3-methylthio-1,2-dithiolylium salts : Reaction with 4-hydroxy-6-methyl-2H-pyran-2-one and 4-hydroxycoumarin

The reaction of 4- and 5-aryl-3-methylthio-1,2-dithiolylium iodides with 4-hydroxy-6-methyl-2$\text{H}$-pyran-2-one and 4-hydroxycoumarin has been studied. 4-Substituted salts yielded 3-aryl-7-methyl-2-thioxo-2$\text{H}$,5$\text{H}$-pyrano [3,2-c]pyran-5-ones and 3-aryl-2-thioxo-2H,5H-pyrano[3,2-c]benzo[e]pyran-5-ones, respectively, whereas 5-substituted salts gave rise to 3-(5′-aryl-1′,2′-dithiol-3′-ylidene)-6-methyl-2$\text{H}$-pyran-2,4-diones and 3-(5′-aryl-1′,2′-dithiol-3′-ylidene)-2$\text{H}$-benzo [b]-pyran-2,4-diones.     

Ab initio and density functional theory studies on the mechanism of nucleophilic vinylic substitution of 4<Emphasis Type="Italic">H</Emphasis>-pyran-4-one and 2-methyl-4<Emphasis Type="Italic">H</Emphasis>-pyran-4-one with ammonia

 Nucleophilic vinylic substitutions of 4H-pyran-4-one and 2-methyl-4H-pyran-4-one with ammonia were calculated by the B3LYP method using the 6-31G(d,p) basis set. Bulk solvent effects of aqueous solution were estimated by the polarized continuum and Poisson–Boltzmann self-consistent reaction field models using the 6-311+G(d,p) basis set. In the gas phase different mechanisms were found for the two reaction systems calculated. The reaction of 4H-pyran-4-one proceeds through enol, whereas a feasible path for the less reactive 2-methyl-4H-pyran-4-one is the mechanism through a keto intermediate. Addition of ammonia in concert with proton transfer is the rate-determining step ofthe reaction. The mechanism proceeding either by a bimolecular nucleophilic substitution (S_N2) or by one involving a tetrahedral zwitterionic intermediate is shown to be unlikely in the gas phase or nonpolar solution. The effects of bulk solvent not only consist in a reduction of the various activation barriers by about 25–40 kJ mol⁻¹ but also in a change in the reaction mechanism. Received 26 May 2002 / Accepted 26 July 2002 / Published online: 14 February 2003     

Reactivity of 4-azido- and 4-amino-6-methyl-2H-pyran-2-one. Preparation of 1-(6-methyl-2-oxopyran-4-yl)-1,2,3-triazoles and 5-oxopyrano[4,3-b]pyridines

1,3-Dipolar cycloadditions of stable 4-azido-6-methyl-2H-pyran-2-one 1 with electron-rich alkenes and alkynes lead to 4,5-substituted 1-(6-methyl-2-oxopyran-4-yl)-1,2,3-triazoles. Iminophosphoranes derived from 1 have also been synthesized. 5-Oxopyrano[4,3-b]pyridines are prepared by reaction of 4-amino-6-methyl-2H-pyran-2-one 2 with β-dicarbonyl compounds.     

New,Convenient, One-Pot Method for the Synthesis of Thiazolyl-pyrazolones from Dehydroacetic Acid Derivative via a Multicomponent Approach

A convenient one-pot method for the synthesis of thiazolyl-pyrazolones was described in excellent yields. Reaction of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one with thiosemicarbazide and ethyl 2-(2-arylhydrazono)-3-oxobutanoates in anhydrous ethanol under reflux conditions afforded the corresponding 4-(2-arylhydrazono)-1-(4-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)thiazol-2-yl)-3-methyl-1H-pyrazol-5(4H)-one in good yields. The structures of newly synthesized compounds were established on the basis of elemental analysis, infrared, ¹H NMR, and mass spectroscopic studies.     

Synthesis of 3-(3-Methyl-1-aryl-1H-pyrazol-5-yl)-2H-2-chromen-2-one Derivatives via a One-Pot,Three-Component Reaction

An efficient synthesis of 3-(3-methyl-1-aryl-1H-pyrazol-5-yl)-2H-2-chromen-2-one derivatives by the reaction of salicylaldehydes, 4-hydroxy-6-methyl-2H-pyran-2-one, and arylhydrazine in acetonitrile under reflux condition and in the presence of piperidine is reported. This three-component reaction has some advantages such as ease of handling, good yields, and easy purification. All structures were confirmed by infrared, mass, ¹H NMR, and ¹³C NMR spectroscopy.     

The reactions of 4-hydroxy-2-pyrones with 2-hydroxybenzaldehydes. A note of warning

The reaction between 2-hydroxybenzaldehyde and 4-hydroxy-6-methyl-2-pyrone (triacetic acid lactone) affords 3-acetoacetyl-2-chromenone, 7 , instead of 3-(2-hydroxybenzylidene)-6-methyl-3,4-dihydro-2H-pyran-2,4-dione, 6 . The structures previously reported in the literature for the products formed in the reactions of 4-hydroxy-2-chromenone with 2-hydroxybenzaldehydes in a molar ratio 1:1 are considered erroneous. Thus, the previously reported 3-(2-hydroxybenzylidene)chroman-2,4-dione, 10 , should be formulated as 3-(2-hydroxybenzoyl)-2-chromenone, 11 .     

Reactions of 2- and 4-pyrones with secondary phosphine chalcogenides: a facile synthesis of functional phosphorylated pyrones

The oxidative cross-coupling between 4-hydroxy-6-methyl-2-pyrone or 3-hydroxy-2-methyl-4-pyrone and secondary phosphine chalcogenides proceeds in CCl₄/Et₃N under mild conditions (20–52 °С, 0.75–10 h) through the hydroxyl group to give O-(6-methyl-2-oxo-2H-pyran-4-yl) diorganylphosphinochalcogenoates or O-(2-methyl-4-oxo-4H-pyran-3-yl) diorganylphosphinochalcogenoates, in high yields.     

4-氧代-3（4H）-喹唑啉-5-羧酸的合成

以2-氨基-6-甲基苯甲酸为起始原料,通过合环反应生成两种4-氧代-3(4H)-喹唑啉-5-羧酸衍生物(1a, 1b), 1a, 1b分别经高锰酸钾氧化合成了4-氧代-3(4H)-喹唑啉-5-羧酸（2a, 2b）,其结构经¹H NMR, ¹³C NMR和MS表征。研究了投料比｛r［n(高锰酸钾) :n(5-甲基-3(4H)-喹唑啉-4-酮)］｝和反应温度等对收率的影响。结果表明：在最佳反应条件（r=7:1,中性高锰酸钾氧化,于90 ℃反应）下合成2总收率可达66%。     

Reaction between isocyanides and dialkyl acetylenedicarboxylates in the presence of strong CH-acids: one-pot synthesis of highly functionalized annulated 4H-pyrans

The highly reactive 1:1 adduct, produced from the reaction between dialkyl acetylenedicarboxylates and alkyl isocyanides, was trapped by strong cyclic CH-acids such as 4-hydroxy-6-methyl-2H-pyran-2-one or 4-hydroxycoumarin to yield dialkyl 2-(alkylamino)-5-oxo-4H,5H-pyrano[3,2-c]chromene-3,4-dicarboxylates or dialkyl 7-methyl-2-(alkylamino)-5-oxo-4H,5H-pyrano[4,3-b]pyran-3,4-dicarboxylates in good yields at room temperature.     

Synthesis of 1,5-Disubstituted 3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines

A series of 1,5-disubstituted 3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines were synthesized by the reaction of α,β-unsaturated ketones derived from dehydroacetic acid and hydrazine in hot acetic acid or propionic acid. The structures of all new compounds were elucidated by microanalyses, ¹H and ¹³C NMR, IR, and mass spectroscopic measurements.     

An improved synthesis and some reactions of diethyl 4-oxo-4H-pyran-2,5-dicarboxylate

The reaction of ethyl 2-(dimethylamino)methylene-3-oxobutanoate with diethyl oxalate in the presence of sodium hydride in THF gave diethyl 4-oxo-4H-pyran-2,5-dicarboxylate, from which 4-oxo-4H-pyran-2,5-dicarboxylic and 4-oxo-1-phenyl-1,4-dihydropyridine-2,5-dicarboxylic acids and their derivatives were obtained in good yields.     

Synthesis of 1,5-Disubstituted 3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines

Summary. A series of 1,5-disubstituted 3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines were synthesized by the reaction of α,β-unsaturated ketones derived from dehydroacetic acid and hydrazine in hot acetic acid or propionic acid. The structures of all new compounds were elucidated by microanalyses, ¹H and ¹³C NMR, IR, and mass spectroscopic measurements.     

Reaction of dialkyl 2-aryl-4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylates with aliphatic amines

Benzylamine, phenethylamine, and homoveratrylamine reacted with dialkyl 2-aryl-4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylates at the endocyclic carbonyl group with conservation of the enolic hydroxy group to give dialkyl 4-alkylamino-2-aryl-6-hydroxy-6-methylcyclohex-3-ene-1,3-dicarboxylates. The reaction of dimethyl 4-hydroxy-4-methyl-6-oxo-2-phenylcyclohexane-1,3-dicarboxylate with tryptamine was accompanied by dehydration with formation of dimethyl 4-[2-(1H-indol-3-yl)ethylamino]-6-methyl-2-phenylcyclohexa-3,5-diene-1,3-dicarboxylate, presumably due to basic properties of the indole nitrogen atom.     

4(3H)-喹唑啉酮类Schiff碱的合成与抗烟草花叶病毒活性

采用邻氨基苯甲酸经醋酐酰化闭环得2-甲基苯并噁嗪-4-酮, 水合肼回流合成2-甲基-3-氨基-4(3H)-喹唑啉酮, 在无水乙醇中与芳醛反应得4(3H)-喹唑啉酮类Schiff碱. 经元素分析, IR, 1H NMR, 13C NMR对所合成的化合物进行了结构确认和表征. 初步生物活性测试表明, 化合物3t具有较高的抗烟草花叶病毒活性.     

10-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-3-methyl-1H,10H-pyrano[4,3-b] chromen-1-ones from a pseudo-multicomponent reaction and evaluation of their antioxidant activity

A series of novel 10-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-3-methyl-1H,10H-pyrano[4,3-b]chromen-1-ones were synthesized by a pseudo-three-component reaction of 4-hydroxy-6-methyl-2-oxo-2H-pyran-2-one (TAL) with 2-hydroxyarylaldehydes using different acids as catalysts and solvents. The approach relies on a regioselective cascade reaction involving two molar equiv of the TAL iteratively acting as active methylene in a Knoevenagel condensation and in a Michael addition. The antioxidant activity of the synthesized compounds were determined using the DPPH scavenging assay, being the results dependent on the nature and number of chromone substituents. The compound bearing an ortho-dihydroxy (catechol) moiety showed excellent activity at lower concentrations, while derivatives bearing alkoxy groups as substituents present pro-oxidant activity.     

Reaction of sulfene and dichloroketene with open-chain N,N-disubstituted α-aminomethyleneketones. Synthesis of N,N-disubstituted 4-amino-3,4-dihydro-(5-methyl-6-phenyl)(5,6-diphenyl)-1,2-oxathiin 2,2-dioxides and of 4-amino-3-chloro-5-methyl-6-phenyl-2H-pyran-2-ones

Cycloaddition of sulfene to N,N-disubstituted 3-amino-2-methyl-1-phenyl-2-propen-1-ones (I) and 3-amino-1,2-diphenyl-2-propen-1-ones (II) occurred in good to moderate yield only in the case of aliphatic N-substitution to give 4-dialkylamino-3,4-dihydro-(5-methyl-6-phenyl)(5,6-diphenyl)-1,2-oxathiin 2,2-dioxides. Polar 1,4-cycloaddition of dichloroketene to I and II occurred only in the former case, giving in good to moderate yield N,N-disubstituted 4-amino-3,3-dichloro-3,4-dihydro-5-methyl-6-phenyl-2H-pyran-2-ones which were dehydrochlorinated with DBN to N,N-disubstituted 4-amino-3-chloro-5-methyl-6-phenyl-2H-pyran-2-ones. In the reaction of 2-methyl-1-phenyl-3-diphenylamino-2-propen-1-one with dichloroketene, a product was isolated which was proven by uv, ir, nmr and chemical evidence to be the dipolar ion VI, the supposed intermediate of the polar 1,4-cycloaddition of dichloroketene to N,N-disubstituted enaminones.     

新型6-氯-4(3H)-喹唑啉酮类Schiff碱的合成及其抑菌活性

以6-氯邻氨基苯甲酸为起始原料,与醋酐酰化关环制得6-氯-2-甲基噁嗪-4-酮(1);1在80%水合肼中回流反应制得6-氯-2-甲基-3-氨基-4(3H)-喹唑啉酮(2);2与羟基芳醛反应合成了4种新型的6-氯-4(3H)-喹唑啉酮类Schiff碱(4a~4d),其结构经1H NMR,13C NMR,IR和元素分析表征。采用琼脂扩散法研究了4a~4d对金黄色葡萄球菌(A)、大肠杆菌(B)和枯草杆菌(C)的抑制活性。结果表明:用药浓度为300 mg·m L~(-1)时,4a~4d对A~C均有一定的抑制活性,其中6-氯-2-甲基-3-(5-甲基-2-羟基苯亚甲氨基)-4(3H)-喹唑啉酮(4c)抑菌活性最强,对A~C的抑菌圈直径分别为8.8 mm,11.9 mm和9.6 mm。     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. X. Synthesis of N,N-disubstituted 6-alkyl-4-amino-3,3-dichloro-3,4-dihydro-2H-pyran-2-ones and of 6-alkyl-4-amino-3-chloro-2H-pyran-2-ones

Cycloaddition of dichloroketene to N,N-disubstituted 1-amino-4-methyl-1-penten-3-ones and 1-amino-4,4-dimethyl-1-penten-3-ones occurred in moderate to fair yield only in the case of aromatic N-substitution to give N,N-disubstituted 6-alkyl-4-amino-3,3-dichloro-3,4-dihydro-2H-pyran-2-ones, which were dehydrochlorinated with DBN to afford in good yield N,N-disubstituted 6-alkyl-4-amino-3-chloro-2H-pyran-2-ones. In the case of aliphatic N,N-disubstitution, cyclo-addition led directly to 6-alkyl-4-dialkylamino-3-chloro-2H-pyran-2-ones only for N,N-disubstituted 1-amino-4,4-dimethyl-1-penten-3-ones. The reaction between 1-dimethylamino-4-methyl-1-penten-3-one and dichloroketene gave 3-chloro-4-dimethylamino-3,6-dihydro-6-isopropylidene-2H-pyran-2-one in low yield.     

Facile synthesis of caerulomycin E by the formation of 2,2′-bipyridine core via a 2-pyridyl substituted 4H-pyran-4-one. Formal synthesis of caerulomycin A

A new approach to caerulomycins A and E via a 6-methyl-2-(2-pyridyl)-4H-pyran-4-one is described. The pyranone precursor is prepared by Claisen condensation of acetylacetone enol ether with ethyl picolinate.     

The Reaction of 2-Aminoethyl- and 3-Aminopropyl-substituted Heterocycles with 2-Formyl-1,3-cyclanediones and 4-Oxo-3,1-benzoxazines

The reaction of 2-formyl-1,3-cyclohexanedione, its 5,5-dimethyl, 5-phenyl and 5-(2-furyl) derivatives and of 2-formyl-1,3-indanedione and dehydroacetic acid with histamine, 3-(1-imidazolyl)propylamine, 3-(4-morpholyl)propylamine, 3-(2-pyrrolidon-1-yl)propylamine, 2-(1-piperazinyl)ethylamine, tryptamine, and 2-(aminomethyl)pyridine gave fifteen 2-aminomethylene derivatives. The reaction of these amines with 2-methyl-4-oxo-3,1-benzoxazine gave the 3-substituted 2-methyl-4(3H)-quinazolinones and with 4-oxo-2-phenyl-3,1-benzoxazine the monosubstituted N-benzoylanthranilic acid amides.