A substituent directed regioselective synthesis of aryl/pyronyl pendant unusual adipate and tetrahydronaphthalene

Article abstract of DOI:10.1016/j.tetlet.2008.02.148

An efficient regioselective synthesis of pyronyl pendant ethyl methylthiocarbonylalkanoates 5 has been delineated from the base catalyzed reaction of suitably functionalized 2-pyranone 1 and 2-carbethoxycycloalkanones 2, 6 through successive substitution

Full text of DOI:10.1016/j.tetlet.2008.02.148

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3011–3014
A substituent directed regioselective synthesis of aryl/pyronyl
pendant unusual adipate and tetrahydronaphthalene
a,
b,
*
*
Ramendra Pratap , Vishnu Ji Ram
a Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USA
b Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226 001, India
Received 12 February 2008; revised 20 February 2008; accepted 26 February 2008
Available online 4 March 2008
Abstract
An efficient regioselective synthesis of pyronyl pendant ethyl methylthiocarbonylalkanoates 5 has been delineated from the base
catalyzed reaction of suitably functionalized 2-pyranone 1 and 2-carbethoxycycloalkanones 2, 6 through successive substitution and regio-
selective ring opening by in situ generated mercaptide ion. To assess the effect of C-4 substituent on regioselectivity, reactions of 6-aryl-
3-cyano-4-(piperidin-1-yl)-2-oxopyran 8 with 2-carbethoxycyclohexanone 6a and 2-carbethoxy-2-methylcyclohexanone 6b were carried
out separately under analogous reaction conditions but the compounds isolated were identical and characterized as 4-aryl-8-methyl-
2-piperidin-1-yl-5,6,7,8-tetrahydronaphthalene-1-carbonitriles 9. Ethyl 2-(5-amino-40-bromo-4,6-dicyanobiphenyl-3-yl)-5-methylsulfan-
ylcarbonylpentanoate 10 has also been prepared through base catalyzed ring transformation of ethyl 2-[6-(4-bromophenyl)-3-cyano-
2-oxo-2H-pyran-4-yl]-5-methylsulfanylcarbonylpentanoate 5d by malononitrile in DMF.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: 2-Carbethoxycyclopentanone; 2-Oxopyran; Ring transformation; Mercaptide ion
Suitably functionalized 2-pyrones constitute an impor-
tant class of compounds, and are present as substructure
unit in numerous natural products1 of diverse therapeutic
importance as antimalarial,2 antifungal,3 pheromonal,4
androgen like,5 cardiotonic,6 and antiHIV7 agents. Besides
these, they are also very useful building blocks8,9 for the
construction of various congested arenes and heteroarenes.
As a consequence, attention has been focused to explore
the versatility of 2-pyrones through substituent dependent
base catalyzed substitution with successive ring opening
and ring transformation by 2-substituted cycloalkanones
for the construction of pyronyl and aryl pendant ethyl
methylthiocarbonylalkanoates and highly congested
tetrahydronaphthalenes.
A comprehensive literature survey revealed that not a
single example is known so far for the construction of
pyronyl and aryl pendant ethyl methylthiocarbonylalkano-
ates.
A
synthesis of simple ethyl methylsulfanyl-
carbonylalkanoates has been reported from the reaction
of ethyl mercaptan with dicarboxylic acid chloride ester
in pyridine.10 It has also been obtained through the irradi-
ation of S-phenylchlorothioformate and alkyl iodide in the
presence of bis(tributyltin) in benzene.11 Lubell et al.12
have also prepared this class of compounds by the acetyl-
ation of thiophenols with a-tert-butyl N-(PhF)-a-aminoad-
ipate and DCC-DMAP in acetonitrile as intermediate. The
lack of appropriate procedures to introduce ethyl methyl-
sulfanylcarbonylalkanoate as a substituent to aryl or
heteroaryl ring system, necessitated to develop an easy
access to the synthesis of this class of compounds to
explore their chemistry and biodynamic properties.
*
Corresponding authors. Tel.: +1 646 748 4979; fax: +1 212 650 6107
The precursors employed in this study were 6-aryl-3-
cyano-4-methylsulfanyl-2-oxopyrans 1 and 6-aryl-3-cyano-
4-(piperidin-1-yl)-2-oxopyrans 8, in which the former was
(R.P.); tel.: +91 522 2612411; fax: +91 522 2623405 (V.J.R.).
E-mail addresses: ramendrapratap@gmail.com (R. Pratap), vjiram@
yahoo.com (V. J. Ram).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.148

3012
R. Pratap, V. J. Ram / Tetrahedron Letters 49 (2008) 3011–3014
prepared13 from the reaction of aryl methyl ketone and
methyl 2-cyano-3,3-dimethylthioacrylate, while the latter
was obtained14 by the amination of 1 with piperidine in
boiling ethanol.
Herein, we report a short and efficient synthesis of ethyl
2-(6-aryl-3-cyano-2-oxopyran-4-yl)-5-methylsulfanylcarbon-
ylpentanoates 5 and ethyl 2-(6-aryl-3-cyano-2-oxopyran-
4-yl)-6-methylsulfanylcarbonylhexanoate 7 should base
catalyzed successive substitution and regioselective ring
opening by mercaptide ion, generated in situ from the reac-
tion of 6-aryl-3-cyano-4-methylsulfanyl-2-oxopyran 1 and
2-carbethoxycycloalkanones in DMF. In these reactions
sibly initiated by an attack of a carbanion generated from
2-carbethoxycycloalkanone at C-4 of the pyran ring to give
a substitution product as an intermediate A with the liber-
ation of methyl mercaptan which intern acts as a nucleo-
phile and attacks regioselectively at carbonyl function of
cycloalkanone ring of the intermediate with ring opening
to afford ethyl 2-(6-aryl-3-cyano-2-oxopyran-4-yl)meth-
ylsulfanylcarbonylalkanoates 5 and 7 (Schemes 1 and 2).
There are two other possibilities for the formation of
products 3 and 4 depending upon the attack of carbanion
at C-6 or C-4 of 2-pyrone 1. The formation of product 3
may possibly arise through the attack of carbanion at C-
6 with ring closure involving C-3 of pyran and carbethoxy
of 2, while the formation of the other expected product 4 is
based on the attack of carbanion at C-4 with the liberation
of methyl mercaptan followed by enolization and Michael
addition as depicted in Scheme 1. The proton NMR and
HRMS data of the isolated compounds did not match with
the proposed structures 3 and 4. In addition, the presence
2-carbethoxycyclopentanone
2 and 2-carbethoxycyclo-
hexanone 6 were used as a source of carbanion. The opti-
mization of reaction conditions is presented in Table 1.
The presence of carbonyl function adjacent to the carbon
linked to the carbethoxy substituent made position 2 highly
reactive. Thus, a reaction of 1 and 2 or 6 separately is pos-
Table 1
Optimization of reaction conditions
SCH3
O
CN
S.No.
Pyran-2-one
Ketone
Product
Conversion
(%)
COOC2H5
+
Ar
O
O
2
1
DMF/KOH
H
SCH3
O
C2H5OOC
O
CN
X
H3CS
H
O
1
100
CN
O
N
O
O
O
O
O
O
SCH3
C
C2H5OOC
C2H5OOC
Ar
O
CN
CN
O
C2H5OOC
Ar
N
O
H3CS
X
C-OC2H5
O
O
O
CH3S
Ar
C2H5OOC
O
H
2
3
CN
O
—
0a,b
O
OH
C2H5OOC
Ar
SCH3
CN
C2H5OOC
Ar
O
O
C
N
CN
OC2H5
H3CS
O
O
Ar
O
SCH3
O
O
A
O
CN
C2H5OOC
O
CN
i. Hydrolysis
80a,c
O
ii. Michael add. of CH3SH
C2H5OOC
O
O
SCH3
O
O
H
SCH3
C2H5OOC
SCH3
CN
O
O
C2H5OOC
Ar
CN
O
Ar
O
O
Ar
O
CN
O
O
C2H5OOC
SCH3
EtOOC
N
O
O
O
4
3
4
5
CN
O
100
O
CN
O
Ar
O
5
SCH3
O
1, 5
a
b
c
d
e
f
g
h
i
Ar
C6H5
4-F-C6H4
4-Cl-C6H4
Yields (%)
EtOOC
CN
O
89
94
87
96
89
84
95
90
91
—
0b
4-Br-C6H4
CN
4-CH3-C6H4
4-CH3O-C6H4
2,4-(CH3)2-C6H3
2-thienyl
O
N
6
CN
100
O
O
2-naphthyl
a
Starting material recovered through column chromatography.
No product formation.
b
c
Scheme 1. Plausible mechanism for the synthesis of ethyl 2-(6-aryl-3-
Reaction performed using NaH/THF.
cyano-2-oxopyran-4-yl)-5-methylsulfanylcarbonylpentanoates 5.

R. Pratap, V. J. Ram / Tetrahedron Letters 49 (2008) 3011–3014
3013
CH3
O
CH3
O
SCH3
N
CN
N
O
CN
6c
N
H
EtOH/
CN
O
H3C
O
O
DMF/KOH
O
+
DMF/KOH
Path b
O
O
Ar
O
O
Ar
O
C2H5OOC
O
SCH3
Ar
8
1
O
SCH3
O
CN
CN COOC2H5
Yield = 39%
6b
7
Path a
1e
6a
A Complex
Mixture
COOC2H5
H3C
6b
H
Scheme 2. Synthesis of ethyl 2-(6-p-tolyl-3-cyano-2-oxopyran-4-yl)-6-
methylsulfanylcarbonylhexanoate 7.
+
CN
N
HOOC
CN
C2H5OOC
CN
O
N
N
Ar
Ar
Ar
of CN frequency (2210–2260 cmꢀ1) in the IR spectrum
completely ruled out the possibility of product 4.
B
-CO2
+
H
H
It was interesting to note that the ring opening of 2-car-
bethoxycyclohexanon-2-yl pendant intermediate by mer-
captide ion, generated in situ from the reaction of 1e and
6a, gave ethyl 2-[6-(4-methylphenyl)p-tolyl-3-cyano-2-oxo-
pyran-4-yl]-6-methylsulfanylcarbonylhexanoate 7 in 39%
yields. Under analogous conditions, a reaction of 3-
cyano-6-(4-methylphenyl)-4-(piperidin-1-yl)-2H-pyran-2-one
8 with 2-carbethoxycyclohexanone 6a ended with the
recovery of starting materials while with 2-methylcyclo-
hexanone 6c under identical conditions afforded 4-aryl-
2-(piperidin-1-yl)-8-methyl-5,6,7,8-tetrahydronaphthalene-
1-carbonitriles 9. Attempts to force the ring transformation
of 2-pyrone 1 by 2-carbethoxy-2-methylcyclohexanone 6b
to obtain 4-aryl-2-methylsulfanyl-8-methyl-5,6,7,8-tetrahy-
dronaphtha-lene-1-carbonitrile failed and ended with an
inseparable complex mixture, while under analogous con-
ditions a reaction of 8 with 6b produced a ring transformed
product 9. This reaction is possibly initiated by the attack
of a carbanion at C-6 of the pyran ring with ring closure
followed by the loss of carbon dioxide and water to
form an intermediate, 4-aryl-2-(piperidin-1-yl)-8-carbethoxy-
CN
OH
CN
N
N
CN
O
N
Ar
Ar
H
Ar
9
9
Ar
C6H5
4.Cl-C6H4
4.Br-C6H4
2-naphthyl
aYields (%)
bYields (%)
a
b
c
33
29
43
39
79
71
77
69
d
Scheme 3. A plausible mechanism involved in the formation of 4-aryl-2-
(piperidin-1-yl)-8-methyl-5,6,7,8-tetrahydronaphthalene-1-carbonitriles 9.
SCH3
SCH3
O
C2H5OOC
SCH3
O
C2H5OOC
NCCH2CN
DMF/KOH
O
O
C2H5OOC
O
O
CN
O
O
CN
CN
O
N
NH
CN
CN
Br
5d
Br
Br
8-methyl-5,6,7,8-tetrahydronaphthalene-1-carbonitriles
B
SCH3
which under experimental conditions hydrolyzed and
decarboxylated to afford 9. These reactions confirmed the
impact of substituents at C-4 of 2-pyranone and C-2 posi-
tion of cycloalkanones on the regioselectivity of the reac-
tion. Attempts were made to trap the intermediate but
could not succeed. The reaction of 8 with 2-methylcyclo-
hexanone 6c followed the same mechanism to produce 9.
The probable mechanism and yields of the compounds
are shown in Scheme 3.
C2H5OOC
O
H2N
NC
CN
CN
O
H3CS
Br
NH
NC
H
Br
COOC2H5
10
Scheme 4. Mechanism for the synthesis of ethyl 2-(5-amino-40-bromo-4,6-
dicyanobiphenyl-3-yl)-5-methylsulfanylcarbonylpentanoate 10.
Our attempts for the ring transformation of 2-[6-
(4-bromophenyl)-3-cyano-2-oxo-2H-pyran-4-yl)]-5-methyl-
sulfanylcarbonylpentanoate 5d by malononitrile succeeded,
and the isolated compound was characterized as ethyl 2-(5-
amino-40-bromo-4,6-dicyanodiphenyl-3-yl)-5-methylsulfan-
ylcarbonylpentanoate 10 in moderate yield.
In this reaction, the carbanion generated at the reactive
methylene carbon attacks at C-6 with ring closure involv-
ing C-3 of the pyran ring and nitrile functionality of the
malononitrile. The probable mechanism of the reaction is
shown in Scheme 4.
In conclusion, we have developed a substituent directed
regioselective concise synthesis of pyronyl pendant ethyl
methylsulfanylcarbonylalkanoates from the reaction of 6-
aryl-3-cyano-4-methylsulfanyl-2-oxopyran with 2-carbeth-
oxycycloalkanones separately through substitution fol-
lowed by ring opening of the latter by methyl mercaptide
ion, generated in situ. The highly congested aryl tethered
ethyl methylsulfanylcarbonylpentanoate has also been pre-
pared through the ring transformation of ethyl 2-[6-(4-
bromophenyl)-3-cyano-2-oxo-2H-pyran-4-yl]-5-methylsulf-
anylcarbonylpentanoate. The yields of the product were
directly related to the stability of 2-carbethoxycycloalka-
none rings. An increase in the size of the cycloalkanone
All the synthesized compounds were characterized by
HRMS and other spectroscopic techniques.15

3014
R. Pratap, V. J. Ram / Tetrahedron Letters 49 (2008) 3011–3014
purified on silica gel column, using 40% hexane in chloroform as
eluent. It was isolated as a yellow solid; yield: 356 mg (89%); mp: 56–
58 °C; IR: (KBr) 2367, 2210, 1697, 1600, 1449, 1352, 1282, 1227, 1173,
1064, 906, 765, 733, 687 cmꢀ1; 1H NMR: (300 MHz, CDCl3): 1.29 (t,
J = 7.11 Hz, 3H, CH3), 1.65–1.88 (m, 2H, CH2), 1.90–1.97 (m, 1H,
CH), 2.15–2.27 (m, 1H, CH), 2.28 (s, 3H, SCH3), 2.65 (t, J = 6.97 Hz,
2H, CH2), 3.98 (t, J = 7.30 Hz, 1H, CH), 4.17–4.30 (m, 2H, CH2),
6.97 (s, 1H, ArH), 7.49–7.60 (m, 3H, ArH), 7.90 (d, J = 7.92 Hz, 2H,
ArH); 13C NMR: (75 MHz, CDCl3): 10.3, 12.8, 21.7, 28.3, 29.6, 41.5,
48.6, 61.0, 97.5, 99.2, 125.4, 128.0, 128.4, 131.6, 156.7, 162.8, 162.7,
168.3, 197.4; MS m/z 400 (M++1); HRMS: (EI, 70 eV) calcd for
C21H21NO5S 399.1140 (M+) found for m/z 399.1138. Compound (5e):
It was obtained from the reaction of 1e (257 mg, 1 mmol) and 2
(0.234 mL, 1.5 mmol) in the presence of powdered KOH (112 mg,
2 mmol) in dry DMF. Usual work-up and purification on silica gel
column using 40% hexane in chloroform as eluent afforded yellow
solid; yield: 359 mg (89%); mp: 98–100 °C; IR: (KBr) 2965, 2367,
2219, 1728, 1686, 1613, 1525, 1456, 1348, 1276, 1236, 1207, 1159,
rings from 5 to 6 reduced the yield due to higher stability of
the cyclohexanone ring. The presence of 4-(piperidin-
1-yl) substituent in 2-pyranone ring changes the course of
the reaction from substitution to ring transformation. This
methodology opens a new avenue for the synthesis of
various aryl and pyronyl pendant alkyl methylsulfanyl-
carbonylalkanoates not obtainable by any available litera-
ture procedures.
Acknowledgements
V.J.R. and R.P. are thankful to CSIR, New Delhi for
financial support and Sophisticated Analytical Instrument
Facility, CDRI, Lucknow for providing spectroscopic
data.
1062, 1017, 858, 824, 768, 712 cmꢀ1 1H NMR: (300 MHz, CDCl3):
;
1.28 (t, J = 7.13 Hz, 3H, CH3), 1.66–1.81 (m, 2H, CH2), 1.82–1.91 (m,
1H, CH), 2.12–2.22 (m, 1H, CH), 2.29 (s, 3H, SCH3), 2.43 (s, 3H,
CH3), 2.63 (t, J = 6.89 Hz, 2H, CH2), 3.97 (t, J = 7.13 Hz, 1H, CH),
4.18–4.25 (m, 2H, CH2), 6.87 (s, 1H, ArH), 7.31 (d, J = 8.16 Hz, 2H,
ArH), 7.78 (d, J = 8.28 Hz, 2H, ArH); 13C NMR: (75 MHz, CDCl3):
10.3, 12.8, 20.4, 21.7, 29.8, 41.5, 48.6, 61.6, 96.8, 98.4, 112.0, 125.5,
125.7, 128.7, 128,8, 142.8, 150.8, 162.9, 163.3, 168.5, 197.4: MS m/z
414 (M++1); HRMS: (EI, 70 eV) calcd for C22H23NO5S
413.1296(M+) found for m/z 413.1293.
References and notes
1. (a) Marrison, L. R.; Dickinson, J. M.; Ahmed, R.; Fairlamb, I. J. S.
Tetrahedron Lett. 2002, 43, 8853–8857; (b) Almtorp, G. T.; Hazell, A.
C.; Torssel, K. B. G. Phytochemistry 1991, 30, 3753.
2. (a) Yao, T.; Larock, R. C. J. Org. Chem. 2003, 68, 5936–5942; (b)
Fairlamb, I. J. S.; Marrison, L. R.; Dickinson, J. M.; Lu, F.-J.;
Schmidt, J. P. Bioorg. Med. Chem. 2004, 12, 4285–4299; (c) Culter, H.
G.; Cox, R. H.; Crumley, F. G.; Cole, P. D. Agric. Biol. Chem. 1986,
50, 2943–2945.
3. (a) Claydon, N.; Allan, M. Trans. Br. Mycol. Soc. 1987, 503–513; (b)
Simon, A.; Dunlop, R. W.; Ghisalberti, E. L.; Silvasithamparam, K.
Soil Biol. Biochem. 1988, 20, 263–264.
4. Shi, X.; Leal, W. S.; Liu, Z.; Schrader, E.; Meinwald, J. Tetrahedron
Lett. 1995, 36, 71–74.
5. Schlingmann, G.; Miline, L.; Carter, G. Tetrahedron 1998, 54, 13013–
13022.
6. Chen, K. K.; Kovarikova, A. J. Pharm. Sci. 1967, 56, 1535–1541.
7. Katritzky, A. R.; Wang, Z.; Wang, M.; Hall, C. D.; Suzuki, K. J. Org.
Chem. 2005, 70, 4854–4856.
8. (a) Hsung, R. P.; Shen, H. C.; Douglas, C. J.; Morgan, C. D.; Degen,
S. J.; Yao, L. J. J. Org. Chem. 1999, 64, 690–691; (b) Danieli, B.;
Lesma, G.; Martinelli, M.; Passarella, D.; Peretto, I.; Silvani, A.
Tetrahedron 1998, 54, 14081–14088; (c) Chen, C. H.; Liao, C.-C. Org.
Lett. 2000, 2, 2049–2052; (d) Liu, Z.; Meinwald, J. J. Org. Chem.
1996, 61, 6693–6699.
General procedure for the synthesis of 4-aryl-2-(piperidin-1-yl)-8-
methyl-5,6,7,8-tetrahydronaphthalene-1-carbonitriles (9): A mixture of
6-aryl-3-cyano-4-(piperidin-1-yl)-2-oxopyran 8 (1.0 mmol) and 2-carb-
ethoxy-2-methylcyclohexanone 6b (230 mg, 1.5 mmol) or 2-methyl-
cyclohexanone (160 mg, 1.5 mmol) in DMF (5.0 mL) in the presence
of powdered KOH (112 mg, 2 mmol) was stirred for 1–1.5 h. Excess
of DMF was removed under reduced pressure and the residue poured
onto crushed ice with vigorous stirring. The aqueous solution was
neutralized with 10% HCl (5.0 mL) and the precipitate obtained was
filtered, washed with water and purified on silica gel column, using
hexane/chloroform mixture (70:30) as eluent. Compound (9b): White
powder, yield: 260 mg (71%); mp: 126–128 °C; IR: (KBr) 3021, 2934,
2367, 2216, 1522, 1365, 1216, 1024, 910, 763, 670 cmꢀ1 1H NMR:
;
(200 MHz, CDCl3): 1.38 (d, J = 7.0 Hz, 3H, CH3), 1.57–1.62 (m, 2H,
CH2), 1.72–1.77 (m, 8H, CH2), 2.38–2.45 (m, 2H, CH2), 3.05–3.12 (m,
4H, NCH2), 3.38–3.42 (m, 1H, CH), 6.65 (S, 1H, ArH), 7.18 (d,
J = 8.72 Hz, 2H, ArH), 7.38 (d, J = 8.38 Hz, 2H, ArH); MS m/z 365
(M++1); HRMS: (EI, 70 eV) calcd for C23H25ClN2 364.1706 (M+)
found for m/z 364.1707.
9. Afarinkia, K.; Vinader, V.; Nelson, T. D.; Posner, G. H. Tetrahedron
1992, 48, 9111.
Synthesis of ethyl 2-(5-amino-40-bromo-4,6-dicyanobiphenyl-3-yl)-5-
methylsulfanylcarbonylpentanoate (10):
A mixture of 5d (96 mg,
10. (a) Liu, H.-J.; Bukownik, R. R.; Pednekar, P. R. Synth. Commun.
1981, 11, 599–603; (b) Yamada, Y.; Ishii, T.; Kimura, M.; Hosaka, K.
Tetrahedron Lett. 1981, 22, 1353–1354.
11. Kim, S.; Jon, S. Y. Chem. Commun. 1998, 815–816.
12. Gosselin, F.; Lubell, W. T. J. Org. Chem. 1998, 63, 7463–7471.
13. (a) Ram, V. J.; Verma, M.; Hussaini, F. A.; Shoeb, A. Liebigs Ann.
Chem. 1991, 1229–1231; (b) Ram, V. J.; Verma, M.; Hussaini, F. A.;
Shoeb, A. J. Chem. Res., Synop. 1991, 98–99.
0.2 mmol), malononitrile (18 mg, 0.25 mmol) and KOH (17 mg,
0.3 mmol) in DMF (2.0 mL) was stirred for 1–2 h. Completion of
the reaction was monitored by TLC. After completion, the reaction
mixture was poured onto crushed ice with vigorous stirring followed
by neutralization with 10 % HCl. The precipitate obtained was
filtered, washed with water, dried and purified with silica gel column
chromatography using hexane/chloroform (1:1) mixture as eluent
affording light yellow crystalline solid. Yield: 78 mg (78%); mp: 108–
110 °C; IR: (KBr) 3452, 3357, 3242, 2920, 2850, 2218, 1731, 1687,
1635, 1581, 1492, 1467, 1441, 1393, 1369, 1280, 1190, 1073, 1011, 827,
14. Pratap, R.; Sil, D.; Ram, V. J. Tetrahedron Lett. 2004, 45, 5743.
15. Representative procedure for the synthesis of ethyl 2-(3-cyano-2-oxo-6-
phenyl-2H-pyran-4-yl)-5-methylsulfanylcarbonylpentanoate (5a):
A
759 cmꢀ1 1H NMR: (200 MHz, CDCl3): 1.23–1.30 (m, 3H, CH3),
;
mixture of 3-cyano-4-methylsulfanyl-6-phenyl-2-oxopyran 1a
(243 mg, 1 mmol) and 2-carbethoxycyclopentanone 2 (0.234 mL,
1.5 mmol) in DMF (5 mL) in the presence of powdered KOH
(112 mg, 2 mmol) was stirred for 6 h. Excess of DMF was removed
under reduced pressure and the residue poured onto crushed ice with
vigorous stirring. The aqueous solution was neutralized with 10% HCl
(5 mL) and the gummy material obtained was washed with water and
1.66–1.84 (m, 3H, CH2 and CH), 2.10–2.15 (m, 1H, CH), 2.28 (s, 3H,
SCH3), 2.59 (t, J = 6.78 Hz, 2H, CH2), 3.91 (t, J = 6.85 Hz, 1H, CH),
4.09–4.22 (m, 2H, CH2), 5.33 (br s, 2H, NH2), 6.81 (s, 1H, ArH), 7.41
(d, J = 8.38 Hz, 2H, ArH), 7.63 (d, J = 8.25 Hz, 2H, ArH); MS m/z
500 (M+) and 502 (M++2); HRMS: (EI, 70 eV) calcd for
C23H22BrN3O3S 499.056(M+) found for m/z 499.0563.