Three-Step One-Pot Synthesis of 1,4-Dihydropyrazolo[4,3-b]indoles Using Copper Catalysis

Article abstract of DOI:10.1002/ejoc.201301380

A convenient three-step one-pot copper-catalysed method has been developed for the preparation of pyrazolo[4,3-b]indoles, new indole-based compounds with potential biological activity. Treatment of various hydrazines, including alkyl hydrazines, with indole-2-carbaldehydes generated the corresponding products in moderate to good yields without protection of the indole N-1 moiety. In addition, LiOH was used as a base in the copper-catalysed coupling reaction. Microwave heating was used to accelerate the iodination of indoles and the C-N bond formation. Diversely substituted pyrazolo[4,3-b]indoles, based on a new indole-containing skeleton, were prepared in a three-step one-pot procedure from unprotected indole-2-carbaldehydes and various hydrazines. LiOH was used as an alternative base in the copper-catalysed protocol.

Full text of DOI:10.1002/ejoc.201301380

Eur. J. Org. Chem. 2014 · © WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2014 · ISSN 1099–0690
SUPPORTING INFORMATION
DOI: 10.1002/ejoc.201301380
Title: Three-Step One-Pot Synthesis of 1,4-Dihydropyrazolo[4,3-b]indoles Using Copper Catalysis
Author(s): Hailong Liu, Lei Zhang, Fei Zhao, Hong Liu*

1-phenyl-1H,4H-pyrazolo[4,3-b]indole (3a)
1H NMR (400 MHz, CDCl3) spectrum
of the product 3a.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 3a.

1-(4-fluorophenyl)-1H,4H-pyrazolo[4,3-b]indole (3b)
1H NMR (400 MHz, CDCl3) spectrum
of the product 3b.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 3b.

1-(4-chlorophenyl)-1H,4H-pyrazolo[4,3-b]indole (3c)
1H NMR (400 MHz, DMSO) spectrum
of the product 3c.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 3c.

1-(4-bromophenyl)-1H,4H-pyrazolo[4,3-b]indole (3d)
1H NMR (400 MHz, CDCl3) spectrum
of the product 3d.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 3d.

1-(4-methoxyphenyl)-1H,4H-pyrazolo[4,3-b]indole (3e)
1H NMR (400 MHz, CDCl3) spectrum
of the product 3e. Dicloromethane and
warter was the solvent residue.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 3e.

1-(4-nitrophenyl)-1H,4H-pyrazolo[4,3-b]indole (3f)
1H NMR (400 MHz, DMSO) spectrum
of the product 3f. Ethyl acetate was the
solvent residue.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 3f.

1-(2-fluorophenyl)-1H,4H-pyrazolo[4,3-b]indole (3g)
1H NMR (400 MHz, DMSO) spectrum
of the product 3g.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 3g.

1-(3-fluorophenyl)-1H,4H-pyrazolo[4,3-b]indole (3h)
1H NMR (400 MHz, DMSO) spectrum
of the product 3h.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 3h.

1-(2,4-dimethylphenyl)-1H,4H-pyrazolo[4,3-b]indole (3i)
1H NMR (400 MHz, CDCl3) spectrum
of the product 3i.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 3i.

1-benzyl-1H,4H-pyrazolo[4,3-b]indole (3j)
1H NMR (400 MHz, CDCl3) spectrum
of the product 3i.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 3j.

1-tert-butyl-1H,4H-pyrazolo[4,3-b]indole (3k)
1H NMR (400 MHz, CDCl3) spectrum
of the product 3k.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 3k.

7-fluoro-1-phenyl-1H,4H-pyrazolo[4,3-b]indole (5a)
1H NMR (400 MHz, CDCl3) spectrum
of the product 5a. Dicloromethane and
warter was the solvent residue.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 5a.

7-bromo-1-phenyl-1H,4H-pyrazolo[4,3-b]indole (5b)
1H NMR (400 MHz, DMSO) spectrum
of the product 5b.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 5b.

7-chloro-1-phenyl-1H,4H-pyrazolo[4,3-b]indole (5c)
1H NMR (400 MHz, CDCl3) spectrum
of the product 5c. Dicloromethane and
warter was the solvent residue.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 5c.

7-methyl-1-phenyl-1H,4H-pyrazolo[4,3-b]indole (5d)
1H NMR (400 MHz, CDCl3) spectrum
of the product 5d. Dicloromethane and
warter was the solvent residue.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 5d.

7-methoxy-1-phenyl-1H,4H-pyrazolo[4,3-b]indole (5e)
1H NMR (400 MHz, DMSO) spectrum
of the product 5e.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 5e.

7-nitro-1-phenyl-1H,4H-pyrazolo[4,3-b]indole (5f)
1H NMR (400 MHz, DMSO) spectrum
of the product 5f.
DEPT135 (125 MHz, top) and13C NMR
(bottom) spectra of the product 5f.