Synthesis and characterization of benzenesulfonyl hydrazones and benzenesulfonamides

Article abstract of DOI:10.1080/00397910600941455

In the search for structural cyclic imide analogues of therapeutic interest, the syntheses and characterization of benzenesulfonyl hydrazones and benzenesulfonamides are described. The benzenesulfonyl chlorides (2) and (3) were obtained through the Diels-

Full text of DOI:10.1080/00397910600941455

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Synthesis and Characterization of
Benzenesulfonyl Hydrazones and
Benzenesulfonamides
Kely Navakoski de Oliveira a & Ricardo José Nunes a
a Chemistry Department , Universidade Federal de Santa Catarina ,
Florianópolis, Santa Catarina, Brazil
Published online: 23 Nov 2006.
To cite this article: Kely Navakoski de Oliveira & Ricardo José Nunes (2006) Synthesis and
Characterization of Benzenesulfonyl Hydrazones and Benzenesulfonamides, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:22, 3401-3409, DOI:
10.1080/00397910600941455
To link to this article: http://dx.doi.org/10.1080/00397910600941455
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Synthetic Communicationsw, 36: 3401–3409, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600941455
Synthesis and Characterization of
Benzenesulfonyl Hydrazones and
Benzenesulfonamides
´
Kely Navakoski de Oliveira and Ricardo Jose Nunes
Chemistry Department, Universidade Federal de Santa Catarina,
´
Florianopolis, Santa Catarina, Brazil
Abstract: In the search for structural cyclic imide analogues of therapeutic interest, the
syntheses and characterization of benzenesulfonyl hydrazones and benzenesulfonamides
are described. The benzenesulfonyl chlorides (2) and (3) were obtained through the
Diels–Alder reaction between N-p-chloro-sulfonylfenylmaleimide (1) and furan or
2-methylfuran. The reactions of (2) and (3) with hydrazine and amines afforded the
hydrazides and sulfonamides, respectively. The sulfonylhydrazones were obtained
through a condensation between the sulfonylhydrazides with different benzaldehydes.
Keywords: Benzenesulfonyl chlorides, Diels–Alder reaction, sulfonamides,
sulfonylhydrazones
INTRODUCTION
Sulfonylhydrazones and sulfonamides have been shown to be active in several
pharmacological tests, demonstrating antibacterial, antitumor, diuretic,
antiviral, and antinociceptive activity.[1–5]
This study aims to synthesize and characterize benzenesulfonamides (4–
8) and benzenesulfonylhydrazones (11–20). The sulfonylchloride (1) was
obtained as previously described.[6] The chlorides (2) and (3) were prepared
through a Diels–Alder reaction of (1) with furan or 2-methylfuran. The sulfo-
namides (4–8) and the sulfonylhydrazides (9) and (10) were obtained from (2)
or (3) with pyrrolidine or morpholine and hydrazine hydrate. The hydrazides
Received in the USA April 19, 2006
Address correspondence to Ricardo Jose Nunes, Chemistry Department,
´
´
Universidade Federal de Santa Catarina, Florianopolis, Santa Catarina, Brazil.
E-mail: nunes@qmc.ufsc.br
3401

3402
K. N. de Oliveira and R. J. Nunes
(9) and (10) were characterized by the condesation with benzaldehydes to
yield the sulfonylhydrazones (11–20) (Scheme 1).
1
The structures were confirmed through H NMR and 13C NMR spectro-
scopic analysis and CNH elemental analysis.
Under the experimental conditions only the exo-isomers were isolated.
The formation of exo-isomers was detected, initially, by thin-layer
1
chromatography (TLC) and later confirmed through H NMR, 13C NMR,
and elementary CHN analysis.
The 1H NMR spectrum, in two dimensions spectroscopy (COSY), of the
exo-isomers shows a sharp singlet for the H6a,10a hydrogens with no coupling
with H2,5 hydrogens because the dihedral angle between them is approxi-
mately 908.[7] This is in contrast with the four-line pattern observed for the
exo-protons of the endo-isomers.[8,9]
EXPERIMENTAL
1
All compounds were characterized by H NMR, 13C NMR, IR, and micro-
analysis. The purity of these compounds was determined by TLC. Infrared
Scheme 1.

Synthesis and Characterization of Benzenesulfonyl Hydrazones
3403
spectra were obtained with a Perkin Elmer 16PC spectrophotometer
(Perkin Elmer, Wellesley, MA, USA). 1H NMR and 13C NMR spectra
were recorded with
a Bruker AC-200F spectrometer (Rheinstetten,
Germany) (at 200 MHz and 50 MHz, respectively). CDCl3 and DMSO were
used as solvents with tetramethylsilane (TMS) as the internal standard;
chemical shifts (d) are reported in parts per million. For the CHN analysis,
a Perkin Elmer 2400 CHN elemental analyser (Boston, MA, USA) was
used. In the TLC, aluminium sheets with 60 F-254 silica gel (0.2 mm thick)
were utilized.
General Experimental Procedure
4-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzenesulfonyl Chloride (1)
Chloride 1 was obtained as described in the literature.[6] Yield: 84%. Mp
138.5–139.4 8C (lit.[6] mp 138–1398C). IR (KBr)nMax: 1780, 1718 (C55O),
1374, 1186 (–SO2), 838 (arom.).
4-[(2R,6S)-3,5-Dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]
benzenesulfonyl Chloride (2)
Chloride 2 was obtained as described in the literature.[6] Yield: 88%. Mp
136.5–137.4 8C (lit.[10] Mp 137–1398C). IR (KBr)nMax: 1782, 1720
(C55O), 1363, 1166 (–SO2), 870 (arom.).
4-[(2R,6S)-1-Methyl-3,5-dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]dec-8-
en-4-yl]benzenesulfonyl Chloride (3)
Chloride 3 was obtained as described in the literature.[10] Yield: 79%. Mp
113.9–115.3 8C (lit.[10] mp 115–1178C). IR (KBr)nMax: 1779, 1704
(C55O), 1373, 1181 (–SO2), 839 (arom.).
(2R,6S)-4-[4-(Pyrrolidin-1-ylsulfonyl)phenyl]-10-oxa-4-
azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione (4)
Pyrrolidine (0.63 mL, 8.82 mmol) was added dropwise to a mixture of 4-(3,5-
dioxo-10-oxa-4-azatricyclo[5.2.1.02,6] dec-8-en-4-yl)benzenesulfonyl chloride
(2) (1.50 g, 4.42 mmol) in methanol (10 mL) in an ice bath. The formed solid
was filtered off with suction. The product was crystallized from ethanol–ethyl
acetate (2:1). Yield: 47%. Mp 144.1–144.58C. Anal. calcd. for C18H18N2O5
S: C, 57.74; H, 4.85; N, 7.48; S, 8.56. Found: C, 56.20; H, 4.90; N, 7.34; S,
8.46. 1H NMR d ppm, DMSO-d6: ArH (2d: 7.97 and 7.50, J ¼ 7.4 Hz);
-CH55CH- (s: 6.62); -CH-O-CH- (s: 5.27); -CH2-N-CH2- and H6a and H10a (m:
3.13); -(CH2)2- (m: 1.70). 13C NMR d ppm, DMSO-d6: CH2-CH2-CH2-N

3404
K. N. de Oliveira and R. J. Nunes
(24.80); CH2-N-CH2- (47.69); (CH-C55O)2 (47.91); CH-O-CH- (80.96); C
Ar (127.44; 128.19); -CH55CH- and -HC-SO2 Ar (135.76); -CH-N-Ar
(136.73); C55O (175.44). Using this procedure, the following sulfonamides
were prepared.
(2R,6S)-4-[4-(Morpholin-4-ylsulfonyl)phenyl]-10-oxa-4-
azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione (5)
Yield: 26%. Mp 139.5–140.28C. Anal. calcd. for C18H18N2O6S: C, 55.38; H,
1
4.65; N, 7.18; S, 8.21. Found: C, 55.16; H, 4. 67; N, 7.08; S, 8.07. H NMR
d ppm, DMSO-d6: ArH (2d: 7.91 and 7.55, J ¼ 6.9 Hz); -CH55CH- (s: 6.62);
-CH-O-CH- (s: 5.28); -CH2-O-CH2- (s broad: 3.64); (-CH-C55O)2; H6a and
H10a (s: 3.14); -CH2-N-CH2- (s, broad: 2.90). 13C NMR d ppm, DMSO-d6:
CH2-N-CH2- (46.57); (CH-C55O)2 (48.81); CH2-O-CH2- (65.64); CH-O-
CH- (81.19); C Ar (129.05; 129.39); -CH55CH- (134.79); -HC-SO2 Ar
(136.79); -CH-N-Ar (137.68); C55O (176.02).
N,N-Dimethyl-4-[(2R,6S)-1-methyl-3,5-dioxo-10-oxa-4-
azatricyclo[5.2.1.02,6]dec-8-en-4-yl]benzenesulfonamide (6)
Yield: 40%. Mp 124.8–125.7 8C. Anal. calcd. for C17H18N2O5S: C, 56.34; H,
5.01; N, 7.73; S, 8.85. Found: C, 55.93; H, 5.05; N, 7.67; S, 8.77. 1H NMR d
ppm, DMSO-d6: ArH (2d: 7.92 and 7.53, J ¼ 7.1 Hz); -CH55CH- (2d: 6.63
and 6.44, J ¼ 5.7 Hz); -CH-O- (s: 5.16); H6a and H10a (d: 3.27–2.97,
J ¼ 6.4 Hz); CH3-N-CH3 (s: 2.57); -CH3- (s: 1.65). 13C NMR d ppm,
DMSO-d6: CH3 (15.57); CH3-N-CH3 (34.36); CH-10 (49.64); CH-6
(50.82); CH-O (80.59); C-O (88.01); C Ar (126.19; 127.44); -CH-CH55CH-
(134.94); -C-CH55CH (135.87); -HC-SO2 Ar (137.07); -CH-N-Ar (140.47);
C55O-7 (173.96); C55O-9 (175.29).
(2R,6S)-1-Methyl-4-[4-(pyrrolidin-1-ylsulfonyl)phenyl]-10-oxa-4-
azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione (7)
Yield: 40%. Mp 1398C. Anal. calcd. for C19H20N2O5S: C, 58.75; H, 5.19; N,
1
7.21; S, 8.26. Found: C, 58.17; H, 5.23; N, 7.20; S, 8.13. H NMR d ppm,
DMSO-d6: ArH (2d: 7.96 and 7.51, J ¼ 7.4 Hz); -CH55CH- (2d: 6.62 and
6.44, J ¼ 5.9 Hz); -CH-O- (s: 5.16); H6a and -CH2-N-CH2- (m: 3.26–3.18);
H10a (d: 2.99 and 2.96, J ¼ 6.7 Hz); -CH3 and -(CH2)2- (s broad: 1.66). 13C
NMR d ppm, DMSO-d6: CH3 (15.61); NCH2CH2-CH2 (24.80); CH2-N-
CH2- (47.91); CH-10 (49.68); CH-6 (50.87); CH-O (80.06); C-O (80.64); C
Ar (127.49; 128.18); C3 (135.81); C4 (135.95); -HC-SO2 Ar (137.12); -CH-
N-Ar (140.52), C55O-7 (174.05); C55O-9 (175.37).

Synthesis and Characterization of Benzenesulfonyl Hydrazones
3405
(2R,6S)-1-Methyl-4-[4-(morpholin-4-ylsulfonyl)phenyl]-10-oxa-4-
azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione (8)
Yield: 62%. Mp 138.1–139.38C. Anal. calcd. for C19H20N2O6S: C, 56.42; H,
4.98; N, 6.93; S, 7.93. Found: C, 55.92; H, 5.04; N, 6.80; S, 7.73. 1H NMR d
ppm, DMSO-d6: ArH (2d: 7.87 and 7.55; J ¼ 7.4 Hz); -CH55CH- (2d: 6.61
and 6.38; J ¼ 5.9 Hz); -CH-O- (s: 5.33); -CH2-O-CH2- (t: 3.79–3.73,
J ¼ 3.7 Hz); H6a (d: 3.19 and 3.16; J ¼ 7.4 Hz); -CH2-N-CH2- (m: 3.06–
3.01); H10a (d: 2.93 and 2.90; J ¼ 7.4 Hz); -CH3 (s: 1.80). 13C NMR d ppm,
DMSO-d6: CH3 (15.66); CH2-N-CH2 (45.84); CH-10 (49.55); CH-6
(50.66); CH2-O-CH2 (65.97); -C-O- (81.19); CH-O- (88.73); C Ar (126.80;
128.49); C3 (134.88); C4 (135.82); -HC-SO2 Ar (137.06); -CH-N-Ar
(140.71); C55O-7 (173.34); C55O-9 (175.61).
4-[(2R,6S)-3,5-Dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]
benzenesulfonohydrazide (9)
Compound 9 was obtained as previously described in the literature.[11] Yield:
63%. Mp 210.5–213.88C. IR (KBr)nMax: 3370 (-NH2), 3294 (n-NH), 1780,
1718 (C55O), 1375, 1166 (-SO2), 1201 (-C-N-), 850 (arom.).
4-[(2R,6S)-1-Methyl-3,5-dioxo-10-oxa-4-azatricyclo[5.2.1.02,6
dec-8-en-4-yl]benzenesulfonohydrazide (10)
]
Compound 10 was obtained as previously described in the literature.[11] Yield:
69%. Mp 141.1–143.08C. IR (KBr)nMax: 3383 (-NH2), 3192 (-NH), 1777,
1708 (C55O), 1387, 1193 (-SO2), 1173(-C-N-), 837 (arom.).
4-[(2R,6S)-3,5-Dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-
N0-[(1E)-(4-methoxyfenyl)methylene]benzenesulfonohydrazide (11)
4-Methoxybenzaldehyde (0.23 g, 1.64 mmol) was added to a mixture of
4-(3,5-dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl)benzenesulfono-
hydrazide (4) (0.50 g, 1.49 mmol) in ethanol (10 mL), along with a drop of
hydrochloric acid as the catalyst. The reaction was left under stirring at
room temperature for 1 h. The solid formed was filtered off with suction.
The product was crystallized from ethanol–ethyl acetate (2:1). Yield: 72%.
Mp 155.2–155.58C. Anal. calcd. for C22H19N3O6S: C, 58.27; H, 4.22; N,
1
9.27; S, 7.07. Found: C, 58.19; H, 4.30; N, 9.10; S, 6.94. H NMR d ppm,
DMSO-d6: -NH-N55 (s: 11.44); ArH (2d: 7.97 and 7.50 J ¼ 9.0 Hz);
-N55CH-Ph (s: 7.82); ArH (2d: 7.47 and 6.97 J ¼ 9.0 Hz); -CH55CH-
(s: 6.60); -CH-O-CH- (s: 5.25); -OCH3 (s: 3.77); H6a and H10a (s: 3.18). 13C
NMR d ppm, DMSO-d6: OCH3 (47.64); CH-6 and 10 (55.28); CH-O-CH
(80.87); C Ar (114.29; 126.13; 127.34; 128.15; 135.72); -CH55CH-
(128.51); -HC-SO2 Ar (136.66); -CH-N-Ar (138.59); CH-O-Ar

3406
K. N. de Oliveira and R. J. Nunes
(147.77); -N55C- (160.89); C55O (175.33). Using this procedure the
following sulfonylhydrazides were prepared.
4-[(2R,6S)-3,5-Dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-
N0;-[(1E)-(4-nitrophenyl)methylene]benzenesulfonohydrazide (12)
Yield: 69%. Mp .2708C. Anal. calcd. for C21H16N4O7S: C, 53.84; H, 3.44; N,
11.96; S, 6.85. Found: C, 53.16; H, 3.48; N, 11.74; S, 6.71. 1H NMR d ppm,
DMSO-d6: -NH-N55 (s: 12.11); ArH (2d: 8.26–8.02; J ¼ 10.0 Hz); -N55CH-
Ph (s: 8.06); ArH (2d: 7.88 and 7.50; J ¼ 10.0 Hz); -CH55CH- (s: 6.60); -CH-
O-CH- (s: 5.25); H6a and H10a (s: 3.11). 13C NMR d ppm, DMSO-d6: CH-6
and 10 (55.28); CH-O-CH (80.87); C Ar (124.03; 127.48; 127.62; 128.10;
136.64); -CH55CH- (135.94); -HC-SO2 (138.36); -CH-NO2 (139.66); N-CH
Ar (145.06); -N55C- (147.92); C55O (175.31).
4-[(2R,6S)-3,5-Dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-
N0-[(1E)-(4-hydroxyphenyl)methylene]benzenesulfonohydrazide (13)
Yield: 79%. Mp 141.0–143.78C. Anal. calcd. for C21H17N3O6S: C, 57.40; H,
3.90; N, 9.56; S, 7.30. Found: C, 57.34; H, 3.93; N, 9.50; S, 7.22. 1H NMR d
ppm, DMSO-d6: -NH-N55 (s: 11.32); -OH (s broad: 9.92); ArH (2d: 8.02 and
7.48, J ¼ 9.1 Hz); -N55CH- (s: 7.84); ArH (2d: 7.43 and 6.75, J ¼ 9.1 Hz);
-CH55CH- (s: 6.60); -CH-O-CH- (s: 5.24); H6a and H10a (s: 3.11). 13C NMR
d ppm, DMSO-d6: CH-6 and 10 (48.77); CH-O-CH (81.23); C Ar (116.98;
125.25; 127.48; 128.55; 128.95); -CH55CH- (128.71); -HC-SO2 Ar (136.37);
-CH-N-Ar (139.33); CH-OH Ar (149.70); -N55C- (160.09); C55O (176.03).
4-[(2R,6S)-3,5-Dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-
N0-[(1E)-phenylmethylene]benzenesulfonohydrazide (14)
Yield: 48%. Mp 142.6–143.48C. Anal. calcd. for C22H19N3O5S: C, 60.40; H,
4.38; N, 9.61; S, 7.33. Found: C, 60.16; H, 4.44; N, 9.47; S, 7.24. 1H NMR d
ppm, DMSO-d6: -NH-N55 (s: 11.64); ArH and -N55CH-Ph (m: 8.04–7.40);
-CH55CH- (2d: 6.61 and 6.42, J ¼ 6.7 Hz); -CH-O- (s: 5.13); H6a and H10a
(2d: 3.24 and 2.94, J ¼ 4.8 Hz); -CH3 (s: 1.62). 13C NMR d ppm, DMSO-
d6: CH3 (15.54); CH-10 (49.67); CH-6 (50.81); C-O (80.54); CH-O (87.98);
C
Ar (126.86; 127.42; 128.09; 128.12; 130.21; 134.91); HC-SO2
Ar(135.83); C3 (138.50); C4 (140.46); -CH-N-Ar (147.67); -C55N-
(169.38); C55O-7 (173.90); C55O-9 (175.25).
4-[(2R,6S)-3,5-Dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-
N0-[(1E)-(4-methylphenyl)methylene]benzenesulfonohydrazide (15)
Yield: 76%. Mp 134.8–135.38C. Anal. calcd. for C23H21N3O5S: C, 61.18; H,
4.69; N, 9.31; S, 7.10. Found: C, 60.83; H, 4.78; N, 9.12; S, 7.06. 1H NMR d

Synthesis and Characterization of Benzenesulfonyl Hydrazones
3407
ppm, DMSO-d6: -NH-N55 (s: 11.54), ArH (2d: 8.03–7.49, J ¼ 10.0 Hz);
-N55CH-Ph (s: 7.92); ArH (2d: 7.46–7.19, J ¼ 9.0 Hz); -CH55CH- (2d:
6.60 and 6.42, J ¼ 6.0 Hz), -CH-O- (s: 5.13), H6a and H10a (2d: 3.24 and
2.94, J ¼ 8.00 Hz), -CH3-Ph (s: 1.92); -CH3 (s: 1.62). 13C NMR d ppm,
DMSO-d6: CH3-CH-O (15.55); CH3 –CH Ar (21.02); CH-10 (49.63); CH-6
(50.82); C-O (80.55); CH-O (87.99); C Ar (126.56; 128.10; 129.40; 130.21;
134.91; 138.53); HC-SO2 Ar (135.83); C3 (140.08); C4 (140.46); -CH-N-Ar
(147.81); -C55N- (172.04); C55O-7 (173.91); C55O-9 (175.26).
1-Methyl-4-[(2R,6S)-3,5-dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]dec-8-
en-4-yl]-N0-[(1E)-(4-methoxyphenyl)methylene]
benzenesulfonohydrazide (16)
Yield: 84%. Mp 136.4–137.48C. Anal. calcd. for C23H21N3O6S: C, 59.09; H,
4.53; N, 8.99; S, 6.86. Found: C, 58.75; H, 4.60; N, 8.87; S, 6.74. 1H NMR d
ppm, DMSO-d6: -NH-N55 (s: 11.44); ArH (2d: 8.02 and 7.51, J ¼ 9.1 Hz);
-N55CH-Ph (s: 7.89); ArH (2d: 7.48 and 6.93, J ¼ 9.1 Hz); -CH55CH- (2d:
6.58 and 6.42, J ¼ 4.5 Hz); -CH-O- (s: 5.13); -OCH3 (s: 3.77); H6a (d: 3.24
and 3.21, J ¼ 7.3 Hz); H10a (d: 2.97 and 2.94, J ¼ 7.3 Hz); -CH3 (s: 1.62).
13C NMR d ppm, DMSO-d6: CH3- (16.52); O-CH3 (50.68); CH-6 and 10
(50.70); C-O (80.71); CH-O (81.77); C Ar (115.69; 127.54; 128.59; 128.70;
136.46); C3 (128.92); C4 (129.70); HC-SO2 Ar (138.04); -CH-N- Ar
(139.26); Ar-CH-O-CH3 (148.30); -C55N- (161.58); C55O-7 (174.60);
C55O-9 (175.95).
1-Methyl-4-[(2R,6S)-3,5-dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]dec-8-en-
4-yl]-N0-[(1E)-(4-nitrophenyl)methylene]benzenesulfonohydrazide (17)
Yield: 84%. Mp 130.9–131.68C. Anal. calcd. for C22H18N4O7S: C, 54.77; H,
3.76; N, 11.61; S, 6.65. Found: C, 54.52; H, 3.83; N, 11.43; S, 6.54. 1H NMR d
ppm, DMSO-d6: -NH-N55 (s: 12.18); ArH (2d: 8.25 and 8.02, J ¼ 7.9 Hz);
-N55CH-Ph (s: 8.02); ArH (2d: 7.87 and 7.51, J ¼ 8.9 Hz); -CH55CH- (2d:
6.57 and 6.42, J ¼ 3.0 Hz); -CH-O- (s: 5.14); H6a (d: 3.23–3.20,
J ¼ 5.9 Hz); H10a (d: 2.92–2.89, J ¼ 5.9 Hz); -CH3 (s: 1.63). 13C NMR d
ppm, DMSO-d6: CH3- (15.70); CH-6 and 10 (51.54); C-O (80.57); CH-O
(80.96); C Ar (124.81; 128.35; 128.67; 128.77, 128.88); C3 (136.78); C4
(139.02); -CH-SO2 Ar (137.16); -CH-NO2 Ar (140.37); -CH-N-Ar (145.96);
-C55N- (148.22); C55O-7 (174.10); C55O-9 (176.11).
1-Methyl-4-[(2R,6S)-3,5-dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]dec-8-
en-4-yl]-N0-[(1E)-(4-hydroxyphenyl)methylene]
benzenesulfonohydrazide (18)
Yield: 68%. Dec. 1858C. Anal. calcd. for C22H19N3O6S: C, 58.27; H, 4.22; N,
9.27; S, 7.07. Found: C, 57.97; H, 4.29; N, 9.08; S, 6.96. H NMR d ppm,
1

3408
K. N. de Oliveira and R. J. Nunes
DMSO-d6: -NH-N55 (s: 13.33); ArH (2d: 8.02 and 7.53; J ¼ 9.1 Hz);
-N55CH-Ph (s: 7.84); -OH (s broad: 7.63); ArH (d: 7.48 and 6.75;
J ¼ 9.1 Hz); -CH55CH- (d: 6.61–6.42, J ¼ 5.4 Hz); -CH-O- (s: 5.14); H6a
and H10a (2d: 3.21–2.93, J ¼ 7.3 Hz); -CH3 (s: 1.62); 13C NMR d ppm,
DMSO-d6: CH3- (15.80); CH-6 and 10 (51.85); C-O (80.70); CH-O (81.70);
C Ar (116.98; 125.24; 127.52; 128.57; 128.90); -CH-CH55CH- (128.80);
-C-CH55CH- (129.81); -CH-SO2 Ar (136.39); -CH-N-Ar (139.25); -CH-
OH-Ar (149.13); -C55N- (160.10); C55O-7 (174.63); C55O-9 (175.99).
1-Methyl-4-[(2R,6S)-3,5-dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]dec-8-
en-4-yl]-N0-[(1E)-(4-chlorophenyl)methylene]
benzenesulfonohydrazide (19)
Yield: 63%. Mp 131.4–132.28C. Anal. calcd. for C22H18Cl N3O5S: C, 55.99;
H, 3.84; Cl, 7.51; N, 8.90; S, 6.79. Found: C, 55.71; H, 3.89; N, 8.74; S, 6.67.
1H NMR d ppm, DMSO-d6: -NH-N55 (s: 11.75); -N55CH-Ph (s: 8.73); ArH
(m: 8.03 and 7.90); -ArH (m: 7.61 and 6.48); -CH55CH- (d: 6.61–6.49,
J ¼ 5.5 Hz); -CH-O- (s: 5.14); H6a and H10a (2d: 3.23–2.96, J ¼ 7.5 Hz);
-CH3 (s: 1.63). 13C NMR d ppm, DMSO-d6: CH3- (16.18); CH-6 and 10
(51.89); C-O (80.55); CH-O (81.59); C Ar (127.60; 128.87; 129.36; 129.64;
130.54); -CH-Cl Ar (135.35); C3 (136.54); C4 (139.12); -CH-SO2 Ar
(141.32); -CH-N-Ar (146.91); -C55N- (147.18); C55O-7 (174.60); C55O-9
(175.94).
1-Methyl-4-[(2R,6S)-3,5-dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]dec-8-
en-4-yl]-N0-[(1E)-(3,4-dichlorophenyl)methylene]
benzenesulfonohydrazide (20)
Yield: 81%. Mp 127.5–128.08C. Anal. calcd. for C22H17Cl2N3O5 S: C, 52.18;
H, 3.38; Cl, 14.00; N, 8.30; S, 6.33. Found: C, 51.84; H, 3.44; N, 8.14; S, 6.29.
1H NMR d ppm, DMSO-d6: -NH-N55 (s: 11.91); ArH (m: 8.04 and 7.95);
-N55CH-Ph (s: 7.44); ArH (m: 7.82 and 7.52); -CH55CH- (d: 6.61–6.44,
J ¼ 5.4 Hz); -CH-O- (s: 5.14); H6a and H10a (2d: 3.24–2.96, J ¼ 7.4 Hz);
-CH3 (s: 1.63). 13C NMR d ppm, DMSO-d6: CH3- (16.25); CH-6 and 10
(51.85); C-O (80.55); CH-O (81.70); C Ar (127.68; 128.88; 131.33;
132.37); -CH-m-Cl Ar (133.15); -CH-p-Cl Ar (134.65); C3 (134.99); C4
(138.61); -CH-SO2 Ar (139.07); -CH-N- Ar (145.52); -C55N- (145.81);
C55O-7 (174.62); C55O-9 (175.96).
ACKNOWLEDGMENTS
The authors are grateful to CNPq for financial support of this work.

Synthesis and Characterization of Benzenesulfonyl Hydrazones
REFERENCES
3409
1. Rollas, S.; Gulerman, N.; Erdeniz, H. Synthesis and antimicrobial activity of some
new hydrazones of 4-fluorobenzoic acid hydrazide and 3-acetyl-2,5-disubstituted-
1,3,4-oxadiazolines. Farmaco 2002, 57 (2), 171–174.
2. Ozawa, Y.; Sugi, N. H.; Nagasu, T.; Owa, T.; Watanabe, T.; Koyanagi, N.;
Yoshino, H.; Kitoh, K.; Yoshimatsu, K. E7070, a novel sulfonamide agent with
potent antitumour activity in vitro and in vivo. Eur. J. Cancer 2001, 37,
2275–2282.
3. Betz, U. A. K.; Fischer, R.; Kleymann, G.; Hendrix, M.; Ru¨bsamen-Waigmann, H.
Potent in vivo antiviral activity of the herpes simplex virus primase-helicase
inhibitor BAY 57-1293. Antimicrob. Agents Chemother. 2002, 46, 1766–1772.
´
4. Bhattacharya, G.; Herman, J.; Delfın, D.; Salem, M. M.; Barszcz, T.; Mollet, M.;
Riccio, G.; Brun, R.; Werbovetz, K. A. Synthesis and antitubulin activity of N1-
and N4-substituted 3,5-dinitro sulfanilamides against African trypanosomes and
leishmania. J. Med. Chem. 2004, 47, 1823–1832.
5. Lima, L. M.; Amarante, E. G.; Miranda, A. L. P.; Fraga, C. A. M.; Barreiro, E. J.
Syntheses and antinociceptive profile of novel acidic sulphonylhydrazone deriva-
tives from natural safrole. Pharm. Pharmacol. Commun. 1999, 5, 673–678.
6. Kremlev, M. M.; Kul’chitskaya, M. E.; Biba, A. D.; Romanenko, V. D. Synthesis
of derivatives of N-(sulfamoylaryl)maleinimides. Ukr. Khim Zh. 1971, 37 (9),
924–927; Chem. Abstr. 1972, 77, 19296n.
7. Andrade, E. S.; Nunes, R. J.; Uieara, M. Synthesis and characterization of exo-
endo and endo-endo benzenesulfonylaziridine. Synth. Commun. 2004, 34,
3073–3081.
8. Baldwin, J. E.; Pinschmidt, R. K.; Andrist, A. H. Bicyclo[2.1.0]pent-2-ene: Tests
for the retro-ene mechanism of thermal isomerization. J. Am. Chem. Soc. 1970,
92 (17), 5249–5250.
9. Chang, A. C.; Young, P. R. Characterization of geometric isomers of norbornene
end-capped imides. J. Heterocycl. Chem. 1983, 20 (1), 177–182.
10. Lopez, S. N.; Sortino, M.; Escalante, A.; de Campos, F.; Correa, R.; Cechinel
Filho, V.; Nunes, R. J.; Zacchino, S. A. Antifungal properties of novel N- and
a,b-substituted succinimides against dermatophytes. Arzneimittel-Forschung
2003, 53 (4), 280–288.
11. Cremlyn, R.; Swinbourne, F.; Nunes, R. Diels–Alder reactions using N-[p-(chlor-
osulfonyl)phenyl]maleimide as dienophile. Phosphorus, Sulfur Rela. Elem. 1987,
33 (1–2), 65–75.