Novel tandem reactions of 2,2′-sulfonylbis(1,3-diarylprop-2-en-1-ones) with hydrazine: Formation of 3,6-diarylpyridazines and 3,5-diarylpyrazoles

Article abstract of DOI:10.1016/S0040-4020(02)00095-9

The 2,2′-sulfonylbis(1,3-diarylprop-2-en-1-ones) undergo tandem reactions with hydrazine affording 3,6-diarylpyridazines and 3,5-diarylpyrazoles unexpectedly, the latter predominating.

Full text of DOI:10.1016/S0040-4020(02)00095-9

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 2227±2230
Novel tandem reactions of
2,20-sulfonylbis(1,3-diarylprop-2-en-1-ones) with hydrazine:
formation of 3,6-diarylpyridazines and 3,5-diarylpyrazoles
M. Gnanadeepam,a S. Selvaraj,b,p S. Perumalb and S. Renugaa
aDepartment of Chemistry, Fatima College, Madurai 625 018, India
bSchool of Chemistry, Madurai Kamaraj University, Madurai 625 021, India
Received 4 October 2001; revised 12 December 2001; accepted 17 January 2002
AbstractÐThe 2,20-sulfonylbis(1,3-diarylprop-2-en-1-ones) undergo tandem reactions with hydrazine affording 3,6-diarylpyridazines and
3,5-diarylpyrazoles unexpectedly, the latter predominating. q 2002 Elsevier Science Ltd. All rights reserved.
We have been interested in the synthesis and/or reactions of
bis(aroylmethyl) sul®des,1 sulfoxides2 and sulfones,3 2,20-
thiobis-4 and 2,20-sulfonylbis- (1,3-diarylprop-2-en-1-
ones)5 in view of their multi-functionalities and synthetic
potential. Our recent studies have disclosed that 2,20-
However, the reaction of 1 with hydrazine hydrate in acetic
acid under re¯ux gave a mixture of 3,6-diarylpyridazines 4
and 3,5-diaryl-1H-pyrazoles 5 (Scheme 2), the latter pre-
dominating (Table 1). Neither 4-amino-2,6-diaroyl-3,5-
diaryltetrahydro-1,4-thiazine-1,1-dioxides 2 nor bis(3,5-
sulfonylbis(1,3-diarylprop-2-en-1-ones)
1
react with
diaryl-4,5-dihydro-1H-pyrazol-4-yl) sulfones 3 arising
respectively out of double aza-Michael addition or cyclo-
condensation of 1 was obtained.
ammonia6 and methylamine3 to give very good yields of
2,6-diaroyl-3,5-diaryltetrahydro-1,4-thiazine-1,1-dioxides
by double aza-Michael addition. In contrast, the reaction of
1 with ethylamine furnished only moderate yields of tetra-
hydro-1,4-thiazine-1,1-dioxides along with bis(aroyl-
methyl) sulfones,7 the latter formed by the cleavage of 1,
probably because of the enhanced steric interaction between
the aryl groups at 3,5-positions and the N-ethyl group in the
thiazine-1,1-dioxides. These results prompted us to
investigate the reaction of 1 with the ambident nucleophile,
hydrazine, which could lead to 4-amino-2,6-diaroyl-3,5-
diaryltetrahydro-1,4-thiazine-1,1-dioxides 2 and/or bis(3,5-
diaryl-4,5-dihydro-1H-pyrazol-4-yl) sulfones 3 (Scheme 1).
A comparison of the mp and the NMR spectra of the
products of the present study with those available in the
literature clearly shows that the products formed are
pyridazines and pyrazoles.8±11 The unexpected formation
of pyridazines 4 in one pot is tentatively explicable by
Scheme 3 via a tandem sequence involving: (i) cleavage
of 1 affording bis(aroylmethyl) sulfones 63,12 triggered by
the aza-Michael addition of hydrazine over both the CvC
bonds sequentially, (ii) condensation of 6 with hydrazine to
3,6-diaryl-2,7-dihydro-1,4,5-thiadiazepine-1,1-dioxides 7,
Scheme 1.
Keywords: pyridazines; pyrazoles; sulfones; hydrazines; mechanisms; NMR.
Corresponding author. Tel.: 191-452-858-246; fax: 191-452-859-139; e-mail: ssselvaraj@rediffmail.com
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00095-9

2228
M. Gnanadeepam et al. / Tetrahedron 58 (2002) 2227±2230
Scheme 2.
(iii) tautomerisation of 7 to 8, (iv) isomerisation of 8 into the
acyclic heterotriene 9, (v) electrocyclic ring closure of 9 to
dihydropyridazines 10 and (vi) elimination of sulfoxylic
acid from 10 affording the heteroaromatics, 3,6-diaryl-
pyridazines 4.
cyclocondensations of 2,20-sulfonylbis(1,3-diarylprop-2-
en-1-ones) 1 with hydrazine. These 3 presumably undergo
eliminations affording two pyrazole molecules 5, whose
aromatic stability providing the required impetus.
It is pertinent to note that in previous studies,8,13 4 were
obtained by the thermal decomposition of either 7 or its
sul®de counterpart 2,7-dihydro-3,6-disubstituted-1,4,5-
thiadiazepines 11 which in turn, were obtained by the
reaction of corresponding bis(aroylmethyl) sulfones or
sul®des with hydrazine. The formation of the 3,6-diaryl-
pyridazines 4 from 11 was explained by reactions similar
to those shown for the transformation of thiadiazepine-1,1-
dioxides 7 into 4 in Scheme 3.8 The formation of 7 via a
mechanism involving cyclization by reaction of hydrazine
at both carbonyl groups followed by a double reverse
Knoevenagel reaction is also possible.
1. Experimental
1.1. Reaction of 2,20-sulfonylbis(1,3-diarylprop-2-en-1-
ones) 1 with hydrazine: a typical procedure
Hydrazine hydrate (8 mL, 99% w/w) was added to a
solution
of
2,20-sulfonylbis(1,3-diphenylprop-2-en-1-
one)14 (4.78 g, 10 mmol) in acetic acid (500 mL). The
mixture was re¯uxed for 2 h and kept aside at room
temperature for 24 h. The mixture was then poured into
ice water. The solid obtained was ®ltered and the products
separated by column chromatography over silica gel using
petroleum ether±chloroform (1:4 v/v) mixture as eluent.
3,6-Diarylpyridazines 4 eluted ®rst followed by 3,5-diaryl-
1H-pyrazoles 5. Both pyridazines and pyrazoles were
crystallized from chloroform±ethanol mixture. The 1H
NMR data of the compounds are in consonance with the
structures. Representative NMR spectroscopic data are
The formation of the major product, pyrazoles 5, occurs
presumably as shown in Scheme 4 via bis(3,5-diaryl-4,5-
dihydro-1H-pyrazol-4-yl) sulfones 3 formed from double
Table 1. Yield and mp of pyridazines 4 and pyrazoles 5
1
given as follows for 4b and 5b. H NMR of 4b (DMSO-
Reactant
Product
Yield (%)
Mp (8C)
Lit. mp (8C)
d6): 8.38 (s, 2H); 8.28 (d, 4H); 7.66 (d, 4H). 1H NMR of 5b
(DMSO-d6): 13.43 (s, 1H); 7.23 (s, 1H); 7.37±7.84 (m, 9H).
1a
1b
1c
1d
1e
4a
5a
4a
5b
4b
5c
4b
5d
4c
5e
26
48
26
51
20
52
23
61
27
53
220±222
198±200
220±222
215±217
268±269
238±240
268±269
223±224
230±231
182±183
222±2238
199±2009
222±2238
214±2159
265±2678
23710
Acknowledgements
265±2678
22811
M. G. and S. R. thank the Correspondent and the Principal,
Fatima College, Madurai 625 018 for providing facilities.
S. P. thanks the CSIR, New Delhi for a Major Research
231±2328
183±1849

M. Gnanadeepam et al. / Tetrahedron 58 (2002) 2227±2230
2229
Scheme 3.
Scheme 4.

2230
M. Gnanadeepam et al. / Tetrahedron 58 (2002) 2227±2230
6. Gnanadeepam, M.; Selvaraj, S.; Perumal, S.; Murugan, R.;
Lycka, A. Indian J. Chem. 1999, 38B, 962.
Project and S. S. and S. P. thank the UGC for funding under
the Special Assistance Programme.
7. Gnanadeepam, M.; Selvaraj, S.; Perumal, S.; Renuga, S.
Phosphorus, Sulfur Silicon 2002 in press.
8. Nakayama, J.; Konishi, T.; Ishu, A.; Hoshino, M. Bull. Chem.
Soc. Jpn 1989, 62, 2608.
References
9. Baddar, F. G.; Al-Hajjar, F. H.; El Rayyes, N. R.
J. Heterocycl. Chem. 1976, 13, 257.
1. Selvaraj, S.; Dhanabalan, A.; Mercy Pushpalatha, A.;
Arumugam, N. Phosphorus, Sulfur Silicon 1991, 63, 295.
2. Selvaraj, S.; Dhanabalan, A.; Arumugam, N. Tetrahedron
Lett. 1991, 32, 7469.
10. Lipp, M.; Ballacker, F.; Mionnes, S. Annalens 1958, 618, 110.
11. Holla, B. S.; Udupa, K. V. Indian J. Chem. 1990, 29B, 887.
12. Gnanadeepam, M.; Selvaraj, S.; Perumal, S.; Renuga, S.
Unpublished results, Madurai Kamaraj University, Madurai.
13. Loudon, J. D.; Young, L. B. J. Chem. Soc. 1963, 5496.
14. Gnanadeepam, M.; Renuga, S.; Selvaraj, S.; Perumal, S.;
Dhanabalan, A.; Hewlins, M. J. E. Phosphorus, Sulfur Silicon,
submitted for publication.
3. Gnanadeepam, M.; Selvaraj, S.; Perumal, S.; Hewlins, M. J. E.;
Lycka, A. Phosphorus, Sulfur Silicon 1999, 155, 167.
4. Selvaraj, S.; Dhanabalan, A.; Arumugam, N. Sulfur Lett. 1993,
15, 233.
5. Renuga, S.; Selvaraj, S.; Perumal, S.; Hewlins, M. J. E.
Tetrahedron 1999, 55, 9309.