Reactions of 2-aminobenzenethiols with 4-hydroxycoumarin,maleic anhydride and p-chlorobenzoylacetone: A single step synthesis of heterocycles containing the 1,4-thiazine nucleus

A single step and convenient synthesis of some heterocycles containing the 1,4-thiazine nucleus are reported by the condensation and cyclization of substituted 2-aminobenzenethiols with 4-hydroxycoumarin, maleic anhydride and p-chlorobenzoylacetone.     

Synthesis and antimicrobial activity of structurally flexible heterocycles with the 1,4-thiazine heterosystem

In this work, 4H-1,4-benzothiazines were synthesized by an efficient synthetic method in a single step involving heterocyclization of substituted 2-aminobenzenethiols with β-ketoester. The structures of the synthesized compounds were confirmed by their analytical and spectral data. The synthesized compounds were evaluated for their antimicrobial activity against bacterial species; E. coli and Bacillus cereus. The synthesized compounds showed significant activity against microorganisms, which can be correlated with the privileged heterocyclic structural scaffolds.     

An Efficient Synthesis and Antimicrobial Studies of Bioactive 4H-1,4-Benzothiazine and Their Sulfone Derivatives

Abstract

4H-1,4-benzothiazines were prepared by condensation followed by oxidative cyclization of substituted 2-aminobenzenethiols with β-diketones in dimethylsulfoxide. On refluxing with 30% hydrogen peroxide in glacial acetic acid, 4H-1,4-benzothiazines yielded 4H-1,4-benzothiazine-1,1-dioxides. Structural evaluation has been done by spectral and elemental analysis. All the synthesized compounds were evaluated for their antibacterial and antifungal activity and all these have shown moderate to high activity against the test microbes.

Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures and tables.     

A step forward in the field of drug design: 1,5-benzothiazepines and their nucleosides

(±)cis-2-(4-methoxyphenyl)-3-hydroxy/methoxy-6-methoxy/8-methoxy-2,3-dihydro-1,5-benzothiazepin-4-[5H/5-chloroacetyl/5-(4′-methylpiperazino-1′)acetyl]-ones and nucleosides viz; (±)cis-2-(4-methoxyphenyl)-3,6-dimethoxy-2,3-dihydro-1,5-benzothiazepin-4-[5-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)]-one and (±)cis-2-(4-methoxyphenyl)-3,8-dimethoxy-2,3-dihydro-1,5-benzothiazepin-4-[5-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)]-one have been synthesized by the condensation of substituted-2-aminobenzenethiols with methyl (±)trans-3-(4-methoxyphenyl)glycidate in xylene and by stirring the 3-methoxy derivative of 1,5-benzothiazepin-4(5H)-ones with sugar namely β-D-ribofuranosyl-1-acetate-2,3,5-tribenzoate at 155–160 °C in vacuo for 10 hours, respectively. The synthesized compounds have been characterized by the elemental analyses and spectral data and screened for their antimicrobial activity.     

Syntheses of 1,5-Benzothiazepines: Part XXXVI—Syntheses and Antimicrobial Evaluation of 2-(2-Chlorophenyl)-4-(4-chlorophenyl/2-thienyl)-2,5-dihydro-8-substituted-1,5-benzothiazepines

Six 5-substituted-2-aminobenzenethiols have been reacted with 3-(2-chlorophenyl)-1-(4-chlorophenyl)-2-propenone and 3-(2-chlorophenyl)-1-(2-thienyl)-2-propenone in dry ethanol saturated with dry HCl gas, to obtain twelve new compounds, 8-substituted-2-(2-chlorophenyl)-4-(4-chlorophenyl/2-thienyl)-2,5-dihydro-1,5-benzothiazepines in satisfactory yields. The structures of the final products have been assigned by elemental microanalyses data for elements, C, H, and N and by IR, ¹ H NMR, and mass spectroscopies. The synthesized compounds have been evaluated for their relative antimicrobial activity against the gram-positive bacteria, Staphylococcus aureus, gram-negative bacteria, Pseudomonas aeruginosa and the fungus, Candida albicans. The compounds have been found to show little antibacterial activity, but interestingly, showed significant antifungal activity.     

A New Synthesis of 2-Arylbenzothiazoles from 1,2,3-Benzodithiazole-2-Oxides

The reaction of 6-substituted-1,2,3-benzodithiazole-2-oxides (3a-3d) with aromatic aldehydes, carboxylic acids, and their chlorides in the presence of an organic base provides a new method for the synthesis of 6-substituted-2-arylbenzothiazoles (4a-4d) without involving the preparation of intermediate 2-aminobenzenethiols.     

Synthesis and antimicrobial activity of 2,4-diaryl-2,3-dihydrobenzo[b][1,4]thiazepines

A new series of structurally diverse 2,3-dihydrobenzo[b][1,4]thiazepines (2,3-dihydro-1,5-benzothiazepines) with substituted phenyl groups at C(2) and C(4) have been synthesized by reaction of 3-(5-bromo-2-methoxyphenyl)-1-arylpropen-1-ones with 2-aminobenzenethiols. The structures of all the synthesized compounds were confirmed by their analytical and spectral data (IR, ¹H NMR, ¹³C NMR). All the synthesized compounds were evaluated for antibacterial and antifungal activity against a variety of bacterial and fungal strains and interesting results were obtained. Some of the compounds had antibacterial and antifungal activity comparable to that of ciprofloxacin and fluconazole.     

A General and Efficient Synthesis of 2-Phenylbenzothiazoles From Diphenyl Disulfides

Benzothiazoles containing a substituted-phenyl at the 2 position can be synthesized cleanly and efficiently from the corresponding bis(2-aminophenyl) disulfide. Bis(2-aminophenyl) disulfides represent a stable source of 2-aminobenzenethiols.     

Synthesis of benzothiazoles from 2-aminobenzenethiols in the presence of a reusable polythiazolium precatalyst under atmospheric pressure of carbon dioxide

Synthesis of benzothiazoles from 2-aminobenzenethiols and carbon dioxide was carried out using poly(3,4-dimethyl-5-vinylthiazolium) iodide as a precatalyst to in situ generation of NHCs by deprotonation. The reaction was successfully carried out under mild conditions (1 atm of CO₂ and 60–70 °C) with a broad substrate scope and functional group tolerance. The precatalyst salt was recovered and reused for several times without any loss of activity.     

One-pot synthesis of 2-trifluoromethyl and 2-difluoromethyl substituted benzo-1,3-diazoles

2-Trifluoromethyl and 2-difluoromethyl substituted benzimidazole, benzoxazole and benzothiazole derivatives were efficiently prepared through a one-pot reaction of trifluoroacetic acid and difluoroacetic acid, respectively, with commercially available o-phenylenediamines, 2-aminophenols, and 2-aminobenzenethiols in good to excellent yields. Subsequential bromination of 2-difluoromethyl groups by photolysis with NBS led to the formation of bromodifluoromethyl benzo-1,3-diazoles which may be utilized to prepare the new generation of gem-difluoromethylene linked identical or non-identical twin molecules for drug synthesis.     

Syntheses of 1,5-Benzothiazepines-Part XXXI: Syntheses and Antimicrobial Studies of 10-Substituted-7- (monochlorophenyl/dichlorophenyl)-6H-6a,7-dihydro-6-phenyl[1]benzopyrano[3,4-c]-[1,5]benzothiazepines

Abstract

Two flavindogenides, 3-(2-chlorobenzylidene)-flavanone and 3-(2,4-dichloro- benzylidene)-flavanone reacted with six 5-substituted-2-aminobenzenethiols, the substituents being fluoro, chloro, bromo, methyl, methoxyl, and ethoxyl, to give respective 12 new compounds, 10-substituted-7-(2-chlorophenyl/2,4-dichlorophenyl)- 6H-6a,7-dihydro-6-phenyl[1]benzopyrano[3,4?c][1,5]benzothiazepines (5a–l) in 60–70% yields. The products were characterized on the basis of microanalytical data for elements and IR, ¹ H, and ¹³ C NMR and mass spectral studies. All the synthesized compounds were evaluated for their antimicrobial activity against the bacteria,Escherichia coli and GFC,and the fungi,Aspergillus niger, Aspergillus flavus,and Curvularia lunata.     

“Green synthesis” of benzothiazepine library of indeno analogues and their in vitro antimicrobial activity

A novel series of indeno-benzothiazepine derivatives was synthesised via a “green” route. Synthesis of these compounds involves the treatment of dinucleophiles such as 2-aminobenzenethiols with α,β-unsaturated ketones in poly(oxyethylene) (poly(ethylene glycol), PEG-400) catalysed by acetic acid. The synthone α,β-unsaturated ketones were obtained by Claisen-Schmidt condensation of indan-1-one with substituted pyrazole-2-carbaldehydes prompted by bleaching earth (pH 12.5) as catalyst and PEG-400 as “green” reaction solvent. Screening of all the synthesised compounds for antimicrobial activity revealed that most of these compounds exhibited moderate to significant antimicrobial activity.     

Multigram Solution‐Phase Synthesis of Three Diastereomeric Tripeptidic Second‐Generation Dendrons Based on (2S,4S)‐, (2S,4R)‐, and (2R,4S)‐4‐Aminoprolines

Three diastereomeric second‐generation (G2) dendrons were prepared by using (2S,4S)‐, (2S,4R)‐, and (2R,4S)‐4‐aminoprolines on the multigram scale with highly optimized and fully reproducible solution‐phase methods. The peripheral 4‐aminoproline branching units of all the dendrons have the 2S,4S configuration throughout, whereas those units at the focal point have the 2S,4S, 2S,4R, and 2R,4S configurations. These latter configurations led to the dendrons being named (2S,4S)‐ 1 , (2S,4R)‐ 1 , and (2R,4S)‐ 1 , respectively. The 4‐aminoproline derivatives used in this study are new, although many closely related compounds exist. Their syntheses were optimized. The dendron assembly involved amide coupling, the efficiency of which was also optimized by employing the following well‐known reagents: EDC/HOBt, DCC/HOSu, TBTA/HOBt, TBTU/HOBt, BOP/HOBt, pentafluorophenol, and PyBOP/HOBt. It was found that the use of PyBOP is by far the best for dendrons (2S,4S)‐ 1 and (2R,4S)‐ 1 , and pentafluorophenol active ester is best for (2S,4R)‐ 1 . Because of their multigram scale, all couplings were done in solution instead of by solid‐phase procedures. Purifications were, nevertheless, easy. The optical purities of the key intermediates as well as the three G2 dendrons were analyzed by chiral HPLC analysis. These novel, diastereomeric second‐generation dendrons have a rather compact and conformationally highly rigid structure that makes them interesting candidates for applications, for example, in the field of dendronized polymers and in organocatalysis.     

2-Benzoylamino-6,7-dimethoxy-4H-3,1-benzoxazin-4-one: Synthesis and investigation of serine protease inactivation

Summary 2-Benzoylamino-6,7-dimethoxy-4H-3,1-benzoxazin-4-one was prepared by thermal treatment of 2-(3-benzoylthioureido)-4,5-dimethoxybenzoic acid and by benzoylation of 2-amino-6,7-dimethoxy-4H-3,1-benzoxazin-4-one. The inactivation of chymotrypsin and human leukozyte elastase by the title compound and 2-benzoylamino-4H-3,1-benzoxazin-4-one is reported.

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2-Benzoylamino-6,7-dimethoxy-4H-3,1-benzoxazin-4-on: Synthese und Untersuchung der Inaktivierung von Serin-Proteasen

Zusammenfassung 2-Benzoylamino-6,7-dimethoxy-4H-3,1-benzoxazin-4-on wurde durch thermische Behandlung von 2-(3-Benzoylthioureido)-4,5-dimethoxybenzoesäure und durch Benzoylierung von 2-Amino-6,7-dimethoxy-4H-3,1-benzoxazin-4-on hergestellt. Über die Inaktivierung von Chymotrypsin und humaner Leukozyten-Elastase durch die Titelverbindung und 2-Benzoylamino-4H-3,1-benzoxazin-4-on wird berichtet.

     

1,2,5-Selenadiazoles. Synthesis and properties

4-Amino-1, 2, 5-selenadiazole-3-carboxylic acid and 4-amino-1, 2, 5-selenadiazole-3-carboxamides have been prepared by ring-cleavage of [1, 2, 5]selenadiazolo[3, 4-d]pyrimidin-7(6H)-one by basic reagents. The primary amide (III), as well as an N-alkyl amide, may be produced by the action of a primary amine. Hydrazine reductively cleaves the selenadiazole ring. The preparation of similar 4-ureido derivatives by ring-cleavage of [1,2,5]selenadiazolo[3, 4-d]pyrimidine-5, 7(4 H, 6H)-dione has been demonstrated with two examples. N-Butyl-4-ureido-1, 2, 5-selenadiazole-3-carboxamide is easily hydrolyzed in aqueous base to the corresponding acid, and it has been shown that this reaction proceeds by way of [1, 2, 5]selenadiazolo[3,4-d]pyrimidine-5, 7 (4H, 6H)-dione. The 4-amino-1, 2, 5-selenadiazole-3-carboxylic acid derivatives have marked cytotoxic, antibacterial, and antifungal activity.     

Five-membered 2,3-dioxo heterocycles: LXXVIII. Acylation of fischer’s base with aroylketenes. Crystalline and molecular structure of (1E, 3Z)-4-(4-chlorophenyl)-4-hydroxy-1-(1,3,3-trimethyl-2,3-dihydro-1H-indol-2-ylidene)but-3-en-2-one

Aroylketenes generated by thermolysis of 6-aryl-2,2-dimethyl-4H-1,3-dioxin-4-ones reacted with 1,3,3-trimethyl-2-methylidene-1,3-dihydro-2H-indole (Fischer’s base) to produce (1E,3Z)-4-aryl-4-hydroxy-1-(1,3,3-trimethyl-1,3-dihydro-2H-indol-2-ylidene)but-3-en-2-ones. The crystalline and molecular structures of (1E,3Z)-4-(4-chlorophenyl)-4-hydroxy-1-(1,3,3-trimethyl-2,3-dihydro-1H-indol-2-ylidene)but-3-en-2-one were determined by X-ray analysis.     

Synthesis, spectroscopic properties and crystal structure determination of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole derivatives

Substituted 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole derivatives 2, 3 and 6 were synthesized. 2-(2-Pyridin-4-yl-vinyl)-1H-benzimidazole 2 and 6-methyl-2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 3 were prepared by condensation reaction from 3-pyridin-4-yl-acrylic acid and corresponding 1,2-phenylenediamines in polyphosporic acid (PPA). 2,7,11-b-Triaza-benzo[c]fluorene 4 was prepared by photochemical dehydrocyclization reaction of ethanolic solution of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 2. 2-(2-Pyridin-4-yl-vinyl)-3H-benzimidazole-6-carbonitrile 6 was prepared by condensation reaction from 3-pyridin-4-yl-propenal and 4-cyano-1,2-phenylenediamine using p-benzoquinone as oxidants. The structure of novel benzimidazole derivatives has been studied by ¹H and ¹³C NMR, IR, MS, UV/Vis and fluorescence spectroscopy. The structure of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 2 was confirmed by X-ray single crystal structure analysis. The conformation of the molecule is E in regard to substituents position around vinyl double C=C bond. The non-planar molecules are mutually connected via the N–H···N and C–H···N type of intermolecular hydrogen bonds into infinite chains spreading along y axis.     

Bemerkungen zur Synthese von 5-Amino-m-xylol-2-sulfonsäure und 5-Amino-m-xylol-4-sulfonsäure

Some comments on the syntheses of 5-amino-m-xylene-2-sulfonic acid and 5-amino-m-xylene-4-sulfonic acid Treatment of 5-amino-m-xylene ( 1 ) with oleum led to a 55:45 mixture of 5-amino-m-xylene-2-sulfonic acid ( 2 ) and 5-amino-m-xylene-4-sulfonic acid ( 3 ). The structure of both isomers was proven by reaction of sulfur dioxide with the diazonium chlorides derived from 2-amino-5-nitro-m-xylene ( 5 ) and 4-amino-5-nitro-m-xylene ( 8 ) giving 5-nitro-m-xylene-2-sulfonyl chloride ( 6 ) and 5-nitro-m-xylene-4-sulfonyl chloride ( 9 ) respectively, followed by hydrolyses to the corresponding sulfonic acids 7 and 10 , and final Béchamp reductions. The sulfonic acid 2 was also prepared by sulfonation of 5-acetylamino-m-xylene ( 4 ) to 5-acetylamino-m-xylene-2-sulfonic acid ( 11 ) and subsequent hydrolysis. A further procedure for the synthesis of 3 was sulfonation of 5-amino-2-chloro-m-xylene ( 12 ) – prepared by Béchamp reduction of 2-chloro-5-nitro-m-xylene ( 13 ) – or of 5-amino-2-bromo-m-xylene ( 15 ) – prepared by bromination of 4 and subsequent hydrolysis – to 5-amino-2-chloro-m-xylene-4-sulfonic acid ( 16 ) and 5-amino-2-bromo-m-xylene-4-sulfonic acid ( 17 ) respectively, followed by hydrogenolysis.     

Syntheses,Crystal Structures and Properties of the Tetrametaphosphimates MII2(PO2NH)4 · 8 H2O with MII = Mg,Mn, Co and Zn

Mg₂(PO₂NH)₄ · 8 H₂O ( 1 ), Mn₂(PO₂NH)₄ · 8 H₂O ( 2 ), Co₂(PO₂NH)₄ · 8 H₂O ( 3 ) and Zn₂(PO₂NH)₄ · 8 H₂O ( 4 ) were obtained as microcrystalline powders by combining aqueous solutions of K₄(PO₂NH)₄ · 4 H₂O and MX₂ · y H₂O (M = Mg, Mn, Co, Zn; X = Cl, NO₃). Single crystals were obtained by crystallization in gelatine gels in U‐tubes or test‐tubes. 2 and 4 were characterized by thermogravimetry and 4 was additionally characterized by temperature dependend in situ powder diffractometry. The structures of 1 , 2 , 3 and 4 were found to be isotypic and were solved by single‐crystal X‐ray methods: P 2₁/c, Z = 2 ( 1 : a = 645.4(2), b = 1050.1(2), c = 1283.3(3) pm, β = 104.66(3)°; 2 : a = 648.7(2), b = 1063.1(2), c = 1310.8(3) pm, β = 103.93(3)°; 3 : a = 643.3(2), b = 1049.0(2), c = 1286.7(3) pm, β = 104.28(3)°; 4 : a = 644.18(5), b = 1049.22(7), c = 1282.43(8) pm, β = 104.122(6)°). The structure is composed of MO₆ octahedra and (PO₂NH)₄^4— anions. The P₄N₄ rings of the (PO₂NH)₄^4— anions exhibit a slightly distorted chair conformation, which is supported by IR data and has been described by torsion angles, Displacement Asymmetry Parameters and Puckering Parameters. Via M²⁺ ions and hydrogen bonds, the tetrametaphosphimate anions are connected forming layers perpendicular to [100]. These layers are connected by hydrogen bonds.     

Facile addition of methyl lithium to a 4-vinylpyridine system

The rapid addition of methyl lithium to the 4-vinylpyridine system present in 4-{2,6-dihydroxy-4-(3-methyl-2-octyl)phenyl}-2-methyl-4-(4-pyridyl)but-3-en-2-ol ( 2 ) is reported. The α and β-4-{2,6-dihydroxy-4-(3-methyl-2-octyl)phenyl}-2,3-dimethyl-4-(4-pyridyl)butan-2-ols 4 and 5 formed, are cyclised by heating with 5N hydrochloric acid to trans and cis-3,4-dihydro-5-hydroxy-7-(3-methyl-2-octyl)-4-(4-pyridyl)-2,2,3-trimethyl-2H-1-benzopyran 6 and 7 respectively.