Synthesis of new stable arylthiopyridinium N-arylimide zwitterions. Part 20: Fused azolium salts

Article abstract of DOI:10.1016/S0040-4020(02)00293-4

3-Aryltetrazolopyridinium salts react with thiophenolates to afford stable arylthio substituted pyridinium N-arylimide zwitterions as red crystals. The angularly fused tetrazolo[1,5-a]quinolinium salt react analogously and also yielded a blue zwitterionic product. The new zwitterions underwent solvolysis in methanol to give N-anilinopyridones, their alkylation yielding stable N-alkyl substituted salts and their reaction with dipolarophiles results in the formation of stable cycloadducts.

Full text of DOI:10.1016/S0040-4020(02)00293-4

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 3613±3618
Synthesis of new stable arylthiopyridinium N-arylimide
zwitterions. Part 20: Fused azolium saltsq
p
Â
Andras Messmer, Peter Kover, Zsuzsanna Riedl, Agnes Gomory and Gyorgy Hajos
Â
Â
Â
Â
È
È È
È
aChemical Research Center, Central Research Institute for Chemistry, Hungarian Academy of Sciences,
P.O. Box 17, H-1525 Budapest, Hungary
Received 1 January 2002; revised 11 February 2002; accepted 7 March 2002
AbstractÐ3-Aryltetrazolopyridinium salts react with thiophenolates to afford stable arylthio substituted pyridinium N-arylimide zwitter-
ions as red crystals. The angularly fused tetrazolo[1,5-a]quinolinium salt react analogously and also yielded a blue zwitterionic product. The
new zwitterions underwent solvolysis in methanol to give N-anilinopyridones, their alkylation yielding stable N-alkyl substituted salts and
their reaction with dipolarophiles results in the formation of stable cycloadducts. q 2002 Elsevier Science Ltd. All rights reserved.
Earlier studies2±5 on reactivity of azolopyridinium salts
revealed that these ring systems (e.g. tetrazolopyridinium
salt 1) readily react with nucleophiles and, in most cases,
undergo ring opening reactions. In these transformations
(see Scheme 1), two major types of reactions of 1 have
been observed: secondary amines, most alkoxides or carbon
nucleophiles attack the pyridine-carbon atom adjacent to the
bridgehead nitrogen atom to give an intermediate addition
product (2), which rapidly undergoes a retro-electrocycli-
zation to afford a tetrazolyldiene (3).
(i.e. at the other carbon centre adjacent to the positively
charged bridgehead nitrogen atom). The ®rst addition
product (4) formed in this way undergoes nitrogen elimi-
nation and results in the formation of N-anilinopyridones
(5).
In this paper we report a novel extension of these studies and
describe the reactivity of 1 with thiophenolates.
Reaction of the bicyclic salt 1 with sodium thiophenolates
(generated from thiophenols with sodium hydride in tetra-
hydrofuran) under mild conditions (2358C) yielded arylthio
substituted pyridinium N-arylimides (7) (Scheme 2). Upon
addition of the reagent the color of the reaction mixture
With other nucleophiles (like hydroxide ion or some
alkoxide reagents in a side-reaction) the attack of the
nucleophile takes place at the bridgehead carbon atom
Scheme 1.
q For part XIX, see Ref. 1.
Keywords: 1,3-dipolar cycloaddition; zwitterion; ring opening; nitrogen elimination.
Corresponding author. Tel.: 136-1-3257-550; fax: 136-1-3257-683; e-mail: ghajos@chemres.hu
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00293-4

3614
A. Messmer et al. / Tetrahedron 58 (2002) 3613±3618
Scheme 2.
turned to deep red, gas evolution was observed and ®nally
the red crystalline product was isolated in good yield by
addition of ether to the ®ltered and evaporated reaction
mixture.
also yielded the quinolone derivative 10, the same
compound obtained earlier from 8 by addition of tetra-
methylammonium hydroxide.4
Extensive literature has already appeared6,7 on the synthesis
of pyridinium arylimide zwitterions. Most of these proce-
dures imply quaternization of a pyridine derivative and a
subsequent deprotonation of the quaternary salt. An entirely
different method was applied by Huisgen and Temme.8±12
These authors carried out a Zincke reaction of N-dinitrophe-
nyl-pyridinium salts using arylhydrazines. The majority of
the zwitterionic derivatives published in the literature
proved to be fairly unstable and could only be isolated in
the form of their adducts. Our new crystalline zwitterions
proved to be relatively stable upon storing in the solid
state. Their solutions, however, gradually decomposed on
storage.
Comparison of this ®nding with our earlier results suggests
that, similar to the formation of 4, the thiophenolates ®rst
form an addition product (6) which undergoes nitrogen
elimination to yield 7. The highly polarized zwitterionic
structure of the product was found to be in accordance
with the NMR spectra (e.g. appearance of the proton and
carbon peaks: 8.61 ppm (H-6) and 151.2ppm (C-2), respec-
tively). When the new zwitterions were treated with metha-
nol, solvolysis took place and N-anilinopyridone (5) was
formed in good yield. Transformation of 7 to 5 is most
probably accounted for by the high sensitivity of the arylthio
group in 7 towards nucleophiles and traces of water in
methanol resulting in hydrolysis to yield 5.
The new zwitterions could be easily alkylated with methyl
iodide. Thus, the red pyridinium arylimide 7 and its blue
quinoline analogue 9 yielded stable N-methyl salts (11
and 12, respectively) as yellow crystals in good yields
(Scheme 4).
Similar to the reactivity of 1, its angularly fused benzolo-
gue: tetrazolo[1,5-a]quinolinium salt (8) also reacted with
sodium p-tolylthiophenolate to give the blue zwitterion 9
(Scheme 3). This zwitterion when dissolved in methanol
Scheme 3.
Scheme 4.

A. Messmer et al. / Tetrahedron 58 (2002) 3613±3618
3615
Scheme 5.
In accordance with some recent publications8±12 on related
pyridinium arylimide zwitterions we have also found that
the new products can participate in 1,3-dipolar cyclo-
additions. Thus, 7 when treated with N-phenylmaleinimide
at room temperature yielded the stable cycloadduct 13
(Scheme 5). DNOE experiment revealed that 3a, 3b, and
8a protons in this compound are situated on the same
side of the polycyclic skeleton. Oxidation of 13 with
2,6-dichloro-3,5-dicyanoquinone (DDQ) resulted in aroma-
tization of the pyridine moiety accompanied by the cleavage
of the N±N bond to give 14.
carbon atom of the pyridine ring participates in the trans-
formation and the cycloaddition is terminated in the form of
the cycloadduct (13). In the benzologue case (i.e. with 9),
only the other C-atom is available for the cycloaddition
reaction because the other carbon atom is a bridgehead
atom. In this cycloadduct (i.e. 15) elimination of thiophenol
molecule is possible allowing the formation of a second
intermediate (16) and, subsequently, the ®nal product 17.
Detailed investigation of the reaction of the fused tetra-
zolium salts with phenolates as well as the reactivity of
the new zwitterions in dipolar cycloaddition reactions is in
progress.
Although quinolinium N-arylimide 9 also reacted with
N-phenylmaleinimide, an essentially different course of
reaction was observed. Thus, a 2-substituted quinoline
derivative (17) was isolated in poor yield (10%). This
is interpreted by formation of the cycloadduct 15, a subse-
quent elimination of thiophenol to give a second inter-
mediate 16, and the ®nal aromatization step involving
N±N bond cleavage to form the end product 17 (Scheme
6). The difference between the behavior of the pyridinium
and quinolinium zwitterions (7 and 9, respectively) is
caused by the different regioselectivity of the two
compounds: in the case of 7 the sterically less hindered
1. Experimental
1.1. General
Melting points were determined by a BuÈchi apparatus
and are uncorrected. The IR spectra were recorded with a
Nicolet Magna 750 FT-IR, spectrophotometers; the NMR
spectra were recorded with a Varian UNITY INOVA
1
spectrometer (400 MHz for H and 100 MHz for 13C). The
Scheme 6.

3616
A. Messmer et al. / Tetrahedron 58 (2002) 3613±3618
mass spectra were measured on a VG ZAB2-SEQ tandem
mass spectrometer using FAB and EI techniques for
ionization. For Cl and Br containing molecules the high-
resolution mass measurements were carried out using 35Cl
or 79Br isotopic peaks.
isolated as red crystals, 1.72g, (92%); mp: 90±92 8C; nmax
(KBr): 3020, 1577, 1477, 1468, 1420, 1305, 1255, 1228,
1170, 829, 747, 689, 503 cm21; dH (CDCl3): 6.58 (m, 1H,
H-3), 6.91 (m, 1H, H-4), 6.93 0(m, 1H, H-5), 6.95 (m, 2H,
H-20, H-60), 7.15 (m, 2H, H-3 , H-50), 7.50 (m, 3H, H-300,
H-400, H-500), 7.65 (m, 2H, H-200, H-600), 8.60 (m, 1H, H-6);
dC (CDCl3): 117.8 (C-20, C-60), 120.7 (C-5), 123.3 (C-3),
1.1.1. N-Anilinopyridin-2(1H)one (5). A solution of
phenol (639 mg, 6.8 mmol) in tetrahydrofuran (10 mL)
was added to a suspension of sodium hydride (314 mgÐ
calculated for a 50% dispersion, 6.5 mmol) in tetrahydro-
furan (10 mL) with vigoros stirring and ice cooling. The
mixture was re¯uxed for 10 min, cooled down to 2358C
and, then, a solution of tetrazolopyridinium salt 14 (1.9 g,
6 mmol) in acetonitrile (25 mL) was added dropwise. The
whole manipulation was executed under an argon atmos-
phere. The reaction mixture was allowed to warm up to
room temperature. The solvent was removed in vacuo,
and the residue was dissolved in methanol, some impurities
were removed by ®ltration, the ®ltrate was evaporated, and
the redish solid residue was treated with ether. The resulting
solid was ®ltered off, and crystallized from ethanol to afford
white crystals. 927 mg (70%) mp: 209±2138C (lit.4 1988C).
The product proved to be identical (NMR, TLC) with an
authentic sample obtained by a previous procedure.
123.5 (C-40), 125.6 (C-4), 129.7 (C-30, C-50), 130.0 (C-100),
00
130.5 (C-300, C-500), 130.6 (C-400), 134.2(C-6), 136.2(C-2
,
C-600), 150.8 (C-2), 151.4 (C-10); HRMS (FAB) for
C17H12N2ClS [M1H]1 found: 313.0565, calcd: 313.0566.
1.2.3. 2-(4-Chlorophenylthio)pyridinium-N-(4-chloro)-
phenylimide (7c, Arˆ4-chlorophenyl, XˆCl). This
compound was isolated as red crystals, 1.5 g (92%) mp
141±1428C; nmax (KBr): 3070, 1576, 1480, 1472, 1420,
1307, 1255, 1170, 1092, 1013, 836, 751, 503 cm21; dH
(CDCl3): 6.55 (dd, 1H, Jˆ8, 2Hz, H-3), 6.86 (ddd, 1H,
Jˆ8.5, 8, 1.5 Hz, H-4), 6.91 (ddd, 1H, Jˆ8.5, 7, 2Hz,
H-5), 6.96 (m, 2H, H-200, H-600), 7.16 (m, 2H, H-300,
H-500), 7.19 (m, 2H, H-20, H-60), 7.25 (m, 2H, H-30, H-50),
8.57 (dd, 1H, Jˆ7, 1.5 Hz, H-6); dC (CDCl3): 117.9, 120.5,
122.8, 123.4, 124.1, 128.6, 129.5, 130.4, 132.6, 136.8,
137.2, 148.5, 151.1; HRMS (FAB) for C17H12N2Cl2S
[M1H]1 found: 347.0177, calcd: 347.0176.
1.2. General procedure for preparation of pyridinium
and quinolinium N-arylimides
1.2.4. 2-(4-Tolylthio)quinolinium-N-(4-bromo)phenyl-
imide (9). This compound was isolated as blue crystals,
2.32 g (92%) mp: 159±1618C; UV l (nm) log e in aceto-
nitrile: 224 (4.408), 266 (4.463), 326 (4.254), 588 (3.025);
nmax (KBr): 3027, 3010, 1587, 1574, 1560, 1472, 1301,
1252, 1169, 806, 505 cm21; dH (CDCl3): 2.42 (s, 3H,
H±Me), 6.08 (b, 2H, H-20, H-60), 6.88 (d, 1H, Jˆ9 Hz,
H-3), 7.06 (m, 2H, H-30, H-50), 7.32(m, 2H, H-3 00, H-500),
7.49 (m, 2H, H-200, H-600), 7.58 (ddd, 1H, Jˆ8.5, 7.5, 1 Hz,
H-7), 7.72(ddd, 1H, Jˆ9, 7.5, 1 Hz, H-6), 7.87 (dd, 1H,
Jˆ9, 1 Hz, H-8), 7.91 (dd, Jˆ9, 1 Hz, H-4), 8.24 (ddd, 1H,
Jˆ8.5, 1, 1 Hz, H-5); dC (CDCl3): 21.3, 103.5, 111.9, 119.5,
120.4, 125.8, 127.1, 127.5, 129.2, 131.1, 131.5, 132.8,
134.6, 135.5, 141.2, 142.0, 156.4, 164.3; HRMS (FAB)
for C22H17N2BrS [M]1 found: 420.0272, calcd: 420.0296.
A solution of the appropriate thiophenol (6.8 mmol) in tetra-
hydrofuran (10 mL) was added to a suspension of sodium
hydride (314 mg, 6.5 mmol, calculated for a 50% dispersion
with respect to NaH) in tetrahydrofuran (20 mL) with
vigorous stirring and ice cooling. The mixture was re¯uxed
for 10 min, then it was cooled down to 2358C and a solution
of the appropriate tetrazolium salt (6 mmol) in acetonitrile
(25 mL) was added dropwise. The whole manipulation was
executed under an argon atmosphere. The reaction mixture
was allowed warm up to room temperature. The solvent
was removed in vacuo, and the residue was dissolved
in dichloromethane. This mixture was ®ltered from the
insoluble inorganic material (sodium tetra¯uoroborate),
the ®ltrate was evaporated again, and the residue was treated
with ether. The resulting solid was ®ltered off and washed
with ether.
1.3. Reaction of 2-(4-chlorophenylthio)-pyridinium
N-(4-chlorophenyl)imide (7c) with methanol
1.2.1.
2-(4-Tolylthio)pyridinium-N-(4-chloro)phenyl-
Crystalline 7c (400 mg, 1.15 mmol) was suspended in
methanol (10 mL). The mixture was re¯uxed for 1 h, the
solvent was evaporated, the residue was treated vith ether,
and the precipitated solid was ®ltered off. The crude product
was crystallized from methanol to yield N-(4-chloro)ani-
linopyridin-2(1H)one (5) as white crystals: 216 mg (85%),
mp: 209±2128C (lit.,4 1988C).
imide (7a, Arˆ4-chlorophenyl, XˆCH3). This compound
was isolated as red crystals, 1.76 g (90%), mp 138±1408C;
UV l (nm) log e in acetonitrile: 224 (4.226), 288 (4.095),
444 (3.761); nmax (KBr): 3020, 1573, 1490, 1477, 1467,
1312, 1253, 1225, 829, 810, 743, 501 cm21; dH (CDCl3):
2.42 (s, 3H, H±Me), 6.60 (m, 1H, H-3), 6.92 (m, 1H, H-4),
6.93 (m, 1H, H-5), 6.94 (m, 2H, H-20, H-60), 7.15 (m, 2H,
H-30, H-50), 7.31 (m, 2H, H-300, H-500), 7.50 (m, 2H, H-200,
H-600), 8.61 (m, 1H, H-6); dC (CDCl3): 21.6 (C±Me), 116.5
(C-400 or C-40), 117.7 (C-20, C-60), 120.6 (C-5), 123.4 (C-3),
126.2 (C-4), 128.8 (C-40 or C-400), 129.7 (C-30, C-50), 131.3
(C-300, C-500), 134.8 (C-6), 136.1 (C-200, C-600), 141.1 (C-100),
151.3 (C-2), 151.8 (C-10); HRMS (FAB) for C18H15N2ClS
[M1H]1 found: 327.0714, calcd: 327.0723.
1.3.1. N-(4-Bromoanilino)quinolin-2(1H)one (10). 2-(4-
Tolylthio)quinolinium N-(4-bromophenyl)imide 9 (300
mg, 0.71 mmol) was added to methanol (10 mL), where-
upon a fast reaction occurred indicated by the disappearance
of the blue color of the starting compound. The solvent
was removed, the residue was treated with ether, and the
precipitated solid was ®ltered off. Recrystallization from
methanol afforded colorless crystals. Yield: 186 mg
(83%), mp: 176±1788C (lit.,4 1968C). Physical data (TLC,
1.2.2. 2-(Phenylthio)pyridinium-N-(4-chloro)phenylimide
(7b, Arˆ4-chlorophenyl, XˆH). This compound was

A. Messmer et al. / Tetrahedron 58 (2002) 3613±3618
3617
NMR spectra) of the product proved to be identical with that
of the authentic sample.
2H, H-200, H-600), 7.19 (m, 2H, H-30, H-50), 7.25 (m, 2H, H-20,
H-60), 7.33 (m, 2H, H-2000, H-6000), 7.43 (m, 1H, H-4000), 7.49
(m, 2H, H-3000, H-5000); dC (CDCl3): 21.4 (C±Me), 54.4 (C-3a),
62.5 (C-3b), 65.1 (C-8a), 98.0 (C-6), 113.9 (C-4), 116.2 (C-20,
C-60), 125.0 (C-5), 126.2 (C-2000, C-6000), 126.4 (C-40), 127.4
(C-100), 129.0 (C-4000), 129.3 (C-3000, C-5000), 129.5 (C-30, C-50),
1.3.2. 2-(4-Tolylthio)-N-methyl-N-(4-chloroanilino)pyri-
dinium iodide (11). A mixture of 2-(4-tolylthio)pyri-
dinium-N-(4-chlorophenyl)imide 7a (200 mg, 0.61 mmol),
methyliodide (0.5 mL) and acetonitrile (3 mL) was stirred at
room temperature for 1 h. The solvent was removed, the
residue was treated with ether, and the precipitated solid
material was ®ltered off to yield the product, 250 mg
(90%), mp: 136±1388C, yellow crystals; nmax (KBr):
3017, 2983, 1601, 1557, 1493, 1464, 1279, 1092, 816,
811 cm21; dH (CDCl3): 2.50 (s, 3H, H±Me), 3.80 (s, 3H,
H±N±Me), 7.01 (m, 2H, H-20, H-60), 7.13 (dd, 1H, Jˆ9,
00
130.2(C-3 , C-500), 135.7 (C-200, C-600), 139.7 (C-400), 148.0
(C-10), 151.4 (C-7), 172.0 (C-3), 172.3 (C-1); LRMS (FAB):
500, 499; HRMS (FAB) for C28H22N3ClO2S [M]1 found:
499.1082, calcd: 499.1121.
1.4.2. 8-(4-Chlorophenyl)-2-phenyl-7-p-phenylthio-3a,3b,8,
8a-tetrahydro-2,7a,8-triaza-cyclopenta[a]indene-1,3-dione
(13b, Arˆ4-chlorophenyl, XˆH). This compound was
obtained as colorless crystals, 544 mg (80%); mp: 103±
1058C; nmax (KBr): 3057, 2970, 1785, 1720, 1593, 1540,
1488, 1379, 1175, 826, 810, 749 cm21; dH (CDCl3): 3.62
(dd, 1H, Jˆ8, 7.5 Hz, H-3a), 4.40 (dd, 1H, Jˆ7.5, 5 Hz,
H-3b), 4.48 (dd, 1H, Jˆ6, 1 Hz, H-6), 4.66 (d, 1H, Jˆ
8 Hz, H-8a), 5.76 (ddd, 1H, Jˆ9.5, 5, 1 Hz, H-4), 5.98
(dd, 1H, Jˆ9.5, 6 Hz, H-5), 7.18 (m, 2H, H-20, H-60), 7.24
(m, 2H, H-30, H-50), 7.25±7.34 (m, 7H, H-0200 00, H-300, H-400,
H-500, H-600, H-2000, H-6000), 7.42(m, 1H, H-4 ), 7.49 (m, 2H,
H-3000, H-5000); dC (CDCl3): 54.2, 62.2, 65.0, 98.4, 114.0,
116.0, 124.8, 126.0, 127.2, 129.1, 129.2, 129.3, 130.0,
131.8, 135.3, 147.7, 150.6, 171.8, 172.0; HRMS (FAB)
for C27H20N3ClO2S [M]1 found: 485.0941, calcd: 485.0965.
0
2Hz, H-3), 7.37 (m, 2H, H-3 , H-50), 7.44 (m, 2H, H-300,
H-500), 7.64 (m, 2H, H-200, H-600), 7.91 (ddd, 1H, Jˆ7, 6.5,
2Hz, H-5), 8.34 (ddd, 1H, Jˆ9, 7, 1 Hz, H-4), 9.42(dd, 1H,
Jˆ6.5, 1 Hz); dC (CDCl3): 21.7, 42.6, 119.3, 120.6, 125.8,
126.0, 130.4, 131.3, 136.2, 143.6, 144.0, 145.3, 146.3,
166.0; HRMS (FAB) for C19H18N2ClS [M2I]1 found:
341.0881, calcd: 341.0879.
1.3.3. 2-(4-Tolylthio)-N-methyl-N-(4-bromoanilino)quino-
linium iodide (12). A mixture of 2-(4-tolylthio)quinolinium
N-(4-bromo)phenylimide 9 (200 mg, 0.47 mmol), methyl-
iodide (0.5 mL) and acetonitrile (3 mL) was stirred at
room temperature for 1 h. The solvent was removed, the
residue was treated with ether, and the precipitated solid
material was ®ltered off to yield the product, 244 mg
(91%), mp: 119±1218C; nmax (KBr): 3032, 2970, 1613,
1592, 1561, 1488, 1447, 1141, 814, 762 cm21; dH
(CDCl3): 2.48 (s, 3H, H±Me), 3.91 (s, 3H, H±N±Me),
6.53 (m, 2H, H-20, H-60), 7.24 (d, 1H, Jˆ9 Hz, H-3), 7.43
(m, 2H, H-300, H-500), 7.45 (m, 2H, H-30, H-50), 7.53 (dd, 1H,
Jˆ9, 1 Hz, H-8), 7.72(m, 2H, H-2 00, H-600), 7.76 (ddd, 1H,
Jˆ8, 7, 1 Hz, H-6), 7.92(ddd, 1H, Jˆ9, 7, 2Hz, H-7), 8.47
(ddd, 1H, Jˆ8, 2, 1 Hz, H-5), 9.14 (dd, 1H, Jˆ9, 1 Hz, H-4);
dC (CDCl3): 21.8, 39.6, 114.2, 115.6, 116.6, 120.1, 121.0,
128.6, 129.6, 132.4, 132.6, 133.5, 136.2, 136.6, 139.6,
142.8, 143.9, 146.5, 173.1; HRMS (FAB) for
C23H20N2BrS [M2I]1 found: 435.0502, calcd: 435.0530.
1.4.3. 8-(4-Chlorophenyl)-2-phenyl-7-p-4-chlorophenyl-
thio-3a,3b,8,8a-tetrahydro-2,7a,8-triaza-cyclopenta-
[a]indene-1,3-dione (13c, Arˆ4-chlorophenyl, XˆCl).
This compound was obtained as colorless crystals, 624 mg
(80%); mp: 132±1348C; nmax (KBr): 3061, 2900, 1789,
1719, 1547, 1488, 1387, 1192, 1174, 1092, 826,
753 cm21; dH (CDCl3): 3.63 (dd, 1H, Jˆ8, 7.5 Hz, H-3a),
4.38 (dd, 1H, Jˆ7.5, 5 Hz, H-3b), 4.53 (dd, 1H, Jˆ6, 1 Hz,
H-6), 4.65 (d,1H, Jˆ 8 Hz, H-8a), 5.78 (ddd, 1H, Jˆ9.5, 5,
1 Hz, H-4), 6.00 (dd, 1H, Jˆ9.5, 6 Hz, H-5), 7.13 (m, 1H,
H-20, H-60), 7.17 (m, 4H, H-200, H-300, H-500, H-600), 7.24 (m,
2H, H-30, H-50), 7.30 (m, 2H, H-2000, H-6000), 7.44 (m, 1H, H-
4000), 7.49 (m, 2H, H-3000, H-5000); dC (CDCl3): 54.2, 62.1,
64.9, 98.9, 114.5, 115.8, 124.6, 125.7, 127.3, 128.4, 128.7,
129.1, 129.2, 129.3, 131.6. 135.4, 136.3, 147.5, 149.7,
171.6, 171.9; HRMS (FAB) for C27H19N3Cl2O2S [M]1
found: 519.0590, calcd: 519.0575.
1.4. General procedure for cycloaddition of the
zwitterion with N-phenylmaleimide
To a solution of the appropriate pyridinium-N-arylimide
(1.5 mmol) in dichloromethane (10 mL) was added
N-phenyl-maleimide (294 mg, 1.7 mmol). The reaction
mixture was stirred at room temperature for 15 min. A
fast reaction occured indicated by disappearence of the
red color. The solvent was removed, the residue was treated
with ether and the resulting solid was ®ltered off.
1.5. General procedure for oxidation of cycloadduct 13
with dicyanodichloroquinone (DDQ)
A suspension of the appropriate derivative of 13 (1.5 mmol),
DDQ (409 mg, 1.8 mmol) in toluene (10 mL) was re¯uxed
for two hours. The solvent was removed, the residue was
mixed with dichloromethane (40 mL), and some impurities
were removed by ®ltration. Alumina (2g) was added to the
®ltrate, the mixture was stirred for a few minutes, and the
mixture was ®ltered. The organic solvent was evaporated,
and the residue was crystallized from acetonitrile.
1.4.1. 8-(4-Chlorophenyl)-2-phenyl-7-p-tolylthio-3a,3b,8,
8a-tetrahydro-2,7a,8-triaza-cyclopenta[a]indene-1,3-dione
(13a, Arˆ4-chlorophenyl, XˆCH3). This compound was
obtained as colorless crystals, 636 mg (85%); mp: 140±
1418C; nmax (KBr): 3057, 2920, 1786, 1725, 1546, 1491,
1387, 1192, 1175, 820, 810, 751 cm21; dH (CDCl3): 2,30 (s,
3H, H±Me), 3.60 (dd, 1H, Jˆ8, 7.5 Hz, H-3a), 4.39 (dd, 1H,
Jˆ7.5, 5 Hz, H-3b), 4.44 (dd, 1H, Jˆ6, 1 Hz, H-6), 4.65 (d,
1H, Jˆ8 Hz, H-8a), 5.74 (ddd, 1H, Jˆ9.5, 5, 1 Hz, H-4), 5.98
(dd,1H, Jˆ9.5, 6 Hz, H-5), 7.03 (m, 2H, H-300, H-500), 7.17 (m,
1.5.1. 3-(4-Chloroanilino)-1-phenyl-4-(6-p-tolylthiopyridin-
2-yl)-pyrrole-2,5-dione (14a). This compound was
obtained as orange crystals, 499 mg (67%); mp: 191±
1938C; nmax (KBr): 2920, 1757, 1711, 1636, 1545, 1497,
1399, 1161, 1096, 799, 752cm 21; dH (CDCl3): 2.08 (s,

3618
A. Messmer et al. / Tetrahedron 58 (2002) 3613±3618
00
3H, H±Me), 6.92(m, 2H, H-2 , H-600), 6.93 (m, 2H, H-20,
H-60), 6.96 (m, 2H, H-300, H-500), 6.98 (dd, 1H, Jˆ8, 1 Hz,
H-3), 7.23 (m, 2H, H-30, H-50), 7.24±7.31 (m, 2H, H-2000,
H-6000), 7.35±7.4 (m, 3H, H-3000, H-4000, H-5000), 7.56 (dd, 1H,
Jˆ8, 8 Hz, H-4), 8.17 (dd, 1H, Jˆ8, 1 Hz, H-5), 10.7 (b, 1H,
N±H); dC (CDCl3): 21.3, 99.7, 118.5, 119.2, 126.6, 126.8,
127.7, 128.8, 129.0, 130.6, 131.6, 132.3, 134.7, 136.3,
137.4, 139.6, 144.6, 152.7, 158.7, 163.9, 168.7; HRMS
(FAB) for C28H20N3ClO2S [M1H]1 found: 498.1052,
calcd: 498.1043.
(m, 2H, H-30, H-50), 7.21 (m, 2H, H-200, H-600), 7.33 (m, 1H,
H-400), 7.38 (ddd, 1H, Jˆ8, 7, 1 Hz, 6-H), 7.42(m, 2H,
H-300, H-500), 7.51 (d, 1H, Jˆ9 Hz, H-3), 7.57 (ddd, 1H,
Jˆ8.5, 7, 1 Hz, H-7), 7.62(dd, 1H, Jˆ8, 1 Hz, H-5), 7.65
(d, 1H, Jˆ9 Hz, H-4), 8.11 (dd, 1H, Jˆ8.5, 1 Hz, H-8), 10.9
(s, 1H, N±H); dC (CDCl3): 91.9, 113.2, 115.7, 117.2, 122.2,
125.3, 125.9, 126.2, 127.1, 127.6, 127.9, 128.8, 131.6,
132.3, 132.7, 134.5, 141.2, 142.5, 153.5, 166.1, 166.9;
HRMS (EI) for C25H16N3BrO2 [M]1 found: 469.0418,
calcd: 469.0426.
1.5.2. 3-(4-Chloroanilino)-1-phenyl-4-(6-p-chlorophenyl-
thiopyridin-2-yl)-pyrrole-2,5-dione (14c). This compound
was obtained as orange crystals: 505 mg (65%); mp: 225±
2278C; nmax (KBr): 3089, 3057, 1767, 1708, 1627, 1570,
1495, 1387, 1157, 1091, 802, 760 cm21; dH (DMSO-d6):
dH (DMSO-d6): 7.04 (m, 2H, H-20, H-60), 7.12(dd, 1H,
Jˆ8, 1 Hz, H-3), 7.29 (m, 2H, H-30, H-50), 7.32(m, 2H,
H-300, H-500), 7.35±7.40 (m, 3H, H-3000, H-4000, H-5000), 7.46
(m, 2H, H-2000, H-6000), 7.49 (m, 2H, H-200, H-600), 7.79 (dd,
1H, Jˆ8, 8 Hz, H-4), 7.98 (dd, 1H, Jˆ8, 1 Hz, H-5), 10.34
(b, 1H, N±H); dC (DMSO-d6): 99.4, 118.9, 119.4, 125.7,
126.9, 127.5, 128.2, 128.6, 128.9, 129.7, 130.1, 131.7,
134.2, 135.5, 136.4, 137.9, 143.8, 151.7, 156.9, 163.7,
168.5; HRMS (FAB) for C27H17N3SCl2O2 [M1H]1 found:
518.0524, calcd: 518.0497.
Acknowledgements
Research fund OTKA 35176 is gratefully appreciated.
References
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