hz, CH, aromatic), 7.02 (1H, s, CH, aromatic), 7.12 (1H,d, J = 8.6 Hz, CH, aromatic), 7.74(1H, s, N=CH-, cyclic); GC-MS (70eV) m/z (%): 258 (M+), 119, 92, 63; Anal. Calcd (%) for C14H1ClN2O: C, 65.00; H, 4.29; N, 10.83. Found: C, 65.12; H, 4.32; N, 10.86.

6-nitro-1-phenyl-1H-indazole, 4j

Dark brown, Solid, yield 85%; Rf = 0.61 m.p. 183-185 °C; IR [v, cm-1, KBr]: 3077 (C-H, aromatic), 1622 (N=CH-, cyclic), 1569, 1355 ( Ar-NO2); 1H NMR [400 MHz, CDCl3]: δ 6.87 (5H, m, CH, aromatic ), 7.26 (1H, d, J = 8.8 Hz, CH, aromatic), 7.29 (1H, d, J = 8.8 Hz, CH, aromatic), 7.58 (1H, s, CH, aromatic), 7.73 (1H, s, N=CH-, cyclic); GC-MS (70eV) m/z (%): 239 (M+), 119, 92, 66; Anal. Calcd (%) for C13H9N3O2: C, 65.27; H, 3.79; N, 17.56. Found: C, 65.28; H, 3.75; N, 17.61.

4, 6-dibromo-1-phenyl-1H-indazole, 4k

Fain brown, Solid, yield 82%; Rf = 0.55 m.p. 197-199 °C; IR [v, cm-1, KBr]: 3071 (C-H, aromatic), 1596 (N=CH-, cyclic), 678 (Ar-Br); 1H NMR [400 MHz, CDCl3]: δ 6.82 (5H, m, CH, aromatic ),7.10 (1H, s, CH, aromatic), 7.38 (1H, s, CH, aromatic), 7.97 (1H, s, N=CH-, cyclic); GC-MS (70eV) m/z (%): 349 (M+), 118, 91, 63; Anal. Calcd (%) for C13H8 Br2 N2: C, 44.35; H, 2.29; N, 7.96. Found: C, 44.39; H, 2.31; N, 7.94.

6-bromo-1- (4-bromophenyl)-4-ethoxy-1H-indazole, 4l

Dark yellow, Solid, yield 78%; Rf = 0.52 m.p. 164-166 °C; IR [v, cm-1, KBr]: 3032 (C-H, aromatic), 2936 (methyl), 1578 (N=CH-, cyclic), 1213 (Ar-OCH3) 663 (Ar-Br); 1H NMR [400 MHz, CDCl3]: δ 3.81 (3H, s, CH3, methoxy), 6.59 (1H, d, J = 8.8 Hz, CH, aromatic), 6.83 (1H, s, CH, aromatic), 6.91 (1H, s, CH, aromatic), 7.08 (1H, d, J = 8.8 Hz, CH, aromatic), 7.76 (1H, s, N=CH-, cyclic); GC-MS (70eV) m/z (%): 379 (M+ + 1), 118, 92, 65; Anal. Calcd (%) for C14H10Br2N2O: C, 44.01; H, 2.64; N, 7.33. Found: C, 44.13; H, 2.65; N, 7.38.

6-chloro-1-(4-chlorophenyl)-4-ethoxy-1H-indazole, 4m

Fain brown, Solid, yield 81%; Rf = 0.53m.p. 167-169 °C; IR [v, cm-1, KBr]: 3061 (C-H, aromatic), 2942 (methyl), 1579 (N=CH-, cyclic), 1210 (Ar-OCH3) 669 (Ar-Br); 1H NMR [400 MHz, CDCl3]: δ 3.85 (3H, s, CH3, methoxy), 6.56 (1H, d, J = 8.4 Hz, CH, aromatic), 6.83 (1H, s, CH, aromatic), 6.93 (1H, s, CH, aromatic), 7.11 (1H, d, J = 8.8 Hz, CH, aromatic), 7.74 (1H, s, N=CH-, cyclic); GC-MS (70eV) m/z (%): 379 (M+ + 1), 119, 92, 64; Anal. Calcd (%) for C14H10Cl2N2O: C, 49.81; H, 2.99; N, 8.30. Found: C, 49.86; H, 2.85; N, 8.32.

CONCLUSION:

A simple and highly efficient one pot two step method has been developed. The method can be successfully applied for synthesis of library of derivatives of indazoles in good yield and lesser time. The method is found to be eco-friendly and is convenient for synthesizing novel derivatives of indazoles for various therapeutically important categories of molecules in future.

ACKNOWLEDGEMENTS:

Authors are thankful to the Management of Maharashtra Academy of Engineering and Educational Research, Pune for providing necessary facilities for carrying out research work. Authors are also thankful to BCUD section of Pune University for providing necessary financial support.

REFERENCE:

1) Chittari P, Hong-Jun W, Susan R. M, Zhen-Jia C, Todd M. S, and Brian T. G. Microwave-assisted synthesis of 1-aryl-1H-indazoles via one-pot two-step Cu-catalyzed intramolecular N-arylation of arylhydrazone.Tetrahedron Lett. 46; 2005: 7553-7557.

2) Chu X, Li S, Feher V. A, Kahalili M, Nie Z, Margosiak S, Nikulin V, Levin J, Sprankle K. G, Tedder M. E, Almassy R, Appelt K, Yager K. M. Structure-Based Design, Synthesis, and Antimicrobial Activity of Indazole-Derived SAH/MTA Nucleosidase Inhibitors.J. Med. Chem. 46; 2003: 5663-5673.

3) Zhang H. C, Derian C. K, McComsey D. F, White K. B, Ye H, Hecker L. R, Li J, Addo M. F, Croll D, Eckardt A. J, Smith C. E, Li Q, Cheung W. M, Conway B. R, Emanuel S, Demarest K. T, Andrade-Gordon P, Damiano B. P, Maryanoff B. E. Novel Indolylindazolylmaleimides as Inhibitors of Protein Kinase C-β: Synthesis, Biological Activity, and Cardiovascular Safety. J. Med. Chem. 48; 2005: 1725-1728.

4) Keppler B. K, Hartmann M. New tumor-inhibiting metal complexes. Chemistry and antitumor properties. Met. Based Drugs. 1; 1994: 145-149.

5) Banno K, Kawahata T, Ikeda T, Nakagawa K, Dohi T. Japanese Patent 48048407 973. Chem. Abstr. 1973: 7992214.

6) Babbedge R.C, Bland-Ward P.A, Hart S.L, Moore P.K. Characterization of the novel nitric oxide synthase inhibitor 7-nitro indazole and related indazoles: antinociceptive and cardiovascular effects. Br. J. Pharmacol. 110;1993: 225-228.

7) Andreas S, Ariane B, Bohdan S. Recent Advances in the Chemistry of Indazoles. Eur. J. Org. Chem 24; 2008: 4073-4095.

8) Guofu Q, Jiangtao S, Xichun F, Lamei W, Wenjin X, Xianming H. The Synthesis of Substituted Indazoles via Cyclization of Various Hydrazones in the Presence of Polyphosphoric Acid (PPA). J. Heterocycl Chem. 41;2004: 601-604.

9) Vina D, Olmo E, Lopez-Pe´rez J. L, Feliciano A. S. Regioselective Synthesis of 1-Alkyl- or 1-Aryl-1H-indazoles via Copper-Catalyzed Cyclizations of 2-Haloarylcarbonylic Compounds.Org. Lett. 9; 2007: 525-528.

10) Kazzouli S. E, Bouissane L, Khouilib M, Guillaumet G. Synthesis and biological evaluation of N-(7-indazolyl) benzenesulfonamide derivatives as potent cell cycle inhibitors. Tetrahedron lett. 49; 2008: 2472-2475.

11) (a) Krishnan R, Lang S. A.et.al. Reactions of Hydroxybenzophenone with Hydrazines. J. Heterocycle. Chem. 25;1988:447-449; (b) Cheng C. Y, Mo M, Grima J, Saso L, Tita B, Mruk D, Silvestrini B. Male fertility: core chemical structure in pharmacological research. Contraception. Contraception 65; 2002: 265-268.

12) Brenda C. W, James P. S. Synthesis of N-Arylindazoles and Benzimidazoles from a Common Intermediate. Org. Lett. 12; 2010: 4576-4579.

13) a)Strauss C. R, Trainor R. W. Developments in Microwave-Assisted Organic Chemistry. Aust. J. Chem. 48; 1995: 1665-1692; (b) Varma R. S. Solvent-free accelerated organic syntheses using microwaves.Pure Appl. chem. 73; 2001: 193-198; (c). Sangshetti J. N, Chabukswar A. R, Shinde D. B. Microwave assisted one pot synthesis of some novel 2,5-disubstituted 1,3,4-oxadiazoles as antifungal agents. Bioorg. Med. Chem. Lett. 21;2011: 444-448; (d) Upadhyay A, Srivastava S.K, Srivastava S.D. Conventional and microwave assisted synthesis of some new N-[(4-oxo-2-substituted aryl -1, 3-thiazolidine)-acetamidyl]-5-nitroindazoles and its antimicrobial activity Eur. J. Med. Chem. 45; 2010: 3541-3543.

14) Bose A K, Manhas M. S, Ghosh M, Shah M. Microwave enhanced greener synthesis of indazoles via nitrenes. J. Org. Chem 56; 1991: 6968-6970.

15) Diaz-Ortiz A, Hoz A, Langa F Microwave irradiation in solvent-free conditions: an eco-friendly methodology to prepare indazoles, pyrazolopyridines and bipyrazoles by cycloaddition reactions. Green chem. 2; 2000: 165-172.

16) Pabba C, Wang H J, Mulligan S. R, Chen Z J, Stark T. M, Gregg B. T. Microwave-assisted synthesis of 1-aryl-1H-indazoles via one-pot two-step Cu catalyzed intramolecular N-arylation of arylhydrazones. Tetrahedron Lett. 46; 2005: 7553-7557.

17) Varughese D. J, Manhas M. S, Bose A. K. Microwave enhanced greener synthesis of indazoles via nitrenes. Tetrahedron Lett. 47; 2006: 6795-6797.

18) Lokhande P. D, Raheem A, Sabale S. T, Chabukswar A. R, Jagdale S. C. An efficient synthesis of 1-H indazoles. Tetrahedron Lett. 2007: 48; 6890-6892.

Received on 31.08.2012 Modified on 10.09.2012

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