Microwave assisted synthesis of 4,6-diarylpyridazin-3(2H)-ones in solid state

Article abstract of DOI:10.1081/SCC-100103250

Microwave assisted synthesis of dihydropyridazin-3(2H)-ones and the subsequent dehydrogenation using selenium dioxide are described.

Full text of DOI:10.1081/SCC-100103250

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MICROWAVE ASSISTED
SYNTHESIS OF 4,6-
DIARYLPYRIDAZIN-3(2H)-ONES
IN SOLID STATE
C. Meenakshi a , V. Ramamoorthy a , S.
Muthusubramanian b & S. Sivasubramanian a
a Department of Organic Chemistry, Madurai
Kamaraj University, Madurai, 625 021, India
b Department of Organic Chemistry, Madurai
Kamaraj University, Madurai, 625 021, India
Published online: 16 Aug 2006.
To cite this article: C. Meenakshi , V. Ramamoorthy , S. Muthusubramanian
& S. Sivasubramanian (2001) MICROWAVE ASSISTED SYNTHESIS OF 4,6-
DIARYLPYRIDAZIN-3(2H)-ONES IN SOLID STATE, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry,
31:5, 645-651, DOI: 10.1081/SCC-100103250
To link to this article: http://dx.doi.org/10.1081/SCC-100103250
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SYNTHETIC COMMUNICATIONS, 31(5), 645–651 (2001)
MICROWAVE ASSISTED SYNTHESIS OF
4,6-DIARYLPYRIDAZIN-3(2H)-ONES IN
SOLID STATE
C. Meenakshi, V. Ramamoorthy, S. Muthusubramanian,*
and S. Sivasubramanian
Department of Organic Chemistry, Madurai Kamaraj
University, Madurai – 625 021, India
ABSTRACT
Microwave assisted synthesis of dihydropyridazin-
3(2H)-ones and the subsequent dehydrogenation using sele-
nium dioxide are described.
Microwave initiated reactions, being an unconventional way of carry-
ing out the reactions – especially in a solvent free condition, are becoming
popular and a number of papers are appearing towards the end of the last
millenium. Several heterocyclic compounds have been synthesized using this
technique.1 Dehydrogenation under microwave conditions is an area where
much work has not been carried out. Reports on the reactions of selenium
dioxide under microwave conditions are also meagre.2 This paper describes
the microwave initiated dehydrogenation of 4,6-diaryl-4,5-dihydropyrida-
zin-3(2H)-ones with selenium dioxide in the solid state.
Many pyridazine derivatives exhibit biological activity and some are
used as drugs.3,4 4,6-Diaryl-4,5-dihydropyridazin-3(2H)-ones have been
synthesized from ꢀ-aroyl-ꢁ-arylpropionic acids obtained either from ꢀ-
aroyl acrylic acids5 or from chalcones.6 They can be easily dehydrogenated
* Corresponding author.
645
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

646
MEENAKSHI ET AL.
to give 4,6-diaryl-3-(2H)-pyridazinones6 by bromination followed by dehy-
drohalogenation or using copper chloride.7 Dehydrogenation using sele-
nium dioxide both under conventional and microwave conditions are
described here. It should be noted that selenium dioxide has been used for
dehydrogenation in some selective compounds of this type.8
Different substituted chalcones 1, prepared by the conventional
method,9 were converted to the ꢂ-ketocyanides 2 either by the addition of
the potassium cyanide in acetic acid10 or of acetone cyanohydrin.11 The ꢂ-
ketocyanides were then converted to the respective methyl esters (3a–f) with
methanol and sulfuric acid. Condensation of hydrazine or phenylhydrazine
with the methyl esters (3) afforded 4,6-diaryl-4,5-dihydropyridazin-3(2H)-
ones. The treatment of these dihydropyridazin-3(2H)-ones with selenium
dioxide in acetic acid effected the dehydrogenation resulting in 4,6-diaryl-
pyridazin-3(2H)-ones (5a–f). The yields, physical constants and the 1H
NMR spectral data of the compounds are presented in Table 1. It should
be mentioned that this sequence of synthesizing 4,6-diarylpyridazin-3(2H)-
ones from chalcones has the ester 3 as the intermediate instead of the cor-
responding acid as reported in a previous work.6 We have used selenium
dioxide in acetic acid medium requiring only 90min in some cases but
require more time in some other cases (Table 1).
To investigate the dehydrogenation ability of selenium dioxide under
microwave conditions, the conversion of 4 to 5 was carried out in a solvent
free solid state in a domestic microwave oven. It is interesting to note that
dehydrogenation takes place effectively with relatively high yields in short
duration under these conditions. The time required, power of microwave
used and the yields obtained are presented in Table 1.
Scheme 1.

4,6-DIARYLPYRIDAZIN-3(2H)-ONES
647
4,6-Diaryl-4,5-dihydropyridazin-3(2H)-ones have also been obtained
within 3 min from the respective acids and hydrazine under microwave
conditions as given in Scheme 2.
Scheme 2.
EXPERIMENTAL
Melting points were uncorrected. The 1H NMR spectra were recorded
on a Perkin-Elmer R32 spectrometer with TMS as the internal standard and
CDCl3 (Compounds 4) or DMSO-d6 (Compounds 5) as the solvent, while
IR spectra were recorded in a Perkin-Elmer 575 instrument by mounting the
samples as KBr discs. Domestic microwave oven (LG, 1300 W, 28L
capacity) was used. Chalcones 1 were prepared by literature method.9
1a, c and f were converted to ꢂ-ketocyanides using potassium cyanide and
acetic acid10 while 1 was converted to 2b, d and e respectively with acetone
cyanohydrin.9 The ꢂ-ketocyanides 2 (0.01 mol) were taken in methanol
(sufficient to dissolve the compound) and sulfuric acid (0.377 g) and refluxed
(the reaction time is indicated in Table 1). The reaction mixture was
cooled well, diluted with water and the solid obtained was filtered, and
crystallized from ethanol to give 3. Compound 4g was obtained from ꢀ-
benzoylpropionic acid by hydrazine addition. The N-phenyl compounds 4h
and 4i were prepared by the reaction of phenylhydrazine with ꢀ-benzoyl-
nzoylpropionic acid and ꢁ-phenyl-ꢀ-benzoyl Propionic acid respectively.
Compounds 2f, 3b, 3c, 3e and 3f show satisfactory C,H,N analysis and
spectral features.
4,6-Diaryl-4,5-dihydropyridazin-3(2H)-ones: Typical Procedure – A
mixture of 0.5 g of ester 3a, (1.8 mmol), 1 ml of hydrazine hydrate (100%)
and 15 ml of diethylene glycol was heated over a steam bath for the period of
time specified in the table. The reaction mixture was poured into crushed ice.
The solid obtained was collected, washed repeatedly with water and dried to
give 4,6-diphenyl-4,5-dihydropyridazin-3(2H)-ones (4a).

648
MEENAKSHI ET AL.

4,6-DIARYLPYRIDAZIN-3(2H)-ONES
649

650
MEENAKSHI ET AL.
Microwave Assisted Preparation of Dihydropyridazine-3(2H)-ones
A mixture of 0.5 g of acid (6) and 1 ml of hydrazine hydrate (100%)
was heated in a microwave oven (540W) for 3 min. The solid 4,6-diaryl/
4-aryl-4,5-dihydropyridazin-3(2H)-ones (7) obtained was collected. The
yields of 7a and 7b were 82% and 80% respectively.
4,6-Diarylpyridazin-3(2H)-ones: Typical Procedure – A mixture of 0.5 g
of 4,6-diphenyl-4,5-dihydropyridazin-3(2H)-ones (4a), (2 mmol), 1 g of sele-
nium dioxide (9 mmol) and 15 ml of acetic acid was heated over a steam bath
for the period of time specified in Table 1. The mixture was filtered to
remove selenium and the filtrate was poured into crushed ice. The solid
4,6-diphenylpyridazin-3(2H)-ones obtained was collected, washed thor-
oughly with water to remove any adhering acetic acid and dried in air to
give 5a.
Microwave Assisted Dehydrogenation of Dihydropyridazin-3(2H)-
ones with Selenium Dioxide
A mixture of 0.5 g of 4,6-dihenyl-4,5-dihydropyridazin-3(2H)-ones
(4a), (2 mmol), 1 g of selenium dioxide (9.0mmol) was ground well in a
mortar and placed in a petri dish. It was placed in the microwave oven
for the period of time specified in Table 1. The progress of the reaction
was monitored by TLC. After the completion of the reaction, the contents
were dissolved in chloroform, boiled well for 10min and the precipitated
selenium was removed by filtration. Evaporation of solvent gave pure solid
4,6-diphenylpyridazin-3(2H)-ones.
ACKNOWLEDGMENTS
S.M. thanks UGC, New Delhi for financial assistance, V.R. thanks
CSIR New Delhi for a SRF and C.M. thanks M.K. University for a
fellowship.
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