The photochemical synthesis of novel heterocyclic compounds from s-triazolo[4,3-b]pyridazine

s-Triazolo[4,3-b]pyridazine (I) photochemically reacted with cyclooctene, cyclododecene, bicyclo[2.2.2]oct-2-ene, bicyclo[2.2.1]hept-2-ene and indene to form tri and tetracyclic triazoles (II-X). Generally, two or more products were formed. For example the reaction with cyclooctene gave 4a,5,7,8,9,10,10a,11-octahydro-11-methylene-6H-cycloocta[4,5]-pyrrole[1,2-b]-s-triazole (II) and the corresponding 11-cyanomethyl product (III). When I was reacted with open chain alkenes, various isomers of the substituted pyrrolo[1,2-b]triazoles (XI-XV) were formed. Since the reaction was not stereospecific, cycloaddition must be a two step process.     

Synthesis of new s-triazolo[4,3-b] pyridazines

A new synthesis of s-triazolo[4,3-b]pyridazine derivatives has been achieved starting from 3,6-dichloropyridazine. The method opens the way to substitutions in the 2- or 3- positions. A tri-cycloderivative, a bis-s-triazolopyridazine, has also been synthesized.     

Synthesis of bridgeheaded nitrogen systems. s-triazolo[4,3-b]-as-triazine,s-triazolo[4,3-d]-as-triazine and s-triazolo[3,4-b]-1,3,4-Thiadiazole ring systems

By the reactions of hydrazino-as-triazines ( 1a-d and 5 ) with cyanogen bromide were synthesized s-triazolo-as-triazines ( 2a-d ) and ( 6 ). Likewise, similar reactions of amino-s-triazolethiols ( 7a-e ) gave s-triazolo-1,3,4-thiadiazoles ( 8a-e ). Compound 2a was brominated to 2g.     

The photochemical synthesis of novel heterocyclic compounds from s-triazolo[4,3-b]pyridazine (II)

s-Triazolo[4,3-b Jpyridazine (I) photochemically reacted with dihydropyran; 2,3-dihydro-p-dioxin; 2,5-dihydrofuran; 2,5-dimethoxy-2,5-dihydrofuran; and 1,3-dioxep-5-ene to give a new series of substituted pyrrolo[1,2-b]-.s-triazoles (II-IX). In most reactions, two or more products were formed. The following compounds have been prepared from I: 9-methylene-4a,5,6,7,8a,9-hexahydropyrano[2,3 :4,5]pyrrolo[1,2-b]-s-triazole (Ha), the corresponding 9-cyanomethyl product (III), and 9-methylene-4a,7,8,8a-tetrahydro-6H,9H-pyrano[3′,2′:4,5]pyrrolo[1,2-b]-s-triazole (IIb) from dihydropyran; 9-methylene-4a,6,7,8a-tetrahydro-9H-p-dioxino[2′,3′:4,5]-pyrrolo[1,2-6]-s-triazole (IV) from 2,3-dihydro-p-dioxin; 8-methylene-4a,5,7a,8-tetrahydro-7H-furo[3′,4′:4,5]pyrrolo[1,2-b]-s-triazole (V) and the corresponding 8-cyanomethyl product (VI) from 2,5-dihydrofuran; 8-cyanomethyl-5,7-dimethoxy-4a,5,7a,8-tetrahydro-7H-furo[3′,4′:4,5]-pyrrolo[1,2-6]-s-lriazole (VII) from 2,5-dimethoxy-2,5-dihydrofuran; and 10-methylene-4a,5,9a,10-tetrahydro-9H-[1,3]dioxepino[5′,6′:4,5]pyrrolo[1,2-b]-s-triazole (VIII) and the corresponding 10-cyanomethyl product (IX) from 1,3-dioxep-5-ene. The addition of several other compounds (1,2,3,6-tetrahydropyridine, 1-acetylimidazole, 3-sulfolene, 2,3-dihydro-p-dithiin, and vinylene carbonate) was attempted, but no reactions were observed.     

Synthesis of s-triazolo[4,3-b]pyridazine C-nucleosides

A one step synthesis of s-triazolo[4,3-b]pyridazine using 3-chloro-6-hydrazinopyridazine and an appropriate thioformimidate is described. Applying this procedure to 5-O-benzoyl-1-benzylthio-1-formimidate-D-ribofuranose, 5′ benzoyl-6-chloro-3β-D-ribofuranosyl-s-triazolo[4,3-b]pyridazine was obtained. Substitutions of chlorine by nucleophilic reagents afforded some derivatives of a new series of C-nucleo-sides. Structural determination including anomeric configuration assignment is discussed based mainly on ¹H nmr spectroscopy.     

The oxidation of s-triazolo[4,3-b]pyridazines with selenium dioxide

Some s-triazolo[4,3-b]pyridazines were oxidized to 2,3-dihydro-s-triazolo[4,3-b]pyridazin-3-ones with selenium dioxide in nitrobenzene at 160–165° (external temperature) for 1–2 hours in 30–40% yields.     

The photo cycloaddition of alkenes to s-triazolo[4,3-b] and [2,3-b]pyridazines

s-Triazolo[4,3-b]pyridazine (I) reacted with cyclohexene under the influence of ultraviolet light to yield 4a,5,7,8,8a,9-hexahydro-9-methylene-6H-s-triazolo[1,5-a]indole (IV) and 9-cyanomethyl-4a,5,7,8,8a,9-hexahydro-6H-s-triazolo[1,5-a]indole (V). These products were formed by the addition of the alkene to the 1,8 positions of I with a concurrent cleavage of the N₄? N₅ bond. Similar additions were observed with cyclopentene and 2,3-dimethyl-1,3-butadiene. The isomeric s-triazolo[2,3-b]pyridazine (III) reacted with cyclohexene to form an isomer of IV, 4a,5,7,8,8a,9-hexahydro-9-methylene-6H-s-triazolo[4,3-a]indole (XV) and two [2 + 2] cycloadducts (XVI and XVII).     

The photochemical synthesis of novel heterocyclic compounds from s-triazolo [4,3-b] pyridazine,III

s-Triazolo[4,3-b]pyridazine (I) reacted photochemieally with bieyélo[2.2.1] hepla-2,5-diene, 1,5-cyclooctadiene, 1,3-cyclooctadiene, methylene cyclohexane, diethyl cis-1,2,3,6-tetrahydro-phthalate and ethyl 2-cyclopentene-1-acetate to givt: the following products: the endo and exo isomers of 4a, 5, 8a, 9-tetrahydro-9-rnethylene-5,8-rnethano-8H-s-triuzolo[1, 5-a]indole (II) and the endo and exo-9-cyanometliyl products (III and IV) from bicyclo[2.2.1] hepta-2,5-diene; 4a,5,-9, 10, 10a, 11-huxahydro-11-methylene-6H-cycloocta[4,5]pyrrolo[1,2-b]-s-triazole (V) and the 11-cyanomethyl product VI from 1,5-cyclooctadiene: 4a,7,8,9,10,10a-hexahydro-11 -inethylene-11H-cycloocta[4,5]pyrrolo[1,2-b]-s-triazole(VII),4a, 5, 7, 8, 10a, 11-hexahydro-11-methylene-6H-cycloocta[4,5]pyrroIo[1,2-b]-s-triazole (VIII) and their respective 9-cyanomethyl products (X and 1X) from 1,3-cyclooctadiene; 6′, 7′ -dihydro-7′ -methylenespiro[cyclohexane-1, 5′-[5H] pyr-rolo[1,2-b]-s-triazole] (XI), 6′, 7′-dihydro-7′-meth) lene. spiro cyclohexane-1, 6′-[5H]pyrrolo[1,2-b]-s-triazole] (XII) and their respective 7 -eyanomethyl products (XIII and XIV) from melhylene cyclohexane; 6,7-dicarbethoxy-9-cyanomelhyl-4a, 5, 7, 8, 8a, 9-hexahydro-6H-s-triazolo[1,5-a]indole (XV) from diethyl cis-1, 2, 3, 6-tetrahydrophlhalate: and 5-earl)elhoxymethyl-8-eyanomethyl-4a, 5, 6, 7, 7a, 8-hexahydrocyclopenta[4,5]pyrrolo( 1, 2-b]-s-triazole (XVI) from ethyl 2, 2-cyclo-pentene-1-acetate. Many other alkenes, particularly the phenyl ethylenes, did not react with compound 1. In general, more than one product was isolated for each reaction except in the case of the two ester alkenes where a single eyanomethyl product was observed.     

A new fused tetrazole ring system: Tetrazolo [1,5-b] isoquinoline

Tetrazolo[1,5-α]isoquinoline ( 5b ), the linear benzologue of tetrazolopyridine, has been prepared. In contrast to the angular isomers ( 1b and 2 ) the linear system exists in solution predominantly in the tautomeric azido-form ( 5a ) and even in the crystalline state contains a certain amount of 3-azidoisoquinoline ( 5a ). The tautomeric equilibrium in solution was studied by nmr spectroscopy.     

Pyridazines. XXXIV. Electron-impact induced fragmentation of some s-triazolo[4,3-b] pyridazines,tetrazolo[1,5-b] pyridazines and related compounds

Mass spectra of several 4-triazolo[4,3-b]pyridazines and tetrazolo[1,5-b]pyridazines were examined in order to establish their fragmentation patterns. Two distinct patterns could be observed upon electron impact of s-triazolo[4,3-b]pyridazines and tetrazolo[1,5-b]pyridazines. Azidotetrazolopyridazines show a loss of six nitrogens. This can be accounted for by a path proceeding via a molecular ion with a bis-tetrazolo structure.     

Syntheses in the pyridazine series. XXX. Protonation and quaternization studies on imidazo[1,2-b] pyridazines and s-triazolo[4,3-b] pyridazines

Sterically unhindered s-triazolo[4,3-b] pyridazines form N₁-methiodides, whereas 3- and/or 8-substituted analogs form a mixture of N₁- and N₂-methiodides. In some cases thermal rearrangement occurred. Imidazo[1,2-b]pyridazines form N₁-methiodides and here also steric interactions were observed as evidenced by the NMR spectra.     

The synthesis and transformations of 9H-imidazo[1,2-b]pyrazolo[4,3-d]-pyridazine and 9H-pyrazolo[4,3-d]-s-triazolo[4,3-b]pyridazine derivatives

The nucleophilic and electrophilic substitutions of 6-substituted 9,9-dimethyl-9H-imidazo[1,2-b]pyrazolo- [4,3-d]pyridazines 2 , nucleophilic substitutions of 6-substituted 9,9-dimethyl-9H-pyrazolo[4,3-d]-s-triazolo- [4,3-b]pyridazines 7 and some other transformations to give compounds 3 and 8 , respectively, were studied. It was shown that both heterocyclic systems are stable under the conditions employed in these transformations.     

A reinvestigation of the synthesis of 3H-[1,2]diazepino[5,6-b]indoles. The synthesis of pyrido[4,3-b]indoles

Recently reported [1] syntheses of 6-methyl-1,2,4,5-tetrahydro-1,4-dioxo-3H[1,2]diazepino[5,6-b]indole ( 5 ) and 4-hydroxy-6-methyl-3H[1,2]diazepino[5,6-b]indole ( 12 ) were reinvestigated and shown to be in error. The correct assignments for these respective structures are 3-amino-1,9-dihydro-9-methyl-2H-pyrido[4,3-b]indol-2,4(3H)-dione ( 6 ) and 3-amino-3,9-dihydro-9-methyl-2H-pyrido[4,3-b]indol-2-one ( 13 ). Condensation of 6 and 13 with p-nitrobenzaldehyde produced benzylidene derivatives, which confirmed the presence of the amino groups.     

The mass spectra of some s-triazolo[4,3-a]pyrazines

s-Triazolo[4,3-a]pyrazine underwent decomposition by loss of nitrogen from its molecular ion whereas in the 3-alkyl derivatives the corresponding alkyl cyanide was eliminated from the 5-membered ring. The introduction of a carbonyl or thiocarbonyl group into the 3-position resulted in predominant loss of the triazole ring in the fragmentation process; however, with a 3-amino substituent, the first fragment eliminated from the molecular ion was cyanamide. Methyl substitution in the 6-membered ring resulted in the formation of ring expanded ions. On phenyl substitution, however, an interesting 1,2-phenyl migration was observed. The mass spectra of several analogous s-triazolo[1,5-a]pyrazines are also described.     

Acetals of lactams and acid amides. 36. Some reactions of enamines of the isoquinoline series and synthesis of pyrimido[4,3-a]isoquinolines

The reactions of 1-methylene-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives with acyl chlorides were investigated. 2-Oxopyrimido[4,3-a]isoquinoline derivatives were obtained by the reaction of 1-carbamidomethylene-6,7-dimethoxy-1,2, 3,4-tetrahydroisoquinoline with dimethylformamide and dimethylacetamide diethylacetals. The reaction of the latter with phosphorus oxychloride and then with primary amines was used to synthesize a number of hydrochlorides that are derivatives of 2-iminopyrimido[4,3-a]isoquinoline.See [1] for Communication 35.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1095–1099, August, 1982.     

Condensed Isoquinolines. 14. Spirocyclic Systems Containing a Benzo[5,6][1,2,4]thiadiazino[4,3-b]isoquinoline Ring

We propose a convenient preparative method for synthesis of derivatives of novel heterospirane systems with a benzo[5,6][1,2,4]thiadiazino[4,3-b]isoquinoline ring, based on the reaction of 1-(2-bromomethylphenyl)-1-cyclopentanecarbonitrile and 4-(2-bromomethylphenyl)-3,4,5,6-tetrahydro-2H-pyran-4-carbonitrile with o-aminobenzenesulfamide.     

Facile synthesis of some novel triazolo[3,4-b]thiadiazines and triazolo[4,3-b]tetrazines

4-Amino-5-ethyl-4H-1,2,4-triazole-3-thiol was used as a key intermediate for the synthesis of triazolo[3,4-b][1,3,4]thiadiazines, triazolo[4,3-b][1,2,4,5]tetrazines and Schiff’s base via reactions with various hydrazonoyl halides and salicyaldehyde, respectively. Moreover triazolyl-N-N′-triazole derivatives were prepared from reaction of Schiff’s base with various hydrazonoyl halides. The structures of all the newly synthesized heterocyclic compounds were established by considering elemental analysis and spectral data.     

Syntheses and interconversions of some s-triazolo[3,4-a]isoquinolines

s-Triazolo[3,4-a]isoquinoline (II) and its 3-methyl analogue (III) have been synthesized from 1-isoquinolylhydrazine (I) by cyclisation with formic and acetic acid. The 3-hydroxy derivative (IV) has been shown to exist in the lactam form. Methylation with methyl iodide gave the N-methyl derivative (V). Dimethyl sulphate and diazomethane also led exclusively to the same product. The O-methyl derivative (IX) could be obtained only through the 3-chloro compound (VIII). The chlorine atom in VIII undergoes nucleophilic replacement easily. The 3,6-dichloro derivative (X) has also been prepared. Several interconversions in the series are described. Aryl hydrazones (XVIII) prepared from (I) have been oxidatively cyclised to give 3-aryl-s-triazolo[3,4-a]isoquinolines (XIX). U.V., I.R. and P.M.R. spectra have been recorded and used for assignment of structures in some cases.