Diastereodirected alkylation of ketones and 1,3-diketones with N-[1H-Indol-3-yl(phenyl)methyl]-N-methylamine by the Michael reaction

Article abstract of DOI:10.1007/s10593-005-0213-5

A method has been developed for introducing the 1H-indol-3-yl(phenyl)methyl residue into position 2 of ketones and 1,3-diketones. The principle of bringing in controlled diastereoselectivity based on the configuration of intermediates is demonstrated. 2005 Springer Science+Business Media, Inc.

Full text of DOI:10.1007/s10593-005-0213-5

Chemistry of Heterocyclic Compounds, Vol. 41, No. 6, 2005
DIASTEREODIRECTED ALKYLATION OF
KETONES AND 1,3-DIKETONES WITH
N-[1H-INDOL-3-YL(PHENYL)METHYL]-
N-METHYLAMINE BY THE MICHAEL REACTION
B. B. Semenov1, Yu. I. Smushkevich1, I. I. Levina2, L. N. Kurkovskaya2, K. A. Lysenko3,
and V. V. Kachala4
A method has been developed for introducing the 1H-indol-3-yl(phenyl)methyl residue into position 2 of
ketones and 1,3-diketones. The principle of bringing in controlled diastereoselectivity based on the
configuration of intermediates is demonstrated.
Keywords: gramine, CH-acids, α-phenyl-nor-gramine, diastereoselectivity in the Michael reaction,
X-ray structural analysis, NMR.
The present work is devoted to a study of the possibility of alkylating carbonyl compounds with
α-phenyl-nor-gramine (1), and in a diastereospecific manner. Previously we showed the possibility of the
nondiastereoselective alkylation of nitroalkanes with N-[1H-indol-3-yl(phenyl)methyl]-N-methylamine
(α-phenyl-nor-gramine) (1) [1]. It is also known that compound 1 is readily converted into 2-(1H-indol-3-yl)-2-
phenylacetonitrile on interaction with KCN [2]. Based on this we suggested that compound 1 will be a
convenient reagent for introducing a 1H-indol-3-yl(phenyl)methyl residue into position 2 of ketones and
1,3-diketones. The following were used as model compounds: cyclohexanone (3a), cyclopentanone (3b),
1,2-cyclohexanedione (3c), 1,3-cyclohexanedione (3d), 5,5-dimethyl-1,3-cyclohexanedione (dimedone) (3e),
esters of 3-oxobutyric acid: methyl (3f), ethyl (3g), isopropyl (3h), and benzyl (3i), 1,3-indanedione (3j), acetone
(3k), acetophenone (3l), esters of cyanoacetic acid: methyl (3m), ethyl (3n), and α-tetralone (3o).
Compound 1 was obtained by the addition of indole at the double bond of benzylidenemethylamine by
the method of Passerini [3].
The alkylation of carbonyl compounds 3 was carried out in 90% aqueous 2-propanol or ethanol using
potassium carbonate as catalyst. The yields of alkylation products 4 are given in Table 1. Alkylation probably
occurs through the intermediate formation of 3-[(Z)-phenylmethylidene]-3H-indole (2) with subsequent addition
to it of a CH-acid enolate according to Michael.
__________________________________________________________________________________________
1
Moscow D. I. Mendeleev University of Chemical Technology, Moscow 125190; e-mail:
semenovb@mail.ru, mu@muctr.edu.ru. 2 N. M. Emanuel Institute of Biochemical Physics, Russian Academy of
3
Sciences, Moscow 117977. A. N. Nesmeyanov Institute of Organoelement Compounds, Moscow 117813,
Russia; e-mail: kostya@xrlab.ineos.ac.ru. 4 N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of
Sciences, Moscow 117913; e-mail: kachala@ioc.ac.ru. Translated from Khimiya Geterotsiklicheskikh
Soedinenii, No. 6, pp. 848-857, June, 2005. Original article submitted October 28, 2003; revision submitted
March 22, 2005.
730
0009-3122/05/4106-0730©2005 Springer Science+Business Media, Inc.

R1
R2
O
H
Ph
H
Ph
N
K2CO3,
3
Me
–H2NMe
N
N
H
R1
2
1
O
Ph
R2
N
H
4
According to literature data 2-methyl-3-[(Z)-phenylmethylidene]-3H-indole [4] exists as one isomer.
According to our ab initio calculations intermediate 2 also has the Z-configuration [5].
In the case of compounds 3d,e,i-k the alkylation products 4d,e,i-k were not formed under these
conditions, and polymeric products of the self-condensation of the initial compound 1 were obtained. Probably
the rate of polymerization in this case is higher than Michael addition of the enolates of the carbonyl compounds.
For compounds 3d,e significant steric obstacles also evidently hinder alkylation.
Unlike gramine [6-9], in our case only products of the monoalkylation of compounds 3a-c, f-h, l-o were
formed. The formation of bisalkylation products was not observed even chromatographically.
The method developed by us has enabled investigation of the stereochemistry of the process of
alkylating cyclic ketones 3a,b,o with α-phenyl-nor-gramine (1). Previously it was suggested that compound 1
eliminates methylamine on treatment with basic catalysts and forms an intermediate 3-[(Z)-phenylmethylidene]-
3H-indole (2), having a planar structure [5]. We proposed that if in the Michael reaction the enolates of
cyclopentanone or α-tetralone, having the E-configuration, are used as second component, then the alkylation
products 4 will have an (R*,S*)-structure. As a result of coordination of the metal cation with a nitrogen atom of
one ring and an oxygen atom of another ring both fragments are disposed to one another on the Si and Re sides,
which corresponds to unlike attack [10-13].
We have established that for cyclohexanone the reaction does not go diastereoselectively (de 0%). In the
case of α-tetralone enolate, having a planar rigidity in the 1,3-butadiene fragment, the reaction proved to be
diastereospecific (de 100%), and for cyclopentanone enolate a fairly high diastereoselectivity was observed (de
92%).
TABLE 1. Yields of Alkylation Products
Com-
pound
Yield,
%
Com-
pound
Yield,
%
R1
R2
R1
R2
4a
4b
4c
4d
4e
4f
R1 = R2 = (CH2)4
60
75
50
—
—
65
71
4h
4j
Me
COOPr-i
65
—
—
—
70
65
25
R1 = R2 = (CH2)3
R1 = R2 = C6H4CO
R1 = R2 = CO(CH2)3
R1 = R2 = CO(CH2)3
R1 = R2 = COCH2CMe2CH2
4k
4l
4m
4n
4o
Me
Ph
OMe
OEt
H
H
CN
CN
Ме
Ме
COOМе
4g
COOEt
R1 = R2 = CH2C6H4
731

X
3
X
O
H
O
M+
H+
M+OH–
H
Ph
1
–H2NMe
N
H
N
2
NH2
4
6
N
N2H4
Ph
N
H
5
M = Li, K, Na; 3, 4 a X = (CH2)2; b X = CH2; o X = C6H4
Compound, yield, %; de, %; configuration: 4a, 60, 0, E; 4b, 75, 92, E; 4o, 25, 100, E
Alkylation of carbonyl compounds 3a,b,o was carried out in 90% aqueous 2-propanol or ethanol using
potassium carbonate as catalyst. The use of different solvents, as was shown in the example of preparing
compound 4b, has no effect on the size of de and only insignificantly influenced the yield of alkylation products.
The de was 75% in 90% aqueous isopropyl alcohol and 69% in 90% aqueous ethanol.
The ratio of diastereomers in the reaction to form compound 4b was established by comparing the
integral intensities of the doublets of the CH protons in the 1H NMR spectra of both diastereoisomers.
We have established that this stereochemical result may not be the result of a separation of the mixture
of diastereoisomers in the process of recrystallization. If the reaction is stopped 1 h after the start by the addition
1
of water, then, according to data of H NMR spectroscopy the ratio of diastereomers is 96:4. Consequently the
reason for the diastereoselectivity is either kinetic or thermodynamic control (equilibrium isomerization of one
diastereomer into the other through the enolic form of the ketone). A choice between these was made on the
basis of the following experiment. If 10 mol. % C5D5N is added to the pure (R*,S*)-diastereomer in CDCl3 then
the formation of the second diastereomer is not observed at room temperature for 48 h. It was not successfully
detected on maintaining the (R*,S*)-diastereomer in pure pyridine at room temperature for 96 h. In our opinion
this is explained sterically by the more ready possibility of forming the enol form of compound 4b with the
participation of the protons of a methylene group of the cyclopentanone ring. However after maintaining the
pure (R*,S*)-diastereomer in 90% aqueous 2-propanol in the presence of potassium carbonate for 30 h, we
recorded a mixture of (R*,S*)- and (S*,S*)-isomers in a ratio of 75:25 (de 50%), but on using 90% aqueous
ethanol as solvent the ratio was 60:40 (de 20%).
On alkylating compound 3b in anhydrous isopropyl alcohol compound 4b was obtained and the ratio of
(R*,S*)- and (S*,S*)-diastereomers amounted to 75:25 (de 50%). On treating this mixture with a 20-fold excess
1
of hydrazine hydrate the ratio of diastereomers in the resulting hydrazone 5, according to data of H NMR
spectroscopy, was unchanged and probably the (R*,S*)-isomer predominates. Such a stereochemical result
points to the enolization of ketone 4b under the given conditions being in the direction of the more hydrogenated
carbon atom. Consequently the reason for the diastereoselectivity is evidently kinetic control.
The configuration of the major (R*,S*)-diastereomer of compound 4b was confirmed by data of 1H and
13C NMR spectra (Table 2) and of X-ray structural analysis (Fig. 1).
732

TABLE 2. NMR Spectra of Compound 4b
4"
O
5
3"
1
6
4
2" 1"
3a'
4'
2
3
3'
5'
6'
2'
N
H
7a'
7'
4b
Numbering
of atoms
13C, δ, ppm
R*,S*
1H, δ, ppm
S*,S*
R*,S*
S*,S*
1
41.6
42.1
53.7
5.05
2.95
2.30; 1.75
1.70
2.30; 1.85
—
4.95
2.95
2
53.7
26.4
3
27.6
2.35; 1.90
1.70
2.30; 1.85
—
4
20.8
20.7
5
6
38.8
38.8
219.9
122.1
118.4
127.1
119.4
119.3
121.5
110.9
136.4
141.5
129.3
128.1
126.4
220.1
123.5
117.1
127.1
120.1
119.3
121.8
111.0
136.2
143.5
128.1
128.2
126.1
2'
3'
3a'
4'
5'
6'
7'
7a'
1''
2''
3''
4''
7.15
—
7.00
—
—
—
7.20
6.95
7.15
7.35
—
7.25
6.95
7.10
7.35
—
—
—
7.15
7.30
7.20
7.40
7.25
7.15
Fig. 1. General form of the compound 4b molecule.
733

1
13
All the signals in the H and C NMR spectra of compound 4b were unequivocally assigned using the
13C APT (attached proton test) and the HSQC and HMBC two-dimensional heteronuclear procedures (Table 2).
Based on data of X-ray structural analysis it was established that in the crystal of the
(R*,S*)-diastereomer of compound 4b the cyclopentanone fragment has an envelope conformation with the C(17)
atom emerging 0.55 Å from the plane of the remaining ring atoms. The dihedral angle between the phenyl and
indole fragments was 99.6°. Analysis of the crystal packing showed that the molecules are connected by
intermolecular hydrogen bonds N–H···O [N···O is 2.875(3) Å] in a spiral directed along the c crystal axis. The
spirals interweave with one another with the formation of channels of diameter ~4.60 Å.
On alkylating cyclohexanone in 90% alcohol, in the presence of potassium carbonate or NaOH as
catalyst, a mixture was obtained of diastereomers of compound 4a, though the content of each diastereomer was
1
50% according to data of H NMR spectra. This stereochemical result is probably the result of isomerization of
one diastereomer into the other through the enolic form of ketone 4a.
In the case of α-tetralone 3o when using sodium acetate, potassium carbonate, or pyridine as base a
difficultly identifiable mixture of polymeric compounds was obtained, and the use of sodium alcoholate or
sodium dimsyl leads to complete resinification of the mixture. However the use of LiOH, KOH, or NaOH
1
enabled compound 4o to be obtained in 25% yield. According to data of H NMR compound 4o exists as only
one diastereomer.
1
All signals in the H and 13C NMR spectra of compound 4o were unequivocally assigned using the
13C APT method and two-dimensional heteronuclear HSQC and HMBC procedures (Table 3).
1
The H and 13C NMR spectra were interpreted with the aid of HSQC and HMBC two-dimensional
procedures in deuterochloroform at 30°C (Bruker DRX 500).
TABLE 3. NMR spectra of Compound 4o
4"
3"
2"
O
1"
9
6
4'
7'
10
5
3'
3a'
7a'
8
7
5'
6'
1
11
4
2
3
2'
N
H 1'
Numbering
of atoms
Numbering
of atoms
13С, δ, ppm
1Н, δ, ppm
5.22
13С, δ, ppm
1Н, δ, ppm
1
2
40.9
52.4
1'
2'
—
121.6
117.8
127.0
119.7
119.3
122.1
111.0
135.8
140.7
129.2
128.2
126.3
8.05
7.26
—
3.45
2.30; 1.85
3.10
—
3
26.5
3'
4
28.3
3a'
4'
—
5
126.8
128.7
126.7
133.2
127.9
143.1
197.3
7.28
6.95
7.13
7.33
—
6
7.22
7.25
7.45
7.96
—
5'
7
6'
8
9
7'
7a'
1''
2''
3''
4''
10
11
—
—
7.36
7.24
7.16
734

Fig. 2. General form of the compound 4o molecule.
The configurations of the asymmetric carbon atoms in compound 4o were established on the basis of
X-ray structural analysis (Fig. 2). The main geometric parameters of compound 4b were close to the
corresponding parameters of the 4o molecule. The cyclohexane ring has a chair conformation with atom C(17)
emerging by 0.68 Å. The dihedral angle between the phenyl and indole fragments was unchanged and in the 4o
molecule was 95°. We note that apart from the molecular geometry the supramolecular organization also remains
unchanged. In compound 4o the molecules are connected by intermolecular hydrogen bonds N–H···O [N···O is
2.995(3) Å] in spirals which interweave with one another forming channels of a scarcely lesser diameter (4.34
Å).
TABLE 4. Main Crystallographic Parameters and Refinement
Characteristics for Compounds 4b and 4o
4b
4o
Formula
M
C20H19NO
308.28
110
C25H21NO
351.43
110
Т, K
Space group
a, Å
Fdd2
C2/c
29.272(7)
33.235(8)
6.368(1)
87.89(2)
6195(2)
2464
23.555(7)
6.971(1)
23.488(7)
108.79(2)
3651(1), 8
1488
b, Å
c, Å
β, °
V, Å3, Z
F(000)
ρ
calc, cm-3
1.241
1.279
2θmax, °
56
50
Number of reflections
measured (Rint)
independent
observed with I > 2σ(I)
10519 (0.0366)
3669
4389 (0.0686)
2895
2631
1209
R1
0.0485
0.1091
0.985
0.0815
0.1774
1.119
WR2
GOF
735

Attempts to obtain the second diastereomer by heating in 90% ethanol or isopropyl alcohol in the
presence of alkali gave no result. The reaction forming compound 4o is probably subject to kinetic control.
Compound 4g [14] was isolated as a mixture of two diastereomers with a predominance of the
(R*,R*)-isomer (de 90%). It is curious that compound 4c exists only in the enolic form. Compounds 4a,f,h,m,n
were isolated as mixtures of diastereomers, the content of each isomer was 50%.
On attempting to alkylate the benzyl ester of 3-oxobutyric acid 3i in 90% isopropyl alcohol we
unexpectedly isolated compound 3h, which may be the result of transesterification.
The method proposed by us enables the preparation of compounds 4 containing an indolylphenylmethyl
fragment in the position α to the carbonyl group with a known diastereomeric excess. In the Z/E case
predominantly (R*,S*)-diastereomers are formed. The introduction of planes of rigidity enables the Michael
reaction to be carried out with 100% de. In the Z/Z case predominantly (R*,R*)-diastereomers are formed.
EXPERIMENTAL
1
The H NMR spectra were obtained on a Bruker WP 200 (200 MHz) instrument in acetonitrile-d3
1
(4a,f,h, 5), deuterochloroform (4c), pyridine-d5 (4m), DMSO-d6 (4n), internal standard was TMS. The H and
13C NMR spectra of compounds 4b,o were recorded on a BRX 500 instrument (500 and 125 MHz respectively)
in deuterochloroform at 30°C. All experiments were conducted according to standard Bruker procedures. Two-
dimensional HSQC and HMBC spectra were obtained using the gradient method. The 13C spectra were recorded
in APT mode, number of accumulations 34000. Mass spectra were recorded on a Finnigan MAT SSQ 710
spectrometer at an energy of the ionizing radiation of 70eV. Analysis by TLC was carried out on Silufol UV 254
plates. The X-ray diffraction investigations were carried out on a Smart CCD diffractometer (MoKα radiation,
graphite monochromator, ω-scanning). The main crystallographic parameters and the refinement characteristics
are given in Table 4. Structures were solved by the direct method and refined by a full matrix least squares
method in an anisotropic approach according to F2. All calculations were carried out with the SHELXTL PLUS
set of programs Ver. 5.1.
α-Phenyl-nor-gramine (1). A 33% methylamine solution (150 g, 1.59 mol) was added to benzaldehyde
(106 g, 1 mol) during 20 min. Reaction occurs with a significant evolution of heat. To complete the reaction the
mixture was kept for 12 h at ~20°C. The mixture was then saturated with sodium chloride solution, and extracted
with ether. The ether extract was dried over MgSO4, and the ether distilled. The residue was then distilled.
Benzylidenemethylamine (83 g, 70%) was obtained; bp 183-185°C {bp 92-93°C (34 mm) [15]}.
A solution of indole (30 g, 0.26 mol) in benzylidenemethylamine (36 g, 0.30 mol) was heated at 70°C
for 40 h, then maintained at room temperature until crytallization was complete. The solid was filtered off. After
recrystallization from benzene a white crystalline substance was obtained, turning pink in the air. Yield 49 g
(65%); mp 139-141°C (mp 139-141°C [16]).
Preparation of Compounds 4 (General Procedure). A solution of potassium carbonate (0.1 g) in water
(1 ml) and CH-acid 3 (0.625 mmol) were added to a boiling solution of α-phenyl-nor-gramine 1 (1.0 g, 0.42
mmol) in 90% alcohol (10 ml). The mixture was boiled in a current of inert gas until disappearance of the
starting material (check by TLC on Silufol UV 254, ethyl acetate–CCl4, 1:4). The reaction mixture was cooled to
room temperature. Compounds 4a-c,f-h,o crystallized from aqueous alcohol, 4m-n from aqueous acetic acid.
2-[1H-Indol-3-yl(phenyl)methyl]cyclohexanone (4a). White crystals; mp 118-119°C (aqueous
1
2-propanol). H NMR spectrum, δ, ppm: 1.7-2.37 (8H, m, cyclohexane); 3.38-3.58 (1H, m, IndCHPhCH);
4.57-4.59 (1H, m, IndCHPh); 6.9-7.3 (9H, m, Ind and Ph); 7.18 (1H, m, H-2Ind); 9.09-9.15 (1H, br. s, NH). Mass
spectrum, m/z (Irel, %): 303 (11) [M]+, 206 (100) [IndCHPh]+. Found, %: C 83.43; H 7.04; N 4.32. C21H21NO.
Calculated, %: C 83.13; H 6.98; N 4.62.
736

2-[1H-Indol-3-yl(phenyl)methyl]cyclopentanone (4b) (R*,S*). White crystals; mp 182-184°C
(aqueous 2-propanol). 1H NMR spectrum, δ, ppm (J, Hz): 1.6-1.9 [6H, m, (CH2)3]; 3.02 (1H, m, CHCHPh); 4.72
(1H, d, J = 5.37, CHPh); 6.86 (1H, m, H-5Ind); 7.06 (1H, m, H-6Ind); 7.1-7.2 (6H, m, Ph and Ind); 7.29 (1H, d,
1
J = 2.19, H-2Ind); 7.36 (1H, m, H-7Ind); 10.77 (1H, s, NH). H NMR spectrum (C5D5N), δ, ppm (J, Hz): 1.5-2.2
[6H, m, (CH2)3]; 3.12 (1H, m, CHCHPh); 5.28 (1H, d, J = 3.97, CHPh); 7.05 (1H, m, H-5Ind); 7.25 (3H, m, HPh);
7.25 (1H, m, H-6Ind); 7.43 (2H, m, o-HPh); 7.48 (1H, m, H-4Ind); 7.55 (1H, m, H-7Ind); 7.62 (1H, dd, J = 2.45,
1
J = 0.6, H-2Ind); 11.97 (1H, s, NH). Characteristic signal for the (R*,R*)-isomer in the H NMR spectrum
(C5D5N), δ, ppm: 5.14 (1H, d, J = 3.97, CHPh). Mass spectrum, m/z (Irel, %): 289 (22) [M]+, 205 (100)
[IndCHPh]+. Found, %: C 83.2; H 6.73; N 4.41. C20H19NO. Calculated, %: C 83.01; H 6.62; N 4.84.
2-Hydroxy-3-[1H-indol-3-yl(phenyl)methyl]-2-cyclohexen-1-one (4c). White crystals; mp 121-123°C
1
(aqueous 2-propanol). H NMR spectrum, δ, ppm (J, Hz): 1.92-2.50 (6H, m, cyclohexane); 5.9 (1H, s,
IndCHPh); 6.32 (1H, s, OH); 6.86 (1H, d, J = 7.2, H-2Ind); 7.05 (1H, m, H-5Ind); 7.2-7.3 (7H, m, Ind and Ph);
7.37 (1H, m, H-4Ind); 7.57 (1H, m, H-7Ind); 8.08 (1H, br. s, NH). Mass spectrum, m/z (Irel, %): 317 (20) [M]+, 206
(100) [IndCHPh]+. Found, %: C 80.2; H 6.43; N 4.21. C21H19NO2. Calculated, %: C 79.47; H 6.03; N 4.41.
2-[1H-Indol-3-yl(phenyl)methyl]-3-oxobutyric Acid Methyl Ester (4f). White crystals;
mp 147-149°C (aqueous 2-propanol). 1H NMR spectrum, δ, ppm (J, Hz): 2.07-2.16 (3H, m, COCH3); 3.51-3.55
(3H, m, OCH3); 4.64-4.73 (1H, m, IndCHPhCH); 5.01-5.03 (1H, m, IndCHPh); 7.01 (1H, m, H-5Ind); 7.11 (1H,
m, H-6Ind); 7.17 (1H, m, p-HPh); 7.27 (2H, m, m-HPh); 7.29 (1H, m, H-2Ind); 7.37 (1H, m, H-7Ind); 7.42 (2H, m,
o-HPh); 7.57 (1H, m, H-4Ind); 9.02 (1H, br. s, NH). Mass spectrum, m/z (Irel, %): 321 (24) [M]+, 206 (100)
[IndCHPh]+. Found, %: C 74.95; H 6.07; N 4.26. C20H19NO3. Calculated, %: C 74.75; H 5.96; N 4.36.
2-[1H-Indol-3-yl(phenyl)methyl]-3-oxobutyric Acid Isopropyl Ester (4h). White crystals;
1
mp 111-119°C (aqueous 2-propanol). H NMR spectrum, δ, ppm (J, Hz): 0.94-1.11 [6H, m, (CH3)2]; 2.10-2.18
(3H, m, COCH3); 4.79 (1H, m, OCH); 4.58-4.68 (1H, m, IndCHPhCH); 4.99-5.01 (1H, m, IndCHPh); 7.00 (1H,
m, H-5Ind); 7.11 (1H, m, H-6Ind); 7.16 (1H, m, p-HPh); 7.27 (2H, m, m-HPh); 7.31 (1H, m, H-2Ind); 7.37 (1H, m,
H-7Ind); 7.43 (2H, m, o-HPh); 7.59 (1H, m, H-4Ind); 9.21 (1H, br. s, NH). Mass spectrum, (Irel, %): 349 (18) [M]+,
206 (100) [IndCHPh]+. Found, %: C 75.82; H 6.83; N 3.93. C22H23NO3. Calculated, %: C 75.62; H 6.63; N 4.01.
2-Cyano-3-(1H-indol-3-yl)-3-phenylpropionic Acid Methyl Ester (4m). White crystals;
1
mp 146-147°C (aqueous AcOH). H NMR spectrum, δ, ppm (J, Hz): 3.56 (3H, s, CH3); 5.25 (1H, d, J = 7.2,
CNCHCOCH3); 5.57 (1H, d, J = 7.2, IndCHPh); 7.1-7.7 (9H, m, Ind and Ph); 8.11 (1H, m, H-2Ind); 12.36 (1H,
br. s, NH). Mass spectrum, m/z (Irel, %): 304 (14) [M]+, 206 (90) [IndCHPh]+. Found, %: C 75.01; H 5.2; N 9.15.
C19H16N2O2. Calculated, %: C 74.98; H 5.3; N 9.2.
2-Cyano-3-(1H-indol-3-yl)-3-phenylpropionic Acid Ethyl Ester (4n). White crystals; mp 91-93°C
(aqueous AcOH). 1H NMR spectrum, δ, ppm (J, Hz): 0.97-1.00 (3H, m, CH2CH3); 4.02-4.05 (2H, m, CH2CH3);
4.92-4.95 (1H, m, CNCHCOEt); 5.00-5.09 (1H, m, IndCHPh); 7.1-7.8 (10H, m, Ind and Ph); 10.97 (1H, br. s,
NH). Mass spectrum m/z, (Irel, %): 318 (8) [M]+, 206 (90) [IndCHPh]+. Found, %: C 75.57; H 5.58; N 8.70.
C20H18N2O2. Calculated, %: C 75.45; H 5.70; N 8.80.
(2S*)-2-[(R*)-1H-Indol-3-yl(phenyl)methyl]-3,4-dihydro-1-(2H)-naphthalenone (4o). White crystals;
mp 138-139°C (aqueous 2-propanol). Mass spectrum m/z (Irel, %): 351 (17) [M]+, 206 (100) [IndCHPh]+.
Found, %: C 85.63; H 6.04; 3.87. C25H21NO. Calculated, %: C 85.44; H 6.02; N 3.99.
2-[1H-Indol-3-yl(phenyl)methyl]cyclopentanone Hydrazone (5). Compound 4b (0.303 g, 0.1 mmol)
and anhydrous hydrazine hydrate (0.64 g, 20 mmol) were mixed in alcohol (5 ml). The mixture was maintained
at room temperature until disappearance of the starting material (check by TLC on Silufol UV 254, ethyl
acetate–CCl4, 1:4). The reaction mixture was poured into water and the white crystals were filtered off;
1
mp 162-163°C (aqueous 2-propanol). H NMR spectrum, δ, ppm: 1.65-2.4 (6H, m, cyclopentyl); 3.35-3.6 (1H,
m, IndCHPhCH); 4.57-4.59 (1H, m, IndCHPh); 6.9-7.3 (9H, m, Ind and Ph); 7.2 (1H, m, H-2Ind); 9.1-9.18 (1H,
br. s, NH). Mass spectrum, m/z (Irel, %): 303 (25) [M]+, 206 (100) [IndCHPh]+. Found, %: C 80.03; H 7.04;
N 12.93. C20H21N3. Calculated, %: C 79.17; H 6.98; N 13.85.
737

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