Fischer synthesis of 3-(N-acylamino)-2-phenylindoles

Article abstract of DOI:10.1023/A:1021244929340

Phenylhydrazones were obtained by the reaction of phenylhydrazine with ω-(N-acylamino)-acetophenones and were converted into 3-(N-acylamino)indoles by the Fischer cyclizaction.

Full text of DOI:10.1023/A:1021244929340

Chemistry of Heterocyclic Compounds, Vol. 38, No. 9, 2002
FISCHER SYNTHESIS OF
3-(N-ACYLAMINO)-2-PHENYLINDOLES
N. M. Przheval'skii, N. S. Skvortsova, and I. V. Magedov
Phenylhydrazones were obtained by the reaction of phenylhydrazine with ω-(N-acylamino)-
acetophenones and were converted into 3-(N-acylamino)indoles by the Fischer cyclizaction.
Keywords: 3-(N-acylamino)indoles, phenylhydrazine, phenylhydrazones.
The synthesis of indole derivatives, including aminoindoles, remains crucial in connection with their
wide range of biological activity [1, 2]. 3-Aminoindoles are produced by hydrolysis of isocyanates [3] or by
reduction of the salts of isonitrosoindoles [4]. Only one paper is known in which the Fischer synthesis of
3-(N-acylamino)indole is described [5].
Earlier we reported on the synthesis of new derivatives of indole containing diethyldithiocarbamic [6]
and xanthic [7] groups at position 3. In the present work we propose a convenient single-stage method for the
synthesis of 3-(N-acylamino)-2-phenylindoles by Fischer cyclization of the phenylhydrazines of
ω-(N-acylamino)acetophenones (see [8]).
O
R
O
R
O
R
+
NH
Ph
NH
Ph
H
NH
+
NH2
+
N
H
Ph
– NH4
O
N
N
N
H
H
1a–p
2a–p
3a–p
1-3 a R = C6H4Br-4, b R = C6H4Cl-4, c R = Ph, d R = C6H4Ph-4, e R = 3-(2-chlorophenyl)-5-methyl-4-isoxazolyl,
f R = 2-oxo-2H-chromen-3-yl, g R = CH2C6H4Cl-4, h R = CH2OC6H4Cl-4, i R = (CH2)3OPh, j R = (CH2)2C6H11,
k R = (CH2)2C6H4OMe-4, l R = 1-adamantyl, m R = CH2SCH2Ph, n R = CH2C6H3(OMe)2-3,4, o R = CH=CHC6H4Cl-4,
p 3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolyl
The N-acylaminoacetophenones (1) were synthesized from ω-aminoacetophenone and the respective
acid chlorides in the presence of bases. The characteristics of compounds 1a-p are given in Tables 1 and 2.
When boiled a mixture of equimolar amounts of the ketones 1 and phenylhydrazine in ethanol in the
presence of catalytic amounts of acetic acid gives the phenylhydrazones 2. In a number of cases they were
isolated (see Experimental) and were then converted into the indoles 3 by heating with a twofold molar amount
of thionyl chloride in ethanol. In other cases the hydrazones 2 without isolation were rearranged under the same
conditions to aminoindoles 3 (Table 1).
__________________________________________________________________________________________
K. A. Timiryazev Moscow Agricultural Academy, Moscow 127550, Russia; e-mail: ibs@ibisc.msk.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1210-1216, September, 2002. Original
article submitted July 19, 2001.
0009-3122/02/3809-1055$27.00©2002 Plenum Publishing Corporation
1055

TABLE 1. Characteristics of Compounds 1 and 3
Found, %
——————
Com-
Empirical
formula
Yield, %
(method)
Calculated, %
Name
pound
mp, °С
C
4
H
5
N
6
1
2
3
7
8
N-(2-Oxo-2-phenylethyl)-4-bromobenzamide
N-(2-Oxo-2-phenylethyl)-4-chlorobenzamide
N-(2-Oxo-2-phenylethyl)benzamide
C15H12BrNO2
C15H12ClNO2
C15H13NO2
C21H17NO2
C19H15ClN2O3
C18H13NO4
C16H14ClNO2
C16H14ClNO3
C18H19NO3
C17H23NO2
C18H19NO3
C19H23NO2
C17H17NO2S
C18H19NO4
C17H14СlNO2
56.47
56.63
3.72
3.80
4.12
4.40
159-160
48 (A)
42 (A)
84 (C)
72 (B)
60 (B)
64 (D)
33 (A)
34 (D
16 (B)
75 (D)
62 (D)
51 (D)
38 (D)
56 (D)
61 (D)
1a
(i-PrOH aq.)
65.72
4.29
5.42
163-164
1b
1c
1d
1e
1f
65.82
4.42
5.12
(i-PrOH aq.)
75.43
75.30
5.42
5.48
5.42
5.85
130-131
(i-PrOH aq.)
N-(2-Oxo-2-phenylethyl)-4-phenylbenzamide
80.13
5.37
4.33
100-101
79.98
5.43
4.44
(i-PrOH aq.)
3-(2-Chlorophenyl)-5-methyl-N-(2-oxo-2-phenylethyl)-
4-isoxazolecarboxamide
64.60
64.32
4.33
4.26
7.89
7.90
78-79
(i-PrOH aq.)
2-Oxo-N-(2-oxo-2-phenylethyl)-2H-3-chromenecarboxamide
2-(4-Chlorophenyl)-N-(2-oxo-phenylethyl)acetamide
2-(4-Chlorophenoxy)-N-(2-oxo-2-phenylethyl)acetamide
N-(2-Oxo-2-phenylethyl)-4-phenoxybutanamide
70.14
4.14
4.44
207-208
70.35
4.26
4.56
(CH3CN)
66.60
66.79
5.07
4.90
4.81
4.87
210-211
1g
1h
1i
(i-PrOH aq.)
63.50
4.71
4.82
155-156
63.27
4.65
4.61
(i-PrOH)
72.84
72.71
6.49
6.44
4.67
4.71
109-110
(toluene)
N-(2-Oxo-2-phenylethyl)-3-cyclohexylpropanamide
3-(4-Methoxyphenyl)-N-(2-oxo-2-phenylethyl)propanamide
N-(2-Oxo-phenylethyl)-1-adamantanecarboxamide
2-(Benzylthio)-N-(2-oxo-2-phenylethyl)acetamide
74.53
8.44
5.20
115-116
1j
74.69
8.48
5.12
(i-PrOH)
72.82
72.71
6.49
6.44
4.89
4.71
118-119
1k
1l
(i-PrOH)
76.61
7.87
4.77
158-159
76.74
7.80
4.71
(i-PrOH)
68.36
68.20
5.64
5.72
4.85
4.68
90-91
1m
1n
1o
(i-PrOH)
2-(3,4-Dimethoxyphenyl)-N-(2-oxo-2-phenylethyl)acetamide
3-(4-Chlorophenyl)-N-(2-oxo-2-phenylethyl)-2-propenamide
69.14
6.02
4.39
92-93
69.00
6.11
4.47
(i-PrOH)
68.27
68.12
4.62
4.71
4.59
4.67
205-206
(i-PrOH aq.)

TABLE 1 (continued)
1
2
3
4
5
6
7
8
56 (D)
42
3-(6-Fluoro-2-chlorophenyl)-5-methyl-N-(2-Oxo-2-
phenylethyl)-4-isoxazolecarboxamide
3-(4-Bromobenzoylamino)-2-phenyl-1H-indole
3-(4-Chlorobenzoylamino)-2-phenyl-1H-indole
3-Benzoylamino-2-phenyl-1H-indole
C19H14ClFN2O3
C21H15BrN2O
C21H15ClN2O
C21H16N2O
61.39
61.22
3.74
3.79
7.47
7.51
72-73
1p
3a
3b
3c
3d
3e
3f
(i-PrOH aq.)
64.33
3.95
7.01
194-195
64.47
3.86
7.16
(i-PrOH)
72.79
72.73
4.45
4.36
8.21
8.08
210-211
33
(i-PrOH)
80.64
5.21
8.88
198-199
62
80.75
5.16
8.97
(i-PrOH)
52*
2-Phenyl-3-(4-phenylbenzoylamino)-1H-indole
C27H20N2O
83.64
83.48
5.27
5.19
7.15
7.21
132-133
11
(i-PrOH)
3-(2-Chlorophenyl)-5-methyl-N-(2-phenyl-1H-3-indolyl)-
4-isoxazolecarboxamide
2-Oxo-N-(2-phenyl-1H-3-indolyl)-2H-
C25H18ClN3O2
C24H16N2O3
C22H17ClN2O
C22H17ClN2O2
C24H22N2O2
C23H26N2O
70.00
4.15
9.96
228-229
62
70.18
4.24
9.82
(i-PrOH)
41*
75.90
75.78
4.32
4.24
7.50
7.36
258-259
83
3-chromenecarboxamide
(CH3CN)
65*
3-(4-Chlorophenylacetylamino)-2-phenyl-1H-indole
3-(4-Chlorophenoxyacetylamino)-2-phenyl-1H-indole
2-Phenyl-3-(phenoxypropylcarbonylamino)-1H-indole
3-(Cyclohexylethylcarbonylamino)-2-phenyl-1H-indole
73.14
4.80
7.84
210-211
35
11
20
28
30
31
44
3g
3h
3i
73.23
4.75
7.76
(i-PrOH)
70.25
70.12
4.62
4.55
7.29
7.43
240-241
(i-PrOH)
77.93
5.94
7.76
66-67
77.81
5.99
7.56
(i-PrOH)
79.54
79.73
7.61
7.56
8.13
8.09
120-121
3j
(i-PrOH)
3-(4-Methoxyphenylethylcarbonylamino)-2-phenyl-1H-indole C24H22N2O2
77.93
5.90
7.37
157-158
3k
3l
77.81
5.99
7.56
(i-PrOH)
3-(1-Adamantylcarbonylamino)-2-phenyl-1H-indole
3-(Benzylthioacetylamino)-2-phenyl-1H-indole
C25H26N2O
81.17
81.05
7.00
7.07
7.60
7.56
307-308
(AcOH)
C23H20N2OS
C24H22N2O3
C23H17ClN2O
C25H17ClFN3O2
74.09
5.37
4.34
157-158
(AcOH)
3m
3n
3o
3p
74.16
5.41
7.52
3-(3,4-Dimethoxyphenylacetylamino)-2-phenyl-1H-indole
74.72
74.59
5.81
5.74
7.39
7.25
93-94
49
(i-PrOH)
32*
3-(4-Chlorophenylethenylcarbonylamino)-2-phenyl-
1H-indole
74.18
4.62
7.47
120-121
28
74.09
4.60
7.51
(i-PrOH)
15*
3-(2-Chloro-6-fluorophenyl)-5-methyl-N-(2-phenyl-1H-3-
67.26
67.34
3.75
3.84
9.56
9.42
198-199
18
indolyl)-4-isoxazolecarboxamide
(i-PrOH)
_______
* The yield obtained after by-passing the stage involving the formation of the hydrazone.

TABLE 2. The 1H NMR Spectra of Compounds 1
Chemical shifts, δ, ppm, (SSCS, J, Hz)
Com-
Phenyl-
о-Н, m, m-Н, m,
p-Н, m
R
NH,
br. s
pound
СН2, d
CH3, CH2, CH=
—
Phenyl or hetaryl
8.06; 7.68; 7.73
4.89 (J = 4.6)
7.48
7.99 (2H, d, J = 12.0, H-2, H-6);
7.87 (2H, d, J = 12.0, H-3, H-5)
1a
8.06; 7.58; 7.70
7.89; 7.52; 7.52
4.86 (J = 4.6)
4.87 (J = 5.5)
7.43
7.43
—
—
7.87 (2H, d, J = 9.0, H-2, H-6); 7.54 (2H, d, J = 9.0, H-3, H-5)
1b
1c
8.07 (2H, d, J = 8.5, H-2, H-6); 7.70 (1H, t, J = 14.5, H-4);
7.58 (2H, t, J = 14.5, H-3, H-5)
8.06; 7.66; 7.79
4.82 (J = 5.0)
7.76
—
7.76 (2H, t, J = 8.0, H-3, H-5); 7.60 (2H, t, J = 8.0, H-2, H-6);
7.33 (2H, t, J = 8.0, H-2′, H-6′);
1d
7.27 (2H, t, J = 8.0, H-3′, H-5′); 7.20 (1H, t, J = 6.5, H-4′)
7.60-7.50 (4H, m, СН arom.)
7.95; 7.67; 7.67
8.03; 7.57; 7.69
4.72 (J = 6.5)
4.95 (J = 6.5)
6.59
9.30
2.76 (3H, s, CH3)
1e
1f
—
8.05 (1Н, s, Н-4); 8.03 (1H, m, H-5);
7.78 (1H, t, J = 16.5, H-7); 7.53 (1H, m, H-8);
7.45 (1H, t, J = 16.5, H-6)
7.99; 7.54; 7.67
8.00; 7.53; 7.67
4.66 (J = 6.0)
4.74 (J = 7.5)
6.82
7.44
3.62 (2H, s, CH2)
4.56 (2H, s, CH2)
7.38 (2H, d, J = 6.0, H-2, H-6); 7.35 (2H, d, J = 6.0, H-3, H-5)
1g
1h
7.34 (2H, d, J = 12.0, H-3, H-5);
7.01 (2H, d, J = 12.0, H-2, H-6)
8.02; 7.55; 7.67
7.98; 7.52; 7.64
7.98; 7.52; 7.65
4.69 (J = 5.5)
4.62 (J = 5.5)
4.64 (J = 4.5)
6.86
6.74
6.76
4.05 (2H, t, J = 14.0, OCH2);
7.31 (2H, t, J = 16.5, H-3, H-5); 6.95 (3H, m, H-2, H-4, H-6)
1i
2.46 (2H, t, J = 14.0, CH2); 2.07 (2H, m, CH2)
2.22 (2H, m, CH2); 1.71-0.92 (11H, m, cyclohexyl)
—
1j
1k
1.47 (2H, m, CH2)
3.75 (3H, s, OCH3); 2.85 (2H, t, J = 17.0, CH2);
2.51 (2H, t, J = 17.0, CH2)
2.02-1.75 (15H, m, adamantyl)
3.86 (2H, s, CH2); 3.15 (2H, s, CH2)
3.81 (3H, s, OCH3); 3.79 (3H, s, OCH3);
7.16 (2H, d, J = 8.5, H-2, H-6); 6.83 (2H, d, J = 8.5, H-3, H-5)
7.98; 7.52; 7.65
8.00; 7.54; 7.67
7.96; 7.51; 7.64
4.60 (J = 4.5)
4.66 (J = 5.5)
4.63 (J = 6.5)
6.65
7.30
6.74
—
1l
1m
1n
7.30-7.20 (5H, m, CH arom.)
6.94 (1H, m, H-2); 6.90 (1H, m, H-5); 6.85 (1H, m, H-6)
3.51 (2H, s, CH2)
8.01; 7.53; 7.66
7.95; 7.67; 7.67
4.79 (J = 5.0)
4.67 (J = 6.5)
7.04
6.52
7.57 (1H, d, J = 14.0, CH=);
6.76 (1H, d, J = 14.0, CH=)
2.56 (3H, s, CH3)
7.59 (2H, d, J = 8.3, H-2, H-6); 7.41 (2H, d, J = 8.3, H-3, H-5)
1o
1p
7.30-7.20 (3H, m, CH arom.)

TABLE 3. The 1H NMR Spectra of Compounds 3
Chemical shifts, δ, ppm (SSCS, J, Hz)
Com-
2-phenyl,
–R
Indole ring
N
indH,
NH,
br. s
pound
о-Н, m, m-Н, m,
p -Н, m
Н-4, m, Н-5, m, Н-6, m, Н-7, m
br. s
CH3, CH2, CH=
Phenyl or hetaryl
7.40-7.50; 7.12; 7.24;
7.40-7.50
8.50
8.58
8.51
8.54
9.58
9.63
9.65
9.64
7.69; 7.35; 7.20
7.77; 7.47; 7.36
7.76; 7.45; 7.35
—
—
—
—
7.87 (2H, d, J = 9.3, H-2, H-6);
7.72 (2H, d, J = 9.3, H-3, H-5)
3а
3b
3c
3d
7.40-7.50; 7.12; 7.24;
7.99 (2H, d, J = 9.3, H-2, H-6);
7.40-7.50
7.57 (2H, d, J = 9.3, H-3, H-5)
7.40-7.50; 7.10; 7.21;
7.40-7.50
7.98 (2H, d, J = 8.0, H-2, H-6);
7.40-7.50 (3H, m, H-3, H-4, H-5)
7.40-7.50; 7.10; 7.22;
7.70-7.50;
8.07 (2H, d, J = 9.6, H-2, H-6); 7.81 (2H, d,
7.40-7.50
7.70-7.50; 7.36
J = 9.6, H-3, H-5); 7.70-7.50 (5H, m, СН arom.)
7.38; 7.11; 7.21; 7.43
7.71
9.62
9.63
10.28
7.60-7.40
7.78; 7.47; 7.36
7.60-7.40 (4H, m, СН arom.)
3e
3f
2.75 (3H, s, CH3)
7.50-7.40; 7.11; 7.23;
—
8.96 (1H, s, H-4); 7.87 (1H, m, H-5);
7.50-7.40
7.75 (1H, m, H-7); 7.47 (2H, m, H-6, H-8)
7.45-7.40; 7.10; 7.21;
7.45-7.40
8.00
8.42
7.89
9.61
9.59
9.55
7.62; 7.45-7.40;
7.45-7.40
3.74 (2H, s, CH2)
4.74 (2H, s, CH2)
7.35 (4H, m, СH arom.)
3g
3h
3i
7.45-7.40; 7.09; 7.20;
7.67; 7.50-7.40;
7.36 (2H, m, H-3, H-5); 7.06 (2H, m, H-2, H-6)
7.45-7.40
7.50-7.40
7.40; 7.06; 7.18; 7.30
7.98; 7.70; 6.69
7.72; 7.43; 7.43
4.07 (2H, t, J = 14.0, OCH2);
2.61 (2H, t, J = 14.0, CH2);
2.05 (2H, m, CH2)
7.30 (2H, m, H-3, H-5);
6.97 (3H, m, H-2, H-4, H-6)
7.40-7.30; 7.08; 7.18;
7.40-7.30
7.80
7.73
9.55
9.47
2.42 (2H, m, CH2); 1.76-0.96 (11H,
—
3j
m, cyclohexyl); 1.61 (2H, m, CH2)
7.50-7.40; 7.16; 7.05;
7.66; 7.50-7.40;
7.50-7.40
3.79 (3H, s, OCH3); 2.98 (2H, t,
J = 17.7, CH2); 2.86 (2H, t,
J = 17.7, CH2)
2.08-1.79 (15H, m, adamantyl)
3.90 (2H, s, CH2); 3.31 (2H, s, CH2)
7.23 (2H, m, H-2, H-6); 6.89 (2H, m, H-3, H-5)
3k
7.50-7.40
7.33; 7.07; 7.18; 7.42
7.36; 7.10; 7.20; 7.45
9.59
8.20
12.07
9.60
7.70; 7.48; 7.38
—
3l
3m
7.76; 7.48-7.30;
7.45-7.35 (5H, m, CH arom.)
7.48-7.30
7.40; 7.07; 7.18; 7.40
7.43; 7.09; 7.20; 7.35
7.38; 7.11; 7.21; 7.43
7.71
8.05
7.71
9.40
9.65
9.63
7.61; 7.40; 7.40
7.70-7.40
3.83 (3H, s, OCH3); 3.81 (3H, s, OCH3); 7.02 (1H, m, H-2); 6.96 (2H, m, H-5, H-6)
3.67 (2H, s, CH2)
3n
3o
3p
7.64 (1H, d, J = 7.6, CH=);
7.70-7.40 (4H, m, CH arom.)
6.85 (1H, d, J = 7.6, CH=)
7.60-7.40
2.58 (3H, s, CH3)
7.20-7.10 (3H, m, CH arom.)

The indoles 3 are also formed in the reaction of phenylhydrazine with ketones 1 and thionyl chloride
(boiling in ethanol) but with lower yields (see 3c,e,n,o, Table 1). The structure of the indoles 3a-p was
demonstrated by 1H NMR (Table 3). We did not encounter any fundamental difficulties in the cyclization of the
hydrazones 2 with such substituents R as aryl, heteroaryl, alkyl, cycloalkyl, alkoxy, alkylthio, and alkenyl. The
proposed method for the synthesis of 3-(N-acylamino)-2-phenylindoles therefore seems fairly general. At
present we are studying the effect of substituents in the benzene ring and at the nitrogen atom of the
phenylhydrazine on the rearrangement of the hydrazone 2.
EXPERIMENTAL
The 1H NMR spectra of compounds 1-3 were recorded on a Bruker WM-250 instrument at 250 MHz in
CD3CN. The reactions were monitored by TLC on Silufol plates in 4:1 carbon tetrachloride–ethyl acetate.
Synthesis of ω-(N-Acylamino)acetophenones (1) (General Procedure). To a solution of
ω-aminoacetophenone hydrochloride (1 mol) in a suitable solvent we added the respective base (method A,
water, sodium acetate (1.1 mol); B, methylene chloride, triethylamine (2.5 mol); C, water, sodium carbonate
(3 mol); D, chloroform, pyridine (4 mol)). At 0°C with stirring we added dropwise the acid chloride (1.05 mol).
The mixture was stirred for a further 4 h. A, C: The precipitate was filtered off, washed with water, and
recrystallized. B, D: The organic solvent was washed with water and dilute hydrochloric acid (method D) and
evaporated, and the product was recrystallized.
General Procedure for the Production of the Hydrazone 2. To a solution of phenylhydrazine (5.4 g,
0.05 mol) and the ketone 1 (0.05 mol) in the smallest amount of ethanol (5-10 ml) we added a few drops of
glacial acetic acid. The mixture was boiled with a reflux condenser for 2 h. The alcohol was evaporated, and the
remaining oil was crystallized or rearranged to the aminoindoles 3 without further purification.
N-(2-Phenyl-2-phenylhydrazonoethyl)benzamide (2c). Yield 62%; mp 174-175°C (ethanol). 1H NMR
spectrum, δ, ppm, J (Hz): 10.22 (1H, s, NH–N=C); 7.96-6.87 (15H, m, CH arom.); 7.76 (1H, br. s, NH); 4.68
(2H, d, J = 6.6, CH2). Found %: C 76.71; H 5.84; N 12.75. C21H19N3O. Calculated %: C 76.59; H 5.77; N 12.76.
3-(2-Chlorophenyl)-5-methyl-N-(2-phenyl-2-phenylhydrazonoethyl)-4-isoxazolecarboxamide (2e).
1
Yield 49%; mp 194-195°C (ethanol). H NMR spectrum, δ, ppm, J (Hz): 9.80 (1H, s, NH–N=C); 7.73-6.88
(14H, m, CH arom.); 6.83 (1H, br. s, NH); 4.46 (2H, d, J = 7.0, CH2); 2.67 (3H, s, CH3). Found %: C 67.37;
H 4.64; N 12.75. C25H21ClN4O2. Calculated %: C 67.49; H 4.72; N 12.59.
2-(3,4-Dimethoxyphenyl)-N-(2-phenyl-2-phenylhydrazonoethyl)-acetamide (2n). Yield 70%;
1
mp 160-161°C (ethanol). H NMR spectrum, δ, ppm, J (Hz): 9.91 (1H, s, NH–N=C); 7.82-6.78 (13H, m, CH
arom.); 7.25 (1H, br. s, NH); 4.40 (2H, d, J = 9.0, CH2); 3.72 (3H, s, OCH3); 3.65 (3H, s, OCH3); 3.45 (2H, s,
CH2). Found %: C 71.37; H 6.18; N 10.35. C24H25N3O3. Calculated %: C 71.44; H 6.25; N 10.41.
3-(4-Chlorophenyl)-N-(2-phenyl-2-phenylhydrazonoethyl)-2-propenamide (2o). Yield 70%;
1
mp 184-185°C (ethanol). H NMR spectrum, δ, ppm, J (Hz): 10.20 (1H, s, NH–N=C); 7.87-6.84 (14H, m, CH
arom.); 7.59 (1H, d, J = 10.6, CH=); 6.54 (1H, d, J = 10.6, CH=); 7.4 (1H, br. s, NH); 4.52 (2H, d, J = 6.00,
CH2). Found %: C 70.99; H 5.26; N 10.65. C23H20ClN3O. Calculated %: C 70.86; H 5.17; N 10.78.
General Procedure for the Production of Indoles 3 from Hydrazones 2. To a solution of the
hydrazone 2 (0.02 mol) in ethanol (10-20 ml) we added a solution of thionyl chloride (4.8 g, 0.04 mol) in
ethanol (10 ml). The mixture was boiled with a reflux condenser for 3-4 h. The alcohol was evaporated, and the
residue was crystallized, or the indole 3 was isolated by chromatography (silica gel L 100 × 250 µ, eluent 4:1
carbon tetrachloride–ethyl acetate).
General Procedure for the Production of Indoles 3 from Phenylhydrazine and Ketones 1. To a
solution of phenylhydrazine (1.4 g, 0.013 mol) and the ketone 1 (0.01 mol) in ethanol (10 ml) we added a
solution of thionyl chloride (2.4 g, 0.02 mol) in ethanol (10 ml). The mixture was boiled with a reflux condenser
for 4-5 h. The alcohol was distilled, and the indole was isolated by column chromatography (under the same
conditions as in the production of indoles from hydrazones).
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