Microwaves in organic synthesis: Synthesis of pyridazinones, phthalazinones and pyridopyridazinones from 2‐oxo‐arylhydrazones under microwave irradiation

Abstract

The phenylhydrazones 1a‐d condensed with ethyl cyanoacetate to yield pyridazinones 2a‐d that reacted with sulphur in presence of piperidine to yield the aminothienopyridazineones 3a,b that reacted with electron poor olefins and acetylenes to yield phthalazines 10‐12. The condensed aminothiophenes 3a,b reacted with dimethylformamide dimethylacetal to yield amidines 13a,b. Compounds 2a,b condensed with dimethylformamide dimethylacetal to yield the trans enamines 16a,b that cyclized readily into the pyridopyridazinones 17a,b on treatment with ammonium acetate in presence of acetic acid. Compounds 2a‐d reacted also with benzylidenemalononitrile to yield the phthalazinones 21a‐d. The reactions were conducted both by microwave heating and conventional heating. Better yields in much shorter reaction times were achieved by microwave heating.

Chitosan as an eco-friendly heterogeneous catalyst for Michael type addition reactions. A simple and efficient route to pyridones and phthalazines

“…Additional studies showed that chitosan also catalyzes condensation reactions between benzaldehyde, malononitrile and pyridazinone 26 yielding the pthalazinone 28 (Scheme 7) that was reported [17] earlier to be produced in pyridine assisted reactions of the substrates. We believe that the initial step in this process involves benzaldehyde condensation with malononitrile to yield benzylidene-malononitrile, a reaction that has been reported to occur under mild conditions [18,19].…”

Multicomponent reactions under increased pressure: on the reaction of arylhydrazonals, aromatic aldehydes and malononitrile in Q-Tube

“…We have found that arylhydrazonal derivative (1h) reacts with malononitrile (6) and aromatic aldehyde (7a-e) to yield the pyridazinonaphthyridine derivatives (8a-e) (Scheme 2).…”

“…Although, in a previous article, Moustafa et al [18] reported the formation of pyridazino [5,4,3-de] [1,6]naphthyridine derivatives via reaction of ethyl 3-oxo-2-arylhydrazono butanoate, malononitrile and aromatic aldehydes under high pressure but they could not conclude exact mechanism of the process leading to the formation of the tricyclic system. In our efforts described above the reactions are also conducted in a Q-tube, as in more than one situation, products resulting from initial condensation with malononitrile as the case of compound 1j and 1k and subsequent reaction with arylidene malononitrile have been observed which decisively excluded the initial dimerization of malononitrile.…”

“…These were also obtained via reacting compounds 1a-e, aromatic aldehydes (7) and active methylene nitriles (6). However, subsequent investigations indicated that the reaction product is depending on the nature of aryl substituent in compound 1.…”

“…We have also recently surveyed utility of multicomponent reactions in our area [2]. Since 1997, we investigated extensively utility of microwave to accelerate reaction rates [3][4][5][6]. As we became convinced that microwave techniques is very expensive to scale up and it is just allow reactions to proceed at higher temperature than that of the medium via formation of hot spots thus increasing the rate.…”