1414
D. Bevk, J. Svete, and B. Stanovnik
Vol. 42
1.19 (t, 3H, J = 6.97, OCH CH ); 4.11 (q, 2H, J = 7.16,
When we carried out the transformation of phenylhydra-
2
3
OCH CH ); 4.18 (s, 2H, CH ); 7.09–7.18 (m, 2H, indole);
zone 3a in sulfuric acid at –5 °C two compounds were iso-
lated ethyl 3-carboxyindol-2-yl acetate (5a) and ethyl (5-
ethoxy-1-phenyl-1H-pyrazol-3-yl)acetate (6) in 42% and
4% yield, respectively, while from phenylhydrazone 3b
only methyl 3-carboxyindol-2-ylacetate 5b was isolated in
30% yield. On the other hand, when hydrazone (8), pre-
pared from phenylhydrazone (1) and ethyl acetoacetate
(7), was added to concentrated sulfuric acid at –5 °C, four
compounds were isolated: ethyl 2-methylindol-3-carboxy-
late (9), 2-methylindol-3-carboxylic acid (10), 2-methylin-
dole (11), 5-ethoxy-3-methyl-1-phenyl-1H-pyrazole (12)
in 2%, 3%, 32% and 14% yield, while 3-methyl-1-phenyl-
1H-pyrazol-5-one (13) was detected only in traces, on thin
layer chromatography (Scheme 1).
2
3
2
7.40–7.43 (m, 1H, indole); 7.94–7.98 (m, 1H, indole); 11.82
(broad s, 1H, NH); 12.02 (broad s, 1H, COOH). ir: 3310, 1720,
1670, 1560, 1460, 1210, 740. ms: m/z (EI) 247 (M ); hrms: m/z
+
(EI) calcd. for C
H NO : 247.084458. found: 247.084950.
13 13 4
Anal. Calcd. for C
H NO : C, 63.15; H, 5.30; N, 5.67.
13 13 4
Found: C, 62.96; H, 5,51; N 5.42.
Ethyl (5-Ethoxy-1-phenyl-1H-pyrazol-3-yl)acetate (6).
This compound was obtained as colorless oil, (4 %, 1060 mg)
1
H nmr (CDCl ): δ 1.27 (t, 3H, J = 7.17, OCH CH ); 1.42 (t, 3H,
3
2
3
J = 6.96, OCH CH ); 3.65 (s, 2H, CH ); 4.11–4.22 (m, 4H,
2
3
2
2xOCH CH ); 7.19–7.25 (m, 1H, phenyl); 7.35–7.42 (m, 2H,
2
3
phenyl); 7.68–7.72 (m, 2H, phenyl) (The compound is identical
with the compound reported in the literature [11]).
2-(2-Methoxy-2-oxoethyl)-1H-indole-3-carboxylic Acid (5b).
The structures of new compounds were determined by ir,
H nmr, mass spectra, and elemental analyses for C, H, and
1
Phenylhydrazine (1) (18 g) and dimethyl 2-oxopropane-1,3-
dicarboxylate (2b) (20 g) in ether (100 ml) with two drops of
acetic acid at 0 °C for 1 h, followed by evaporation of solvent at
room temperature, was added dropwise to concentrated sulfuric
acid (70 ml) at –5 °C with vigorous stirring during 5 min. After
0.5 h at that temperature the mixture was poured into ice, and
extracted with ether to give white solid 12.7 g (30%), mp =
N. The known compounds were identified by comparison
with authentic samples, prepared according to procedures
described in the literature.
EXPERIMENTAL
1
176–180 °C (toluene) H nmr (CDCl ): δ 3.83 (s, 3H, OCH );
3
3
1
4.44 (s, 2H, CH ); 7.25–7.29 (m, 2H, Ph); 7.39–7.43 (m, 1H,
Melting points were taken on a Kofler micro hot stage. The H
2
indole); 8.18–8.21 (m, 1H, indole); 9.92 (broad s, 1H, NH).
NMR and 2D NMR HMBC, NOESY spectra were obtained on a
Bruker Avance DPX 300 (300 MHz) spectrometer with DMSO-
d or CDCl as solvent and TMS as internal standard (δ in ppm, J
(DMSO): δ 3.64 (s, 3H, OCH ); 4.20 (s, 2H, CH ); 7.10–7.19 (m,
3
2
2H, indole); 7.39–7.42 (m, 1H, indole); 7.94–7.97 (m, 1H,
indole); 11.83 (broad s, 1H, NH); 12.05 (broad s, 1H, COOH). ir:
3380, 3120, 1730, 1650, 1460, 1210, 740.
6
3
in Hz). IR spectra were recorded with Perkin–Elmer Spectrum
BX FTIR and BIO RAD Excalibur Series FTS 3000 MX FTIR
–1
Anal. Calcd. for C
H NO : C, 61.80; H, 4.75; N, 6.01.
spectrophotometers (KBr discs, ν in cm ). MS spectra were
12 11 4
Found: C, 61.86; H, 4,73; N 6.31.
obtained on an Autospeck Q spectrometer. The microanalyses for
C, H, and N were obtained on a Perkin Elmer Series II CHN
Analyser 2400. Medium pressure chromatography (MPLC) was
performed with a Büchi isocratic system with detection on silica
gel (Merck, silica gel 40, 0.015–0.035 mm); column dimensions
(wet filled) 15x460 mm; backpressure 25–30 bar; detection: UV
254 nm; sample amount 200 mg of mixture.
Reaction of Phenylhydrazone of Ethyl Acetotacetate in Sulfuric
Acid. Preparation of compounds 9–13.
Phenylhydrazine (1) (18 g) and ethyl acetotacetate (7) (15 g) in
ether (100 ml) with two drops of acetic acid at 0 °C for 1 h, fol-
lowed by evaporation of solvent at room temperature, was added
dropwise to concentrated sulfuric acid (70 ml) at –5 °C with vig-
orous stirring during 5 min. After 0.5 h at that temperature the
mixture was poured into ice, and extracted with ether. Organic
phase was dried with anhydrous sodium sulfate, and evaporated
in vacuo. Oily mixture of products was separated by chromatog-
raphy. Fractions containing product were evaporated in vacuo to
give 9, 10, 11, and 12 in 2, 3, 32, and 14% yields, respectively. 3-
Methyl-1-phenyl-1H-pyrazole-5-one (13) was present in traces,
identified only by thin layer chromatography by comparison with
an authentic sample.
Reaction of Phenylhydrazone of Dialkyl 2-Oxopropane-1,3-
dicarboxylates in Sulfuric Acid. Preparation of 5a,b and 6.
Phenylhydrazine (1) (18 g) and diethyl 2-oxopropane-1,3-
dicarboxylate (2a) (21 g) in ether (100 ml) with two drops of
acetic acid at 0 °C for 1 h, followed by evaporation of solvent at
room temperature, was added dropwise to concentrated sulfuric
acid (70 ml) at –5 °C with vigorous stirring during 5 min. After
0.5 h at that temperature the mixture was poured into ice, and
extracted with ether. Organic phase was dried with anhydrous
sodium sulfate, and evaporated in vacuo. Oily mixture of prod-
ucts was separated by chromatography. Fractions containing
products were evaporated in vacuo to give 5a and 6 in 42 and 4%
yield, respectively.
Ethyl (2-Methylindol-3-yl)carboxylate (9).
1
This compound was obtained in 2 %, 480 mg; H nmr (CDCl ):
3
δ 1.40 (t, 3H, J = 7.1, OCH CH ); 2.28 (s, 3H, CH ); 4.24 (q, 2H,
2
3
3
J = 7.1, OCH CH ); 7.25–7.32 (m, 2H, indole); 7.41–7.43 (m, 2H,
2
3
2-(2-Ethoxy-2-oxoethyl)-1H-indole-3-carboxylic Acid (5a).
indole), 7.84 (broad s, 1H, NH) (The compound is identical with
the compound reported in the literature [9]).
This compound was obtained as white solid (42%, 12 g) mp =
1
194–198 °C (ethanol/water) H nmr (CDCl ): δ 1.33 (t, 3H, J =
3
2-Methyl-1H-indole-3-carboxylic acid (10).
7.16, OCH CH ); 4.27 (q, 2H, J = 7.16, OCH CH ); 4.41 (s, 2H,
2
3
2
3
1
CH ); 7.21–7.26 (m, 2H, indole); 7.38–7.42 (m, 1H, indole);
This compound was obtained in 3 %, 640 mg; H nmr
2
8.18–8.21 (m, 1H, indole); 10.06 (broad s, 1H, NH). (DMSO): δ
(CDCl ): δ 2.79 (s, 3H, CH ); 7.21–7.26 (m, 2H, indole);
3
3