1252
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 6, June, 2009
Usachev et al.
sealed tube for 16 h at 110 °C. Pyridine (3 mL) was added to the
cooled mixture with stirring, the solvent was evaporated in vacuo,
the residue was vigorously shaken with a toluene—Et2O solvent
mixture (1 : 1, 300 mL) and water (20 mL). The upper organic
layer was separated, passed through silica gel (10 cm3), the
solvent excess was evaporated from the filtrate, keeping the bath
temperature under 100—110 °C, the evaporated solvent was
again passed through the same layer of silica gel, the filtrates
were combined. After evaporation of solvents from the combined
filtrate in a hot water bath in vacuo, ester 8 was obtained. The
yield was 6.90 g (76%), a glassy solid compound, transforming
into a viscous liquid on heating. IR, ν/cm–1: 3400—2500, 1725,
1627, 1608, 1580, 1523, 1500. MS (EI, 70 eV), m/z (Irel (%)):
243 [M]+ (23), 199 [M – CO2]+ (12), 171 [M – C3H4O2]+
(100). Found: m/z 243.08989 [M]+. C14H13NO3. Calculated: M
3ꢀ(1,5ꢀDiphenylꢀ1Hꢀpyrazolꢀ3ꢀyl)ꢀ1Hꢀindoleꢀ2ꢀcarboxylic
acid (14). Concentrated HCl (3 drops) was added to a solution
of hydrazone 10 (0.2 g, 0.5 mmol) in AcOH (5 mL), the mixture
was refluxed for 4 h and cooled. A precipitate was filtered off,
sequentially washed with AcOH and water. After recrystallization
from AcOH, indole 14 was obtained (0.13 g, 68%) as colorless
crystals with m.p. 280 °C. IR, ν/cm–1: 3312, 1693, 1678, 1596,
1562, 1536, 1499, 1488. Found (%): C, 75.68; H, 4.38; N, 10.92.
C24H17N3O2. Calculated (%): C, 75.97; H, 4.52; N, 11.08.
1H NMR, δ: 7.16 (ddd, 1 H, H(5), J = 8.4 Hz, 7.0 Hz, 1.1 Hz);
7.31—7.50 (m, 12 H, H(6), H(4´), 2 Ph); 7.53 (d, 1 H, H(7),
J = 8.4 Hz); 8.31 (d, 1 H, H(4), J = 8.3 Hz); 11.97 (s, 1 H, NH);
13.8 (br.s, 1 H, OH). 13C NMR, δ: 109.12 (d, C(4´), J = 179.6
Hz); 111.97 (dd, C(3), J = 5.5 Hz, 2.1 Hz); 112.50 (dd, C(7),
J = 165.1 Hz, 7.4 Hz); 120.66 (dd, C(5), J = 160.4 Hz, 7.8 Hz);
122.90 (dd, C(4), J = 162.5 Hz, 7.3 Hz); 124.67 (d, C(2),
J = 4.3 Hz); 124.94 (dm, C(6), J = 161.3 Hz); 125.04 (ddd,
C(2″), C(6″), J = 163.6 Hz, 7.5 Hz, 5.1 Hz); 126.03 (m, C(3a));
127.82 (dt, C(4″), J = 162.3 Hz, 7.7 Hz); 128.57 (C(4´´´));
128.60 (C(3´´´), C(5´´´)); 128.65 (C(2´´´), C(6´´´)); 129.24 (dd,
C(3″), C(5″), J = 162.8 Hz, 7.5 Hz); 129.83 (m, C(1´´´)); 136.07
(ddd, C(7a), J = 10.2 Hz, J = 7.3 Hz, J = 2.7 Hz); 139.44 (t,
C(1″), J = 8.3 Hz); 142.95 (dt, C(5´), J = 8.3 Hz, J = 4.1 Hz);
146.25 (d, C(3´), J = 4.3 Hz); 162.39 (C=O).
1
243.08954. H NMR, δ: 1.34 (t, 3 H, Me, J = 7.0 Hz); 4.36 (q,
2 H, OCH2, J = 7.0 Hz); 7.42—7.50 (m, 5 H, H(3), H(5)arom);
8.03—8.07 (m, 2 Harom); 11.17 (s, 1 H, OH).
4ꢀHydroxyꢀ6ꢀphenylpyridineꢀ2ꢀcarbohydrazide (9). Ester 8
(0.22 g, 0.9 mmol) in 65% aq. hydrazine hydrate (2 mL) was
refluxed for 1 h. Then, the water and hydrazine hydrate excess
was evaporated, the residue was diluted with water (6 mL), a
colorless precipitate was filtered off, washed with water, dried,
and recrystallized from butanol. The yield was 0.12 g (58%),
colorless crystals with m.p. 222—223 °C. Found (%): C, 63.08;
H, 4.84; N, 18.40. C12H11N3O2. Calculated (%): C, 62.87;
H, 4.84; N, 18.33. IR, ν/cm–1: 3317, 3250, 1666, 1598, 1572,
1517, 1499. 1H NMR, δ: 4.59 (s, 2 H, NH2); 7.37 (d, 1 H, H(3),
J = 2.2 Hz); 7.42 (d, 1 H, H(5), J = 2.2 Hz); 7.43—7.50 (m,
3 Harom); 8.21—8.25 (m, 2 Harom); 9.92 (s, 1 H, NH); 11.05
(br.s, 1 H, OH).
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 06ꢀ03ꢀ04004ꢀ
NNIO) and German Research Society (Grant 436 RUS
113/901/0ꢀ1).
References
3ꢀ(1,5ꢀDiphenylꢀ1Hꢀpyrazolꢀ3ꢀyl)ꢀ2ꢀ(2ꢀphenylhydrazono)ꢀ
propionic acid (10). A mixture of 6ꢀphenylcomanic acid 2 (1.0 g,
4.63 mmol) and phenylhydrazine (1.1 g, 10.2 mmol) in dioxane
(20 mL) was refluxed for 2.5 h, the solvent excess was evaporated,
the residue was diluted with 1% aq. NaHCO3 (50 mL). Excess
phenylhydrazine was extracted with toluene (10 mL), the
aqueous layer was separated and mixed with conc. HCl (5 mL).
A precipitate formed was recrystallized from CCl4. The yield
was 0.37 g (20%), colorless crystals with m.p. 187—189 °C.
Found (%): C, 72.88; H, 4.90; N, 13.93. C24H20N4O2. Calcuꢀ
lated (%): C, 72.71; H, 5.08; N, 14.13. IR, ν/cm–1: 3393, 3321,
1666, 1605, 1579, 1534, 1507, 1494. 1H NMR, δ: 4.07 (s, 2 H,
CH2); 6.42 (s, 1 H, H(4)); 6.90 (tt, 1 H, H(4´), J = 7.3 Hz,
1.2 Hz); 7.18—7.40 (m, 14 Harom); 10.30 (s, 1 H, NH); 12.10
(br.s, 1 H, OH). 13C NMR, δ: 23.65 (t, CH2, J = 130.0 Hz);
107.08 (dt, C(4), J = 175.8 Hz, 2.5 Hz); 113.86 (dt, C(2´),
C(6´), J = 161.4 Hz, 6.1 Hz); 121.00 (dt, C(4´), J = 160.0 Hz,
7.4 Hz); 124.96 (ddd, C(2″), C(6″), J = 164.0 Hz, 7.3 Hz,
5.6 Hz); 127.48 (dt, C(4´´´), J = 162.7 Hz, 7.1 Hz); 128.30 (dm,
2 Carom, J = 162.0 Hz); 128.33 (dm, C(4″), J = 161.0 Hz);
1. US Pat. 0232880, Chem. Abstr., 2001, 135, 257153.
2. W. Borsche, W. Peter, Lieb. Ann. Chem., 1927, 453, 158.
3. G. Soliman, L. Rateb, J. Chem. Soc., 1956, 3663.
4. M. Stiles, J. P. Selegue, J. Org. Chem., 1991, 56, 4067.
5. H. Schiefer, G. Henseke, Angew. Chem., 1965, 77, 547.
6. UK Pat. GB 2123813 A, Chem. Abstr., 1981, 94, 121322.
7. Y. Honma, Y. Sekine, T. Hashiyama, M. Takeda, Y. Ono,
K. Tsuzurahara, Chem. Pharm. Bull., 1982, 30, 4314.
8. B. I. Usachev, I. A. Bizenkov, V. Ya. Sosnovskikh, Izv. Akad.
Nauk, Ser. Khim., 2007, 537 [Russ. Chem. Bull., Int. Ed.,
2007, 56, 558].
9. Y. Honma, K. Oda, T. Hashiyama, K. Hanamoto, H. Nakai,
H. Inoue, A. Ishida, M. Takeda, Y. Ono, K. Tsuzurahara,
J. Med. Chem., 1983, 26, 1499.
10. P. L. Ornstein, D. D. Schoepp, M. B. Arnold, J. D. Leander,
D. Lodge, J. W. Paschal, T. Elzey, J. Med. Chem., 1991, 34,
90.
11. C. B. Vicentini, M. Manfrini, M. Mazzanti, M. Manferdini,
C. F. Morelli, A. C. Veronese, Heterocycles, 2000, 53, 1285.
128.57 (dm, 2 Carom, J = 162.8 Hz); 129.00 (dm, 4 Carom
,
J = 162.2 Hz); 129.88 (m, C(1´´´)); 132.41 (td, C=N, 2J = 6.2 Hz,
3J = 3.4 Hz); 139.58 (tt, C(1″), J = 8.9 Hz, 2.3 Hz); 143.28 (dt,
C(5), 2J = 8.0 Hz, 3J = 4.0 Hz); 144.12 (dtt, C(1´), J = 8.7 Hz,
8.4 Hz, 1.6 Hz); 148.17 (td, C3, 2J = 7.8 Hz, 4.6 Hz); 166.05
(t, C=O, 3J = 3.8 Hz).
Received August 12, 2008;
in revised form November 28, 2008