Synthesis of mesoionic 4-(para-substituted phenyl-5-2,4-dichlorophenyl)-1, 3-4-thiadiazolium-2-aminides by direct cyclization via acylation of thiosemicarbazides

Article abstract of DOI:10.1080/00397910600941398

The synthesis of ten novel mesoionic 4-[para-substituted (H, CH ₃, OCH₃, NO₂, Cl, Br, OH, t-C₄H ₉, C₆H₅, C₄H₉) phenyl-5-2,4-dichlorophenyl]-1,3-4-thiadiazolium-2-aminides, as hydrochlorides, are described. The synthesis strategy utilized the corresponding para-substituted isothiocyanates as starting materials to obtain the thiosemicarbazides through reaction with phenylhydrazine (61-98%), which were then submitted to acylation with 2,4-dichloro benzoyl chloride and direct cyclization to generate the desired substituted mesoionic compounds in good yields (ca. 80%). Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600941398

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Synthesis of Mesoionic 4‐(para‐substituted
Phenyl‐5‐2,4‐dichlorophenyl)‐1,3‐4‐thiadiazolium
by Direct Cyclization via Acylation of
Thiosemicarbazides
Marcelo Moreira Britto a , Tânia Mara Grigolli Almeida a , Andrei Leitão
a , Claudio Luis Donnici a , Míriam Tereza Paz Lopes b & Carlos Alberto
Montanari c
a Departamento de Química, Instituto de Ciências Exatas, Universidade
Federal de Minas Gerais, Belo Horizonte, Brazil
b Departamento de Farmacologia, Instituto de Ciências Biológicas,
Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
c Instituto de Química, Universidade de São Paulo, São Carlos, Brazil
Version of record first published: 23 Nov 2006.
To cite this article: Marcelo Moreira Britto , Tânia Mara Grigolli Almeida , Andrei Leitão , Claudio
Luis Donnici , Míriam Tereza Paz Lopes & Carlos Alberto Montanari (2006): Synthesis of Mesoionic
4‐(para‐substituted Phenyl‐5‐2,4‐dichlorophenyl)‐1,3‐4‐thiadiazolium‐2‐aminides by Direct Cyclization
via Acylation of Thiosemicarbazides, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 36:22, 3359-3369
To link to this article: http://dx.doi.org/10.1080/00397910600941398
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Synthetic Communicationsw, 36: 3359–3369, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600941398
Synthesis of Mesoionic 4-(para-substituted
Phenyl-5-2,4-dichlorophenyl)-1,3-4-
thiadiazolium-2-aminides by Direct
Cyclization via Acylation
of Thiosemicarbazides
ˆ
Marcelo Moreira Britto, Tania Mara Grigolli Almeida,
Andrei Leita˜o, and Claudio Luis Donnici
´ ˆ
Departamento de Quımica, Instituto de Ciencias Exatas,
Universidade Federal de Minas Gerais, Belo Horizonte Brazil
´
Mıriam Tereza Paz Lopes
ˆ
´
Departamento de Farmacologia, Instituto de Ciencias Biologicas,
Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Carlos Alberto Montanari
Instituto de Quımica, Universidade de Sa˜o Paulo, Sa˜o Carlos, Brazil
´
Abstract: The synthesis of ten novel mesoionic 4-[para-substituted (H, CH3, OCH3,
NO2, Cl, Br, OH, t-C4H9, C6H5, C4H9) phenyl-5-2,4-dichlorophenyl]-1,3-4-thiadiazo-
lium-2-aminides, as hydrochlorides, are described. The synthesis strategy utilized the
corresponding para-substituted isothiocyanates as starting materials to obtain the thio-
semicarbazides through reaction with phenylhydrazine (61–98%), which were then
submitted to acylation with 2,4-dichloro benzoyl chloride and direct cyclization to
generate the desired substituted mesoionic compounds in good yields (ca. 80%).
Keywords: Cyclization by direct benzoylation of thiosemicarbazides, para-substituted
isothiocyanates, para-substituted phenyl-5-2,4-dichlorophenyl]-1,3-4-thiadiazolium-
2-aminides
Received in the USA May 4, 2006
Address correspondence to Claudio Luis Donnici, Departamento de Quımica,
´
Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627 Belo Horizonte,
MG, 31270-901, Brazil. E-mail: cdonnici@terra.com.br
3359

3360
M. M. Britto et al.
INTRODUCTION
Mesoionic compounds are heterocyclic betaines[1] that are very useful in
medicinal chemistry because of their well-known range of pharmacological
activities[2] and low toxicity.[3,4] Their anticancer activity is especially
remarkable[5] because of very promising in vivo results.[6] This has
prompted us to undertake the synthesis of new analogues to gauge their
potential as chemotherapeutic agents. Previously, our research group syn-
thesized 1,3,4-oxadiazolium-2-aminide and 1,3,4-oxadiazolium-2-olate
mesoionics and evaluated their antimicrobial activity.[7] We investigated
the antimicrobial activity of those mesoionic compounds by the biological
microcalorimetric technique[8] and also elucidated their structures.[9–11]
Among the studied mesoionic, 1,3,4-thiadiazolium-2-aminides that
showed good activity against Staphyloccocus aureus, Staphyloccocus
epidermidis, and Bacilus cereus, the 5-(2,4-dichlorophenyl) derivative (1a,
X ¼ H) (Fig. 1) has the lowest minimum inhibitory concentration
(MIC ¼ 0.14 mMmL21).8 More recently,[12,13] we investigated the
synthesis and the lipophilicity of some 1,3,4-thiadiazolium-2-aminides 1
with para-substituents at the mesoionic ring. In that work, we synthesized
several mesoionic compounds through cyclization of 1-aroyl-2-phenyl-1,4-
thiosemicarbazides, which were also isolated, studied, and in turn obtained
by the reaction of acid chlorides with the corresponding 1,4-diphenyl-
thiosemicarbazide, under basic conditions, to avoid premature ring closure.
For the present study, the novel mesoionic compounds were prepared
without isolation of any intermediates, and they were isolated as the sole
product under acid conditions. Via this route, we synthesized ten novel
mesoionic 4-[para-substituted (X ¼ H, CH3, OCH3, NO2, Cl, Br, OH,
t-C4H9, C6H5, C4H9) phenyl-5-2,4-dichlorophenyl]-1,3-4-thiadiazolium-2-
aminides hydrochlorides 1. The substituents were chosen to allow further
evaluations on structure–activity relationships related to their electronic
and lipophilic effects.
Figure 1. Synthesized mesoionic 4-para-substituted phenyl-5-2,4-dichlorophenyl]
-1, 3-4-thiadiazolium-2-aminides hydrochlorides.

Synthesis of Mesoionic by Direct Cyclization
RESULTS AND DISCUSSION
3361
The synthetic route investigated in this work (Scheme 1) used para-substituted
isothiocyanates 2 as starting materials. The corresponding para-substituted
phenylthiosemicarbazides 3 were obtained (61–98%) through the reaction
with phenylhydrazine in toluene. After acylation of the thiosemicarbazides
3 with 2,4-dichloro benzoyl chloride (4),[14,15] cyclization led directly to the
desired substituted mesoionic compounds in good yield (70–84%), without
isolation of the corresponding acylthiosemicarbazide intermediates. The
hydrochloric acid evolved in the acylation reaction might work as a catalyst
to promote the direct mesoionic cyclization. In fact, the direct and regioselec-
tive intramolecular cyclization to the mesoionic compounds is the key step of
the synthesis (Scheme 1).
The results obtained in the acylation–cyclization reactions are depicted in
Table 1.
Compounds 1a–g are obtained in good yields (70–84%), and analysis of
the spectroscopic data shows formation of only 1,3-4-thiadiazolium-2-
aminides. It is noteworthy that this synthesis is highly selective because no
traces of 1,3,4-triazolium-2-thiolate, the other possible isomer, were detected
(Scheme 2) as described in other analogousworks[9–11] or even in our own.[12,13]
However, it is noteworthy that reactions with the thiosemicarbazides 2d,
2e, and 2f (entries 4, 5, and 6) are much slower, maybe because of the electron-
withdrawing effect of those substituents (X ¼ NO2, Br, and Cl) that might
diminish the electron density of the sulfur atom (possible nucleophilic
reaction center) of the corresponding acylthiosemicarbazides. Finally, it is
noteworthy to point out that this synthetic route is highly regio- and chemio-
selective: no secondary products or any other isomeric mesoionic compound
were detected.
Scheme 1.

3362
M. M. Britto et al.
Table 1. Direct cyclization reactions for mesoionic hydrochlorides
(1a–i) obtained during the acylation of para-substituted thiosemicarba-
zides (3a–i) with 2,4-dichlorobenzoyl chloride
Hydrochloride mesoionic 1
Entry
Thiosemicarbazide 3
Time (h)
Mp (8C)
1 (%)
1
2
a (X ¼ H)
2.0
2.0
2.0
2.5
2.5
2.5
2.0
2.0
2.0
2.0
262–264
267–270
271–272
288 (dec.)
269–271
272–273
284–285
277–288
274–275
278–280
84
80
85
76
72
70
74
82
73
83
b (X ¼ Me)
c (X ¼ OMe)
d (X ¼ NO2)
e (X ¼ Cl)
3
4
5
6
f (X ¼ Br)
7
g (X ¼ OH)
h (X ¼ C6H5)
i (X ¼ t-C4H9)
j (X ¼ C4H9)
8
9
10
EXPERIMENTAL
General
Melting points were determined on a Mettler apparatus and are uncorrected. 1H
and 13C NMR spectra were recorded on a Bruker instrument (AC-200 MHz)
Scheme 2.

Synthesis of Mesoionic by Direct Cyclization
3363
in CDCl3 using tetramethylsilane as an internal standard.
FT-IR spectra were recorded on a Mattson instrument, model Galaxy 3000.
Microanalyses were carried out on a Perkin-Elmer CHNS 2400 elemental
analyzer. Column chromatography was performed on SiO2 (Merck, 70–
230 mesh, Kieselgel 60). 2,4-Dichloro-benzoyl chloride was freshly
prepared from the corresponding benzoic acid and thionyl chloride. Phenyl
isothiocyanate (3a) and the corresponding para-chloro- (3e) and para-
bromo-phenylisothiocyanate (3f) were commercially available. Para-
methyl- (3b), -methoxy- (3c), -phenyl- (3g), t-butyl- (3h), -hydroxy-(3i),
and -butyl phenylisothiocyanates (3j) were made (55–91%) by condensation
of the corresponding dithiocarbamates with ethyl chloroformate followed by
acid hydrolysis. These dithiocarbamates were first obtained through the
well-known reaction between the para-substituted anilines and carbon
disulfide.[16] The para-nitro-phenyl isothiocyanate (3d) only could be
prepared by another synthetic route: condensation (64%) between diethylthio-
carbamoyl chloride and para-nitroaniline.[17]
General Procedure for the Reaction of Phenylhydrazine
with para-Phenyl-isothiocyanates 2a–j
To a solution of phenylhydrazine (5.4 g, 4.9 mL, 0.05 mol) in toluene
(50 mL), phenylisothiocyanate (2a, 6.75 g, 0.05 mol) was added. Then this
mixture was heated under reflux for 30 min, and a white solid precipitated.
After cooling, filtration, diethyl ether washings, further purification by recrys-
tallization (with ethanol), and drying, the pure product was obtained.
Thiosemicarbazide 3a: 70% yield: white solid; mp 319–3218C (lit. 319–
3208C.) IR nmax (KBr)/cm21 3290, 3200, 3180, 1280, 1210. 1H NMR
(DMSO-d6) d 6.77–7.25 (m, 5H), 7.27–7.56. (m, 5H), 8.07 (s, 1H), 9.71
(s, 1H), 9.83 (s, 1H). 13C NMR (DMSO-d6) d 113.10, 119.84, 124.74,
125.04, 127.91, 128.89, 139.19, 148.03, 181.14. Anal. calc. for C13H13N3S:
C, 64.17; H, 5.38; N, 17.27; S, 13.18. Found: C, 64.18; H, 5.35; N, 17.24;
S, 13.20.
Thiosemicarbazide 3b (X 5 Me): 72% yield: white solid; mp 177–1798C.
IR nmax (KBr)/cm21 3310, 3220, 3170, 1270, 1200. 1H NMR (CDCl3)
d 2.23 (s, 3H), 6.75–7.26 (m, 5H), 7.07 (d, 2H, J ¼ 8.4 Hz), 7.32 (d, 2H,
J ¼ 8.4 Hz), 8.06 (s, 1H), 9.66 (s, 1H), 9.75 (s, 1H). 13C NMR (CDCl3)
d 20.49, 113.02, 119.72, 125.06, 125.39, 128.82, 136.58, 148.02, 152.61,
181.18. Anal. calc. for C14H15N3S: C, 65.34; H, 5.87; N, 16.33; S, 12.4.
Found: C, 65.38; H, 5.88; N, 16.35; S, 12.51.
Thiosemicarbazide 3c (X 5 OMe): 62% yield: white solid; mp 184–1868C.
IR nmax (KBr)/cm21 3300, 3270, 3200, 1280, 1220. 1H NMR (CDCl3) d 3.79

3364
M. M. Britto et al.
(s, 3H), 6.73–7.24 (m, 5H), 7.12 (d, 2H, J ¼ 8.7 Hz), 7.41 (d, 2H,
J ¼ 8.7 Hz), 8.02 (s, 1H), 9.57 (s, 1H), 9.72 (s, 1H). 13C NMR (DMSO-d6)
d 55.94, 112.78, 119.46, 120.01, 125.99, 128.59, 135.98, 147.64, 153.72,
181.04. Anal. calc. for C14H15N3OS: C, 61.51; H, 5.53; N, 15.37; S, 11.73.
Found: C, 61.53; H, 5.55; N, 15.39; S, 11.78.
Thiosemicarbazide 3d (X 5 NO2): 76% yield: light yellowish solid; mp
234–2368C. IR nmax (KBr)/cm21 3250, 3200, 3150, 1490, 1330, 1290,
1
1220. H NMR (CDCl3) d 6.77–7.27 (m, 5H), 8.04 (d, 2H, J ¼ 9.2 Hz),
8.17 (d, 2H, J ¼ 9.2 Hz), 8.34 (s, 1H), 10.12 (s, 1H), 10.32 (s, 1H). 13C
NMR (CDCl3) d 113.31, 120.16, 123.58, 123.94, 128.93, 143.07, 145.77,
147.74, 180.89. Anal. calc. for C13H12N4O2S: C, 54.15; H, 4.19; N, 19.43;
S, 11.12. Found: C, 54.18; H, 4.15; N, 19.46; S, 11.19.
Thiosemicarbazide 3e (X 5 Cl): 78% yield: white solid; mp 202–2048C. IR
n
max (KBr)/cm21 3250, 3180, 3090, 1290, 1210, 1090, 820. 1H NMR (CDCl3)
d 6.74–7.25 (m, 5H), 7.34 (d, 2H, J ¼ 8.8 Hz), 7.57 (d, 2H, J ¼ 8.8 Hz), 8.06
(s, 1H), 9.78 (s, 1H), 9.93 (s, 1H). 13C NMR (CDCl3) d 113.08, 119.82,
125.37, 126.73, 127.70, 128.62, 138.21, 147.92, 181.20. Anal. calc. for
C13H12ClN3S: C, 56.21; H, 4.35; N, 15.13; S, 11.54. Found: C, 56.18; H,
4.33; N, 15.11; S, 11.52.
Thiosemicarbazide 3f (X 5 Br): 72% yield: white solid; mp 207–2088C. IR
n
max (KBr)/cm21 3250, 3200, 3170, 1280, 1210, 1075, 770. 1H NMR (CDCl3)
d 6.74–7.26 (m, 5H), 7.45 (d, 2H, J ¼ 8.9 Hz), 7.50 (d, 2H, J ¼ 8.9 Hz), 8.08
(s, 1H), 9.81 (s, 1H), 9.96 (s, 1H). 13C NMR (CDCl3) d 113.06, 116.78,
119.79, 127.00, 128.79, 130.60, 138.63, 147.88, 181.12. Anal. calcd. for
C13H12BrN3S: C, 48.46; H, 3.75; N, 13.04; S, 9.95. Found: C, 48.43; H,
3.71; N, 13.07; S, 9.99.
Thiosemicarbazide 3g (X 5 C6H5): 98% yield: white solid; mp 209–2118C.
IR nmax (KBr)/cm21 3290, 3180, 1280, 1220. 1H NMR (CDCl3) d 6.78–7.28
(m, 5H), 7.36–7.67 (m, 5H), 7.59 (d, 2H, J ¼ 8.6 Hz), 7.67 (d, 2H,
J ¼ 8.6 Hz), 8.09 (s, 1H), 9.77 (s, 1H), 9.92 (s, 1H). 13C NMR (CDCl3)
d 113.13, 119.86, 125.22, 125.40, 126.08, 126.40, 127.17, 128.89, 136.35,
138.35, 147.97, 147.99, 181.07. Anal. calcd. for C19H17N3S: C, 71.44; H,
5.36; N, 13.15; S, 10.03. Found: C, 71.43; H, 5.41; N, 13.12; S, 10.10.
Thiosemicarbazide 3h (X 5 t-C4H9): 68% yield: white solid; mp 227–
1
2308C. IR nmax (KBr)/cm21 3300, 3170, 1290, 1210. H NMR (CDCl3)
d 1.36 (s, 9H), 6.76–7.26 (m, 5H), 7.30 (d, 2H, J ¼ 8.7 Hz), 7.45 (d, 2H,
J ¼ 8.7 Hz), 8.05 (s, 1H), 9.65 (s, 1H), 9.73 (s, 1H). 13C NMR (CDCl3)
d 31.10, 34.09, 113.09, 119.80, 124.87, 125.38, 128.84, 136.54, 147.00,
148.04, 181.03. Anal. calcd. for C17H21N3S: C, 68.19; H, 7.07; N, 14.03; S,
10.71. Found: C, 68.23; H, 7.10; N, 14.02; S, 10.78.

Synthesis of Mesoionic by Direct Cyclization
3365
Thiosemicarbazide 3i (X 5 OH): 87% yield: white solid; mp 220–2218C.
IR nmax (KBr)/cm21 3400, 3290, 3180, 1280, 1200. 1H NMR (CDCl3)
d 6.74–7.26 (m, 5H), 7.14 (d, 2H, J ¼ 8.9 Hz), 7.54 (d, 2H, J ¼ 8.9 Hz),
8.06 (s, 1H), 9.74 (s, 1H), 9.90 (s, 1H). 13C NMR (CDCl3) d 112.88,
119.59, 120.40, 126.03, 128.64, 136.82, 147.78, 152.89, 181.05. Anal.
calcd. for C13H13N3OS: C, 60.21; H, 5.05; N, 16.20; S, 12.36. Found: C,
60.19; H, 5.06; N, 16.19; S, 12.41.
Thiosemicarbazide 3j (X 5 n-C4H9): 83% yield: white solid; mp
212–2148C. IR nmax (KBr)/cm21 3300, 3180, 1280, 1220. 1H NMR
(CDCl3) d 0.89 (t, 3H, J ¼ 8.0 Hz), 1.30 (m, 2H), 1.53 (m, 2H), 2.48
(t, 2H, J ¼ 7.6 Hz), 6.75–7.25 (m, 5H), 7.27 (d, 2H, J ¼ 8.6 Hz), 7.43
(d, 2H, J ¼ 8.6 Hz), 8.06 (s, 1H), 9.66 (s, 1H), 9.75 (s, 1H). 13C NMR
(CDCl3) d 21.02, 31.16, 34.05, 35.21, 112.99, 119.99, 124.79, 125.32,
128.75, 136.45, 146.93, 147.96, 180.98. Anal. calcd. for C17H21N3S: C,
68.19; H, 7.07; N, 14.03; S, 10.71. Found: C, 68.22; H, 7.09; N, 14.04;
S, 10.70.
General Procedure for the Preparation of Mesoionic 4-(para-
Substituted-phenyl-5-2,4-dichlorophenyl)-1,3-4-thiadiazolium-2-
aminides-hydrochlorides 1
To a stirred solution of 1,4-diphenyl-thiosemicarbazide 3 (0.01 mol) in anhydrous
1,4-dioxane (8 mL), 2,4-dichloro benzoyl chloride (2.09 g, 0.01 mol) was added
dropwise. Additional stirring and heating under reflux for 2 h generated a crude
yellowish solid product, which was purified by silica column chromatography
(hexane/ethyl acetate 1:1 vol/vol as eluent). After solvent evaporation, the crys-
tallization of the residue generated the pure mesoionic products 1.
Mesoionic hydrochloride 1a (X 5 H): 84% yield: yellowish solid; mp 262–
1
2648C (lit. 264–2658C) IR nmax (KBr)/cm21 2820, 1550, 1370. H NMR
(CDCl3) d 12.79 (s, 1H), 8.41–6.72 (m, 13H). 13C NMR (CDCl3) d 118.96,
121.20, 123.93, 125.40, 128.38, 128.80, 129.64, 131.39, 130.17, 134.02,
134.75, 137.69, 138.16, 139.89, 158.53, 162.03. Anal. calcd. for
C20H14N3Cl3S: C, 51.25; H, 3.25; N, 9.67; S, 7.38. Found: C, 51.18; H,
3.20; N, 9.56; S, 7.29.
Mesoionic hydrochloride 1b (X 5 Me): 81% yield: yellowish solid; mp
1
267–2698C. IR nmax (KBr)/cm21 2830, 2730, 1590, 1540, 1370. H NMR
(CDCl3) d 2.29 (s, 3H), 7.89–7.25 (m, 12H), 12.35 (s, 1H). 13C NMR
(CDCl3) d 20.46, 118.84, 121.56, 125.43, 128.29, 129.78, 129.85, 130.35,
131.42, 132.35, 133.81, 134.98, 135.75, 137.23, 139.69, 159.36, 162.20.
Anal. calcd. for C21H16N3Cl3S: C, 56.20; H, 3.59; N, 9.36; S, 7.14. Found:
C, 56.10; H, 3.51; N, 9.25; S, 7.09.

3366
M. M. Britto et al.
Mesoionic hydrochloride 1c (X 5 OMe): 85% yield: yellowish solid; mp
271–2728C. IR nmax (KBr)/cm21 2840, 1560, 1370. 1H NMR (CDCl3)
d 3.73 (s,3H), 6.99–8.12 (m, 12H), 12.73 (s, 1H). 13C NMR (CDCl3)
d 56.20, 115.55, 121.35, 122.49, 126.20, 129.16, 130.66, 130.78, 132.37,
132.54, 134.58, 135.17, 138.15, 139.49, 156.99, 159.72, 163.59. Anal.
calcd. for C21H16N3OCl3S: C, 54.27; H, 3.47; N, 9.04; S, 6.89. Found: C,
54.13; H, 3.41; N, 8.95; S, 6.80.
Mesoionic hydrochloride 1d (X 5 NO2): 80% yield: yellow solid;
mp . 2958C (decomposition). IR nmax (KBr)/cm21 2830, 1570, 1380.
1H NMR (CDCl3) d 13.74 (s, 1H), 7.30–8.35 (m, 12H). 13C NMR (CDCl3)
d 121.33, 123.47, 124.30, 125.83, 128.51, 129.75, 130.27, 131.63, 134.24,
134.63, 137.88, 139.91, 143.85, 145.75, 159.92, 162.28. Anal. calcd. for
C20H14N4O2Cl3S: C, 49.96; H, 2.94; N, 11.65; S, 6.67. Found: C, 49.83; H,
2.91; N, 11.65; S, 6.59.
Mesoionic hydrochloride 1e (X 5 Cl): 78% yield: yellowish solid; mp
1
269–2718C. IR nmax (KBr)/cm21 2830, 1560, 1380, 1095, 820. H NMR
(CDCl3) d 12.89 (s, 1H), 7.33–7.92 (m, 12H). 13C NMR (CDCl3) d 120.22,
121.81, 125.40, 128.87, 129.44, 129.84, 130.02, 131.22, 133.92, 134.72,
134.79, 137.11, 137.94, 158.97, 161.78. Anal. calcd. for C20H13N3Cl4S: C,
51.20; H, 2.79; N, 8.96; S, 6.83. Found: C, 51.13; H, 2.71; N, 8.84; S, 6.79.
Mesoionic hydrochloride 1f (X 5 Br): 75% yield: yellowish solid; mp 272–
2738C. IR nmax (KBr)/cm21 2820, 1560, 1370, 1080, 775. 1H NMR (CDCl3) d
13.06 (s, 1H), 6.98–7.90 (m, 12H). 13C NMR (CDCl3) d 116.07, 121.17,
121.71, 125.39, 128.81, 129.83, 130.49, 130.75, 132.33, 133.87, 134.58,
137.48, 136.19, 139.62, 158.91, 162.07. Anal. calcd. for C20H13N3BrCl3S:
C, 46.76; H, 2.55; N, 8.18; S, 6.24. Found: C, 46.83; H, 2.51; N, 8.14; S, 6.19.
Mesoionic hydrochloride 1g (X 5 C6H5): 80% yield: yellowish solid; mp
277–2788C. IR nmax (KBr)/cm21 2810, 1560, 1370. 1H NMR (CDCl3)
d 12.72 (s, 1H), 6.95–9.01 (m, 12H), 9.10–9.95 (m, 5H). 13C NMR
(CDCl3) d 119.19, 121.16, 125.53, 126.42, 127.01, 127.35, 128.48, 128.73,
129.76, 130.29, 131.51, 134.16, 134.59, 136.61, 137.52, 137.72, 140.07,
140.24, 158.64, 161.82. Anal. calcd. for C26H18N3Cl3S: C, 61.13; H, 3.55;
N, 8.23; S, 6.28. Found: C, 61.01; H, 3.51; N, 8.78; S, 6.20.
Mesoionic hydrochloride 1h (X 5 t-C4H9): 74% yield: yellowish solid; mp
274–2758C. IR nmax (KBr)/cm21 2820, 1540, 1370. 1H NMR (CDCl3) d 1.27
(s, 9H), 7.43–7.95 (m, 12H), 13.05 (s, 1H). 13C NMR (CDCl3) d 32.38, 34.54,
119.18, 121.09, 125.60, 128.81, 128.93, 129.17, 130.19, 130.72, 134.19,
134.88, 137.22, 137.90, 139.43, 145.25, 158.51, 161.52. Anal. calcd. for
C24H22N3Cl3S: C, 58.72; H, 4.52; N, 8.56; S, 6.53. Found: C, 58.61; H,
4.47; N, 8.48; S, 6.40.

Synthesis of Mesoionic by Direct Cyclization
3367
Mesoionic hydrochloride 1i (X 5 OH): 81% yield: yellowish solid; mp
284–2858C. IR nmax (KBr)/cm21 3380, 2730, 1540, 1370. 1H NMR
(CDCl3) 7.16–8.44 (m, 12H), 12.92 (s, 1H). 13C NMR (CDCl3) d 119.59,
121.05, 121.34, 125.31, 128.32, 129.63, 130.15, 131.40, 133.97, 134.70,
135.84, 137.59, 139.93, 153.37, 158.79, 161.74. Anal. calcd. for
C20H14N3OCl3S: C, 53.29; H, 3.13; N, 9.32; S, 7.11. Found: C, 53.13; H,
3.11; N, 9.25; S, 7.08.
Mesoionic hydrochloride 1j (X 5 C4H9): 81% yield: yellowish solid; mp
278–2808C. IR nmax (KBr)/cm21 2730, 1540, 1370. 1H NMR (CDCl3)
d 0.91 (t, 3H, J ¼ 7.3 Hz), 1.28 (m, 2H), 1.51 (m, 2H), 2.49 (t, 2H,
J ¼ 7.2 Hz), 6.89–8.35 (m, 12H), 12.60 (s, 1H). 13C NMR (CDCl3)
d 13.95, 22.29, 33.52, 35.01, 119.03, 121.31, 125.40, 128.39, 128.67,
129.61, 130.17, 131.34, 134.04, 134.70, 137.75, 137.94, 138.68, 139.84,
158.11, 161.99. Anal. calcd. for C24H22N3Cl3S: C, 58.72; H, 4.52; N, 8.56;
S, 6.53. Found: C, 58.51; H, 4.44; N, 8.46; S, 6.38.
ACKNOWLEDGMENTS
`
The authors thank FAPEMIG (Fundac¸a˜o de Amparo a Pesquisa de Minas
´
Gerais) and CNPq (Conselho Nacional de Desenvolvimento Cientıfico e
´
Tecnologico) for financial support and fellowships.
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