Syntheses of [1,2,3]selenadiazolo[4,5‐e]benzofuran or benzothiophene, [1,2,3]thiadiazolo[4,5‐e]benzofuran or benzothiophene,and 2‐benzofuranyl‐1,3,4‐oxodiazole derivatives

Dehydrogenation of ethyl 3‐methyl‐4‐oxo‐4,5,6,7‐tetrahydrobenzofuran‐2‐carboxylate 1 with 2,2′‐azobi‐sisobutyronitrile and N‐bromosuccinimide gave ethyl 4‐hydroxy‐3‐methylbenzofuran‐2‐carboxylate 3 . Reaction of compounds 3–4 with hydrazine hydrate afforded the corresponding hydrazides 5a‐b . The reaction of 5a‐b with aldehydes yielded substituted hydrazones 6a‐l . Compounds 7a‐d were prepared from compounds 6a‐d and bromine in acetic acid. Lead tetraacetate oxidation of compounds 6e‐l afforded substituted oxadiazoles 8e‐l . Selenium dioxide oxidation of 4‐oxo‐4,5,6,7‐tetrahydrobenzofuran semicarbazones 9, 14a and 4‐oxo‐4,5,6,7‐tetrahydrobenzothiophene 14b gave the tricyclic 1,2,3‐selenadiazoles 10, 15a and 15b respectively. Reaction of semicarbazones 9, 14a and 14b with thionyl chloride afforded the corresponding 1,2,3‐thiadiazoles 12, 16a and 16b respectively.     

Selenium heterocycles XXIII. Synthesis of 4,5-dihydrophenanthro[1,3-d]-1,2,3-selenadiazoles and 10,11 -dihydrophenanthro[1,2-d]-1,2,3-selenadiazoles

The selenium dioxide oxidation of a series of 1,2,3,4-tetrahydrophenanthrone and 1,2,3,4-tetrahydrophenanthren-4-one semicarbazones afforded 4,5-dihydrophenanthro[4,3-d]-1,2,3-selenadiazoles and 10,11-dihydrophenanthro[1,2-d]-1,2,3-selenadiazoles. The latter series which represent a new type of selenaazasteroidal compounds were pyrolyzed and gave the corresponding 1,4-deselenine derivatives.     

Synthesis and tautomerization of 6,7‐dihydro‐(1,2,3)‐triazolo[1,5‐a]pyrimidines

The condensation of 5‐amino‐4‐phenyl‐1,2,3‐triazole ( 1 ) with chalcones 2a‐e or 3‐dimethylamino‐propiophenone ( 4f ) leads to the 6,7‐dihydro‐(1,2,3)‐triazolo[1,5‐a]pyrimidines 3a‐f. The equilibrium of 3 and the tautomeric 4,7‐dihydro‐(1,2,3)‐triazolo[1,5‐a]pyrimidines 3′ is described.     

Syntheses of oxazolo[4,5‐c]pyridine and 6‐azaindole

The preparation of oxazolo[4,5‐c]pyridine and 6‐azaindole from 4‐bromo‐3‐pivaloylaminopyridine ( 8 ) is reported. The oxazolopyridine 2‐tert‐butyl‐oxazolo[4,5‐c]pyridine ( 9 ) was successfully prepared from 8 in 78% yield by a new base/TBAB promoted non‐catalyzed microwave cyclisation strategy (10 min) or, alternatively, in 54% yield by conventional heating (48 hrs) and CuI catalysis. The 6‐azaindole 2‐phenyl‐1‐(trimethylacetyl)‐6‐azaindole ( 13 ) was prepared from 8 in a two step procedure, including a Sonogashira coupling reaction.     

Selective synthesis of some 4,5‐dihydro‐2H‐benzo[g]indazoles and 8,9‐dihydro‐2H‐benzo[e]indazoles via the vilsmeier‐haack reaction under thermal and microwave assisted conditions

A selective and easy method is described for the synthesis of 4,5‐dihydro‐2H‐benzo[g]indazoles and 8,9‐dihydro‐2H‐benzo[e]indazoles by the Vilsmeier‐Haack reaction of various tetralone phenylhydrazones under thermal and microwave irradiation conditions.     

New 1,2,3‐triazolo[4,5‐d]1,2,4‐triazolo[3,4‐b]pyridazine derivatives II

New tricyclic 1,2,3‐triazolo‐1,2,4‐triazolo‐pyridazine derivatives, bearing a methyl substituent on the 1,2,3‐triazole ring, were prepared as potential biological agents. N‐Methylation of dimethyl 1,2,3‐triazole‐4,5‐dicarboxylate allowed synthesis of the isomeric 1‐methyl‐4,7‐dihydroxy and 2‐methyl‐4,7‐dihydroxy triazolo‐pyridazines 4a and 4b which, by a chlorination reaction, gave the corresponding 1‐methyl‐4‐chloro‐( 6a ), 1‐methyl‐7‐chloro‐ ( 6b ) and 2‐methyl‐4‐chloro‐ ( 9 ) substituted 1,2,3‐triazolo‐pyridazines. The nucle‐ophilic substitution with hydrazine hydrate and the suitable cyclization to form the 1,2,4‐triazole ring, provided the expected tricyclic isomeric derivatives 8a, 8b and 11 respectively. The p‐methoxybenzyl substituent, introduced as a leaving group to obtain either v‐triazolo‐pyridazine or v‐triazolo‐s‐triazolo‐pyri‐dazine derivatives unsubstituted on the 1,2,3‐triazole ring, appeared inadequate. Some compounds underwent binding assays toward the adenosine A₁and A_2A receptors.     

New 1,2,3‐triazolo[4,5‐e]1,2,4‐triazolo[4,3‐c]pyrimidine derivatives II

The 7‐chloro‐3‐(2‐chlorobenzyl)‐ and 7‐chloro‐3‐(2‐fluorobenzyl)‐1,2,3‐triazolo[4,5‐d]pyrimidines ( 1 and 4 ), by nucleophilic replacement with some hydrazides, gave the corresponding 7‐hydrazidoderivatives ( 2a‐e and 5a‐e ). These, by heating in Dowtherm, underwent an intramolecular cyclization to form the new tricyclic 7‐substituted‐3‐(2‐chlorobenzyl)‐ and 3‐(2‐fluorobenzyl)‐1,2,3‐triazolo[4,5‐e]1,2,4‐triazolo[4,3‐c]pyrimidines ( 3a‐d and 6a‐d ). The 7‐hydrazino‐3‐(2‐chlorobenzyl)‐ and 7‐hydrazino‐3‐(2‐fluorobenzyl)‐triazolo‐pyrimidines ( 9a and 9b ) were also prepared via the corresponding mercapto ( 7a and 7b ) and thiomethyl ( 8a and 8b ) derivatives.     

Selenium heterocycles. XLI . Syntheses of substituted thiazolo,selenazolo, 1,2,3-thiadiazolo and 1,2,3-selenadiazoloquinolines

The reaction of thionyl chloride with the semicarbazone 2 gave 4,5-dihydro[1,2,3]thiadiazolo[4,5-f]quinoline. Selenium dioxide oxidaion of compound 2 gave 4,5-dihydro[1,2,3]selenadiazolo[4,5-f]quinoline ( 4 ) and the aromatic analog 5 . Thermolysis of compound 5 yielded [1,4]diselenino[2,3-f:5,6-f′]diquinoline ( 6 ). Reaction of selenourea with α-bromoketone 7 gave 2-amino-4,5-dihydroselenazolo[4,5-f]quinoline ( 8 ). Compounds 9 and 10 were prepared from the reaction of selenobenzamide and thiobenzamide with compound 7 .     

1,2‐Methyl shift in the reaction of 4,7‐dihydro‐4,5‐dimethyl‐7‐phenyl‐(1,2,4)‐triazolo[1,5‐a]pyrimidine with tosyl azide

The reaction of the heterocyclic enamine 1 with tosyl azide ( 2 ) leads to the tosylimino derivative 4 of 1,2,4‐triazolo[1,5‐a]pyrimidine. The extrusion of nitrogen from the primary adduct 3 is followed by a 1,2‐shift of a methyl group. The structure determination of 4 is based on ¹H and ¹³C nmr spectra including NOE measurements.     

Syntheses of 2,3‐dicyano‐5a,8a‐dihydro‐5a‐hydroxycyclopentano[1′,2′:4,5]pyrrolo[2,3‐b]pyrazines and 2,3‐dicyanocyclohexano[1′,2′:4,5]pyrrolo‐[2,3‐b]pyrazines

Previously synthesized 2‐(3′‐chloro‐5′,6′‐dicyanopyrazin‐2′‐yl)cyclopentan‐1‐one 1 , obtained from the reaction of 2,3‐dichloro‐5,6‐dicyanopyrazine with 1‐pyrrolidino‐1‐cyclopentene, was further reacted with primary alkylamines to give mixtures of diastereomer of 5‐alkyl‐2,3‐dicyano‐5a,8a‐dihy‐dro‐5a‐hydroxycyclopentano[1′,2′:4,5]pyrrolo[2,3‐b]pyrazines 3a‐h in high yield. The reaction of 2‐alkylamino‐3‐chloro‐5,6‐dicyanopyrazine with 1‐pyrrolidino‐1‐cyclohexene gave 5‐alkyl‐2,3‐dicyanocyclopentano[1′,2′:4,5]pyrrolo[2,3‐b]pyrazines 5a‐b together with 5‐alkylamino‐2,3‐dicyano‐6‐pyrrolidinopyrazines 6a‐b . The products prepared are all of interest as potential pesticides and new fluorescent chromophores.     

Synthesis and chemiluminescent activity of 8,9‐dihydrobenzo[g] pyridazino[4,5‐b]indole‐7,10(11H)‐diones

Substituted and unsubstituted naphthylamines were transformed into the corresponding triazole derivatives, which were converted to dimethyl 1H‐benz[g]indole‐2,3‐dicarboxylates by photocyclization. The reaction of the diesters with hydrazine hydrate gave the corresponding 8,9‐dihydrobenzo[g]‐pyridazino[4,5‐b]indole‐7,10(11H)‐diones (5) . One of compounds 5 was found to have chemiluminescent activity similar to luminol.     

Pyrrolo[3,4‐e][1,2,3]triazolo[1,5‐a]pyrimidine and pyrrolo[3,4‐d] [1,2,3]triazolo[1,5‐a]pyrimidine. New tricyclic ring systems of biological interest

Derivatives of the new ring system pyrrolo[3,4‐e][1,2,3] triazolo[1,5‐a]pyrimidine 6 were prepared in high yields in one step by reaction of 3‐azidopyrrole 3 and substituted acetonitriles. Compound 6b rearranged, upon heating in dimethyl sulfoxide in the presence of water, to pyrrolo[3,4‐d][1,2,3]triazolo‐[1,5‐a]pyrimidine 7.     

One‐step ring‐closure procedure for 4,5‐dihydro‐1,3‐thiazino[5,4‐b]indole derivatives with Lawesson's reagent. The fifth dihydro‐1,3‐thiazino[b]indole isomer

We report a convenient approach for the synthesis of a new ring system: 4,5‐dihydro‐1,3‐thiazino[5,4‐b]indoles. The procedure involves the use of Lawesson's reagent in the presence of silica to achieve the one‐step ring‐closure reactions of 2‐benzoylamino‐3‐hydroxymethylindole intermediates to furnish 4,5‐dihydro‐2‐aryl‐1,3‐thiazino[5,4‐b]indoles. 2‐Phenylimino‐1,3‐thiazino[5,4‐b]indoles were obtained via the corresponding 3‐phenylthiourea‐2‐carboxylic acid ester derivatives by chemoselective reduction of the ester group, followed by ring closure under acidic conditions. The structures of the novel products were elucidated by IR, ¹H‐NMR, and ¹³C‐NMR spectroscopy, including 2D‐HMQC, 2D‐HMBC, and DEPT measurements. J. Heterocyclic Chem., (2011).     

Synthesis of 1‐substituted [1,2,3]triazolo[4,5‐d]pyridazines as precursors for novel tetraazapentalene derivatives

A series of 1‐substituted 4,5‐diformyl‐[1,2,3]triazole derivatives were prepared by 1,3‐dipolar cyclo‐addition of aryl azides with acetylene dicarboxaldehyde mono‐diethylacetal. The triazoles were readily converted into 1‐substituted [1,2,3]triazolo[4,5‐d]pyridazines in good yields. The 1‐(2‐nitrophenyl)‐[1,2,3]triazolo[4,5‐d]pyridazine was found to be a useful intermediate for the generation of the novel 5H‐benzo[1,2,3]triazolo[1′,2′:1,2]triazolo[4,5‐d]pyridazin‐6‐ium inner salt ring system.     

Preparation of substituted 1,3‐dihydro‐2H‐imidazo[4,5‐c]pyridin‐2‐ones

A new synthetic route to 6‐substituted‐imidazo[4,5‐c]pyridin‐2‐ons from 4‐aminopyridine has been investigated. 4‐Aminopyridine protected as alkyl carbamates were nitrated with dinitrogen pentoxide to the corresponding methyl, i‐propyl and t‐butyl 3‐nitropyridin‐4‐yl carbamates ( 5a‐c ) in 51‐63 % yields. Attempts to substitute these in the 6‐position by the ONSH and the VNS techniques succeeded with butyl‐amine and the t‐butyl carbamate 9 . From the methyl or t‐butyl 3‐nitropyridin‐4‐yl carbamates 5a, 5c 1,3‐dihydro‐2H‐imidazo[4,5‐c]pyridin‐2‐one ( 1 ) was formed in 73 and 39 % yields, respectively. t‐Butyl 6‐N‐butylamin‐3‐aminopyridin‐4‐yl carbamate ( 6 ) gave 6‐butylamino‐1,3‐dihydro‐2H‐imidazo[4,5‐c]‐pyridin‐2‐one (7) in 53 % yield.     

Synthesis and characterization of 4,5‐dihydro‐1H‐pyrazolo[3,4b][1,4]azaphosphinines

1,3,3‐Trimethyl‐2‐(1‐R‐3‐methyl‐5‐pyrazolyliminoethylidene)indolines were shown to undergo phosphorylation with phosphorus(III) halides at the two nucleophilic carbon centers to give fused 1,4‐azaphosphinine ring systems. Chemical properties of the synthesized compounds were characterized. For some representative compounds, detailed NMR spectroscopic investigations were performed, including the determination of ³¹P, ¹H and ³¹P, ¹³C coupling constants. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 391–398, 1999