2H-indazoles from 2-aminobenzophenones

Full text of DOI:10.1007/s10593-008-0020-x

Chemistry of Heterocyclic Compounds, Vol. 44, No. 2, 2008
2H-INDAZOLES FROM
2-AMINOBENZOPHENONES
S. S. Mochalov, M. I. Khasanov, A. N. Fedotov, and E. V. Trofimova
Keywords: 2-amino-4,5-ethylenedioxybenzophenones, 2,3-diaryl-5,6-ethylenedioxy-2H-indazoles,
4,5-ethylenedioxy-2-phenylazobenzhydrols.
2H-Indazoles have proved difficult to prepare and, hence, have not been studied extensively. Only one
general method is known for the preparation of such compounds, which involves the acid-catalyzed
rearrangement of 2-arylazophenylcyclopropanes [1].
We are the first to show that 4,5-ethylenedioxy-2-phenylazobenzophenones 1 and 2, which may be
readily synthesized from 2-amino-4,5-ethylenedioxybenzophenones by condensation with nitrosobenzene, are
converted by consecutive reduction and acid-catalyzed cyclization to give the corresponding substituted
2H-indazoles 5 and 6 in high yield.
The scope of this transformation as a general method for the synthesis of 2H-indazoles is under
investigation.
R
R
R
O
O
O
O
O
O
NaBH4
OH
N
CF3CO2H
20°C
O
N
Ph
N
N
Ph
N
N Ph
3, 4
1, 3, 5 R = H; 2, 4, 6 R = Cl
5, 6
1, 2
The 1H NMR spectra were taken on a Varian VX2-400 spectrometer at 400 MHz in CDCl3 with residual
CHCl3 as the internal standard.
4,5-Ethylenedioxy-2-phenylazobenzhydrol (3). 4,5-Ethylenedioxy-2-phenylazobenzophenone (1)
(0.69 g, 2 mmol) was added to a solution of NaBH4 (75 mg, 2 mmol) in ethanol. The reaction mixture was stirred
for 3 h at 40°C, cooled to 20°C, and treated with 10% hydrochloric acid until there was no further evolution of
hydrogen gas. The ethanolic solution of the reduction product was poured into 150 ml water, extracted with
CH2Cl2, and dried over MgSO4. The solvent was evaporated off and the residue was subjected to
__________________________________________________________________________________________
M.
V.
Lomonosov
Moscow
State
University,
119992 Moscow,
Russia;
e-mail:
ssmoch@org.chem.msu.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 296-298,
February, 2008. Original article submitted January 16, 2008.
0009-3122/08/4402-0229©2008 Springer Science+Business Media, Inc.
229

chromatography on a column packed with grade-II-activity alumina using 1:1:2 ether–CH2Cl2–petroleum ether
as the eluent to give compound 3 (0.63 g, 91%), mp 115-116°C. 1H NMR spectrum, δ, ppm (J, Hz): 3.92 (1H, d,
J = 6.0, OH); 4.29 (4H, m, OCH2CH2O); 6.57 (1H, d, J = 6.0, CHAr); 6.99 (1H, s); 7.25 (1H, m); 7.35 (2H, m);
7.48 (6H, m); 7.80 (2H, m, Ar). Found, %: C 72.64; H 5.03; N 7.82. C21H18N2O3. Calculated, %: C 72.82; H
5.24; N 8.09.
4'-Chloro-4,5-ethylenedioxy-2-phenylazobenzhydrol (4) was obtained analogously from 4'-chloro-
4,5-ethylenedioxybenzophenone-2-phenylazo (2) (0.76 g, 2 mmol) in 86% yield (0.66 g), mp 73-74°C. 1H NMR
spectrum, δ, ppm (J, Hz): 3.88 (1H, d, J = 5.8, OH); 4.33 (4H, m, OCH2CH2O); 6.51 (1H, d, J = 5.8, CHAr);
6.95 (1H, s); 7.27 (2H, d, J = 7.8); 7.37 (2H, d, J = 7.8); 7.44 (1H, s); 7.52 (3H, m, ArH); 7.77 (2H, m, ArH).
Found, %: C 65.94; H 4.31; N 7.15. C21H17ClN2O3. Calculated, %: C 66.23; H 4.50; N 7.36.
5,6-Ethylenedioxy-2,3-diphenyl-2H-indazole (5). Phenylazobenzhydrazol 3 (0.35 g, 1 mmol) was
dissolved in trifluoroacetic acid (3 ml). The reaction mixture was maintained for 15 min, poured into a 1:1
mixture of ice and water, and neutralized by adding sodium carbonate. The cyclization product was extracted
with chloroform and dried over MgSO4. The solvent was evaporated off and the residue was subjected to
chromatography on a column packed with grade-II-activity alumina using 1:1:3 ether–CH2Cl2–petroleum ether
as the eluent to give compound 5 (0.27 g, 82%), mp 199-200°C. 1H NMR spectrum, δ, ppm (J, Hz): 4.33 (4H, m,
OCH2CH2O); 7.06 and 7.20 (each 1H, 2 s, indazole H-4 and H-7); 7.30-7.45 (10H, m, ArH). Found, %: C 76.53;
H 4.71; N 8.22. C21H16N2O2. Calculated, %: C 76.81; H 4.91; N 8.53.
3-(4-Chlorophenyl)-5,6-ethylenedioxy-2-phenyl-2H-indazole (6) was obtained analogously from
1
phenylazobenzhydrol 4 (0.38 g, 1 mmol) in 86% yield (0.31 g), mp 179-180°C. H NMR spectrum, δ, ppm
(J, Hz): 4.33 (4H, m, OCH2CH2O); 7.06 and 7.20 (each 1H, 2 s, indazole H-4 and H-7); 7.25 (2H, d, J = 8.2);
7.35 (2H, d, J = 8.2); 7.41 (5H, m, ArH). Found, %: C 69.31; H 3.98; N 7.53. C21H15ClN2O2. Calculated, %:
C 69.52; H 4.17; N 7.72.
REFERENCES
1.
A. N. Fedotov, I. N. Shishkina, T. T. Kutateladze, S. S. Mochalov, and Yu. S. Shabarov, Khim.
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