Synthesis of some new fused thiopyrano[2,3-d]thiazoles and their derivatives

A series of some new fused thiopyrano[2,3-d]thiazole derivatives have been synthesized by a stereo-selective hetero-Diels-Alder reaction of 5-(2,4-dihydroxy-benzylidene)-4-thioxo-thiazolidine derivatives 3a,b with acrylonitrile, ethyl acrylate, N-phenylmale-imide, ω-nitrostyrene and N-phenyl-1, 3, 4-triazole-2,5-dione. 5-Amino-9-hydroxy-dihydro-benzopyrano[3′,4′:4,5]thiopyrano[2,3-d]thiazol-6-one derivatives 14a,b have been synthesized by Michael addition of 3a,b with malononitrile. Structures and conceivable mechanisms are discussed.     

An efficient microwave-assisted synthesis of thieno[2,3- b ]quinolines under solvent-free conditions

A novel and efficient method for the synthesis of substituted thieno[2,3-b]quinolines has been developed. A simple one-pot reaction of 3-formyl-2-mercaptoquinolines 2a–l with 1-chloroacetone, 2-chloroacetamide, ethyl chloroacetate and 2-chloro-1-phenylethanone in presence of catalytic amount of potassium carbonate under microwave irradiation and solvent-free conditions gave thieno[2,3-b]quinolin-2-ylethanone derivatives 3a–e, thieno[2,3-b]quinoline-2-carboxamide derivatives 4a–e, ethyl thieno[2,3-b]quinoline-2-carboxylate 5a–e and phenyl(thieno[2,3-b]quinolin-2-yl)methanone derivatives 6a–e compounds respectively. The structures of all the newly synthesised compounds were elucidated on the basis of elemental analysis, IR, ¹H NMR and mass spectral data.     

A short-cut to 2,7-dihydrothiopyrano[2,3-b]pyrrole

A simple original approach to earlier unknown parent 2,7-dihydrothiopyrano[2,3-b]pyrrole (5) from allyl isothiocyanate and propargyl bromide via one-pot synthesis and thermal rearrangement of 2-(prop-2-ynylsulfanyl)-1H-pyrrole (4) has been developed. The compound 5 in the present study was successfully examined as 2,7-dihydrothiopyrano[2,3-b]pyrrole scaffold in the synthesis of corresponding N- and C-pyrrolecarbodithioates.     

Synthesis and anticancer activity of novel thiopyrano[2,3-d]thiazole-based compounds containing norbornane moiety

The series of 9,14-disubstituted 3,7-dithia-5,14-diazapentacyclo[9.5.1.0^{2, 10}.0^{4, 8}.0^{12, 16}]heptadecen-4(8)-triones-6, 13, 15 were synthesized using hetero-Diels-Alder reactions starting from 4-thioxo-2-thiazolidinones and 5-norbornene-2,3-dicarboxylic acid imido-derivatives. Screening of anticancer activity in vitro yielded the most active compounds 5c, 5d, and 7b in micromolar concentrations at the GI₅₀ level (LogGI₅₀ is?6.40 to?4.02 for different cell lines, LogGI₅₀ mean graph midpoint varies from?4.67 to?4.05); moreover, compounds 5c and 5d have a distinctive selectivity against leukemia. The highest sensitivity to compound 5d showed leukemia cell lines CCRF-CEM (LogGI₅₀=?6.40) and SR (LogGI₅₀=?6.06).     

Synthesis of novel 2,3-condensed thieno[2,3- d ]pyrimidin-4-ones via Appel's salt chemistry

The chemistry of imino-1,2,3-dithiazoles possessing a thiophene ring with various alkyl and aromatic diamines was investigated in the expectation of obtaining novel 2,3-condensed thieno[2,3-d]pyrimidinone derivatives. Obtained via Appel's salt's (1) chemistry, methyl N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-2-thiophenecarboxylate (2) is confirmed as a very interesting starting material for access to a variety of novel thiophene bioisosters of bioactive pentacyclic tetraaza-pentaphene-5, 8-diones.     

Pyridine-2(1H)-thione in heterocyclic synthesis: synthesis and antimicrobial activity of some new thio-substituted ethyl nicotinate,thieno[2,3-b]pyridine and pyridothienopyrimidine derivatives

3-(4-Bromophenyl)-2-cyanoprop-2-enethioamide (1) reacted with ethyl 3-oxo-3-phenylpropanoate (2) to give ethyl 4-(4-bromophenyl)-5-cyano-2-phenyl-6-thioxo-1,6-dihydropyridine-3-carboxylate (3). Compound 3 was taken as a starting material for the synthesis of thio-substituted ethyl nicotinate derivatives 5a–d, which underwent cyclization to the corresponding thieno[2,3-b]pyridines 6a–d. Also 3 reacted with hydrazine hydrate to give the pyrazolo[3,4-b]pyridine derivative 7, which upon diazotization gave the diazonium derivative 8. Compound 6a condensed with dimethylformamide–dimethylacetal to afford thieno[2,3-b]pyridine derivative 9, which reacted with different amines 10a–e to afford the pyridothienopyrimidine derivatives 12a–e through the Dimroth rearrangement. Moreover, compound 6a reacted with different reagents to give pyridothienopyrimidine derivatives 14a and b, 17 and pyrazolothienopyridine derivative 18. In addition, acetylating compound 6c with chloroacetylchloride afforded the 3-[(2)-chloroacetylamino]thieno[2,3-b]pyridine derivative 20, which upon cyclization yielded the corresponding 2-chloromethylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine derivative 21. Some of the newly synthesized compounds were screened in vitro for their antimicrobial activities.

     

Pyrido[2,3-d]pyrimidine-2,7-dithiol in heterocyclic synthesis: Synthesis and characterization of several new fused pyridopyrimidine heterocycles

Pyridine-2(1H)-thione 1 reacted with phenyl isothiocyanate to give pyrido[2,3-d]pyrimidine derivative 3. Compound 3 reacted with halogen containing compounds 4a–d and methyl iodide in dimethylformamide/potassium hydroxide solution at room temperature to give 2,7-bisalkylthiopyrido[2,3-b]pyrimidine derivatives 5a–d and 9, respectively. Compounds 5a–d could be cyclized into thienopyrido[2,3-d]pyrimidine derivatives 6a–d by boiling with ethanolic potassium hydroxide solution. Compound 6a reacted with acetic anhydride or formic acid and gave the corresponding pyrimido[4″,5″:4′,5′]thieno[3′,2′:5,6]pyrido[2,3-d]pyrimidine derivatives 8a,b. Compound 9 reacted with hydrazine hydrate to yield pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidine derivative 11 which could be reacted with nitrous acid and dimethylformamide-dimethylacetal (DMF-DMA) and gave the final isolable products corresponding to the pyrazolo[4′,3′:5,6]pyrido[2,3-d]tetrazolo-[5,1-b]pyrimidine and pyrimido[1″,2″:1′,5′]pyrazolo[4′,3′:5,6]pyrido[2,3-d]1 Abbas, A. A., Elneairy, M. A.A. and Mabkhot, Y. N. 2001. J. Chem. Res.(S), 4: 124[Crossref] , [Google Scholar] 2 Riad, B. Y., Negem, A. M., Abdou, S. E. and Daboun, H. A. 1987. Heterocycles, 26: 205[Crossref], [Web of Science ®] , [Google Scholar] 4 Gad-Elkareem, M. A.M. and Abedelhamid, A. O. 2004. Afinidad, 61(513): 427[Web of Science ®] , [Google Scholar]triazolo-[4,3-b] pyrimidine derivatives 13 and 17, respectively. Compound 11 also reacted with some β-dicarbonyl compounds such as acetylacetone (18) and ethyl acetoacetate (20) to yield the corresponding pyrimido[1″,2″:1′,5′]pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidine derivatives 19 and 21, respectively. Finally, compound 11 reacted with chloroacetyl chloride (22) to give the corresponding imidazo[1″′,2″′:1″,5″]pyrazolo[4″,3″:5′,6′]pyrido[3′,2′:5,6]pyrimido[2,1-c]1 Abbas, A. A., Elneairy, M. A.A. and Mabkhot, Y. N. 2001. J. Chem. Res.(S), 4: 124[Crossref] , [Google Scholar] 2 Riad, B. Y., Negem, A. M., Abdou, S. E. and Daboun, H. A. 1987. Heterocycles, 26: 205[Crossref], [Web of Science ®] , [Google Scholar] 4 Gad-Elkareem, M. A.M. and Abedelhamid, A. O. 2004. Afinidad, 61(513): 427[Web of Science ®] , [Google Scholar]triazine derivative 23.     

Facile synthesis and characterization of novel bis(2-S-alkylpyridines) and bis(3-aminothieno[2,3-b]pyridines) incorporating 1,3-diarylpyrazole moiety

3-(4-Hydroxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (1) is condensed with acetophenone to afford the corresponding unsaturated carbonyl compound 4 whose potassium salt is reacted with 1,4-dibromobutane to afford the bis-unsaturated carbonyl compound 3. Both carbonyl compounds 3 and 4 are reacted with 2-cyanoethanethioamide, through Michael addition reaction followed by cyclocondensation, to prepare the starting materials bis(pyridine-2(1H)-thione) derivative 5 and pyridine-2(1H)-thione derivative 8. Two synthetic routes to synthesize the target materials 7 and 14 are described to get the most efficient method for preparation and maximum yield%. The first route came from the direct alkylation of the bis(pyridine-2(1H)-thione) derivative 5 using iodomethane (6a) and benzyl chloride (6b) to afford the corresponding bis(2-S-alkylpyridine) derivatives 7a,b. The reaction of 5 with halo-containing compounds 10a–d to synthesize the target materials bis(3-aminothieno[2,3-b]pyridine) derivatives 14a–d failed under various reaction conditions. The second route involves the reaction of pyridine-2(1H)-thione derivative 8 with 6a,b and 10a–d to afford the corresponding 2-S-alkylpyridine derivatives 9a,b and 3-aminothieno[2,3-b]pyridine derivatives 13a–d, through the formation of 2-S-alkylpyridine derivatives 12a–d followed by a Thrope-Ziegler reaction, whose potassium salts reacted with 1,4-dibromobutane to afford the corresponding target materials 7a,b and 14a–d, respectively. The structures of target molecules were elucidated using elemental analyses and spectral data.     

A simple and versatile protocol for the preparation of functionalized heterocycles utilizing 4-benzoyl-5-phenylamino-2,3-dihydrothiophene-2,3-dione

The reaction of ethyl benzoylpyruvate with phenyl isothiocyanate in alkaline medium yields 4-benzoyl-5-phenylamino-2,3-dihydrothiophene-2,3-dione (1). Reaction of the intermediate 1 with primary aromatic amines such as aniline derivatives, benzidine and secondary aliphatic amines, namely diethylamine, piperidine, morpholine and piperazine afforded the corresponding thiophene 2a–2g and amide 3a–3d derivatives. Compound 1 reacts with N,N′- and N,O-dinucleophiles such as 1,2-diaminoalkanes, 2-aminoethanol, 1-aminoguanidine, guanidine, urea, 1,2-phenylenediamine and 2-amino-4-methylphenol to form the heterocylic compounds 4–10.     

Optimization of fermentation condition for co-production of ethanol and 2,3-butanediol (2,3-BD) from hemicellolosic hydrolysates by Klebsiella oxytoca XF7

Microbial production of ethanol and 2,3-butanediol (2,3-BD) from agro-residues has been attracting interest because of their applications in various industries, including generation of biofuel molecules. In the present investigation, the hemicellulosic fraction of corncob was hydrolyzed by indigenous holocellulase from novel psychrotolerant Aspergillus niger SH3 resulting in high xylose release (34.61?g?L^?1), followed by the bioconversion of xylose to ethanol and 2,3-BD. Taguchi design was adopted to optimize the process which resulted in 5.25- and 3.31-fold increase in 2,3-BD (12.18?±?0.53?g?L^?1) and ethanol (4.08?±?0.03?g?L^?1), as compared with un-optimized condition. For the first time, co-production of ethanol and 2,3-BD from the corncob hemicellulosic hydrolysate was performed using a newly isolated Klebsiella oxytoca XF7 strain, under the optimized fermentation conditions. These results suggest that K. oxytoca XF7 is a promising candidate for co-production of ethanol and 2,3-BD, with high xylose conversion efficiency (96.65%), facilitating the economical production of biofuel molecules.     

Oxidative Coupling of Alkenes with Aldehydes and Hydroperoxides: One‐Pot Synthesis of 2,3‐Epoxy Ketones

A new transition metal‐free oxidative coupling of unactivated terminal alkenes with aldehydes and hydroperoxides in the presence of 10 mol% potassium tert‐butanolate (t‐BuOK) is described thereby realizing trifunctionalization of alkenes toward 2,3‐epoxy ketones. This method is applicable to a wide range of aldehydes, including aryl and alkyl aldehydes, with excellent functional group tolerance, and provides for the one‐step assembly of 2,3‐epoxy ketones.

     

Synthesis and anticorrosion properties of poly(2,3‐dimethylaniline) doped with phosphoric acid

Poly(2,3‐dimethylaniline) (P(2,3‐DMA)) was synthesized chemically by using phosphoric acid (H₃PO₄) as protonic acid. The optimum ratio for n(H₃PO₄)/n(2,3‐DMA)/n(APS) was 2.5/1/2, and the optimum temperature was 30°C. The spectra of ultraviolet‐visible and infrared demonstrate that the structure of P(2,3‐DMA) was similar with polyaniline (PANI) except for the 2,3‐ortho‐substitute methyl. The result of X‐ray diffraction and solubility analysis indicate that owing to the 2,3‐ortho‐substitute benzene ring, the P(2,3‐DMA) has poorly partial crystallinity and better solubility. In addition, the anticorrosion property of P(2,3‐DMA) was better than PANI. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Synthesis,Chiral Resolution and Pharmacological Evaluation of a 2,3‐Benzodiazepine‐Derived Noncompetitive AMPA Receptor Antagonist

2,3‐Benzodiazepine derivatives : 1‐(4‐Aminophenyl)‐3,5‐dihydro‐3‐N‐ethylcarbamoyl‐5‐methyl‐7,8‐methylenedioxy‐4H‐2,3‐benzodiazepin‐4‐one was synthesized, and its enantiomers were separated by chiral HPLC. Pharmacological evaluation of each enantiomer showed that (S)‐(?)‐ 5 appears to be more potent than its optical antipode (R)‐(+)‐ 5 in an AMPA receptor binding assay.

     

Comparison of the reactivities of 2-mercaptoaniline and 2-hydroxyaniline with 2-chloronicotinoyl chloride

The reaction between equimolar 2-chloronicotinoyl chloride and 2-mercaptopyridine in ClCH₂CH₂Cl, after 30 minutes refluxing in ClCH₂CH₂Cl solution, produced pyrido[2,3,b][1,5]benzothiazepin-5(H)one 7, and 6-[3-(2-benzothiazolyl)pyridin-2-yl)thio]-N-[3-(2-benzothiazolyl)pyridin-2-yl]aniline 8. In contrast, the reaction using the same reaction conditions between equimolar 2-chloronico- tinoyl chloride and 2-hydroxypyridine, produced the simple amide, 2-chloro-N-(2-hydroxyphenyl) nicotinamide 9. 2-Chloro-N-(2-mercaptophenyl)nicotinamide was considered to be a common intermediate in the formation of 7 and 8. The characterizations of 7–9 were achieved by X-ray crystallography. The conformations of 7 and 8 in the solid state can be described as “U” and “V”-shaped, respectively.     

Production of 2,3-butanediol from diverse saccharides via fermentation

The present study aimed to evaluate the potential use of whey to produce 2,3-BD via the fermentation of lactose and its monosaccharides, glucose and galactose, in a synthetic culture medium (medium 9, M9) using a modified strain of Escherichia coli K12 MG1655 (E. coli JFR12) at a 0.1 L/L (10 vol%) inoculum ratio, 37 °C, atmospheric pressure, an initial pH 7.4, and 100 rpm for 72 h varying the saccharide concentration from 12.5, 25, and 50 g/L. The 2,3-BD yield was ∼80 % of the theoretical yield using 25 g/L of glucose and lactose, corresponding to 0.38 g/g saccharides at a fermentation time of 48 h (glucose) and 72 h (lactose). However, the 2,3-BD yield was halved (0.19 g/g galactose), fermenting 25 g/L of galactose at 48 h. Taking into account these results, two important conclusions were determined: i) E. coli JFR12 could transform galactose into 2,3-BD although its yield was half of the yield observed with glucose at 48 h; and ii) E. coli JFR12 was as efficient as other natural 2,3-BD producers such as Klebsiella species fermenting lactose. However, the E. coli strain has the advantage of being an innocuous strain. To the best of our knowledge, there is no other study presenting the production of 2,3-BD from galactose and lactose with a genetically modified E. coli strain.     

Synthesis and evaluation of biological activities of 4-cyclopropyl-5-(2-fluorophenyl) arylhydrazono-2,3-dihydrothiazoles as potent antioxidant agents

A new series of 4-cyclopropyl-5-(2-fluorophenyl)arylhydrazono-2,3-dihydrothiazole derivatives was synthesized via the reaction of prepared thiosemicarbazones with 2-bromo-1-cyclopropyl-2-(2-?uorophenyl)ethanone in the presence of Et₃N as a catalyst through a semi Hantzsch cyclization. The optimized reaction conditions for this one-pot reaction were achieved. The products were obtained in short reaction times, high yields and high purities. Antioxidant activity of products was evaluated using DPPH (2,2-diphenyl-2-picrylhydrazyl) and ABTS 2,2-azinobis(3-ethylbenzothiazoline-sulfonate) assays. Products showed higher antioxidant activity using the ABTS method. Compounds 5c and 5g showed lower IC₅₀ values compared with ascorbic acid as a standard. Compounds 5a–5h possessed moderate to high antioxidant activity by both methods. Also, antibacterial activity of 5a–5h was evaluated against gram-positive and gram-negative bacterial strains. None of the compounds inhibited A. hydrophila, while they had moderate to low inhibitory activity against other tested bacterial strains.     

Hydrothermal Preparation, Crystal Structures, Spectroscopic and Thermal Analyses of Cadmium(II) and Cobalt(II) Coordination Polymers With Pyridine-2,3-dicarboxylic Acid

Two novel 1D coordination polymers, [M(μ-2,3-pydc)(H₂O)₃]_n (M = Cd for 1 and Co for 2) (2,3-pydcH₂ = pyridine-2,3-dicarboxylic acid) have been hydrothermally synthesized. Both complexes were characterized by elemental analysis and by IR and UV–Vis spectroscopy. Their molecular and crystal structures were determined by X-ray crystal structure analysis and their thermal stability by TGA-DTA methods. Compound 1 crystallizes in the orthorhombic Pca2 space group, while compound 2 crystallizes in the triclinic P−1 space group. Polymeric chains of 1 and 2 are composed of M(II) ions bridged by pyridine-2,3-dicarboxylate ions (2,3-pydc) in N,O,O′ fashion. Distorted octahedral coordination geometry around the metal ions is completed by three water molecules. A wide range of hydrogen bonding (of the O–H···O type) is also present in the crystal structures. These interactions lead to formation of a 3D structure for 1 and 2D network for 2.     

A novel synthesis of indeno[2',1': 5,6] pyrido[2,3- d ][1,2,4]triazolo[4,3- a ]pyrimidines

Reaction of 5-(4-chlorophenyl)-2-thioxo-2,3-dihydro-1H-indeno[2',1':5,6] pyrido[2,3-d]pyrimidine-4,6-dione with hydrazonoyl chlorides gave 1,2,4-triazolo[4,3-a]pyrimidine derivatives regioselectively in good yields. The structures of the newly synthesized compounds are established on the basis of chemical and spectroscopic evidence as well as their synthesis by alternative methods.     

Chemical defense of giant springtailTetrodontophora bielanensis (Waga) (Insecta: Collembola)

The giant springtail,Tetrodontophora bielanensis (Waga), is characterized by integumental openings (pseudocells) from which small droplets of a sticky defensive fluid are secreted after molestation. The secretion originates initially from secretory cells below the pseudocellae; subsequent irritations result in release of hemolymph, which was identified by both chemical and microscopical methods as well as by scanning electron microscopy. Bioassays with topically treated ground beetlesNebria brevicollis showed that the pseudocellular fluid evokes a total disorientation and cleansing behavior of the beetle. The main constituents were identified as the following pyridopyrazines: 2,3-dimethoxpyrido[2,3-b]pyrazine (1), 3-isopropyl-2-methoxypyrido[2,3-b]pyrazine (2), and 2-methoxy-4H-pyrido[2,3-b]pyrazine-3-one (3). These alkaloids are mainly present in the pseudocellar fluids of female and male springtails but are absent in their food or feces. Minor amounts are found in the hemolymph of adults, while larvae contain traces of2 only. All compounds were synthesized and tested for activity. In natural concentrations, the synthetic alkaloids elicited the same effects from the ground beetles as the pseudocellar fluid.     

Enzymatic preparation of enantiomerically pure sn-2,3-diacylglycerols: A stereoselective ethanolysis approach

Stereoselective ethanolysis of monoacid TAG by immobilized Rhizomucor miehei lipase (RML) was studied for preparation of optically pure sn-2,3-DAG. Trioctanoylglycerol (TO) was used as a model substrate. The enantiomeric purity of the product, sn-2,3-dioctanoylglycerol (sn-2,3-DO), was very high (percent enantiomeric excess >99%) when an excess of ethanol was used. The result indicated that RML was highly stereoselective toward the sn-1 position of TO under conditions of excess ethanol. The stereoselectivity of RML depended on the amount of ethanol. The larger the amount of ethanol was, the higher the stereoselectivity became. After optimizing the parameters such as reactant molar ratio, water content, and temperature, (ethanol/TO molar ratio =31∶1 and water content =7.5 wt% of the reactants at 25°C), optically pure sn-2,3-DO was obtained at 61.1 mol% in the glyceride fraction in 20 min. The above conditions were further applied for ethanolysis of monoacid TAG with different acyl groups such as tridecanoylglycerol (C10∶0), tridodecanoylglycerol (C12∶0), tritetradecanoylglycerol (C14∶0) and trioctadecenoylglycerol [triolein, (C18∶1)]. The yields and enantiomeric purities of 1,2(2,3)-DAG were dramatically reduced when TAG with FA longer than decanoic acid were used.