1,5-Cyclooctadiyne. Preparation and Reactivity

1,5-Cyclooctadiyne 1 was isolated in 2 percent yield from polymerized butatriene 5 . Other oligomers of 5 were detected in the reaction mixture by combined GLC./MS. analysis but have not been identified. Diels-Alder adducts of 1 with two equivalents of 1,3-butadiene and of 2,3-dimethyl-1,3-butadiene have been prepared. In the presence of strong base 1 isomerized to cyclooctatetraene. 5 was reformed by photolysis of 1 . Attempts to prepare transition metal complexes of 1 failed. Effects of ring strain and of transannular interaction on the reactivity of 1 are discussed. The dimerization of 5 to 1 is predicted to be strongly exothermic.     

Beiträge zur Chemie der Silicium-Stickstoff-Verbindungen. CV. Ringschlußreaktionen mit 1,5-Bis(alkylamino)trisildioxanen

1.5-Bis(methylamino)hexamethyltrisildioxane reacts in the presence of triethylamine easily with germanium tetrachloride (equ. 1) and ethyldichlorophosphine (equ.2) to give the formerly unknown inorganic eightmembered ring systems Si₃GeN₂O₂ and Si₃PN₂O₂. Respectively. By analogous reacting of silicon tetrachloride only open chained Cl₃Si? Nme? Sime₂? O? Sime₂? O? Sime? NHme (IV; equ. 3) is formed. With metallated 1.5-bis(alkylamino)trisildioxanes, dischlorodiorganylsilanes do not give the expected asymmetric-, but the symmetric cyclotetrasildioxdiazanes V–VII. Dichlorophenylborane, in an analogous reaction, leads to the novel eightmembered ring system BSi₃N₂O₂, but the exact position of the N and O atoms in the ring could not be fixed beyond any doubt. The novel sixmembered ring system BSi₂Ni₂O was realized in compound IX via equ. (6).     

Pyrazolo[1,5-d]triazines-1,2,4. II étude des pyrazolo[1,5-d]triazinones,des pyrazolo[1,5-d]triazinediones et des pyrazolo[1,5-d]triazinethiones

The synthesis of 1,2-dihydro-l-oxopyrazolo[1,5-d]-1,2,4-triaxine was achieved by rerrangment of 2-(5-pyrazolyl)-1,3,4-oxadiazole under alkaline condition. The cyclization of the N-carbethoxyhydrazone of the pyrazole-5-carboxaldehyde gave the 3,4-dihydro-4-oxopyrazolo[1,5-d]1,2,4-triazine. Electrophilic substitutions of the l-pyrazolotriazinome were made either on the lactam nitrogen with methylsulfate, benzylchloride and monochloracetic axid or on the pyrazole ring with bromine. The synthesis of pyrazolo[1,5-d]-1,2,4-triazine was made from teh l-pyrazolotrizinone via the l-pyrazolotrizinone. The methylation of l-pyrazolotrizinone and 8-bromo-l-pyrazolotrizinone afforded N-and S-methyl derivatives. The sysnthesis of 1,2,3,4-tetrahydropyrazolo[1,5-d]-1,2,4-triazine-1,4-diones was axhived by cyclising N-carbethoxyhydrazides of pyrrole-5-carboxylic acid. The structures of the derivatives were determined by ¹H-nmr.     

Addition of dihalocarbenes to 3H-1,5-benzodiazepines. Synthesis of 2H-bisazirino[1,2-a:2′,1′-d][1,5]benzodiazepines

Addition of dihalocarbenes, generated from haloforms using a phase transfer catalyst, to 3H-1,5-benzodi-azepines gave 2H-Bisazirino[1,2-a:2′,1′-d][1,5]benzodiazepines, a new ring system.     

Reactivity of 7-(2-dimethylaminovinyl)pyrazolo[1,5-a]pyrimidines: Synthesis of pyrazolo[1,5-a]pyrido[3,4-e]pyrimidine derivatives as potential benzodiazepine receptor ligands. 1

A series of 7-methylpyrazolo[1,5-a]pyrimidines were reacted with dimethylformamide dimethylacetal to give the corresponding dimethylaminovinyl derivatives. These were reacted with ammonium acetate affording, through a ring closure, a number of 6-methylpyrazolo[1,5-a]pyrido[3,4-e]pyrimidines bearing various substituents on the pyrazole ring. The 6-acetyl-2-hydroxy-7-methylpyrazolo[1,5-a]pyrimidine was used as starting material for obtaining some O-alkyl derivatives. Catalytic transfer hydrogenation of 2-benzyloxy-6-methylpyrazolo[1,5-a]pyrido[3,4-e]pyrimidine led to the 2-hydroxy derivative.     

The synthesis and chemical reactions of certain pyrazolo[1,5-a]-1,3,5-triazines

3-Aminopyrazole was utilized as a starting material for the preparation of certain pyrazolo-[1,5-a]-1,3,5-triazines. 4-Chloro-2-methylthiopyrazolo[1,5-a]-1,3,5-triazine was prepared and used for studies of nucleophilic displacement reactions, and it has been found that both the chloro and methylthio groups may be displaced by nucleophiles. By modifications of these procedures we have prepared the adenine, hypoxanthine, and xanthine analogs of the pyrazolo-[1,5-a]-1,3,5-triazine ring system. Electrophilic substitution occurs in the 8-position of this ring system. The methyl group was introduced into the 4-position by a novel ring opening and ring closing of the 1,3,5-triazine ring.     

Synthesis of 1,2-dihydroindolo [1,7-AB] [1,5] benzodiazepines and related structures. A new heterocyclic ring system

The synthesis of the novel 1,2-dihydroindolo [1,7-ab][1,5]benzodiazepine ring system 4 is described. Condensation of 2-fluoronitrobenzene with indoline provided the starting material for the synthesis, 1-(2-nitrophenyl)indoline (1a) in high yield. The nitro group was reduced catalytically and the resulting amino function was acylated to afford the heterocycle percursor amide 3. Refluxing this amide in phosphorus oxychloride brought about a Bischler-Napieralski type cyclodehydration to form the target 1,2-dihydroindolo[1,7-ab][1,5]benzodiazepine ring system. Dehydrogenation of the latter led to the fully aromatic indolo[1,7-ab][1,5]benzodiazepine structure 5, while reduction with sodium borohydride provided the 1,2,6,7-tetrahydroindolo[1,7-ab]-[1,5]benzodiazepine tetracycle 6.     

Pyrazolo [1,5-a]indole. 10. Mitteilung über metallogranische reaktionen und folgeprodukte

Pyrazolo[1,5- a ]indoles Treatment of 1-(2-heteroaroyl or aroyl-phenyl)-pyrazoles ( 3 ) with potassium hydroxide in 95% ethanol or with sodium ethanolate in ethanol produces a novel ring closure to new 4-hydroxy-4-(4-heteroaryl or aryl)-4H-pyrazolo [1,5-a]indoles 5 and 6 (Table 1). A 2, 3, or 4-pyridyl at position 4 is easily reduced yielding the 4-(2, 3, or 4-piperidyl)-derivatives 7 and 8 (Table 2). Water is split off from these piperidyl-derivatives 7 or 8 to give the piperidylidene derivatives 9 or 10 (Table 3) which may be considered as heterocyclic analogues to known tricyclic psychopharmaceuticals with antidepressant or neuroleptic activities.     

New routes to the v-triazolo[1,5-a]pyridine and pyrazolo[1,5-a]pyridine ring systems

New routes to the v-triazolo[1,5-a]pyridine and pyrazolo[1,5-a]pyridine ring systems are described. Treatment of the N-amine salts of 2-picolinealdehyde oxime or 2-pyridyl ketone oximes with polyphosphoric acid gave v-triazolo[1,5-a]pyridines in fair yields. Treatment of 2-picolyl ketones or their oximes with O-mesitylenesulfonylhydroxylamine produced directly pyrazolo-[1,5-a]pyridines. These reactions were extended to the quinoline cases.     

1,5,-Electrocyclizations—An Important Principle of Heterocyclic Chemistry

The principle of orbital control of pericyclic reactions has deepened our understanding of reaction phenomena and provided an excellent classification of these one-step processes. The electrocyclic reaction of the pentadienyl anion ? cyclopentenyl anion type is relatively unimportant in all-carbon systems and has not even been verified in the case of the parent compound. In the heterocyclic series, however, where up to five C-atoms of the pentadienyl anion are replaced by heteroatoms, a multitude of ring closures and ring openings find their ordering principle in the mentioned electrocyclic reaction. The replacement of the carbon atoms by heteroatoms can take place isoinically, i. e., with retention of the anionic character, or isoelectronically. An isoelectronic replacement of CR₂ in position 1 by NR₂ OR, and or CR in position 3 by NR or O leads to a charge-free resonance structure for the open-chain species; the migration of the charge during the electrocyclization results in a correlation with a cyclic zwitterion. Conversely, isoelectronic exchange of CR in position 2 by NR or O produces a conjugated 1,3-dipole, which cyclizes to a charge-free unsaturated five-membered ring. Twofold isoelectronic exchange allows the whole process to take place in a cation. Selected examples are to shed light on the classification and the thermodynamics of this electrocyclic reaction.     

Synthesis of some novel 2-phenylpyridazino[4,5-b][1,5]thiazepines

Synthesis of some derivatives of the pyridazino[4,5-b][1,5]thiazepine ring system is reported. Thus, 5-benzyl-8-methyl-2-phenyl-2,3.4,5-tetrahydro-5H-pyridazino[4,5-b][1,5]thiazepin-9(8H)-one ( 5 ) was prepared by an intramolecular S-alkylation reaction, whereas the thiazepine ring of sulfone analogue 21 , and that of the novel tricyclic pyrrolidino fused ring system 22 was elaborated by an intramolecular C-alkylation reaction. Unexpected formation of bicyclic pyrido- and thiazine fused pyridazine systems are also discussed.     

On triazoles XXX. Synthesis of [1,2,4]triazolo-[1,5-d][1,2,4,6]tetrazepine-5-thiones

Different 2-Q-6,7,8,9-(bi-, tri- or tetra)substituted[1,2,4]triazolo[1,5-d][1,2,4,6]tetrazepine-5-triione derivatives representing a novel ring system were synthesised. In the case of 8-aryl-substituted derivatives ring-chain tautomerism was observed in DMSO-d₆ or deuteriochloroform solutions. In some cases both ring and chain tautomers could be isolated in crystalline form. The structure of products obtained was proved by nmr using also model compounds prepared for this purpose.     

Ring opening reactions of 6-oxo-substituted spiro-pyrrolidinediones: Synthesis of 4-substituted-1,5-dihydro-3-hydroxy-2-oxo-1,5-diphenyl-2H-pyrroles

Reaction of 2-oxocylalkaneglyoxylate esters with N-phenylmethyleneaniline yields spiro compounds such as 2-aza-3,4,6,-trioxo-1,2-diphenylspiro[4.4]nonane 4 and cycloalkane-2-aza-3,4,6-trioxo-1,2-diphenylspiro-[4.5]decanes 5–7 . These undergo solvolytic opening of the the oxocycloalkane ring to yield 4-substituted-1,5-dihydro-3-hydroxy-2-oxo-1,5-diphenyl-2H-pyrroles 12–17 .     

Polycondensed nitrogen heterocycles. X. 5,6,7,8-Tetrahydropyrrolo[1,2-e][1,5]benzodiazocin-7-ones. A new ring system

The synthesis of a new heterocyclic ring system is described. Condensation of 1,4-diketones 1a,b with β-alanine gave the substituted propionic acids 2a,b which upon reduction with palladium on charcoal afforded compounds 3a,b . Title compounds 4a,b were obtained by refluxing 3a,b in toluene with p-toluenesulphonic acid as catalyst.     

On triazoles. XXXIX. Synthesis and structure of some 1,2,4-triazolo[1,5-a]pyrimidin-5-one oximes

Some 1,2,4-triazolo[1,5-a]pyrimidin-5-one derivatives 1 and their alicyclic condensed ring analogues 2-3 were converted through the corresponding “imino chlorides” 4-6 to the oximes 7-9 . The “E” isomeric structure of the products obtained was proven with the use of cmr using the spectral data of the corresponding “benzyloximino” derivatives 10-12 prepared as model compounds.     

Ring contractions of dihydro- and tetrahydro-1,5-benzodiazepines in electron ionization mass spectrometry

Electron ionization mass spectra of a series of 2,4-disubstituted dihydro- and tetrahydro-1,5-benzodiazepines are discussed. The fragmentation of these compounds is dominated by ring contractions of diazepine, which give both five- and six-membered rings, benzimidazoles and quinoxalines. Tetrahydro compounds showed a tendency to eliminate one nitrogen from the ring system and give quinoline rings through NH₂ and NH₄ eliminations. The electron ionization spectra of cis and trans isomers of tetrahydro compounds are identical.     

Nuclear magnetic resonance spectra of psychotherapeutic agents. V*—conformational analysis of 1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-ones

The conformational analysis of biologically active lofendazam (7-chloro-5-phenyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one) is carried out by means of lanthanide shift reagent assisted ¹H NMR spectroscopy: the lanthanide induced shift computer simulation suggests that in deuteriochloroform the heterocyclic ring of lofendazam assumes a cycloheptene-like chair conformation, where 1-N moves away from trigonal stereochemistry to a very flattened pyramidal structure. At room temperature the conformational equilibrium is markedly shifted (85%) towards the conformer showing pseudoaxial H-1 and 5-Ph. The remarkable influence of steric requirements in controlling conformation, and the importance of 3- and/or 4-methyl groups in hindering the ring inversion at room temperature, have been verified by conformational analysis of suitable analogous 1,3,4,5-tetraydro-2H-1,5-benzodiazepin-2-ones.     

Thiophene systems. 6. An unexpected bromine migration during the synthesis of thieno[3,4-b][1,5]benzoxazepin-10-ones

7-Bromothieno[3,4-b][1,5]benzoxazepin-10-one ( 1a ) was unexpectedly formed upon acid catalyzed ring closure of 5-bromo-4-ethoxy-2′-hydroxy-3-thiophenecarboxanilide ( 2a ). Ring closure of the chlorine analogue 2c proceeded normally to give 3-chlorothieno[3,4-b][1,5]benzoxazepin-10-one ( 1b ).     

Lewis Acid-Mediated Ring Contraction of 2,4-Diaryl-2,3-dihydro-1H-1,5-benzodiazepines: Access to 2-Aryl-1-styrylbenzimidazoles

2,4-Diaryl-2,3-dihydro-1H-1,5-benzodiazepines readily undergo a ring contraction to generate 2-aryl-1-styrylbenzimidazoles in the presence of some Lewis acids. Copper acetate shows high efficiency compared with other Lewis acids. The ring contraction includes Lewis acid-catalyzed intramolecular addition, ammonium-induced ring-opening of the generated four-membered azetidine ring, deprotonation, and amine-promoted nucleophilic styryl 1,2-shift and elimination. Copper acetate serves as Lewis acid, base, and oxidant. The current reaction provides an efficient method for the convenient synthesis of 2-aryl-1-styrylbenzimidazole derivatives from readily available 2,4-diaryl-2,3-dihydro-1H-1,5-benzodiazepines.     

A new heterocyclic structure. The [1,2,3]triazolo[1,5-d][1,2,4]triazine

The hydrazone derivatives of 4-benzoyl-1,2,3-triazole can easily be cyclised by reaction with various organic reagents (ortho esters, aldehyde and ketone compounds, phosgene, etc) which result in the incorporation of the introduced reagent's carbon atom into the new six membered ring. The newly created C-N bond of the resulting [1,2,3]triazolo[1,5-d][1,2,4]triazines displays a particular sensitivity due to the electron attracting effect of the triazole ring. Some mechanistic considerations are proposed to account for the observed results.