Diaziridines. III. Reactions of some 1-alkyl- and 1,1-dialkyl-1H-diazirino[1,2b]phthalazine-3,8-diones

Abstract

l,l-Dialkyl-1H-diazirino[l,2-b]phthalazine-3,S-d~ones isomerize in boiling toluene into 2-(l-alken-l-yl)-4-hydroxy-l(2H)-phthalazinones and react with enamines and ynamines to yield derivatives of pyrazolo[l,2-b]-and indazolo[l,2-b]phthalazinediones.The thermal conversions of 1-(2,4-dinitropheny1)-3,3-dialkyl-and 1-(2,4-dinitropheny1)-2,3,3-trialkyldiaziridines into 2,4-dinitrophenylhydrazones and 2-alkyl-6-nitrobenzotriazole 1-oxides, respectively, and the addition of 3,3-dialkyl-and 1,3,3-trialkyldiaziridines to electrophilic acetylenes have been the subjects of earlier reports in this series.1$2 In the present paper the synthesis and reactions of 1-alkyl-and 1,l-dialkyl-1H-diazirino[l,2-b lphthalazine-3,8-diones (1-7) and the related systems 8 and 9 are described. These versatile compounds are thermally isomerized into 2-(1 -alken-1-yl) -4-hydroxy-1 -( 2H)phthalazinones and react with ynamines and enamines to give pyrazolo[l,2-b]-and indazolo[l,2-b]phthalazinediones. Reactions with I nitrones are presented in the following paper.Resultswere prepared by the addition of phthaloyl chloride to ethereal solutions of 3,3-dialkyldiaziridines containing triethylamine (Scheme I, Table I). The l-alkyllH-diazirino[l,2-b]phthalazine-3,8-diones 6 and 7 were synthesized by generating the 3-alkyldiaziridines in The Scheme I EtBN o-C,H,(COCl), + HN-NHvTable I 1-Alkyl-and 1,l-Dialkyl-1H-diazirino [ 1,2-b]phthalazine-3,8-dionesa Compd b R1 R2 Yield,c % Mp, OC 1 Me Me 58 98-99 2 Et Et 35 70-71 3 n -P r n -P r 47 108-109 4 -(CH2)5-75 110-111 5 Me Et 71 76-77 6 H n -Pr 61 71-72.5 110-111 7 H t -Bu 51 a Satisfactory analytical data for C, H, and N were obtained for all compounds listed in the table. Ed. Compounds 1-7 were recrystallized from cyclohexane. c Yields are reported on the basis of recrystallized products.situ from the corresponding chloral adducts, R b m C H ( O H ) C H C C l 3 , in the presence of o-phthaloyl chloride. Compounds 8 and 9 were made in much the same / \ manner as 1-5 by employing the appropriate diacid chlo-R' R2 ride and 3,3-~entamethylenediaziridine.The structures of 1-9 were assigned on the basis of elemental analyses, nmr spectroscopy, and by the hydrolysis H+* $r + ~1~2~0 of 2,4, and 7 into 4-hydroxy-l(2H)-phthalazinone (10) and the corresponding carbonyl compounds 3-pentanone, cyclohexanone, and pivalaldehyde, respectively (Scheme I). The nmr spectrum of l,l-dimethyl-lH-diazirino[1,2-0 1-7 10 blphthalazine-3,B-dione (1) taken in C6D6 shows two peaks a t 6 1.45 and 1.25 for the two methyl groups on the diaziridinyl carbon. On heating to about 60" the two peaks coalesce to a broad singlet which on further heating to 75O becomes a sharp singlet a t 6 1.55. If the temperature is lowered to 40° the two signals for the methyl groups reappear. The temperature variance of the nmr spectrum of 1 indicates inversions of the nitrogen atoms (Scheme 11) and is of some interest, since the N-aroyl moieties are perforce cis to 0 R1 0 CH,OH-H,O OH 0 8 9 3187

Caesium carbonate supported on hydroxyapatite‐encapsulated Ni0.5Zn0.5Fe2O4 nanocrystallites as a novel magnetically basic catalyst for the one‐pot synthesis of pyrazolo[1,2‐b]phthalazine‐5,10‐diones

“…The ideal synthesis of a large diversity of heterocyclic compounds such as bridge‐head hydrazine heterocycles has attracted considerable attention of scientists because these compounds show some pharmacological properties and biological activities . As an example, pyrazole derivatives are acknowledged to possess a wide range of bioactivities and exhibit important biological properties such as anti‐inflammatory, antifungal, anticancer, antiviral, antitumor, anticoagulant, antibacterial and antihypoglycaemic activities …”

A Rapid and an Efficient Route to the One‐pot, Multicomponent Synthesis of 1H‐Pyrazolo[1,2‐b]phthalazine‐5,10‐dione Ring Systems

“…The development of new efficient methods to synthesize N ‐heterocycles with structural diversity is one of the major interests of modern synthetic chemists . Among a large variety of nitrogen‐containing heterocyclic compounds, heterocycles containing bridgehead hydrazine have attracted immense attention because of their pharmacological properties and clinical applications . Similarly, pyrazole ring is a key fragment in numerous biologically active compounds .…”

Solvent-free synthesis of 2H-indazolo[2,1-b] phthalazine-triones promoted by cavitational phenomenon using iodine as catalyst

“…Among a large variety of heterocyclic compounds, nitrogencontaining heterocycles are widespread and their applications in biologically active pharmaceuticals, agrochemicals, and functional materials are becoming more and more important [2][3][4][5][6]. Among a large variety of nitrogen-containing heterocyclic compounds, heterocycles containing bridgehead hydrazine have received considerable attention because of their pharmacological properties and clinical applications [7][8][9][10][11][12][13][14][15][16]. One such group of heterocyles are phthalazine derivatives, they were reported to possess cardiotonic [17], vasorelaxan [18], cytotoxic [19], antimicrobial [20], antifungal [21], anticancer [22], anti-inflammatory [23] and anticonvulsant [24] activities.…”