Studies with phenylsulfone derivatives: Synthesis of pyrrole, thiophene and their fused derivatives

Article abstract of DOI:10.1002/jhet.5570450451

(Chemical Equation Presented) Diethyl 2-(1-phenyl-2-(phenylsulfonyl) ethylidene)malonate 3 has been prepared via the reaction of 6 with sodium benzenesulfinate. Compound 3 proved to be highly reactive towards various reagents and underwent numerous chemical transformation, resulting in the construction of a wide range of heterocyclic sulfone systems.

Full text of DOI:10.1002/jhet.5570450451

Jul-Aug 2008
1237
Studies with Phenylsulfone Derivatives: Synthesis Of Pyrrole,
Thiophene And Their Fused Derivatives.
Yehya M. Elkholy
Chemistry Department, Faculty of Science, Helwan University.
Ain-Helwan, Cairo, Egypt.e-mail:y_elkholy@yahoo.com
Received August 16, 2007
EtO2C
Ph
OH
ArNH2
N
EtOH/Et3N, /
C6H4Cl-p
EtO2C
Ph
CO2Et
EtO2C
CO2Et
SO2Ph
C6H6,
8
SO2Ph
Br
Br2
CO2Et
Ph
SO2Ph
3
7
-HBr
-2HOEt
PhO2S
O
N
R 1
CO2Et
NH2
O
S
R2
-
R1, R2 = -
R2
S
R 1
(CH )
2 4
13
12
Diethyl 2-(1-phenyl-2-(phenylsulfonyl)ethylidene)malonate 3 has been prepared via the reaction of 6
with sodium benzenesulfinate. Compound 3 proved to be highly reactive towards various reagents and
underwent numerous chemical transformation, resulting in the construction of a wide range of heterocyclic
sulfone systems.
J. Heterocyclic Chem., 45, 1237 (2008).
INTRODUCTION
which reacted with NBS to afford compound 6 [2], the
latter product reacted with equimolar amounts of sodium
benzenesulfinate in ethanolic solution to yield compound
3. Trials to prepare compound 3 by the reaction of 1 with
arylsulfonyl acetophenone 4 in acidic or basic media
failed (Scheme 1).
Compound 3 proved to be highly reactive towards
various reagents and underwent numerous chemical
transformations, resulting in the construction of a wide
range of heterocyclic sulfone systems. Thus, compound 3
could be brominated when equimolar amounts of 3 and
bromine in dry benzene were boiled under reflux to afford
the corresponding diethyl 2-(2-bromo-1-phenyl-2-
(phenylsulfonyl)ethylidene)malonate 7. Treatment of 7
Phenyl sulfone derivatives have proven to be valuable
synthons for the preparation of a wide variety of
biologically active heterocyclic systems [1-6]. Phenyl
sulfones shows anti-ulcer effect [7], and used for
synthesis of KDN- ꢀ-C-glycosides and various stilbenes
such as resveratrol [8,9]. Our aim in the work presented
herein was to synthesize heterocyclic sulfone derivatives
using phenylsulfone derivatives as building blocks.
RESULTS AND DISCUSSION
Diethyl malonate 1 reacts with acetophenone in
benezene/ammonium acetate mixture to give compound 5
Scheme 1
NH4OAc
benzene
EtO2C
CO2Et
CH3
EtO2C
EtO2C
NBS
CH2
CCl4
/
PhCOCH3
1
2
5
Ph-CO-CH2-SO2Ph
EtO2C
CO2Et
SO2Ph
EtO2C
CO2Et
Br
4
PhSO2Na
3
6

1238
Y. M. Elkholy
Vol 45
with the appropriate primary aromatic amine in ethanolic/
triethylamine solutions afforded the corresponding ethyl
1-(4-chlorophenyl)-2-hydroxy-4-phenyl-5-(phenylsulfonyl)-
1H-pyrrole-3-carboxylate 8. In a one-pot reaction ethyl
5-oxo-2-phenyl-1-(phenylsulfonyl)pyrrolo[2,1-b]benzo-
[d][1,3]oxazine-3-carboxylte 11, and ethyl 6,7,8,9-tetra-
hydro-5-oxo-2-phenyl-1(phenylsulfonyl)-pyrrolo[2,1-b]-
thieno[2,3-b][1,3]oxazine-3-carboxylate 13 were obtained
upon treating compound 7 with 2-aminobenzonitrile and
ethyl 2-aminothiophene-3-carboxylate derivative 12
[10,11], respectively (Scheme 2).
Compound 3 reacted with arylidenemalononitrile 14 to
yield the corresponding ethyl benzoate derivatives 16.
Compound 16 is assumed to be formed via addition of 3
to the activated double bond in 14 to yield the Michael
adducts 15 which intra-molecularly cyclized and
Scheme 2
EtO2C
Ph
OH
EtO2C
Ph
CO2Et
ArNH2
Br2
3
N
Br
C6H6,
EtOH/Et3N, /
C6H4Cl-p
SO2Ph
SO2Ph
7
8
R1
R2
CO2Et
NH2
CN
-HBr
-2HOE
NH2
dry dioxane/
Et3N-
S
12
9
CO2Et
Ph
CO2Et
Ph
Ph
CO2Et
PhO2S
O
N
PhO2S
PhO2S
OH
CN
O
O
N
O
N
S
R2
R1
13
-
10
11
R1 , R2 = - (CH2)4
Scheme 3
OH
CN
CO2Et
EtO2C
CN
Ph
EtO2C
Ph
- EtOH
- HCN
CN
Ph
Ph
SO2Ph
SO2Ph
CH2(CN)2
16
15
CN
CN
CO2Et
EtO2C
Ph
PhCHO
Ph
EtOH/
Et3N
Ph
SO2Ph
14
O
17
CO2Et
NHAr
EtO2C
Ph
Ar
EtO2C
Ph
N
N
+
-
EtOH/NaOAc
Ar - N N Cl
EtOH/NaOAc
3
N
SO2Ph
SO2Ph
O
dioxane
19
18
Ph
NCS
Ar= 4-ClC6H4
O
O
Ph
EtO2C
Ph
COPh
EtO2C
Ph
N
N
ClCH2CN
EtOH/K2CO3
CN
/
S
SH
SO2Ph
SO2Ph
20
21

Jul-Aug 2008
Studies with Phenylsulfone Derivatives
1239
pyridine-6-carboxylate 24 upon treatment with an
equimolar proportion of sodium nitrite in glacial acetic
acid (Scheme 4). Treatment of 22 with ethyl
2-aminothiophene-3-carboxylate 12 in absolute ethanol
solution containing glacial acetic acid under reflux,
furnished the corresponding ethyl 10-phenyl-7,8-dioxo-
11-(phenylsulfony)-l,3,4,5,6-tetrahydro-1H-pyrido[1,2-a]-
thieno[2,3-d]pyrimidine-9-carboxylate 25. Similarly,
ethyl 9,10-dihydro-9,11-dioxo-7-phenyl-6-(phenyl-
sulfonyl)-5H-pyrido[2,1-a]quinazoline-8-carboxylate 26
could be obtained upon treatment of 22 with 2-
aminobenzonitrile 9.
aromatized via loss of HCN to give the final isolated ethyl
benzoate derivatives 16. Compound 16 could be prepared
via an independent route involving the condensation of 3
with benzaldehyde and subsequent addition of
malononitrile to the so-formed benzylidene derivative 17
(Scheme 3). Compound 3 coupled readily with equimolar
amounts of arenediazonium chlorides to yield a coupling
product which may be formulated as the hydrazone form
18 or its cyclic pyridazine form 19. The hydrazone form
1
18 is preferred on the basis of H NMR spectra which
revealed the presence of multiplet signals corresponding
to the two ester functions. Furthermore, pyridazines 19
could be obtained upon boiling hydrazone 18 in ethanolic
sodium acetate solution. Ethyl 1-benzoyl-4-phenyl-1,2-
dihydro-2-oxo-6-mercapto-5-(phenylsulfonyl)pyridine-3-
carboxylate 20 was obtained in a good yield from the
reaction of 3 with benzoylisothiocyanate in boiling dry
dioxane. Compound 20 also reacted with
chloroacetonitrile in the presence of K2CO3 to yield the
corresponding ethylthiazolo[2,3-a]pyridine-6-carboxylate
derivative 21.
EXPERIMENTAL
All melting points were measured on a Gallenkamp melting
point apparatus and are uncorrected. IR spectra were recorded
(KBr) on a Pye Unicam SP-1000 spectrometer. 1H NMR spectra
were obtained on a Varian Gemini 200 MHz spectrometer using
TMS as an internal reference. Chemical shifts are expressed as ꢀ
(ppm). Mass spectra were recorded on a GCMS-QP 1000 EX
mass spectrometer operating at 70 eV. Micro analytical data
were performed by the Micro analytical Unit, Cairo University,
Egypt.
Diethyl 2-(1-phenyl-2-(phenylsulfonyl)ethylidene)malonate
3. To a solution of 6 (0.02 mol) in ethanol (50 mL), sodium
benzenesulfinate (0.02 mol) was added. The reaction mixture
was refluxed for 3 h and the solvent was triturated with cold
H2O (20 mL). The solid product, so formed, was collected by
filtration, washed thoroughly with H2O, dried and crystallized
from ethanol. Yield 65%, mp. 121°C; ir (KBr)ꢁ/max cm-1 3000-
2950 (CH2), 1715, 1700 (2 C=O).1H nmr (ꢀ, ppm, DMSO-d6):
1.08-1.30 (m, 6H, 2CH3), 3.80-4.28 (m, 4H, 2CH2), 4.66 (s, 2H,
CH2), 6.90-7.85 (m, 10H, Ar-H); MS m/z: 402 (M+, 18%). Anal.
calcd. for C21H22O6S (402.46): C, 62.67; H, 5.51; S, 7.97. Found:
C, 62.39; H, 5.38; S, 7.64%.
Compound 3 reacted with equimolar amounts of
trichloroacetonitrile in ethanolic sodium acetate solutions
to produce exclusively the corresponding ethyl 6-
(trichloromethyl)-1,2-dihydro-2-oxo-4-phenyl-5-(phenyl-
sulfonyl)pyridine-3-carboxylate 22. The trichloro methyl
group in 22 proved to be highly reactive towards
nucleophilic reagents. Thus, compound 22 reacted readily
with equimolar amounts of hydrazine hydrate in ethanol
under reflux to yield the corresponding ethyl 6-hydrazino-
pyridine-3-carboxylate 23. Compound 23 could be
successfully cyclized into the corresponding ethyl 1,5-
dihydro-5-oxo-7-phenyl-8-(phenylsulfonyl)tetrazolo[1,5-a]-
Scheme 4
O
O
CO2Et
CO2Et
NH2. NH2
EtOH/
CCl3CN
NH
NH
3
EtOH/NaOAc
Ph
NHNH2
SO2Ph
Ph
CCl3
SO2Ph
22
23
NH2
CN
R1
NaNO2
AcOH
/
CO2Et
H2N
EtOH/AcOH
R2
S
9
12
O
O
O
O
R1
O
CO2Et
CO2Et
CO2Et
N
N
N
N
R2
N
S
N
H
Ph
N
N
H
Ph
Ph
H
SO2Ph
SO2Ph
SO2Ph
25
26
24
R1R2=-(CH2)4-

1240
Y. M. Elkholy
Vol 45
Diethyl 2-(2-bromo-1-phenyl-2-(phenylsulfonyl)ethyl-
collected by filtration, dried and crystallized from dioxane.
Yield 66%, mp. 229-230°C; ir (KBr)ꢀ/max cm-1: 3495-3450
(OH), 2218 (CN), 1710 (CO). H nmr (ꢁ, ppm, DMSO-d6): 0.92
idene)malonate 7. To a solution of 3 (0.02 mol) in dry benzene
(50 mL), bromine (0.02 mol) was added dropwise. The reaction
mixture was heated under reflux for 3 h. The solvent was then
evaporated in vacuo. The residue was triturated with ethanol; the
solid product so formed was collected by filtration, dried and
crystallized from ethanol. Yield 59%, mp. 154-156°C; ir
1
(t, 3H, J = 8.2 Hz, CH3), 2.94 (s, 1H, OH, exchangeable), 4.23
(q, 2H, J = 8.2 Hz, CH2), 6.90-7.83 (m, 15H, Ar-H). Anal. calcd.
for C28H21NO5S(483.45): C, 69.55; H, 4.37;N, 2.89;S, 6.61.
Found: C, 69.73; H, 4.56; N, 2.54; S, 6.70%.
Method B. A mixture of 17 (0.002 mol) and malononitrile
(0.002 mol) in ethanol (25 mL) containing Et3N (0.5mL) was
refluxed for 3 h. The reaction mixture was poured onto cold
water and neutralized with dilute HCl. The solid product so
formed was collected by filtration, dried, crystallized from
ethanol, and found to be identical in all aspects (mp., mixed mp.
and IR spectrum) with an authentic sample of 16 prepared
according to Method A.
1
(KBr)ꢀ/max cm-1 1718, 1705(2 C=O). H nmr (ꢁ, ppm, DMSO-
d6): 1.05-1.33 (m, 6H, 2CH3), 3.85-4.45 (m, 4H, 2CH2), 4.61 (s,
1H, CH), 6.95-7.90 (m, 10H, Ar-H); Anal. calcd. for
C21H21BrO6S( 481.36): C, 52.40; H, 4.40; S, 6.66. Found: C,
52.32; H, 4.60; S, 6.71%.
Ethyl 1-(4-chlorophenyl)-2-hydroxy-4-phenyl-5-(phenyl-
sulfonyl)-1H-pyrrole-3-carboxylate 8. To a warm solution of 7
(0.003 mol) in absolute ethanol (25 mL) containing anhydrous
Et3N (0.5 mL), the appropriate primary aromatic amine (0.03
mol) was added. The reaction mixture was refluxed for 2 h,
poured into cold water, and then neutralized with dilute HCl.
The solid product so formed was collected by filtration, washed
with water, dried and crystallized from methanol. Yield 56%,
mp. 190-192°C; ir (KBr)ꢀ/max cm-1: 3500-3325(OH), 1712
Diethyl 2,4-diphenyl-3-(phenylsulfonyl)but-1,3-diene-1,1-
dicarboxylate 17. A mixture of 3 (0.003 mol) and benzaldehyde
(0.003 mol) in absolute ethanol (30 mL) containing Et3N (0.5
mL) was refluxed for 3 h allowed to cool poured into ice-cold
water and neutralized with dilute HCl. The solid product formed
was collected by filtration, dried and crystallized from ethanol.
Yield 69%. mp. 186°C; ir (KBr)ꢀ/max cm-1: 1715, 1708 (2 C=O),
1
(C=O). H nmr (ꢁ, ppm, DMSO-d6): 1.28 (t, 3H, J = 8.2 Hz,
1
CH3), 3.10 (s, 1H, OH, exchangeable), 4.51 (q, 2H, J = 8.2 Hz,
CH2), 6.95-7.80 (m, 14H, Ar-H). Anal. calcd. for C25H20ClO5NS
(481.95): C, 62.30; H, 4.18; N, 2.91; S, 6.65. Found: C, 62.21;
H. 4.35; N. 2.60;S. 6.55 %.
1650 (C=C). H nmr (ꢁ, ppm, DMSO-d6): 0.95-1.35 (m, 6H,
2CH3), 3.92-4.25 (m, 4H, 2 CH2), 6.75-7.83 (m, 16H, Ar-H
+ylidene-CH). Anal. calcd. for C28H26O6S (490.57): C, 68.55; H,
5.34; S, 6.54. Found: C, 68.67; H, 5.41; S, 6.63%.
Ethyl 5-oxo-2-phenyl-1-(phenylsulfonyl)pyrrolo[2,1-b]-
benzo[d][1,3]oxazine-3-carboxylate11. A mixture of 7 (0.003
mol) and 2-aminobenzonitrile 9 (0.003 mol) in dry dioxane (30
mL) containing anhydrous Et3N (1.0 mL) was refluxed for 3 h.
The reaction mixture was left aside at room temperature
overnight, poured into an ice water mixture and neutralized with
dilute HCl. The solid product so formed was collected by
filtration, washed with water, dried and crystallized from
dioxane. Yield 45%, mp.212°C; ir (KBr)ꢀ/max cm-1: 1715, 1708
Diethyl 2-phenyl-3-(4-chlorophenyl)hydrazono-3-(phenyl-
sulfonyl)but-1,1-di- carboxylate 18. To a stirred solution of 3
(0.003 mol) in ethanol (50 mL) NaOAc (2.0 g), the appropriate
arene diazonium chloride (0.003 mol) [prepared by adding
NaNO2 (0.006 mol) to the appropriate primary aromatic amine
(0.003 mol) in concentrated HCl (2 mL) at 0-5 °C while stirring]
was added drop wise while cooling at 0-5°C and stirring. The
solid product so formed was collected by filtration, dried and
crystallized from ethanol. Yield 65%, mp. 222 °C; ir (KBr)ꢀ/max
1
(2C=O). H nmr (ꢁ, ppm, DMSO-d6): 1.24 (t, 3H, J = 8.2 Hz,
1
cm-1: 3350-3320 (NH), 1718, 1700 (2 C=O). H nmr (ꢁ, ppm,
CH3), 4.55 (q, 2H, J = 8.2 Hz, CH2), 6.88-7.92 (m, 14H, Ar-H).
MS m/z: 473 (M+, 16%). Anal. calcd. for C26H19NO6S (473.42):
C, 65.95; H, 4.04; N, 2.95; S, 6.74. Found: C, 56.51; H, 4.25;
N, 2.55; S, 6.59%.
DMSO-d6): 0.96-1.25 (m, 6H, 2CH3), 3.95-4.05 (m, 4H, 2CH2),
6.73-7.56 (m, 14H, Ar-H), 11.28 (br s, 1H, NH, exchangeable).
Anal. calcd. for C27H25N2ClO6S(541.02): C, 59.94; H, 4.66; N,
5.18; S,5.93. Found: C, 59.86; H, 4.77; N, 5.46; S, 5.83%.
Ethyl 6,7,8,9-tetrahydro-5-oxo-2-phenyl-1-(phenylsulfonyl)-
pyrrolo[2,1-b]thieno[2,3-b][1,3]oxazine-3-carboxylate 13.
Ethyl 2-(4-chlorophenyl)-2,3-dihydro-3-oxo-5-phenyl-6-
(phenylsulfonyl)-pyridazine-4-carboxylate 19. A solution of
18 (0.002 mol) in ethanol (30 mL) containing NaOAc (1.0 g)
was refluxed for 3 h. The reaction mixture was poured onto cold
water and neutralized with dil. HCl. The resulting precipitated
solid was collected by filtration, dried and crystallized from
dioxane. Yield 55%, mp 193-195°C; ir (KBr)ꢀ/max cm-1:1718,
A
mixture of 7 (0.003 mol) and the appropriate ethyl 2-
aminothiophene-3-carboxylate 12 (0.003 mol) in a dry dioxane
(30 mL) containing Et3N (1.0 mL) was refluxed for 3 h. The
reaction mixture was poured into cold water and neutralized
with dilute HCl. The resulting precipitate was collected by
filtration, dried and crystallized from dioxane. Yield 42%,
mp.218°C; ir (KBr)ꢀ/max cm-1: 2218 (CN), 1720, 1712 (2 C=O).
1H nmr (ꢁ, ppm, DMSO-d6): 1.22 (t, 3H, J= 8.2 Hz, CH3), 1.77-
1.84(m, 4H, 2CH2), 2.63-2.68(m,2H, CH2), 2.84-2.91(m,2H,
CH2),4.15 (q, 2H, J = 8.2 Hz, CH2), 6.85-7.96 (m,10H, Ar-H).
MS m/z: 533 (M+, 14%). Anal. calcd. for C28H23NO6S2 (533.47):
C, 63.03; H, 4.34; N, 2.62; S, 11.99. Found: C, 63.43; H, 4.74;
N, 2.75; S, 12.59%.
1
1695 (2 C=O) H nmr (ꢁ, ppm, DMSO-d6): 1.21 (t, 3H, J = 8.2
Hz, CH3), 4.25 (q, 2H, J = 8.2 Hz, CH2), 6.91-7.43 (m, 14H, Ar-
H). MS m/z: 494(M+, 14%). Anal. calcd. for C25H19N2O5ClS
(494.95): C, 57.97; H, 3.69; N, 5.40; S, 6.19. Found: C, 57.30;
H, 3.54; N, 5.81; S, 6.52%.
Ethyl 1-benzoyl-4-phenyl-1,2-dihydro-2-oxo-6-mercapto-5-
(phenylsulfonyl)pyridine-3-carboxylate 20. To a suspension of
NH4SCN (0.005 mol) in dioxane (50 mL), benzoyl chloride (0.7
g, 0.005 mol) was added. The reaction mixture was refluxed for
15 min., then treated with 3 (0.005 mol). The reaction mixture
was then refluxed for an additional 2 h, poured onto ice water,
whereby the solid product so formed was collected by filtration
and crystallized from dioxane. Yield 66%, mp. 174-176°C; ir
(KBr)ꢀ/max cm-1: 2250(SH), 1718, 1705, 1684 (3 C=O).1H nmr
(ꢁ, ppm, DMSO-d6): 1.20 (t, 3H, J = 8.2 Hz, CH3), 3.24 (s, 1H,
Ethyl 6-phenyl-3-cyano-2-hydroxy-4-phenyl-5-(phenyl-
sulfonyl)benzoate 16.
Method A. A mixture of 3 (0.002 mol) and the appropriate
arylidenemalononitrile 14 (0.002 mol) in ethanol (25 mL)
containing Et3N (0.5 mL) was heated under reflux for 3 h. The
reaction mixture was evaporated in vacuo, triturated with cold
water and neutralized with dilute HCl. The solid product was

Jul-Aug 2008
Studies with Phenylsulfone Derivatives
1241
SH, exchangeable), 4.25 (q, 2H, J = 8.2 Hz, CH2), 6.90-7.68 (m,
15H, Ar-H). MS m/z: 519 (M+,12%). Anal. calcd. for
C27H21NO6S2(519.08): C, 62.41; H, 4.07; N, 2.70; S, 12.34
Found: C, 62.76; H, 4.3; N, 2.37; S, 12.33%.
(q, 2H, J =8.2 Hz, CH2), 6.85-7.55 (m, 10H, Ar-H), 9.65 (brs,
1H, NH, exchangeable). Anal. calcd. for C20H16N4O5S(424.43):
C, 56.60; H, 3.80; N, 13.20; S, 7.55. Found: C, 57.72; H, 3.65;
N, 13.13; S, 7.45%.
Ethyl 2-cyano-5-oxo-3,7-diphenyl-8-(phenylsulfonyl)-5H-
thiazolo[3,2-a]pyridine-6-carboxylate 21. To a suspension of
20 (0.002 mol) in ethanol (30 mL), an aqueous solution of
K2CO3 (0.004 mol) (20 mL) and chloroacetonitrile (0.002 mol)
were added. The reaction mixture was refluxed for 2 h, left to
cool at room temperature and poured into cold water. The solid
product formed was collected by filtration and crystallized from
ethanol. Yield 62%, mp. 255°C; ir (KBr)ꢀ/max cm-1: 2218 (CN),
Ethyl 10-phenyl-7,8-dioxo-11-(phenylsulfonyl)-3,4,5,6-
tetrahydro-1H-pyrido-[1,2-a]-thieno[2,3-d]pyrimidine-9-
carboxylate 25. To a solution of 22 (0.002 mol) in absolute
ethanol (30 mL) containing glacial acetic acid (1 mL), ethyl-2-
aminothiophene-3-carboxylate 12 (0.002 mol) was added. The
reaction mixture was refluxed for 2 h, left aside to cool at room
temperature and then poured onto cold water. The solid
precipitated was collected by filtration, washed thoroughly with
water and crystallized from DMF. Yield 64%, mp. >300°C; ir
(KBr)ꢀ/max cm-1 3450-3420 (NH), 2220 (CN), 1718, 1710, 1700
1
1715, 1700 (2 C=O). H nmr (ꢁ, ppm, DMSO-d6):1.15 (t, 3H, J
= 8.2 Hz, CH3), 4.12 (q, 2H, J = 8.2 Hz, CH2), 6.93-7.55 (m,
15H, Ar-H). MS m/z: 540(M+, 16%). Anal. calcd. for
C29H20N2O5S2 (540.61): C, 64.43; H, 3.73; N, 5.18; S, 11.86.
Found: C, 64.22; H, 3.74; N, 5.34; S, 11.65%.
1
(3 C=O). H nmr (ꢁ, ppm, DMSO-d6): 1.12 (t, 3H, J =8.2 Hz,
CH3), 1.77-1.84(m, 4H, 2CH2), 2.63-2.68(m, 2H, CH2), 2.84-
2.91(m, 2H, CH2), 4.17 (q, 2H, J = 8.2Hz, CH2), 6.88-7.56(m,
10H, Ar-H), 9.61 (brs, 1H, NH, exchangeable). Anal. calcd. For
C29H24N2O6S2 (542.5): C, 64.20; H, 4.45; N, 5.16; S, 8.47.
Found: C, 64.54; H, 4.93; N, 5.25; S, 8.51%.
Ethyl 6-(trichloromethyl)-1,2-dihydro-2-oxo-4-phenyl-5-
(phenylsulfonyl)pyridine-3-carboxylate 22. To a solution of 3
(0.003 mol) in ethanol (30 mL) containing NaOAc (0.5 g),
trichloroacetonitrile (0.005 mol) was added. The reaction
mixture was heated for 2 h and left aside at room temperature
overnight. The mixture was poured into ice water and
neutralized with dilute HCl. The solid that formed was collected
by filtration, washed with water, dried and crystallized from
ethanol. Yield 61%, mp. 228-230°C; ir (KBr) ꢀ/max cm-13370
Ethyl 9,10-dihydro-9,11-dioxo-7-phenyl-6-(phenylsulfonyl)-
5H-Pyrido[2,1-a]quinazoline-8-carboxylate 26. To a solution
of 22 (0.002 mol) in absolute ethanol (30 mL) containing glacial
acetic acid (10 mL), 2-aminobenzonitrile 9 (0.002 mol) was
added. The reaction mixture was refluxed for 2 h, left to cool
and then poured into ice-cold water. The solid product
precipitated was collected by filtration, dried and crystallized
from DMF. Yield 59%, mp. 273°C; ir (KBr)ꢀ/max cm-1 3445-
3400 (NH), 1720, 1712, 1705 (3 C=O).1H nmr (ꢁ, ppm, DMSO-
d6): 0.98 (s, 3H, J = 8.2 Hz, CH3), 4.12 (q, 2H, J = 8.2 Hz, CH2),
6.95-7.81 (m, 14H, Ar-H), 9.73 (brs, 1H, NH, exchangeable).
Anal. calcd. for C27H20N2O6S(500.52): C, 64.79; H, 4.03; N,
5.60; S, 6.41. Found: C, 64.83; H, 4.13; N, 5.83; S, 6.52%.
1
(NH), 1715, 1700 (2C=O). H nmr (ꢁ, ppm, DMSO-d6): 1.12 (t,
3H, J = 8.2 Hz, CH3), 4.12 (q, 2H, J = 8.2 Hz, CH2), 6.70-7.82
(m, 10H, Ar-H), 9.98 (br s, 1H, NH, exchangeable). Anal. calcd.
For C21H16NCl3O5S (500.78): C, 50.37; H, 3.22; N, 2.80; S, 6.40.
Found: C, 50.54; H, 3.62; N, 2.65; S, 6.51%
Ethyl 6-hydrazinyl-1,2-dihydro-2-oxo-4-phenyl-5-(phenyl-
sulfonyl)pyridine-3-carboxylate 23. A mixture of 22 (0.003
mol) and hydrazine hydrate (0.003 mol) in ethanol (30 mL) was
refluxed for 30 min. and then left to cool. The mixture was
poured into cold water, whereby the solid product so formed was
collected by filtration and crystallized from dioxane. Yield 65%,
mp. 197-199°C; ir (KBr)ꢀ/max cm-13420-3380 (NH2, NH), 1712,
REFERENCES
[1] Mukerjee, A. K.; Ashare, R. Chem. Rev. 1991, 91, 1.
[2] Simpkins, N. S. "Introduction to sulfone chemistry" In
Sulfones in organic synthesis'(Oxford, pergaman press); 1995, pp1-3.
[3] Sharma, S. Sulfur Rep. 1989, 8, 328.
1
1700 (2 C=O). H nmr (ꢁ, ppm, DMSO-d6): 1.10 (t, 3H, J = 8.2
Hz, CH3), 3.25 (br s, 2H, NH2, exchangeable), 4.14 (q, 2H, J =
8.2 Hz, CH2), 6.29 (br s, 1H, NH, exchangeable), 6.89-7.48 (m,
10H, Ar-H), 8.35 (br s, 1H, NH, exchangeable). Anal. calcd. for
C20H19N3O5S(413.45): C, 58.10; H, 4.63; N, 10.16; S, 7.76.
Found: C, 58.52; H, 4.72; N, 10.5; S, 7.52%.
Ethyl 1,5-dihydro-5-oxo-7-phenyl-8-(phenylsulfonyl)tetra-
zolo[1,5-a]pyridine-6-carboxylate 24. A solution of 23 (0.002
mol) in glacial acetic acid (25 mL) was treated with NaNO2
(0.004 mol) portion wise while stirring at room temperature. The
reaction mixture was stirred for an additional 1 h, whereby the
solid product that separated was collected by filtration, washed
with water and crystallized from acetic acid. Yield 61%, mp.
279°C; ir (KBr)ꢀ/max cm-1 3450-3415 (NH), 1715, 1705 (2 C=O).
1H nmr (ꢁ, ppm, DMSO-d6): 0.95 (t, 3H, J = 8.2 Hz, CH3), 4.00
[4]
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