A novel synthesis of fused heterocyclic sulfones

Article abstract of DOI:10.1002/jccs.200500014

The applicability and synthetic potency of the novel reagent di ethyl 2-aryl-3-phenylsulfonylpropen-1,1-dicarboxylate 3 is reported. Compound 3 proved to be a key pre cursor in heterocyclic sulfones syntheses. Chemical and spectroscopic evidence for the structure of the newly synthesized compounds are described.

Full text of DOI:10.1002/jccs.200500014

Journal of the Chinese Chemical Society, 2005, 52, 97-102
97
A Novel Synthesis of Fused Heterocyclic Sulfones
S. M. Batterjee
Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 10093, Jeddah 21433,
Kingdom of Saudi Arabia
The applicability and synthetic potency of the novel reagent diethyl 2-aryl-3-phenylsulfonylpropen-1,1-
dicarboxylate 3 is reported. Compound 3 proved to be a key precursor in heterocyclic sulfones syntheses.
Chemical and spectroscopic evidence for the structure of the newly synthesized compounds are described.
Keywords: Heterocyclic sulfones; Pyrrole; Thiophenes; Oxazines; Quinazolines.
Scheme I
INTRODUCTION
In view of the diverse biological and physiological ac-
tivities of sulfones,1-7 and in connection with our previous ef-
forts directed towards the facile synthesis of heterocyclic ring
systems,8-12 we designed a specific simple program aimed at
the development of a convenient synthetic approach of het-
erocyclic sulfone systems of expected potential bioresponses
utilizing the novel reagent 3 as a unique key precursor. The
newly synthesized sulfone derivatives appear to be promis-
ing for further chemical transformations as well as biological
activity evaluations.
RESULTS AND DISCUSSION
matic amine in ethanolic/tri-ethylamine solutions afforded
the corresponding ethyl 1,4-diaryl-2-hydroxy-5-phenylsul-
fonylpyrrole-3-carboxylates 8. The latter reaction yields the
corresponding ethyl 5-oxo-1-phenylsulfonylpyrrolo[2,1-b]-
benzo[d][1,3]oxazine-3-carboxylate 11, in a one-pot reac-
tion, if anthranilonitrile 9 is used. Similarly, the pyrrole[2,1-
b]thieno[2,3-d][1,3]oxazines 13 are obtained on treatment of
7 with the appropriate ethyl 2-aminothiophene-3-carboxylate
12 (Scheme II).
All attempts to prepare the key precursor diethyl 2-
aryl-3-phenylsulfonylpropen-1,1-dicarboxylate 3 via con-
densation of equimolar amounts of diethyl malonate 1 with
the appropriate arylsulfonylacetophenone 2 utilizing a vari-
ety of acidic or alkaline conditions failed. On the other hand,
the precursor 3 could be prepared stepwise. Thus, diethyl
2-aryl-3-bromopropen-1,1-dicarboxylate 6 recently pre-
pared in our laboratories3 reacted with equimolar amounts of
sodium benzenesulfinate in ethanolic solution to furnish the
target reagent 3 (Scheme I).
Compound 3 reacted with arylidenemalononitrile 14 to
yield the corresponding ethyl 4-aryl-3-cyano-2-hydroxy-6-
hydroxy-6-phenyl-5-phenylsulfonylbenzoates 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
intramolecularly cyclized, aromatised via loss of HCN to
give the final isolable 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 ben-
Compound 3 proved to be highly reactive towards vari-
ous reagents and underwent numerous chemical transforma-
tions, resulting in the construction of a wide range of het-
erocyclic sulfone systems. Thus, compound 3 could be bro-
minated when equimolar amounts of 3 and bromine in dry
benzene were boiled under reflux to afford the corresponding
diethyl 2-aryl-3-bromo-3-phenylsulfonylpropen-1,1-dicar-
boxylates 7. Treatment of 7 with the appropriate primary aro-

98 J. Chin. Chem. Soc., Vol. 52, No. 1, 2005
Batterjee
idine-3-carboxylate derivative 20 was obtained in a good
yield from the reaction of 3 with benzoyl isothiocyanate in
boiling dry dioxane. Compound 20 also reacted with chloro-
acetonitrile or ethyl chloroacetate in the presence of K2CO3
to yield the corresponding ethyl thiazolo[2,3-a]pyridine-6-
carboxylate derivatives 21.
Scheme II
Compound 3 reacted with equimolar amounts of tri-
chloroacetonitrile in ethanolic/NaOAc solutions to produce
exclusively the corresponding ethyl 4-aryl-6-trichlorometh-
ylpyridine-3-carboxylate derivatives 22. The trichlorometh-
yl group in 22 proved to be highly reactive towards nucleo-
philic reagents. Thus, compound 22 reacted readily with
equimolar amounts of hydrazine hydrate in ethanol under re-
flux to give the corresponding ethyl 6-hydrazinopyridine-3-
carboxylate derivatives 23. Compound 23 could be success-
fully cyclized into the corresponding ethyl 5-oxo-7-bromo-
7-phenylsulfonyltetrazolo[1,5-a]pyridine-6-carboxylate 24
upon treatment with an equimolar proportion of NaNO2 in
glacial acetic acid (Scheme IV).
Scheme III
Treatment of 22 with ethyl 2-amino-4-cyano-5-methyl-
thiophene-3-carboxylate 1213 in absolute ethanol solution
containing glacial acetic acid under reflux, furnished the cor-
responding ethyl 8-aryl-4,6-dioxo-9-phenylsulfonyl-10H-
pyrido[1,2-a]thieno[2,3-d]pyrimidine-7-carboxylate 25.
Similarly, ethyl pyrido[2,1-b]quinazoline-8-carboxylates 26
could be obtained upon treatment of 22 with anthranilonitrile
9.
Scheme IV
zylidene derivative 17 (Scheme III).
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 cy-
clic pyridazine form 19. The hydrazone form 18 is preferred
on the basis of its 1H NMR spectra which revealed the pres-
ence of multiplet signals corresponding to two ester func-
tions. Furthermore, after boiling the hydrazone 18 in eth-
anolic sodium acetate solutions, the pyridazines 19 could be
obtained.
EXPERIMENTAL
All melting points are uncorrected. IR spectra were re-
1
corded (KBr) on a Pye Unicam SP-1000 spectrometer. H
Ethyl 1-benzoyl-4-bromophenyl-5-phenylsulfonylpyr-

A Novel Synthesis of Fused Heterocyclic Sulfones
J. Chin. Chem. Soc., Vol. 52, No. 1, 2005 99
NMR spectra were obtained on a Varian Gemini 200 MHz
spectrometer using TMS as an internal reference. Chemical
shifts are expressed as d (ppm). Mass spectra were recorded
on a GCMS-QP 1000 EX mass spectrometer operating at 70
eV. Microanalytical data were performed by the Micro-
analytical Unit, Cairo University. Compound 6 has been pre-
pared according to previously reported methodology.13
3500-3325 (OH), 1712 (C=O) cm-1; 1H NMR (DMSO-d6) d:
1.28 (t, 3H, J = 8.2 Hz, CH3), 3.10 (s, 1H, OH, exchangeable),
4.51 (q, 2H, J = 8.2 Hz, CH2), 6.95-7.80 (m, 12H, Ar-H).
Anal. calcd. for C25H19ClBrO5N5 (564.22); C 53.22, H 3.39,
Cl 6.28, N 2.48, S 5.68, Br 14.16; found: 53.21, H 3.35, Cl
6.25, N 2.30, S 5.65, Br 14.13%.
Ethyl 5-oxo-2-(p-bromophenyl)sulfonylpyrrolo[2,1-b]-
benzo[d]-[1,3]oxazine-3-carboxylte (11)
Diethyl 2-(p-bromophenyl)-3-phenylsulfonylpropen-1,1-
dicarboxylate (3)
A mixture of 7 (1.68 gm, 0.003 mol) and anthranilo-
nitrile (9) (0.35 gm, 0.003 mol) in dry dioxane (30 mL) con-
taining anhydrous Et3N (1.0 mL) was refluxed for 3 h. The re-
action mixture was left aside at room temperature overnight,
poured onto an ice/water mixture and neutralized with dilute
HCl. The solid product soformed was filtered off, washed
with water, dried and crystallized from the appropriate sol-
vent. Yield (0.64 g, 45%), mp. 210-212 °C (dioxane); IR:
1715, 1708 (2C=O) cm-1; 1H NMR (DMSO-d6) d: 1.24 (t, 3H,
J = 8.2 Hz, CH3), 4.55 (q, 2H, J = 8.2 Hz, CH2), 6.88-7.92 (m,
13H, Ar-H). MS m/z: 552 (M+, 16%). Anal. calcd. for
C26H18NO6BrS (552.41); C 56.53, H 3.28, N 2.53, S 5.80, Br
14.46; found: 56.51, H 3.25, N 2.55, S 5.59, Br 14.42%.
To a solution of 6 (8.4 gm, 0.02 mol) in ethanol (50
mL), sodium benzenesulfinate (3.5 gm, 0.02 mol) was added.
The reaction mixture was refluxed for 3 h and the solvent was
triturated with cold H2O (20 mL), whereby the solid product
soformed was collected by filtration, washed thoroughly with
H2O, dried and crystallized from the appropriate solvent.
Yield (5.2 g, 65%), mp. 120-121 °C (ethanol); IR: 3000-2950
1
(CH2), 1715, 1700 (2 C=O) cm-1; H NMR (DMSO-d6) d:
1.08-1.30 (m, 6H, 2CH3), 3.80-4.28 (m, 4H, 2CH2), 4.66 (s,
2H, CH2), 6.90-7.85 (m, 9H, Ar-H); MS m/z: 481 (M+, 18%).
Anal. calcd. for C21H21BrO6S (481.37); C 52.40, H 4.39, Br
16.59, S 6.66; Found: C 52.39, H 4.38, Br 16.57, S 6.64%.
Diethyl 3-bromo-2-(p-bromophenyl)-3-phenylsulfonyl-
propen-1,1-dicarboxylate (7)
Ethyl 6-cyano-7-methyl-5-oxo-2-(p-bromophenyl)-1-phen-
yl-sulfonylpyrrolo[2,1-b]thieno[2,3-b][1,3]oxazine-3-car-
boxylate (13)
To a solution of 3 (9.62 gm, 0.02 mol) in dry benzene
(50 mL), bromine (1.6 gm, 0.02 mol) was added dropwise.
The reaction mixture was refluxed for 3 h and the solvent was
then evaporated in vacuo. The residue was triturated with eth-
anol, whereby the solid product soformed was collected by
filtration, dried and crystallized from the appropriate solvent.
Yield (5.6 g, 59%), mp. 154-156 °C (ethanol); IR: 1718, 1705
Amixture of 7 (1.68 gm, 0.003 mol) and the appropriate
ethyl 2-aminothiophene-3-carboxylate 1213 (0.67 gm, 0.003
mol) in a dry dioxane (30 mL) containing Et3N (1.0 mL) was
refluxed for 3 h. The reaction mixture was poured onto cold
water and neutralized with dilute HCl. The resulting precipi-
tate was collected by filtration, dried and crystallized from
the appropriate solvent. Yield (0.65 g, 42%), mp. 218-220 °C
(dioxane); IR: 2218 (CN), 1720, 1712 (2 C=O) cm-1; 1H NMR
(DMSO-d6) d: 0.95 (s, 3H, CH3), 1.22 (t, 3H, J = 8.2 Hz,
CH3), 4.15 (q, 2H, J = 8.2 Hz, CH2), 6.85-7.96 (m, 10H,
Ar-H). MS m/z: 581 (M+, 14%). MS m/z: 581 (M+, 14%).
Anal. calcd. for C26H17O5BrN2S2 (581.46); C 53.70, H 2.94,
N 4.81, Br 13.74, S 11.02; found: C 53.69, H 2.99, N 4.8, Br
13.7, S 11.0%.
1
(2 C=O) cm-1; H NMR (DMSO-d6) d: 1.05-1.33 (m, 6H,
2CH3), 3.85-4.45 (m, 4H, 2CH2), 4.61 (s, 1H, CH), 6.95-7.90
(m, 9H, Ar-H); Anal. calcd. for C21H20Br2O6S (560.26); C
45.02, H 3.59, Br 28.52, S 5.72; Found: C 45.07, H 3.60, Br
28.55, S 5.71%.
Ethyl 1-(p-chlorophenyl)-4-(p-bromophenyl)-2-hydroxy-
5-phenylsulfonylpyrrole-3-carboxylate (8)
To a warm solution of 7 (1.68 gm, 0.003 mol) in abso-
lute 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
onto cold water, then neutralized with dilute HCl. The solid
product soformed was collected by filtration, washed with
water, dried and crystallized from the appropriate solvent.
Yield (0.86 g, 56%), mp. 190-192 °C (ethanol); IR:
Ethyl 6-(p-bromophenyl)-3-cyano-2-hydroxy-4-phenyl-5-
phenylsulfonylbenzoate (16)
Method A
Amixture of 3 (0.96 gm, 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

100 J. Chin. Chem. Soc., Vol. 52, No. 1, 2005
Batterjee
cold water and neutralized with dilute HCl. The solid product
was collected by filtration, dried and recrystallized from the
appropriate solvent. Yield (0.68 g, 66%), mp. 229-230 °C
(dioxane); IR: 3495-3450 (OH), 2218 (CN), 1710 (CO) cm-1;
1H NMR (DMSO-d6) d: 0.92 (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, 14H, Ar-H). Anal. calcd. for C28H20BrNO5S
(562.44); C 59.79, H 3.58, Br 14.20, N 2.49, S 5.70; found: C
59.7, H 3.5, N, 2.50, Br 14.2, S 5.70%.
2CH2), 6.73-7.56 (m, 13H, Ar-H), 11.28 (br s, 1H, NH, ex-
changeable). MS m/z: 637 (M+, 18%). Anal. calcd. for
C27H24N2BrClO6S (637.93); C 50.83, H 3.779, Cl 5.55, N
4.39, Br 12.52, S 5.02; found: C 50.8, H 3.7, Cl 5.5, N 4.4, S
5.03, Br 12.5%.
Ethyl 5-bromophenyl-2-(p-chlorophenyl)-2,3-dihydro-3-
oxo-6-phenylsulfonylpyridazine-4-carboxylate (19)
A solution of 18 (1.27 gm, 0.002 mol) in ethanol (30
mL) containing NaOAc (1.0 g) was refluxed for 3 h. The re-
action mixture was poured onto cold water and neutralised
with dil. HCl. The resulting precipitated solid was filtered
off, dried and crystallised from the proper solvent. Yield
(0.54 g, 55%), mp 193-195 °C; IR: 1718, 1695 (2 C=O) cm-1;
1H NMR (DMSO-d6) d: 1.21 (t, 3H, J = 8.2 Hz, CH3), 4.25 (q,
2H, J = 8.2 Hz, CH2), 6.91-7.43 (m, 13H, Ar-H). MS m/z: 573
(M+, 14%). Anal. calcd. for C25H18N2O5BrClS (573.85); C
52.32, H 3.16, N 4.90, S 5.58, Br 13.92, Cl 6.17; found: C
52.30, H 3.10, N 4.8, S 5.5, Br 13.9, Cl 6.1%.
Method B
Amixture of 17 (1.14 gm, 0.002 mol) and malononitrile
(0.13 gm, 0.002 mol) in ethanol (25 mL) containing Et3N (0.5
mL) was refluxed for 3 h. The reaction mixture was poured
onto cold water and neutralized with dilute HCl. The solid
product soformed was collected by filtration, dried, crystal-
lized 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.
Diethyl 2-(p-bromophenyl)-4-phenyl-3-phenylsulfonylbut-
1,3-diene-1,1-dicarboxylate (17)
Ethyl 1-benzoyl-4-(bromophenyl)-1,2-dihydro-2-oxo-6-
mercapto-5-phenylsulfonylpyridine-3-carboxylate (20)
To a suspension of NH4SCN (0.38 gm, 0.005 mol) in
dioxane (50 mL), benzoyl chloride (0.7 gm, 0.005 mol) was
added. The reaction mixture was refluxed for 2 min., then
treated with 3 (2.40 gm, 0.005 mol). The reaction mixture
was refluxed for 2 h, poured onto ice/water, whereby the
solid product soformed was filtered off and crystallized from
dioxane. Yield (1.90 g, 66%), mp. 174-175 °C; IR: 2250
(SH), 1718, 1705, 1684 (3 C=O) cm-1; 1H NMR (DMSO-d6)
d: 1.20 (t, 3H, J = 8.2 Hz, CH3), 3.24 (s, 1H, SH, exchange-
able), 4.25 (q, 2H, J = 8.2 Hz, CH2), 6.90-7.68 (m, 14H, Ar-
H). MS m/z: 598 (M+, 12%). Anal. calcd. for C27H20NO6BrS2
(598.49); C 54.18, H 3.36, N 2.34, Br 13.35, S 5.35; found: C
54.15, H 3.3, N 2.3, Br 13.3, S 5.3%.
A mixture of 3 (1.26 gm, 0.003 mol) and benzaldehyde
(0.003 mol) in absolute ethanol (30 mL) containing Et3N (0.5
mL) was refluxed for 3 h. The reaction mixture was left to
cool at room temperature, poured onto cold water and neu-
tralized with dilute HCl. The solid product formed was fil-
tered off, dried and crystallized from ethanol. Yield (1.0 g,
69%), mp. 186-187 °C (ethanol); IR: 1715, 1708 (2 C=O),
1650 (C=C) cm-1; 1H NMR (DMSO-d6) d: 0.95-1.35 (m, 6H,
2CH3), 3.92-4.25 (m, 4H, 2CH2), 6.75-7.83 (m, 15H, Ar-H +
ylidene-CH). Anal. calcd. for C28H25O6BrS (569.47); C 59.05,
H 4.42, Br 14.03, S 5.63; found: C 59.01, H 4.4, Br 14.02, S
5.63%.
Diethyl 2-(p-bromophenyl)-3-(p-chlorophenyl)hydrazono-
3-phenylsulfonylbut-1,1-dicarboxylate (18)
To a stirred solution of 3 (1.26 gm, 0.003 mol) in etha-
nol (50 mL) containing NaOAc (2.0 g), the appropriate
arenediazonium chloride (0.003 mol) [prepared by adding
NaNO2 (0.46 gm, 0.006 mol) to the appropriate primary aro-
matic amine (0.003 mol) in concentrated HCl (2 mL) at 0-5
°C while stirring] was added dropwise while cooling at 0-5
°C and stirring. The reaction mixture was left aside at room
temperature for 3 h, whereby the solid product soformed was
collected by filtration, dried and crystallized from the appro-
priate solvent. Yield (1.0 g, 65%), mp. 221-222 °C (ethanol);
Ethyl 2-cyano-7-(bromophenyl)-3-phenyl-5-oxo-8-phenyl-
sulfonylthiazolo[3,2-a]pyridine-6-carboxylate (21)
To a suspension of 20 (1.20 gm, 0.002 mol) in ethanol
(30 mL), an aqueous solution of K2CO3 (0.5 gm, 0.004 mol)
(20 mL) and the appropriate a-chloro compound (0.002 mol)
were added. The reaction mixture was refluxed for 2 h, left to
cool at room temperature and poured onto cold water. The
solid product formed was filtered off and crystallized from
the appropriate solvent. Yield (0.67 g, 62%), mp. > 250 °C;
IR: 2218 (CN), 1715, 1700 (2 C=O) cm-1; 1H NMR (DMSO-
d6) d: 1.15 (t, 3H, J = 8.2 Hz, CH3), 4.12 (q, 2H, J = 8.2 Hz,
CH2), 6.93-7.55 (m, 14H, Ar-H). MS m/z: 619 (M+, 16%).
1
IR: 3350-3320 (NH), 1718, 1700 (2 C=O) cm-1; H NMR
(DMSO-d6) d: 0.96-1.25 (m, 6H, 2CH3), 3.95-4.05 (m, 4H,

A Novel Synthesis of Fused Heterocyclic Sulfones
J. Chin. Chem. Soc., Vol. 52, No. 1, 2005 101
Anal. calcd. for C29H19N2O5BrS2 (619.51); C 56.22, H 3.09,
N 4.52, Br 12.89, S 10.35; found: C 56.2, H 3.1, N 4.5, Br
12.9, S 10.3%.
exchangeable). Anal. calcd. for C20H15N4O5BrS (503.27); C
47.73, H 3.00, N 11.13, Br 15.87, S 6.37; found: C 47.7, H
3.0, N 11.13, Br 15.90, S 6.4%.
Ethyl 4-(p-bromophenyl)-1,2-dihydro-2-oxo-5-phenylsul-
fonyl-6-trichloromethylpyridine-3-carboxylate (22)
To a solution of 3 (1.44 gm, 0.003 mol) in ethanol (30
mL) containing NaOAc (0.5 g), trichloroacetonitrile (0.72
gm, 0.005 mol) was added. The reaction mixture was heated
under reflux for 2 h and left aside at room temperature over-
night. The mixture was poured onto an ice/water mixture,
neutralized with dilute HCl, filtered off, washed with water,
dried and crystallized from the appropriate solvent. Yield
(1.53 g, 61%), mp. 228-230 °C; IR: 3370 (NH), 1715, 1700 (2
C=O) cm-1; 1H NMR (DMSO-d6) d: 1.12 (t, 3H, J = 8.2 Hz,
CH2), 6.70-7.82 (m, 10H, Ar-H), 9.98 (br s, 1H, NH, ex-
changeable). MS m/z: 579 (M+, 12%). Anal. calcd. for
C21H15NCl3O5BrS (579.68); C 43.51, H 2.60, Cl 18.37, N
2.41, S 5.53, Br 13.78; found: C 43.5, H 2.6, Cl 18.4, N 2.4, S
5.5, Br 13.8%.
Ethyl 8-(p-bromophenyl)-3-cyano-4,6-dioxo-2-methyl-9-
phenylsulfonyl-10H-pyrido[1,2-a]thieno[2,3-d]pyrimidine-
7-carboxylate (25)
To a solution of 22 (1.15 gm, 0.002 mol) in absolute
ethanol (30 mL) containing glacial acetic acid (1 mL), ethyl
2-amino-4-cyano-5-methylthiophene-3-carboxylate (12a)13
(0.67 gm, 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 product precipitated
was filtered off, washed thoroughly with water and crystal-
lized from the appropriate solvent. Yield (0.70 g, 64%), mp. >
270 °C (DMF); IR: 3450-3420 (NH), 2220 (CN), 1718, 1710,
1700 (3 C=O) cm-1; 1H NMR (DMSO-d6) d: 1.12 (t, 3H, J =
8.2 Hz, CH3), 2.15 (s, 3H, CH3), 4.17 (q, 2H, J = 8.2 Hz,
CH2), 6.88-7.56 (m, 9H, Ar-H), 9.61 (br s, 1H, NH, ex-
changeable). Anal. calcd. for C27H18N2O6BrS (614.53); C
52.77, H 2.95, N 4.55, Br 13.00, S 5.21; found: C 52.7, H 2.9,
N 4.5, Br 13.0, S 5.2%.
Ethyl 4-(p-bromophenyl)-1,2-dihydro-6-hydrazino-2-oxo-
5-phenylsulfonylpyridine-3-carboxylate (23)
Amixture of 22 (1.73 gm, 0.003 mol) and hydrazine hy-
drate (0.003 mol) in ethanol (30 mL) was refluxed for 30 min
and then left at room temperature overnight. The mixture was
poured onto cold water, whereby the solid product soformed
was filtered off and crystallized from the appropriate solvent.
Yield (0.80 g, 65%), mp. 195-196 °C (ethanol); IR: 3420-
3380 (NH2, NH), 1712, 1700 (2 C=O) cm-1; 1H NMR (DMSO-
d6) d: 1.10 (t, 3H, J = 8.2 Hz, CH3), 3.25 (br s, 2H, NH2, ex-
changeable), 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 C20H18BrN3O5S
(492.35); C 48.79, H 3.68, Br 16.22, S 6.51; found: C 48.8, H
3.7, N 8.5, Br 16.2, S 6.5%.
Ethyl 7-(p-bromophenyl)-9,11-dioxo-6-phenylsulfonyl-
pyrido[2,1-a]quinazoline-8-carboxylate (26)
To a solution of 22 (1.15 gm, 0.002 mol) in absolute
ethanol (30 mL) containing glacial acetic acid (10 mL),
anthranilonitrile (9) (0.25 gm, 0.002 mol) was added. The re-
action mixture was refluxed for 2 h, left aside overnight and
then poured onto cold water. The solid product precipitated
was filtered off, dried and crystallized from the appropriate
solvent. Yield (2.95 g, 59%), mp. > 270 °C; IR: 3445-3400
(NH), 1720, 1712, 1705 (3 C=O) cm-1; 1H NMR (DMSO-d6)
d: 0.98 (s, 3H, J = 8.2 Hz, CH3), 4.12 (q, 2H, J = 8.2 Hz, CH2),
6.95-7.81 (m, 13H, Ar-H), 9.73 (br s, 1H, NH, exchange-
able). Anal. calcd. for C27H19N2O6BrS (579.43); C 55.96, H
3.30, N 4.83, Br 13.79, S 5.53; found: C 55.9, H 3.3, N 4.8, Br
13.8, S 5.5%.
Ethyl 5-oxo-7-(p-bromophenyl)-8-phenylsulfonyltetrazolo-
[1,5-a]pyridine-6-carboxylate (24)
A solution of 23 (0.98 gm, 0.002 mol) in glacial acetic
acid (25 mL) was treated with NaNO2 (0.2 gm, 0.004 mol)
portionwise while stirring at room temperature. The reaction
mixture was stirred for an additional 1 h, whereby the solid
product separated was filtered off, washed with water and
crystallized from acetic acid. Yield (0.52 g, 61%), mp. > 270
°C; IR: 3450-3415 (NH), 1715, 1705 (2 C=O) cm-1; 1H NMR
(DMSO-d6) d: 0.95 (t, 3H, J = 8.2 Hz, CH3), 4.00 (q, 2H, J =
8.2 Hz, CH2), 6.85-7.55 (m, 9H, Ar-H), 9.65 (br s, 1H, NH,
Received April 10, 2003.
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