Synthesis of alkyl 2-[2-oxopyridin-1(2H)-yl]acrylates by nucleophilic addition of alkyl propiolates catalysed by Ph3P

Article abstract of DOI:10.3184/030823408X377771

2-Hydroxypyridine undergoes a smooth reaction with alkyl propiolates in the presence of triphenylphosphine (15 mol%) to produce the corresponding alkyl 2-[2-oxopyridin-1(2H)-yl]acrylates in good yields. When the reaction was performed by 2-hydroxyquinoline and 2-hydroxyisoquinoline similar α-substituted alkyl acrylates were obtained.

Full text of DOI:10.3184/030823408X377771

JOURNAL OF CHEMICAL RESEARCH 2008
OCTOBER, 601–603
RESEARCH PAPER 601
Synthesis of alkyl 2-[2-oxopyridin-1(2h)-yl]acrylates by nucleophilic
addition of alkyl propiolates catalysed by Ph3P
Bita Mohtata, Sepideh Jabbara, Abdollah Ghasemia and Issa Yavarib*
aChemistry Department, Islamic Azad University, Karaj, Iran
bChemistry Department, Science & Research Campus, Islamic Azad University, Ponak, Tehran, Iran
2-Hydroxypyridine undergoes a smooth reaction with alkyl propiolates in the presence of triphenylphosphine
(15 mol%) to produce the corresponding alkyl 2-[2-oxopyridin-1(2H)-yl]acrylates in good yields. When the reaction was
performed by 2-hydroxyquinoline and 2-hydroxyisoquinoline similar a-substituted alkyl acrylates were obtained.
Keywords: NH-acids, 2-hydroxypyridine, 2-hydroxyquinoline, 2-hydroxyisoquinoline, alkyl acrylates, alkyl propiolates,
triphenylphosphine
Organophosphorus compounds have been used in organic
CO2R
synthesis as useful reagents as well as ligands of a number
of transition metal catalysts.1-3 However, there are a few
Ph3P (15 mol%)
reactions in which organophosphorus(III) species work
N
O
+
as catalysts.4-8 The phosphine induced isomerisation of
alkynoates and addition to the a-position of these substrates
indicated the possibility of a new reactivity pattern for
alkynoates-nucleophilic addition at the a-position as a new
source of a-substituted alkyl acrylates.
CH2Cl2
N
OH
H
CO2R
R'
1
2
R'
3
An important point is the ability of the nucleophile to
undergo Michael addition in preference to the a-attack since
phosphines could also serve as general base catalysts for
conjugate additions.1-3 Alkyl propiolates should be particularly
prone to undergo such Michael additions.
R
2, 3
a
b
c
R'
Me
H
Et
H
Et
Ph
In this regard, triphenylphosphine (Ph3P) have received
increasing attention as versatile and mild reagent in many
occasions for various organic transformations under neutral
conditions in recent years.9-12 The addition reaction between
electron-deficient acetylenic compounds and nitrogen-
containing hetrocycles has been extensively investigated.13,14
Recently, we reported15 the synthesis of the E/Z isomers
Scheme 1
between Ph3P and the acetylenic compound (Scheme 2).17 The
intermediate 4 is then protonated by the OH-acidic 1 to afford
5. The latter might be attacked by the N-atom of the bidentate
anion 6 to afford the ylide 7. This intermediate undergoes a
proton transfer to furnish the 1,3-diionic structure 8, which is
converted to the final product by loss of Ph3P (Scheme 2).
When the reaction is carried out using 2-hydroxyquinoline
and 2-hydroxyisoquinoline the same a-substituted alkyl
acrylates (9 and 10) are obtained in excellent overall yields
(Scheme 2). Compounds 9 and 10 were identified based
of
dialkyl
2-(2-oxopyridin-1(2H)-yl)but-2-enedioates
through the reaction of 2-hydroxypyridine with dialkyl
acetylenedicarboxylates in the presence of triphenylphosphine
(Ph3P). In this work, we present the nucleophilic a-addition of
2-hydroxypyridine (1) to alkyl propiolates (2) in the presence
of Ph3P under neutral conditions. Thus, alkyl propiolate
undergoes a smooth reaction with the 2-hydroxypyridine in
the presence of Ph3P to produce alkyl 2-[2-oxopyridin-1(2H)-
yl]acrylates (3) in good yields (Scheme 1).
on their elemental analyses and their IR, H, and l3C NMR
1
spectral data.
In conclusion, we have described a convenient route to
a-substituted alkyl acrylates, through nucleophilic addition
to alkyl propiolate. These functionalised acrylates may be
considered as potentially useful synthetic intermediates
because they possess atoms with different oxidation states.
The present method has the advantages that not only are
the reaction performed under neutral conditions, but also
the substances can be mixed without any modification. The
simplicity of the present procedure makes it an interesting
alternative to other approaches.
The products were separated by column chromatography
and identified as 3 based on their elemental analyses and their
IR, 1H, and l3C NMR spectral data. The mass spectra of these
compounds displayed molecular ion peaks at appropriate m/z
1
values. The H NMR spectrum of 3a exhibited a single sharp
line for the methyl group at d = 3.77 ppm, together with two
singlet at d = 5.80 and 6.38 ppm for the C=CH2 protons. The
13C NMR spectrum of 3a showed nine distinct resonances in
agreement with the methyl 2-[2-oxopyridin-1(2H)-yl]acrylate
structure. The 1H and 13C NMR spectra of 3b and 3c are similar
to those of 3a except for the alkoxy moieties, which exhibited
characteristic resonances with appropriate chemical shifts.
NMR spectroscopy was employed to distinguish between
(Z)-3c and (E)-3c. The (Z) and (E) configurations of the
carbon–carbon double bonds in 3c are based on the chemical
Experimental
General procedure
Compounds 1, 2 and Ph3P were obtained from Fluka and were used
without further purification. M.p. Electrothermal-9100 apparatus. IR
Spectra: Shimadzu IR-460 spectrometer. H- and 13C NMR spectra:
1
Bruker DRX-500 AVANCE instrument; in CDCl3 at 300 and 75 MHz,
respectively; d in ppm. EI-MS (70 eV): Finnigan-MAT-8430 mass
spectrometer, in m/z. Elemental analyses (C, H, N) were performed
with a Heraeus CHN-O-Rapid analyser.
1
shift of the olefinic proton.16 The H NMR spectra of (Z)-3c
showed olefinic proton at 7.00 ppm, while the (E)-3c isomer
exhibited the olefinic proton at 7.82 ppm.
Mechanistically, it is conceivable that the reaction involves
the initial formation of a zwitterionic 1:1 intermediate 4
Typical procedure for preparation of (3)
To a stirred solution of 0.52 g of Ph3P (2 mmol) and 0.19 g 1
(2 mmol) in 10 ml of CH2CI2 was added, drop wise, a mixture of 2
(2 mmol) in 4 ml of CH2Cl2 at –5°C over 10 min. The reaction
* Correspondent. E-mail: yavarisa@modares.ac.ir; isayavar@yahoo.com

602 JOURNAL OF CHEMICAL RESEARCH 2008
R'
R'
1
+
CO2R
+
2
PPh3
CO2R
+
Ph3P
Ph3P
N
O
4
5
6
_
Alfa-addition
PPh3
N
O
PPh3
3
N
O
PPh3
RO2C
RO2C
R'
R'
7
8
Scheme 2
t, J = 9.3Hz, CH), 7.82 (1 H, s, CH). 13C NMR: 14.1 (Me), 62.0,
(OCH2), 106.8, 121.9, 128.9, 130.0, 130.5, 132.0 (8 CH), 132.1(C),
137.4, 137.7 (2 CH), 140.7 (C), 162.4, 163.4 (2 C=O). EI-MS: m/z
(%) = 256 (M+, 9), 164 (71), 120 (25), 96 (23), 77 (68), 73 (25). Anal.
Calcd for C16H15NO3 (256.28): C, 71.36; H, 5.61; N, 5.20; found: C,
71.56; H, 7.35; N, 5.30%.
3
N
CO2R
N
O
O
Methyl 2-[2-oxoquinolin-1(2H)-yl]acrylate (9a): Yellow oil, yield:
H
CO2R
1
0.32 g (70%). IR (KBr): 1726, 1650 (C=O). H NMR: 3.79 (3 H, s,
H
R'
3
OMe), 6.01 (1 H, s, CH), 6.71 (1 H, d, J = 9.6Hz, CH), 6.96 (1 H,
R'
s, CH), 7.17 (1 H, d, 3J = 8.1Hz, CH), 7.22 (1 H, t, 3J = 7.6Hz, CH),
R
R
3
3
9
a
R'
R'
10
a
b
c
7.47 (1 H, t, J = 8.1Hz, CH), 7.59 (1 H, d, J = 7.6Hz, CH), 7.75
(1 H, d, J = 9.6Hz, CH). 13C NMR: 52.8 (OMe) 114.8 (CH), 120.4
3
Me
Me
H
H
Et
b
Et
H
H
(C), 121.6 (CH2), 122.7, 128.8, 129.5, 130.7 (4 CH), 135.0, 139.8
(2 C), 140.4 (CH), 161.8, 163.0 (2 C=O). EI-MS: m/z (%) = 229 (M+,
23), 214 (14), 201 (44), 170 (75), 128 (30), 115 (40). Anal. Calcd for
C13H11NO3 (229.23): C, 68.11; H, 4.84; N, 6.11; found: C, 68.31; H,
4.95; N, 6.24%.
Et
Ph
Scheme 3
mixture was then allowed to warm up to room temperature and stirred
for 24 h. The solvent was removed under reduced pressure and the
residue was separated by column chromatography (SiO2; n-hexane:
EtOAc = 1:1) to afford the pure title compounds.
Ethyl 2-[2-oxoquinolin-1(2H)-yl]acrylate (9b): Yellow oil, yield:
1
0.36 g (75%). IR (KBr): 1735, 1650 (C=O). H NMR: 1.26 (3 H,
3
3
t, J = 7.1Hz, Me), 4.26 (2 H, q, J = 7.1Hz, OCH2), 6.01 (1 H, s,
CH), 6.70 (1 H, d, 3J = 9.6Hz, CH), 6.95 (1 H, s, CH), 7.17 (1 H, d,
3J = 8.4Hz, CH), 7.23 (1 H, t, 3J = 7.6Hz, CH), 7.48 (1 H, t,
3J = 8.4Hz, CH), 7.56 (1 H, d, 3J = 7.6Hz, CH), 7.75 (1 H, d,
3J = 9.6Hz, CH). 13C NMR: 14.0 (Me), 62.0 (OCH2) 114.8 (CH)
120.4 (C), 121.7 (CH2), 122.6, 128.7, 129.22, 130.6 (4 CH), 135.3,
139.8 (2 C), 140.3 (CH), 162.5, 163.6 (2 C=O). EI-MS: m/z (%) =
243 (M+, 38), 229 (71), 214 (20), 170 (34), 73 (13). Anal. Calcd for
C14H13NO3 (243.26): C, 69.12; H, 5.39; N, 5.76; found: C, 69.34;
H, 5.33; N, 5.84%.
Methyl 2-[2-oxopyridin-1(2H)-yl]acrylate (3a): Yellow oil, yield:
0.26 g (75%). IR (KBr): 1737 and 1675 (C=O). 1H NMR: 3.77 (3 H,
s, OMe), 5.80 (1 H, s, CH), 6.19 (1 H, t, 3J = 6.8Hz, CH), 6.38 (1 H,
s, CH), 6.51 (1 H, d, 3J = 9.3Hz, CH), 7.16 (1 H, d, 3J = 6.8Hz, CH),
3
7.43 (1 H, t, J = 9.3Hz, CH). 13C NMR: 52.7 (OMe), 106.1 (CH),
121.3 (CH2), 123.5, 137.2 (2 CH), 140.1 (C), 140.5 (CH), 161.9,
162.6 (2 C=O). EI-MS: m/z (%) = 179 (M+, 20), 83 (87), 59 (40), 39
(75). Anal. Calcd for C9H9NO3 (179.17): C, 60.33; H, 5.06; N, 7.82;
found: C, 60.66; H, 5.15; N, 7.74%.
Ethyl 2-[2-oxopyridin-1(2H)-yl]acrylate (3b): Yellow oil, yield:
0.26 g (60%). IR (KBr): 1737 and 1673 (C=O). 1H NMR: 1.26
(3H,t,3J=7.1Hz,Me),4.25(2H,q,3J=7.1Hz,OCH2),5.80(1H,s,CH),
6.18 (1 H, t, 3J = 6.7Hz, CH), 6.39 (1 H, s, CH), 6.52 (1 H, d, 3J = 9.3Hz,
CH), 7.17 (1 H, d, 3J = 6.7Hz, CH), 7.38 (1 H, t, 3J = 9.3Hz,
CH). 13C NMR: 14.0 (Me), 62.0 (OCH2), 106.1 (CH), 121.3 (CH2),
123.2, 137.3 (2 CH), 140.5 (C), 140.6 (CH), 161.9, 162.2, (2 C=O).
EI-MS: m/z (%) = 193 (M+, 4), 164 (100), 120 (25), 96 (23), 51 (25).
Anal. Calcd for C10H11NO3 (193.2): C, 62.17; H, 5.74; N, 7.25;
found: C, 62.54; H, 5.57; N, 7.68%.
Methyl 2-[2-oxo-isoquinolin-1(2H)-yl]acrylate (10a): Yellow oil,
yield: 0.32 g (72%). IR (KBr): 1753 and 1659 (C=O). 1H NMR: 3.80
(3 H, s, OMe), 5.84 (1 H, d, 3J = 0.6Hz, CH), 6.42 (1 H, d, 3J = 0.6Hz,
3
3
CH), 6.51 (1 H, d, J = 7.4Hz, CH), 7.01 (1 H, d, J = 7.4Hz, CH),
3
3
7.44 (1 H, t, J = 7.4Hz, CH), 7.49, (1 H, d, J = 8.2Hz, CH), 7.63
(1 H, t, J = 8.2Hz, CH), 8.37 (1 H, d, J = 7.4Hz, CH). 13C NMR:
52.7 (OMe), 106.8 (CH), 123.2 (CH2), 125.9 (C), 126.1, 127.2, 127.9,
131.3, 132.8 (5 CH), 137.3, 140.4 (2 C), 161.7, 163.2 (2 C=O).
EI-MS: m/z (%) = 229 (M+, 12), 214 (14), 201 (44), 170 (75), 128
(30), 115 (40). Anal. Calcd for C13H11NO3 (229.23): C, 68.11; H,
4.84; N, 6.11; found: C, 68.26; H, 4.75; N, 6.20%.
3
3
Ethyl (2Z)-2-[2-oxopyridin-1(2H)-yl]-3-phenylacrylate (Z-3c):
Yellow oil, yield: 0.12 g (25%). IR (KBr): 1721 and 1668 (C=O).
Ethyl 2-[2-oxoquinolin-1(2H)-yl]acrylate (10b): Yellow oil, yield:
1
0.38 g (78%). IR (KBr): 1735, 1667 (C=O). H NMR: 1.28 (3 H,
3
3
1H NMR: 1.10 (3 H, t, J = 7.1Hz, Me), 4.18 (2 H, q, J = 7.1Hz,
3
3
t, J = 7.1Hz, Me), 4.27 (2 H, q, J = 7.1Hz, OCH2), 5.83 (1 H, d,
3J = 0.8Hz, CH), 6.41 (1 H, d, 3J = 0.8Hz, CH), 6.51 (1 H, d,
3J = 7.4Hz, CH), 6.98 (1 H, d, 3J = 7.4Hz, CH), 7.44 (1 H, t,
3J = 7.4Hz, CH), 7.49 (1 H, d, 3J = 7.1Hz, CH), 7.63 (1 H, t,
3J = 7.1Hz, CH), 8.37 (1 H, d, 3J = 7.4Hz, CH). 13C NMR: 14.1 (Me),
61.9 (OCH2), 106.7 (CH), 122.9 (CH2), 126.0 (C), 126.1, 127.2,
128.1, 131.4, 132.8 (5 CH), 137.2, 140.7 (2 C), 161.7, 162.7 (2 C=O).
EI-MS: m/z (%) = 243 (M+, 38), 229 (71), 214 (20), 170 (34), 73
(13). Anal. Calcd for C14H13NO3 (243.26): C, 69.12; H, 5.39; N,
5.76; found: C, 69.25; H, 5.35; N, 5.84%.
OCH2), 6.23 (1 H, t, 3J = 6.7Hz, CH), 6.55 (1 H, d, 3J = 9.3Hz, CH),
3
7.00 (1 H, s, CH), 7.15 (1 H, d, J = 6.7Hz, CH),7.17–7.42 (5 H,
m, 5CH) 7.44 (1 H, t, J = 9.3Hz, CH). 13C NMR: 13.5 (Me), 61.5,
3
(OCH2), 106.4, 121.1, 128.4, 128.6, 130.2, 131.5 (8 CH), 131.9
(C), 134.7, 137.9 (2 CH), 140.5 (C), 162.2, 163.4 (2 C=O). EI-MS:
m/z (%) = 256 (M+, 9), 164 (71), 120 (25), 96 (23), 77 (68), 73 (25).
Anal. Calcd for C16H15NO3 (256.28): C, 71.36; H, 5.61; N, 5.20;
found: C, 71.66; H, 5.75; N, 5.34%.
Ethyl (2E)-2-[2-oxopyridin-1(2H)-yl]-3-phenylacrylate (E-3c):
Yellow oil, yield: 0.30 g (60%). IR (KBr): 1721 and 1668 (C=O).
Ethyl (2Z)-2-[2-oxoquinolin-1(2H)-yl]-3-phenylacrylate (Z-10c):
3
3
1
1H NMR: 1.31 (3 H, t, J = 7.1Hz, Me), 4.30 (2 H, q, J = 7.1Hz,
OCH2), 6.16 (1 H, t, 3J = 6.7Hz, CH), 6.67 (1 H, d, 3J = 9.8Hz, CH),
7.16 (1 H, d, 3J = 6.8Hz, CH), 7.19–7.41 (5 H, m, 5 CH), 7.43 (1 H,
Yellow oil, yield: 0.22 g (35%). IR (KBr): 1721 and 1668 (C=O). H
NMR: 1.09 (3 H, t, 3J = 7.1Hz, Me), 4.21 (2 H, q, 3J = 7.1Hz, OCH2),
6.58 (1 H, d, 3J = 7.4Hz, CH), 6.76 (1 H, d, 3J = 7.4Hz, CH),7.05 (1 H,

JOURNAL OF CHEMICAL RESEARCH 2008 603
References
s, CH), 7.20–7.27 (5 H, m, 5CH), 7.35 (1 H, t, 3J = 7.4Hz, CH), 7.50 (1
H, d, 3J = 7.1Hz, CH), 7.65 (1 H, t, 3J = 7.1Hz, CH), 8.40 (1 H, d, 3J =
7.4Hz, CH). 13C NMR: 13.5, (Me), 61.5, (OCH2), 107.4 (CH), 126.2 (C),
126.3, 127.0, 128.9, 130.1, 130.3, 130.4, 131.6, 131.8, 132.9 (11 CH),
137.1, 137.2, 137.4 (3 C), 162.1, 164.0 (3 C=O). EI-MS: m/z (%) = 319
(M+, 10), 229 (21), 214 (20), 170 (34), 77 (60), 73 (13). Anal. Calcd for
C20H17NO3 (319.35): C, 75.22; H, 5.37; N, 4.39; found: C, 75.36; H, 5.38;
N, 4.44%.
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2
3
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Yellow oil, yield: 0.34 g (55%). IR (KBr): 1721 and 1668 (C=O).
4
5
6
7
8
9
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3
1H NMR: 1.29 (3 H, t, J = 7.1Hz, Me), 4.31 (2 H, q, J = 7.1Hz,
OCH2), 6.51 (1 H, d, 3J = 7.4Hz, CH), 6.76 (1 H, d, 3J = 7.4Hz, CH),
3
7.20–7.27 (5 H, m, 5CH), 7.29 (1 H, t, J = 7.4Hz, CH), 7.53 (1 H,
d, 3J = 7.1Hz, CH), 7.69 (1 H, t, 3J = 7.1Hz, CH), 7.83 (1 H, s, CH),
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3
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(2 C=O). EI-MS: m/z (%) = 319 (M+, 10), 229 (21), 214 (20), 170
(34), 77 (60), 73 (13). Anal. Calcd for C20H17NO3 (319.35): C, 75.22;
H, 5.37; N, 4.39; found: C, 75.46; H, 5.45; N, 4.45%.
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We thank the Islamic Azad University of Karaj for support of
this work.
Received 23 June 2008; accepted 18 August 2008
Paper 08/0015 doi: 10.3184/030823408X377771
Published online: 17 October 2008
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