Novel Synthesis and Antimicrobial Activity of 3‐Substituted 5‐bromo‐7‐methyl‐1,2,4‐triazolo‐[3,4‐b]‐benzothiazoles

4‐Methyl acetanilide ( 1 ) on treatment with bromine in acetic acid, followed by hydrolysis with dilute HCl/NaOH solution, yielded 2‐bromo‐4‐methyl aniline ( 2 ), which on treatment with sodium thiocyanate in acetic acid afforded 2‐amino‐4‐bromo‐6‐methyl benzothiazole ( 3 ). Compound 3 in ethylene glycol was heated at 150°C with 80% hydrazine hydrate to get 4‐bromo‐2‐hydrazino‐6‐methyl benzothiazole ( 4 ). This hydrazino compound 4 on heating with formic acid for 3 h yielded 4‐bromo‐2‐hydrazinoformyl‐6‐methyl benzothiazole ( 5 ). Same compound 4 when heated independently with formic acid for 6 h/urea for 3 h/carbon disulfide in alkali afforded 5‐bromo‐7‐methyl ( 6 )/5‐bromo‐3‐hydroxy‐7‐methyl ( 7 )/5‐bromo‐3‐mercapto‐7‐methyl ( 8 )‐1,2,4‐triazolo‐[3,4‐b]‐benzothiazoles, respectively. Compound 4 on heating with acetic acid/acetic anhydride gave acetyl benzothiazolyl derivative 9 , which on cyclization with orthophosphoric acid yielded 5‐bromo‐3,7‐dimethyl‐1,2,4‐triazolo‐[3,4‐b]‐benzothiazole ( 10 ). All these newly synthesized compounds were screened for antimicrobial activity against Escherichia coli (Gram ?ve), Bacillus subtilis (Gram +ve), Erwinia carotovora, and Xanthomonas citri using ampicillin, streptomycin, and penicillin as a standard for comparison.     

Synthesis of 5‐[2‐(guanin‐9‐yl)‐ and 5‐[2‐(2‐aminopurin‐9‐yl)ethyl]‐2‐D‐ribo‐(1,2′,3′,4′‐tetrahydroxybutyl)‐1,3‐dioxane

Stereoselective synthesis of 5‐[2‐(guanin‐9‐yl)‐ and 5‐[2‐(2‐aminopurin‐9‐yl)ethyl]‐2‐D‐ribo‐(1′,2′,3′,4′‐tetrahydroxybutyl)‐1,3‐dioxane, 2‐5, as potential prodrugs of penciclovir, has been accomplished in six steps from readily available 2,3,4,5‐tetra‐O‐acetyl‐aldehydo‐D‐ribose ( 6 ) and the 1,3‐diol 7 . It has been demonstrated that the use of boron trifluoride diethyl etherate (BF₃·Et₂O) in dichloromethane along with excess anhydrous copper(II) sulfate was crucial for the efficient formation of cyclic acetal 8 . In addition, the chromatographic separation of cis and trans isomers of the cyclic acetal at the bromide stage 10 was feasible, which was requisite for the successful stereoselective synthesis of the ribosyl derivatives 2–5 .     

Synthesis and Antibacterial Activity of 3‐(5‐Methylisoxazol‐3‐yl) −1,2,4‐triazolo [3,4‐b]‐1,3,4‐thiadiazine Derivatives

The condensed products 2‐10 of 4‐amino‐5‐mercapto‐3‐(5‐methylisoxazol‐3‐yl)‐l,2,4‐triazole (1) with chloroacetaldehyde, 2‐bromocyclohexanone, chloranil, ωbromo‐ω‐(1H‐1, 2,4‐triazol‐l‐yl)acetophenone, 2‐bromo‐4′‐substituted acetophenones and 2‐bromo‐6′‐methoxy‐2′‐acetonaphthone were described. The antibacterial activities were also evaluated.     

An Efficient Synthesis of a Potential (−)‐Reserpine Intermediate from (−)‐Shikimic Acid of the Chiral Pool

A highly stereoselective route to the polysubstituted chiral octahydrobenzofuran 12 , a potential synthon for the E‐ring core in the (?)‐reserpine synthesis, is described. The α‐bromo acetal 11 was obtained from inexpensive (?)‐shikimic acid ( 3 ) through a series of highly stereoselective chemical reactions (Scheme). Et₃B/Bu₃SnH‐Mediated intramolecular radical cyclization of 11 led to compound 12 with the required configuration.     

Synthesis of (+) or (-)-2-(8′-Diphenylphosphino-1′-naphthyl)oxazoline Ligands and Their Application in Pd-Catalyzed Allylic Alkylation Reaction

ＩｎｔｒｏｄｕｃｔｉｏｎＷｉｔｈｔｈｅｆａｍｏｕｓＤＩＯＰｌｉｇａｎｄ ,ＫａｇａｎｉｎｔｒｏｄｕｃｅｄｔｈｅｉｍｐｏｒｔａｎｔｃｏｎｃｅｐｔｏｆＣ2 ｓｙｍｍｅｔｒｙｉｎｌｉｇａｎｄｄｅｓｉｇｎ .1Ｈｏｗｅｖｅｒ ,ｉｔｉｓｎｏｔａｌｗａｙｓｔｒｕｅｔｈａｔａＣ2 ｓｙｍｍｅｔｒｉｃｌｉｇａｎｄｓｈｏｕｌｄｎｅｃｅｓｓａｒｉｌｙｂｅｓｕｐｅｒｉｏｒｔｏａｎｏｎ ｓｙｍｍｅｔｒｉｃｃｏｕｎ ｔｅｒｐａｒｔ .Ｔｒａｎｓｉｔｉｏｎｍｅｔａｌ ｃａｔａｌｙｚｅｄａｌｌｙｌｉｃａｌｋｙｌａｔｉｏｎｖｉａｓｙｍｍｅ…     

Efficient synthesis and dehydration reaction of trichloromethylated 2‐(3‐phenyl‐5‐hydroxy‐4,5‐dihydro‐1H‐pyrazol‐1‐yl)‐4‐aryl‐5‐alkylthiazoles

A convenient method for the synthesis of a novel series of 11, specifically substituted, noncondensed 5,5‐bicycles 2‐[3‐phenyl‐5‐hydroxy‐5‐trichloromethyl‐4,5‐dihydro‐1H‐pyrazol‐1‐yl]‐4‐aryl‐5‐alkylthiazoles ( 3a–k ; 65–94% yield) from the reactions of 3‐phenyl‐5‐hydroxy‐5‐trichloromethyl‐4,5‐dihydro‐1H‐1‐pyrazolethiocarboxyamide ( 1 ) with substituted 2‐bromo‐4′‐acetophenones ( 2a–f ) and 2‐bromo‐4′‐propiophenones ( 2g–k ) is reported. Dehydration of compounds 3a–k with a mixture of concentrated sulfuric acid/chloroform furnished the corresponding 2‐[3‐phenyl‐5‐trichloromethyl‐1H‐pyrazol‐1‐yl]‐4‐aryl‐5‐alkylthiazoles ( 4a–k ) in good yields (61–93%). © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:132–137, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10113     

N,N,N′,N′‐Tetrabromobenzene‐1,3‐Disulfonamide and Poly(N‐Bromo‐N‐Ethyl‐Benzene‐1,3‐Disulfonamide) as Efficient Catalysts for the Methoxymethylation of Alcohols under Solvent‐Free Conditions

Methoxymethylation of a variety of alcohols was performed using formaldehyde dimethyl acetal in the presence of N,N,N′,N′‐tetrabromobenzene‐1,3‐disulfonamide [TBBDA] and poly(N‐bromo‐N‐ethylbenzene‐1,3‐disulfonamide) [PBBS] as catalysts at room temperature and solvent‐free conditions. The methoxymethyl ethers (MOM‐ethers) were obtained with good to excellent yields.     

Regioselective grignard metathesis reaction of 2,5‐dibromo‐3‐(6′‐hexylpyridine‐2′‐yl)thiophene and kumada coupling polymerization

2,5‐Dibromo‐3‐(6′‐hexylpyridine‐2′‐yl)thiophene ( DBPyTh ) was synthesized by the Suzuki coupling reaction between two aromatic compounds followed by the bromination. The Grignard metathesis reaction of DBPyTh with isopropylmagnesium chloride proceeded in 85% conversion and the regioselective halogen–metal exchange at the 2‐position was confirmed. Namely, 5‐bromo‐2‐chloromagnesio‐3‐(6′‐hexylpyridine‐2′‐yl)thiophene and 2‐bromo‐5‐chloromagnesio‐3‐(6′‐hexylpyridine‐2′‐yl)thiophene were generated in 90:10 molar ratio. Subsequently, the Kumada coupling polymerization was carried out using 1,3‐bis(diphenylphosphinopropane)nickel(II) dichloride to obtain poly(3‐(6′‐hexylpyridine‐2′‐yl)thiophene) ( PolyPyTh ). The polymer molecular weight could be roughly controlled by the catalyst concentration and the molecular weight distribution ranged from 1.25 to 1.80. The gas chromatograph analysis indicated that 5‐bromo‐2‐chloromagnesio‐3‐(6′‐hexylpyridine‐2′‐yl)thiophene was preferentially polymerized in 90% conversion and the percentage of the head‐to‐tail content (regioregularity) was calculated to be 96%. The matrix‐assisted laser desorption/ionization time‐of‐fright mass spectrum indicated that both polymer chain ends were substituted with the hydrogen atom. The absorption maxima of polymer in CHCl₃ and thin film were observed at 447 and 457 nm, respectively, which were blue‐shifted compared with poly(3‐(4′‐octylphenyl)thiophene). From the CV measurement of the polymer thin film, highest occupied molecular orbital (HOMO) (?5.31 eV) and lowest unoccupied molecular orbital (LUMO) (?3.76 eV) energy levels were calculated from the oxidation and reduction onset potentials, respectively, and the electrochemical band gap energy was determined to be 1.62 eV. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Liquid‐Phase Synthesis of 2‐Methyl‐2‐Aryloxypropanoic Acid Derivatives from Polyethylene Glycol) Supported 2‐Bromo‐2‐Methylpropanoate

An efficient liquid‐phase synthesis of 2‐methyl‐2‐aryloxypropanoic acid derivatives with good yields and high purity on soluble polyethylene glycol (PEG) has been developed by treatment of PEG‐bound 2‐bromo‐2‐methylpropanoate with phenoxides in the presence of a catalytic amount of NBu₄I and KI, and subsequent cleavage from the PEG.     

Unusual tosyl transfer solvolysis reaction to 3‐n‐butyl‐4‐methyl‐5,5‐di‐p‐toluenesulfonyl‐ 3 ‐pyrrolin‐2‐one

The title compound ( 1 ) was isolated in 20‐30% recovery following solvolysis of a mixture of 5‐bromo‐3‐n‐butyl‐4‐methyl‐2‐p‐toluenesulfonylpyrrole ( 4b ) and 5‐bromo‐4‐n‐butyl‐3‐methyl‐2‐p‐toluenesulfonyl‐pyrrole ( 4a ) in trifluoroacetic acid and water, a reaction designed to produce 5‐p‐toluenesulfonyl‐3‐pyrrolin‐2‐ones, e.g., 5a and 5b .     

Synthesis of 5,6‐dihydro‐2‐trifluoromethyl‐1,4‐dioxin‐3‐carboxanilides through polymer‐bound activated ester: Construction of dihydro‐1,4‐dioxin

A new construction of dihydro‐1,4‐dioxin and a synthesis of 5,6‐dihydro‐2‐trifluoromethyl‐1,4‐dioxin‐3‐carboxanilides 22 through polymer‐bound activated ester are described. An intermediate β‐hydroxy ether 18 was prepared from the substitution reaction of α‐thio‐α‐chloro compound 8 with ethylene glycol followed by treatment with Raney Ni. Replacement of hydroxy by chlorine and then dehydrochlorination afforded trifluoromethyl dihydro‐1,4‐dioxin ester 15. The polymer‐bound trifluoromethyl dihydro‐1,4‐dioxin‐3‐carboxylic acid, 4‐hydroxy‐3‐nitrobenzophenone ester ( 21 ) was prepared through the reaction of polystyrene‐bound 4‐hydroxy‐3‐nitrobenzophenone ( 19 ) with the trifluoromethyl dihydro‐1,4‐dioxin‐3‐carbonyl chloride ( 20 ). Refluxing of 21 with substituted aniline in acetonitrile gave the corresponding carboxanilide 22. The reaction rate depended on the nucleophilicity of nitrogen of the aniline.     

Selective α-Bromination of β-Keto Esters in Reusable PEG-400 under Mild and Catalyst-free Conditions

An efficient bromination protocol for the synthesis of α-bromo-β-keto esters has been developed. In PEG-400 （poly（ethylene glycol-400））, a variety of β-keto esters were treated with NBS （N-bromosuccinimide） at room temperature to selectively afford the corresponding α-monobromination products in excellent yields. It is noteworthy that the reaction was conducted under mild, environmentally benign and catalyst-free conditions.     

7‐Halogenated 7‐Deaza‐2′‐deoxyxanthine 2′‐Deoxyribonucleosides

The synthesis of the 7‐halogenated derivatives 1b (7‐bromo) and 1c (7‐iodo) of 7‐deaza‐2′‐deoxyxanthosine ( 1a ) is described. A partial Br→I exchange was observed when the demethylation of 6‐methoxy precursor compound 4b was performed with Me₃SiCl/NaI. This reaction is circumvented by the nucleophilic displacement of the MeO group under strong alkaline conditions. The halogenated 7‐deaza‐2′‐deoxyxanthosine derivatives 1b , c show a decreased S‐conformer population of the sugar moiety compared to the nonhalogenated 1a . They are expected to form stronger triplexes when they replace 1a in the 1 ?dA?dT base triplet.     

An Efficient Synthesis of 5,6‐Dimethoxy 1‐ and 2‐Naphthols via Teuber Reaction

Based on the oxidation of 1,5‐naphthalenediol ( 4 ) and 6‐bromo‐2‐naphthol ( 9 ) via Teuber reaction, an efficient synthesis of 5,6‐dimethoxy‐1‐naphthol ( 1 ) and 5,6‐dimethoxy‐2‐naphthol ( 2 ) was achieved with high overall yield (16% for 1 and 25% for 2 ). The key steps of the synthetic strategy involved the oxidation of naphthols ( 4 and 9 ) to the corresponding naphthoquinones ( 5 and 10 ) and the conversion of 5,6‐dimethoxy‐2‐naphthaldehyde to 5,6‐dimethoxy‐2‐naphthol formate through Baeyer‐Villiger oxidation‐rearrangement.     

Synthesis of (E)‐4‐Bromo‐3‐methoxybut‐3‐en‐2‐one,the Key Fragment in the Polyhydroxylated Chain Common to Oscillariolide and Phormidolides A–C

The terminal bromomethoxydiene (BMD) moiety of the polyhydroxylated chain present in phormidolides and oscillariolides has been synthesized for first time. Several strategies for the stereoselective synthesis of the 4‐bromo‐3‐methoxybut‐3‐en‐2‐ones are described. Furthermore, a preliminary study to successfully introduce the BMD within the polyol chain and the fatty acid allowed us to corroborate the end structure of the polyol.     

Palladium‐catalyzed amination with benzophenone imine as a new,safe and practical alternative to nitration for the synthesis of 7‐amino‐2,1,3‐benzothiadiazoles

Palladium‐catalyzed amination of 7‐bromo‐4‐methyl‐2,1,3‐benzothiadiazole ( 7 ) with benzophenone imine as an ammonia equivalent is described as a new, safe and practical alternative to nitration for the synthesis of 7‐amino‐4‐methyl‐2,1,3‐benzothiadiazole ( 1 ) in high yield. This methodology was successfully scaled‐up in the pilot plant on 14.0‐kg scale of 7 and was also utilized for the synthesis of 7‐amino‐4,6‐dimethyl‐2,1,3‐ben‐zothiadiazole ( 12 ) by the amination of 7‐bromo‐4,6‐dimethyl‐2,1,3‐benzothiadiazole ( 10 ).     

Heterocyclic Systems Containing Bridged Nitrogen Atom: Synthesis and Antibacterial Activity of 3‐(2‐Phenylquinolin‐4‐yl)/3‐(1‐p‐Chlorophenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazine Derivatives

The condensation of 4‐amino‐5‐mercapto‐3‐(2‐phenylquinolin‐4‐yl)/3‐(1‐p‐chlorophenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,2,4‐triazoles 1a‐b with chloroacetaldehyde 2a‐b , ω‐bromo‐ω‐(1H‐1,2,4‐triazol‐1‐yl)acetophenone 3a‐b , chloranil 4a‐b , 2‐bromocyclohexanone 5a‐b , 2,4′‐dibromoacetophenone 6a‐b and 2‐bromo‐6′‐methoxy‐2′‐acetonaphthone 7a‐b are described. The structures of the compounds synthesized were confirmed by elemental analyses, IR, 1H NMR and mass spectra. The antibacterial activities were also evaluated.     

Two‐Step Synthesis of 1,3‐Disubstituted 3,4‐Dihydro‐4‐thioxoquinazolin‐2(1H)‐ones from 1‐Bromo‐2‐fluorobenzenes

An efficient synthesis of 3‐alkyl‐3,4‐dihydro‐4‐thioxobenzoquinazolin‐2(1H)‐ones 3 has been accomplished in two steps and in satisfactory yields from 1‐bromo‐2‐fluorobenzenes 1 . Thus, the reaction of 1‐fluoro‐2‐lithiobenzenes, generated by the Br/Li exchange between 1 and BuLi, with alkyl isothiocyanates, gives N‐alkyl‐2‐fluorobenzothioamides 2 , which, in turn, react with a series of isocyanates in the presence of NaH to give the desired products 3 .     

Design and Synthesis of Novel 6‐(5‐Methyl‐1H‐1,2,3‐triazol‐4‐yl)‐5‐[(2‐(thiazol‐2‐yl)hydrazono)methyl]imidazo[2,1‐b]thiazoles as Antimicrobial Agents

Novel 6‐(1,2,3‐triazol‐4‐yl)‐5‐[(2‐(thiazol‐2‐yl)hydrazono)methyl]imidazo[2,1‐b ]thiazoles 7 , 9a , 9b , 9c , 9d , and 11 were prepared by reaction of thiosemicarbazone 5a , 5b with either hydrazonoyl chloride 6 , phenacylbromides 8 or 2‐bromo‐1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)ethanone 10 respectively. The new products were tested for their antimicrobial activities using 96‐well micro‐plate assay, and compound 7 showed excellent antibacterial activities compared with Vancomycine (reference drugs), while compounds 5b and 9c exhibited good results against yeast. The minimum inhibitory concentration (MIC) was determined, and compound 7 showed the lowest MIC against Gram positive bacteria while compound 5b showed the lowest MIC against yeast.     

Derivatives of α‐ and β‐S‐thiophosphates of 2‐bromo‐2‐deoxy‐D‐hexopyranose

The first examples of S‐thiophosphate derivatives of 2‐bromo‐2‐deoxy sugars 7–12 were synthesized by reacting alkyl ammonium salts 1–4 of thiophosphoric acids with α‐1,2‐cis (5) or α‐1,2‐trans dibromo sugars (6) and addition of free thiophosphoric acids 1a or 2a to 2‐bromo‐D‐glucal (13). It was observed that the solvent determines formation of either the O‐ or S‐glycosyl compound. β‐Thiophosphates can be transformed to the α‐configuration in the presence of acid in quantitative yield. The structures of the synthesized derivatives of 7–12 were confirmed by spectroscopic methods. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 465–470, 1999