Expected and unexpected reactions of 1,3-benzothiazine derivatives, I. Ring transformation of β-lactam-condensed 1,3-benzothiazines into 4,5-dihydro-1,4-benzothiazepines and indolo-1,4-benzothiazepines

The ring-enlargement reactions of monochloro-β-lactam-fused 2-aryl-1,3-benzothiazines revealed that the reactions of ortho-nitro aryl-substituted derivatives with sodium methoxide in methanol provided two products, depending on the amount of the base. With 2 equiv of reagent, the expected 1,4-benzothiazepines were obtained. Somewhat surprisingly, treatment with a large excess of sodium methoxide led to the formation of indolo-1,4-benzothiazepines via a novel rearrangement. The structures of the new ring systems were determined by means of X-ray crystallography and NMR spectroscopy.     

Ring transformations of β-lactam-condensed 1,3-benzothiazines to isoquinoline and thiazole derivatives by sulfur extrusion and addition sequences

The ring transformations of dichloro-β-lactam-fused 2-aryl-1,3-benzothiazines with sodium methoxide were investigated. With 2 equiv of base, the dichloro-β-lactam derivatives underwent rearrangement and dihydro-1,4-benzothiazepines, 3,4-substituted isoquinolines and substituted thiazole disulfides were isolated. A possible reaction mechanism is proposed for the simultaneous formation of the novel products. The formation of isoquinoline and thiazole derivatives can be explained by sulfur extrusion and addition sequences.     

Engaging thieno[2,3-b]indole-2,3-dione for the efficient synthesis of spiro[indoline-3,4′-thiopyrano[2,3-b]indole] by reaction with N-substituted isatilidenes

A simple and efficient method, proceeding through a new mechanistic pathway, for the synthesis of spiro[indoline-3,4-thiopyrano[2.3-b]indole derivatives have been developed by exploiting the reaction of thieno[2,3-b]indole-2,3-dione with N-substituted isatilidenes. The compounds synthesized have been screened for antibacterial activity. The generality of the reaction and mechanistic rationale are presented.     

Pyridazines,LIV: On the synthesis of pyridazine-fused S-heterocycles: Thieno[2,3-c]pyridazine,pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine,and pyridazino[3,4-b][1,4]benzothiazine

Summary Starting from 3-chloro-4-pyridazinecarbonitrile (1), the thienopyridazine derivatives2 and3 were prepared. Condensation of3 with triethyl orthoformate afforded the novel tricyclic system4. Reaction of1 with 2-aminothiophenol, followed by treatment with NaH/DMSO was found to give the diaza-phenothiazine6 instead of the expected condensed thiazepine.Dedicated with best wishes to Prof. Dr. G. Zigeuner on the occasion of his 70^th anniversary     

Synthesis and Some Transformations of Derivatives of Pyrido[3,2-b]indole (δ-Carboline)

The reactions of 2-dimethyliminomethyl-3-(p-nitrophenyl)aminoindole chloride with compounds with an active methylene center have been studied. A series of derivatives of -carboline have been synthesized. By the reaction of 3-ethoxycarbonyl-2-methyl-1-p-nitrophenylpyrido[3,2-b]indolinium chloride with the diethyl acetal of DMF the corresponding 2-dimethylaminovinyl derivative was synthesized which was converted into 5-p-nitrophenyl-1-oxo-1,10-dihydropyrano[3',4':5,6]pyrido[3,2-b]indol-5-ium chloride in the presence of acid.     

Unprecedented N→C[1,4] Boc migration: synthesis of 3-carboxyl functionalized 7-azaindolo[2,1-c][1,4]benzoxazine ring system

Use of 1 equiv excess n-BuLi in synthesis of azaindolo[2,1-c][1,4]benzoxazine heterocycles furnished the corresponding 3-(tert-butyloxycarbonyl) derivatives presumably via an unprecedented intramolecular N→C[1,4] Boc migration. Thus, treatment of N-Boc-2-aminopicoline 1a with 3 equiv of n-BuLi at ?15 °C, to generate the dianion Li₂-1a, followed by the reactions with Weinreb amides 2a–h at ?40 °C, and then allowing the reaction mixture to warm upto rt in a controlled manner (?40 to 0 °C, 2 h; 0 °C to rt, 16 h) led to formation of a series of Boc-group migrated products 7a–h generally in good yield (～70% isolated yield). Surprisingly, going from cyclopentylene to cyclohexylene cases (2d–e to 2g–h), the desired [1,4] Boc migration was found to be a minor fate (yield ～20%). In these instances, N→ortho-C[1,3] Boc-migrated compounds 9g–h (to ortho-aryl position) were obtained as major products. Plausible mechanisms have been invoked for the formation of tetracyclic heterocycle 3a, as well as for the observed N→C[1,4] Boc-group migration phenomena supported by data from anion quenching experiments.     

Synthesis of Furano[3,2-c]- and Pyrano[3,2-c]quinolines upon Imino Diels-Alder Reactions Initiated by Nitrosonium （NO^＋）

Efficient nitrosonium （NO＋）-initiated aza-Diels-Alder reactions of N-arylimines with 2,3-dihydrofuran or 3,4-dihydro-2H-pyran allowed access to furano[3,2-c]- or pyrano[3,2-c]quinolines. A mixture of cis and trans-quinoline isomers was obtained in various ratios and yields.     

N-Arylindne 1,4-Cycloaddition Reaction.Preparation of Substituted Hexahydrofurol[3,2-c]quinolines

Thesynthesisofnitrogenheterocyclesthroughcycloadditionreactionofimineshasstimulatedmuchpreparativeandmechanistic.ork'.ThereactionofShiffbaseswithelectron~richolefinshasbeenutilizedfOrthesysthesisofquinolinederi.ati.es2'3.WehavestudiedthecycloadditionofN-arylideneanilineIwith2,3-dihydrofuranandobtainedagroupofsubstitutedhexahydrofuro[3,2-c]quinolines.Generally,thereactionofbenzaldehydewithanilinegiveseasilythecorrespondingN-benzilideneaniline'.Butbenzaldehydewithanelectron-donatinggroupandani…     

Synthesis of Novel 5H-1,2,4-Triazolo[5′,1′:2,3] [1,3]Thiazino[5,6-c]Quinoline-5-Ones

4-chloroquinoline-3-carboxylates 2 and 5-mercapto-1,2,4-triazoles 3 have been cyclised to a novel heterocyclic system 4 .     

Mild and efficient Winterfeldt oxidation of 1,2,3,4-tetrahydro-γ-carbolines for the synthesis of dihydropyrrolo[3,2-b]-quinolones and pyrrolo[3,2-b]quinolones

The Winterfeldt oxidation (NaOH, DMF, air, rt) of substituted 1,2,3,4-tetrahydro-γ-carbolines has been developed, which provides a convenient and efficient method for the synthesis of the corresponding dihydropyrrolo[3,2-b]quinolones in moderate to excellent yields (38-94%). The generality and substrate scope of this reaction are explored and a possible mechanism is proposed. The results imply that electron-withdrawing groups on N2 of tetrahydro-γ-carbolines and N5-H are necessary. The synthesis of 5 or 7-substituted pyrrolo[3,2-b]quinolones in near quantitative yields was also achieved through deprotection and aromatization of N1-Boc-dihydropyrrolo[3,2-b]quinolones.     

A useful ring transformation route to novel thiazepino[7,6-b]indoles from monochloro-β-lactam-fused 1,3-thiazino[6,5-b]indoles,analogues of cyclobrassinin

The Staudinger ketene-imine cycloaddition reactions of cyclobrassinin phytoalexin analogues 2-aryl-4,9-dihydro-1,3-thiazino[6,5-b]indoles with chloroacetyl chloride as a ketene source were investigated under different conditions. Both β-lactam ring formation and the N-chloroacetylation of the indole moiety took place. The indole N-chloroacetyl group can be easily removed by treatment in the presence of silica gel in methanol at reflux temperature. The selective β-lactam formation can be also achieved in certain cases under milder Staudinger conditions. The treatment of azeto[2,1-b]thiazino[6,5-b]indole-1-one derivatives with sodium ethoxide in ethanol provided the novel thiazepino[7,6-b]indole ring systems in a one-step ring transformation. The structures of the new ring systems were determined by means of IR and NMR spectroscopy.     

Thieno[2,3-b]pyridine-2-carbohydrazide in Polyheterocyclic Synthesis: The Synthesis of Pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine,Pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]triazine,and Pyrazolyl,Oxadiazolylthieno[2,3-b]pyridine Derivatives

Pyrdine-2(1H)-thione 1 reacted with ethyl chloroacetate 2 to give 2-S-ethoxy-carbonylmethylpyridine derivative 3, which could be cyclized into thieno[2,3-b]-pyridine-2-carbohydrazide derivative 5 by boiling with hydrazine hydrate. The latter compound reacted with cinnamonitrile derivatives 6a, b, triethylorthoformate, formic acid, dimethylformamide-dimethylacetal, and diethyl carbonate to give the corresponding shiff base 7a, b and pyrido[3′,2′;-4,5]thieno[3,2-d]pyrimidine derivatives 10–13 in respective manner. On the other hand, compound 5 also reacted with carbondisulphide and phenyl isothiocyanate to afford the corresponding 2-(1,3,4-oxadiazolo-2-yl)thieno[2,3-b]pyridine derivatives 18 and 22. Finally, compound 5 reacted with some β-dicarbonyl compounds, such as ethyl acetoacetate, acetylacetone and ethyl β-arylazoacetoacetate, to yield the corresponding 2-(pyrazol-1-yl-carbonyl)thieno[2,3-b]pyridine derivatives 24, 25, and 27 respectively.     

Synthesis of Spiro[1,4-benzothiazine-2,2′-pyrroles] by Reaction of Pyrrolo[1,2-c][4,1]benzoxazepinetriones with 2-Aminobenzenethiol

Russian Journal of Organic Chemistry - 3-Aroylpyrrolo[1,2-c][4,1]benzoxazepine-1,2,4-triones reacted with 2-aminobenzenethiol to give...     

Synthesis,photophysical and antioxidant properties of pyrrolo[3,2-c]carbazole and dipyrrolo[3,2-c:2′,3′-g]carbazole compounds

Research on Chemical Intermediates - The synthesis of (6-ethyl-1,6-dihydropyrrolo[3,2-c]carbazol-2-yl)methanol 5 and...     

One-pot synthesis of highly functionalized pyrano[2,3-c]pyrazole-4,4′-diacetate and 6-oxo-pyrano[2,3-c]pyrazole derivatives catalyzed by urea

A facile one-pot, multicomponent protocol for the synthesis of 1,4-dihydro-pyrano[2,3-c]pyrazole derivatives using a urea catalyst is reported. This transformation proceeds via a four-component reaction of ethyl acetoacetate, a hydrazine, 3-oxo-pentanedioic acid dimethyl ester, and malononitrile. The bifunctional nature of urea means that it catalyzes many steps in this transformation, including domino Knoevenagel condensation, Michael addition, and ring opening and closing reactions. This synthetic method has several advantages, including good yield, simple work-up, harmless by-products, and simple purification.     

Synthesis of Angular [1,2,5]Oxadiazolo[3,4-b]pyrazino-[1′,2′ : 1,2]pyrrolo[2,3-e][1,4]diazepine by Stepwise Reaction of Pyrrolo[1,2-a]pyrazinetrione with 3,4-Diaminofurazan

Russian Journal of Organic Chemistry - Diaminofurazan reacted with 8-benzoyl-2-phenyl-3,4-dihydropyrrolo[1,2-a]pyrazine-1,6,7(2H)- trione to give addition product of the amino group to the double...