新型含取代哌嗪的5-(吡啶-3-基)-1,2,4-三唑Mannich碱和双Mannich碱的合成及生物活性

根据药物分子设计的活性基团组合原理,通过在1,2,4-三唑环的5位引入吡啶基,同时在4位芳基亚甲氨基的苯环上引入氟或三氟甲基,设计合成了一系列含氟、吡啶和哌嗪基团的1,2,4-三唑Mannich碱和双Mannich碱类化合物.通过核磁共振氢谱(~1H NMR)、碳谱(~(13)C NMR)和元素分析确证了目标化合物的结构.生物活性测试结果表明,部分化合物对油菜具有一定的除草活性;化合物2a,2d和2f(50 mg/L)对苹果轮纹病菌表现出较好的抑制活性,与对照药三唑酮活性相当;化合物2a,2b,2d和2i(180 mg/L)对酮醇酸还原异构酶(KARI酶)表现出了显著的离体抑制活性(抑制率51.7%~88.7%).     

含1-[二-(4-氟苯)甲基]哌嗪均三氮唑环的Mannich碱的合成及表征

微波辐射下,在冰醋酸中,3-甲基-4-氨基-1,2,4-三氮唑-5-硫酮1与芳香醛经微波辐射制得相应的中间体Schiff碱2(a~j),然后中间体2与1-[二-(4-氟苯)甲基]哌嗪于室温反应制得10个新的Mannich碱3(a~j).合成的10个目标化合物通过熔点测定和质谱、红外光谱、核磁共振氢谱分析、元素分析对其结构进行确证。     

An expeditious one‐pot synthesis of substituted phenylazetidin‐2‐ones in the presence of zeolite

In this study, one‐pot rapid and efficient series of phenylazetidin‐2‐ones were synthesized from N,N‐dimethylaminobenzaldehyde, different substituted aromatic amines and phenylacetyl chloride in the presence of zeolite catalyst under microwave irradiation. We also reported schiff bases (1a–j) by classical and conventional microwave technique. The titled compounds are evaluated for their antimicrobial properties. The activities are due to C?O, C? N, linkages in 2‐azetidinones. All the compounds have shown comparable antibacterial activities. J. Heterocyclic Chem., (2011).     

含嘧啶环的1,3,4-噁二唑Mannich碱的合成及生物活性

以芳香酸为原料, 通过酯化、 肼解及环化反应制得中间体5-芳基取代-1,3,4-噁二唑-2-硫酮(C1~C3), 然后中间体与甲醛和取代氨基嘧啶(D1~D5)发生Mannich反应得到一系列新型含有嘧啶环的1,3,4-噁二唑类衍生物(E1~E15). 所得目标化合物的结构经元素分析、 IR及 ¹H NMR确认. 初步的生物活性测定结果表明, 大部分目标化合物对植物病原菌有很好的抑制作用, 其中化合物E3和E8的抑菌效果优于对照药三唑酮.     

Facile one pot microwave induced solvent-free synthesis and antifungal, antitubercular screening of spiro [1,5]-benzothiazepin-2,3'[3'H]indol-2[1'H]-ones

Microwave activation coupled with dry media technique as a green chemistry procedure has been applied to synthesis of a series of some new title compounds. They have been obtained by the reaction of in situ synthesized 1,3-dihydro-3-[2-(phenyl/4-fluorophenyl)-2-oxoethylidene)-indol-2(1H)-one (4a, b) with substituted aminobenzenethiols (5a-d). The key intermediates 4a, b were also prepared in one step by this improved technique by reacting isatin and substituted acetophenones (2a, b). The results obtained under microwave irradiation when compared with that following conventional method demonstrate the versatility of the process. The title compounds 7a-e have also been screened for their antifungal and antitubercular activity, 7a and 7e showing maximum inhibition of growth of Alternaria alternata and Fusarium oxysporium and 7b, c, e revealing significant antitubercular activity.     

Microwave promoted synthesis and antimicrobial activity of 3-thiazole substituted 2-styryl-4(3H)-quinazolinone derivatives

The present paper describes an optimized reaction condition for the microwave promoted synthesis of newer 3-thiazole substituted 2-styryl-4(3H)-quinazolinone derivatives, which in turn were prepared in good yield by the treatment of various 2-styryl benzoxazinone derivatives with various 2-aminothiazoles using co-solvent under microwave irradiation. All the compounds were characterized by various spectroscopic techniques and analytical methods. All newly synthesized compounds have been screened for their in vitro antibacterial and antifungal activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus megaterium,Bacillus subtilis, and Aspergillus niger.     

Syntheses and reactions of hexavalent organotellurium compounds bearing five or six tellurium-carbon bonds

A variety of hexaorganotellurium compounds, Ar(6-n)(CH3)nTe [Ar=4-CF3C6H4, n=0 (1a), n=1 (3a), n=2 (trans-4a and cis-4a), n=3 (mer-5a), n=4 (trans-6a); Ph, n=0 (1b), n=1 (3b), n=2 (trans-4b); 4-CH3C6H4, n=0 (1c), n=1 (3c), n=2 (trans-4c), n=4 (trans-6c); 4-BrC6H4, n=0 (1d)] and Ar5(R)Te [Ar=4-CF3C6H4, R=4-CH3OC6H4 (8); Ar=4-CF3C6H4, R=vinyl (9), Ar=Ph, R=vinyl (10), Ar=4-CF3C6H4, R=PhSCH2 (11), Ar=Ph, R=PhSCH2 (12), Ar=4-CF3C6H4, R=nBu (13)] and pentaorganotellurium halides, Ar5TeX [Ar=4-CF3C6H4, X=Cl (2a-Cl), X=Br (2a-Br); Ar=Ph, X=Cl (2b-Cl), X=Br (2b-Br); Ar=4-CH3C6H4, X=Cl (2c-Cl), X=Br (2c-Br); Ar=4-BrC6H4, X=Br (2d-Br)] and (4-CF3C6H4)4(CH3)TeX [X=Cl (trans-7a-Cl) and X=Br (trans-7a-Br)] were synthesized by the following methods: 1) one-pot synthesis of 1 a, 2) the reaction of SO2Cl2 or Br2 with Ar5Te(-)Li+ generated from TeCl4 or TeBr4 with five equivalents of ArLi, 3) reductive cleavage of Ar(6-m)(CH3)(m)Te (m=0 or 2) with KC8 followed by treatment with CH3I, 4) valence expansion reaction from low-valent tellurium compounds by treatment with KC8 followed by reaction with CH3I, 5) nucleophilic substitution of Ar(6-y-z)(CH3)zTeX(y-z) (X=Cl, Br, OTf; z=0, 1; y=1, 2) with organolithium reagents. The scope and limitations and some details for each method are discussed and electrophilic halogenation of the hexaorganotellurium compounds is also described.     

Synthesis of Mannich bases of 5-hydroxynapthalene-1,8-carbolactone as potential antifungal or antitumor agents

Mannich bases of 5-hydroxynaphthalene-1,8-carbolactone 1 were prepared from various secondary amines or bulky primary amines and formaldehyde. They were isolated in almost all cases as hydrochlorides. These derivatives were submitted to in vitro antifungal and cytotoxic assays. The antifungal assays were performed against three strains of yeasts and five strains of human pathogenic fungi. Two of the tested compounds, 2i and 2j, exhibited interesting antifungal activities against Candida albicans and Candida tropicalis. The cytotoxic activity was evaluated towards L 1210 leukemia cells. Almost all of the Mannich bases had shown significant activity against this tumor cell line as values of IC50 less than or equal to 4 micrograms/ml are considered interesting. Only one derivative 2 developed better cytotoxicity than the parent compound 1.     

Microwave-assisted synthesis and biological activity of new Schiff bases derived from dimers of 4-amino-3-[3-(1-benzyl)indole]-5-thiomethyl-1,2,4-triazole

An expeditious method with microwave irradiation has been developed for synthesis of novel Schiff bases from dimers of 4-amino-3-[3-(1-benzyl)indole]-5-thiomethyl-1,2,4-triazole. Its distinct advantages are short reaction times and good conversion. The structures of these new Schiff bases were established by ¹H NMR, IR, and mass spectroscopy, and elemental analysis. The antibacterial activity of ten novel Schiff bases against three bacterial strains was studied by the disk diffusion method. Preliminary results indicated that some of the compounds had strong antibacterial activity.     

微波辐射下合成2-芳甲酰氨基-5-(2-三氟甲基苯并咪唑-1- 亚甲基)-1,3,4-噻二唑

微波辐射下, 1-肼羰亚甲基-2-三氟甲基苯并咪唑与芳酰基异硫氰酸酯反应合成了1-(2-三氟甲基苯并咪唑-1-乙酰基)-4-芳酰基氨基硫脲(1a～1j), 继而在乙酸中合环得到了一系列的2-芳甲酰氨基-5-(2-三氟甲基苯并咪唑-1-亚甲基)-1,3,4-噻二唑(2a～2j), 反应时间短, 产率高, 副反应少. 标题化合物经元素分析, IR, 1H NMR确证结构.     

Antimicrobial activities of the CH2Cl2-CH3OH (1:1) extracts and compounds from the roots and fruits of Pycnanthus angolensis (Myristicaceae)

This study was designed at evaluating the antimycobacterial, antibacterial and antifungal activities of the CH2Cl2-CH3OH (1:1) extracts and isolated compounds, namely 3,4-dimethoxy-3',4'-methylenedioxy-7,7'-epoxylignan (1), genkwainin (2), pycnanthulignene C (3), 4,5-dimethoxy-3',4'-methylenedioxy-2,7'-cycloligna-7,7'-diene (4), pycnanthulignene A (5) from the roots, and calycosin (6), biochanin A (7) and prunetin (8), from the fruits of Pycnanthus angolensis. The microplate alamar blue assay and the broth microdilution method were used to determine the minimal inhibitory concentration (MIC) and minimal microbicidal concentration of the samples. The H+-ATPase-mediated proton pumping assay was used to evaluate one of the possible mechanisms of action of the extracts and isolated compounds. The results of MIC determinations showed that the extract from roots was able to prevent the growth of all the studied organisms, including mycobacteria, fungi, and Gram-positive and Gram-negative bacteria. All tested compounds showed antimicrobial activities to different extents, compound 1 and 8 exhibiting the best antimicrobial spectrum, with 92.3% of the tested organisms being sensitive. The results obtained in this study also showed that the extracts as well as most of the compounds were able to inhibit the H(+)-ATPase activity. The overall results provided evidence that P. angolensis and some of its components might be potential sources of antimicrobial drugs against tuberculosis, bacterial and fungal diseases.     

A convenient,rapid, and highly selective method for synthesis of new pyrazolo[1,5‐a]pyrimidines via the reaction of enaminones and 5‐amino‐1H‐pyrazoles under microwave irradiation

Twelve new 7‐aryl‐3‐cyanopyrazolo[1,5‐a]pyrimidines ( 3a‐f ) and ethyl 7‐arylpyrazolo[1,5‐a]pyrimidine‐3‐carboxylates ( 3g‐l ) have been conveniently synthesized by the reaction of enaminones with 5‐amino‐1H‐pyrazoles in good yields under microwave irradiation. With one substituded enaminone, only one regioiso‐mer was obtained. The structures of new compounds were fully confirmed by elemental analysis, ir, ¹H nmr and X‐ray diffraction (XRD) analysis. A plausible reaction mechanism for the synthesis of title compounds is presented. The antifungal activities of some compounds are also reported.     

Microwave promoted synthesis of some N-（4-methyl-3-tolylthiazol-2（3H）-ylidene） substituted benzamides

N-(4-Methyl-3-tolylthiazol-2(3H)-ylidene) substituted benzamides(2a-o) were synthesized in good to excellent yields by the base-catalyzed direct cyclization of corresponding 1-tolyl-3-aryl thioureas(1a-o) with 2-bromoacetone through microwave irradiation in a solvent-free medium.Compared to traditional thermal heating,microwave irradiation provides a much more cleaner,efficient and faster method for synthesis of the title compounds.     

Utility of Ketonic Mannich Bases in Synthesis of Some New Functionalized 2‐Pyrazolines

The styryl ketonic Mannich base 2 has been used as a precursor in the synthesis of 2‐pyrazolines having a basic side chain at C‐3 and a phenolic Mannich base at C‐5. Treatment of the bis(styryl ketonic bases) 6a and 8a with phenylhydrazine affords the bis(3‐functionalized 2‐pyrazolines) 7 and 9 . The transamination between the styryl keto base 10 and 4‐aminoantipyrine leads to 12 , which reacts with piperazine to give 13 . N‐Nitrosation of the sec‐Mannich bases 15a – d followed by reductive cyclization affords 2‐pyrazolines 17a – d . The keto base 14b has been used for the synthesis of 2‐pyrazolines having a phenolic Mannich base at C‐3 and its reaction with 3,5‐dimethyl‐1H‐pyrazole affords 23 . The alkylation of 3‐methyl‐1‐phenyl‐2‐pyrazolin‐5‐one with the bis(Mannich base) 25 was investigated.     

Green chemical multi-component one-pot synthesis of fluorinated 2,3-disubstituted quinazolin-4(3H)-ones under solvent-free conditions and their anti-fungal activity

A rapid one-pot solvent-free procedure has been developed for the synthesis of fluorinated 2,3-disubstituted quinazolin-4(3H)-ones by neat three-component cyclocondensation of anthranilic acid, phenyl acetyl chloride and substituted anilines under microwave irradiation. The experimental methodology and microwave conditions described here are well established, allowing significant rate enhancement and good yields compared to conventional reaction conditions. The reaction is generalized for O, M & P substituted anilines to give quinazolin-4(3H)-ones. Synthesized compounds have been screened for their antifungal activity.     

Synthesis and Antimicrobial Activity of 2‐(Pyridine‐3‐yl)‐4H‐chromen‐4‐one Derivatives

An efficiently synthesis of chromones via cyclodehydration of corresponding 1‐(2‐hydroxyphenyl)‐3‐(pyridine‐3‐yl)propane‐1,3‐dione is described under ultrasound irradiation. A series of novel 2‐(pyridine‐3‐yl)‐4H‐chromen‐4‐one derivatives was confirmed on the basis of ¹H‐NMR, mass, IR spectral data, and elemental analysis. The synthesized compounds were evaluated for their antibacterial and antifungal activities. Most of the compounds were found to be comparable potent than the reference standard drugs. Utilization of ultrasound irradiation, simple reaction conditions, isolation, and purification makes this manipulation very interesting from an economic and environmental perspective.     

A Novel Method for Biomimetic Synthesis of Mannich Bases

Since the early studies of Mannich, Mannich reaction has become an important tool for the synthesis of new compounds. Mannich bases can be either directly employed or used as intermediates. In this work, the one‐carbon unit transfer reaction of tetrahydrofolate coenzyme was initiated. 1,3‐Dimethylimidazolidine as a new tetrahydrofolate coenzyme model at formaldehyde oxidation level was used to react with ketone having active hydrogen atoms and amine to give the corresponding Mannich base in good yield by a covert Mannich reaction. A novel method for biomimetic synthesis of various Mannich bases is provided.     

Copper(II)-mediated cross-coupling of arylboronic acids and 2(1H)-pyrazinones facilitated by microwave irradiation with simultaneous cooling

[reaction: see text] Optimized conditions for the decoration of the 2(1H)-pyrazinone scaffold were developed by applying the Chan-Lam protocol. It was demonstrated that this Cu(II)-mediated cross-coupling reaction resulted in significantly improved yields and rates when performed under microwave irradiation with simultaneous cooling at 0 degrees C, applying a mixture of bases Et(3)N/pyridine.     

Aluminum compounds containing eta1- and/or eta5-bidentate dianionic pyrrolyl-methylamide ligands

A series of dialuminum compounds have been synthesized and their reactivity and application for lactide polymerization have been studied. The reaction of AlH3 x NMe3 with [C4H3NH(2-CH2NHtBu)] in diethyl ether generated a dimeric aluminum hydride compound, [[[C4H3N(2-CH2NtBu)]AlH]2] (1). The structure of 1 was confirmed by spectroscopy of a deuterated analogue of 1 with an Al--D function. Direct treatment of [C4H3NH(2-CH2NHtBu)] with LiAlH4 in diethyl ether resulted in colorless crystals of [[Li[micro-eta1:eta5-C4H3N(2-CH2NtBu)]2Al]2] (2) in 80 % yield after recrystallization from a toluene solution. The micro-eta1:eta5-pyrrolyl protons exhibit high-field shifts at delta=5.73, 6.15, and 6.72 comparable to a similar eta5-bonding mode in the literature. Treatment of 1 with 1 equiv acetone oxime or acetone in dichloromethane gave [[[C4H3N(2-CH2NtBu)]Al[varkappaO,varkappaN-(ON==CMe2)]]2] (3) and [[[C4H3N(2-CH2NtBu)]Al(O--CHMe2)]2] (4) in 67 % and 60 % yield, respectively. Compounds 1-4 have been characterized by X-ray diffractometry and were used as catalysts for epsilon-caprolactone polymerization.     

微波促进活性炭负载四氯化锡催化合成乙酰乙酸乙酯缩酮

在微波辐射下,以活性炭负载四氯化锡(SnCl4·5H2O/C)为催化剂,不用溶剂,合成了乙酰乙酸乙酯乙二醇缩酮和乙酰乙酸乙酯1,2-丙二醇缩酮。以乙酰乙酸乙酯与乙二醇缩合为模型反应进行优化,其优化条件是:负载量为20%的SnCl4·5H2O/C催化剂0.1 g,乙酰乙酸乙酯5 mL,乙二醇6 mL,微波辐射功率600 W,辐射时间2.5 min,产率达81.6%。产物经过红外光谱表征。