Synthesis of Dihydrobenzo[h]coumarins and Their 4‐Methyl Analogs

Dihydrobenzo[h]coumarins (5a–7a) and their 4‐methyl analogs (5b–7b) were synthesized from 1‐naphthol via two different synthetic routes. One pathway is the direct condensation of 5,8‐dihydro‐1‐naphthol (9) with malic acid or ethyl acetoacetate, affording 7,10‐dihydrobenzo[h]coumarins 7a and 7b, respectively. The other is through the oxidation of 7,8,9,10‐tetrahydrobenzo[h] coumarins (15a–b), followed by the reduction of the carbonyl group and dehydration of hydroxyl group, giving 7,8-dihydrobenzo[h]coumarins (5a, b) and 9,10-dihydrobenzo[h]coumarins (6a, b). The regio selectivities for the oxidation reactions of 15a, b were rationalized on the basis of quantum chemical calculations and further confirmed by the X‐ray crystallographic analysis of the derivatives of oxidation products.     

Synthesis of new thioxanthenes by organocatalytic intramolecular Friedel–Crafts reaction

An efficient organocatalytic route has been developed to synthesize novel substituted thioxanthenes (2a–2v) starting from diaryl thioether alcohols (1a–1v) using the intramolecular Friedel–Crafts reaction. The starting materials were obtained in two stages via a coupling reaction followed by the Grignard reaction. In this study, we tried for the first time to use some organic Brønsted acids as organocatalysts (3a–3h) in the intramolecular Friedel–Crafts cyclization reaction of thioether alcohols. The synthesis of original substituted thioxanthenes was achieved within 15?minutes by using N-triflylphosphoramide (3h) with quantitative yields in THF at room temperature.     

Synthesis of Terpenoid-Like Bischalcones from α- and β-Ionones and Their Biological Activities

Ionone-based terpenoid-like bischalcones (3a–h and 4a–h) were synthesized from the reaction of α- and/or β-ionones with aldehyde derivatives in excellent yields. The antibacterial activities of synthesized compounds were screened against human pathogenic micro-organisms by employing the disk-diffusion technique.     

Zur Synthese der 4-Dialkylamino-5,6-dihydro-2(1H)-pyridinthione sowie entsprechender 4-Alkylamino- bzw. 4-Arylaminoverbindungen

The rearrangement of 1-alkyl- and 1-aryldihydro-6-methyl-2(1H)-pyrimidinethiones (1 a) or-ones (1 b) and of methylene compounds (2a, 2b) resp., to 4-alkylamino- and 4-arylaminodihydro-2(1H)-pyridinethiones (4 a) or-ones (4 b) takes place via the corresponding 3-alkylamino- and 3-aryl-amino-3-butenylisothiocyanates (3 a) or-isocyanates (3 b). Dialkylamino-dihydro-2(1H)-pyridinethiones (10) are formed by heating dihydro-6-methyl-2(1H)-pyrimidinethiones (6 a) and 3,4-dihydro-6-methyl-1,3-thiazin-2-thiones (6 b) with dialkylformamides and by the reaction of secondary amines with tetrahydro-6-hydroxy-6-methyl-1,3-thiazin-2-thiones (5 a), with N,N-dialkyl-N-(3-oxobutyl)-thioureas (7) and 3-oxobutyl isothiocyanates (8). A general method for the preparation of10 is the reaction of dialkylammoniumrhodanides12, N,N-dialkylthioureas13 and dialkylammonium chlorides and KCNS, resp., with 3-alken-2-ones14 and 4-hydroxy-2-alkanones15, resp. Methyl ketones such as acetone, which readily undergo the aldol condensation, behave analogously. The reactions described take place via the intermediate aminoalkenyl isothiocyanates (9).     

Novel supramolecular columnar liquid crystals based on thiosemicarbazides

Novel liquid crystal materials based on 3,4-di-n-alkoxybenzoylthiosemicarbazides (3a–h, n = 5–10, 12, 14) were synthesised. The mesomorphic properties of these compounds were characterised and studied by differential scanning calorimetry, polarising optical microscopy and X-ray diffraction. Compound 3a did not show mesomorphic properties; 3b shows a monotropic hexagonal columnar (Col_h) phase. Compounds 3c–h display an enantiotropic Col_h phase. The mesomorphic properties were found to be dependent on the length of alkoxy side chains. In N,N-dimethylformamide solution, all the compounds displayed a room temperature emission with λ_max at 361–332 nm. A thermogravimetric analysis also was performed.     

Organogelation and cytotoxic evolution of phosphonate ester functionalised hydrophobic alkanediamide motifs

Here we report various rigid alkanediamide derivatives, with three different substitution patterns of phosphonate ester for investigation of organogelation properties. The gelation properties of these compounds can be tuned by altering the number and position of the phosphonate esters. It was found that supramolecular self-assembly of the bisphosphonate esters (1a, 1d, 1h and 2a–b) resulted gel formation, whereas that of the tetraphosphonate esters (3a, 3d, 3h) resulted in construction of nanospheres and microspheres. The diverse morphology of the gel formation appears to depend predominantly on the substituted phenyl ring of the phosphonate ester functionality. Subsequent in vitro cytotoxic screening against four human tumour cell lines (A549, MDA-MB-231, MCF-7 and HeLa) using MTT assays revealed that derivatives 1f–h and 3a show cytotoxic potencies at concentrations less than 5 μM (IC₅₀ values). Compounds 1f–h exhibited promising activity against A549 cell line, 1g–h were highly effective against MDA-MB-231, 1f and 3a show potential against MCF-7 and 1f–g were active against the HeLa cell line.     

Synthesis of Some Novel Fluorinated Pyrazolo[3,4‐b]Pyridines

Abstract

Reaction of 5‐amino‐3‐substituted pyrazoles (1a–c) and 5‐amino‐1,3‐disubstituted pyrazoles (1d–i) with fluorinated‐β‐diketones (2) results in the formation of the single isomer of pyrazolo[3,4‐b]pyridines (4a–h). A one‐pot procedure for the synthesis of title compounds starting from α‐cyanoacetophenones along with a possible mechanistic pathway for the formation of the title compounds is described.     

Esters derived from 7-decanoyloxychromone-3-carboxylic acid: synthesis and mesomorphic properties

The synthesis and liquid crystalline properties of a new series of calamitic liquid crystals containing 4-H-benzopyran-4-one (chromone) within the central core is reported. The first homologue in the series display SmA phase (8a), the homologues (8b–e) exhibit SmA and SmC mesophases and the homologues (8f–h) exhibit only a SmC mesophase.     

Reactions with Hydrazonoyl Halides 341: Synthesis of Some New 2,3-Dihydro-1,3,4-thiadiazoles

Hydrazonoyl halides 4a–h have been caused to react with each of alkyl carbodithioates (3, 13–17)a,b in the presence of triethylamine to give 2,3-dihydro-1,3,4-thiadiazoles in good yields. Structures of the new compounds were elucidated on the basis of elemental analyses, spectral data, and alternative methods of synthesis whenever possible.     

Cyclodesulfurization of Substituted Thiosemicarbazides into 1,3,4-Oxadiazoles via Hydrazonoyl Chlorides

Abstract

The reaction of thiosemicarbazides 1a–h with hydrazonoyl chlorides 2a–g at ambient temperature, in the presence of triethylamine yielded, in each case, two products. The structure of these compounds was confirmed as 1,3,4-oxadiazoles 14a–h and hydrazonothioates 15a–g. The structure of 15b was confirmed through single crystal X-ray diffraction. A mechanism was proposed for this cyclodesulfurization reaction.     

Base-mediated one-pot synthesis of 3,4,5,6-tetrahydro-4-substituted benzo[h]quinazoline-2(1H)-thione derivatives and evaluation of their antioxidant activity

One-pot three-component Beginelli-like reactions of a ketone 1, an aryl aldehyde 2, and thiourea 3 in the presence of sodium hydroxide are described. In this reaction, 3,4,5,6-tertrahydro-4-substituted quinazoline-2(1H)-thione derivatives 4a–h were obtained in good yields (73–85%). The compound 4a has been characterized by single crystal X-ray analysis. All the synthesized compounds 4a–h and 5a–b were screened for their in vitro antioxidant activity. Compounds 4c, 4e, and 4h have exhibited an excellent than the standard ascorbic acid. Compounds 4d, 4f, and 4g have also shown good activity. Remaining compounds show moderate antioxidant activity.     

New Synthetic Approach to 4-N-Arylaminoazuleno[2,1-d]pyrimides

1-Cyano-2-N,N-dimethylformamidinylazulenes as new synthons directed to heterocycle-fused azulenes were obtained by the condensation of 2-amino-1-cyanoazulenes and N,N-dimethylformamide dimethyl acetal (DMFDMA). 1-Cyano-2-N,N-dimethylformamidinylazulene (2a) and 1-bromo-3-cyano-2-N,N-dimethylformamidinylazulene (2b) reacted with anilines (3a–h) to give 4-N-arylaminoazuleno-[2,1-d]pyrimidines in moderate yields. This reaction provides a new procedure for synthesis of pyrimidine-fused azulenes.     

Synthesis of H‐Phosphinates by the UV Light–Mediated Fragmentation‐Related Phosphorylation Using Simple P‐Heterocycles

Photolysis of aryl‐substituted 2,5‐dihydrophosphole oxides (5a–e and 8) in the presence of methanol afforded methyl aryl‐H‐phosphinates (2a–e) in good yields. In the case of 1‐ethyl‐, cyclohexyl‐, or ethoxy‐2,5‐dihydrophosphole oxides, the reaction was much slower (5f and 5h) or did not take place at all (5g). In such instances, the presence of an additional skeletal methyl group (7) or the use of the more strained 7‐phosphanorbornene derivatives (6) promoted the fragmentation‐related phosphorylations. Furthermore, the effect of the ring saturation in 8 and the possible extensions to 2‐phosphabicyclo[3.1.0]hexanes (10a and 10f), a 1,2‐dihydrophosphinine oxide (11), and a 1,2,3,4,5,6‐hexahydrophosphinine oxide (12) were also investigated. Model compounds with P‐phenyl substituent that are of sufficient ring strain (8, 10a, and 11) could be utilized well.     

新型四硫富瓦烯硫杂冠醚衍生物的合成

在高度稀释条件下, 经4,5-二溴甲基-1,3-二硫杂环戊烯-2-硫酮(7)和多缩乙二醇的1,ω-二巯基衍生物的缩合反应, 方便地合成了4,5-位带二硫杂冠醚残基的2-硫代-1,3-二硫杂环戊烯的衍生物8a～8d, 中间体硫杂冠醚8c～8d的合成中有明显的“模板效应”. 在亚磷酸三乙酯存在下, 8a～8d经自偶联生成新型的对称双臂四硫富瓦烯(TTF)硫杂冠醚衍生物10a～10d, 而与4,5-二甲硫基-1,3-二硫杂环戊烯-2-酮(9)经交叉偶联生成新型的非对称单臂四硫富瓦烯硫杂冠醚衍生物11a～11d. 用循环伏安法研究了上述目标化合物的电化学性质和离子传感性质.     

Microwave-Promoted Syntheses of Pyridine Carboxamides and tert-Carboximides from Novel 6-Acetylpyridine-2-carboxylic Acid

A novel 6-acetylpyridine-2-carboxylic acid (4) was obtained occasionally during the synthesis of asymmetric ethyl 6-acetylpyridine-2-carboxylate (3) from 2,6-dipiclinic acid (1). Compounds 3 and 4 could transform mutually under some specific conditions. Two reactions of distinctive types occurred when they reacted with the aromatic amines as precursors, due to different functional groups on the 2-position of pyridine in the molecules of 3 and 4: one was Schiff base condensation and the other was an amidation reaction. From the latter reaction, two series of new compounds, pyridine carboxamides (5a–d) and pyridine tert-carboximides (6a–h), resulted. The relevant reaction mechanism is discussed in detail.     

Synthesis of Novel Benzisothiazolone Derivatives as Potential Antifoulants

Novel antifoulant 2‐(3‐oxobenzo[d]isothiazol‐2(3H)‐yl)acetohydrazide (2) and 3‐oxobenzo[d]isothiazol‐2(3H)‐yl acetic acid [1‐phenylmethylidene]‐hydrazides (3a–3h) were synthesized in good yields, and their structures were characterized by means of UV, IR, ¹H NMR, MS, and elemental analysis.     

Stereoselective production of (S)-1-aralkyl- and 1-arylethanols by freshly harvested and lyophilized yeast cells

Substituted (S)-1-phenyl- 2a–h and (S)-1-benzyl-propan-2-ols 4a and b, and (S)-1-phenylethanol 6 were produced from prochiral ketones 1a–h, 3a,b and 5 by reductions with freshly harvested Zygosaccharomyces rouxii and Debaryomyces hansenii cells. The bioreductions were also performed by lyophilized cells. Comparison of the secondary alcohols from the bioreductions 2b–e,g,h and 4a and authentic (S)-alcohols (S)-2b–e,g,h and (S)-4a synthesized from enantiopure (S)-methyloxirane 7 proved the absolute configuration of the products.     

Preparation and Oxidative-Chlorination Splitting of Nitro Derivatives OF 1,4-Dithiino[2,3-C:5,6-C′]Diquinoline as a Source of 4-Substituted 5- and 8-Nitro-3-Quinolinesulfonic Acid Derivatives

Abstract

Treatment of 1,4-dithiino[2,3-c:5,6-c′]diquinoline (a thioquinanthrene) (1a) with an excess of nitrating mixture (0 °C, 14 days) led to a mixture of mono- and dinitrothioquinanthrene 7-oxides 2b–e and 2f–h. This mixture was: (i) reduced to a mixture of mono- and dinitrothioquinanthrenes 1b– e, or (ii) oxidatively chlorinated with a gaseous chlorine/80% acetic acid/hydrochloric acid system to a mixture of 4-chloro-3-chlorosulfonylquinoline 3a and its 5- and 8-nitroderivatives 3b and 3d. Sulfochlorides 3a– d were independently synthesized from 3,4′-diquinolinyl sulfides 4 and converted to the respective 4-dimethylamino-3-quinoline-N,N-dimethylsulfonamides 9a–d.     

Utility of 1‐Chloro‐3,4‐dihydronaphthalene‐2‐carboxaldehyde in the Synthesis of Novel Heterocycles with Pharmaceutical Interest

Ethyl α‐cyano‐β‐(1‐chloro‐3,4‐dihydronaphthalene‐2‐yl) acrylate (2) was prepared by the Knoevenagel condensation of 1 with ethyl cyanoacetate. Compound 2 was used as the key intermediate to prepare Schiff bases (3a, b), benzo[c]acridine (4), naphthyl thiopyrimidine (5), and pyrazolo[2,3‐a]‐benzo[h]quinazoline (6) derivatives through its reaction with hydrazines, p‐ansidine, thiourea, and 3,5‐diamino‐4‐phenylazopyrazole, respectively. Base‐catalyzed cyclocondensation of 1 with hippuric acid gives oxazolone derivative (7). Reaction of compound 7 with aniline gave imidazolone derivative (9). Treatment of compound 1 with different types of diaminopyrazoles gave 6,7‐dihydro‐pyrazolo[2,3‐a]‐benzo[h]quinazoline (10–13) derivatives. The multicomponent reaction of compound 1 with pyrazolone and malononitrile in the presence of ammonium acetate furnished pyrazolo[3,4‐b]‐benzo[h]quinoline (14) while in the presence of piperidine afforded benzo[h]chromeno[2,3‐c]pyrazole derivative 15.     

3-(4-β-D-吡喃阿洛糖苷-苯基)-4-芳基-5-芳基-1,2,4-噁二唑啉的合成及其镇静活性的研究

以豆腐果苷为原料, 与盐酸羟胺缩合反应生成4-β-D-吡喃阿洛糖苷-苯甲醛肟(2), 2与次氯酸叔丁酯发生取代反应生成4-β-D-吡喃阿洛糖苷-α-氯苯甲醛肟(3); 再将3与Schiff碱通过1,3-偶极环加成生成一系列3-(4-β-D-吡喃阿洛糖苷-苯基)-4-芳基-5-芳基-1,2,4-噁二唑啉(5a～5h). 3和 5a～5h共9个化合物均未见文献报道, 其结构经¹H NMR, IR和MS (HRMS)加以确认, 并对5a～5h进行了药理活性筛选. 结果表明, 部分化合物具有良好的镇静活性. 其中, 化合物5g (200, 100 mg•kg^－1)和5h (200, 100 mg•kg^－1)与豆腐果苷相比较具有更强的活性.