Three-Component Reaction of Dimethyl Malonate with α,β-Acetylenic Aldehydes and Amines. Synthesis of Push–Pull Buta-1,3-dienes

Article abstract of DOI:10.1134/S1070428020100140

Abstract: Three-component reaction of dimethyl malonate with α,β-acetylenic aldehydes and cyclic secondary amines (pyrrolidine, piperidine, morpholine, and piperazine) under mild conditions afforded dimethyl 2-(3-aminoprop-2-en-1-ylidene)malonates in 50–9

Full text of DOI:10.1134/S1070428020100140

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2020, Vol. 56, No. 10, pp. 1758–1763. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Organicheskoi Khimii, 2020, Vol. 56, No. 10, pp. 1590–1597.
Three-Component Reaction of Dimethyl Malonate
with α,β-Acetylenic Aldehydes and Amines.
Synthesis of Push–Pull Buta-1,3-dienes
S. A. Sokova,b, I. S. Odinb, S. S. Zlotskiia, and A. A. Golovanovb,*
a Ufa State Petroleum Technological University, Ufa, 450062 Russia
b Togliatti State University, Togliatti, 445020 Russia
*e-mail: aleksandgolovanov@yandex.ru
Received July 10, 2020; revised July 21, 2020; accepted July 25, 2020
Abstract—Three-component reaction of dimethyl malonate with α,β-acetylenic aldehydes and cyclic secondary
amines (pyrrolidine, piperidine, morpholine, and piperazine) under mild conditions afforded dimethyl
2-(3-aminoprop-2-en-1-ylidene)malonates in 50–91% yields. The products were formed preferentially as E
isomers, and the described reaction provides a convenient method for the synthesis of push–pull buta-1,3-dienes
that are interesting as fluorescent, solvatochromic, and nonlinear optical materials and starting compounds in
the synthesis of carbo- and heterocycles. A plausible reaction mechanism involves Knoevenage condensation of
dimethyl malonate with α,β-acetylenic aldehyde to give dimethyl 2-(prop-2-yn-1-ylidene)malonate and
subsequent nucleophilic addition of cyclic amine to the latter.
Keywords: multicomponent reactions, prop-2-ynals, cyclic amines, dimethyl malonate, stereoselectivity,
Knoevenagel condensation, nucleophilic addition, buta-1,3-dienes
DOI: 10.1134/S1070428020100140
Di- and polyenes containing electron-donating and
electron-withdrawing functional groups at the opposite
ends of a conjugated bond chain (push–pull di- and
polyenes) possess a combination of valuable physical
and chemical properties. Due to strong polarization of
the π-electron system, such compounds exhibit fluo-
rescence [1, 2] and solvatochromic properties [3, 4]
and are promising as dyes [5, 6] and nonlinear optical
materials [7, 8]. Push–pull dienes are used in organic
synthesis, in particular for the preparation of carbo-
and heterocycles [9–11] and polyunsaturated carbonyl
compounds [12]. Development of simple and efficient
procedures for the synthesis of push–pull di- and
polyenes from accessible starting materials is of great
importance for the design of modern smart materials
and organic synthesis.
enyne and nucleophilic addition into a single three-
component synthetic procedure. Therefore, the present
work was aimed at developing a one-pot procedure for
the synthesis of push–pull buta-1,3-dienes by three-
component condensation of dimethyl malonate,
α,β-acetylenic aldehyde, and cyclic amine.
As expected, 3-phenylprop-2-ynal (1a) reacted with
dimethyl malonate (2) and pyrrolidine (3a) in methanol
to give the target product, dimethyl 2-[3-(pyrrolidin-1-
yl)-3-phenylprop-2-en-1-ylidene]malonate (4a). In the
optimal case, an equimolar amount of amine 3a was
added to a solution of ester 2 and aldehyde 1a. The
addition of 3a was accompanied by strong evolution of
heat, so that cooling of the reaction mixture in the
initial period was necessary. Under these conditions,
the maximum yield of 4a (91%) was achieved in 48 h.
Likewise, the reactions of aldehydes 1a–1d with di-
methyl malonate (2) and amines 3a–3c afforded 50–
82% of 4a–4g (Scheme 1).
We previously synthesized 5-amino- and 5-sulfanyl-
penta-2,4-dien-1-ones by nucleophilic addition of the
corresponding amines and thiols to activated enynes
[13–15] which were prepared in turn by condensation
of prop-2-ynals with carbonyl compounds containing
an active methylene group [13, 16]. It seemed reason-
able to combine the stages of preparation of activated
In the reaction of aldehyde 1a with ester 2 and
piperazine (3d) (molar reactant ratio 1:1:0.5) we isolat-
ed tetraester 5 but with a lower yield (42%). It should
1758

THREE-COMPONENT REACTION OF DIMETHYL MALONATE
1759
Scheme 1.
R
4
2
O
O
X
α
MeOH, r.t., 48 h
COOMe
R
CHO
+
+
N
( )n
1
β
3
MeO
OMe
N
H
( )n
COOMe
γ X
1a–1d
2
3a–3c
4a–4g
Ph
4
O
2
1
MeO
O
MeOH, r.t., 48 h
NH
N
OMe
OMe
3
1a
+ 2 +
3'
1'
HN
MeO
N
4'
O
2'
O
Ph
3d
5
1, R1 = Ph (a), 4-MeC6H4 (b), Me (c), 5-bromofuran-2-yl (d); 3, X = CH2, n = 1 (a); X = CH2, n = 2 (b); X = O, n = 2 (c); X = NH,
n = 2 (d); 4, R = Ph, X = CH2, n = 1 (a); R = Ph, X = CH2, n = 2 (b); R = Ph, X = O, n = 2 (c); R = 4-MeC6H4, X = CH2, n = 2 (d);
R = 4-MeC6H4, X = O, n = 2 (e); R = Me, X = CH2, n = 2 (f); R = 5-bromofuran-2-yl, X = CH2, n = 2 (g).
1
be noted that we failed to isolate the corresponding
monoadduct like 4 even when excess amine (1–
1.5 equiv) was used. Similar results were obtained
previously in the reactions of piperazine with 1,5-di-
arylpent-2-en-4-yn-1-ones [17].
by H NMR data minor isomers (Z)-4c and (Z)-g (see
Experimental) whose concentration in the reaction
mixture was the largest among to the other derivatives.
A probable mechanism of the three-component
condensation is shown in Scheme 2. We believe that
the reaction begins with 1,2-addition of amine 3 to
aldehyde 1 [18] with the formation of adduct A which
then reacts with anion B generated from ester 2 by the
action of base 3. The subsequent protonation and
dehydration lead to dimethyl 2-(1-aminoprop-2-yn-1-
yl)malonate 6, and elimination of secondary amine
from the latter yields conjugated enyne 7. It should be
noted that the formations of intermediate products A,
6, and 7 are, in fact, the main stages of the Knoevenagel
condensation. Final products (E)-4 and (Z)-4 are
formed as a result of nucleophilic addition of amine 3
to the triple bond of enyne 7.
1
According to the H NMR and TLC data, com-
pounds 4a–4g and 5 were isolated as almost pure
stereoisomers. The double C3=C4 bond was reliably
assigned E configuration on the basis of the two-
1
dimensional H–1H NOESY spectrum which showed
a correlation between the Hα and 3-H protons (Fig. 1a).
1
According to the H–13C HMQC and HMBC spectra,
the 2-H and 3-H protons of the diene fragment reso-
nated at δ 7.3–8.1 and 6.2–7.0 ppm, respectively
(3JHH = 12.5–13.1 Hz). The C1 (C1′), C2 (C2′), C3 (C3′),
and C4 (C4′) signals were located at δC 104–112, 150–
153, 98–101, and 152–166 ppm, respectively, in the
13C NMR spectra; their positions demonstrated charge
alternation typical of conjugated π-systems. The ester
groups are magnetically nonequivalent, and their
signals appeared separately in both proton and carbon
spectra.
We succeeded in confirming intermediacy of com-
pounds 6 and 7 and their role in the overall mechanism.
For this purpose, the reaction of aldehyde 1a with
dimethyl malonate (2) and morpholine (3c) was carried
out on cooling. After 1 h, compound 6a separated as
a colorless powder (yield 56%). When a solution of 6a
in ethanol was kept at room temperature for 48 h, it
The fraction of the corresponding Z isomers did not
exceed 5%. We succeeded in partially characterizing
(a)
(b)
R
H
2
O
O
H
Hα'
N
OMe
3
Hα'
COOMe
E
( )n
H
X
N
3
O
δ(Hα) 3.50–3.56 ppm
H
COOMe
Hα
H
δ(Hα′) 3.08–3.18 ppm
H
δ(3-H) 6.46 ppm (3JHH = 13.1 Hz)
Hα
H
(E)-4a
(E)-4
Fig. 1. Principal correlations in the (a) NOESY and (b) HMQC and HMBC spectra of compound (E)-4a.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 10 2020

SOKOV et al.
1760
Scheme 2.
O
O
2
+
3
+
[3·H]+
MeO
OMe
B
O
N
O
MeO
OMe
O
MeO
HN
OMe
O
O
OH
R
[3·H]+
R
R
R
–3
1
N
( )n
X
( )n
7
–H2O, –3
( )n
X
( )n
X
HN
X
A
6
3
3
(E)-4 + (Z)-4
was completely converted to push–pull buta-1,3-diene
EXPERIMENTAL
(E)-4c with an impurity of isomer (Z)-4c (Scheme 3).
The 1H and 13C NMR spectra were recorded at 25°C
on a Bruker Avance III 400 spectrometer at 400 and
100 MHz, respectively, using CDCl3 (or C6D6 for 6a)
as solvent and reference. The IR spectra were recorded
in KBr on an FSM-1201 spectrometer with Fourier
transform. Elemental analyses for carbon, hydrogen,
and bromine were carried out by express gravimetry
using standard equipment [21]. The reaction mixtures
were analyzed, and the purity of the isolated products
was checked, by TLC on Sorbfil plates using ethyl
acetate–petroleum ether (1:5) as eluent; spots were
visualized by treatment with iodine vapor. The melting
points were measured in open capillaries and are
uncorrected.
Dimethyl 2-(3-phenylprop-2-yn-1-ylidene)malonate
(7a) was synthesized independently by heating alde-
hyde 1a with ester 2 in acetic anhydride [19]. Con-
jugated enyne 7 reacted with piperidine (3b) under the
same conditions as for the three-component reaction to
afford 65% of (E)-4b with an impurity of its Z isomer.
Thus, we have developed a one-pot procedure for
the stereoselective synthesis of push–pull buta-1,3-di-
enes by three-component condensation of preparatively
accessible [20] α,β-acetylenic aldehydes, dimethyl
malonate, and cyclic secondary amines. The reaction
involves initial formation of the corresponding
Knoevenagel condensation product [dimethyl 2-(prop-
2-yn-1-ylidene)malonate], followed by nucleophilic
addition of cyclic amine to the triple bond of inter-
mediate conjugated enyne.
Initial cyclic amines and dimethyl malonate were
commercial products. α,β-Acetylenic aldehydes were
synthesized as described in [20].
Scheme 3.
O
MeOH, 0–5°C, 1 h
N
O
MeOH, r.t., 48 h
1a
+
2
+
3c
4c
OMe
OMe
Ph
O
6a
O
2, Ac2O, 130°C, 4 h
3b, MeOH, r.t., 48 h
OMe
OMe
1a
4b
Ph
O
7a
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 10 2020

THREE-COMPONENT REACTION OF DIMETHYL MALONATE
1761
134.2 (Carom), 151.0 (C2), 164.3 (C4), 167.0 (C=O),
167.5 (C=O). Found, %: C 65.64; H 6.61. C18H21NO5.
Calculated, %: C 65.24; H 6.39.
Dimethyl 2-(3-aminoprop-2-en-1-ylidene)malo-
nates 4a–4g (general procedure). A solution of 3 mmol
of aldehyde 1a–1d and 3 mmol of dimethyl malonate
(2) in 1.5 mL of methanol was cooled with ice, and
3 mmol of amine 3a–3c or a solution of 129 mg
(1.5 mmol) of piperazine (3d) in 0.5 mL of methanol
was added dropwise with stirring. The mixture was
stirred for 48 h at room temperature and cooled with
an ice–salt mixture, and the precipitate was rapidly
filtered off, washed on a filter with a minimum amount
of ice-cold methanol, and dried in air.
Dimethyl (Z)-2-[3-(morpholin-4-yl)-3-phenyl-
prop-2-en-1-ylidene]malonate [(Z)-4c] was charac-
terized as a minor impurity in the reaction mixture.
1H NMR spectrum: δ 6.88 ppm, d (1H, 3JHH = 8.9 Hz);
no other signals were identified.
Dimethyl (E)-2-[3-(4-methylphenyl)-3-(piperi-
din-1-yl)prop-2-en-1-ylidene]malonate [(E)-4d].
Yield 670 mg (65%), yellow needles, mp 119–120°C
(from petroleum ether). IR spectrum, ν, cm–1: 1703,
Dimethyl (E)-2-[3-phenyl-3-(pyrrolidin-1-yl)-
prop-2-en-1-ylidene]malonate [(E)-4a]. Yield 861 mg
(91%), yellow prisms, mp 97–98°C (from petroleum
1
1683. H NMR spectrum, δ, ppm: 1.59–1.74 m (6H,
β-H, γ-H), 2.42 s (3H, MeC6H4), 3.24–3.42 m (4H,
α-H), 3.61 s (3H, OMe), 3.82 s (3H, OMe), 6.95 d (1H,
1
ether). IR spectrum, ν, cm–1: 1694, 1674. H NMR
spectrum (CDCl3), δ, ppm: 1.82–1.90 m (2H, β-H),
2.01–2.06 m (2H, β-H), 3.08–3.13 m (2H, α-H), 3.50–
3.56 m (2H, α-H), 3.60 s (3H, OMe), 3.82 s (3H,
3
3-H, JHH = 12.8 Hz), 7.13–7.16 m (2H, Harom), 7.24–
3
7.31 m (2H, Harom), 7.38 d (1H, 2-H, JHH = 12.8 Hz).
13C NMR spectrum, δC, ppm: 21.4 (MeC6H4), 24.3
(Cγ), 26.0 (Cβ), 50.0 (Cα), 51.2 (OMe), 51.3 (OMe),
99.5 (C3), 106.4 (C1), 129.4 (2C, Carom), 131.8 (Carom),
139.7 (Carom), 153.4 (C2), 165.7 (C4), 167.5 (C=O),
167.9 (C=O). Found, %: C 69.77; H 7.50. C20H25NO4.
Calculated, %: C 69.95; H 7.34.
3
OMe), 6.46 d (1H, 3-H, JHH = 13.1 Hz), 7.23–7.26 m
3
(2H, Harom), 7.39 d (1H, 2-H, JHH = 13.1 Hz), 7.45–
7.48 m (3H, Harom). 13C NMR spectrum (CDCl3), δC,
ppm: 25.0 (Cβ), 25.3 (Cβ), 48.7 (Cα), 51.2 (OMe), 51.3
(OMe), 99.2 (C3), 105.0 (C1), 128.6 (Carom), 128.7
(Carom), 129.3 (Carom), 134.9 (Carom), 152.7 (C2), 163.2
(C4), 167.7 (C=O), 168.0 (C=O). Found, %: C 68.61;
H 6.79. C18H21NO4. Calculated, %: C 68.55; H 6.71.
Dimethyl (E)-2-[3-(4-methylphenyl)-3-(morpho-
lin-4-yl)prop-2-en-1-ylidene]malonate [(E)-4e].
Yield 518 mg (50%), yellow needles, mp 118–119°C
(from petroleum ether). IR spectrum, ν, cm–1: 1702,
Dimethyl (E)-2-[3-phenyl-3-(piperidin-1-yl)prop-
2-en-1-ylidene]malonate [(E)-4b]. Yield 692 mg
(70%), yellow needles, mp 82–83°C (from petroleum
1
1685. H NMR spectrum, δ, ppm: 2.42 s (3H,
1
ether). IR spectrum, ν, cm–1: 1694, 1674. H NMR
MeC6H4), 3.24–3.27 m (4H, β-H), 3.64 s (3H, OMe),
3.69–3.76 m (4H, α-H), 3.83 s (3H, OMe), 6.43 d (1H,
spectrum, δ, ppm: 1.64–1.71 m (6H, β-H, γ-H), 3.31–
3.42 m (4H, α-H), 3.61 s (3H, OMe), 3.83 s (3H,
3
3
3-H, JHH = 12.5 Hz), 7.15 d (2H, Harom, JHH
=
3
7.9 Hz), 7.25–7.30 m (2H, Harom), 7.38 d (1H, 2-H,
3JHH = 12.5 Hz). 13C NMR spectrum, δC, ppm: 21.4
(MeC6H4), 48.8 (Cα), 51.5 (OMe), 51.6 (OMe), 66.6
(Cβ), 99.9 (C3), 110.3 (C1), 129.5 (Carom), 129.7 (Carom),
131.1 (Carom), 140.0 (Carom), 151.3 (C2), 164.7 (C4),
167.1 (C=O), 167.5 (C=O). Found, %: C 66.37;
H 6.82. C19H23NO5. Calculated, %: C 66.07; H 6.71.
OMe), 6.62 d (1H, 3-H, JHH = 12.8 Hz), 7.25–7.28 m
3
(2H, Harom), 7.34 d (1H, 2-H, JHH = 12.8 Hz), 7.46–
7.51 m (3H, Harom). 13C NMR spectrum, δ, ppm: 24.3
(Cγ), 26.0 (Cβ), 49.9 (Cα), 51.3 (OMe), 51.4 (OMe),
99.4 (C3), 106.9 (C1), 128.7 (Carom), 129.4 (Carom),
129.6 (Carom), 134.9 (Carom), 153.1 (C2), 165.3 (C4),
167.4 (C=O), 167.8 (C=O). Found, %: C 69.44;
H 7.12. C19H23NO4. Calculated, %: C 69.28; H 7.04.
Dimethyl (E)-2-[3-(piperidin-1-yl)but-2-en-1-
ylidene]malonate [(E)-4f]. Yield 615 mg (80%),
orange needles, mp 91–92°C (from petroleum ether).
IR spectrum, ν, cm–1: 1687, 1680. 1H NMR spectrum,
δ, ppm: 1.61–1.69 m (6H, β-H, γ-H), 2.18 s (3H, Me),
3.48–3.50 m (4H, α-H), 3.74 s (3H, OMe), 3.79 s (3H,
Dimethyl (E)-2-[3-(morpholin-4-yl)-3-phenyl-
prop-2-en-1-ylidene]malonate [(E)-4c]. Yield 815 mg
(82%), yellow prisms, mp 97–98°C (from petroleum
1
ether). IR spectrum, ν, cm–1: 1685, 1674. H NMR
spectrum, δ, ppm: 3.25–3.27 m (4H, β-H), 3.64 s (3H,
OMe), 3.73–3.76 m (4H, α-H), 3.84 s (3H, OMe),
3
OMe), 6.54 d (1H, 3-H, JHH = 13.1 Hz), 8.11 d (1H,
3
2-H, JHH = 12.8 Hz). 13C NMR spectrum, δC, ppm:
3
6.47 d (1H, 3-H, JHH = 12.8 Hz), 7.26–7.30 m (2H,
15.3 (Me), 24.3 (Cγ), 25.9 (Cβ), 48.8 (Cα), 51.2 (OMe),
51.4 (OMe), 97.7 (C3), 104.2 (C1), 151.0 (C2), 160.9
(C4), 167.9 (C=O), 168.1 (C=O). Found, %: C 63.07;
H 7.83. C14H21NO4. Calculated, %: C 62.90; H 7.92.
Harom), 7.34 d (1H, 2-H, 3JHH = 12.5 Hz), 7.46–7.50 m
(3H, Harom). 13C NMR spectrum, δC, ppm: 48.8 (Cα),
51.57 (OMe), 51.58 (OMe), 66.5 (Cβ), 100.0 (C3),
110.7 (C1), 128.8 (Carom), 129.7 (Carom), 129.9 (Carom),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 10 2020

SOKOV et al.
1762
Dimethyl (E)-2-[3-(5-bromofuran-2-yl)-3-(piper-
128.4 (Carom), 129.6 (Carom), 131.9 (Carom), 166.5
(C=O), 166.6 (C=O). Found, %: C 65.43; H 6.47.
C18H21NO5. Calculated, %: C 65.24; H 6.39.
idin-1-yl)prop-2-en-2-ylidene]malonate [(E)-4g].
Yield 645 mg (54%), yellow needles, mp 92–93°C
(from petroleum ether). IR spectrum, ν, cm–1: 1701,
Isomerization of compound 6a to 1,3-diene 4c.
A solution of 331 mg of compound 6a in 1.5 mL of
methanol was kept at room temperature until the
conversion was complete (48 h, TLC). The solvent was
removed under reduced pressure, and the residue was
rerecrystallized from petroleum ether to obtain 249 mg
(75%) of (E)-4c.
1
1681. H NMR spectrum (CDCl3), δ, ppm: 1.65–
1.71 m (6H, β-H, γ-H), 3.22–3.25 m (4H, α-H), 3.72 s
(3H, OMe), 3.83 s (3H, OMe), 6.43 d (1H, 3-H, 3JHH
=
12.5 Hz), 6.47 d and 6.58 d (1H each, 3′-H, 4′-H,
3
3JHH = 3.4 Hz), 7.74 d (1H, 2-H, JHH = 12.5 Hz).
13C NMR spectrum, δC, ppm: 24.3 (Cγ), 25.7 (Cβ), 50.4
(Cα), 51.5 (OMe), 51.7 (OMe), 101.4 (C3), 110.2 (C1),
113.3 and 118.9 (C3′, C4′), 124.8 and 148.5 (C2′, C5′),
149.9 (C2), 151.8 (C4), 167.1 (C=O), 167.4 (C=O).
Found, %: C 51.52; H 5.27; Br 19.60. C17H20BrNO5.
Calculated, %: C 51.27; H 5.06; Br 20.06.
Dimethyl 2-(3-phenylprop-2-yn-1-ylidene)malo-
nate (7a) [19]. A mixture of 2.56 g (19.7 mmol) of
aldehyde 1a, 6.99 g (52.9 mmol) of dimethyl malonate
2, and 3 mL of acetic anhydride was stirred for 4 h at
130°C. The product was isolated by vacuum distillation
in a nitrogen atmosphere. Yield 3.61 mg (75%), light
yellow liquid which crystallized to form colorless
needles on storage, bp 190–191°C (3 mm Hg), mp 46–
46.5°C (from petroleum ether). IR spectrum, ν, cm–1:
Dimethyl (Z)-2-[3-(5-bromofuran-2-yl)-3-(piper-
idin-1-yl)prop-2-en-1-ylidene]malonate [(Z)-4g] was
characterized as a minor impurity in the reaction mix-
1
ture. H NMR spectrum, δ, ppm: 6.33 d (1H, HFu,
3
3JHH = 3.4 Hz), 6.62 d (1H, HFu, JHH = 3.4 Hz); no
1
2199, 1734, 1703, 1688. H NMR spectrum, δ, ppm:
other signals were identified.
3.86 s (3H, OMe), 3.94 s (3H, OMe), 7.16 s (1H,
Tetramethyl 2,2′-[(2E,2′E)-piperazine-1,4-diyl-
bis(3-phenylprop-2-en-3-yl-1-ylidene)]dimalonate
[(E)-5]. Yield 724 mg (42%), yellow powder, mp 224–
225°C (from petroleum ether). IR spectrum, ν, cm–1:
1721, 1699. 1H NMR spectrum, δ, ppm: 3.29–3.37 m
(8H, α-H, β-H), 3.63 s (6H, OMe), 3.82 s (6H, OMe),
≡CCH), 7.33–7.48 m (3H, Harom), 7.48–7.54 m (2H,
H
arom). 13C NMR spectrum, δC, ppm: 52.5 (OMe), 52.7
(OMe), 84.7 and 105.4 (C≡C), 121.8, 125.9, 128.6,
130.0, 132.3, 134.3, 163.7 (C=O), 164.6 (C=O).
Found, %: C 68.59; H 4.74. C14H12O4. Calculated, %:
C 68.85; H 4.95.
3
6.41 d (2H, 3-H, JHH = 12.5 Hz), 7.25–7.29 m (4H,
Harom), 7.30 d (2H, 2-H, 3JHH = 12.5 Hz), 7.44–7.50 m
(6H, Harom). 13C NMR spectrum, δC, ppm: 47.8 (Cα,
Cβ), 51.60 (OMe), 51.61 (OMe), 100.3 (C3), 111.6
(C1), 128.9 (Carom), 129.6 (Carom), 130.0 (Carom), 134.0
(Carom), 150.3 (C2), 163.3 (C4), 166.8 (C=O), 167.3
(C=O). Found, %: C 66.65; H 6.13. C32H34N2O8. Cal-
culated, %: C 66.89; H 5.96.
Nucleophilic addition of morpholine (3c) to
enyne 7a. A solution of 244 mg (1 mmol) of enyne 7a
and 96 mg (1.1 mmol) of morpholine (3c) in 1.5 mL of
methanol was kept at room temperature for 48 h. The
mixture was cooled to 0°C, and the precipitate of
(E)-4c was filtered off, washed with a minimum
amount of ice-cold methanol, and dried in air.
Yield 255 mg (77%).
Dimethyl 2-[1-(morpholin-4-yl)-3-phenylprop-2-
yn-1-yl]malonate (6a). The amounts of the reactants
were the same as in the synthesis of 4c, but the reaction
mixture was stirred for 1 h at 0–5°C, and the precipitate
of 6a was rapidly filtered off, washed on a filter with
a minimum amount of ice-cold methanol, and dried for
1 h under reduced pressure. Yield 553 mg (56%),
colorless powder, mp 89–90°C (from petroleum ether).
IR spectrum: ν 1740 cm–1. 1H NMR spectrum, δ, ppm:
2.55–2.62 m and 3.10–3.14 m (4H, α-H), 3.33 s (3H,
OMe), 3.36 s (3H, OMe), 3.44–3.57 m (4H, β-H),
ACKNOWLEDGMENTS
The authors thank K.V. Gordon for performing elemental
analyses.
FUNDING
This study was performed under financial support by the
Russian Foundation for Basic Research (project no. 20-33-
80004/20).
3
3.99 d (1H, 1-H, JHH = 11.3 Hz), 4.59 d (1H, 2-H,
3JHH = 11.3 Hz), 7.35–7.42 m (2H, Harom), 6.94–7.00 m
(3H, Harom). 13C NMR spectrum, δC, ppm: 50.9 (Cα),
51.6 (OMe), 51.8 (OMe), 55.9 (CH), 57.5 (CH), 65.9
(Cα), 66.8 (Cβ), 83.7 and 87.8 (C≡C), 128.2 (Carom),
CONFLICT OF INTEREST
The authors declare the absence of conflict of interest.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 10 2020

THREE-COMPONENT REACTION OF DIMETHYL MALONATE
1763
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