Synthesis of isocoumarin, 1-isoquinolone and 4(1H)-quinolone derivatives via seleno-intermediates

The reaction of 2-styrylbenzoic acids 2 with N-phenylselenosuccinimide (N-PSS) affords 3-phenyl-iso-coumarin derivatives 3 and 3,4-dihydro-3-phenyl-4-(phenylseleno)isocoumarins 4 via selenolactonization. The reaction of 2-styrylbenzamides 5 and 1-(2-aminophenyl)-3-phenyl-2-peropen-1-one derivatives 11 with N-PSS also resulted in the formation of 1-isoquinolone 6 and 4(1H)-quinolone derivatives 12 , respectively.     

Preparation of Resin-Bound Bismethylene Cyclic Malonic Acid Ester and Facile Solid-Phase Synthesis of 2-Alkylthio-4(1H)-quinolone and 2-Alkyl-4(1H)-quinolone

Abstract

The resin-bound bismethylthiomethylene cyclic malonic acid ester 3 was built up efficiently. Resin 3 can react with arylamines and subsequent thermal cyclizations give 2-alkylthio-4-(1H)-quinolones. Furthermore, conjugate addition of Grignard reagents to the resin 3 forms the resin 6 which was reacted with aryl amines and subsequent thermal-cyclization-cleavages afford the 2-alkyl-4-(1H)-quinolones.     

Photochromism of bis(2-alkyl-1-benzofuran-3-yl)perfluorocyclopentene derivatives

[reaction: see text] Photochromic diarylethene derivatives having benzofuran heteroaryl groups, bis(2-methyl-1-benzofuran-3-yl)perfluorocyclopentene and bis(2-butyl-1-benzofuran-3-yl)perfluorocyclopentene, were synthesized, and their photochromic performance was examined in hexane solution as well as in the single-crystalline phase. The compounds exhibited photochromic reactivity even in the single-crystalline phase.     

Studies on ketene and its derivatives. CXI . Photoreaction of diketene with 2(1H)-quinolone derivatives

Photoreaction of diketene with 4-methyl-2(1H)-quinolone and 1,4-dimethyl-2(1H)-quinolone gave 2R*,2aR*,SbR*- and 2R*,2aS*8bS*-8b-methyl-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]quinoline-2-spiro-2′-(oxetan)-4′-one ( 6a and 6b ), and their 4-methyl derivatives 7a and 7b , respectively. Thermolysis of compounds 6 and 7 afforded 2aR*,8bS*-8b-methyl-2-methylene-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]quinoline ( 8 ) and its 4-methyl derivatives 9 , respectively. Similarly, photolysis of diketene and 4-acetoxy-2(1H)-quinolone gave 1R*,2aS*,8bS*- and 1R*,2aR*,8bR*-8b-acetoxy-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]-quinoline ( 11a and 11b ). Alcoholysis of compounds 11a and 11b with hydrogen chloride in methanol gave 1-hydroxy-1-(methoxycarbonyl)methylcyclobuta[c]quinoline derivative 12 and 13 which were transformed to 4-acetyl-3-methyl-2(1H)-quinolone ( 15 ) by further alcoholysis. Photoreaction of diketene with 2(1H)-quinolone derivatives gave the corresponding cyclobuta[c]quinoline spirooxetanone derivatives 18 and 23 , which, by thermolysis, were transformed to 2-methylenecyclobuta[c]quinoline 23 and 25 , respectively.     

Regioselective methylation of 1-benzyl-Δ9, 10-octahydro-4-quinolone

The methylation of 1-benzyl-⁹,¹⁰-octahydro-4-quinolone with methyl iodide in the presence of lithium diethylamide in tetrahydrofuran is a regioselective electrophilic substitution reaction, and, depending on the reaction conditions, takes place in the 3 or 8 position of the quinolone system. Deuteration under the same conditions takes place only in the 3 position.Communication 1 from the series Methylated cis-enamino ketones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 780–784, June, 1982.     

Steric controls in the preparation of 1-benzyl-1,4-dihydro-3-(2H)isoquinolones and 1-benzyl-1,2,4,5-tetrahydro(3H)-2-benzazepin-3-ones via Beckmann rearrangement

The effect of substituents in the 1-position of 2-indanones and 2-tetralones on the course of Beckmann rearrangement reactions was studied. Nmr spectral anaylses of the intermediate oximes and final products demonstrated that steric controls were operative both before and during rearrangement. Use of the appropriate substituents and reaction conditions makes this reaction scheme attractive for preparation of the title compounds.     

4-羟基-2(1H)-吡啶酮-3-甲酰胺类冬青生菌素类似物的合成与生物活性

以反式-4-羟基肉桂酸为起始原料,经乙酰化、酰基叠氮、curtius重排、加成和环合等6步反应合成了4-羟基-2(1 H)-吡啶酮-3-甲酰胺类冬青生菌素类似物,总收率17%.随后用滤纸片扩散法对该化合物的抑菌性能进行了初步研究.实验表明,该化合物对于白色念珠菌具有较好的抑制作用,对于酵母菌抑制作用较弱,对大肠杆菌和金黄色葡萄球菌基本无抑制作用.     

Synthesis of 6-nitro-8-chloro-2,3-dieydro-4(1H)-quinolone

6-Nitro-8-chloro-2,3-dihydro-4(1H)-quinolone and its dehydrogenation product-6-nitro-8-chloro-4-hydroxyquinoline — were isolated in the cyclization of N-(2-chloro-4-nitrophenyl--alanine in polyphosphoric acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 954–956, July, 1978.     

Synthesis of unnatural 1-methyl-2-quinolone derivatives

Unnatural 1-methyl-2-quinolone derivatives were synthesized by regioselective C-C bond formation. When 1-methyl-3,6,8-trinitro-2-quinolone (TNQ) was treated with enamines, nucleophilic addition readily occurred at the 4-position, and succeeding hydrolysis of enamine moiety followed by elimination of nitrous acid furnished 4-acylmethyl-1-methyl-6,8-dinitro-2-quinolones. The same products could be prepared by the reaction of TNQ with ketones in the presence of triethylamine. The present reaction enabled the introduction of various kinds of acylmethyl groups substituted with alkyl, aryl or hetaryl groups.     

Synthesis of 3-arylamino-4(3H)quinazolinone derivatives from 1-acetyl- or 1-ethoxycarbonylmethylene-2-arylhydrazines

By reacting 1-acetyl- or 1-ethoxycarbonylehloromethylene-2-arylhydrazines ( 2a-c ) with anthranilic acids (1a-b) the corresponding C-acetyl- or C-ethoxyearbonylcarbohydrazonamide derivatives (3a-d) were obtained. Ring closure of the carbohydrazonamides with acetic anhydride afforded 2-carboethoxy- or 2-acetyl-3-arylamino-4(3H)quinazolinones ( 4a-d ). The ester derivatives undergo basic hydrolysis with decarboxylation to 3-arylamino-4(3H)quinazolinones ( 5a-b ).     

Solid-phase synthesis of 4(1H)-quinolone and pyrimidine derivatives based on a new scaffold-polymer-bound cyclic malonic acid ester

An efficient method for the preparation of polymer-bound cyclic malonic acid ester starting from Merrifield resin has been developed. Reaction of the resin-bound cyclic malonic acid ester with triethyl orthoformate and subsequent double substitution with nucleophilic reagents, such as arylamine, urea, thiourea, 2-aminobenzothiazoles, or isothiosemicarbazones, afforded the corresponding polymer-bound substituted aminomethylene cyclic malonic acid esters, which upon thermal treament led to 4(1H)-quinolones, 3-substituted uracils and thiouracils, 4H-pyrimido[2,1-b]benzothiazol-4-ones, and 1-(N-alkylidene or benzylideneamino)-1,6-dihydro-2-methylthio-6-oxo-pyrimidines, depending on the structures of the nucleophilic reagents.     

非催化条件下合成取代2,3-二氢-4(1H)-喹唑啉酮衍生物的研究

在乙醇/水混合溶剂中,回流条件下,无需使用催化剂,靛红酸酐、芳香醛和铵盐或伯胺三组分"一锅法"反应,可合成单取代和双取代的2,3-二氢-4(1H)-喹唑啉酮。考察了溶剂对产率的影响,结果表明,当乙醇/水体积比为1∶3时,产品产率较高。产物的结构通过熔点、IR、1H NMR和元素分析进行测定和结构表征。     

Microwave synthesis and anticonvulsant activity of 2-benzyl-1(2H)-phthalazinones

Microwave irradiation of 1(2H)-phthalazinone with benzyl halides and potassium carbonate in dimethyl-formamide afforded 2-benzyl-1(2H)phthalazinones in modest yields. These products were tested in mice and rats in maximal electroshock and pentylenetetrazole seizure models for anticonvulsant activity, and in the rotorod test for neurotoxicity. A majority of the compounds exhibited anticonvulsant protection. The p-aminobenzyl analog 1f was the most active compound in the maximal electroshock assay; it's ED₅₀ value was 19.46 mg/kg and the TD₅₀ was 61.35 mg/kg. In the rat, the values were 3.71 mg/kg and >125 mg/kg, respectively.     

A convenient preparation of 4,8-dimethoxy-3-substituted-2(1H)-quinolones by an electrophilic reaction through base-induced deprotonation and its synthetic application for the synthesis of new alkaloids, 3,4,8-trimethoxy-2(1H)-quinolone and 3-formyl-4,7,8-trimethoxy-2(1H)-quinolone(glycocitridine)

Some 4,8-dimethoxy-3-substituted-2(1H)-quinolones were prepared by electrophilic reaction of 4,8-dimethoxy-2(1H)-quinolone with electrophiles in the presence of n-butyllithium-N,N,N',N'-tetramethylethyl-enediamine in fairly good yields. This present method was successfully applied for the synthesis of two new alkaloids bearing the 4,8-dimethoxy-2(1H)-quinolone skeleton.     

Synthesis and antimycobacterial screening of new 4-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-pyrazol-3-yl)quinoline derivatives

A new series of 4-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-pyrazol-3-yl)quinoline ( 6a-t ) have been synthesized by a click reaction of 4-(4-ethynyl-1-phenyl-1H-pyrazol-3-yl)quinoline ( 4a-d ) with a substituted benzyl azide ( 5a-e ). The starting alkyne derivatives 4a-d are obtained from Bestmann-Ohira reaction of 1-phenyl-3-(quinolin-4-yl)-1H-pyrazole-4-carbaldehyde and dimethyl(1-diazo-2-oxopropyl)phosphonate. The newly synthesized compounds are screened against M. tuberculosis H37Ra dormant and active, Escherichia coli, Pseudomonas fluorescence, Staphylococcus aureus and Bacillus subtilis strains at 30 μg/mL concentration. Most of the screened compounds showed good to moderate antibacterial activity against S. aureus, B. subtilis, and Mycobacterium tuberculosis H37Ra strains. The synthesized derivatives of quinolinyl-pyrazole-4-carbaldehyde and quinolinyl-pyrazole-4-ethyne reportd good to moderate activity against both strains of M. tuberculosis H37Ra. Ten derivatives of quinolinyl-pyrazole presented good activity against B. subtilis. These results suggested that further optimization and development of quinolinyl-pyrazolyl-1,2,3-triazole moeity could serve as lead compounds for antimycobacterial activity.     

Synthesis of α-Oxo and α-hydroxy-1-benzyl-1,4-dihydro-3(2H)-isoquinolinones

The reaction of some primary amines with the methyl 2-[(α-oxobenzyl)-(α-bromo)methyl]phenylacetate ( 5 ) afforded the isoquinolinones 7a-d , which in turn were hydrogenated to 10a-d . The synthesis of these compounds was designed on the basis of a potential depressant and antiinflammatory activity found in other structurally related compounds.     

1-benzoyl-2-(2-naphthyl)-selenourea

During our synthesis of N-benzoyl-N'-aryl selenourea derivatives, we isolated the title compound. One of them was selected optically for the diffraction study. The crystal belongs to the Monoclinic space group P21/n, Mr = 353.27, a = 11.073(1)A, b = 5.745(1) A, c = 24.356(5) A, β= 92.10 (1) °, V= 1548.3 (4) A3, Z = 4, Dx=1.515 Mg/m3, λ (Mo Kα )=0.71073 A, θ = 1.67-25, μ= 2.428 mm-1 , T = 296 (2) K.View of the molecule showing the labeling of the non-H atoms are described as:The selenourea and thiourea have analogous structure, a few literatures have reported the crystal of N-benzoyl-N'-aryl thiourea derivative1,2. In the reported crystal structure of N-benzoyl-N'-aryl thiourea derivative, there is a intermolecular hydrogen bond between the carbonyl O and H atom on N', in each -C(O)-NH-N'H- moiety, forming a planar six-membered ring. In this title compound,[2.654(2)A], C (8), N (1) and C (7)l.In the crystal structure of N-benzoy-N'-aryl thiourea derivative, there have a two dimensional With the intramolecular hydrogen bond [2.654(2)A] they form the planar four-membered ring between every molecular. The atom of Se dose not link the moleculars like the S atom of N-benzoyl-N'-aryl thiourea derivative, and it is only out of six-membered ring, which forms by N (2)H…O, C (8), N (1) and C (7).