A Novel synthesis of 6-hydroxyalkyl-and 6-hydroxy-aralkyl-6H-dibenz[c,e][1,2]oxaphosphorin 6-Oxides

A new strategy for the synthesis of 6-hydroxyalkyl- and 6-hydroxyaralkyl-6H-dibenz[c,e][1,2]oxaphosphorin 6-oxides 3 was achieved by the reaction of 2-(2-hydroxyphenyl)phenylphosphonic acid ( 1 ) with various carbonyl compounds 2 . The desired products 3 were obtained in acceptable yields.     

Deep eutectic solvent-mediated expedient multicomponent synthesis of oxazine scaffolds

A simple, efficient, and eco-friendly protocol for the synthesis of 1,3-oxazine derivatives, viz. 7-aryl-7,8-dihydro-6H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-e][1,3]oxazines and 3-aryl-3,4-dihydro-2H- naphtho[2,3-e][1,3]oxazine-5,10-diones, involving one-pot multicomponent condensation reaction of various amines and formaldehyde with sesamol/2-hydroxy-1,4-naphthoquinone, respectively, catalyzed by a choline chloride–oxalic acid deep eutectic solvent has been developed. The method offers several advantages, including mild reaction conditions, simple operating procedure, recyclable and biodegradable catalyst, short reaction times, and excellent yields of the target products.

     

Mass spectrometric studies of 6-chloro-6H-dibenz[c,e] [1,2]oxaphosphorine-6-sulphide and its derivatives

The electron-impact induced fragmentation of 6-chloro-6H-dibenz[c,e] [1,2]oxaphosphorine-6-sulphide and its 6-ethoxy and 6-hydroxy derivatives has been studied and it has been found that formation of the dibenz[c,e] [1,2]oxaphosphorin system and elimination of HCP are common features. β-Hydrogen rearrangement, in the case of the ethoxy derivative, is comparable to ethers with a P? O? CH₂? CH₃ linkage.     

Insertion of carbon disulfide and the nitrile group into the diaziridine ring of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes in ionic liquids catalyzed by BF<Subscript>3</Subscript> · Et<Subscript>2</Subscript>O

The present study revealed two new reactions resulting in the diaziridine ring expansion, viz., the insertion of the CS₂ molecule and the CN group of activated nitriles into the C—N bond of the diaziridine fragment of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes. These reactions can be performed only in ionic liquids in the presence of BF₃ · Et₂O as the catalyst. Based on these reactions, we developed simple one-pot methods for the synthesis of 3-aryldihydro-5 H-pyrazolo[1,2- c][1,3,4]thiadiazole-1-thiones and 1-aryl-6,7-dihydro-1 H,5H-pyrazolo-[1,2-a][1,2,4]triazoles in high yields. Dipolar intermediates of new reactions, which are direct precursors of the final products, were detected by NMR methods. One of the intermediates was isolated and characterized. The reaction of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with benzoyl cyanide affords (2-benzoyrpyrazolidin-1-yl)(aryl)acetonitriles.     

Simple and efficient preparation of 3-substituted 6-(4-chlorophenyl)-9-methyl-12H-[1]benzofuro[3,2-e][1,2,4]triazolo[4,3-b][1,2]diazepines via a silylation–amination reaction

Abstract  

A series of new 3-substituted 6-(4-chlorophenyl)-9-methyl-12H-[1]benzofuro[3,2-e][1,2,4]triazolo[4,3-b][1,2]diazepines was synthesized from the corresponding bicyclic 1-(4-chlorophenyl)-3,5-dihydro-8-methyl-4H-[1]benzofuro[2,3-d][1,2]diazepin-4-one. The synthesis strategy makes use of silylation–amination as the key step, allowing a wide range of derivatives to be prepared.     

Reaction of 3,6-di(<Emphasis Type="Italic">tert</Emphasis>-butyl)-1,2-benzoquinone with terminal alkylacetylenes in the presence of phosphorus trichloride

A reaction of 3,6-di(tert-butyl)-1,2-benzoquinone with alkynes in the presence of phosphorus trichloride leads to a predominant formation of 4-alkyl- and 4-haloalkyl-5,8-di(tert-butyl)-2,6-dichloro-2 H- benzo[e][1,2]oxaphosphinine 2-oxide. An ipso-substitution of the tert-butyl group at ortho-position to the oxygen atom of the benzophosphinine system with the formation of 4-alkyl-5- tert-butyl-2,8-dichloro-2 H-benzo[e][1,2]oxaphosphinine 2-oxide was the minor route of the reaction with alkylacetylenes. Molecular structures of 4-butyl-5,8-di( tert-butyl)-2,6-dichloro-2 H- benzo[e][1,2]oxaphosphinine 2-oxide and 5,8-di( tert-butyl)-2,6-dichloro-4-hexyl-2 H-benzo[e][1,2]oxaphosphinine 2-oxide were studied by X-ray analysis.     

Synthesis of novel imidazo[1,2-a][3,1]benzothiazines 4, imidazo[1,2-a]-[1,2,4]benzotriazines 5, and 4H-imidazo[2,3-c]pyrido[2,3-e][1,4]oxazines 6

Starting from the readily available 2-aminobenzhydrols ( 7 ), 3-amino-1,2,4-benzotriazine ( 11 ) and 2-amino-3-pyridinol ( 12 ), novel derivatives of 5-phenyl-5H-imidazo[1,2-a][3,1]benzothiazine-2-carboxylic acid, ethyl ester ( 4 ), imidazo[2,1-c][1,2,4]benzotriazine-2-carboxylic acid, ethyl ester ( 5 ) and 4H-imidazo[2,3-c]pyrido-[2,3-e][1,4]oxazine ( 6 ) were prepared.     

Synthesis of Some New Nitrogen Bridge‐head Triazolopyridines,Pyridotriazines, and Pyridotriazepines Incorporating 6‐Methylchromone Moiety

Some new triazolo[1,5‐a]pyridines, pyrido[1,2‐b][1,2,4]triazines, and pyrido[1,2‐b][1,2,4]triazepines incorporating 6‐methylchromone moiety were prepared from the reaction of 1,6‐diamino‐4‐(6‐methyl‐4‐oxo‐4H‐chromen‐3‐yl)‐2‐oxo‐1,2‐dihydropyridine‐3,5‐dicarbonitrile ( 4 ) with some electrophilic reagents.     

Solvent-free synthesis of dibenzo[b,j][1,10]phenanthroline derivatives using Eaton’s reagent as catalyst

A new class of dibenzo[b,j][1,10]phenanthrolines has been prepared. The synthon acridones were achieved in very good yield by a one-pot reaction of 2-amino-5-chloro or 2′-chloro/flouro-substituted benzophenones with 1,2-cyclohexanedione in the presence of freshly prepared Eaton’s reagent (phosphorus pentoxide–methanesulfonic acid) without solvent, through Friedländer synthesis. Then these intermediates were reacted with 2-amino-3,5-dibromobenzaldehyde to afford 1,3-dibromo-10-chloro-8-aryl-6,7-dihydrodibenzo[b,j][1,10]phenanthroline. Also an one-pot reaction between 2?mol of 2-amino-5-chloro aryl benzophenones with 1?mol of 1,2-cyclohexanedione to get 3,10-dichloro-5,8-diaryl-6,7-dihydrodibenzo[b,j][1,10]phenanthroline has also been reported. The newly synthesized structures of the compounds were deduced by spectroscopic techniques.     

Reaction of sulfenes with heterocyclic N,N-disubstituted α-aminomethyleneketones. XII. Synthesis of [1]benzothiepino[4,5-e][1,2]oxathiin derivatives

The 1,4-cycloaddition of sulfene to N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro[1]benzothiepin-5(2H)-ones I occurred only in the case of aliphatic N,N-disubstitution to give in good yield 4-dialkylamino-3,4,5,6-tetrahydro[1]benzothiepino[4,5-e][1,2]oxathiin 2,2-dioxides, which are derivatives of the new heterocyclic system [1]benzothiepino[4,5-e][1,2]oxathiin. Also the reaction of I with chlorosulfene occurred only in the case of aliphatic N,N-disubstitution to afford chiefly trans-4-dialkylamino-3-chloro-3,4,5,6-tetrahydro-[1]benzothiepino[4,5-e][1,2]oxathiin 2,2-dioxides III in satisfactory yield. Adducts III were dehydrochlorinated with DBN to 4-dialkylamino-5,6-dihydro[1]benzothiepino[4,5-e][1,2]oxathiin 2,2-dioxides in good yield.     

Utilization of cleavage of the [1]benzofuro[2,3‐e][1,2,4]triazine ring for the synthesis of oxygen,nitrogen and sulfur derivatives of [1,2,4]triazine

A series of 6‐azacytosines 4a‐4k and 5a‐5c were prepared by nucleophilic cleavage of furan ring of [1]benzofuro[2,3‐e][1,2,4]triazine derivative 1 . Some of them were used for the preparation of derivatives of [1,2,4]triazolo[4,3‐d][1,2,4]triazine ( 6a‐6d ) and tetrazolo[1,5‐d][1,2,4]triazine (7). The reaction of 1 with hydrogen sulfide afforded the corresponding 6‐(2‐hydroxyphenyl)‐2‐phenyl‐5‐thioxo‐4,5‐dihydro‐1,2,4‐tri‐azin‐3(2H)‐one ( 8 ), while with hydrogen selenide 6‐(2‐hydroxyphenyl)‐2‐phenyl‐4,5‐dihydro‐1,2,4‐triazin‐3(2H)‐one ( 9 ) was formed. The prepared compounds were tested for biological activity.     

Synthesis of Fused 9,10‐Dihydro‐6H‐Azepino‐ and 9,10‐Dihydro‐6H‐[1,3]Diazepino[1,2‐e]Purines via Ring Closing Metathesis as Antilipid Peroxidation Agents

Ring closing metathesis of 8‐allyl‐9‐butenylpurines or N,9‐diallyl‐N‐methyl‐9H‐purin‐8‐amines with the Grubbs second generation catalyst resulted in fused 9,10‐dihydro‐6H‐azepino[1,2‐e]purines or 9,10‐dihydro‐6H‐[1,3]diazepino[1,2‐e]purines, respectively. The 8‐allyl‐9‐butenylpurines were prepared from 8‐bromo‐9‐butenylpurines after Stille coupling with allyltributyltin. The N,9‐diallyl‐N‐methyl‐9H‐purin‐8‐amines were synthesized from 9‐allyl‐8‐bromopurines after treatment with allylamine in H₂O under MW irradiation, followed by methylation with MeI in KOH. The new compounds were tested as inhibitors of lipid peroxidation. 6‐Methyl‐4‐(morpholin‐4‐yl)‐7,10‐dihydro‐6H‐[1,3]diazepino[1,2‐e]purine presents interesting results and could serve as a lead compound.     

Heterocyclic systems. II. Synthesis of 4H,6H-pyrrolo[1,2-a][4,1]benzoxazepine

The reduction of 1-(2-methoxycarbonylphenyl)pyrrole-2-carboxaldehyde by lithium aluminum hydride led to 1-(2-hydroxymethylphenyl)-2-hydroxymethylpyrrole, which was in turn transformed into 4H,6H-pyrrolo-[1,2-a][4,1]benzoxazepine through intramolecular dehydration. The reductive action of sodium borohydride, instead, allowed the preparation of 6-oxo-4H-pyrrolo[1,2-a][4,1]benzoxazepine.     

[3 + 2]-Cycloaddition of azomethine ylide at 1,3-dimethyl-6-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)-3a,9a-diphenyl-3,3a,9,9a-tetrahydroimidazo[4,5-e][1,3]thiazolo[3,2-b][1,2,4]triazine-2,7(1H,6H)-diones

[3 + 2]-Cycloaddition of azomethine ylide generated from formaldehyde and sarcosine at the double bond of 1,3-dimethyl-6-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)-3a,9a-diphenyl-3,3a,9,9a-tetrahydroimidazo[4,5e][1,3]thiazolo[3,2-b][1,2,4]triazine-2,7(1H,6H)-diones occurs stereospecifically at the face opposite to the phenyl substituents. Product 3a crystallizes as a conglomerate.     

Microwave‐assisted synthesis of new regioisomeric 6,7‐dihydroindeno[1,2‐e]pyrimido[4,5‐b][1,4]diazepin‐5(5aH)‐ones

Novel 11‐amino‐6‐aryl‐6,7‐dihydroindeno[1,2‐e] pyrimido[4,5‐b][1,4]diazepin‐5(5aH)‐ones 4a‐f were prepared regioselectively by the tricomponent reaction of 4,5,6‐triaminopyrimidine 1, 1,3‐indandione 2 and aromatic aldehydes 3a‐f. The bicomponent approach, using 2,4,5,6‐tetraaminopyrimidine 5 and 2‐aryl‐ideneindandiones 6a‐f as reagents, afforded 9,11‐diamino‐6‐aryl‐6,7‐dihydroindeno[1,2‐e]pyrimido[4,5‐b]‐[1,4]diazepin‐5(5aH)‐ones 7a‐f in good yields and the regioisomeric 8,10‐diamino derivatives 8a‐c in lower yields. Both, bi‐ and tricomponent approaches were performed by microwave irradiation and all products were fully characterized by detailed NMR measurements.     

Annelated piperazinyl-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidines

Tricyclic analogs of piperazinylthiopyrano[3,2-d]pyrimidine hypoglycemic agents were prepared. The angular tricyclic systems, 8,9-dihydro-7H-thiopyrano[2,3-e][1,2,4]triazolo[4,3-a]pyrimidine and 8,9-dihydro-7H-tetrazolo[1,5-a]thiopyrano[2,3-e]pyrimidine derivatives were synthesized from 2,4-dichloro-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine in three step sequences. Derivatives of the linear tricyclic system, 5,6-dihydro-7H-thiopyrano[3,2-d][1,2,4]triazolo[2,3-a]pyrimidine, were prepared by condensation of 3-amino-1,2,4-triazole with ethyl 3-oxo-tetrahydropyran-2-carboxylate. The tricyclic heteroaryl-piperazines lacked significant hypoglycemic activity.     

Synthesis of [1,2,5]selena(or thia)diazolo[3,4‐e][1,4]diazepines, [1,2,5]selena(or thia)diazolo[3,4‐e][1,4]oxazepines and [1,2,5]selena(or thia)diazolo[3,4‐c] [1,2,6]thiadiazines

Novel heterocycles [1,2,5]selenadiazolo[3,4‐e][1,4]diazepines 3a‐c , [1,2,5]thiadiazolo[3,4‐e]‐[1,4]diazepines 7a‐c , [1,2,5]selenadiazolo[3,4‐e][1,4]oxaepines 4a,b , [1,2,5]thiadiazolo[3,4‐e]‐[1,4]oxazepines 9a‐c and [1,2,5]selena(or thia)diazolo[3,4‐c][1,2,6]thiadiazines 10a,b were synthesized starting form 4,6‐dimethyl[1,2,5]se]enadiazolo[3,4‐d]pyrimidine‐5,7(4H,6H)‐dione 1 or 4,6‐dimethyl‐[1,2,5]thiadiazolo[3,4‐d]pyrimidine‐5,7(4H,6H)‐dione 5 .     

Novel heterocycles. Synthesis of 2,3-dihydro-6-methyl-2-phenyl-4H,6H-pyrano[3,2-c][2,1]benzothiazin-4-one 5,5-dioxide and related compounds

The reaction of 2-chloro-4-(methylsulfonyl)benzoyl chloride ( 5 ) with 1-methyl-1H-2,1-benzothiazin-4-(3H)-one 2,2-dioxide ( 4 ) gave the O-benzoyl compound, 1-methyl-2,2-dioxido-1H-2,1-benzothiazin-4-yl 2-chloro-4-(methylsulfonyl)benzoate ( 6 ), which rearranged to give the C-benzoyl isomer, [2-chloro-4-(methylsulfonyl)phenyl] (4-hydroxy-1-mefhyl-2,2-dioxido-1H-2,1-benzothiazin-3-yl)methanone ( 7 ). The O-cinnamoyl compound 13 that resulted from the addition of 2,4-dichlorocinnamoyl chloride ( 11 ) to compound 4 rearranged to give the C-cinnamoyl compound, 3-(2,4-dichlorophenyl)-1-(4-hydroxy-1-methyl-2,2-dioxido-1H-2,1-benzothiazin-3yl)-2-propen-1-one ( 15 ). On the other hand, 1-methyl-2,2-dioxido-1H-2,1-benzothiazin-4-yl 3-phenyl-2-propenoate ( 19 ) (from cinnamoyl chloride ( 17 ) and compound 4 ) rearranged to give 2,3-dihydro-6-methyl-2-phenyl-4H,6H-pyrano[3,2-c][2,1]benzothiazin-4-one 5,5-dioxide ( 21 ), an example of a hitherto unknown ring system. Additional examples of this novel heterocycle were prepared from 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 23 ) and 1-methyl-1H-thieno[3,2-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 8 ).     

An alternate route to substituted 6,7-dihydro 5H-dibenz[c,e]azepines from allylbenzamides derived from the Morita–Baylis–Hillman adducts

An acid-catalyzed modular synthesis of substituted 5H-dibenz[c,e]azepines from a biaryl allylbenzamides prepared from the MBH adducts via a cascade dearoylation and intramolecular cyclization is described. The utility of the product for preparing 7,9-dihydro-4bH-dibenz[c,e]pyrrolo[1,2-a]azepine is also presented.     

Regioselective construction of six-membered fused heterocyclic rings via Pd/C-mediated C-C coupling followed by iodocyclization strategy: a new entry to 2H-1,2-benzothiazine-1,1-dioxides

We describe a practical and elegant method of constructing a thiazine ring fused with benzene under mild reaction conditions. A variety of 4-iodo-2H-benzo[e][1,2]thiazine-1,1-dioxides were prepared with high regioselectivity via a two-step process involving Pd/C-mediated C-C coupling of o-halobenzenesulfonamides with terminal alkynes, followed by iodocyclization of the resulting o-(1-alkynyl)arenesulfonamide using elemental iodine in acetonitrile. The coupling reaction was carried out using 10% Pd/C-PPh₃-CuI as a catalyst system in the presence of Et₃N. The process worked well for bromides and iodides, and a wide array of terminal alkynes containing alkyl and aryl substituents were employed. The iodocyclization step tolerated a variety of functional groups such as hydroxy, chloro, cyano, and methoxy, producing the six-membered heterocyclic ring selectively. The resulting 4-iodo-2H-benzo[e][1,2]thiazine-1,1-dioxides participated in Sonogashira, Heck, and Suzuki reactions producing a wide range of functionally substituted benzothiazines in good yields.