Ring transformations of heterocyclic compounds. XXI. Diastereoselective built‐up of an aroylcyclohexadiene moiety as second spiro‐connected ring at spiroindolines by pyrylium ring transformation

2,4,6‐Triarylpyrylium perchlorates 1 react with methyleneindolines 3 in situ generated from the corresponding methylindolium salts 2 , which are spiro‐fused with a cycloalkane, benzanellated cycloalkene or a heterocyclic system. These diastereoselective 2,5‐[C₄+C₂] pyrylium ring transformations are carried out in the presence of triethylamine/acetic acid in boiling ethanol to give the dispiroindolines 4 with a trans configuration of the more bulky substituents at the cyclohexadiene ring. By the same type of transformation the dispiro compounds 7/10 with an additional fused benzene ring are obtained from the pyrylium salt 1a and 6/9 , the benzo‐fused analogues of 3 . Spectroscopic data of the transformation products as well as their mode of formation are discussed.     

Ring transformations of heterocyclic compounds. XVI. Spiro[cyclohexadiene-dihydroacridines]. A novel class of spirodihydroacridines by ring transformation of pyrylium salts with 9-methylacridine and its quaternary salts

2,4,6-Triarylpyrylium salts 1 react with the in situ generated anhydrobase of 9,10-dimethylacridinium methosulfate ( 2a ) in the presence of anhydrous sodium acetate in ethanol by a 2,5-[C₄+C₂] pyrylium ring transformation to give the hitherto unknown 6-aroyl-3,5-diaryl-10′-methylspiro[cyclohexa-2,4-diene-1,9′-9′,10′-dihydro-acridines] 3 . When the pyrylium perchlorate 1a is treated under the same conditions with the N-ethyl, N-allyl or N-benzyl substituted acridinium salts 2b-d a dealkylation of these salts occurs and the N-unsubstituted spiro[cyclohexadiene-dihydroacridine] 4a is formed. The same compounds 4 can also be obtained by transformation of the pyrylium salts 1 with 9-methylacridine ( 7 ) and triefhylamine/acetic acid in ethanol. Structure elucidation is performed by an X-ray crystal structure determination of the spiro[cyclohexadiene-dihydroacridine] 3a . Spectroscopic data of the transformation products and their mode of formation are discussed.     

Ring transformations of heterocyclic compounds. XVIII . Spiro[cyclohexadiene-indolines] with three stereocenters from pyrylium salts and chiral methyleneindolines — an example of a high diastereoselective ring transformation

The diastereoselective synthesis of 6-aroyl-3,5-diarylspiro[cyclohexa-2,4-diene-1,2′-indolines] 4 possessing three stereocenters from 2,4,6-triarylpyrylium perchlorates 1 and chiral methyleneindolines 3 (generated in situ by deprotonation of the corresponding 3H-indolium perchlorates 2 ) in the presence of triethylamine/acetic acid in ethanol by a 2,5-[C₄+C₂] pyrylium ring transformation is reported. Structure elucidation is performed by X-ray structure determinations of the spiro[cyclohexadiene-indolines] 4a, 4p and 4t . The influence of various substituents at C-3 of the methyleneindolines 3 on the stereochemistry of the transformation, mechanistic details as well as spectroscopic data of the products 4 are discussed.     

Ring transformations of heterocyclic compounds. XX Benzo‐fused spiro[cyclohexadiene‐dihydroindoles] by ring transformation of pyrylium salts with anhydrobases of benzo[e]‐ and benzo[g]indolium salts

The diastereoselective synthesis of 6‐aroyl‐3,5‐diarylspiro[cyclohexa‐2,4‐diene‐1,2′2′,3′‐dihydro‐1′H‐benzo[e]indoles] 6 and ‐benzo[g]indoles] 7 from 2,4,6‐triarylpyrylium perchlorates 1 and in situ generated 2‐methylene‐2,3‐dihydro‐1H‐benzo[e]indoles 3 or ‐benzo[g]indoles 5 (anhydrobases of the corresponding 2‐methyl‐1H‐benzo[e]indolium perchlorates 2 and 2‐methyl‐3H‐benzo[g]indolium perchlorates 4 , respectively) in the presence of triethylamine/acetic acid in ethanol by a 2,5‐[C₄+C₂] pyrylium ring transformation is reported. Spectroscopic data of the transformation products and their mode of formation are discussed.     

Ring transformations in reactions of heterocyclic compounds with nucleophiles (XX). Conversion of 5-nitropyrimidine into 3,5-dinitropyridine. A novel ring transformation

Heating of 5-nitropyrimidine with acetic acid in water leads to the formation of 3,5-dinitro-pyridine. The mechanism proposed for this novel ring transformation involves a fragmentation of the pyrimidine ring, leading to the formation of a two-atom and a four-atom moiety, which on condensation gives the pyridine ring. With hydrazine hydrate, 5-nitropyrimidine undergoes ring contraction into 4-nitropyrazole.     

Ring transformations of heterocyclic compounds. XXV. Phenanthrene aldehyde imines via ring transformation of pyrylium salts with methylenedihydroisoquinolines—A novel access to the phenanthrene skeleton

The ring transformation of 2,4,6‐triarylpyrylium salts 1 with 2‐methylenedihydroisoquinolines 6 , generated in situ from the related 2‐methylisoquinolinium salts 2 , in the presence of bases is reported. Whereas the transformation of 1 with 2 ( 6 ) and sodium methoxide in methanol leads to 2‐(2,4,6‐triarylphenyl)isoquinolinium salts, with sodium ethoxide in ethanol the aryl substituted phenanthrene‐9‐carbaldehyde imines 4 are obtained, the structure of which was confirmed by an X‐ray structure determination of the 1‐(4‐methylphenyl) substituted derivative. Acid catalyzed hydrolysis of the imines 4 gives rise to the parent phenanthrene aldehydes. The transformation 1 + 2 ( 6 ) → 4 represents a novel access to the phenanthrene skeleton.     

Theoretical studies on geometry,solvent effect,and photochromic mechanism of two bis‐heterocyclic compounds containing pyrazolone ring

Two bis‐heterocyclic compounds containing pyrazolone ring, 1‐phenyl‐3‐methyl‐4‐(6‐hydro‐4‐amino‐5‐sulfo‐2,3‐pyrazine)‐pyrazole‐5‐one and 1‐phenyl‐3‐methyl‐4‐(6‐hydro‐4‐methylamino‐5‐sulfo‐2,3‐pyrazine)‐pyrazole‐5‐one, are investigated to gain a deeper insight into their geometries and photochromic mechanism by applying density functional theory. The solvent effects are simulated using the polarizable continuum model of the self‐consistent reaction field theory. Bader's atom‐in‐molecule theory is used to investigate the nature of hydrogen bonds. The data of energy, dipole moments, and the condensed Fukui functions have been calculated to assess the stability and reactivity of the title compounds. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

Ring transformations of heterocyclic compounds. XXII. Pyrido[1,2‐a]indolium salts from 2‐methyl‐3H‐indoles by pyrylium mediated three carbon annelation

The synthesis of pyrido[1,2‐a]indolium perchlorates 8,11 from 2,4,6‐triarylpyrylium perchlorates 1 and 2‐methyl‐3H‐indoles 6,9 in the presence of a basic condensing agent (anhydrous sodium acetate, piperidine acetate, triethylamine/acetic acid, triethylamine) in ethanol by a 2,4‐[C₃+C₂N] pyrylium ring transformation is reported. Spectroscopic data of the transformation products and their mode of formation are discussed.     

Ring transformations of heterocyclic compounds. XV. N-(2-hydroxyphenyl) substituted 2-alkylamino-4,6-diarylbenzophenones by ring transformation of 2,4,6-triarylpyrylium salts with anhydrobases of benzoxazolium salts

The synthesis of hitherto unknown N-(2-hydroxyphenyl) substituted 2-alkylamino-4,6-diarylbenzophenones 3 from 2,4,6-triarylpyrylium salts 1 and 3-alkyl-2-methylbenzoxazolium salts 2 in the presence of triethylamine in ethanol by a 2,5-[C₄+C₂] pyrylium ring transformation is reported. Structure elucidation is performed by an X-ray crystal structure determination of the benzophenone 3a. Spectroscopic data of the transformation products and their mode of formation via anhydrobases of the salts 2 are discussed.     

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.     

Studies on the chemistry of thienoannelated O,N‐ and S,N‐containing heterocycles. 24 [1]. Synthesis of imidazo[1,5‐d]thieno[2,3‐b][1,4]‐thiazine derivatives as potential receptor ligands

A facile synthesis of the imidazo[1,5‐d]thieno[2,3‐b][1,4]thiazine ring system is described. Reaction of 6‐benzyl‐2,3‐dihydro‐1H‐thieno[2,3‐b][1,4]thiazine‐2‐one ( 1 ) with potassium tert‐butoxide and diethylchlorophosphate gave intermediate 2 which resulted in the disired ring system after adding the corresponding isocyanides and potassium tert‐butoxide.     

Studies on the chemistry of thienoannelated O,N‐ and S,N‐containing heterocycles. 17. Preparation of 1H‐thieno[2,3‐b][1,4]thiazine‐1‐carboxarnides as smooth muscle relaxants

A new series of substituted thieno[1,4]thiazines with an urea moiety has been designed. The synthesis and results of replacement of the quinoline and indoline moieties of lead structure 1 are described. The key step in preparation was the substitution with 4‐nitrophenyl chloroformate to obtain the required reactivity for substitution with diamines. Structural modifications of the amino side chain with the aim of finding tissue specific compounds were carried out. Pharmacological testings explored the presumed calcium‐channel‐antagonistic and potassium‐channel‐opening activities.     

Research on nitrogen containing heterocyclic compounds. XVII. Synthesis of 8H-diimidazo[1,5-a:2′,1′-c][1,4]benzodiazepine,a novel tetracyclic ring of pharmaceutical interest

The synthesis of 8H-diimidazo[1,5-a:2′,1′-c][1,4]benzodiazepine 6 , a novel nitrogen-containing tetracyclic ring, is reported starting from 5H-imidazo[2,1-c][1,4]benzodiazepine 7. Reaction of this compound with nitromethane and subsequent reduction of the obtained nitromethyl derivative 8 afforded 11-aminomethyl-10,11-dihydro-5H-imidazo[2,1-c][1,4]benzodiazepine 9. Treatment of the latter compound with formaldehyde led to 1,2,3,3a-tetrahydro-8H-diimidazo[1,5-a:2′,1′-c][1,4]benzodiazepine 10 , which was then oxidized to the title compound.     

Ring transformations of heterocyclic compounds. XXIII. The UV irradiation product of photochromic 2,4,6‐triaryl‐1‐(spiro[2H‐l‐benzopyran‐2,2′‐indoline]‐6‐yl)pyridinium salts ‐ A phenolate betaine or a pyridinium substituted merocyanine dye?

The synthesis of the novel 2,4,6‐triaryl‐1‐(spiro[2H‐1‐benzopyran‐2,2′‐indoline]‐6‐yl)pyridiniumper‐chlorates 4 by reaction of 5 ‐nitrosalicylaldehydes 6 with 1,3,3‐trimethyl‐2‐methyleneindoline ( 7 ) to 6‐nitro‐spiro[2H‐1‐benzopyran‐2,2′‐indolines] 1 , their stannous chloride reduction to the 6‐amino derivatives 8 , followed by a 2,6‐[C₅+N] ring transformation with 2,4,6‐triarylpyrylium perchlorates 9 , is reported. UV irradiation experiments in twenty solvents of different polarity prove their photochromic properties and show that the photochemically generated negative solvatochromic dyes 5 , formed by ring opening of the benzopyran moiety of 4 , are rather merocyanine than pyridinium phenolate betaine dyes.     

Synthesis of a novel ring‐expanded nucleoside analogue containing the imidazo[4,5‐e][1,3]diazepine ring system with a guanidinocarbamoyl‐substituted cyclopropylidene group in place of a sugar moiety

The synthesis of a novel ring‐expanded nucleoside analogue, (Z)‐1‐((2‐Guanidinocarbamoyl‐cyclopropylidene)methyl)‐4,5,7,8‐tetrahydro‐6H‐6‐iminoimidazo[4,5‐e][1,3]diazepine‐4,8‐dione ( 1 ) has been reported. It was prepared starting from methyl imidazole‐4,5‐dicarboxylate by sequential condensations with 2‐bromo‐2‐bromomethylcyclopropane‐1‐carboxylate and guanidine. The overall yield for the two‐step synthesis is 46%.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 23 . Naphtho[2′,1′:4,5]thieno‐[2,3‐c]naphtho[2,1‐f]quinoline

A previously unknown heterocyclic ring system, naphtho[2′,1′:4,5]thieno[2,3‐c]naphtho[2,1‐f]quinoline ( 14 ), was synthesized via oxidative photocyclization of 3‐chloro‐N‐(2‐phenanthryl)naphtho[1,2‐b]‐thiophene‐2‐carboxamide ( 9 ). Further elaboration of the lactam 10 yielded the unsubstituted ring system 14 . Structural confirmation of compound 14 was accomplished by a total assignment of its ¹H and ¹³C nmr spectra utilizing the concerted two‐dimensional nmr spectroscopic methods.     

Synthesis of a novel purine‐containing heterocyclic ring system: 8,10‐Dimethylindolo[2′,3′:5,6][1,2,4]triazino[4,3‐f]purine‐9,11(8H, 10H, 13H)‐dione

The preparation of a novel purine containing heterocyclic ring system, indolotriazinopurine, by the condensation of 8‐hydrazinotheophylline with 5‐substituted isatins via the intermediate hemiaminal and hydrazone derivatives, is described.     

Synthesis of a novel ring‐expanded (“fat”) nucleotide analogue of phosphonomethoxyethylguanine (PMEG) containing the imidazo[4,5‐e][1,3]diazepine ring system

The synthesis of 6‐amino‐4,5‐dihydro‐8H‐1‐(2‐phosphonylmethoxyethyl)imidazo[4,5‐e][1,3]diazepine‐4,8‐dione (7), a novel ring‐expanded (“fat”) acyclic nucleotide analogue of phosphonomethoxyethylguanine (PMEG), has been reported. It was prepared in 4 steps in 51% overall yield starting from dimethyl imida‐zole‐4,5‐dicarboxylate.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 22 Dibenzo[f,h]benzothieno[2,3‐c]quinoline,dibenzo[f,h]benzothieno[2,3‐c][1,2,4]triazolo[4,3‐a]quinoline and dibenzo[f,h]naphtho[2′,1′:4,5]thieno[2,3‐c]quinoline

Photocyclization of 3‐chloro‐N‐(9‐phenanthryl)benzo[b]‐thiophene‐2‐carboxamide ( 3 ) and 3‐chloro‐N‐(9‐phenanthryl)‐naphtho[1,2‐b]thiophene‐2‐carboxamide ( 10 ) yielded dibenzo[f,h]benzothieno[2,3‐c]‐quinolin‐10(9H)‐one ( 4 ) and dibenzo[f,h]naphtho[2′,1′:4,5]thieno[2,3‐c]quinolin‐10(9H)‐one ( 11 ), respectively. Further elaboration of the lactams provided three novel unsubstituted new ring systems.