Massenspektrometrie kondensierter N-Heterocyclen. 1–Elektronenstoßinduzierte Bildung von Cyclaziniumionen aus 5-Aryl(Hetaryl)-9-methyl-s-triazolo[4,3-c]tetrazolo-[1,5-a]pyrimidinen

The electron impact mass spectra of 5-aryl(hetaryl)-9-methyl-s-triazolo[4,3-c]tetrazolo[1,5- a]pyrimidines have been investigated. There is a general fragmentation mechanism, which forms stable cyclazinium ions by cyclization. In the case of the 5-hetaryl derivatives the proposed structures were confirmed by means of a comparison of mass analysed ion kinetic energy spectra with suitable model compounds.     

Preparation of 5-substituted- and 3,5-disubstituted-s-triazolo[4,3-a]pyridines

Cyclization of N-acyl-N′-(6-chloropyrid-2-yl)hydrazines ( 2a-2e ) with phosphorus oxychloride has produced several 5-chloro-s-triazolo[4,3-a]pyridines ( 3a-3e ). Nucleophilic displacement of the chlorosubstituent of 5-chloro-s-triazolo[4,3-a]pyridine ( 3a ) availed the 5-ethoxy ( 4a ) and 5-thioethoxy ( 4b ) derivatives and di(s-triazolo[4,3-a]pyrid-5-yl)sulfide ( 8 ) while reaction of 5-ethylsulfonyl-s-triazolo[4,3-a]pyridine ( 4d ) with potassium hydroxide yielded the 5-hydroxy/5-one system ( 4c or 6 ). Further reaction of 3a with bromine to give 3-bromo-5-chloro-s-triazolo-[4,3-a]pyridine ( 3g ) has provided the corresponding 3-cyano- and 3-carboxamido-5-chloro-s-triazolo[4,3-a]pyridine derivatives ( 3h and 3i ). Treatment of 6-chloro-2-hydrazinopyridine ( 1 ) with cyanogen bromide has provided 3-amino-5-chloro-s-triazolo[4,3-a]pyridine ( 3f ) which, with bromoacetaldehyde dimethyl acetal, transformed into 7-chloroimidazo[1,2-b]-s-triazolo[4,3-a]-pyridine ( 7 ). Finally, attempts at cyclizing N-oxalyl-N′-(6-chloropyrid-2-yl)hydrazine derivatives ( 2g-2i ) with intentions of preparing various 3-acyl-5-chloro-s-triazolo[4,3-a]pyridines for entry into other 3,5-disubstituted systems were unsuccessful.     

A solution of structural ambiguity: s-Triazolo[1,5-a] – and s-triazolo[4.3-a] pyrimidines

The condensation of 3-amino-5-benzylthio-s-triazole ( 2 ) with acetylacetone in refluxing acetic acid has been reported to have given 3-benzylthio-5,7-dimethyl-s-triazolo[4,3-a]pyrimidine ( 3 ). However, it has now been established, with the aid of ¹³C spectra and a modification of the original synthetic work, that only 2-benzylthio-5,7-dimethyl-s-triazolo[1,5-a]pyrimidine ( 4 ) can be obtained by this method of condensation. The erroneously reported, but previously unknown 6 was synthesized and its structure and that of 4 was firmly established by ir, uv, pmr,¹³ C nmr, tlc and mixed melting point data. The correct structures of 3-mercapto-5,7-dimethyl-s-triazolo-[4,3-a]pyrimidine ( 5 ) and 2-mercapto-5,7-dimethyl-s-triazolo[1,5-a]pyrimidine ( 6 ) were also established and the facile rearrangement of 5 to 6 was demonstrated.     

Formycin analogs. I. Model studies in the preparation of an isomer of formyein and related derivatives (s-triazolo[4,3-a] pyrazines)

The synthesis of a number of 8-substituted- and 3-methyl-8-substituted-.s-triazolo[4,3-a]-pyrazines as model molecules for an isomer of formyein (i.e., 8-amino-3-(β-D-ribofuranosyl)-s-triazolo[4,3-a ]pyrazine ( 2 )) and some of its derivatives (including aglycone) is reported. The C-8 subslituents include amino ( 3a and 4a ), chloro ( 3b and 4b ), hydroxy (as the 8 -ones 8a and 9a ), mercapto (as the 8 -thiones 8c and 9c ), hydroxylamino ( 3e and 4e ), selenoxy (as the 8 -selenones 8d and 9d ), metlioxy ( 3g and 4g ), and thiomethoxy ( 3h and 4h ). Also described are 7-methyl-s-triazolo[4,3-a]pyrazin-8(7H) one ( 8b ) and its 3-methyl derivative ( 9b ) together with imidazo[1,2-g]-s-triazolo[4,3-a]pyrazine ( 10a ) and its 3-methyl derivative ( 10b ). Complete spectral data for all of these molecules is presented.     

Research on nitrogen containing heterocyclic compounds. XVIII. Synthesis of 9H-pyrrolo[2,1-c]-s-triazolo[4,3-a][1,4]benzodiazepine,a novel tetracyclic ring of pharmaceutical interest

Reaction of di-4-morpholinylphosphinic chloride on 5,10-dihydro-9H-pyrrolo[2,1-c][1,4]benzodiazepin-11-one 9 afforded 11-(di-4-morpholinylphosphinyloxy)-5H-pyrrolo[2,1-c][1,4]benzodiazepine 10 . Displacement of di-4-morpholinylphosphinyloxy group of 10 by formylhydrazine with concomitant intramolecular cyclization led directly to 9H-pyrrolo[2,1-c]-s-triazolo[4,3-a][1,4]benzodiazepine 7, a novel nitrogen heterocyclic ring of pharmaceutical interest. A new procedure for the synthesis of 9 is also described.     

Synthesis and reactivity of 1,2,4-triazolo[1,5-c]quinazolines

The preparation of 1,2,4-triazolo[1,5-c]quinazolines 4a-d , 5 , 8a-d by cyclocondensation of 1a-c with carboxylic acids and carboxylic anhydrides, respectively, is described. By different pathways, the 5-thioxo-5,6-dihydro-1,2,4-triazolo[1,5-c]quinazolines 4a-d react with hydrazine hydrate or amines with the formation of 5-substituted 1,2,4-triazolo[1,5-c]quinazolines 9 and 10a-d . Cyclocondensation of 9 with carboxylic acids, carboxylic anhydrides, and nitrous acid, respectively, leads to the new anellated heterocycles bis-1,2,4-triazolo[4,3-a:1,5-c]quinazoline 13 and tetrazolo [1,5-a]-1,2,4-triazolo[1,5-c]quinazoline ( 14 ).     

Synthèse et étude physicochimique des 1,2,4-triazolo[4,3-a]-pyridines et des 1,2,4-triazolo[2,3-a]pyridines

The synthesis of 1,2,4-triazolo[4,3-a] and [2,3-a]pyridines 7, 8 was achieved by cyclization of 2-hydrazino-8-nitropyridine 3a with formic acid. The 4,5,6,7-tetrahydro-1,2,4-triazolo[2,3-a]pyridine 13 and 8-amino-1,2,4-triazolo[2,3-a]pyridine 9 were obtained by catalytic hydrogenation. The reduction of triazolo pyridine 8 using stannous chloride led to the intermediate compound 10 which with acetic anhydride afforded 8-acetylamino-5-chloro-1,2,4-triazolo[2,3-a]pyridine 10a . The structure of the derivatives was determined by ¹H-nmr (DMSO-d₆).     

1,2,4-Triazoles. XXV. The effect of pyridine substitution on the isomerization of s-Triazolo[4,3-a] pyridines into s-Triazolo[1,5-a] pyridines

The isomerization of s-triazolo[4,3-a]pyridines into s-triazolo[1,5-a]pyridines is greatly facilitated by electron withdrawing nitro substituents in the pyridine ring and retarded by electron donating amino groups.     

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).     

Studies on the synthesis and interconversion of isomeric triazolotheinopyrimidines. Part II. Effect of 5-substituents on the dimroth rearrangement of 1,2,4-triazolo[4,3-c]thieno[3,2-e]pyrimidines

The triazolothienopyrimidines obtained by the cyclization of 4-hydrazino-2-phenylthieno[2,3-d]pyrimidines with triethyl orthoformate or formic acid presumed to be the triazolo[2,3-c] isomers are now assigned the 5-phenyl-1,2,4-triazolo[4,3-c]thieno[3,2-e]pyrimidine structure. While these [4,3-c]triazoles resist isomerization under acidic conditions, they undergo isomerization to 5-phenyl-1,2,4-triazolo[2,3-e]thieno[3,2-e]pyrimidines under basic conditions.     

Synthesis of 2-substituted cinchoninic acid amides and their cyclization into 1,2,4-triazolo[4,3-α]-quinoline-9-and 1,2,4-triazino[4,3-a]quinoline-10-carboxylic acid amides

Substituted amides of 2-hydrazino- and 2-ethylhydrazinocinchoninic acids react with pyruvic acid and its ethyl ester to give amides of 3-methyl-4-oxo-1,2,4-triazino[4,3-a]quinoline-10-carboxylic acid. On reaction with aromatic aldehydes they are converted into amides of 2-ethyl-3-phenyl-2,3-dihydro-1,2,4-triazolo[4,3-a]quinoline-9-carboxylic acid, or, in the case of unsubstituted hydrazines, into amides of 2-arylidene-hydrazinocinchoninic acid, which was oxidized to substituted 1,2,4-triazolo[4,3-a]quinolines.Perm Pharmaceutical Academy, Perm 614600. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 701–705, May, 1977.     

Condensed Pyridopyrimidines. 7. Synthesis of Condensed Triazolo[4,3-c]- and Tetrazolo[1,5-c]pyrimidines

Novel dihydro-5H-pyrano[3',4':5',6']pyrido[2,3-d]-1,2,4-triazolo[4,3-c]pyrimidines and 1,2,3,4-tetrazolo[1,5-c]pyrimidines have been synthesized from 2-amino-3-cyano-7,7-dimethyl-7,8-dihydro-5H-pyrano[4,3-b]pyridine.     

On triazoles XXIII [1]. The reaction of 5-amino-1,2,4-triazoles with thiacyclohexane β-oxo esters [2]

Six novel isomeric ring systems, namely the thiopyrano[4,3-d]-1,2,4-triazolo[1,5-a]pyrimidine, the thiopyrano[3,4-e]-1,2,4-triazolo[1,5-a]pyrimidine, the thiopyrano[3,4-d]-1,2,4-triazolo[1,5-a]pyrimidine, the thiopyrano[4,3-e]-1,2,4-triazolo[1,5-a]pyrimidine, the thiopyrano[3,2-d]-1,2,4-triazolo[1,5-a]pyrimidine and the thiopyrano[2,3-e]-1,2,4-triazolo[1,5-a]pyrimidine were synthesised. Spectroscopical evidence was given for the structure of compounds obtained.     

13C-NMR-Untersuchungen zur Azido-Tetrazol-Valenzisomerie. Tetrazolo[1,5-α]pyrimidine

¹³C NMR has been used to study the azido-tetrazolo valence isomerism of three tetrazolo[1,5-α]pyrimidines. Large chemical shift variations of C-4 carbons were found to be useful to distinguish between azido and tetrazolo isomers. Furthermore, the structure of new heterocycles has been proved and the report of LaNoce and Giuliani concerning 9-methyl-s-triazolo[4,3-c]tetrazolo[1,5-α]pyrimidine is shown to be incorrect.     

A Convenient Synthesis of NovelDerivatives of Pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine-5,6-dione

Summary.  Reaction of 6-Amino-2-thiouracil with hydrazonoyl halides yielded regioselectively 7-amino-1,3-disubstituted-1,2,4-triazolo[4,3-a]pyrimidine derivatives. Upon treatment with methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate, the corresponding methyl (Z)-2-benzoylamino-3-([1,2, 4]triazolo[4,3-a]pyrimidin-7-yl)-amino propenoates were obtained which cyclized in the presence of sodium ethoxide to afford novel derivatives of pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine-5,6-(1H,8H)-diones. E-mail: mosselhi@chem-sci.cairo.eun.eg Received February 8, 2002; accepted (revised) March 18, 2002     

Reactions with 2-mercaptopyrimidines. Synthesis of some new thiazolo[3,2-a]- and triazolo[4,3-a]pyrimidines

Alkylation of 5-cyano-4-oxo-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine I with methyl iodide, chloroacetic acid or 3-chloro-2,4-pentanedione, afforded the S-alkyl derivatives IIa-c. 2-Carboxymethylthio and 2-(2′,4′-dioxopentan-3-ylthio) derivatives IIb and IIc could be cyclised by acetic anhydride or polyphosphoric acid to give 6-cyano-3,5-dioxo-5H-7-phenylthiazolo[3,2-a]pyrimidine III and 2-acetyl-6-carboxamido-5H-3-methyl-7-phenylthiazolo[3,2-a]pyrimidine-5-one IX , respectively. Benzoylation of 2-hydrazinopyrimidine derivative XII , in anhydrous dioxan, afforded the N-benzoyl derivative XIII , which could be cyclised by heating in dimethylformamide to give 5-amino-6-cyano-3,7-diphenyl-s-triazolo[4,3-a]pyrimidine ( XIV ). The 2-hydrazinopyrimidine derivatives XII and XV reacted with benzoyl isothiocyanate in dioxane to yield 4-benzoylthiosemicarbazide derivatives XVI and XVII , which were converted into the 2-s-trizolopyrimidine derivatives XVIII and XIX , respectively. Also, XVI and XVII reacted with 2,4-pentanedione and 3-chloro-2,4-pentanedione to yield 2-pyrazolopyrimidine derivatives XX and XXI , respectively.     

The synthesis of [1]benzothieno[2,3-c]quinolines, [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline,and [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline

Photocyclization of 3-chloro-N-phenylbenzo[b]thiophene-2-carboxamide 10 afforded [1]benzothieno[2,3-c]-quinolin-6(5H)-one 11 which was chlorinated to 6-chloro[1]benzothieno[2,3-c]quinoline 12 followed by dechlorination to give [1]benzothieno[2,3-c]quinoline 5 . A series of 6-substituted alkoxy and thioalkoxy[1]benzothieno[2,3-c]quinoline derivatives were prepared along with the N-methyl quaternary salt 13 of 5 . 6-Chloro[1]-benzothieno[2,3-c]quinoline 12 was converted into 6-hydrazino[1]benzothieno[2,3-c]quinoline 23 which upon treatment with formic acid yielded [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline 6 . Treatment of 23 with nitrous acid resulted in [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline 7 . Compounds 6 and 7 are novel heterocyclic ring systems.     

Dimroth rearrangement in the row of new pyrano[3,4-c][1,2,4]triazolo[4,3-a][1,5-a]pyridines and synthesis of new heterocyclic systems: Pyranopyrazolo[4,3-e][1,2,4]triazolopyridines

New and effective methods for the synthesis of derivatives of pyrano[3,4-c][1,2,4]triazolo[4,3-a][1,5-a]pyridines were developed. Synthesized new tetracyclic heterocyclic systems containing pyrano[3,4-c]pyridine ring unknown in the literature were obtained for the first time. The rearrangement of Dimroth in the triazolo[4,3-a]pyridine systems for the first time was studied. The possibility of rearrangement of Dimroth in the new heterocyclic system has been investigated.     

Synthesis of 3- and 4-(β-D-ribofuranosyl)-s-triazolo[2,3-a] pyrimid-7-one,isomers of inosine containing a bridgehead nitrogen atom

The first synthesis of a purine nucleoside analog containing a bridgehead nitrogen atom is here reported. The direct glycosylation of the trimethylsilyl derivative of s-triazolo[2,3-a] pyrimid-7-one has been shown to give 3-(β-D-ribofuranosyl)-s-triazolo[2,3-a]pyrimid-7-one (V) and 4-(β-D-ribof'uranosyl)-s-lriazolo[2,3-α]pyrimid-7-one (VII). The nueleoside V may he considered a close analog of inosine in which the nitrogen N₁ and C₅ of inosine have been interchanged. Bro-minalion of the tri-O-acelyl derivative IV gave, after deblocking, 6-bromo-3-(β-D-ribofurnaosyl)-s-triazolo[2,3-a] pyrimid-7-one (IX). Structural assignments of the nucleosides were made on the basis of comparison of the ultraviolet absorption spectral characteristics with 3-methyl-s-triazolo-[2,3-a]pyrimid-7-one (XI) and 4-methyl-s-lriazolo[2,3-a Jpyrimid-7-one (XII) prepared by a standard procedure from 7-methoxy-s-triazolo(2,3-a] pyrimidine (X).     

A new method for the synthesis of fused 3-amino-s-triazole ring systems

Reaction of 2-methyl-2-thiopseudourea sulfate with 1-hydrazinophthalazine gave 3-amino-s-triazolo[3,4-a] phthalazine in good yield. 1-Amino-4-methyl-s-triazolo[4,3-a]quinoxaline and 1-amino-s-triazolo[4,3-a]quinoxalin-4(5H)one were similarly perpared.