Diastereoselective multicomponent synthesis of (4RS,6SR)-4,6-diaryl-5,5-dicyano-2-methyl-1,4,5,6-tetrahydropyridine-3-carboxylates

Article abstract of DOI:10.1007/s11172-018-2327-9

Multicomponent reaction of benzylidenemalononitrile, 2-acetyl-3-arylacrylates, and aqueous ammonia in alcohols at room temperature proceeds stereoselectively to give (4RS,6SR)-4,6-diaryl-5,5-dicyano-2-methyl-1,4,5,6-tetrahydropyridine-3-carboxylates in 55

Full text of DOI:10.1007/s11172-018-2327-9

Russian Chemical Bulletin, International Edition, Vol. 67, No. 11, pp. 2049—2053, November, 2018
2049
Diastereoselective multicomponent synthesis of
4RS,6SR)-4,6-diaryl-5,5-dicyano-2-methyl-1,4,5,6-tetrahydropyridine-3-
(
carboxylates*
A. N. Vereshchagin, K. A. Karpenko, T. M. Iliyasov, M. N. Elinson, E. O. Dorofeeva,
A. N. Fakhrutdinov, and M. P. Egorov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
4
7 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 6390. E-mail: vereshchagin@ioc.ac.ru
Multicomponent reaction of benzylidenemalononitrile, 2-acetyl-3-arylacrylates, and aque-
ous ammonia in alcohols at room temperature proceeds stereoselectively to give (4RS,6SR)-
4
,6-diaryl-5,5-dicyano-2-methyl-1,4,5,6-tetrahydropyridine-3-carboxylates in 55—87% yields.
In this reaction, ammonia acts as both the catalyst and the source of nitrogen for constructing
tetrahydropyridine cycle.
Key words: tetrahydropyridines, multicomponent reactions, stereoselectivity, benzyliden-
emalononitriles, 2-acetyl-3-arylacrylates.
2
5,26
and cyclohexanes27) and heterocyclic
(
(
cyclopropanes
Tetrahydropyridine and its analogs, such as 1,4-dihydro-
pyridine, piperidine, and pyridine, exhibit a wide range
2
8
29,30
31
pyrrolidines, spiro-pyrimidines,
chromenes,
3
2
1
—4
pyranopyridines, etc.), in the present work we describe
multicomponent synthesis of substituted tetrahydropyrid-
ines from alkylidenemalononitriles, 2-acetyl-3-aryl-
acrylates, and aqueous ammonia as a source of the nitrogen
atom for tetrahydropyridine cycle (Scheme 1, Table 1; for
clarity, in Scheme 1 only one enantiomer for each structure
is shown).
of biological and pharmacological activities.
Thus,
tetrahydropyridines are efficiently used for the treatment
of hypertension and stenocardia5,6 and are well known for
other types of pharmacological activities, e.g., neuro-
protection, noncompetitive inhibition of topoisomerase I,
7
—9
antitumor activity, and inhibition of HIV protease.
Tetrahydropyridine and its analogs are valuable building
blocks for construction of different fused polycyclic
1
0,11
12—14
systems
and nitrogen heterocycles.
Tetrahydro-
Scheme 1
pyridines are commonly synthesized from imines, the
nitrogen atom of which serves as a source of nitrogen for
the newly forming tetrahydropyridine cycle. Syntheses of
tetrahydropyridines by aza-Diels—Alder1
5,16
reactions
(
both aza-dienophiles and aza-dienes can be employed)
1
7,18
and domino addition—cyclization reactions
involving
imines were also described. The reactions of the last type
are multicomponent ones. Over the years, the multi-
component synthesis is recognized as a versatile tool of
the organic chemistry.19 Several publications were devoted
to multicomponent synthesis of 4-aminotetrahydropyrid-
ines from aromatic amines, CH acids, and aromatic
aldehydes.2
0,21
Recently, we have synthesized substituted
piperidines using ammonium acetate as the source of
nitrogen for the piperidine cycle.2
2—24
In continuation of
i. MeOH, ~20 °C.
our research on the application of electron-deficient olefins
as the building blocks in the synthesis of various cyclic
Compound
Ar
R
Compound
1—3
e
f
Ar
R
1
a
b
c
d
—3
Ph
4-MeC H
4-MeOC H
Me
Et
Me
Me
2-ClC H
4-ClC H
4-BrC H
Me
Me
Me
Me
6
4
4
6
4
6
*
Dedicated to Academician of the Russian Academy of Sciences
g
h
6
4
6 4
B. A. Trofimov on the occasion of his 80th birthday.
4-FC H
4- O NC H
2 6 4
6
4
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2049—2053, November, 2018.
066-5285/18/6711-2049 © 2018 Springer Science+Business Media, Inc.
1

2
050 Russ. Chem. Bull., Int. Ed., Vol. 67, No. 11, November, 2018
Table 1. Multicomponent synthesis of (4RS,6SR)-4,6-diaryl-
Vereshchagin et al.
5
,5-dicyano-2-methyl-1,4,5,6-tetrahydropyridine-3-carb-
oxylates 3a—h from benzylidenemalononitriles 1a—h, 2-ace-
tyl-3-arylacrylates 2a—h, and aqueous ammoniaa
Entry
Reactants
t/h
Product
Yield (%)b
Fig. 1. Proton correlation in NOESY NMR spectrum of com-
pound 3a.
1
2
3
4
5
6
7
8
1a + 2a
1b + 2b
1c + 2c
1d + 2d
1e + 2e
1f + 2f
4
8
3a
3b
3c
3d
3e
3f
79
70
66
78
73
72
87
55
12
4
addition of anion A to 2-acetyl-3-arylacrylate 2 gives
anion B. Subsequent intramolecular cyclization dictated by
steric reasons gives the unstable intermediate (4RS,6SR)-
4
4
1g + 2g
1h + 2h
4
3g
3h
2
-hydroxypiperidine C. Decomposition of intermediate C
2
results in the final product 3.
a
Reaction conditions: compound 1 (3 mmol), compound 2
3 mmol), ammonia (6 mmol, 25% aqueous solution), MeOH
5 mL), stirring, room temperature. TLC-monitoring of the
(
(
Scheme 2
reaction progress (TLC plates were developed with hexane—
ethyl acetate, 5 : 1).
b
Isolated yields.
The reaction of benzylidenemalononitrile 1a, methyl
-acetyl-3-phenylacrylate 2a, and ammonium acetate in
2
refluxing MeOH for 2 h (optimal reaction conditions for
the synthesis of 2,6-diphenyl-3,3,5,5-tetracyanopiperidine
from benzylidenemalononitrile, paraformaldehyde, and
2
2
NH OAc ) proceeds with very low conversion of the
4
starting olefins and gives only trace amounts of the target
tetrahydropyridine 3a.
3
3
Recently, we published multicomponent synthesis
of piperidines that employed ammonia. The replacement
of ammonium acetate with 25% aqueous ammonia dra-
matically changed the reaction outcome. Thus, significant
conversion of the starting olefins and formation of product
3
a were observed after stirring compounds 1a, 2a, and
ammonia in MeOH at room temperature for 2 h. After 4 h
stirring, complete conversion of compounds 1a and 2a was
achieved and the yield of tetrahydropyridine 3a reached
7
9%. Tetrahydropyridines 3b—h were synthesized under
In summary, we succeeded in synthesizing (4RS,6SR)-
4,6-diaryl-5,5-dicyano-2-methyl-1,4,5,6-tetrahydropyr-
idine-3-carboxylates in 55—87% yields by the multicom-
ponent reaction between benzylidenemalononitrile,
2-acetyl-3-arylacrylates bearing both electron-withdraw-
ing and electron-donating substituents at the aromatic
ring, and aqueous ammonia. The reaction is simple, easy
to perform, and clean; the products can be isolated pure
by filtration.
similar conditions (see Table 1). It is of note that the reac-
tions with the substrates bearing electron-withdrawing
groups at the aromatic ring proceed faster (2—4 h, en-
tries 1, 4—8) than the reactions involving substrates with
electron-donating substituents (8 and 12 h, entries 2 and
3
, respectively).
All the recorded H and 13C NMR spectra of com-
1
pounds 3 show one set of the signals evidencing the forma-
tion of only one diastereomer. The NOESY NMR ex-
periment revealed the dipolar coupling between the 4- and
Experimental
6
-protons thus unambiguously indicating the 4RS,6SR
configuration (Fig. 1).
1H and 13C NMR spectra were run on a Bruker AM-300
instrument with working frequencies of 300.13 and 75.47 MHz,
respectively. Mass spectrometry was performed with a Finningan
MAT INCOS 50 instrument. IR spectra were recorded with
a Specord M82 FTIR spectrometer in KBr pellets using Soft
A plausible mechanism of the reaction is given in
Scheme 2. Ammonia acting as both the nitrogen source
and the base adds to benzylidenemalononitrile 1 via the
aza-Michael addition mechanism. Further nucleophilic

Polyfunctional tetrahydropyridines
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 11, November, 2018
2051
Spectra software. Melting points were measured with a Gallen-
kamp apparatus.
(s, 3 H, OCH ); 3.79 (s, 3 H, OCH ); 4.73 (s, 1 H, CH); 5.17
3 3
(s, 1 H, CH); 6.92 (d, 2 H, Ar, J = 8.8 Hz); 7.07 (d, 2 H, Ar,
J = 8.8 Hz); 7.21 (d, 2 H, Ar, J = 8.8 Hz); 7.40 (s, 1 H, NH);
Compounds 1 and 2 were synthesized by Knoevenagel con-
densation of aromatic aldehydes with malononitrile and ethyl
1
3
7.54 (d, 2 H, Ar, J = 8.8 Hz). C NMR (DMSO-d ), δ: 19.0
6
3
4
acetoacetate, respectively, using AcONa as a catalyst. Thin
layer chromatography was carried out with Merck precoated plates
(s, CH ); 40.4 (s, C(CN) ); 45.9 (s, CH); 48.4 (s, OCH ); 55.0
3 2 3
(s, OCH ); 55.2 (s, OCH ); 55.3 (s, OCH ); 59.0 (s, CH—N);
3
3
3
DC-Alufolien Kieselgel 60 F254
.
94.6 (s, C(CO Me)); 113.1 (s, CN); 113.5 (s, 2 C, Ar); 113.6
2
Multicomponent synthesis of (4RS,6SR)-4,6-diaryl-5,5-
(s, 2 C, Ar); 114.0 (s, CN); 128.6 (s, 1 C, Ar); 128.6 (s, 1 C, Ar);
dicyano-2-methyl-1,4,5,6-tetrahydropyridine-3-carboxylates 3
129.8 (s, 2 C, Ar); 130.8 (s, 2 C, Ar); 153.5 (s, C(CH )); 158.8
3
–
1
(
general procedure). A mixture of benzylidenemalononitrile 1
(s, C=O); 160.4 (s, 1 C, Ar); 166.5 (s, 1 C, Ar). IR (KBr), ν/cm :
(
mmol), 2-acetyl-3-arylacrylate 2 (3 mmol), 25% aqueous am-
3387 (N—H), 3063 (C—H, Ar), 2937 (C—H, Ar), 2253 (C≡N),
1445 (C—H), 1432 (C=C), 1130 (C—N). MS (EI, 70 eV), m/z
monia (0.45 mL, 6 mmol), and MeOH (5 mL) was stirred for
the time specified in Table 1. The reaction progress was monitored
by TLC (development with hexane—ethyl acetate, 5 : 1). After
the reaction completion, the mixture was maintained at –10 °C
for 30 min for the complete precipitation of the product, the
precipitate was collected by filtration and dried to give pure
tetrahydropyridine 3.
+
+
(Irel (%)): 417 [M] (39), 232 [M – C H N O – H] (100), 184
11
8
2
+
+
[M – C H NO ] (18), 134 [M – C H NO – 2 CN] (43).
13
15
3
13 15
3
Found (%): C, 69.03; H, 5.56; N, 10.06. C H N O . Calculat-
2
4
23
3
4
ed (%): C, 69.05; H, 5.55; N, 10.07.
Methyl (4RS,6SR)-5,5-dicyano-4,6-bis(4-fluorophenyl)-2-
methyl-1,4,5,6-tetrahydropyridine-3-carboxylate (3d). Yield 0.92 g
1
Methyl (4RS,6SR)-5,5-dicyano-2-methyl-4,6-diphenyl-1,4,5,6-
tetrahydropyridine-3-carboxylate (3a). Yield 0.84 g (79%), white
(78%), white powder, m.p. 210—211 °C. H NMR (DMSO-d ),
6
δ: 2.34 (s, 3 H, CH ); 3.18 (s, 3 H, OCH ); 4.87 (s, 1 H, CH);
3
3
1
powder, m.p. 218—219 °C. H NMR (DMSO-d ), δ: 2.32 (s, 3 H,
5.33 (s, 1 H, CH); 7.25 (t, 2 H, Ar, J = 8.8 Hz); 7.33—7.45
6
1
CH ); 3.11 (s, 3 H, OCH ); 4.83 (s, 1 H, CH); 5.27 (s, 1 H, CH);
(m, 4 H, Ar); 7.62 (s, 1 H, NH); 7.69 (dd, 2 H, Ar, J = 8.9 Hz,
3
3
1
2
13
7
.28—7.34 (m, 5 H, Ar + NH); 7.52 (dd, 4 H, Ar, J = 5.9 Hz,
J = 5.7 Hz). C NMR (DMSO-d ), δ: 19.2 (s, CH ); 47.9
6 3
2
13
J = 1.6 Hz); 7.63 (m, 2 H, Ar). C NMR (DMSO-d ), δ: 19.0
(s, C(CN) ); 48.2 (s, CH); 49.9 (s, OCH ); 58.7 (s, CH—N);
2 3
6
(
(
s, CH ); 47.8 (s, C(CN) ); 49.1 (s, CH); 49.7 (s, OCH ); 59.5
94.3 (s, C(CO Me)); 112.8 (s, CN); 113.9 (s, CN); 115.2 (d, 2 C,
3
2
3
2
2
2
s, CH—N); 94.4 (s, C(CO Me)); 112.8 (s, CN); 114.0 (s, CN);
Ar, J
= 22.1 Hz); 115.7 (d, 2 C, Ar, J
= 22.1 Hz); 130.5
C—F
= 245.5 Hz); 163.0
2
C—F
C—F
3
4
1
27.5 (s, 1 C, Ar); 127.9 (s, 2 C, Ar); 128.2 (s, 2 C, Ar); 128.4
s, 2 C, Ar); 128.6 (s, 2 C, Ar); 129.9 (s, 1 C, Ar); 134.3 (s, 1 C, Ar);
39.1 (s, 1 C, Ar); 153.9 (s, C(CH )); 166.3 (s, CO Me). IR
(d, 4 C, Ar, J
= 8.8 Hz); 135.2 (d, 2 C, Ar, J
= 3.3 Hz);
C—F
1
(
154.1 (s, C(CH )); 161.7 (d, 1 C, Ar, J
(d, 1 C, Ar, J
3
C—F
1
1
= 245.5 Hz); 166.2 (s, CO Me). IR (KBr),
3
2
C—F 2
–
1
–1
(
KBr), ν/cm : 3387 (N—H), 3063 (C—H, Ar), 2839 (C—H,
ν/cm : 3351 (N—H), 3004 (C—H, Ar), 2844 (C—H, Ar), 2251
Ar), 2253 (C≡N), 1645 (C—H), 1431 (C=C), 1142 (C—N). MS
(C≡N), 1507 (C—H), 1435 (C=C), 1249 (C—F), 1118 (C—N).
+
+
+
+
+
(
(
EI, 70 eV), m/z (Irel (%)): 357 [M] (78), 298 [M – CO Me]
MS (EI, 70 eV), m/z (Irel (%)): 393 [M] (66), 334 [M – CO Me]
2
2
40), 202 [M – 2 Ph – H]+ (100), 154 [M – C H NO ] (15),
+
(19), 220 [M – C H FN – H] (100), 172 [M – C H FNO ]
+
12
13
2
10
5
2
12 12
2
+
+
1
27 [M – C H NO – CN – H] (43), 103 [M – C H NO –
(20), 145 [M – C H FNO – CN – H] (17). Found (%):
12
13
2
12 13
2
12 12 2
+
–
2 CN] (41). Found (%): C, 73.91; H, 5.37; N, 11.73.
67.15; H, 4.37; F, 9.66; N, 10.68. C H F N O . Calculated (%):
22 17 2 3 2
C22H N O . Calculated (%): C, 73.93; H, 5.36; N, 11.76.
C, 67.17; H, 4.36; F, 9.66; N, 10.68.
19
3
2
Ethyl (4RS,6SR)-5,5-dicyano-2-methyl-4,6-bis(4-methyl-
Methyl (4RS,6SR)-4,6-bis(2-chlorophenyl)-5,5-dicyano-2-
phenyl)-1,4,5,6-tetrahydropyridine-3-carboxylate (3b). Yield
methyl-1,4,5,6-tetrahydropyridine-3-carboxylate (3e). Yield 0.93 g
1
1
0
.83 g (70%), white powder, m.p. 224—225 °C. H NMR
(73%), white powder, m.p. 230—231 °C. H NMR (CDCl ), δ:
3
(
DMSO-d ), δ: 0.59 (t, 3 H, CH , J = 7.3 Hz); 2.31 (s, 6 H,
2.48 (s, 3 H, CH ); 3.47 (s, 3 H, OCH ); 5.34 (s, 1 H, CH); 5.38
6
3
3
3
1
2
CH ); 2.37 (s, 3 H, CH ); 3.64 (qd, 2 H, OCH , J = 12.2 Hz,
(s, 1 H, CH); 7.36—7.52 (m, 3 H, Ar); 7.53—7.73 (m, 5 H,
3
3
2
2
1
13
J = 6.6 Hz); 4.76 (s, 1 H, CH); 5.21 (s, 1 H, CH); 7.20 (dd, 4 H,
Ar + NH); 7.84 (d, 1 H, Ar, J = 7.3 Hz); 8.06 (s, 1 H, Ar).
C
1
2
Ar, J = 8.8 Hz, J = 2.2 Hz); 7.33 (d, 2 H, Ar, J = 8.1 Hz); 7.42
NMR (CDCl ), δ: 20.1 (s, CH ); 44.8 (s, C(CN) ); 45.7 (s, CH);
50.6 (s, CH—N); 57.3 (s, OCH ); 98.3 (s, C(CO Me)); 112.0
3
3
2
13
(
s, 1 H, NH); 7.52 (d, 2 H, Ar, J = 8.1 Hz). C NMR (DMSO-d ),
6
3 2
δ: 13.4 (s, CH ); 18.9 (s, CH ); 20.6 (s, CH ); 20.8 (s, CH );
(s, CN); 112.4 (s, CN); 127.1 (s, 1 C, Ar); 128.0 (s, 2 C, Ar); 128.1
(s, 1 C, Ar); 129.5 (s, 1 C, Ar); 129.9 (s, 1 C, Ar); 130.6 (s, 1 C,
Ar); 131.0 (s, 1 C, Ar); 131.7 (s, 1 C, Ar); 134.9 (s, 1 C, Ar); 135.0
3
3
3
3
4
9
8.0 (s, C(CN) ); 48.9 (s, CH); 58.1 (s, CH—N); 59.3 (s, OCH );
2
2
4.5 (s, C(CO Me)); 113.0 (s, CN); 114.1 (s, CN); 128.2 (s, 2 C,
2
Ar); 128.6 (s, 2 C, Ar); 129.1 (s, 2 C, Ar); 129.6 (s, 2 C, Ar); 131.4
s, 1 C, Ar); 136.2 (s, 1 C, Ar); 137.0 (s, 1 C, Ar); 139.5 (s, 1 C,
Ar); 153.6 (s, C(CH )); 165.8 (s, C=O (CO Et)). IR (KBr),
(s, 1 C, Ar); 135.3 (s, 1 C, Ar); 152.8 (s, C(CH )); 166.3
3
–
1
(
(s, CO Me). IR (KBr), ν/cm : 3410 (N—H), 3065 (C—H, Ar),
2
2833 (C—H, Ar), 2250 (C≡N), 1476 (C—H), 1436 (C=C), 1155
3
2
–
1
+
ν/cm : 3366 (N—H), 3097 (C—H, Ar), 2902 (C—H, Ar), 2263
(C—N), 745 (C—Cl). MS (EI, 70 eV), m/z (I (%)): 425 [M]
rel
+
+
(
C≡N), 1458 (C—H), 1372 (C=C), 1120 (C—N). MS (EI, 70 eV),
(71), 390 [M – Cl] (76), 366 [M – CO Me] (100), 236
2
+
+
+
+
m/z (Irel (%)): 399 [M] (28), 298 [M – CO Et] (28), 230
[M – C H ClN – H] (73), 202 [M – 2 (2-Cl)C H – H]
2
10 5 2 6 4
+
+
+
[
1
M – C H N – H] (100), 202 [M – 2 (4-Me)C H – CH ] (32),
(53),188 [M – C H ClNO ] (14). Found (%): C, 61.97;
12 12 2
1
1
8
2
6
4
3
+
58 [M – C H NO ] (18). Found (%): C, 75.14; H, 6.32;
H, 4.03; Cl, 16.63; N, 9.86. C22H Cl N O . Calculated (%):
14
17
2
17
2
3
2
N, 10.50. C25H N O . Calculated (%): C, 75.16; H, 6.31;
C, 61.99; H, 4.02; Cl, 16.63; N, 9.86.
15
3
2
N, 10.52.
Methyl (4RS,6SR)-4,6-bis(4-chlorophenyl)-5,5-dicyano-2-
Methyl (4RS,6SR)-5,5-dicyano-4,6-bis(4-methoxyphenyl)-
-methyl-1,4,5,6-tetrahydropyridine-3-carboxylate (3c). Yield
methyl-1,4,5,6-tetrahydropyridine-3-carboxylate (3f). Yield 0.92 g
1
7
0
(
(72%), white powder, m.p. 181—182 °C. H NMR (CDCl ), δ:
3
1
.82 g (66%), white powder, m.p. 155—156 °C. H NMR
2.34 (s, 3 H, CH ); 3.19 (s, 3 H, OCH ); 4.87 (s, 1 H, CH); 5.32
(s, 1 H, CH); 7.34 (d, 2 H, Ar, J = 7.7 Hz); 7.49 (d, 2 H, Ar,
3
3
DMSO-d ), δ: 2.29 (s, 3 H, CH ); 3.14 (s, 3 H, OCH ); 3.75
6
3
3

2
052 Russ. Chem. Bull., Int. Ed., Vol. 67, No. 11, November, 2018
Vereshchagin et al.
J = 7.7 Hz); 7.65 (s, 4 H, Ar + NH). 13C NMR (CDCl ), δ: 19.2
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3
(
(
s, CH ); 47.5 (s, C(CN) ); 48.2 (s, CH); 50.0 (s, CH—N); 58.7
3 2
s, OCH ); 94.0 (s, C(CO Me)); 112.6 (s, CN); 113.7 (s, CN);
3
2
1
28.4 (s, 2 C, Ar); 128.8 (s, 4 C, Ar); 130.2 (s, 2 C, Ar); 132.5
(
1
s, 1 C, Ar); 133.1 (s, 1 C, Ar); 134.8 (s, 1 C, Ar); 138.1 (s, 1 C, Ar);
–
1
54.4 (s, C(CH )); 166.1 (s, CO Me). IR (KBr), ν/cm : 3403
3 2
(
(
N—H), 3068 (C—H, Ar), 2991 (C—H, Ar), 2253 (C≡N), 1623
C—H), 1433 (C=C), 1126 (C—N), 836 (C—Cl). MS (EI, 70
+
+
eV), m/z (Irel (%)): 425 [M] (62), 366 [M – CO Me] (18), 236
2
+
+
[
M – C H ClN – H] (44), 188 [M – C H ClNO ] (12),
10 5 2 12 12 2
+
1
38 [M – C H ClNO – 2 CN] (95). Found (%): C, 61.96;
12
12
2
H, 4.03; Cl, 16.62; N, 9.86. C22H Cl N O . Calculated (%):
17
2
3
2
C, 61.99; H, 4.02; Cl, 16.63; N, 9.86.
Methyl (4RS,6SR)-4,6-bis(4-bromophenyl)-5,5-dicyano-2-
methyl-1,4,5,6-tetrahydropyridine-3-carboxylate (3g). Yield 1.34 g
1
(
87%), white powder, m.p. 197—198 °C. H NMR (DMSO-d ),
6
δ: 2.34 (s, 3 H, CH ); 3.19 (s, 3 H, OCH ); 4.85 (s, 1 H, CH);
3
3
5
.31 (s, 1 H, CH); 7.27 (d, 2 H, Ar, J = 8.5 Hz); 7.60 (dd, 4 H,
1
2
Ar, J = 8.5 Hz, J = 2.9 Hz); 7.66 (s, 1 H, NH); 7.79 (d, 2 H,
Ar, J = 8.5 Hz). 13C NMR (DMSO-d ), δ: 20.4 (s, CH );
6
3
4
7.7 (s, C(CN) ); 50.4 (s, CH); 50.8 (s, CH—N); 61.2 (s,
2
OCH ); 97.4 (s, C(CO Me)); 111.6 (s, CN); 113.4 (s, CN); 122.6
3
2
(
s, 1 C, Ar); 125.3 (s, 1 C, Ar); 129.5 (s, 4 C, Ar); 131.9 (s, 2 C,
Ar); 132.1 (s, 1 C, Ar); 132.7 (s, 2 C, Ar); 136.8 (s, 1 C, Ar);
–
1
1
(
(
7
2
(
52.4 (s, C(CH )); 166.5 (s, CO Me). IR (KBr), ν/cm : 3408
3 2
N—H), 3063 (C—H, Ar), 2842 (C—H, Ar), 2250 (C≡N), 1461
C—H), 1316 (C=C), 1130 (C—N), 679 (C—Br). MS (EI,
+
+
0 eV), m/z (Irel (%)): 515 [M] (6), 456 [M – CO Me] (4),
2
+
+
80 [M –C H BrN – H] (35), 153 [M – C H BrNO – Br]
10
5
2
12 12
2
31). Found (%): C, 51.27; H, 3.34; Br, 31.02; N, 8.15.
C22H Br N O . Calculated (%): C, 51.29; H, 3.33; Br, 31.02;
17
2
3
2
N, 8.16.
Methyl (4RS,6SR)-5,5-dicyano-2-methyl-4,6-bis(4-nitro-
phenyl)-1,4,5,6-tetrahydropyridine-3-carboxylate (3h). Yield
0
.73 g (55%), white powder, m.p. 250—251 °C. 13C NMR
(
(
DMSO-d ), δ: 2.40 (s, 3 H, CH ); 3.19 (s, 3 H, OCH ); 5.10
6 3 3
s, 1 H, CH); 5.55 (s, 1 H, CH); 7.61 (d, 2 H, Ar, J = 8.8 Hz);
7
.02 (d, 3 H, Ar + NH, J = 8.8 Hz); 8.31 (s, 2 H, Ar, J = 8.8 Hz);
13
8
.46 (d, 2 H, Ar, J = 8.8 Hz). C NMR (DMSO-d ), δ: 19.4
6
(
(
s, CH ); 46.5 (s, C(CN) ); 48.2 (s, CH); 50.0 (s, CH—N); 58.6
3
2
s, OCH ); 93.6 (s, C(CO Me)); 112.2 (s, CN); 113.2 (s, CN);
3
2
1
23.6 (s, 2 C, Ar); 123.8 (s, 4 C, Ar); 130.0 (s, 2 C, Ar); 140.7
(
s, 1 C, Ar); 146.7 (s, 1 C, Ar); 147.3 (s, 1 C, Ar); 148.7 (s, 1 C,
–
1
Ar); 155.1 (s, C(CH )); 165.8 (s, CO Me). IR (KBr), ν/cm
:
3
2
3
362 (N—H), 3087 (C—H, Ar), 2852 (C—H, Ar), 2253 (C≡N),
1
7
3
553 (C—H), 1438 (C=C), 1348 (N—O), 1125 (C—N). MS (EI,
+
+
0 eV), m/z (Irel (%)): 447 [M] (100), 416 [M – OMe] (60),
+
+
88 [M – CO Me] (100), 247 [M – C H N O – H] (44).
2
10
5
3
2
Found (%): C, 59.04; H, 3.84; N, 15.65. C22H N O . Calculat-
17
5
6
ed (%): C, 59.06; H, 3.83; N, 15.65.
This work was financially supported by the Russian
Science Foundation (Project No. 17-73-20260).
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Received August 1, 2018;
in revised form October 10, 2018;
accepted October 11, 2018