Reaction of Dimethyl Sulfoxide with 4-Acyloxycoumarins

Dimethyl sulfoxide converts 4-acetoxycoumarin (1) exclusively to 2-(2-hydroxybenzoyl)-2-[(methylthio)methyl]-2,3-dihydro-4 H-furo[3,2-c]chromen-4-one (3) at 180°C under a nitrogen atmosphere, but in the absence of nitrogen, the products obtained are dicoumarol and its dehydrative cyclization products 7 H-bis[1]benzopyrano[4,3-b: 3′,4′-c]pyran-6,8-dione (9) and (3). Under similar conditions, 4-benzoyloxycoumarin (1a) affords benzoic acid, 4-hydroxy-3-({2-[(methylthio)methyl]-3-oxo-2,3-dihydro-1-benzofuran-2-yl}methyl)-2H-chromen-2-one (7), and 3-(2-hydroxybenzoyl)-3,4-dihydro-2H,5H-pyrano[2,3-b] chromen-5-one (8).     

7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉和喹啉-1(2H)-酮衍生物的合成及抗惊厥活性

合成了7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉(3a～3g)和7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹表明啉-1(2H)-酮(4a～4g)类衍生物. 以最大电惊厥法和戊四唑法测定了抗惊厥活性, 以旋转棒法测定了神经毒性. 结果表明, 化合物7-(4-氟苯氧基)-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉-1(2H)-酮(4c)显示最强的抗惊厥作用和低的神经毒性, 其抗电惊厥ED₅₀为6.8 mg/kg, 神经毒性TD₅₀为88.0 mg/kg, 保护指数PI为12.9, 明显优于对照药苯妥英钠.     

新型螺环树状化合物的合成

利用环己二酮单腙芳构化反应, 得到9H, 9H, 11H, 11H, 12H, 12H-六氢化苯并[9,10]-(1H, 1H, 3H, 3H, 4H, 4H, 5H, 5H, 7H, 7H, 8H, 8H-十二氢)菲-2, 6, 10-三酮腙, 然后与季戊四醇反应, 得到9H, 9H, 11H, 11H, 12H, 12H-六氢化苯并[9,10]-(1H, 1H, 3H, 3H, 4H, 4H, 5H,5H, 7H, 7H, 8H, 8H-十二氢)菲-2,6,10-三酮缩三(2,2-二羟甲基-1,3-丙二醇), 再与9-[4-(2,6-二硫杂环己基)苯基]-3-[4-(二甲酯基甲基)苯基]-2,4,8,10-四氧杂螺[5.5]十一烷反应, 制成标题化合物. 中间体和标题化合物经过IR, 1H NMR, MS和元素分析表征.     

Design and Synthesis of 3,4-Dihydropyrrolo[2, 1-c][1, 4]oxazin-1-oneand its 7-Acyl Derivatives

Starting from 1H-pyrrole, unreported 3, 4-dihydropyrrolo[2, 1-c][l, 4]oxazin-1-one 4, 7-(4-chlorobenzoyl)-3, 4-dihydropyrrolo[2, 1-c][1, 4]oxazin-1-one 5 and 7-benzoyl-3, 4-dihydro-pyrrolo [2, 1-c][1, 4]oxazin-1-one 9 were designed and synthesized. They may have antipyretic and analgesic activities.     

Modified Coumarins. 11. Synthesis and Biological Activity of Mannich Bases of Substituted 1,3-Dihydrocyclopenta[c]chromen-4-ones

Mannich bases containing the dialkylaminomethyl group in the 6- and 8-positions of 2,3-di-hydrocyclopenta[c]chromen-4-ones were prepared by condensation of 7- and 9-hydroxy-2,3-dihydrocyclopenta[c]chromen-4-ones with substituted 1,1-diaminomethanes. The effects of 8-chloro-7-hydroxy-6-(1-pyrrolidinylmethyl)-2,3-dihydrocyclopenta[c]chromen-4-one and 8-chloro-7-hydroxy-6-(morpholinomethyl)-2,3-dihydrocyclopenta[c]chromen-4-one on the central and peripheral nervous systemwere defined and enable the presence of tranquilizing and neuroleptic properties to be predicted.     

Synthesis of New Pyrido[4″,3″:4″,5″]thieno[2″,3″:4,5]pyrimido[2,1-b][1,3,4]thiadiazine Derivatives

Ethyl 2-methyl-11-oxo-9, 10-dihydro-1 H , 11 H -pyrido[4",3":4',5']thieno[2',3':4,5]pyrimido[2,1-b][1,3,4]thiadiazine-8(7 H )-carboxylate 7 has been synthesised by the reaction of ethyl 3-amino-4-oxo-2-thioxo-1,3,4,5,6,8-hexahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-7(2 H )-carboxylate 2 with allylbromide followed by treatment with bromine and subsequent dehydrobromination of the brominated product 5 with ethanolic sodium hydroxide. Its isomeric ethyl 2-methyl-11-oxo-9,10-dihydro-3 H ,11 H -pyrido[4",3Prime;:4',5']thieno[2',3':4,5]pyrimido[2,1-b][1,3,4]thiadiazine-8(7 H )-carboxylate 8 has been obtained by condensation of 2 with chloroacetone followed by cyclization of the intermediate 9 with p -toulenesulfonic acid. The thiadiazino derivatives 11 , 13 , 15 were prepared through the reaction of 2 with the appropriate f -halocarbonyl compounds followed by cyclization reactions of the intermediates 10 , 12 , 14 .     

Calix[4]quinones III: The Synthesis of p‐Hydroxycalix[4]arenes by Wolff‐Kishner Reduction

The Wolff‐Kishner reduction of the half‐protected ketal calix[4]monoquinone 3 and its basic hydrolysis product 4 produced a partially reducing product 5 . When the same reduction conditions were applied to the calix[4]quinone benzoates 1 and 2 , the corresponding title compounds, p‐hydroxycalix[4]arenes ( 6 and 7 ), were afforded in one step.     

Tri- and pentacalix[4]pyrroles: synthesis, characterization and their use in the extraction of halide salts

Calixpyrrole-based oligomeric compounds were synthesized by "click chemistry" from the corresponding alkyne- and azide-functionalized calix[4]pyrroles. Calix[4]pyrrole 3, possessing an alkyne functional group, was prepared through a mixed condensation of pyrrole with acetone and but-3-ynyl 4-oxopentanoate. Another alkyne-group-containing calix[4]pyrrole 5 was obtained by treatment of 4'-hydroxyphenyl-functionalized calixpyrrole 4 with propargyl bromide. Tetrakis(azidopentyl)-functionalized calix[4]pyrrole 7 was synthesized by reacting NaN(3) with tetrabromopentyltetraethylcalix[4]pyrrole 6, which was prepared through a condensation reaction of pyrrole and 7-bromohept-2-one. Oligomeric calixpyrrole compounds were found to be capable of extracting tetrabutylammonium chloride and fluoride salts from aqueous media. Extraction abilities of the oligomeric compounds were monitored by NMR and UV/Vis spectroscopy and thermogravimetric analysis.     

Ionic Liquid-Mediated Facile Synthesis and Antimicrobial Study of Thiazolo [2,3-b]Benzo[h]Quinazolines and Thiazino[2,3-b] Benzo-[h]Quinazolines

Abstract

8-Methoxy-4-phenyl-3,4,5,6-tetrahydrobenzo[h]quinazoline-2(1H)-thione, obtained by the condensation of 2-benzylidene-6-methoxy-3,4-dihydronapthalene-1(2H)-one with thiourea, on reaction with chloroacetic acid and 3-chloropropanoic acid in the presence of the ionic liquid N-methylpyridinium tosylate furnishes 3-methoxy-7-phenyl-7,10-dihydro-5H- benzo[h]thiazolo[2,3-b]quinazoline-9(6H)-one and 3-methoxy-7-phenyl-5,6,10,11-tetrahydro- benzo[h][1,3]thiazino[2,3-b]quinazoline-9(7H)-one. Further, condensation of the thione with 1,2-dibromoethane and 1,3-dibromopropane yields 3-methoxy-7-phenyl-6,7,9,10-tetrahydro-5 H-benzo[h]thiazolo[2,3-b]quinazoline and 3-methoxy-7-phenyl-5,6,7,9,10,11-hexahydrobenzo [h][1,3]thiazino[2,3-b]quinazoline respectively. Arylidene derivatives have been obtained by two routes. The structures of the cyclized compounds have been established on the basis of elemental analysis and spectroscopic data. The synthesized compounds were screened for antimicrobial activity. Some of the compounds showed promising antimicrobial activities.     

Modified Coumarins. II. Mannich Reaction of Substituted 4-Phenylcoumarins

Aminomethylation of 5-hydroxy- and 7-hydroxy-4-phenylcoumarins by substituted 1,1-diaminomethanes is studied. Mannich condensation of amino acids and their esters with 7-hydroxy-4-phenylcoumarin gives a series of 8-aminoacylmethylcoumarins and 4-phenyl-9,10-dihydro-2H,8H-chromeno[8,7-e][1,3]oxazin-2-ones     

Synthesis of 3-Substituted Pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidines and Related Fused Thiazolo Derivatives

New ethyl 3-(substituted)-4-oxo-2-thioxo-1,2,3,4,5,6,7,8-octahydropyrido[4',3':4,5]thieno-[2,3-d]pyrimidine-7-carboxylates ( 3a , b ), ( 6 ),( 11-13 ), ethyl 3-methyl-5-oxo-2,3,6,9-tetrahydro 5 H -pyrido[4',3':4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidine-8(7H)-carboxylate ( 4 ), and ethyl 2-methyl-5-oxo-2,3,6,9-tetrahydro-5 H -pyrido[4',3':4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]-pyrimidine-8(7H)-carboxylate ( 8 ) have been synthesized from diethyl 2-isothiocyanato-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,6-dicarboxylate 1. The structure of these compounds as well as their intermediates have been established by their spectral data.     

A NOVEL SYNTHESIS OF 2-SUBSTITUTED-4H-THIENO [2,3-d][1,3] OXAZIN-4-ONE AND 2,3-DISUBSTITUTED THIENO [2,3-d]PYRIMIDIN-4(3H)-ONE DERIVATIVES

Abstract

The synthesis of acetic 2-{[1-methyl-2-(4-oxo-5,6,7,8-tetrahydro-4H-benzo [4,5]-thieno [2,3-d] [1,3-oxazin-2-yl)ethylidene]amino}-4,5,6,7-tetrahydrohenzo[b]thiophene ?3-carboxylic acid anhydride 5 and 2-(oxopropyl)-5,6,7,8-tetrahydro-4H-benzo-[4,5] thieno[2,3-d][1,3]oxazin-4-one 7, has been achieved in three steps from ethyl 2-amino-4,5,6,7-tetrahydrobenzo(b]thiophene-3-carboxlate 1 via the reaction with ethyl acetoacetate followed by hydrolysis and acetic anhydride-induced cyclization. The 2-substituent in compound 5 has two functional groups i.e. active methylene and acid anhydride which are suitably located for intramolecular transformation. Thermal and/or base catalyzed intramolecular cyclization of 5 afforded 2-(4-acetoxy-(hydroxyl)-2-methyl-5,6,7,8-tetrahydrobenzo[4,5] thieno[2,3-b]pyridin-3-yl)-5,6,7,8- tetrahydro-4H-benzo[4,5]thieno[2,3-d] [1,3]oxazin-4-one 10 and 9 respectively. Treatment of 5 with hydrazine hydrate, aromatic and/or heterocyclic amines induced the same intramolecular cyclization with a concomitant oxazine-pyrimidine interconversion to give 3-amino(aryl or heteryl)-2-(4-hydroxy-5,6,7,8-tetrdhydrobenzo-[4,5]thieno[2,3-b]pyridin-3-yl)-3,4,5,6,7,8-hexahydrobenzo[4,5] thieno[2,3-d] pyrimid in-4-one 11–14 respectively.     

Synthesis of pyrido[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidines by condensation of ethyl 1-benzyl-3-oxopiperidine-4-carboxylate with morpholine-4-carboxamidine

A method has been developed for the synthesis of 4-amino-substituted 7-benzyl-2-morpholin-4-yl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidines by condensation of ethyl 1-benzyl-3-oxopiperidine-4-carboxylate with morpholine-4-carboxamidine and subsequent reaction of the 7-benzyl-2-morpholin-4-yl-5,6,7,8-tetrahydro-3H-pyrido[3,4-d]pyrimidin-4-one with trifluoromethanesulfonic anhydride and secondary amines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 762–768, May, 2007.     

Unprecedented cyclisations of calix[4]arenes under the Mitsunobu protocol. Part 3: Thiacalix[4]crowns versus dimers

Intermolecular couplings versus intramolecular ring closures were observed in the reaction of p-tert-butylthiacalix[4]arene and diethylene glycols affording dimers 2 and/or the inherently chiral 1,2-thiacalix[4]crown-3 derivatives 5 under the Mitsunobu protocol. The enantiomeric separation of 5a was achieved by chiral HPLC. The reaction of thiacalix[4]monocrowns 1 with diethylene glycols failed to give crowned thiacalix-tubes 7, instead biscrowns 8 were formed. Partially alkylated double thiacalix[4]arenes 10, 11 were obtained via the base promoted alkylations of a thiacalixarene dimer 2a containing diethyleneoxy linkers.     

Novel One-Pot Multicomponent Synthesis of Substituted 2,3-Dihydro-2-(6-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)phthalazine-1,4-diones and Substituted 3-[3-(N′-Benzylidene-hydrazino)-7H-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazin-6-yl]-4-hydroxy-6-methyl-pyran-2-ones

A one-pot procedure has been developed for the synthesis of substituted 2,3-dihydro-2-(6-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7H-[1,2,4]triazolo[3,4-b] [1,3,4]thiadiazin-3-yl)phthalazine-1,4-diones by reaction of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and phthalic anhydrides in acetic acid medium. Similarly, a one-pot, three-component synthetic procedure has been developed for substituted 3-[3-(N¹-benzylidene-hydrazino)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-yl]-4-hydroxy-6-methyl-pyran-2-ones from 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and various aromatic aldehydes in absolute ethanol and a few drops of glacial acetic acid.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Modified Coumarins. 4. Synthesis and Biological Properties of Cyclopentaneannelated Furocoumarins

Psoralen and allopsoralen analogs that contain an annelated cyclopentane were synthesized from 7-hydroxyand 9-hydroxy-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-ones. 9-Phenyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one exhibited low toxicity, acted as a CNS stimulant, and exhibited cardiotropic activity.     

异色满酮-4及其衍生物的合成(Ⅳ)——辛可宁酸类似物的合成

由异色满酮-4(1)与邻氨基苯甲醛或邻氨基胡椒醛进行Friedlender缩合反应得到异色满并喹啉衍生物异色满并[4,3-b]喹啉(2)和9,10-亚甲二氧基异色满并[4,3-b]喹啉(3).     

替格瑞洛的合成工艺改进

以2-丙硫基-4,6-二氢-5-氨基嘧啶和2-{［(3aR,4S,6R,6aS)-6-氨基-2,2-二甲基四氢-3aH-环戊基［d］［1,3］二氧-4-基］氧}-1-乙醇L-酒石酸盐为原料,经C-N偶联,亲核取代和环合反应制得2-{［(3aR,4S,6R,6aS)-6-(7-氯-5-丙硫基-3H-［1,2,3］三唑［4,5-d］嘧啶-3-基)-2,2-二甲基四氢-3aH-环戊基［d］［1,3］二氧-4-基］氧}-1-乙醇(4); 4与(1R,2S)-2-(3,4-二氟苯基)环丙胺D-扁桃酸盐经亲核取代反应后酸解脱除丙酮叉保护基合成替格瑞洛,总收率58.7%,纯度99.2%,其结构经¹H NMR, MS(ESI)和XRD确证。     

Comparative study on the transition metal complexes of a novel thiacalix[4]arene derivative

A comparative study on Zn²⁺ and Cu²⁺ complexes of the novel compound 5,11,17,23-tetra-tert-butyl-25,27-bis{[4-(methoxycarbonyl)phenyl]methoxy}-2,8,14,20-tetrathiacalix[4]arene, that possesses potential as a core unit for the construction of molecular receptors, is presented using semiempirical AM1 calculation. The possible structures of each metal complex and their corresponding energetic data are compared with the parent 5,11,17,23-tetra-tert-butyl-2,8,14,20-tetrathiacalix[4]arene. The complexation ability of both thiacalix[4]arenes towards the two metal ions is discussed on the basis of binding energies. Both thiacalix[4]arene 1:1 complexes show higher complexation ability towards Cu²⁺. However, 5,11,17,23-tetra-tert-butyl-25,27-bis{[4-(methoxycarbonyl)phenyl]methoxy}-2,8,14,20-tetrathiacalix[4]arene presents lower complexation ability when compared with the 5,11,17,23-tetra-tert-butyl-2,8,14,20-tetrathiacalix[4]arene. The results of liquid–liquid extraction experiments of the thiacalix[4]arenes are in good agreement with the theoretical calculations.     

Synthesis of a functionalised calix[4]arene and its interactions with hemicucurbit[6,7]urils and cucurbit[8]uril

In the present work, we synthesised a functionalised calix[4]arene with 5,11-di(N-methyl-E-(4-pyridylethylene) moiety (CX[4]), and investigated interactions of it with HemiMeQ[6], HemiMeQ[7], and Q[8]) in both water and DMSO using fluorescence spectrophotometry and ¹H NMR spectroscopy. Titration ¹H NMR spectra revealed that Q[n]s prefers to include the N-methyl-E-(4-pyridylethylene) moiety. In particular, the interaction of CX[4] with Q[8] in water resulted in intense fluorescence emission, and this interaction system can respond to compounds such as amantadine.