Unprecedented 'ring transformation-rearrangement' of pyran-2-ones into 5,6-dihydropyran-2-ones through insertion of acetol

Article abstract of DOI:10.1016/j.tetlet.2009.12.051

One-pot efficient synthesis of functionalized 5,6-dihydropyran-2-ones has been delineated by reacting 2H-pyran-2-ones and acetol in the presence of a base at room temperature. The formation of 5,6-dihydropyran-2-ones revealed that the reaction proceeded in a unique 'ring transformation-rearrangement' sequence.

Full text of DOI:10.1016/j.tetlet.2009.12.051

Tetrahedron Letters 51 (2010) 961–965
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Unprecedented ‘ring transformation-rearrangement’ of pyran-2-ones into
5,6-dihydropyran-2-ones through insertion of acetol q
Amit Kumar a, Salil P. Singh a, Deepti Verma a, Ruchir Kant b, Prakas R. Maulik b, Atul Goel a,
*
a Division of Medicinal and Process Chemistry, Central Drug Research Institute, CSIR, Lucknow 226 001, India
b Division of Molecular and Structural Biology, Central Drug Research Institute, CSIR, Lucknow 226 001, India
a r t i c l e i n f o
a b s t r a c t
Article history:
One-pot efficient synthesis of functionalized 5,6-dihydropyran-2-ones has been delineated by reacting
2H-pyran-2-ones and acetol in the presence of a base at room temperature. The formation of 5,6-dihyd-
ropyran-2-ones revealed that the reaction proceeded in a unique ‘ring transformation-rearrangement’
sequence.
Received 10 September 2009
Revised 8 December 2009
Accepted 10 December 2009
Available online 13 December 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
5,6-Dihydropyran-2-ones
Pyran-2-ones
Acetol
Ring transformation-rearrangement
reaction
Pyran-2-ones and their partially reduced 5,6-dihydropyran-2-
ones are an important class of biologically interesting natural prod-
ucts isolated from higher plants, marine and animal sources.1
Many of the natural 5,6-dihydropyran-2-ones such as (+)-parasor-
bic acid2 (I), tarchonanthuslactone3 (II), (À)-goniothalamin4 (III),
and (+)-kurzilactone5 (IV) possess interesting pharmacological
and cytotoxic6 properties (Fig. 1). Synthetic compounds bearing
this ring skeleton display anti-HIV,7 anti-cancer,8 antileukemic,9
and a broad range of many other relevant pharmacological proper-
ties.10 The wide pharmacological potential of this bioactive scaffold
has aroused considerable interest in developing novel approaches
to their synthesis.
Numerous synthetic methodologies of 5,6-dihydropyran-2-
ones have been reported in the literature. The construction of
5,6-dihydropyran-2-ones skeleton can be achieved by the reaction
of glycals with InCl3/IBX reagent,11 lactonization of substituted
d-hydroxy acid derivatives,12 oxidation of substituted dihydropy-
ran derivatives,13 and by ring-closing metathesis.4,14 Although
these reactions have been widely employed for the synthesis of
natural and unnatural dihydropyran-2-ones, the scope of these
reactions is limited due to the difficulties in obtaining suitably
functionalized acyclic substrates, specialized organometallic
reagents, harsh reaction conditions, and formation of undesired
byproducts. Herein we report a one-pot highly convenient protocol
for the synthesis of 5,6-dihydropyran-2-ones through base-in-
duced ring transformation-rearrangement of pyran-2-ones using
acetol as a source of O-nucleophile.
During our studies on the chemistry of 2H-pyran-2-ones, we
found that 4-methylsulfanyl/amino-2-oxo-6-aryl-2H-pyran-3-car-
bonitriles are susceptible to Michael addition of a conjugate base
of methylene carbonyl compounds at position 6, leading to the for-
mation of a benzene ring at room temperature (Scheme 1).15 The
success of our efficient novel pathway to a benzene ring system
under mild basic conditions encouraged us to explore this method-
ology for the synthesis of functionally congested benzenes, unsym-
metrical biaryls, teraryls, quateraryls, and oligoarenes under mild
basic conditions at room temperature.16 Recently we have demon-
strated that our methodology can be applied to prepare fluorescent
blue materials for efficient organic light emitting diodes.17
Me
O
HO
HO
O
O
O
H
Me
O
O
II
I
O
OH
O
O
O
O
H
H
IV
III
q
CDRI Communication No. 7864.
* Corresponding author. Fax: +91 522 2623405.
E-mail addresses: atul_goel@cdri.res.in, agoel13@yahoo.com (A. Goel).
Figure 1. Examples of natural 5,6-dihydropyranones: (+)-parasorbic acid (I),
tarchonanthuslactone (II), (À)-goniothalamin (III), and (+)-kurzilactone (IV).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.12.051

962
A. Kumar et al. / Tetrahedron Letters 51 (2010) 961–965
O
confirmed the presence of two CH2 groups. Two doublets at dY
6.92 and 7.98 each for 2H showed the characteristic signals of the
4-methoxyphenyl group.
R4
X
X
4
R3
R1
R2
Y
R1
R2
5
6
3
Y
The ESI-mass spectrum of 3a exhibited molecular ion peak
[M+H]+ at m/z 381, which indicated the formation of addition prod-
uct (3a) of the reactants 1 and 2. It was found in agreement with
the molecular formula of compound 3a as C18H21O7S obtained by
HRMS. The mass, NMR and IR studies of product (3) led us to spec-
ulate that 3 had a 5,6-dihydropyran-2-one ring system with a
methyl and a 4-methoxybenzoyloxy methyl groups.
2
base
room temp.
R4
O1
O
R3
Scheme 1. C-Nucleophile induced ring transformed product.
The speculated ring system for 3a was confirmed by the 2D NMR
studies (Fig. 2). In the HMBC spectrum of 3a, the CH2 protons (d 2.73
and 3.04) gave long-range correlation with signals at d 162.98 (C-4),
114.56(C-3), 77.19 (C-6), 66.76 (O-CH2), and 22.17 (CH3) whileother
CH2 protons (d 4.40 and 4.45) gave long-range correlation with sig-
nals at d 164.42 (CO), 77.19 (C-6), 22.17 (CH3), and 33.82 (CH2). This
supports the existence of methyl and (4-methoxybenzoyloxy)
methyl groups at C-6 position of the 5,6-dihydropyran-2-one ring.
The HMBC correlation ( Fig. 2) of aromatic protons (d 7.98) with
d 164.42 (CO) also support the presence of 4-methoxy-benzoyloxy
methyl group at C-6 position of the 5,6-dihydropyran-2-one ring.
The final analysis of all the spectral data of the compound 3a led to
the structure as 6-(4-methoxy-benzoyloxymethyl)-6-methyl-4-
methylsulfanyl-2-oxo-5,6-dihydro-2H-pyran-3-carboxylic acid methyl
ester.
With the demonstration of the utility of this protocol in general,
we attempted a series of reactions with a variety of six-membered
lactones (1a–k). The pyran-2-ones (1a–k) were conveniently pre-
pared in high yields by the reaction of 2-cyano/carbomethoxy-
3,3-bis-(methylsulfanyl)-acrylic acid methyl ester with aryl methyl
ketones under alkaline conditions, followed by the reaction with
secondary amines.15 The synthesis of functionalized 5,6-dihydro-
pyran-2-ones (3a–k) was achieved by stirring an equimolar mix-
ture of 2H-pyran-2-ones (1a–k), acetol (2) and powdered KOH in
DMF for 10–24 h at room temperature (Scheme 3).18
The reaction was monitored by TLC and after completion, the
reaction mixture was poured into ice water and neutralized with
dilute HCl. The crude product thus obtained was filtered and puri-
fied on a silica gel column using 1% methanol in chloroform as an
eluent. The isolated compounds were characterized by spectro-
scopic analysis.18
To understand the reaction mechanism for the formation of 5,6-
dihydropyran-2-ones, we stirred a solution of 2H-pyran-2-ones
1a–k in the presence of KOH in DMF at room temperature. We
found that the lactones are fairly stable in KOH and no ring opening
of the lactones was observed. Interestingly, when we stirred a solu-
tion of 6-aryl-2-oxo-4-(piperidin-1-yl)-2H-pyran-3-carbonitriles
1h–m in the presence of sodium alkoxide at room temperature,
we isolated alkyl 5-aryl-2-cyano-5-oxo-3-(piperidin-1-yl)-pent-2-
enoates (4a–f) in good yield (Scheme 4). These results indicated
that an alkoxide attacked at C-2 position of the lactones 1h–m
leading to the formation of lactone-ring opened products (4a–f).
SMe
COOMe
O
OH
+
Ar
O
O
2
1
Ar = 4-OMeC6H4
KOH DMF
X
X
SMe
SMe
SMe
4
COOMe
COOMe
Ar
COOMe
OH
6
Ar
O
2
O
O
Ar
O
OH
3a
5
4
Scheme 2. Synthesis of methyl 6-(4-methoxy-benzoyloxymethyl)-6-methyl-4-
methylsulfanyl-2-oxo-5,6-dihydro-2H-pyran-3-carboxylic acid ester (3).
When we applied our ring transformation strategy15 on methyl
6-(4-methoxyphenyl)-4-(methylthio)-2-oxo-2H-pyran-3-carboxyl-
ate (1) using acetol (2) as a source of nucleophile to prepare substi-
tuted phenol (4) and/or benzyl alcohol (5) derivatives as shown in
Scheme 2, we isolated an unknown compound in 70% yield (Scheme
2). A careful examination of the spectroscopicanalysis of the isolated
compound including HSQC and HMBC NMR data revealed its struc-
ture as methyl 6-((4-methoxybenzoyloxy)-methyl)-6-methyl-4-
(methylsulfanyl)-2-oxo-5,6-dihydro-2H-pyran-3-carboxylate (3a).
The 1H NMR spectrum of the product (3a) showed four singlets
at dY 1.56, 2.38, 3.83, and 3.87, each for 3H, in which dY 2.38, 3.83,
and 3.87 showed the characteristic signals corresponding to the
SCH3, OMe, and COOMe groups, respectively, but a singlet at dY
1.56 revealed the presence of a methyl group attached to an ali-
phatic system (Fig. 2). Four doublets at 2.73, 3.04, 4.40, and 4.45
each for one proton with coupling constants of 17.7, 17.7, 11.8,
and 11.8 Hz, respectively, revealed the presence of two methylene
groups containing geminal protons. Further DEPT-90 and DEPT-
135 studies on 13C NMR experiments for the compound 3a
H
(2.38, s)
13.67
S
O
O
S
O
(3.04, d)
H
H
H
O
H
162.98
(2.73, d)
163.68
H
54.21
(3.87, s)
H
O
O
H
H
O
114.56
157.88
33.82
77.19
O
162.5
(4.4, d)
H
51.09
(3.83, s)
H
O
120.11
O
164.42
H
O
112.5
(6.92, d)
O
130.62
(7.98, d)
66.76
H
H
O
22.17
(1.56, s)
O
(4.45, d)
Figure 2. 1H NMR and 13C NMR spectral data of 3a and selected 1H to 13C-HMBC correlations in CDCl3.

A. Kumar et al. / Tetrahedron Letters 51 (2010) 961–965
963
O
O
X
O
X
X
4
O
Y
Y
3
Y
5
base
Ar
HO
Ar
HO
OH
2
KOH/DMF
rt
6
O
O
Ar
Ar
O1
1(a-k)
O
O
O
H
H
A
B
C
2
B
H2O
X
X
X
O
Ar
"rearrangement"
O
B
Y
H+/H2O
Y
Y
Ar
O
O
O
O
O
O
H
O
O
O
D
3(a-k)
Entry
a
Ar
X
Y
Time
12
Yield ( 3)
MeO
SMe
SMe
SMe
SMe
SMe
COOMe
70
b
c
d
e
COOMe
COOMe
COOMe
COOMe
14
10
10
16
65
75
73
68
Cl
Br
Me
f
SMe
SMe
COOMe
20
55
COOMe
CN
22
18
60
65
g
h
S
N
N
N
i
j
Br
Cl
Br
CN
CN
16
15
70
70
Cl
k
CN
24
55
N
N
Scheme 3. Plausible reaction mechanism for the formation of 5,6-dihydropyran-2-ones (3a–k).
The structure of one of the compounds 4e was unambiguously con-
firmed by a single crystal X-ray analysis ( Fig. 3, CCDC number
752871).
N
N
O
N
O
CN
O
CN
COOR
H
RONa
rt
Based on the results obtained in Scheme 4, we propose a mech-
anism for the formation of 5,6-dihydropyran-2-ones in Scheme 3.
The transformation of 2H-pyran-2-ones 1a–k into 5,6-dihydropy-
ran-2-ones 3a–k is possibly initiated by an attack of an enolate
of acetol 2 at position C-2 of the lactone 1, followed by intramolec-
ular cyclization to furnish an intermediate B. The hydroxyl group
in the presence of a base may attack the carbonyl functionality
present on C-5 to give an intermediate D, which may undergo
in situ intramolecular rearrangement to afford 5,6-dihydropyran-
2-ones 3a–k in good yields. To the best of our knowledge, such
an in situ intramolecular rearrangement of benzoyl group from po-
sition 5 to hydroxymethyl group is not known in the literature.
In summary, we have developed a convenient protocol for the
synthesis of functionalized 5,6-dihydropyran-2-ones through
base-catalyzed novel ‘ring transformation-rearrangement’ of func-
tionalized 6-aryl-2-pyran-2-ones with acetol in good yields. The
formation of the products 3a–k revealed a unique in situ intramo-
CN
OR
O
Ar
O
Ar
Ar
R = Me, Et
1h-m
4a-f
Entry
Ar
R
Time
(Min)
20
25
25
20
25
30
Yield (4)
(%)
80
a
b
c
d
e
f
phenyl
Et
Et
Et
Et
Et
4-bromophenyl
4-chlorophenyl
4-methoxyphenyl
2-thienyl
87
79
82
75
2-thienyl
Me
70
Scheme 4.

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A. Kumar et al. / Tetrahedron Letters 51 (2010) 961–965
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Figure 3. ORTEP diagram of compound 4e.
lecular ‘rearrangement of benzoyl moiety’ from position 5 of pyr-
an-2-one to the ‘hydroxymethyl group’ of 5,6-dihydropyran-2-
one. This methodology provides an easy access to diverse 5,6-
dihydropyran-2-ones at room temperature under mild reaction
environment.
18. Synthesis of 6-(aroyloxymethyl)-6-methyl-4-substituted-2-oxo-5,6-dihydro-
2H-pyran-3-carbonitrile/carboxylic acid methyl esters (3a–k): In
a typical
example, a mixture of 6-aryl-2H-pyran-2-ones (1, 1 mmol), acetol (2, 1 mmol),
and powdered KOH (2 mmol) in dry DMF (5 mL) was stirred at room
temperature for 10–24 h. At the end, reaction mixture was poured into ice
water with constant stirring and finally neutralized with dilute HCl. The solid
Acknowledgments
thus obtained was filtered and purified on
a silica gel column using 1%
methanol in chloroform as the eluent. Compound 3a: white solid; mp 124–
126 °C; 1H NMR (300 MHz, CDCl3) d 1.56 (s, 3H, CH3), 2.38 (s, 3H, SCH3), 2.73 (d,
J = 17.7 Hz, 1H, CH); 3.04 (d, J = 17.7 Hz, 1H, CH), 3.83 (s, 3H, OCH3), 3.87 (s, 3H,
OCH3), 4.40 (d, J = 11.8 Hz, 1H, CH), 4.45 (d, J = 11.8 Hz, 1H, CH), 6.92 (d,
J = 8.9 Hz, 2H, ArH), 7.98 (d, J = 8.9 Hz, 2H, ArH); 13C NMR (75.5 MHz, CDCl3) d
13.67, 22.17, 33.82, 51.09, 54.20, 77.19, 112.51, 114.56, 120.11, 130.62, 157.88,
162.58, 162.98, 163.6, 164.42; IR (KBr) 1696, 1733 cmÀ1 (CO); MS (ESI) 381
(M++1); HRMS (ESI+) calcd for C18H21O7S: 381.10080, found: 381.10364.
Compound 3b: white solid; mp 98–100 °C; 1H NMR (300 MHz, CDCl3) d 1.59 (s,
3H, CH3), 2.40 (s, 3H, SCH3), 2.76 (d, J = 17.7 Hz, 1H, CH); 3.06 (d, J = 17.7 Hz,
1H, CH), 3.84 (s, 3H, OCH3), 4.45 (d, J = 11.8 Hz, 1H, CH), 4.50 (d, J = 11.8 Hz, 1H,
CH), 7.44–7.50 (m, 2H, ArH), 7.58–7.64 (m, 1H, ArH), 8.01–8.08 (m, 2H, ArH); IR
(KBr) 1689, 1737 cmÀ1 (CO); MS (ESI) 351 (M++1); HRMS (ESI+) calcd for
C17H19O6S: 351.0902, found: 351.0903. Compound 3c: white solid; mp 114–
116 °C; 1H NMR (200 MHz, CDCl3) d 1.57 (s, 3H, CH3), 2.39 (s, 3H, SCH3), 2.75 (d,
J = 17.9 Hz, 1H, CH); 3.03 (d, J = 17.7 Hz, 1H, CH), 3.83 (s, 3H, OCH3), 4.41 (d,
J = 11.9 Hz, 1H, CH), 4.61 (d, J = 11.9 Hz, 1H, CH), 7.43 (d, J = 8.5 Hz, 2H, ArH),
7.97 (d, J = 8.5 Hz, 2H, ArH); 13C NMR (75.5 MHz, CDCl3) d 15.40, 23.88, 35.57,
52.87, 69.10, 78.70, 116.30, 127.88, 129.32, 131.63, 140.57, 168.00, 164.36,
165.31, 165.65; IR (KBr) 1696 and 1733 cmÀ1 (CO); MS (ESI) 385, 387 (M++1,
M++3); HRMS (ESI+) calcd for C17H18ClO6S: 385.05126, found: 385.05014.
Compound 3d: white solid; mp 130–132 °C; 1H NMR (200 MHz, CDCl3) d 1.57
(s, 3H, CH3), 2.39 (s, 3H, SCH3), 2.74 (d, J = 17.7 Hz, 1H, CH); 3.03 (d, J = 17.7 Hz,
1H, CH), 3.83 (s, 3H, OCH3), 4.40 (d, J = 11.9 Hz, 1H, CH), 4.50 (d, J = 11.9 Hz, 1H,
CH), 7.60 (d, J = 8.4 Hz, 2H, ArH), 7.89 (d, J = 8.4 Hz, 2H, ArH); IR (KBr) 1696,
1733 cmÀ1 (CO); MS (ESI) 429 (M++1), 431 (M++3). Compound 3e: white solid;
mp 108–110 °C; 1H NMR (300 MHz, CDCl3) d 1.58 (s, 3H, CH3), 2.40 (s, 3H, CH3),
2.44 (s, 3H, SCH3), 2.74 (d, J = 17.7 Hz, 1H, CH); 3.05 (d, J = 17.7 Hz, 1H, CH),
3.85 (s, 3H, OCH3), 4.44 (d, J = 11.8 Hz, 1H, CH), 4.49 (d, J = 11.8 Hz, 1H, CH),
7.27 (d, J = 8.2 Hz, 2H, ArH), 7.94 (d, J = 8.2 Hz, 2H, ArH); 13C NMR (75.5 MHz,
CDCl3) d 15.42, 22.12, 23.87, 52.83, 79.0, 116.18, 126.70, 129.66, 130.25,
144.84, 159.56, 164.96, 165.39, 166.49; IR (KBr) 1696, 1733 cmÀ1 (CO); MS
(ESI) 365 (M++1). Compound 3f: white solid; mp 102–104 °C; 1H NMR
(300 MHz, CDCl3) d 1.63 (s, 3H, CH3), 2.39 (s, 3H, SCH3), 2.78 (d, J = 17.7 Hz,
1H, CH); 3.11 (d, J = 17.7 Hz, 1H, CH), 3.84 (s, 3H, OCH3), 4.54–4.58 (m, 2H,
CH2), 7.51–7.68 (m, 3H, ArH), 7.92 (d, J = 4.7 Hz, 1H, ArH), 8.09 (d, J = 8.2 Hz,
1H, ArH), 8.20–8.28 (m, 1H, ArH); 8.94 (d, J = 8.6 Hz, 1H, ArH), IR (KBr) 1693,
1725 cmÀ1 (CO); MS (ESI) 401 (M++1). Compound 3g: white solid; mp 104–
106 °C; 1H NMR (200 MHz, CDCl3) d 1.56 (s, 3H, CH3), 2.40 (s, 3H, SCH3), 2.74 (d,
J = 17.7 Hz, 1H, CH); 3.05 (d, J = 17.7 Hz, 1H, CH), 3.84 (s, 3H, OCH3), 4.36–4.42
(m, 2H, CH2), 7.11–7.15 (m, 1H, ArH), 7.62 (d, J = 4.9 Hz, 1H, ArH), 7.84 (d,
The work is supported by the Department of Science and Tech-
nology, New Delhi, under Ramanna Fellowship Scheme to A.G. (SR/
S1/RFPC-10/2006). The authors are grateful to Dr. T. Narender for
valuable discussions on structural elucidation. A.K. and S.P.S. are
grateful to CSIR, and ICMR, New Delhi, for senior research fellow-
ship. The authors thank Sophisticated Analytical Instrument Facil-
ity (SAIF), Central Drug Research Institute, Lucknow, for providing
spectroscopic data of the synthesized compounds.
References and notes
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A. Kumar et al. / Tetrahedron Letters 51 (2010) 961–965
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J = 3.7 Hz, 1H, ArH); IR (KBr) 1696, 1732 cmÀ1 (CO); MS (ESI) 357 (M++1).
Compound 3h: white solid; mp 160–162 °C; 1H NMR (300 MHz, CDCl3) d 1.65
(s, 3H, CH3), 1.68–1.73 (m, 6H, 3CH2), 2.61 (d, J = 15.8 Hz, 1H, CH); 2.82 (d,
J = 15.8 Hz, 1H, CH), 3.64–3.70 (m, 4H, 2CH2), 4.43 (d, J = 11.8 Hz, 1H, CH), 4.48
(d, J = 11.8 Hz, 1H, CH), 7.44–7.53 (m, 2H, ArH), 7.57–7.67 (m, 1H, ArH), 8.00–
8.08 (m, 2H, ArH); IR (KBr) 1684 & 1716 cmÀ1 (CO), 2201 cmÀ1 (CN); MS (ESI)
355 (M++1); HRMS (EI+) calcd for C20H22N2O4: 354.1580, found: 354.1575.
Compound 3i: white solid; mp 160–162 °C; 1H NMR (300 MHz, CDCl3) d 1.53
(s, 3H, CH3), 1.68–1.73 (m, 6H, 3CH2), 2.63 (d, J = 15.9 Hz, 1H, CH); 2.83 (d,
J = 15.9 Hz, 1H, CH), 3.60–3.80 (m, 4H, 2CH2), 4.39 (d, J = 11.8 Hz, 1H, CH), 4.44
(d, J = 11.8 Hz, 1H, CH), 7.61 (d, J = 8.6 Hz, 2H, ArH), 7.89 (d, J = 8.6 Hz, 2H, ArH);
IR (KBr) 1680, 1722 cmÀ1 (CO), 2204 cmÀ1 (CN); MS (ESI) 433 (M++1), 435
(M++3). Compound 3j: white solid; mp 150–152 °C; 1H NMR (300 MHz, CDCl3)
d 1.55 (s, 3H, CH3), 1.60–1.78 (m, 6H, 3CH2), 2.61 (d, J = 15.9 Hz, 1H, CH); 2.82
(d, J = 15.9 Hz, 1H, CH), 3.60–3.80 (m, 4H, 2CH2), 4.42 (d, J = 11.9 Hz, 1H, CH),
4.46 (d, J = 11.8 Hz, 1H, CH), 7.46 (d, J = 8.5 Hz, 2H, ArH), 7.98 (d, J = 8.5 Hz, 2H,
ArH); IR (KBr) 1673, 1727 cmÀ1 (CO), 2206 cmÀ1 (CN); MS (ESI) 389 (M++1),
391 (M++3). Compound 3k: white solid; mp 196–198 °C; 1H NMR (300 MHz,
CDCl3) d 1.54 (s, 3H, CH3), 2.40–2.48 (m, 4H, 2CH2), 2.53 (d, J = 15.9 Hz, 1H, CH);
2.75 (d, J = 15.9 Hz, 1H, CH), 3.70–3.80 (m, 4H, 2CH2), 4.22 (s, 1H, CH), 4.43 (d,
J = 11.6 Hz, 1H, CH), 4.45 (d, J = 11.6 Hz, 1H, CH), 7.29–7.36 (m, 9H, ArH), 7.65
(d, J = 8.5 Hz, 2H, ArH), 7.90 (d, J = 8.5 Hz, 2H, ArH); 13C NMR (75.5 MHz,
CDCl3+DMSO) d 26.91, 37.49, 52.90, 55.14, 72, 75.11, 78.12, 80.59, 121.14,
131.13, 131.62, 132.24, 132.34, 132.48, 132.58, 134.72, 134.79, 135.44, 136.28,
143.83, 144.46, 166.65, 167.41, 168.48; IR (KBr) 1686, 1723 cmÀ1 (CO),
2207 cmÀ1 (CN); MS (ESI) 634 (M++1), 636 (M++3). Compound 4a: white
solid; mp 148–150 °C; 1H NMR (200 MHz, CDCl3) d 1.25 (t, J = 7.0 Hz, 3H, CH3),
1.72–1.76 (m, 6H, 3CH2), 3.63–3.67 (m, 4H, 2CH2), 4.11 (q, J = 7.0 Hz, 2H, CH2),
4.91 (s, 2H, CH2), 7.44–7.67 (m, 3H, ArH), 7.95–8.10 (m, 2H, ArH); IR (KBr)
1668 cmÀ1 (CO), 2194 cmÀ1 (CN); MS (ESI) 327 (M++1). Compound 4b: white
solid; mp 130–132 °C; 1H NMR (200 MHz, CDCl3) d 1.25 (t, J = 7.1 Hz, 3H, CH3),
1.72–1.76 (m, 6H, 3CH2), 3.64–3.68 (m, 4H, 2CH2), 4.11 (q, J = 7.1 Hz, 2H, CH2),
4.84 (s, 2H, CH2), 7.65 (d, J = 8.4 Hz, 2H, ArH), 7.86 (d, J = 8.4 Hz, 2H, ArH); 13C
NMR (50 MHz, CDCl3) d 14.91, 24.05, 26.70, 41.37, 52.91, 60.85, 120.01, 125.54,
129.55, 130.38, 132.60, 135.16, 166.91, 168.11, 193.61; IR (KBr) 1678 cmÀ1
(CO), 2196 cmÀ1 (CN); MS (ESI) 405 (M++1), 407 (M++3). Compound 4c: white
solid; mp 112–114 °C; 1H NMR (200 MHz, CDCl3) d 1.25 (t, J = 7.1 Hz, 3H, CH3),
1.72–1.76 (m, 6H, 3CH2), 3.64–3.68 (m, 4H, 2CH2), 4.11 (q, J = 7.1 Hz, 2H, CH2),
4.84 (s, 2H, CH2), 7.48 (d, J = 6.9 Hz, 2H, ArH), 7.93 (d, J = 6.9 Hz, 2H, ArH); IR
(KBr) 1680 cmÀ1 (CO), 2198 cmÀ1 (CN); MS (ESI) 361 (M++1). Compound 4d:
white solid; mp 140–142 °C; 1H NMR (200 MHz, CDCl3) d 1.25 (t, J = 7.5 Hz, 3H,
CH3), 1.71–1.75 (m, 6H, 3CH2), 3.63–3.67 (m, 4H, 2CH2), 3.89 (s, 3H, OCH3),
4.12 (q, J = 7.0 Hz, 2H, CH2), 4.87 (s, 2H, CH2), 6.96 (d, J = 8.9 Hz, 2H, ArH), 7.97
(d, J = 8.9 Hz, 2H, ArH); 13C NMR (50 MHz, CDCl3) d 14.80, 23.99, 26.80, 41.24,
52.48, 56.05, 60.92, 114.72, 120.34, 128.40, 129.53, 131.02, 164.39, 167.58,
169.64, 192.69; IR (KBr) 1682 cmÀ1 (CO), 2196 cmÀ1 (CN); MS (ESI) 357 (M++1).
Compound 4e: white solid; mp 160–162 °C; 1H NMR (200 MHz, CDCl3) d 1.26
(t, J = 7.0 Hz, 3H, CH3), 1.71–1.75 (m, 6H, 3CH2), 3.64–3.68 (m, 4H, 2CH2), 4.14
(q, J = 7.0 Hz, 2H, CH2), 4.86 (s, 2H, CH2), 7.12–7.21 (m, 1H, ArH), 7.70 (d,
J = 4.7 Hz, 1H, ArH), 7.83 (d, J = 3.4 Hz, 1H, ArH); IR (KBr) 1666 cmÀ1 (CO), 2190
cmÀ1 (CN); MS (ESI) 333 (M++1). Compound 4f: white solid; mp 162–164 °C;
1H NMR (200 MHz, CDCl3) d 1.72–1.76 (m, 6H, 3CH2), 3.66–3.70 (m, 7H, 2CH2
&
CH3), 4.86 (s, 2H, CH2), 7.13–7.21 (m, 1H, ArH), 7.71 (d, J = 4.8 Hz, 1H, ArH),
7.83 (d, J = 3.4 Hz, 1H, ArH); IR (KBr) 1667 cmÀ1 (CO), 2191 cmÀ1 (CN); MS (ESI)
319 (M++1).