Synthesis and antimicrobial evaluation of some pyrazolo-thiazolyl alkoxy-1H-isoindole-1, 3(2H)-dione derivatives

1,3-Thiazolidine-2,4-dione 2 has been synthesized by the cyclisation reaction of thiourea and chloroacetic acid in the presence of ethanol. The reaction of compound 2 with substituted aromatic aldehyde afforded the corresponding derivatives of substituted 5-benzylidene-1,3-thiazolidinone-2,4-dione 3a–d, which upon reflux with ω-bromoalkoxyphthalimide gave 2-{[-5-(substituted benzylidine)-2,4-dioxo-1,3-thiazolidine-3-yl]alkoxy} -1H-isoindole-1,3(2H)-dione 4a–i. Further, compounds 4a–i were treated with phenyl hydrazine and 2,4 dinitro phenyl hydrazine in the DMF to yield the title compound 2-[5-oxo-2,3-substituted diphenyl-2H-pyrazolo[3,4-d][1,3]thiazol-6(5H)-yl)alkoxy]-1H-isoindole-1,3(2H)-dione 5a–r. Structures of newly synthesized compounds were established based on elemental analysis, IR, ¹H NMR and mass spectral data. Synthesized compounds have been assayed for their antibacterial activities against B. subtilis, K. pneumoniae, P. aeruginosa and S. aureus and antifungal activities against A. fumigatus and C. albicans.     

High glass transitions and fluorescence of novel organosoluble poly(arylene ether)s containing kink noncoplanar heterocyclic structures

A novel unsymmetrical and kink noncoplanar heterocyclic bisphenol-like monomer, 4-(4-hydroxynaphthalenyl)phthalazin-1-one (2), was synthesized in a two-step reaction starting from 1-naphthol and phthalic anhydride via Friedel-Crafts acylation reaction and cyclization with hydrazine hydrate. Two heterocyclic poly(arylene ether)s were prepared conveniently from monomer 2 and two activated dihalide monomers by a N-C coupling reaction. The polycondensation proceeded quantitatively in N,N-dimethylacetamide in the presence of anhydrous potassium carbonate and afford the polymers with inherent viscosities of 0.46 and 0.34 dL/g. Thermal analysis showed that the polymers had excellent thermal properties. The glass transition temperatures were 277 °C and 316 °C respectively, and the temperatures of 5% weight loss were all above 500 °C in nitrogen atmosphere. The unsymmetrical and kink noncoplanar structures of the polymers chains could disturb interchain and intrachain interactions and make them amorphous and readily soluble in polar, aprotic solvents. The dilute solution of the polymers in chloroform showed strong optical absorption in ultraviolet region, and exhibited violet-blue fluorescence with emission maxima at 400-470 nm.     

New Bioactive Fused Triazolothiadiazoles as Bcl-2-Targeted Anticancer Agents

A series of 3-(6-substituted phenyl-[1,2,4]-triazolo[3,4-b]-[1,3,4]-thiadiazol-3-yl)-1H-indoles (5a–l) were designed, synthesized and evaluated for anti-apoptotic Bcl-2-inhibitory activity. Synthesis of the target compounds was readily accomplished through a reaction of acyl hydrazide (1) with carbon disulfide in the presence of alcoholic potassium hydroxide to afford the corresponding intermediate potassium thiocarbamate salt (2), which underwent cyclization reaction in the presence of excess hydrazine hydrate to the corresponding triazole thiol (3). Further cyclisation reaction with substituted benzoyl chloride derivatives in the presence of phosphorous oxychloride afforded the final 6-phenyl-indol-3-yl [1,2,4]-triazolo[3,4-b]-[1,3,4]-thiadiazole compounds (5a–l). The novel series showed selective sub-micromolar IC₅₀ growth-inhibitory activity against Bcl-2-expressing human cancer cell lines. The most potent 6-(2,4-dimethoxyphenyl) substituted analogue (5k) showed selective IC₅₀ values of 0.31–0.7 µM against Bcl-2-expressing cell lines without inhibiting the Bcl-2-negative cell line (Jurkat). ELISA binding affinity assay (interruption of Bcl-2-Bim interaction) showed potent binding affinity for (5k) with an IC₅₀ value of 0.32 µM. Moreover, it fulfils drug likeness criteria as a promising drug candidate.     

A Novel Rhodium‐Catalyzed Cascade Cyclization: Direct Synthesis of 3‐Substituted Phthalides from Aldehydes and Aromatic Acids

A novel rhodium(III)‐catalyzed direct functionalization of ortho C H bonds of benzoic acid derivatives and an intramolecular cyclization sequence generates 3‐substituted phthalides in moderate to good yields. This cascade cyclization involves a Grignard‐type arylation of an aldehyde and subsequent intramolecular nucleophilic substitution. No theoretical waste except for water is generated in the reaction.     

一种新型有机电致磷光材料中间体8-甲基-1-苯基-[1,2,4]三唑[4,3-a]喹啉的合成研究

以苯甲酸乙酯与水合肼反应得苯甲酰肼、再与2-氯-7-甲基喹啉得到目标产物8-甲基-1-苯基-[1,2,4]三唑[4,3-a]喹啉,其结构经1HNMR确认。考察了水合肼用量对苯甲酰肼产率的影响、不同溶剂对8-甲基-1-苯基-[1,2,4]三唑[4,3-a]喹啉产率的影响。结果表明,水合肼与苯甲酸乙酯摩尔比为2.1制备苯甲酰肼结果最佳,正丁醇作溶剂制备8-甲基-1-苯基-[1,2,4]三唑[4,3-a]喹啉效果更好。     

Novel one-pot four-component condensation cyclization reactions for the synthesis of thiazolidine-4-one and 3H-thiazoles

ABSTRACT

A novel, simple and efficient synthetic protocol has been developed for the synthesis of a series of thiazolidine-4-one and 3H-thiazole derivatives via a one-pot four-component condensation-cyclization reaction of hydrazine with allyl isothiocyanate and an α-haloketone in the presence of various aldehydes. This new protocol produces novel thiazolidine-4-one and 3H-thiazole derivatives in excellent yields. The remarkable features of this methodology are high yields, easy work-up and a one-pot simple reaction method.     

Efficient synthesis of novel 2,3-dihydro-1,3,5,4-thiadiazaphosphole derivatives

The condensation of various thiosemicarbazones with methyl thiophene-2-carboximidate afforded the corresponding intermediates 2a–2h. Subsequent cyclization of the latter compounds with hexamethylphosphorous triamide constitutes a new route to the synthesis of novel highly functionalized thiadiazaphosphole derivatives 4a–4h. This method offers significant advantages such as efficiency, high yields and mild reaction conditions.     

[3+2] Cycloaddition of Propargylamines and α‐Acylketene Dithioacetals: A Synthetic Strategy for Highly Substituted Pyrroles

A new [3+2] cycloaddition strategy for the direct synthesis of highly substituted pyrroles from the readily available α‐acylketene dithioacetals (or related substrates) and commercially available propargylamines under mild metal‐free conditions has been developed. In this reaction, the acyl group plays a critical role in driving the conjugate addition of propargylamine and further cyclization to give pyrroles. Furthermore, the wide scope was confirmed by the preparation of 1,2,3,4‐tetrasubstituted pyrroles (60–70% yields) via a formal 1,2‐acyl migrating [3+2] cycloaddition pathway with N‐methylprop‐2‐yn‐1‐amine as the secondary amine component.     

Attempted Synthesis of Bowl-Shaped Polycyclic Aromatic Hydrocarbons via Oxidative Electrocyclization. Products from the Dications of Dibenzo [g,p] chrysene,Tetrabenzo[5.5]fulvalene,and Diphenylmethylidenefluorene

Synthesis of diindeno[1,2,3,4-defg: 1′,2′,3′,4′-mnop]chrysene (1), a portion of the C₆₀ surface, was attempted through oxidative cyclization of tetrabenzo[5.5]fulvalene (2), dibenzo[gp]chrysene (3), and diphenylmethylidenefluorene (4) by SbF₅/SO₂CIF. Compounds 2 and 3 were oxidized to dications which then underwent a single cyclization to give precursors to 1. Compound 4 underwent two oxidative cyclizations to give a precursor to 1. AM1 calculations of the possible products from cyclization were consistent with preferential formation of the cyclized product with the lower ΔHf. Oxidative cyclization may offer a one-pot synthetic alternative for the preparation of unusual polycyclic aromatic hydrocarbons.     

Cyclopropyl Building Blocks for Organic Synthesis, 131. Palladium‐Catalyzed Bicyclization with Carbonyl Insertion of Alkenyl‐Tethered Propargyl Carbonates Towards a Scalable Synthesis of Various 2‐(Bicyclo[3.1.0]hex‐1‐yl)acrylates

The Pd‐catalyzed 5‐exo‐trig‐3‐exo‐trig cascade cyclization of 1,6‐enynes with a propargyl carbonate terminus offers the shortest synthetic route to variously substituted 2‐(bicyclo[3.1.0]hex‐1‐yl)acrylates, a novel class of prospective monomers for low‐shrinkage polymers. To apply this reaction to large‐scale preparations of the said bicyclic acrylates, a flexible Pd catalyst system with tunable reactivity has been developed. The dependence of the product and diastereomer distribution on both the reaction conditions, including the type of palladium catalyst used, and on the nature of the substrate has been investigated. A variety of methyl 2‐(bicyclo[3.1.0]hex‐1‐yl)acrylates and parent carboxylic acids as well as some of their derivatives of potential interest towards a technical application were prepared on a multigram scale. A general large‐scale synthesis of the cyclization precursors bearing one or two carbonyl groups in the tether is also disclosed.     

Synthesis of the Ladder Polymers by the Reaction of Catalytic Dehydrocondensation

Abstract

The heterofunctional condensation of cis-1,3.5,7-tetrahydroxy-1,3,5,7-tetraphenylcyclotetrasiloxane with dimethylchlorosilane has been studied.

It was established that when the reaction proceeds under mild conditions tetraphenylcyclotetrasiloxane incompletely substituted with dimethylsiloxy groups is obtained, i.e., 1,3,5-tris(dimethylsiloxy)-7-hydroxy-1,3,5,7-tetraphenylcyclotetrasiloxane, while under certain conditions 1,3,5,7-tetrakis(dimethylsiloxy)-1,3,5,7-tetraphenylcyclotetrasiloxane is formed.

The catalytic dehydrocondensation of 1,3,5-tris(dimethylsiloxy)-7-hydroxy-1,3,5,7-tetraphenylcyclotetrasiloxane both in a dilute and concentrated solutions in the presence of platinochlorohydric acid as a catalyst has been studied. It was shown that the reaction proceeds both by the mechanism of intramolecular cyclization with formation of a bicyclic compound and intermolecularly with formation of a tricyclic compound.

The catalytic dehydrocondensation of 1,3,5,7-tetrakis-(hydriddimethylsiloxy)-1,3,5,7-tetraphenylcyclotetrasiloxane with cis-1,3,5,7-tetrahydroxy-1,3,5,7-tetraphenylcyclotetrasiloxane and with oligotetrols (m = 5, 10) was also studied. The reaction order, activation energies and dehydrocondensation rate constants were found.

It was established that with an increase in the length (m) of the oligotetrols the degree of catalytic dehydrocondensation is reduced. It was shown that if the platinochlorohydric acid catalyst is replaced by anhydrous powdered caustic potassium a different configuration of the cyclotetrasiloxane skeleton is realized in polymers.     

2-芳基苯并呋喃化合物的新法合成与表征

创造了两步合成2-芳基苯并呋喃化合物的新方法。即利用水杨醛或取代水杨醛在低价钛作用下进行交叉McMurry偶联反应,并对交叉偶联产物-邻乙烯基苯酚进行氧化环化获得对应苯并呋喃化合物。此法为脱甲氧基野茉莉醇、野茉莉醇等天然产物的全合成提供了简便有效的方法。     

Synthesis and antioxidant activities of some novel fluorinated spiro[oxindole-thiazolidine] fused with sulfur and phosphorus heterocycles

Facile routes were achieved for the synthesis of novel fluorinated spiro[oxindole-thiazolidinone] fused with some sulfur and phosphorus heterocycles starting from 5-fluoro-3^′-(4-fluorophenyl)-4^′H-spiro[indole-3,2^′-thiazolidine]-2,4^′(1H)-dione (1) via its reaction with trifluoroacetamide, 2-chloro-6-fluorobenzaldehyde and hydrazine hydrate followed by treatment with some suitable sulfur and phosphorus reagents. The antioxidant activities of the synthesized compounds were also evaluated.     

Organo-catalytic synthesis of oxathians from isocyanides,isothiocyanates, and oxiranes

ABSTRACT

A novel three-component reaction between isocyanides, isothiocyanates, and oxiranes has been developed. An array of substituted oxathianes have been obtained in acceptable to good yields. The reaction product could be modulated using Bu₃P or TBPAc as an organo-catalyst. This work offers an opportunity for the further implementation of isocyanides in library design.     

The Regioisomeric Triphenylaminoethanols –Comparison of their Efficiency in Enantioselective Catalysis

Both enantiomers of the novel amino alcohol (R)‐ and (S)‐ 2 are prepared from the corresponding enantiomer of the mandelic acid‐derived ethanediol 3 . The regioisomeric amino alcohols 1 and 2 are converted into the imines 7 and 8 , respectively. Titanium complexes 9 and 10 derived therefrom are used as catalysts for the addition of diethylzinc to benzaldehyde and yield the alcohol 11 in up to 92% ee. On the other hand, the chloro‐substituted titanium complexes 14 and 15 are able to mediate the Torgov cyclization reaction of the diketone 16 to give the estrone derivative 17 . In both reactions titanium complexes 10 and 15 derived of the novel amino alcohol 2 give higher enantioselectivities than the complexes 9 and 14 that are based on the regioisomeric amino alcohol 1 .     

Synthesis of a few cyclothiadiazanones and aminosulfonyl benzamides from saccharin

Saccharin is hydrolyzed with two different acids to yield 1,2-di-acid. The di-acid, on chlorination with phosphorous pentachloride, gave 2-chlorosulfonylbenzoyl chloride. The 2-chlorosulfonylbenzoyl chloride on hydrazinolysis gave benzothiadiazinetrione, while with phenyl hydrazine it selectively yielded 2-phenylbenzothiadiazinetrione. 2-chlorosulfonoylbenzoyl chloride with different aromatic 1,2-diamines resulted in dibenzothiadiazocine derivatives. Electron-donating groups in the diamine facilitate while the electron-withdrawing groups retard the cyclization. However, aliphatic diamines, aniline and substituted anilines readily gave acyclic aminosulfonyl carboxybenzamides on condensation with 2-chlorosulfonylbenzoyl chloride. The di-acid and anhydride did not react with either hydrazine/phenyl hydrazine or amines to give the above products. However, when its ester derivative, isopropyl-2-chlorosulfonylbenzoate, condensed with hydrazine, it gave benzothiadiazinetrione. But the ester failed to react with phenyl hydrazine. All the condensation reactions were carried out at room temperature.     

Synthesis of Substituted Quinolizidines via a Gold‐Catalyzed Double Cyclization Cascade

A novel synthesis of quinolizidines by a cationic gold‐catalyzed double cyclization cascade has been developed. The reaction was initiated by the gold‐catalyzed 6‐exo‐dig cyclization of ynamides, which was followed by a second cyclization of an enamide intermediate to provide the corresponding quinolizidine derivatives. The utility of this reaction was demonstrated by application to the synthesis of multi‐substituted quinolizidines and by the total synthesis of a quinolizidine alkaloid, (±)‐lupinine.

     

Reactions of fatty acid chlorides: II. Synthesis of monohydrazides or dihydrazides by acylation of hydrazine hydrate with saturated fatty acid chlorides

The acylation of hydrazine hydrate with a series of saturated fatty acid chlorides containing from eight to 18 carbon atoms was studied under a variety of conditions in order to obtain the desirable fatty acid monohydrazides. Optimum yields were obtained (ranging from 31.5% to 75% as the series ascended from C-8 to C-18) for the even-numbered monohydrazide members through the use of a large excess of hydrazine hydrate in several organic solvents. Diethyl ether was found to be suitable if the acid chloride is dissolved in it and added slowly to a cold mixture of hydrazine hydrate in ether. The Schotten-Baumann technique was found suitable for the preparation of the symmetrically substituted fatty acid dihydrazides in better than 82% yields when one mole of hydrazine hydrate was acylated with two of acid chlorides. Physical and chemical properties of both series of fatty nitrogen derivatives are briefly treated. Stearic monohydrazide was condensed with acetonylacetone to give a substituted pyrrole. An unsymmetrical dihydrazide was prepared by the acylation of myristic monohydrazide with lauroyl chloride. Stearic dimethylhydrazide was prepared by the acylation of dimethylhydrazine with stearoyl chloride. Two quaternizations of this product were carried out. Part I. JAOCS31, 151 ({dy1954}). Presented at the AOCS Meeting, New York, October 1960.     

Cationic cyclization of purified natural rubber in latex form with a trimethylsilyl triflate as a novel catalyst

Cyclization of deproteinized natural rubber (DPNR) or purified natural rubber latex was effectively performed in latex phase by using trimethylsilyl‐trifluoromethane sulfonate or trimethylsilyl triflate (TMSOTF) as a novel catalyst, which is still not reported in the case of natural rubber latex. Various cyclization conditions affecting the degree of cyclization were studied, such as dry rubber contents, temperature, TMSOTF concentrations, and time. The cyclized products were characterized by FTIR, Raman, ¹H‐, and ¹³C‐NMR spectroscopies, as well as DSC and TGA. The degree of cyclization was estimated by ¹H‐NMR spectrum. It was found that the degree of cyclization in NR was a function of cyclization conditions. The thermal stability of cyclized DPNR increased with the degree of cyclization. Solubility of the obtained rubber was good in chloroform, toluene, cyclohexanone, and cyclohexane, and bad in tetrahydrofuran. The average number molecular weight of cyclized DPNR with 76% degree of cyclization was about 4.2 × 10⁴ g/mol. On the basis of FTIR, Raman, ¹H‐, and ¹³C‐NMR, the C?C of cyclized DPNR dramatically decreased after prolonged reaction time. In addition, the topology of cyclization DPNR particles was rough on its rubber particle as analyzed by TEM. The mechanism for this reaction will also be discussed. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007.     

A new synthetic approach and biological evaluation of novel phenothiazines bearing tert-butyl group

A new and facile synthetic route is proposed for the synthesis of some novel phenothiazines (5a–5g) based on the reaction of 2-amino substituted benzenethiols with p-tert-butyl phenol in good yield. The newly synthesized compounds were characterized by IR, ¹H NMR and mass spectral studies. Their antimicrobial activities against three strains of bacteria: Bacillus subtilis, Bacillus megaterium, Escherichia coli, and two strains of fungi: Aspergillus niger and Aspergillus oryzae, were investigated.