Multicomponent reaction of conjugated enynones with malononitrile and sodium alkoxides: Complex reaction mechanism of the formation of pyridine derivatives

Article abstract of DOI:10.1016/j.tet.2019.06.041

Reaction of conjugated enynones,1,5-diarylpent-2-en-4-yn-1-ones, with malononitrile and sodium alkoxides in the corresponding alcohols at room temperature for 3–23 h results in the formation of two types of compounds (E)-/(Z)-6-aryl-4-(2-arylethenyl)-2-alkoxypyridine-3-carbonitriles (substituted nicotinonitriles), as the major reaction products in yields up to ca. 40–80%, and 6-aryl-4-arylethynyl-2-alkoxypyridines, as the minor reaction products in yields of 5–17%. Plausible mechanism of this complex and multistep reaction is discussed. The obtained pyridines possess fluorescent properties.

Full text of DOI:10.1016/j.tet.2019.06.041

Accepted Manuscript
Multicomponent reaction of conjugated enynones with malononitrile and sodium
alkoxides: Complex reaction mechanism of the formation of pyridine derivatives
Anastasiya V. Kuznetcova, Ivan S. Odin, Alexander A. Golovanov, Iakov M. Grigorev,
Aleksander V. Vasilyev
PII:
S0040-4020(19)30713-6
https://doi.org/10.1016/j.tet.2019.06.041
TET 30433
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 7 May 2019
Revised Date: 21 June 2019
Accepted Date: 25 June 2019
Please cite this article as: Kuznetcova AV, Odin IS, Golovanov AA, Grigorev IM, Vasilyev AV,
Multicomponent reaction of conjugated enynones with malononitrile and sodium alkoxides: Complex
reaction mechanism of the formation of pyridine derivatives, Tetrahedron (2019), doi: https://
doi.org/10.1016/j.tet.2019.06.041.
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ACCEPTED MANUSCRIPT
Multicomponent reaction of conjugated enynones with malononitrile and
sodium alkoxides: complex reaction mechanism of the formation of pyridine
derivatives
Anastasiya V. Kuznetcova,a Ivan S. Odin,b Alexander A. Golovanov,c Iakov M. Grigorev,d
Aleksander V. Vasilyev*a,e
aDepartment of Organic Chemistry, Institute of Chemistry, Saint Petersburg State University,
Universitetskaya nab., 7/9, Saint Petersburg, 199034, Russia.
bResearch Laboratory No. 13 of Organic Synthesis and Analysis of them. S.P. Korshunov, Togliatti
State University, Belorusskaya ul., 14, Togliatti, 445667, Russia.
cDepartment of Chemistry, Chemical Processes and Technologies, Togliatti State University,
Belorusskaya ul., 14, Togliatti, 445667, Russia.
dEducational Research Center of Chemistry of Research Park of Saint Petersburg State University,
Universitetskiy pr., 26, Saint Petersburg, Petrodvoretz, 198504 , Russia
eDepartment of Chemistry, Saint Petersburg State Forest Technical University, Institutsky per., 5,
Saint Petersburg, 194021, Russia
*Corresponding author: A.V. Vasilyev; e-mails: aleksvasil@mail.ru; a.vasilyev@spbu.ru
Keywords: conjugated enynones; pyridines; nicotinonitriles; reaction mechanism, fluorescence
Graphical abstract
Ar1
Ar1
E-/Z-
O
CH2(CN)2,
RONa, ROH
CN
OR
Ar2
+
r. t., 3-23 h
Ar1
Ar2
N
Ar2
N
OR
5-17%
fluorescent substances
17 examples
up to 82%
Abstract
Reaction of conjugated enynones,1,5-diarylpent-2-en-4-yn-1-ones, with malononitrile and sodium
alkoxides in the corresponding alcohols at room temperature for 3-23 h results in the formation of
two types of compounds (E)-/(Z)-6-aryl-4-(2-arylethenyl)-2-alkoxypyridine-3-carbonitriles
(substituted nicotinonitriles), as the major reaction products in yields up to ca. 40-80%, and 6-aryl-
4-arylethynyl-2-alkoxypyridines, as the minor reaction products in yields of 5-17%. Plausible
mechanism of this complex and multistep reaction is discussed. The obtained pyridines possess
fluorescent properties.
1

ACCEPTED MANUSCRIPT
Introduction
Conjugated enynones, pent-2-en-4-yn-1-ones, represent an important class of multifunctional
organic compounds due to the presence of three important functional groups in their structures:
double and triple carbon-carbon bonds, and carbonyl group. Chemistry of these compounds has
been recently reviewed [1]. The conjugated enynone system is a versatile building block for
synthesis of various substances. Reactivity of unsaturated carbon-carbon bonds towards
nucleophilic reagents in these compounds is enhanced by the conjugation with electron
withdrawing carbonyl group. Thus, reactions of conjugated enynones with N- and S-nucleophiles
proceed very easily, forming products of addition to both double or triple carbon-carbon bonds,
depending on reaction conditions [2-5]. There are many examples of preparation of heterocycles by
reactions of enynones under nucleophilic conditions, namely, furans [6-15], aziridines (followed by
their conversion into pyrroles) [16], pyrazols [17,18], triazoles [18], and pyridines [19]. Apart from
that, these conjugated enynones may be transformed into various indane derivatives under
supereletrophilic activation conditions [20,21].
In 1989, a study on the synthesis of 3-cyanopyridines (nicotinonitriles) by the reaction of 1,3-
diarylprop-2-en-1-ones (chalcones) with malononitrile and sodium alkoxides in alcohols was
reported (Scheme 1) [22]. It should be mentioned that such nicotinonitriles have been obtained even
earlier in 1922 [23]. Thereafter, this reaction [24-26] and similar transformations [27-29] were
used to obtain various nicotinonitriles. It should be specially emphasized that substituted
nicotinonitriles have been used in agriculture as antidotes and plant growth regulators [30].
Furthermore, nicotinonitriles possess cytotoxity to cancer cell line [31], and antioxidant [32],
antiviral [33] and antibacterial [34, 35] activities. Many nicotinonitriles are characterized by a
complex of valuable photophysical [36] and photochemical [37] properties. Due to that,
nicotinonitriles are promising as liquid crystals [24], fluorescent [26, 38-40] and nonlinear optical
materials [36]. Thus, the synthesis of these very important compounds is an actual goal of organic
chemistry.
Ar1
CH2(CN)2,
RONa, ROH
O
CN
Ar1
Ar2
Ar2
N
OR
Scheme 1. The reaction of chalcones with malononitrile and sodium alkoxides in alcohols leading
to substituted pyridines (nicotinonitriles) (data from ref. [22]).
2

ACCEPTED MANUSCRIPT
Based on our studies on the chemistry of conjugated enynones [1], and data from the prior
work [22], we undertook a special investigation on transformations of 1,5-diarylpent-2-en-4-yn-1-
ones (see starting enynones in Figure 1) in multicomponent reaction with malononitrile and sodium
alkoxides. The main goals of this study were to find out a regioselectivity of this reaction, which
carbon-carbon bond, double or triple one, takes part in an interaction with nucleophilic species, and
to propose a plausible mechanism for this complex reaction.
O
R1 = R2 = H (a); R1 = H, R2 = Me (b);
R1 = H, R2 = Cl (c); R1 = H, R2 = OMe (d);
R1
R1 = Me, R2 = H (e); R1 = Cl, R2 = H (f);
R1 = OMe, R2 = H (g); R1 = Me, R2 = Cl (h);
R1 = Me, R2 = Br (i); R1 = H, R2 = NO2 (j)
1a-j
R2
Figure 1. Starting 1,5-diarylpent-2-en-4-yn-1-ones used in this study.
Results and discussion
The multicomponent reaction of malononitrile and alkoxides with enynones 1a-j was found to
be much more complicated than the same reaction of chalcones [22-26] (see Scheme 1).
Transformations of enynones 1a-j with malononitrile and sodium alkoxides in the corresponding
alcohols gave mixtures of two types of the reaction products, (E)-/(Z)-isomers of 4-arylethenyl
(styryl) pyridines 2 and 4-arylethynyl (arylacetylene) pyridines 3 (Table 1). Both of the reaction
products 2 and 3 contain an alkoxy group in the position 2 of the pyridine system. Pyridines 2 bear
3-cyano group, however, pyridines 3 do not contain this substituent, which is contrary to data from
the prior work [22] (see Scheme 1). Compounds (E)-/(Z)-2 (yields of 15-82 %) are the major
reaction products, the E- : Z- ratios for them is roughly 1 : 1, with rare exceptions (see Table 1).
Compounds 3 (yields of 5-17%) are the minor reaction products. Structures of pyridines E-2a, Z-2c,
3c and 3p were additionally confirmed by X-ray data (see Table 1). It should be specially noted that
such 6-aryl-4-arylethynyl-2-alkoxypyridines 3 have been obtained for the first time, previously they
were unknown compounds
Various sodium alkoxides may be involved in this reaction. Apart from methoxide, the use of
other sodium alkoxides, generated from ethanol (entries 4, 8, 11, 13, 18), propan-1-ol (entry 5), and
butan-1-ol (entry 6), resulted in the formation of the corresponding 2-alkoxysubstituted pyridines 2
and 3. However, when using alcohols, other than methanol, the combined yields of compounds 2
and 3 were decreased. It was found that electron-donating substituents in aromatic ring at the
carbonyl groups of enynones 1b,d led to the increase of yields of reaction products (entries 7, 8, 10,
11). On the other hand, enynone 1j beraing acceptor nitro group gave rise a complex mixture of
reaction products (entry 19).
3

ACCEPTED MANUSCRIPT
(E)-/(Z)-Isomers of styryl pyridines 2 have very close chromatographic retention parameters.
Thus, in most cases, we were not able to isolate individually each isomer by usual column
chromatography on silica gel. However, preparative HPLC separation of (E)- and (Z)-isomers of 2f
was carried out, as an example of possibility of individual isolation of these isomers. Mixtures of
E,Z-isomers of 2 were analyzed by means of NMR and HRMS. (E)-/(Z)-Configuration of
compounds 2 was determined on the basis of values of spin-spin interaction constants of vinyl
1
protons at the double C=C bond in H NMR and (see Experimental Part and Supporting
Information).
It should be specially emphasized that pyridines 2 and 3 are decomposed on silica gel, and
purification by preparative TLC leads to dramatic decrease of their yields. Table 1 contains the
yields of compounds 2 and 3 before chromatographic separation. These yields were determined for
mixtures of pure compounds 2 and 3 precipitated from the reaction solutions in the corresponding
alcohol. However, in the cases of PrOH and BuOH no precipitation of 2 and 3 was observed, and
these reaction products were isolated by extraction of reaction mixtures (see Experimental Part).
Table 1. Reactions of 1,5-diarylpent-2-en-4-yn-1-ones 1 with malononitrile and sodium alkoxides
in the corresponding alcohols leading to pyridines 2 and 3 (for X-ray structures ellipsoid contours of
probability levels are 50%).
Ar1
Ar1
O
CH2(CN)2,
RONa, ROH
CN
OR
Ar2
+
r. t., 3-23 h
Ar1
Ar2
N
Ar2
N
OR
1
E,Z-2
3
Entry
1
Starting enynone
Reaction
conditions
MeONa,
MeOH,
Reaction products
O
Ph
Ph
Ph
Ph
r.t., 4 h
Ph
1a
CN
CN
+
+
Ph
N
OCH3
Ph
N
OCH3
Ph
N
OCH3
E-2a
Z-2a
3a
13%
39%
35%
4

ACCEPTED MANUSCRIPT
X-ray of E-2a (CCDC 1910130)
Ph
N
2
3
MeONa,
MeOH,
argon,
r.t., 3h
1a
1a
Ph
Ph
CN
CN
+
+
Ph
N
OCH3
Ph
N
OCH3
Ph
OCH3
E-2a
Z-2a
31%
3a
13%
49%
MeONa,
MeOD,
r.t., 4 h
Ph
Ph
D
D
D
D
D
Ph
D
CN
+
D
D
CN
+
Ph
N
OCH3
Ph
N
OCH3
Ph
N
OCH3
E-2b
36%
Z-2b
25%
3b
12%
Ph
4
EtONa,
EtOH,
r.t.,
1a
Ph
Ph
Ph
CN
+
CN
OEt
+
23 h
Ph
N
OEt
N
Ph
N
OEt
E-2c
31%
Z-2c
16%
3c
9%
X-ray of Z-2c
(CCDC 1910133)
X-ray of 3c
(CCDC 1910109)
Ph
Ph
5
PrONa,
PrOH,
r.t.,
1a
Ph
CN
CN
OPr
17 h
+
+
Ph
N
OPr
Ph
N
Ph
N
OPr
E-2d
27%
Z-2d
27%
3d
14%
5

ACCEPTED MANUSCRIPT
Ph
Ph
6
7
BuONa,
1a
BuOH,
r.t.,
17 h
Ph
CN
CN
+
+
Ph
N
OBu
Ph
N
OBu
Ph
N
3e
14%
OBu
Ph
E-2e
Z-2e
32%
19%
O
MeONa,
MeOH,
r.t., 3 h
Ph
Ph
Ph
CN
CH3
CN
OCH3
+
OCH3
+
1b
N
N
N
OCH3
E-2f
46%
H3C
3f
14%
Z-2f
35%
H3C
H3C
Ph
8
EtONa,
EtOH,
r.t.,
1b
Ph
Ph
CN
OEt
CN
17 h
+
+
N
N
OEt
N
OEt
E-2g
35%
Z-2g
32%
3g
6%
H3C
H3C
H3C
O
Ph
9
MeONa,
MeOH,
r.t., 3 h
Ph
Ph
Ph
Cl
CN
CN
1c
+
+
N
OCH3
N
OCH3
N
OCH3
Cl
E-2h
3h
Z-2h
Cl
Cl
24%
10%
24%
O
Ph
Ph
10
11
MeONa,
MeOH,
r.t., 3 h
Ph
Ph
OCH3
CN
+
CN
+
1d
N
OCH3
N
OCH3
N
OCH3
E-2i
H3CO
3i
Z-2i
H3CO
H3CO
38%
43%
16%
Ph
EtONa,
EtOH,
r.t.,
1d
Ph
Ph
CN
CN
+
17 h
+
N
OEt
N
OEt
N
OEt
H3CO
H3CO
3j
H3CO
Z-2j
E-2j
5%
13%
38%
6

ACCEPTED MANUSCRIPT
O
CH3
CH3
12
MeONa,
MeOH,
r.t., 3 h
Ph
H3C
1e
CN
CN
OCH3
+
+
H3C
Ph
N
OCH3
Ph
N
Ph
N
3k
5%
OCH3
E-2k
Z-2k
6%
34%
CH3
13
EtONa,
EtOH,
r.t.,
1e
CH3
17 h
CN
CN
+
H3C
+
Ph
N
OEt
Ph
N
OEt
Ph
N
OEt
Z-2l
5%
3l
5%
E-2l
10%
O
Cl
Cl
14
MeONa,
MeOH,
r.t., 3 h
Ph
Cl
1f
CN
+
CN
Cl
+
Ph
N
OCH3
Ph
N
OCH3
Ph
N
3m
5%
OCH3
OCH3
E-2m
Z-2m
26%
18%
O
OCH3
15
MeONa,
MeOH,
r.t., 4 h
Ph
H3CO
1g
CN
CN
H3CO
+
+
Ph
N
OCH3
Ph
N
OCH3
Ph
N
3n
12%
OCH3
E-2n
45%
Z-2n
41%
O
CH3
16
MeONa,
MeOH,
r.t., 3 h
CH3
Cl
H3C
1h
CN
CN
H3C
Cl
+
+
N
OCH3
N
OCH3
Cl
N
OCH3
Cl
E-2o
Z-2o
3o
17%
26%
32%
7

ACCEPTED MANUSCRIPT
O
CH3
CH3
17
MeONa,
MeOH,
r.t., 4 h
Br
H3C
1i
CN
H3C
+
CN
+
N
OCH3
N
OCH3
N
OCH3
E-2p
38%
Z-2p
34%
3p
14%
Br
Br
Br
X-ray of 3p (CCDC 1910112)
CH3
18
EtONa,
EtOH,
r.t.,
1i
CH3
17 ч
CN
+
CN
H3C
Br
+
N
OEt
N
E-2q
OEt
N
OEt
Z-2q
14%
3q
7%
Br
Br
39%
O
19
MeONa, Complex mixture of reaction products.
MeOH,
r.t., 18 h
Ph
NO2
1j
To elucidate the reaction mechanism additional experiments were carried out. Reaction of
enynone 1a in inert atmosphere of argon (entry 2) afforded the same pyridines (E)-/(Z)-2a and 3a
in similar yields, as experiments in air (entry 1). This means that the use of an inert atmosphere is
not crucial for this reaction and atmosphere oxygen does not participate in any steps of the process.
Then, we carried out the reaction of enynone 1a in deuterated methanol (CH3OD). Incorporation of
deuterium atoms was found in the structures of pyridines (E)-/(Z)-2b and 3b (entry 3). The
formation of deuterated double bonds in (E)-/(Z)-2b reveals that deuterium came from solvent. That
means that, at the formation of compounds 2, triple bond is transformed into double one as a result
of intermolecular process of deuterium (or hydrogen) transfer, rather than intramolecular hydrogen
transfer. Apart from that, incorporation of deuterium atoms in pyridine ring reveals H-D exchange
in intermediate species of this reaction.
The author of the prior work [22] proposed reaction mechanism for similar transformation of
chalcones (see Scheme 1). One of the key step in this mechanism is Dimroth like rearrangement of
pyran ring into tetrahydropyridinone one. However, we propose an alternative way for this complex
and intriguing reaction (Scheme 2).
8

ACCEPTED MANUSCRIPT
Ar1
Ar1
O
N
N
RO-
N
N
ROH
-RO-
Ar2
Ar1
Ar2
O
Ar2
O
B
1
N
N
A
Ar1
Ar1
Ar1
OR
OR
NH
ROH
-RO-
RO-
-ROH
N
CN
CN
Ar2
O
C
O
Ar2
CN
Ar2
O
H2N OR
D
E
Ar1
Ar1
Ar1
CN
OR
CN
OR
CN
OR
-OH-
O
Ar2
HO
Ar2
N
H
N
Ar2
N
F
G
H
Ar1
Ar1
Ar1
CN
OR
RO-
- ROH
CN
Ar2
N
-CN-
Ar2
N
OR
Ar2
N
OR
I
J
3
Ar1
Ar1
Ar1
RO-
ROH
-RO-
CN
OR
CN
OR
CN
OR
Ar2
N
-ROH
Ar2
N
Ar2
N
J'
K
L
Ar1
Ar1
ROH
-RO-
CN
OR
CN
OR
Ar2
N
Ar2
N
L'
2
Scheme 2. Plausible mechanism of the reaction of enynones 1 with malononitrile and sodium
alkoxides leading to pyridines 2 and 3.
9

ACCEPTED MANUSCRIPT
The reaction starts form Michael type addition of malononitrile anion to the carbon-carbon
double bond of starting enynone 1, that gives anion A. The latter withdraws proton from an alcohol
molecule and gives compound B, which is undergone nucleophilic attack of alkoxide anion onto
cyano group affording species C, then D, and enamine E. The latter is cyclized into anion F as a
result of interaction of amino group with carbonyl carbon. Proton transfer in species F leads to N-
centered anion G, which eliminates hydroxide and gives structure H. Isomerization of double bonds
in H may lead to structure I. Deprotonation of the latter results in the formation of propargy-allyl
anion J, which is one of the key intermediates in the reaction. There are two possibilities for further
transformation of this species. First one is an elimination of the cyanide furnishing heteroaromatic
pyridine system of compounds 3. Another pathway is protonation of allenyl mesomeric form J′ of
anion J, which leads to allene K. Deprotonation of the latter in α-position to cyano group gives rise
to anion L. Protonation of vinyl mesomeric form of L′ results finally (E)-/(Z)-isomers of 4-styryl
substituted pyridines 2, as the main reaction products. Of course, this mechanism has speculative
character, since it is very complex and multistep reaction.
The formation of cyanide ion CN– for the reaction of enynone 1a (entry 1, Table) was
additionally proved by gas chromatographic analysis of the vapor phase (headspace GC-analysis).
The analysis over the acidified (H2SO4) reaction solution confirmed the presence of hydrogen
cyanide (see the literature procedure [41] for the determination of HCN). At the same time, the
vapor phase above the solution of malononitrile and MeONa in MeOH in a blank experiment
without 1a, after acidification with H2SO4, did not contain traces of HCN (see details of the
experiments and chromatograms in Supporting Information). The data obtained confirm the
formation of the cyanide ion in reactions of enynones and our assumptions on the reaction
mechanism (Scheme 2).
To investigate the reaction mechanism deeper we carried out the reaction of enynone 1a with
such low nucleophilic base as lithium diisopropylamide (LDA) instead of sodium alkoxides.
Compound 4 was obtained as the main reaction product of Michael type addition to the double C=C
bond of 1a (Scheme 3). Apart from that, compound 5 of the cyclohexane series was isolated, exact
structure of 5 was determined by X-ray analysis (Scheme 3). No formation of pyridine derivatives
was observed. One may propose that low nucleophilic diisopropylamide anion does not attack
cyano group in 4, contrary to alkoxides, which give rise to anions C in Scheme 2. That means that
nucleophilc addition to cyano group is necessary for the pyridine ring formation, that does not take
place in the case of lithium diisopropylamide.
10

ACCEPTED MANUSCRIPT
Ph
Ph
NC CN
NC
CN
O
CH2(CN)2,LDA,
THF, argon
O
+
Ph
Ph
Ph
r. t., 17 h
Ph
Ph
Ph OH
5
O
1a
4
22%
41%
Scheme 3. Reaction of enynone 1a with malononitrile and lithium diisopropylamide (LDA) leading
to compounds 4 and 5, X-ray structure of 5 ellipsoid contours of probability levels are 50%, CCDC
1910129)
(
.
A plausible reaction mechanism is presented in Scheme 4. Michael addition of malononitrile
anion to the double carbon-carbon bond of enynone 1a gives rise to anion M, the protonation of
which affords compound 4. The reaction may stop at this stage or go further leading to anion N.
The latter reacts with one more molecule of 1a affording anion O, which is cyclized into species P
forming cyclohexane ring. Finally, protonation of anion P results in the stereoselective formation of
compound 5.
NC
CN
O
NC
CN
O
H+
O
LDA
N
N
Ph
Ph
Ph
Ph
1a
Ph
M
Ph
4
Ph
Ph
NC CN
Ph
Ph
NC CN
NC
CN
O
1a
H+
O
Ph
Ph
Ph
N
Ph
Ph
O
Ph O
O
O
P
Ph
Ph
NC CN
Ph
Ph OH
O
5
Scheme 4. Plausible mechanism of the reaction of enynone 1a with malononitrile and LDA leading
to compounds 4 and 5.
11

ACCEPTED MANUSCRIPT
Since, it is known that many pyridine derivatives are fluorescent compounds [26, 38-40, 42-
46], we investigated qualitatively fluorescent properties for pyridines 2 and 3. Indeed, it was found
that, at the excitation at 320 nm, the fluorescence peaks were observed at 365-370 nm for
arylethynyl pyridines 3a,f,h, and at 390-410 nm for styryl pyridines E-2a, Z-2a, and for mixture of
isomers E,Z-2f (see details in Supporting Information).
Conclusion
We have developed a synthesis of 4-styryl- and 4-arylethynyl- substituted pyridines, bearing
aryl, alkoxy, and cyano groups, on the basis of an interaction of conjugated enynones, 1,5-
diarylpent-2-en-4-yn-1-ones, with malononitrile and sodium alkoxides in alcohols. Apart from that,
it was found that 1,5-diphenylpent-2-en-4-yn-1-ones in reaction with malononitrile and lithium
diisopropylamide gives product of Michael addition of malononitrile to the double bond and
“dimeric” compound of the cyclohexane series. Intriguing mechanisms of these reactions are
discussed. The obtained arylethynyl- and styryl- substituted pyridines are fluorescent compounds.
Experimental Section
The NMR spectra of solutions of compounds in CDCl3 were recorded on Bruker AVANCE
III 400 spectrometer [at 400, 100 and 61 MHz for 1H, 13C, and 2H(D) NMR spectra respectively] at
1
25 °C. The solvent residual signals CDCl3 (δ 7.26 ppm) for H NMR spectra, the carbon signal of
13
2
CDCl3 (δ 77.0 ppm) for C NMR spectra, and C6H6 (δ 7.15 ppm) for H(D) NMR spectra were
used as references. IR spectra of compounds were taken with Bruker spectrometer. HRMS was
carried out at instrument Bruker maXis HRMS-ESI-QTOF. Fluorescent spectra for solution of
compounds in CH2Cl2 with concentration of 10-5 mol/L were taken with Fluorimax 4P Horiba
machine. Analysis of the vapor phase by the Headspace GC method was performed on a Crystallux-
4000M chromatograph with thermal conductivity detector and a packed column containing
HayeSep Q (60/80 mesh) as a stationary phase. Column length 2 m, diameter 3 mm, temperature
120 ºC, carrier gas – He. The preparative reactions were monitored by thin-layer chromatography
carried out on silica gel plates (Alugram SIL G/UV-254), using UV light for detection. Preparative
TLC was performed on silica gel Chemapol L 5/40respectively. HPLC was done on a Waters
machine using gradient eluation with acetonitrile-water mixtures.
X-ray Diffraction Study. Single crystal X-ray analysis was performed at single crystal
diffractometer Agilent Technologies (Oxford Diffraction) «Supernova». The crystal was kept at
100(2) K during data collection. Using Olex2 [47], the structure was solved with the ShelXS [48]
structure solution program using Direct Methods and refined with the ShelXL refinement package
using Least Squares minimization. CCDC 1910130 – (E-2a), CCDC 1910133 - (Z-2c), CCDC
12

ACCEPTED MANUSCRIPT
1910109 – (3c), CCDC 1910112 − (3p), CCDC 1910129 – (5) contain the supplementary
crystallographic data, which can be obtained free of charge at
www.ccdc.cam.ac.uk/conts/retrieving.html or from the Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; Fax: (internat.) +44-1223-336-033; E-mail:
deposit@ccdc.cam.ac.uk.
Preparation and characterization of starting enynones 1 was previously described [21, 22, 49].
General Procedure for the Synthesis of (Е)- and (Z)-2-alkoxy-6-aryl-4-(2-
arylethenyl)pyridine-3-carbonitriles (E,Z-2a-q) and 2-alkoxy-6-aryl-4-(arylethynyl)pyridines
(3a-q) from 1,5-diarylpent-2-en-4yn-1-ones (1a-i). Malononitrile (2.5 equiv.) was added to
sodium alcoxide (2.5 equiv.) solution (1.08 mmol/mL) in alcohol with stirring. The solution of
enynone 1 (1 equiv.) in 1-6 mL of absolute alcohol was heated (~50°C) till enynone dissolution,
then the obtained solution was added to malononitrile solution and mixture was stirring at room
temperature for 3-23 h. The precipitate was filtered off to give mixture of pure compounds 2 and 3
(in the case of PrOH and BuOH no precipitation). The mother solution was poured into water (30
mL), and was extracted with CH2Cl2 (3×30 mL). The combined organic layers were dried with
Na2SO4. Solvent was evaporated under the reduced pressure. The obtained residue was subjected to
preparative TCL on silica gel with eluation by petroleum ether−ethyl acetate mixtures to get
additional amounts of 2 and 3.
(Е)-2-Methoxy-6-phenyl-4-(2-phenylethenyl)pyridine-3-carbonitrile (E-2a) [50, 51]. Obtained
from 1a (50 mg, 0.22 mmol) and sodium methoxide (0.55 mmol) in a yield of 27 mg (39%).
Obtained from 1a (100 mg, 0.44 mmol) and sodium methoxide (1.1 mmol) under argon in a yield of
67 mg (49%). Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 85:15.
1
Colorless solid. Н NMR, δ, ppm: 4.19 s (3H, OCH3), 7.39-7.47 m (6H), 7.51-7.58 m (2H), 7.65 d
(2H, HPh, J 6.9 Hz), 7.71 s (1H, HPy), 8.13 dd (2H, HPh, J 7.9, 1.6 Hz) 13
. C NMR, δ, ppm: 54.5
(OCH3), 92.9 (CPy-CN), 108.4 (CPy-H), 115.1 (CN), 122.6, 127.3, 127.7, 128.9, 129.0, 129.7, 130.3,
135.4, 137.1, 137.7, 151.5 (CPy-C=C), 157.8 (CPy-Ph), 164.9 (CPy-O). IR (KBr): 2217 cm-1 (CN).
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H17N2O 313.1341; Found 313.1335.
(Z)-2-Methoxy-6-phenyl-4-(2-phenylethenyl)pyridine-3-carbonitrile (Z-2a). Obtained from 1a
(50 mg, 0.22 mmol) and sodium methoxide (0.55 mmol) in a yield of 24 mg (35%). Obtained from
1a (100 mg, 0.44 mmol) and sodium methoxide (1.1 mmol) under argon in a yield of 43 mg (31%).
Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 85:15. Colorless solid.
1Н NMR, δ, ppm: 4.18 s (3H, OCH3), 6.76 d (1H, =CH-, J 12.2 Hz), 7.07 d (1H, =CH-, J 12.2 Hz),
7.24 s (1H, HPy), 7.29-7.33 m (4H), 7.40-7.42 m (4H), 7.75 dd (2H, HPh, J 7.5, 2.0 Hz) 13
ppm: 54.4 (OCH3), 94.0 (CPy-CN), 113.1 (CPy-H), 114.8 (CN), 124.5, 127.1, 128.5, 128.7, 128.7,
. C NMR, δ,
13

ACCEPTED MANUSCRIPT
128.9, 130.2, 132.5, 136.7, 137.4, 152.6 (CPy-C=C), 157.2 (CPy-Ph), 164.7 (CPy-O). IR (KBr): 2222
cm-1 (CN). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H17N2O 313.1341; Found 313.1335.
2-Methoxy-6-phenyl-4-phenylethynylpyridine (3a). Obtained from 1a (50 mg, 0.22 mmol) and
sodium methoxide (0.55 mmol) in a yield of 8 mg (13%). Obtained from 1a (100 mg, 0.44 mmol)
and sodium methoxide (1.1 mmol) under argon in a yield of 16 mg (13%). Purification by
1
preparative TLC with mixture petroleum ether–ethyl acetate, 85:15. Colorless solid. Н NMR, δ,
ppm: 4.08 s (3H, OCH3), 6.83 s (1H, HPy), 7.40-7.52 m (7H), 7.60 dd (2H, HPh, J 6.6, 3.1 Hz), 8.09
d (2H, HPh, J 7.0 Hz).13C NMR, δ, ppm: 53.5 (OCH3), 87.2 (C≡), 92.7 (C≡), 111.1 (CPy-H), 115.2
(CPy-H), 122.3, 126.8, 128.5, 128.6, 129.0, 129.1, 131.9, 134.2, 138.5, 154.9 (CPy-Ph), 163.9 (CPy-
O). IR (KBr): 2219 cm-1 (C≡C). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C20H15NONa
308.1051; Found 308.1046.
(Е)-5-Deutero-2-methoxy-6-phenyl-4-(1,2-dideutero-2-phenylethenyl)pyridine-3-carbonitrile
(
E-2b). Obtained from 1a (100 mg, 0.44 mmol) and sodium methoxide (1.1 mmol) in MeOD.
Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 85:15 in a yield of 50
1
mg (36%). Colorless solid. Н NMR, δ, ppm: 4.20 s (3H, OCH3), 7.38-7.48 m (3H), 7.52-7.55 m
(2H), 7.63-7.67 m (2H), 8.13 dd (2H, HPh, J 7.9, 1.7 Hz) 2Н NMR δ, ppm: 6.13. 13C NMR, δ, ppm:
.
54.4 (OCH3), 85.5 (CPy-CN), 99.2 (CPy-D), 114.9 (CN), 127.1, 127.3, 127.7, 128.4, 128.5, 128.6,
128.69, 128.7, 128.87, 128.96, 129.01, 130.2, 130.3, 152.3 (СPy-C=), 157.1 (CPy-Ph), 164.7 (CPy-O).
IR (KBr): 2220 cm-1 (CN). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H14D3N2O 316.1529;
Found 316.1524.
(Z)-5-Deutero-2-methoxy-6-phenyl-4-(1,2-dideutero-2-phenylethenyl)pyridine-3-carbonitrile
(
Z-2b). Obtained from 1a (100 mg, 0.44mmol) and sodium methoxide (1.1 mmol) in MeOD.
Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 85:15 in a yield of 44
mg (32%). Colorless solid. 1Н NMR, δ, ppm: 4.18 s (3H, OCH3), 7.29-7.34 m (4H), 7.39-7.42 m
(4H), 7.73-7.76 m (2H) .
2Н NMR δ, ppm: 6.17, 6.65, 7.09. 13C NMR, δ, ppm: 54.4 (OCH3), 94.0
(CPy-CN), 112.8 t (CPy-D, J 30.0 Hz), 114.8 (CN), 124.4 t (=CD, J 6.0 Hz), 127.10, 128.5, 128.69,
128.7, 128.9, 130.2, 132.5, 136.6, 137.3, 152.4 (CPy-C=C), 157.1 (CPy-Ph), 164.7 (CPy-O). IR
(KBr): 2220 cm-1 (CN). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H15D3N2ONa 338.1349;
Found 338.1343.
3,5-Dideutero-2-methoxy-6-phenyl-4-phenylethynylpyridine (3b). Obtained from 1a (100 mg,
0.44mmol) and sodium methoxide (1.1 mmol) in MeOD in a yield of 14 mg (12%). Purification by
1
preparative TLC with mixture petroleum ether–ethyl acetate, 85:15. Colorless solid. Н NMR, δ,
ppm: 4.09 s (3H, OCH3), 7.40-7.52 m (6H), 7.61 dd (2H, HPh, J 6.6, 3.0 Hz), 8.10 d (2H, HPh, J 7.2
Hz).
2Н NMR δ, ppm: 6.13, 6.94, 7.46. 13C NMR, δ, ppm: 53.5 (OCH3), 87.2 (C≡), 92.8 (C≡), 111.0
t (CPy-D, J 25.4 Hz), 115.1 t (CPy-D, J 25.4 Hz), 122.3(CPh-C≡), 126.8, 128.5, 129.1, 129.2, 131.9,
14

ACCEPTED MANUSCRIPT
134.1, 138.5, 154.8 (CPy-Ph), 163.9 (CPy-O). IR (KBr): 2216 cm-1 (C≡C). HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C20H14D2N2O 288.1357; Found 288.1352.
(Е)-,(Z)-2-Ethoxy-6-phenyl-4-(2-phenylethenyl)pyridine-3-carbonitrile ((E)-/(Z)-2c). Mixture
of isomers. Obtained from 1a (100 mg, 0.44mmol) and sodium ethoxide(1.1 mmol). Purification by
preparative TLC with mixture petroleum ether–ethyl acetate, 9:1 in a yield of E-2c 44 mg (31%),
1
yield of Z-2c 22 mg (16%). Colorless solid [51]. Н NMR, E-2c (selected signals, obtained from
spectrum of mixture of isomers) δ, ppm:1.54 t (3H, CH3, J 7.0 Hz), 4.67 q (2H, OCH2, J 7.2 Hz),
7.65 d (2H, HPh, J 7.0 Hz), 7.69 s (1H, HPy), 8.12 d (2H, HPh, J 7.6 Hz).1Н NMR, Z-2c (selected
signals, obtained from spectrum of mixture of isomers) δ, ppm: 1.53 t (3H, CH3, J 7.0 Hz), 4.65 q
(2H, OCH2, J 7.0 Hz), 6.77 d (1H, HC=, J 12.2 Hz), 7.07 d (1H, HC=, J 12.2 Hz), 7.72 s (1H,
HPy).1H NMR, (signals of mixture of isomers) δ, ppm: 7.27-7.33 m, 7.37-7.47 m, 7.51-7.58 m, 7.71-
7.74 m.13C NMR, E-2c (selected signals, obtained from spectrum of mixture of isomers) δ, ppm:
14.5 (CH3, OEt), 63.4 (CH2, OEt), 108.2 (CPy-H), 114.6 (CN), 122.8, 158.1, 163.9. 13C NMR, Z-2c
(selected signals, obtained from spectrum of mixture of isomers) δ, ppm: 14.5 (СH3, OEt), 63.2
(CH2, OEt), 94.1, 112.8 (CPy-H), 114.9 (CN), 152.5, 157.1, 164.4. 13C NMR, (signals of mixture of
isomers) δ, ppm: 124.7, 127.1, 127.3, 127.7, 128.4,128.58, 128.66, 128.69, 128.8, 128.9, 129.0,
129.7, 130.0, 130.1, 130.3, 130.6, 132.5, 136.7, 137.5. IR (KBr): 2222 cm-1 (CN). HRMS (ESI-
TOF) m/z: [M + Na]+ Calcd for C22H18N2ONa 349.1317; Found 349.1311. GC-МS, m/z, Irel. (%):
326 M+ (70), 311 (20), 297 (8), 281 (15), 272 (75), 254 (30), 249 (100), 77 (32).
2-Ethoxy-6-phenyl-4-phenylethynylpyridine (3c). Obtained from 1a (100 mg, 0.44 mmol) and
sodium ethoxide(1.1 mmol). Purification by preparative TLC with mixture petroleum ether–ethyl
acetate, 9:1 in a yield of 11 mg (9%). Colorless solid. 1Н NMR, δ, ppm: 1.47 t (3H, CH3, J 7.1 Hz),
4.53 q (2H, OCH2, J 7.1 Hz), 6.81 s (1H, HPy), 7.40-7.45 m (3H), 7.47 s (1H, HPy), 7.48-7.51 m
(3H), 7.58-7.61 m (2H), 8.07 d (2H, HPh, J 7.0 Hz). 13C NMR, δ, ppm: 14.7 (OEt), 61.8 (OEt), 87.3
(C≡), 92.5 (C≡), 111.3 (CPy-H), 115.0 (CPy-H), 122.4, 126.7, 128.5, 128.6, 129.0, 129.1, 131.9,
134.1, 138.6, 154.9, 163.7. IR (KBr): 2211cm-1 (C≡C). HRMS (ESI-TOF) m/z: [M+H]+ Calcd for
C21H18NO 300.1388; Found 300.1383.
(Е)-,(Z)-6-Phenyl-4-(2-phenylethenyl)-2-propoxypyridine-3-carbonitrile
((E)-/(Z)-2d).
Mixture of isomers. Obtained from 1a (50 mg, 0.22mmol) and sodium propoxide (0.55 mmol).
Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 9:1 in a yield of E-2d
1
20 mg (27%), yield of Z-2d 20 mg (27%). Colorless solid. Н NMR, E-2d (selected signals,
obtained from spectrum of mixture of isomers) δ, ppm: 1.13 t (3H, CH3 from OPr, J 7.3 Hz), 1.94
1
sec (2H, CH2 from OPr, J 7.3, 6.9 Hz), 4.56 t (2H, OCH2 from OPr, J 6.7 Hz). Н NMR, Z-2d
(selected signals, obtained from spectrum of mixture of isomers) δ, ppm: 1.12 t (3H, CH3 from OPr,
J 7.5 Hz), 1.93 sec (2H, CH2 from OPr, J 7.3, 6.7 Hz), 4.53 t (2H, OCH2 from OPr, J 6.7 Hz), 6.76
15

ACCEPTED MANUSCRIPT
1
d (1H, HC=, J 12.2 Hz), 7.06 d (1H, HC=, J 12.2 Hz), 7.22 s (1H, HPy). H NMR, (signals of
13
mixture of isomers) δ, ppm:7.28-7.33 m, 7.37-7.45 m, 7.51-7.58 m, 7.66-7.73 m, 8.07-8.13 m. C
NMR, E-2e (selected signals, obtained from spectrum of mixture of isomers)δ, ppm: 11.0 (CH3,
OPr), 23.0 (CH2, OPr), 68.9 (OCH2, OPr), 93.3 (CPy, C-CN), 108.2 (CPy-H), 114.6 (CN), 122.8
13
(C=), 151.5 (CPy, C-C=), 157.8 (CPy, C-Ph), 164.8 (CPy, C-O). C NMR, Z-2d (selected signals,
obtained from spectrum of mixture of isomers) δ, ppm: 10.5 (СH3, OPr), 22.2 (CH2, OPr), 68.8
(OCH2, OPr), 94.1 (CPy, C-CN), 112.8 (CPy-H), 114.8 (CN), 124.6 (C=), 152.5 (CPy, C-C=), 157.1
13
(CPy, C-Ph), 164.6 (CPy, C-O). C NMR, (signals of mixture of isomers) δ, ppm: 127.1, 127.3,
127.6, 128.4, 128.6, 128.7, 128.7, 128.8, 128.9, 128.9, 129.0, 130.1, 132.5, 136.7, 136.9, 137.3,
137.5. IR (KBr): 2221 cm-1 (CN). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H21N2O
341.1654; Found 341.1648.
2-Phenyl-4-phenylethynyl-6-propoxypyridine (3d). Obtained from 1a (50 mg, 0.22 mmol) and
sodium propoxide (0.55 mmol). Purification by preparative TLC with mixture petroleum ether–
1
ethyl acetate, 9:1 in a yield of 10 mg (14%). Colorless solid. Н NMR, δ, ppm: 1.09 t (3H, CH3
from OPr, J 7.4 Hz), 1.88 sec (2H, CH2 from OPr, J 7.2, 7.0 Hz), 4.43 t (2H, OCH2 from OPr, J 6.7
Hz), 6.82 s (1H, HPy), 7.40-7.51 m (4H), 7.58-7.60 m (5H), 8.07 d (2H, HPh, J 7.1 Hz). 13C NMR, δ,
ppm: 10.6 (СH3, OPr), 22.4 (CH2, OPr), 67.7 (OCH2, OPr), 87.3 (C≡), 92.6 (C≡), 111.3 (CPy-H),
115.0 (CPy-H), 122.4, 126.8, 128.5, 128.6, 129.0, 129.1, 131.9, 134.2, 138.6, 154.8 (CPy, C-Ph),
163.9 (CPy, C-O). IR (KBr): 2212 cm-1 (C≡C). HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C22H20NO
314.1545; Found 314.1539.
(Е)-,(Z)-2-Butoxy-6-phenyl-4-(2-phenylethenyl)pyridine-3-carbonitrile ((E)-/(Z)-2e). Mixture
of isomers. Obtained from 1a (50 mg, 0.22 mmol) and sodium butoxide (0.55 mmol). Purification
by preparative TLC with mixture petroleum ether–ethyl acetate, 9:1 in a yield of E-2e 15 mg (19%),
1
yield of Z-2e 25 mg (32%). Colorless solid. Н NMR, E-2e (selected signals, obtained from
spectrum of mixture of isomers) δ, ppm: 1.04 t (3H, CH3 from OBu, J 7.3 Hz), 1.45 sec (2H, CH2
from OBu, J 7.3, 6.4 Hz), 1.90 p (2H, from OBu, J 7.8, 6.7 Hz), 4.60 t (2H, OCH2 from OBu, J 6.7
Hz). 1Н NMR, Z-2e (selected signals, obtained from spectrum of mixture of isomers) δ, ppm: 1.04 t
(3H, CH3fromOBu, J 7.3 Hz), 1.45 sec (2H, CH2 from OBu, J 7.3, 6.4 Hz), 1.89 p (2H, from OBu,
J 7.8, 6.6 Hz), 4.58 t (2H, OCH2 from OBu, J 6.6 Hz), 6.76 d (1H, HC=, J 12.2 Hz), 7.06 d (1H,
1
HC=, J 12.2 Hz), 7.22 s (1H, HPy). H NMR, (signals of mixture of isomers) δ, ppm: 7.29-7.33 m,
7.37-7.47 m, 7.51-7.58 m, 7.65-7.74 m, 8.07-8.12 m.13C NMR, E-2e (selected signals, obtained
from spectrum of mixture of isomers) δ, ppm: 14.0 (CH3, OBu), 19.2 (CH2, OBu), 30.9 (CH2,
OBu), 67.2 (OCH2, OBu), 93.0 (CPy, C-CN), 108.1 (CPy-H), 114.6 (CN), 122.8 (C=), 151.5 (CPy, C-
C=), 157.8 (CPy, C-Ph), 164.8 (CPy, C-O). 13C NMR, Z-2e (selected signals, obtained from spectrum
of mixture of isomers) δ, ppm: 13.9 (СH3, OBu), 19.3 (CH2, OBu), 30.9 (CH2, OBu), 67.1 (OCH2,
OBu), 94.1 (CPy, C-CN), 112.8 (CPy-H), 114.9 (CN), 124.6 (C=), 152.5 (CPy, C-C=), 157.1 (CPy, C-
16

ACCEPTED MANUSCRIPT
Ph), 164.6 (CPy, C-O). 13C NMR, (signals of mixture of isomers) δ, ppm: 127.1, 127.3, 127.7, 128.4,
128.6, 128.66, 128.69, 128.81, 128.84, 128.88, 128.90, 129.0, 130.08, 130.1, 130.2, 132.5, 136.7,
136.9, 137.3, 137.5. IR (KBr): 2222 cm-1 (CN). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C24H22N2ONa 377.1630; Found 377.1624.
2-Butoxy-6-phenyl-4-phenylethynylpyridine (3e). Obtained from 1a (50 mg, 0.22 mmol) and
sodium butoxide (0.55 mmol). Purification by preparative TLC with mixture petroleum ether–ethyl
1
acetate, 9:1 in a yield of 10 mg (14%). Colorless solid. Н NMR, δ, ppm: 1.03 t (3H, CH3 from
OBu, J 7.4 Hz), 1.45 sec (2H, CH2 from OBu, J 7.3, 6.7 Hz), 1.84 p (2H, CH2 from OBu, J 7.2, 6.7
Hz), 4.47 t (2H, OCH2 from OBu, J 6.6 Hz), 6.82 s (1H, HPy), 7.40-7.44 m (2H), 7.47 s (1H, HPy),
7.47-7.50 m (2H), 7.54-7.60 m (2H), 7.72-7.75 m (2H), 8.07 d (2H, HPh, J 7.2 Hz).13C NMR, δ,
ppm: 13.9 (СH3, OBu), 19.4 (CH2, OBu), 31.2 (CH2, OBu), 65.9 (OCH2, OBu), 87.3 (C≡), 92.53
(C≡), 111.3 (CPy-H), 115.0 (CPy-H), 122.4 (CPh-C≡), 126.8, 128.5, 128.6, 129.0, 129.1, 131.9,
134.1, 138.7, 154.9 (CPy, C-Ph), 163.9 (CPy, C-O). IR (KBr): 2217 cm-1 (C≡C). HRMS (ESI-TOF)
m/z: [M+Na]+ Calcd for C23H21NONa 350.1521; Found 350.1515.
(Е)-6-(4-Methylphenyl)-2-methoxy-4-(2-phenylethenyl)pyridine-3-carbonitrile
(E-2f).
Obtained from 1b (50 mg, 0.20mmol) and sodium methoxide (0.51 mmol) in a yield of 31 mg
(48%). Purification by preparative HPLC. Colorless solid. 1Н NMR, δ, ppm: 2.46 s (3H, CH3), 4.19
s (3H, OCH3), 7.34 d (2H, HAr, J 8.0 Hz), 3.38-7.47 m (4H), 7.55 d (1H, CH=, J 16.2 Hz), 7.66-
7.69 m (2H), 7.68 s (1H, HPy), 8.02 dd (2H, HAr, J 13.0, 8.2 Hz). 13C NMR δ, ppm: 21.4 (CH3), 54.4
(OCH3), 92.5 (CPy-CN), 108.0 (CPy-H), 115.2 (CN), 122.7, 127.6, 128.6, 129.0, 129.6, 132.5, 134.9,
135.4, 136.9, 140.7, 151.4 (CPy-C=C), 157.8 (CPy-Ar), 164.9 (CPy-O). HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C22H19N2O 327.1497; Found 327.1492.
(Z)-6-(4-Methylphenyl)-2-methoxy-4-(2-phenylethenyl)pyridine-3-carbonitrile
(Z-2f).
Obtained from 1b (50 mg, 0.20mmol) and sodium methoxide (0.51 mmol) in a yield of 24 mg
1
(37%). Purification by preparative HPLC. Colorless solid. Н NMR δ, ppm: 2.39 s (3H, CH3), 4.17
s (3H, OCH3), 6.75 d (1H, CH=, J 12.2 Hz), 7.06 d (1H, CH=, J 12.2 Hz), 7.19-7.21 m (3H), 7.26-
13
7.32 m (5H), 7.65 d (2H, HAr, J 8.2 Hz). C NMR δ, ppm: 21.3 (CH3), 54.3 (OCH3), 93.6 (CPy-
CN), 112.7 (CPy-H), 115.0 (CN), 124.6, 127.0, 128.4, 128.6, 128.9, 129.5, 134.6, 136.7, 137.3,
140.6, 152.4 (CPy-C=C), 157.3 (CPy-Ar), 164.7 (CPy-O). IR (KBr): 2221 cm-1 (CN). HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C22H19N2O 327.1497; Found 327.1492.
2-(4-Methylphenyl)-6-methoxy-4-(phenylethynyl)pyridine (3f). Obtained from 1b (50 mg,
0.20mmol) and sodium methoxide (0.51 mmol). Purification by preparative TLC with mixture
1
petroleum ether–ethyl acetate, 85:15 in a yield of 9 mg (15%). Colorless solid. Н NMR, δ, ppm:
2.44 s (3H, CH3), 4.07 s (3H, OCH3), 6.80 s (1H, HPy), 7.29 d (2H, HAr, J 8.6 Hz), 7.40-7.41 m
(2H), 7.46 s (1H, HPy), 7.58-7.61 m (3H), 7.99 d (2H, HAr, J 8.2 Hz). 13C NMR, δ, ppm: 21.3 (CH3),
53.4 (OCH3), 87.3 (C≡), 92.5 (C≡), 110.7 (CPy-H), 114.8 (CPy-H), 122.4 (CPh-C≡), 126.6, 128.5,
17

ACCEPTED MANUSCRIPT
129.0, 129.4, 131.9, 134.1, 135.8, 139.2, 154.9 (CPy-C6H4Cl), 163.9 (CPy-O). IR (KBr): 2218 cm-1
(C≡C). HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C21H18NO 300.1388; Found 300.1383.
(Е)-,(Z)-2-Ethoxy-6-(4-methylphenyl)-4-(2-phenylethenyl)pyridine-3-carbonitrile ((E)-/(Z)-
2g). Obtained from 1b (50 mg, 0.20mmol) and sodium ethoxide (0.51 mmol). Purification by
preparative TLC with mixture petroleum ether–ethyl acetate, 85:15 in a yield of E-2g 24 mg (35%),
1
yield of Z-2g 22 mg (32%). Colorless solid. Н NMR, E-2g (selected signals, obtained from
spectrum of mixture of isomers) δ, ppm:1.53 t (2H, OEt, J 7.0 Hz), 2.46 s (3H, Me), 4.65 q (3H,
1
OEt, J 7.2 Hz), 7.54 d (1H, HC=, J 17.1 Hz), 7.69 s (1H, HPy). Н NMR, Z-2g (selected signals,
obtained from spectrum of mixture of isomers) δ, ppm: 1.52 t (2H, OEt, J 7.0 Hz), 2.39 s (3H, Me),
4.64 q (3H, OEt, J 7.2 Hz), 6.75 d (1H, HC=, J 12.2 Hz), 7.05 d (1H, HC=, J 12.2 Hz), 7.62 d (2H,
1
HAr, J 8.2 Hz). H NMR, (signals of mixture of isomers) δ, ppm: 7.19-7.21 m, 7.31-7.34 m, 7.39-
13
7.47 m, 7.66-7.69 m, 7.97-8.03 m. C NMR, E-2g (selected signals, obtained from spectrum of
mixture of isomers) δ, ppm: 14.5 (CH3, OEt), 21.4 (Me), 63.2 (CH2, OEt), 92.6 (CPy-CN), 107.8
(CPy-H), 114.3 (CN), 122.9 (C=), 135.0, 135.5, 136.7, 140.6, 151.4, 157.8, 164.6 (CPy-O). 13C
NMR, Z-2g (selected signals, obtained from spectrum of mixture of isomers) δ, ppm: 14.5 (CH3,
OEt), 21.3 (Me), 63.1 (CH2, OEt), 93.6 (CPy-CN), 112.4 (CPy-H), 115.0 (CN), 124.7 (C=), 134.7,
136.8, 137.1, 140.5, 152.4, 157.2, 164.4 (CPy-O). 13C NMR, (signals of mixture of isomers) δ, ppm:
127.0, 127.2, 127.6, 128.4, 128.6, 128.9, 129.0, 129.4, 129.57, 129.63, 132.4. IR (KBr): 2221 cm-1
(CN). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H21N2O 341.1654; Found 341.1678. GC-МS,
m/z, Irel. (%): 340 M+ (70), 325 (20), 311 (10), 295 (12), 286 (70), 263 (100), 91 (20), 77 (15).
2-Ethoxy-6-(4-methylphenyl)-4-phenylethynylpyridine (3g). Obtained from 1b (50 mg,
0.20mmol) and sodium ethoxide (0.51 mmol). Purification by preparative TLC with mixture
1
petroleum ether–ethyl acetate, 85:15 in a yield of 4 mg (6%). Colorless solid. Н NMR, δ, ppm:
1.47 t (3H, OEt, J 7.0 Hz), 2.43 s (3H, Me), 4.52 q (2H, OEt, J 7.1 Hz), 6.78 s (1H, HPy), 7.28-7.30
m (3H), 7.40-7.41 m (2H), 7.44 s (1H, HPy), 7.54-7.60 m (2H), 7.97 d (2H, HAr, J 8.1 Hz).13C NMR,
δ, ppm: 14.7 (CH3, OEt), 21.3 (Me), 61.8 (CH2, OEt), 87.4 (C≡), 92.4 (C≡), 110.8 (CPy-H), 114.6
(CPy-H), 122.4,128.5, 129.0, 129.3, 130.90, 134.0, 135.9, 139.1, 154.9, 163.6 (CPy-O). IR (KBr):
2219 cm-1 (C≡C). HRMS (ESI-TOF) m/z: [M+H]+Calcd fo rC22H20NO 314.1545; Found 314.1539.
(Е)-,(Z)-6-(4-Chlorophenyl)-2-methoxy-4-(2-phenylethenyl)pyridine-3-carbonitrile ((E)-/(Z)-
2h). Mixture of isomers. Obtained from 1c (50 mg, 0.19 mmol) and sodium methoxide (0.48 mmol).
Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 8:2 in a yield of E-2h
1
16 mg (24%), yield of Z-2h 16 mg (24%). Colorless solid. Н NMR, E-2h (selected signals,
obtained from spectrum of mixture of isomers) δ, ppm: 4.18 s (3H, OCH3), 7.56 d (1H, CH=, J 16.2
1
Hz), 8.08 d (2H, HAr, J 8.6 Hz). Н NMR, Z-2h (selected signals, obtained from spectrum of
mixture of isomers) δ, ppm: 4.16 s (3H, OCH3), 6.76 d (1H, CH=, J 12.2 Hz), 7.09 d (1H, CH=, J
12.2 Hz), 7.18 s (1H, HPy). 1H NMR, (signals of mixture of isomers) δ, ppm: 7.32-7.52 m, 7.65-7.67
18

ACCEPTED MANUSCRIPT
m.13C NMR, E-2h (selected signals, obtained from spectrum of mixture of isomers) δ, ppm: 54.5
(OCH3), 93.2 (CPy-CN), 108.2 (CPy-H), 114.9 (CN), 122.5, 136.3, 136.1, 136.5, 137.3, 151.7 (CPy-
C=C), 156.5 (CPy-Ar), 164.9 (CPy-O). 13C NMR, Z-2h (selected signals, obtained from spectrum of
mixture of isomers) δ, ppm: 54.4 (OCH3), 94.4 (CPy-CN), 112.9 (CPy-H), 114.7 (CN), 124.4, 135.7,
135.8, 136.4, 137.7, 152.7 (CPy-C=C), 155.8 (CPy-Ar), 164.7 (CPy-O). 13C NMR, (signals of mixture
of isomers) δ, ppm: 127.7, 128.3, 128.5, 128.6, 128.7, 128.8, 128.96, 129.02, 129.1, 129.9. IR
(KBr): 2221 cm-1 (CN). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H15ClNONa 369.0771;
Found 369.0765.
2-(4-chlorophenyl)-6-methoxy-4-phenylethynyl–pyridine (3h). Obtained from 1c (50 mg, 0.19
mmol) and sodium methoxide (0.48 mmol). Purification by preparative TLC with mixture
petroleum ether–ethyl acetate, 8:2 in a yield of 6 mg (10%). Colorless solid. 1Н NMR, δ, ppm: 4.07
s (3H, OCH3), 6.84 s (1H, HPy), 7.40-7.42 m (2H), 7.45-7.47 m (2H), 7.54-7.60 m (2H), 7.72-7.74
13
m (2H), 8.03 d (2H, HAr, J 8.6 Hz). C NMR, δ, ppm: 53.5 (OCH3), 87.0 (C≡), 92.9 (C≡), 111.5
(CPy-H), 115.0 (CPy-H), 122.2, 128.01, 128.5, 128.8, 129.1, 131.9, 134.3, 136.2, 137.0, 153.6 (CPy-
Ph), 167.7 (CPy-O). IR (KBr): 2220 cm-1 (C≡C). HRMS (ESI-TOF) m/z: [M+H]+Calcd for
C20H14ClNO 320.0842; Found 320.0837.
(Е)-,(Z)-2-Methoxy-6-(4-methoxyphenyl)-4-(2-phenylethenyl)pyridine-3-carbonitrile
((E)-
/(Z)-2i). Mixture of isomers. Obtained from 1d (50 mg, 0.19 mmol) and sodium methoxide (0.47
mmol). Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 85:15 in a
1
yield of E-2i 25 mg (38%), yield of Z-2i 28 mg (43%). Colorless solid. Н NMR, E-2i (selected
signals, obtained from spectrum of mixture of isomers) δ, ppm: 23.92 s (3H, OCH3), 4.18 s (3H,
OCH3), 7.54 d (1H, CH=, J 16.2 Hz), 7.63 s (1H, HPy), 8.09 dd (2H, HAr, J 14.4, 8.9 Hz). 1Н NMR,
Z-2i (selected signals, obtained from spectrum of mixture of isomers) δ, ppm: 3.86 s (3H, OCH3),
4.16 s (3H, OCH3), 6.74 d (1H, CH=, J 12.2 Hz), 6.91 d (2H, HAr, J 8.9 Hz), 7.05 d (1H, CH=, J
12.1 Hz) 7.17 s (1H, HPy), 7.71 d (2H, HAr, J 8.9 Hz).1H NMR, (signals of mixture of isomers) δ,
ppm: 7.27-7.33 m, 7.37-7.49 m, 7.66-.7.73 m. 13C NMR, E-2i (selected signals, obtained from
spectrum of mixture of isomers) δ, ppm: 54.4 (OCH3), 55.5 (OCH3), 91.9 (CPy-CN), 107.5 (CPy-H),
114.2 (Cap, o-OCH3), 115.3 (CN), 122.8, 128.6, 128.8, 129.0, 129.7, 132.4, 135.4, 136.8, 151.3
(CPy-C=C), 157.5 (CPy-Ar), 161.6 (CAr-O), 164.9 (CPy-O). 13C NMR, Z-2i (selected signals,
obtained from spectrum of mixture of isomers) δ, ppm: 54.3 (OCH3), 55.4 (OCH3), 93.0 (CPy-CN),
112.1 (CPy-H), 114.1 (Cap, o-OCH3), 115.1 (CN), 124.7, 127.6, 128.4, 128.6, 128.9, 129.9, 135.8,
137.2, 152.3 (CPy-C=C), 156.9 (CPy-Ar), 161.5 (CAr-O), 164.6 (CPy-O). IR (KBr): 2219 cm-1 (CN).
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H19N2O 343.1447; Found 343.1441.
2-Methoxy-6-(4-methoxyphenyl)-4-(phenylethynyl)pyridine (3i). Obtained from 1d (50 mg,
0.19 mmol) and sodium methoxide (0.47 mmol). Purification by preparative TLC with mixture
1
petroleum ether–ethyl acetate, 85:15 in a yield of 10 mg (16%). Colorless solid. Н NMR, δ, ppm:
19

ACCEPTED MANUSCRIPT
3.90 s (3H, OCH3), 4.06 s (3H, OCH3), 6.77 s (1H, HPy), 7.01 d (2H, HAr, J 8.9 Hz), 7.28-7.33 m
13
(2H), 7.40-7.42 m (2H), 7.58-7.61 m (2H), 8.05 d (2H, HAr, J 9.0 Hz). C NMR, δ, ppm: 55.4
(OCH3), 87.4 (C≡), 92.5 (C≡), 114.0 (o-OCH3-CAr), 114.1 (CPy-H), 114.4 (CPy-H), 122.4, 128.2.
128.5. 128.9. 129.0, 131.9. 154.6 (CPy-Ar), 160.6 (CPy-O), 163.9 (CAr-O). IR (KBr): 2219 cm-1
(C≡C). HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C21H18NO2 316.1338; Found 316.1332.
(Е)-,(Z)-2-Ethoxy-6-(4-methoxyphenyl)-4-(2-phenylethenyl)pyridine-3-carbonitrile ((E)-/(Z)-
2j). Mixture of isomers. Obtained from 1d (50 mg, 0.19 mmol) and sodium ethoxide (0.48 mmol).
Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 8:2 in a yield of E-2j
27 mg (38%), yield of Z-2j 9 mg (13%). Colorless solid. 1Н NMR, E-2j (selected signals, obtained
from spectrum of mixture of isomers) δ, ppm: 1.52 t (2H, OEt, J 7.0 Hz), 3.91 s (3H, OMe), 4.65 q
(3H, OEt, J 7.0 Hz), 7.53 d (1H, HC=, J 16.2 Hz), 7.61 s (1H, HPy).1Н NMR, Z-2j (selected signals,
obtained from spectrum of mixture of isomers) δ, ppm: 1.51 t (2H, OEt, J 7.0 Hz), 3.86 s (3H,
OMe), 4.63 q (3H, OEt, J 7.2 Hz), 6.74 d (1H, HC=, J 12.2 Hz), 6.90 d (2H, HAr, J 8.9 Hz), 7.14 s
(1H, HPy). 1H NMR, (signals of mixture of isomers) δ, ppm:7.02-7.06 m, 7.29-7.32 m, 7.38-7.51 m,
13
7.64-7.70 m, 8.04-8.10 m. C NMR, E-2j (selected signals, obtained from spectrum of mixture of
isomers) δ, ppm: 14.5 (CH3, OEt), 55.4 (OMe), 63.3 (CH2, OEt), 96.2 (CPy-CN), 107.2 (CPy-H),
114.1, 114.3, 114.3 (CN), 122.9 (C=), 136.6, 137.0, 151.3, 157.8, 161.8, 163.9 (CPy-O). 13C NMR,
Z-2j (selected signals, obtained from spectrum of mixture of isomers) δ, ppm: 14.5 (CH3, OEt), 55.4
(OMe), 63.1 (CH2, OEt), 92.1 (CPy-CN), 111.9 (CPy-H), 113.7, 114.2, 115.4 (CN), 121.4 (C=),
136.5, 138.2, 152.3, 157.4, 161.5, 164.6 (CPy-O). 13C NMR, (signals of mixture of isomers) δ, ppm:
124.8, 127.6, 128.3, 128.6, 128.58, 128.62, 128.76, 128.82, 128.9, 129.0, 129.56, 129.61, 129.9,
130.0, 130.3, 132.4. IR (KBr): 2220 cm-1 (CN). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C23H20N2O2Na 379.1422; Found 379.1417. GC-МS, m/z, Irel. (%): 356 M+ (100), 341 (22), 327
(8), 311 (10), 302 (75), 279 (85), 77 (18).
2-Ethoxy-6-(4-methoxyphenyl)-4-phenylethynylpyridine (3j). Obtained from 1d (50 mg, 0.19
mmol) and sodium ethoxide (0.48 mmol). Purification by preparative TLC with mixture petroleum
ether–ethyl acetate, 8:2 in a yield of 3 mg (5%). Colorless solid. 1Н NMR, δ, ppm:1.47 t (3H, OEt,
J 7.1 Hz), 3.89 s (3H, OMe), 4.51 q (2H, OEt, J 7.0 Hz), 6.75 s (1H, HPy), 7.01 d (2H, HAr, J8.9
Hz), 7.40-7.41 m (4H), 7.58-7.60 m (2H), 8.03 d (2H, HAr, J 8.8 Hz).13C NMR, δ, ppm:14.7 (CH3,
OEt), 55.4 (Me), 61.7 (CH2, OEt), 87.4 (C≡), 92.4 (C≡), 110.3 (CPy-H), 114.0 (CAr), 114.2 (CPy-H),
128.1, 128.5, 129.0, 131.3, 131.9, 134.0, 154.6, 160.6, 163.6 (CPy-O). IR (KBr): 2218 cm-1 (C≡C).
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C22H20NO2 330.1494; Found 330.1489.
(Е)-,(Z)-2-Methoxy-4-(2-(4-methylphenyl)ethenyl)-6-phenylpyridine-3-carbonitrile ((E)-/(Z)-
2k). Mixture of isomers. Obtained from 1e (50 mg, 0.20 mmol) and sodium methoxide (0.50 mmol).
Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 85:15 in a yield of E-
1
2k 22 mg (34%), yield of Z-2k 4 mg (6%). Colorless solid. Н NMR, E-2k (selected signals,
20

ACCEPTED MANUSCRIPT
obtained from spectrum of mixture of isomers) δ, ppm: 2.42 s (3H, CH3), 4.19 s (3H, OCH3), 7.37 d
1
(1H, CH=, J 16.2 Hz), 7.70 s (1H, HPy), 8.13 dd (2H, HAr, J 7.9, 1.6 Hz). Н NMR, Z-2l (selected
signals, obtained from spectrum of mixture of isomers) δ, ppm: 2.37 s (3H, CH3), 4.18 s (3H,
OCH3), 6.70 d (1H, CH=, J 12.2 Hz), 7.02 d (1H, CH=, J 12.2 Hz), 7.12 d (2H, HAr, J 8.1 Hz), 7.17
13
d (2H, HAr, J 8.1 Hz). C NMR, E-2k (selected signals, obtained from spectrum of mixture of
isomers) δ, ppm: 21.5 (CH3), 54.4 (OCH3), 92.7 (CPy-CN), 108.3 (CPy-H), 115.2 (CN), 121.6, 137.0,
13
137.7, 140.1, 151.7 (CPy-C=C), 157.7 (CPy-Ar), 164.9 (CPy-O). C NMR, Z-2k (selected signals,
obtained from spectrum of mixture of isomers) δ, ppm: 21.3 (CH3), 54.4 (OCH3), 113.1 (CPy-H),
114.8 (CN), 123.8, 137.4, 138.5, 140.6, 153.0 (CPy-C=C), 157.1 (CPy-Ar), 164.7 (CPy-O). 13C NMR,
(signals of mixture of isomers) δ, ppm: 127.1, 127.3, 127.6, 128.7, 128.8, 129.3, 129.7, 130.2,
130.3, 132.4, 132.6. IR (KBr): 2219 cm-1 (CN). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C22H19N2O 327.1497; Found 327.1492.
2-Methoxy-4-(4-methylphenyl)ethynyl-6-phenylpyridine (3k). Obtained from 1e (50 mg,
0.20mmol) and sodium methoxide (0.50 mmol). Purification by preparative TLC with mixture
1
petroleum ether–ethyl acetate, 85:15 in a yield of 3 mg (5%). Colorless solid. Н NMR, δ, ppm:
2.41 s (3H, OCH3), 4.07 s (3H, OCH3), 6.82 s (1H, HPy), 7.12-7.56 m (5H), 8.09 d (2H, HAr, J 8.5
Hz). 13C NMR (selected signals – low concentration), δ, ppm: 23.0 (CH3), 54.4 (OCH3), 86.7 (C≡),
93.0 (C≡), 111.0 (CPy-H), 115.3 (CPy-H), 128.7, 128.8, 129.1, 129.3, 131.8, 138.6, 139.4, 154.8
(CPy-Ph), 164.0 (CPy-O). IR (KBr): 2221 cm-1 (C≡C). HRMS (ESI-TOF) m/z: [M+H]+ Calcd for
C21H18NO 300.1388; Found 300.1383.
(Е)-,(Z)-2-Ethoxy-4-(2-(4-methylphenyl)ethenyl)-6-phenylpyridine-3-carbonitrile ((E)-/(Z)-
2l). Mixture of isomers. Obtained from 1e (50 mg, 0.20 mmol) and sodium ethoxide (0.50 mmol).
Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 85:15 in a yield of E-2l
1
17 mg (10%), yield of Z-2l 8 mg (5%). Colorless solid. Н NMR, E-2l (selected signals, obtained
from spectrum of mixture of isomers) δ, ppm: 1.53 t (2H, OEt, J 7.2 Hz), 2.42 s (3H, Me), 4.66 q
1
(3H, OEt, J 7.0 Hz), 7.68 s (1H, HPy), 8.11 d (2H, HAr, J8.2 Hz). Н NMR, Z-2l (selected signals,
obtained from spectrum of mixture of isomers) δ, ppm: 1.52 t (2H, OEt, J 7.0 Hz), 2.37 s (3H, Me),
4.65 q (3H, OEt, J 7.0 Hz), 6.70 d (1H, HC=, J 12.1 Hz), 7.01 d (1H, HC=, J 12.2 Hz), 7.12 d (2H,
1
HAr, J 8.1 Hz), 7.18 d (2H, HAr, J 8.1 Hz), 7.36 s (1H, HPy). H NMR, (signals of mixture of
13
isomers) δ, ppm: 7.22-7.26 m, 7.39-7.42 m, 7.50-7.59 m, 7.24-7.77 m. C NMR, E-2l (selected
signals, obtained from spectrum of mixture of isomers) δ, ppm: 14.5 (CH3, OEt), 21.4 (Me), 63.2
(CH2, OEt), 92.9 (CPy-CN), 108.0 (CPy-H), 114.6 (CN), 121.7 (HC=), 140.1, 151.7, 157.7, 164.7
13
(CPy-O). C NMR, Z-2l (selected signals, obtained from spectrum of mixture of isomers) δ, ppm:
14.5 (CH3, OEt), 21.3 (Me), 63.1 (CH2, OEt), 94.1 (CPy-CN), 112.8 (CPy-H), 115.2 (CN), 123.9
(HC=), 140.6, 152.9, 158.0, 164.4 (CPy-O). 13C NMR, (signals of mixture of isomers) δ, ppm:
127.1, 124.2, 127.6, 128.7, 128.8, 128.86, 128.88, 129.3, 129.4, 129.7, 130.1, 130.2, 130.5, 130.9,
21

ACCEPTED MANUSCRIPT
132.4, 132.7, 132.8, 136.9, 137.1, 137.2, 137.5, 137.8. IR (KBr): 2221 cm-1 (CN). HRMS (ESI-
TOF) m/z: [M + Na]+ Calcd for C23H20N2ONa 363.1473; Found 363.1468.
2-Ethoxy-4-(4-methylphenyl)ethynyl-6-phenylpyridine (3l). Obtained from 1e (50 mg,
0.20mmol) and sodium ethoxide (0.50 mmol). Purification by preparative TLC with mixture
petroleum ether–ethyl acetate, 85:15 in a yield of 6 mg (5%). Colorless solid. 1Н NMR, δ, ppm:1.47
t (3H, OEt, J 7.1 Hz), 2.41 s (3H, Me), 4.53 q (2H, OEt, J 7.1 Hz), 6.79 s (1H, HPy), 7.21 d (2H,
HAr, J 7.9 Hz), 7.40-7.44 m (2H), 7.46 s (1H, HPy), 7.47-7.49 m (3H), 8.07 d (2H, HAr, J 7.1 Hz).
13C NMR, δ, ppm: 13.7 (CH3, OEt), 19.2 (Me), 65.6 (CH2, OEt), 86.8 (C≡), 93.0 (C≡), 111.2 (CPy-
H), 115.1 (CPy-H), 119.3, 126.6, 128.6, 128.9, 129.1, 129.5, 130.9, 131.8, 132.4, 134.4, 138.6,
139.3, 154.8, 163.7, 137.7 (CPy-O). IR (KBr): 2212 cm-1 (C≡C). HRMS (ESI-TOF) m/z: [M+H]+
Calcd for C22H20NO 314.1545; Found 314.1539.
(Е-),(Z)- 4-(2-(4-chlorophenyl)ethenyl)-2-methoxy-6-phenylpyridine-3-carbonitrile ((E)-/(Z)-
2m). Mixture of isomers. Obtained from 1f (50 mg, 0.19 mmol) and sodium methoxide (0.48
mmol). Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 85:15 in a
yield of E-2m 12 mg (18%), yield of Z-2m 18 mg (26%). Colorless solid. 1Н NMR, E-2m (selected
signals, obtained from spectrum of mixture of isomers) δ, ppm: 4.20 s (3H, OCH3), 7.69 s (1H,
HPy), 8.13 dd (2H, HAr, J 7.7, 1.8 Hz).1Н NMR, Z-2m (selected signals, obtained from spectrum of
mixture of isomers) δ, ppm: 4.19 s (3H, OCH3), 6.77 d (1H, CH=, J 12.2 Hz), 6.99 d (1H, CH=, J
1
12.2 Hz), 7.80 dt (2H, HAr, J 7.5, 3.6 Hz). H NMR, (signals of mixture of isomers) δ, ppm: 7.19-
13
7.59 m. C NMR, E-2m (selected signals, obtained from spectrum of mixture of isomers) δ, ppm:
13
54.5 (OCH3), 97.3 (CPy-CN), 108.4 (CPy-H), 151.2 (CPy-C=C), 155.9 (CPy-Ar). C NMR, Z-2m
(selected signals, obtained from spectrum of mixture of isomers) δ, ppm: 54.5 (OCH3), 94.0 (CPy-
CN), 112.9 (CPy-H), 114.7 (CN), 151.2 (CPy-C=C), 157.5 (CPy-Ar), 164.7 (CPy-O). 13C
NMR,(signals of mixture of isomers) δ, ppm: 125.2, 127.1, 127.3, 128.2, 128.7, 128.8, 128.85,
128.88, 128.92, 129.3, 129.6, 130.2, 130.4, 132.6, 134.0, 134.4, 135.8, 137.2. IR (KBr): 2222 cm-1
(CN). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H15ClNONa 369.0771; Found 369.0765.
4-(4-Chlorophenyl)ethynyl-2-methoxy-6-phenylpyridine (3m). Obtained from 1f (50 mg,
0.19mmol) and sodium methoxide (0.48 mmol). Purification by preparative TLC with mixture
1
petroleum ether–ethyl acetate, 85:15 in a yield of 3 mg (5%). Colorless solid. Н NMR, δ, ppm:
4.08 s (3H, OCH3), 6.82 s (1H, HPy), 7.39 d (2H, HAr, J 8.5 Hz), 7.44-7.56 m (4H), 7.73 dd (2H,
HAr, J 5.6, 3.4 Hz), 8.08 d (2H, HAr, J 7.0 Hz).13C NMR (selected signals – low concentration), δ,
ppm: 53.4 (OCH3), 111.2 (CPy-H), 115.1 (CPy-H), 126.8, 128.7, 128.8, 128.9, 130.9, 130.1. IR
(KBr): 2223 cm-1 (C≡C). HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C20H15ClNO 320.0842; Found
320.0837.
(Е)-,(Z)-2-Methoxy-4-(2-(4-methoxyphenyl)ethenyl)-6-phenylpyridine-3-carbonitrile
((E)-
/(Z)-2n). Mixture of isomers. Obtained from 1g (50 mg, 0.16mmol) and sodium methoxide (0.40
22

ACCEPTED MANUSCRIPT
mmol). Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 85:15 in a
yield of E-2n 25 mg (45%), yield of Z-2n 23 mg (41%). Colorless solid. 1Н NMR, E-2n (selected
signals, obtained from spectrum of mixture of isomers) δ, ppm: 3.89 s (3H, OCH3), 4.19 s (3H,
OCH3), 6.83 d (2H, HAr, J 8.8 Hz), 7.68 s (1H, HPy), 7.83 dd (2H, HAr, J 6.5, 3.2 Hz), 8.13 dd (2H,
HAr, J 8.0, 1.6 Hz). 1Н NMR, Z-2n (selected signals, obtained from spectrum of mixture of isomers)
Z
δ, ppm: 3.82 s (3H, OCH3), 4.18 s (3H, OCH3 ), 6.64 d (1H, =CH, J 12.1 Hz), 6.78 d (2H, HAr, J
8.7 Hz), 7.35 s (1H, HPy), 7.97 dd (2H, HAr, J 7.3, 2.3 Hz), 8.10 dd (2H, HAr, J 7.4, 2.3 Hz). 1H
NMR, (signals of mixture of isomers) δ, ppm: 6.93-6.98 m, 7.22-7.30 m, 7.41-7.43 m, 7.50-7.54 m,
7.59-7.64 m. 13C NMR, E-2n (selected signals, obtained from spectrum of mixture of isomers) δ,
ppm: 54.4 (OCH3), 55.3 (OCH3), 94.0 (CN). 13C NMR, Z-2n (selected signals, obtained from
spectrum of mixture of isomers) δ, ppm: 54.4 (OCH3), 55.4 (OCH3), 92.5 (CN). 13C NMR, (signals
of mixture of isomers) δ, ppm: 108.1, 112.9, 114.1, 114.5, 114.3, 114.6, 114.9, 115.3, 120.3, 122.7,
127.1, 127.3, 127.4, 128.0, 128.1, 128.7, 129.2, 128.8, 128.9, 130.17, 130.21, 130.5, 130.6, 134.2,
136.7, 136.8, 137.4, 137.8, 138.8, 151.9, 153.2, 157.2, 157.6, 159.8, 161.0, 161.1, 164.7, 165.0. IR
(KBr): 2221 cm-1 (CN). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H19N2O2 343.1447; Found
343.1441.
2-Methoxy-4-(2-(4-methoxyphenyl)ethynyl)–6-phenylpyridine (3n). Obtained from 1g (50 mg,
0.16mmol) and sodium methoxide (0.40mmol). Purification by preparative TLC with mixture
1
petroleum ether–ethyl acetate, 85:15 in a yield of 6 mg (12%). Colorless solid. Н NMR, δ, ppm:
3.87 s (3H, OCH3), 4.07 s (3H, OCH3), 6.81 s (1H, HPy), 6.93 d (2H, HAr, J 8.8 Hz), 7.41-7.55 m
(6H), 8.09 d (2H, HAr, J 8.5 Hz).13C NMR, δ, ppm: 53.4 (OCH3), 55.3 (OCH3), 86.2, 92.9, 110.8,
114.1, 115.1, 126.7, 128.6, 129.1, 133.5, 134.5, 138.6, 154.7, 160.2, 163.9. IR (KBr): 2219cm-1
(C≡C). HRMS (ESI-TOF) m/z: [M+H]+Calcd for C21H18NO2316.1338; Found 316.1392.
(Е),(Z)-6-(4-chlorophenyl)-2-methoxy-4-(2-(4-methylphenyl)ethenyl)pyridine-3-carbonitrile
((E)-/(Z)-2o). Mixture of isomers. Obtained from 1h (50 mg, 0.18 mmol) and sodium methoxide
(0.45 mmol). Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 85:15 in
a yield of E-2o 17 mg (26%), yield of Z-2o 21 mg (32%). Colorless solid. 1Н NMR, E-2o (selected
signals, obtained from spectrum of mixture of isomers) δ, ppm: 2.43 s (3H, CH3), 4.18 s (3H,
OCH3), 7.66 s (1H, HPy), 8.04 d (2H, HAr, J 8.7 Hz), 8.07 d (2H, HAr, J 8.7 Hz) .1Н NMR, Z-2o
(selected signals, obtained from spectrum of mixture of isomers) δ, ppm: 2.37 s (3H, CH3), 4.16 s
(3H, OCH3), 6.69 d (1H, CH=, J 12.1 Hz), 7.04 d (1H, CH=, J 12.2 Hz), 7.12 d (2H, HAr, J 8.1 Hz),
7.17 d (2H, HAr, J 8.2 Hz), 7.23 s (1H, HPy), 7.37 d (2H, HAr, J 8.7 Hz), 7.69 d (2H, HAr, J 8.7 Hz).
1H NMR, (signals of mixture of isomers) δ, ppm: 7.34-7.39 m, 7.48-7.58 m, 7.67-7.71 m. 13C NMR,
E-2o (selected signals, obtained from spectrum of mixture of isomers) δ, ppm: 21.5 (CH3), 54.5
(OCH3), 93.0 (CPy-CN), 108.1 (CPy-H), 115.0 (CN), 121.4, 132.5, 135.4, 137.3, 138.9, 140.3, 151.9
(CPy-C=C), 156.4 (CPy-Ar), 164.9 (CPy-O). 13C NMR, Z-2o (selected signals, obtained from
23

ACCEPTED MANUSCRIPT
spectrum of mixture of isomers) δ, ppm: 21.3 (CH3), 54.4 (OCH3), 94.4 (CPy-CN), 112.9 (CPy-H),
114.7 (CN), 123.6, 132.4, 132.7, 135.9, 136.4, 138.6, 153.0 (CPy-C=C), 155.8 (CPy-Ar), 164.7 (CPy-
13
O). C NMR, (signals of mixture of isomers) δ, ppm: 27.7, 128.4, 128.5, 128.8, 128.9, 129.0,
129.4, 129.8. IR (KBr): 2222 cm-1 (CN). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H18N2O
361.1108; Found 361.1102.
2-(4-Chlorophenyl)-6-methoxy-4-(4-methylphenyl)ethynylpyridine (3o). Obtained from 1h (50
mg, 0.18mmol) and sodium methoxide (0.45mmol). Purification by preparative TLC with mixture
1
petroleum ether–ethyl acetate, 85:15 in a yield of 10 mg (17%). Colorless solid. Н NMR, δ, ppm:
2.41 s (3H, CH3), 4.06 s (3H, OCH3), 6.83 s (1H, HPy), 7,21 d (2H, HAr, J 7.9 Hz), 7.44-7.49 m
(5H), 8.02 d (2H, HAr, J 8.6 Hz). 13C NMR, δ, ppm: 24.6 (CH3), 53.5 (OCH3), 86.5 (C≡), 93.3 (C≡),
111.3 (CPy-H), 115.0 (CPy-H), 119.1 (CAr-C≡), 128.0, 128.8, 129.3, 131.8, 134.6, 136.1, 137.0,
139.4, 153.5 (CPy-C6H4Cl), 164.0 (CPy-O). IR (KBr): 2219 cm-1 (C≡C). HRMS (ESI-TOF) m/z:
[M+Na]+ Calcd for C20H15NONa 308.1051; Found 308.1046.
(Е)-,(Z)-6-(4-Bbromphenyl)-2-methoxy-4-(2-(4-methylphenyl)ethenyl)pyridine-3-carbonitrile
((E)-/(Z)-2p). Mixture of isomers. Obtained from 1i (50 mg, 0.16 mmol) and sodium methoxide
(0.40 mmol). Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 95:5 in a
1
yield of E-2p 23 mg (38%), yield of Z-2p 21 mg (34%). Colorless solid. Н NMR, E-2p (selected
signals, obtained from spectrum of mixture of isomers) δ, ppm: 2.42 s (3H, CH3), 4.18 s (3H,
1
OCH3), 7.26 d (2H, HAr, J 7.9 Hz), 7.36 d (1H, HC=, J 16.2 Hz), 8.00 d (2H, HAr, J 8.5 Hz). Н
NMR, Z-2p (selected signals, obtained from spectrum of mixture of isomers) δ, ppm: 2.37 s (3H,
CH3), 4.16 s (3H, OCH3), 6.70 d (1H, HC=, J 12.2 Hz), 7.04 d (1H, HC=, J 12.2 Hz), 7.12 d (2H,
1
HAr, J 8.1 Hz), 7.17 d (2H, HAr, J 8.1 Hz), 7.23 s (1H, HPy). H NMR, (signals of mixture of
isomers) δ, ppm: 7.51-7.56 m, 7.61-7.67 m. 13C NMR, E-2p (selected signals, obtained from
spectrum of mixture of isomers) δ, ppm: 21.5 (CH3), 54.5 (OCH3), 93.1 (CPy, C-CN), 108.1 (CPy-
H), 115.0 (CN), 124.9, 151.9, 156.4, 164.9. 13C NMR, Z-2p (selected signals, obtained from
spectrum of mixture of isomers) δ, ppm: 21.3 (CH3), 54.4 (OCH3), 94.4 (CPy, C-CN), 112.9 (CPy-
13
H), 114.7 (CN), 124.8, 153.1, 155.8, 164.7. C NMR, (signals of mixture of isomers) δ, ppm:
121.4, 123.6, 127.7, 128.6, 128.8, 129.3, 129.7, 131.9, 132.0, 132.4, 132.5, 132.7, 136.3, 136.6,
137.3, 137.7, 138.6, 140.3. IR (KBr): 2221 cm-1 (CN). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C22H18BrN2O 405.0603; Found 405.0597.
6-(4-Bromphenyl)-2-methoxy-4-(2-(4-methylphenyl)ethynyl)pyridine (3p). Obtained from 1i
(50 mg, 0.16 mmol) and sodium methoxide (0.40 mmol). Purification by preparative TLC with
1
mixture petroleum ether–ethyl acetate, 95:5 in a yield of 8 mg (14%). Colorless solid. Н NMR, δ,
ppm: 2.41 s (3H, CH3), 4.06 s (3H, OCH3), 6.83 s (1H, HPy), 7.21 d (2H, HAr, J 7.9 Hz), 7.44 s (1H,
HPy), 7.48 d (2H, HAr, J 8.1 Hz), 7.61 d (2H, HAr, J 8.6 Hz), 7.96 d (2H, HAr,J 8.7 Hz). 13C NMR, δ,
ppm: 21.6 (CH3), 53.5 (OCH3), 86.5, 93.2, 111.4, 115.0, 119.1, 123.5, 128.3, 129.3, 131.8, 134.2,
24

ACCEPTED MANUSCRIPT
134.6, 137.5, 139.4, 153.6, 164.0. IR (KBr): 2219 cm-1 (C≡C). HRMS (ESI-TOF) m/z: [M+H]+
Calcd for C21H17BrNO 478.0494; Found 478.0511.
(Е)-,(Z)-6-(4-Bromphenyl)-2-ethoxy-4-(2-(4-methylphenyl)ethenyl)pyridine-3-carbonitrile
((E)-/(Z)-2q). Mixture of isomers. Obtained from 1i (50 mg, 0.16 mmol) and sodium ethoxide (0.40
mmol). Purification by preparative TLC with mixture petroleum ether–ethyl acetate, 85:15 in a
1
yield of E-2q 25 mg (39%), yield of Z-2q 9 mg (14%). Colorless solid. Н NMR, E-2q (selected
signals, obtained from spectrum of mixture of isomers) δ, ppm:1.53 t (2H, OEt, J 7.0 Hz), 2.43 s
1
(3H, Me), 4.64 q (3H, OEt, J 7.2 Hz), 7.34 d (1H, HC=, J 16.2 Hz). Н NMR, Z-2q (selected
signals, obtained from spectrum of mixture of isomers) δ, ppm: 1.52 t (2H, OEt, J 7.0 Hz), 2.37 s
(3H, Me), 4.62 q (3H, OEt, J 7.0 Hz), 6.69 d (1H, HC=, J 12.2 Hz), 7.03 d (1H, HC=, J 12.1 Hz),
7.12 d (2H, HAr, J 8.1 Hz), 7.17 d (2H, HAr, J 8.1 Hz), 7.20 s (1H, HPy), 7.24 d (2H, HAr, J 8.0 Hz).
1H NMR, (signals of mixture of isomers) δ, ppm: 7.50-7.61 m, 7.64-7.75 m, 7.73-7.75 m, 7.94-7.99
m.13C NMR, E-2q (selected signals, obtained from spectrum of mixture of isomers) δ, ppm: 13.7
(CH3, OEt), 21.3 (Me), 66.6 (CH2, OEt), 94.5 (CPy-CN), 107.8 (CPy-H), 114.8 (CN), 121.2 (C=),
13
138.6, 151.9, 156.4, 167.7 (CPy-O). C NMR, Z-2q (selected signals, obtained from spectrum of
mixture of isomers) δ, ppm: 14.5 (CH3, OEt), 19.2 (Me), 63.2 (CH2, OEt), 94.5 (CPy-CN), 112.7
(CPy-H), 114.3 (CN), 123.7 (C=), 137.5, 153.0, 155.8, 164.4 (CPy-O). 13C NMR, (signals of mixture
of isomers) δ, ppm: 127.7, 128.6, 128.7, 128.8, 128.9, 129.3, 129.4, 129.7, 130.9, 131.9, 132.0,
132.1, 132.4, 132.8. IR (KBr): 2223 cm-1 (CN). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C23H20BrN2O 419.0759; Found 419.0754.
2-(4-Bromphenyl)-6-ethoxy-4-(4-methylphenyl)ethynylpyridine (3q). Obtained from 1i (50
mg, 0.16 mmol) and sodium ethoxide (0.40 mmol). Purification by preparative TLC with mixture
petroleum ether–ethyl acetate, 85:15 in a yield of 4 mg (7%). Colorless solid. 1Н NMR, δ, ppm:1.46
t (3H, OEt, J 7.1 Hz), 2.41 s (3H, Me), 4.50 q (2H, OEt, J 7.0 Hz), 6.81 s (1H, HPy), 7.21 d (2H,
HAr, J 7.9 Hz), 7.42 s (1H, HPy), 7.48 d (2H, HAr, J 8.1 Hz), 7.60 d (2H, HAr, J 8.6 Hz), 7.94 d (2H,
13
HAr, J 8.6 Hz). C NMR, δ, ppm: 14.1 (CH3, OEt), 21.6 (Me), 65.6 (CH2, OEt), 86.6 (C≡), 93.2
(C≡), 111.6 (CPy-H), 114.8 (CPy-H), 119.2, 128.3, 128.9, 129.3, 130.9, 131.8, 131.8, 139.4, 153.6,
163.8, 167.7 (CPy-O). IR (KBr): 2214 cm-1 (C≡C). HRMS (ESI-TOF) m/z: [M+H]+ Calcd for
C22H19BrNO 392.0650; Found 392.0645.
Procedure for the Synthesis of 1-cyano-5-oxo-5-phenyl-3-phenylethynylpentannitrile (4)
and
4-hydroxy-3-(oxophenylmethyl)-4-phenyl-2,6-(bis(phenyletynyl)cyclohexane-1,1-
dicarbonitrile (5). Malononitrile (36.3 mg, 0.55 mmol) was added to absolute THF (1 mL), the
flask was filled with argon and the solution (0.2 mL, 2 mmol/mL) of LDA (0.55 mmol) in THF was
dropwise added to obtained mixture. The solution of (Е)-1,5-diphenylpent-2-en-4-yn-1-оne 1a (50
mg, 0.22 mmol) in absolute THF(1 mL) was added to malononitrile solution and mixture was
stirring at room temperature for 17 h. The reaction mixture was poured into water (30 mL), and
25

ACCEPTED MANUSCRIPT
extracted with CH2Cl2 (3×30 mL). The combined organic layers were dried with Na2SO4. Solvent
was evaporated under the reduced pressure. The obtained residue was subjected to preparative TCL
on silica gel with eluation by petroleum ether−ethyl acetate mixture (75 : 25 vol.).
1-Cyano-5-oxo-5-phenyl-3-phenylethynylpentannitrile (4), 4-hydroxy-3-(oxophenylmethyl)-4-
phenyl-2,6-(bis(phenyletynyl)cyclohexane-1,1-dicarbonitrile (5). Mixture of compounds in a yield
of 4 27 mg (41%), yield of 5 13 mg (22%). Yellow crystals. 1Н NMR, 4 (selected signals, obtained
from spectrum of mixture of compounds) δ, ppm: 3.60 d (1H, CH2, J 8.8 Hz), 3.67 d (1H, CH2, J
4.5 Hz), 3.98 dt (1H, CH-C≡C, J 9.0, 4.6 Hz), 4.61 d (1H, CH-(CN)2, J 4.6 Hz), 7.68 t (1H, HPh, J
1
7.4 Hz), 8.02 d (2H, HPh, J 7.3 Hz). Н NMR, 5 (selected signals, obtained from spectrum of
mixture of compounds) δ, ppm: 2.40 s (1H, OH), 3.55 d (1H, CH2, J 8.8 Hz), .3.72 d (1H, CH2, J
4.5 Hz), 4.06 dd (1H, CH-CH2, J 9.8, 6.0 Hz), 4.15 d (1H, CH-CO, J 11.5 Hz), 4.60 d (1H, CH-CH-
CO, J 10.3 Hz), 6.97 d (2H, HPh, J 7.2 Hz), 7.87 d (2H, HPh, J 7.5 Hz). 1H NMR, (signals of mixture
of compounds) δ, ppm: 7.13-7.26 m, 7.33-7.42 m, 7.49-7.57 m. 13C NMR, 4 (selected signals,
obtained from spectrum of mixture of compounds) δ, ppm: 28.0 (CH-(CN)2), 30.6 (CH-C≡C), 40.3
(CH2), 83.9 (C≡), 86.9 (C≡), 111.1 (CN), 111.6 (CN), 128.2, 128.39, 129.0, 132.0, 196.9 (CO). 13C
NMR, 5 (selected signals, obtained from spectrum of mixture of compounds) δ, ppm: 34.3 (CH-
CH2), 37.3 (CH2), 41.9 (C-(CN)2), 46.2 (CH-CH-CO), 49.9 (CH-CO), 73.8 (C-OH), 82.2 (C≡), 83.9
(C≡), 86.7 (C≡), 89.4 (C≡), 112.4 (CN), 113.9 (CN), 202.8 (CO). 13C NMR, (signals of mixture of
compounds) δ, ppm: 120.9, 121.5, 121.7, 124.4, 128.0, 128.1, 128.36, 128.66, 128.72, 128.8,
129.10, 129.14, 131.7, 132.06, 134.4, 135.5, 137.2, 142.8. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd
for 4 C20H14N2ONa 321.1004; Found 321.0998. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for 5
C37H26N2O2Na 553.1892; Found 553.1886. IR (KBr): 1664 cm-1 (CO), 1683 cm-1 (CO), 2219 cm-1
(CN, C≡C).
Acknowledgements
This work was supported by Russian Scientific Foundation (grant no. 18-13-00008). Spectral
studies were performed at Center for Magnetic Resonance, Center for Chemical Analysis and
Materials Research, and Research Center for X-ray Diffraction Studies of Saint Petersburg State
University, Saint Petersburg, Russia.
Supplementary data
1
13
The data contain H, C NMR, IR spectra of compounds, X-Ray data, fluorescent spectra, and
HPLC data.
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