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Pyridazine Derivatives and Related Compounds, Part 15: Photochemical Study of 3-Azido-4,5-Diphenyl-1H-Pyrazolo[3,4-C]Pyridazine

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Pyridazine Derivatives and Related Compounds, Part 15: Photochemical Study of 3-Azido-4,5-Diphenyl-1H-Pyrazolo[3,4-C]Pyridazine id2552765 pdfMachine by Broadgun Software - a great PDF writer! - a great PDF creator! - http://www.pdfmachine.com http://www.broadgun.com OOrrggaanniicc ISSN: 0974 - 7516 Volume 10 Issue 3 CCHHEEMMAn IIInSSdiTTan RRJouYrYnal Full Paper OCAIJ, 10(3), 2014 [83-89] Pyridazine derivatives and related compounds, Part 15: Photochemical study of 3-azido-4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazine Ali Deeb1*, Mohamed F.Zayed2, Atef M.Amer1, Ahmed A.El-Sayed2 1Chemistry Department, Faculty of Science, Zagazig University, Zagazig, (EGYPT). 2Photochemistry Department, National research Centre, Dokki, Giza, (EGYPT) E-mail: [email protected] ABSTRACT KEYWORDS As an extension of our work in the photochemical study of nitrogen Azides; heterocyclic compounds such as 3-diazopyrazolopyridazine derivatives and Pyridazines; [2+2] photocycloaddtion, in this paper we will studying the photolysis of 3- Pyrazoles; azidopyrazolopyridazine derivative in different solvents such as Methanol, …..etc. and reagent as diethyl malonate. The Pyrazolopyridazines; Ethanol, Toluene, Benzene, 3-Azidopyrazolopyridazine; photochemistry of 3-azidopyrazolopyridazine has been investigated. The Photolysis of azidopyrazoles. irradiation of 3-azido-4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazine I in various solvents brings to a photolytic nitrene intermediate, which involve into a ring- opening to give 3-substituted pyridazine derivatives. While the photolysis in toluene and/or anisole the photo attacks reaction of nitrene is faster than the ring opining to give the corresponding 3- anilinopyrazolopyridazine derivatives. The photolysis in the presence of diethyl malonate led to a mixture of three pyridazine derivatives. 2014 Trade Science Inc. - INDIA INTRODUCTION have been used for photo affinity labeling bio-organic molecules and in several industrial processes such as Recently, it has been reported that some pyridazine microlithography[11]. Photolysis of azides in methanol, derivatives display antihypertensive, anticancer, and anti- which have a built-in intramolecular triplet sensitizer, HIV activities[3-6]. In addition, it is well documented that yields mainly carbamates Laser flash-photolysis of azide substituted pyridazines possess antimicrobial, antifun- derivatives shows formation of their triplet-excited ke- gal, and antiviral activities[7-9]. From this view of high tone, which decays by intramolecular energy transfer biological activity of pyridazine the photochemistry to form triplet nitrenes[12]. In contrast, Lwowski and studying of it will be interest. Photolysis of aryl and coworkers demonstrated that photolysis of carbonazidic heteroaryl azides is well documented[10] to give rise to acid methyl ester in matrices yields methoxy isocyan- varied group of products, whose identity is influenced ate, which reacts further to produce isocyanic acid[13]. by many factors such as reaction medium, substituents, It was concluded that the excited state of carbonazidic etc. The formation of aryl nitrenes from aryl azides has acid methyl ester, rather than the singlet carbomethoxy been studied extensively for the last several decades. nitrene, undergoes a Curtius rearrangement to form the Since aryl nitrenes undergo bimolecular reactions they methoxy isocyanate. Similarly, Teles and Maier have 84 Pyridazine derivatives and related compounds, part 15: photochemical study OCAIJ, 10(3) 2014 Full Paper also shown that photolyzing carbonazidic acid methyl c]pyridazine[19] in conc. HCl at room temperature. The ester in matrices yields mainly methoxy isocyanate and processes are quick and are readily carried out in a a small amount of diazenedicarboxylic acid dimethyl beaker or open flask. The reaction progress was com- ester, formaldehyde and isocyanic acid[14]. pleted until no diazo compound could be detected by Rodney and coworkers were the first observation TLC as well as no coupling color with -naphthol. the intermolecular triplet sensitization of alkyl azides leads (Equation 1) to bimolecular reactivity, by forming triplet alkyl nitrenes. Ph Ph The intermolecular triplet-sensitized photolysis of 1- Ph N Ph N azidoadamantane with acetone, acetophenone and ben- 2 3 NaN3/HCl N N N N zophenone leads to the formation of di-(adamantan-1- N N N N yl)-1,2-diazene as the major product via dimerization H of triplet adamantan-1-yl nitrene. The triplet alkyl nitrene I also abstracts an H-atom from the solvent to form Equation 1 adamantan-1-yl amine, adamantan-1-yl-benzyl amine We starting our study by Irradiation of the azido and adamantan-1-yl benzylidene amine15. Generally, derivative I in methanol and/or ethanol resulted in the ‘-bis(4-cyano-5,6-diphenylpyridazine) accepted pathway includes primary formation of an formation of 3,3 [16] open-shell singlet nitrene by lose of N2 followed by II in moderate yield not compound B, which confirmed intersystem crossing (ISC) to the ground state triplet with IR give new strong beak at 2239 cm-1 for the new nitrene and/or cycloaddition to a neighboring C=C two CN groups and the disappearance for the N3 group double bond in arene system. On the other hand, which appear at 2150 cm-1; the 1H-NMR appear new pyridazine derivatives and heterocyclic annelated beaks for two new phenyl groups at 7.60-7.90 ppm. pyridazines continue to attract considerable attention (cf. exp. section). (Scheme 1) for their application in agriculture and in practical for Ph 17,18 their biological activity for use as potential drugs . Ph NHOR Only a few reports can be found about the photolysis N N of aryl azides or alkyl azides and alkoxycarbonyl azides. N N Ph H B There are no reports in the photolysis of heterocyclic Ph N3 n azides derivatives. So, in this paper we will study the h Ph N N EtOH or MeOH N N Ph CN photochemical reaction of 3-azidopyrazolopyridazine H I N N derivatives toward different solvents and reagent. N N RESULTS AND DISCUSSION NC Ph Ph II In a previous paper directed towards the synthesis Scheme 1 of new pyridazine derivatives[1,2], we presented the pho- The mass spectrum exhibited a characteristic 100% tolysis of 3-diazo-4,5-diphenylpyrazolo[3,4- molecular ion peak at m/z 512 and the fragmentations c]pyridazine in different reagents1. As an extension of are outlined as follows: our work we present in this paper reports of the pho- Mechanism for the transformation of I into II could tolysis of azido derivative in different reagents. Pho- involve the formation of a singlet nitrene followed by tolysis at room temperature were carried out with a ring opening concerted with nitrogen molecule and hy- high-pressure mercury lamp (300 w, 320 nm) through drogen radical elimination producing the radical spe- Pyrex filter under argon gas. cies which dimerized to form II (Scheme 3). This means 3-Azido-4,5-diphenyl-1H-pyrazolo[3,4- that methanol or ethanol work only as a solvent not c]pyridazine I was prepared in 85% yield as a yellow reacted with the nitrene and it is a good solvent to make crystals (mp 167 C) by addition of sodium azide in the dimer II. portion-wise to 3-diazo-4,5-diphenylpyrazolo[3,4- Organic CHEAMn IIndSiaTn JRournYal OCAIJ, 10(3) 2014 Ali Deeb et al. 85 Full Paper Ph Ph Ph Ph CN Ph + P N3 Ph Ph CN h h N O - CN N N N N N N N N DMSO N N H N CH2 S Me CN Ph I III NC Ph Ph m/z 486 Ph Equation 2 m/z 512 - CN - 1/2 M they reacted with the reactive intermediate A to have 4- Ph Ph Ph cyano-3,5,6-triphenylpyridazine IV in 50% yield, 4-cy- Ph CN Ph Ph - Ph ano-3(p-hydroxyphenyl),5,6-triphenylpyridazine V in m/z 179 N + N N 89.6% yield, and 4-cyano-3(p-chlorophenyl),5,6- N N N triphenylpyridazine VI in 51.2% yield, respectively All m/z 256 m/z 460 this compounds were confirmed by different spectro- Scheme 2 scopic data such as IR for compound V shows 3454, -1 -1 Ph Ph Ph 3360 cm for new OH group and 2234 cm for the new Ph N Ph N Ph N3 1 h CN group and H-NMR shows the characteristic beaks N N N N N N N N N N N H N H 6.80 and 7.5 (d. of d.) with J = 7.0 for the 4H of new H H I phenol ring and 12.99 for the new OH (D O exchange- Ph 2 Ph Ph Ph Ph CN N Ph CN able) of phenol ring (cf. exp. section).. But in nitroben- -N2 N N N zene we have 3,4-diphenylpyridazine-5-carbonitrile VII N N N N N H -H N H N A in 68.6% yield, hydrogen in position 6 this is means that the nitrobenzene is a very boor solvent and it is a very n o i t a z i unreactive compound it is inhabited also to form the dimer r e m i 1 D II, H-NMR Shows 9.7 ppm for the characteristic Ph Ph CN pyridazine hydrogen-6. (Scheme 4) N N N N Ph Ph CN NC Ph R Ph N II N Scheme 3 Ph R IV, R = 4-H When the irradiation was occurred in dimethyl sul- P N3 V, R = 4-OH h hn VI, R = 4-Cl foxide (DMSO) the reaction take the same mechanism N N N N but dimethylsulphoxide is more reactive than Methanol H or ethanol and reacted with the radical A to give 3- I Ph methanesulfonylmethyl-5,6-diphenylpyridazine-3- Ph CN carbonitrile III as the major product we can isolated Nitrobenzene N from the reaction mixture which confirmed with IR, new N H beak at 2218 and 1065 cm-1 for the new CN and S=O VII groups and the 1H-NMR with two new bands at 2.56 Scheme 4 and 3.38 ppm for the new CH and CH of the sulfoxid 3 2 Moreover, the irradiation of 3-azido derivative I in group (cf.
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