Synthesis of indeno[2,1-b][1,4]benzothiazine derivatives from 2-bromoinden-1-ones

2-Bromoinden-1-ones 2 were condensed with 6-substituted 3-aminopyridine-2(1H)-thiones to produce a new type of 4-azaindeno[2,1-b][1,4]benzothiazine derivatives 3 . Substituted 6-phenylindeno[2,1-b][1,4]benzothiazines 4 were also prepared by reacting 2-bromo-5-methoxy- and 2,6-dibromo-5-methoxyinden-1-ones with o-aminobenzenethiol.     

Microwave‐Assisted Synthesis of 10‐(Phthalimidoalkyl)‐halosubstitutedpyrido [3,2‐b][1,4]‐benzothiazine in Dry Media

N‐Alkylation of 10H‐9‐fluoropyrido[3,2‐b][1,4]‐benzothiazine 5a, 10H‐7‐fluoropyrido[3,2‐b][1,4]‐benzothiazine 5b, and 10H‐7‐chloropyrido[3,2‐b][1,4]‐benzothiazine 5c with different N‐(bromoalkyl)phthalimides using anhydrous K₂CO₃ and tetrabutylammonium bromide (TBAB) under dry conditions with microwave irradiation leads to the formation of 10‐(phthalimidoalkyl)‐halosubstitutedpyrido[3,2‐b][1,4]‐benzothiazine (6a–f) along with some unidentified product. Compound 5a is a new azaphenothiazine derivative and was obtained from hitherto unknown 2‐acetylamino‐3‐fluorophenyl‐3′‐nitro‐2′‐pyridylsulfide 4a via Smiles rearrangement. Compound 4a is required for the synthesis and has been prepared starting from 2‐amino‐3‐fluorobenzenethiol 1a in three steps.     

Synthesis of 2,2′‐Bi‐2H‐3,3′‐diaryl‐1,4‐benzothiazines from α,α‐Dibromoacetophenones and o‐Aminothiophenol

Some 2,2′‐bi‐2H‐3,3′‐diaryl‐1,4‐benzothiazines (5a–f) were synthesized from α,α‐dibromoacetophenones and o‐aminothiophenol.     

Stereospecific Synthesis of β‐Lactams from Heterocyclic Imines Using the Staudinger Reaction

The reactions of the heterocyclic imines 5,6‐dihydro‐2H‐[1,3]oxazines and 2H‐1,4‐benzothiazines with different substituted acetyl chlorides in the presence of triethylamine forming β‐lactams were examined focusing on the stereochemistry of the Staudinger reaction.     

Low‐Valent Titanium Induced Simultaneous Reduction of Nitro Group and S?S Bond in Nitrodisulfides: A Facile Synthesis of 2H‐1,4‐Benzothiazines

The simultaneous reduction of nitro group and S? S bond in nitrodisulfides by TiCl₄/Sm system led to the active intermediates 2, which were “living” double‐anions in situ and reacted smoothly with ω‐bromoketones to afford the desired 2/7–1,4‐benzothiazines in good yields under mild and neutral conditions.     

Intramolecular Sulfenylation Using Sulfides Synthesis of 5H‐Pyrrolo[1,2‐a][3,1]benzothiazines

Treatment of N‐[2‐(methylsulfanylmethyl)aryl]pyrroles ( 4 ) with phenyliodine(III) bis(trifluoroacetate) containing trifluoroacetic acid resulted in an interrupted Pummerer‐type reaction to give 5H‐pyrrolo[1,2‐a][3,1]benzothiazines ( 5 ) rather than the normal Pummerer‐type products.     

Novel Benzothiazine Derivatives via Formylation of 2,3‐Dihydro‐4H‐benzo[e][1,4]thiazin‐3‐on‐1,1‐dioxide

A simple, efficient, and clean protocol for the formylation of 2,3‐dihydro‐4H‐1,4‐benzo[e][1,4]thiazin‐3‐on‐1,1‐dioxide is developed. Novel benzothiazine derivatives are synthesized by the reactions of aminovinyl derivative 6 and carbaldehyde 7 with nucleophiles.     

Intramolecular capture of pummerer rearrangement intermediates. I. Synthesis of pyrrolo[2,1-c][1,4]benzothiazines

Treatment of 1-(2-alkylsulfinylphenyl)pyrroles with trifluoroacetic acid in refluxing toluene gives 4-substituted pyrrolo[2,1-c][1,4]benzothiazines in good yield when the alkyl group bears an electron withdrawing substituent on the α-carbon. In the absence of such a group, starting material is recovered. The sulfoxides are prepared by oxidation (mCBPA) of the corresponding sulfide. The sulfides are prepared from 2-aminobenzenethiol either by S-alkylation followed by conversion to the pyrrole using 1,4-dimethoxytetrahydrofuran in glacial acetic acid or by S-alkylation of 1-(2-phenylmercapto)pyrrole followed by oxidation to the sulfoxide.     

A convenient synthesis of 2‐(1H‐1,2,4‐triazol‐1‐yl)‐2H‐1,4‐benzothiazine derivatives

A series of 2‐(1H‐1,2,4‐triazol‐1‐yl)‐2H‐1,4‐benzothiazines were designed and synthesized by condensation of 1,2,4‐triazole‐substituted ω‐bromoacetophenones and o‐aminothiophenols with the aid of K₂CO₃ under mild conditions with moderate to high yields. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:332–336, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20434     

Reactions of 1,2‐dihydro‐4H‐3,1‐benzothiazine‐2,4‐dithiones (trithioisatoic anhydrides) with N‐substituted benzylamines and trialkyl phosphites

Reactions of 1,2‐dihydro‐4H‐3,1‐benzothiazine‐2,4‐dithiones (trithioisatoic anhydrides) 3 with N‐substi‐tuted benzylamines 9 gave 1,2‐dihydroquinazoline‐4‐thiones 10 , o‐thioureidodithiobenzoic acid 11 , o‐aminothiobenzamides 12 , 2‐amino‐3,1‐benzothiazine‐4‐thiones 13 , or quinazoline‐2,4‐dithiones 14 , depending on the kinds of amine and the reaction solvent. On the other hand, reaction of 3 with trialkyl phosphites afforded dialkyl (1,2‐dihydro‐2‐thioxo‐4H‐3,1‐benzothiazin‐4‐yl)phosphonates 18 .     

Synthesis, reactions, and biological activity of 1,4-benzothiazine derivatives

Abstract  

6,7-Dimethoxy-2H-1,4-benzothiazin-3(4H)-one reacts with dimethylformamide dimethylacetal (DMF-DMA) to give the novel enaminone 2-(dimethylaminomethylene)-6,7-dimethoxy-2H-1,4-benzothiazin-3(4H)-one. The reaction of the latter with various active methylene compounds afforded pyrido[3,2-b][1,4]benzothiazines. Also, coupling of the enaminone with diazotized aniline derivatives gave 2-(arylhydrazono)-6,7-dimethoxy-2H-1,4-benzothiazin-3(4H)-ones. Spectral data indicated that the latter compounds exist predominantly in the hydrazone tautomeric form. In addition, coupling of the enaminone with diazotized heterocyclic amines afforded tetra- and pentaheterocyclic ring systems. The antitumor and antimicrobial activity of some of the synthesized compounds was screened.     

Conversion of bis(o‐nitrophenyl)disulfides to heterocycles containing sulfur and nitrogen by the action of samarium diiodide

Treatment of bis(o‐nitrophenyl)disulfides 1 with SmI₂ led to simultaneous reduction of nitro groups and reductive cleavage of S–S bonds as well as the formation of the active intermediates 2 . The intermediates 2 reacted smoothly with aldehydes or ketones, acid chlorides or anhydrides, α‐bromoketones, and α,β‐unsaturated ketones at room temperature to afford the desired benzothiazolines 3 , benzothiazoles 4 , 2H‐1,4‐benzothiazines 5 , and 2,3‐dihydro‐1,5‐benzothiazepines 6 , respectively, in moderate to high yields under mild and neutral conditions. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:156–160, 2001     

Synthesis, 13C NMR spectrum and crystal structure of 10-Phenylpyrido[3,2-b][1,4]benzothiazine 5-Oxide

The compound 10-phenylpyrido[3,2-b][1,4]benzothiazine 5-oxide, 1 , has been obtained in nearly quantitative yield oxidation of 10-phenylpyrido[3,2-b][1,4]benzothiazine with oxygen in dioxane solution. The ¹³C nmr chemical shift assignments of 1 are reported. Its structure has been determined by X-ray single crystal methods. The crystals of 1 are monoclinic, space group P2₁/n. There are four molecules in a unit-cell of dimensions a = 12.347(3), b = 12.947(3), c = 8.987(1)Å, β = 106.73(1)° and V = 1375.8(5) ų. The central ring is in a boat conformation and the sulfoxide oxygen atom occupies the axial position. The folding angle between the planes of the pyrido and the benzo planes is 161.55(9)°.     

Synthesis of heterocyclic nitrogen derivatives from aryl‐1,4‐benzoquinones

Treatment of 2‐aryl‐3,6‐bis(arylamino)‐1,4‐benzoquinones 2a‐h with different acid chlorides, namely acetyl, phenylacetyl and chloroacetyl chloride yields 3a,7a‐dihydropyrrolo[2,3‐f]indole‐2,6‐dione 3, 5‐(N‐phenylacetylarylamino)‐3‐phenylindole‐2,6‐dione 4 and 3‐chloro‐5‐(N‐chloroacetylarylamino)indole‐2,6‐dione 5 respectively. Stirring 2‐aryl‐1,4‐benzoquinones ( 1 ) with ethylenediamine and/or o‐phenyl‐enediamine in methylene chloride gives pyrazino[2,3‐g]quinoxalines derivative 6 and/or tetrapentacene derivative 7 respectively. The products 5‐aryl‐ and 6‐aryl‐1/H‐indazole‐4,7‐diones 8 and 9 were obtained in the 1,3‐dipolar cycloaddition of diazomethane to ( 1 ).     

Synthesis of tricyclic pyrido[2,3‐b][1,4]‐thiazines via nucleophilic substitution of activated precursors

Pyrido‐anellated compounds analogous to tricyclic 1,4‐benzothiazine derivatives were synthesized. Thus, under mild reaction conditiones substitution of thiolactim 3 with different N‐nucleophiles yielded the precursors for compounds, which were cyclized in a further step to the corresponding tricyclic derivatives.     

Condensation products of 2-bromo-3-substituted-inden-1-ones with several primary amines

2-Bromo-3-substituted-inden-1-ones 2 reacted with L-cysteine or 2-aminobenzenethiol to produce 2,3-dihydro-5-phenylindeno[2,1-b][1,4]thiazine in moderate yield or 6-substituted-indeno[2,1-b][1,4]benzothiazines in good yield. The debrominated oxime and the phenylhydrazone of 2 were separated into their respective E- and Z-conformers by column chromatography and their E- and Z-configurations were obtained from the ¹H nmr spectra.     

Highly cis‐Diastereoselective Synthesis of Coumarin‐Based 2,3‐Disubstituted Dihydrobenzothiazines by Organocatalysis

An efficient and organocatalyzed asymmetric reaction of phenacyl halides with coumarin‐based dihydrobenzothiazoles was developed to afford cis‐2,3‐disubstituted 3,4‐dihydro‐2H‐benzothiazines. This method provides a one‐step and highly diastereoselective route to a wide variety of coumarin‐based 3,4‐dihydro‐2H‐benzothiazines using the cheap and commercially available Cinchona alkaloid quinine hydrochloride.     

Eco‐friendly HClO4–SiO2 catalyzed synthesis of mono‐ and bis‐diaryl‐2h‐1,4 benzothiazines

Mono‐ and bis‐diaryl‐2H‐1,4‐benzothiazines were obtained in quantitative yields through silica‐supported perchloric acid catalyzed reaction cascade of double condensation and 1,4 addition of diaroylacetylenes with 2‐aminothiophenol at room temperature. The structures were confirmed by spectroscopic analyses and X‐ray crystallographic studies. J. Heterocyclic Chem., (2011)     

The synthesis of 4H-imidazo[5,1-c][1,4]benzothiazine derivatives

A facile synthesis of the 4H-imidazo[5,1-c][1,4]benzothiazine ring system is described. The synthesis utilized the annulation of an imidazole ring onto a 2H-1,4-benzothiazin-3(4H)-one via the addition of the anion of ethyl isocyanoacetate. Methods for the functionalization of the 1-, 3-, 4-, and 5-positions of the ring system are presented.     

QM study on regioselectivity in the synthesis of pyrimido[4,5-b][1,4]benzothiazines: kinetic and thermodynamic point of view

In the present study, the experimentally observed regioselectivity in pyrimido[4,5-b][1,4]benzothiazine synthesis has been modeled using density functional theory method at M06/6-311++G** level. Also the tautomerism of all four tautomers of 6-ethyl-2-thio(1H) pyrimidin-(3H)-4-one as an important intermediate through the reaction path in pyrimido[4,5-b][1,4]benzothiazine synthesis has been investigated extensively in the gas and solution phase. The stability order of tautomers was found as A > D > B > C, in gas and chloroform solvent; however, changing to more polar solvents this order was changed as A > B > D > C using polarized continuum model. In the next step, we focused on another significant feature of this synthesis which has major role in the observed regioselectivity. Two proposed reaction paths with two different transition states that it seems the mode of its intermolecular cyclization has a special role in regioselectivity of the final product have been considered. Comparison of our calculated NMR and IR spectrum with those already reported for some pyrimido[4,5-b][1,4]benzothiazines demonstrates a reliable agreement. Moreover, all obtained results in the gas and solution phase confirm that the synthesis of above-mentioned compound is thermodynamically more favorable than the possible regioisomeric product.