2-硝基-2-亚硝基丙烷氧化1,4-二氢Hantzsch酯衍生物的反应机理

4位取代的Hantzsch酯(HEH)衍生物在2-硝基-2-亚硝基丙烷的氧化下生成相应的吡啶类化合物. 将N-氘代1,4-二氢Hantzsch酯(N-d-HEH)和4,4'-双氘代1,4-二氢Hantzsch酯(4,4'-2d-HEH)分别代替HEH与2-硝基-2-亚硝基丙烷反应, 得到的同位素效应常数分别为1.03(k_N-H/k_N-D)和1.78(k_C4-H/k_C4-D), 表明1,4-二氢Hantzsch酯中4位上氢原子所涉及的C4-H键的断裂发生在反应的决速步骤中或在决速步骤之前, 而1位上氢原子所涉及键的断裂则不在决速步骤中. 由4位取代的HEH酯衍生物的氧化电位与2-硝基-2-亚硝基丙烷的还原电位可在热力学上判断该反应不是由电子转移引发的. 向反应体系中加入单电子转移抑制剂对二硝基苯, 反应未受到明显抑制, 进一步证明了上述推断. 据此推测, 反应可能是通过NO⁺直接对HEH酯上氮原子的亲电历程引发的.     

Hydrogenation of olefins using Hantzsch ester catalyzed by palladium on carbon

Hantzsch 1,4-dihydropyridine (HEH), a well-known model compound of coenzyme NAD(P)H was found as an efficient reducing agent in hydrogenation of unactivated olefins catalyzed by Pd/C. α,β-Unsaturated ketones also underwent hydrogenation, affording the corresponding saturated ketones selectively.     

PAA-supported Hantzsch 1,4-dihydropyridine ester: an efficient catalyst for the hydrogenation of α,β-epoxy ketones

A new type of water-soluble polymer-supported NADH co-enzyme model-PAA (polyacrylic acid)-supported Hantzsch 1,4-dihydropyridine ester (PAA–HEH) was designed and synthesized. Catalytic amount of the supported reagent was used in the hydrogenation of α,β-epoxy ketones to the corresponding β-hydroxy ketones and showed great catalytic efficiency in the reduction reaction. This PAA–HEH was an optimal potential for recycling use.     

A convergent construction of 1,4-dihydropyridine scaffold containing indole fragment

Accompanying with the construction of 1,4-dihydropyridine scaffold, indol-3-yl-5-oxo-1,4,5,6,7,8-hexahydroquinoline, and indol-3-yl-1,4-dihydropyridine derivatives were facilely synthesized through three-component reactions of aromatic aldehydes, 3-cyanoacetyl indoles with 3-amino-2-enones in the presence of ammonium acetate. The 1,4-dihydropyridine core structure can be efficiently aromatized in the presence of stoichiometric 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). This chemistry provides an efficient and promising synthetic strategy to diversity-oriented construction of unaromatized and aromatized desired products. The advantages of the present protocol are atom-economy, simple work-up and easy purification of products by non-chromatographic methods.     

Pd/C催化下汉斯酯1,4-二氢吡啶还原芳香叠氮化合物、芳香硝基 化合物以及碳碳双键的反应研究

汉斯酯1,4-二氢吡啶(HEH)在Pd/C催化下可以将取代的芳香叠氮化合物还原为相应的取代苯胺, 反应具有很好的选择性. 该方法也可以用于芳香硝基化合物的还原. 对于Pd/C催化下汉斯酯1,4-二氢吡啶还原碳碳双键的可行性, 论文中也进行了初步的探讨.     

Rapid and efficient aromatization of Hantzsch 1,4-dihydropyridines with Potassium peroxomonosulfate catalyzed by manganese(III) Schiff base complexes

Rapid and efficient oxidation of Hantzsch 1,4-dihydropyridine with Potassium peroxomonosulfate is reported. The Mn(III)-salophen/monopersulfate catalytic system converts 1,4-dihydropyridines to their corresponding pyridine derivatives at room temperature in a 1:1, CH₃CN/H₂O mixture. The ability of various Schiff base complexes in the oxidation of 1,4-dihydropyridine was also investigated.     

Determination of the C4-H bond dissociation energies of NADH models and their radical cations in acetonitrile

Heterolytic and homolytic bond dissociation energies of the C4-H bonds in ten NADH models (seven 1,4-dihydronicotinamide derivatives, two Hantzsch 1,4-dihydropyridine derivatives, and 9,10-dihydroacridine) and their radical cations in acetonitrile were evaluated by titration calorimetry and electrochemistry, according to the four thermodynamic cycles constructed from the reactions of the NADH models with N,N,N',N'-tetramethyl-p-phenylenediamine radical cation perchlorate in acetonitrile (note: C9-H bond rather than C4-H bond for 9,10-dihydroacridine; however, unless specified, the C9-H bond will be described as a C4-H bond for convenience). The results show that the energetic scales of the heterolytic and homolytic bond dissociation energies of the C4-H bonds cover ranges of 64.2-81.1 and 67.9-73.7 kcal mol(-1) for the neutral NADH models, respectively, and the energetic scales of the heterolytic and homolytic bond dissociation energies of the (C4-H)(.+) bonds cover ranges of 4.1-9.7 and 31.4-43.5 kcal mol(-1) for the radical cations of the NADH models, respectively. Detailed comparison of the two sets of C4-H bond dissociation energies in 1-benzyl-1,4-dihydronicotinamide (BNAH), Hantzsch 1,4-dihydropyridine (HEH), and 9,10-dihydroacridine (AcrH(2)) (as the three most typical NADH models) shows that for BNAH and AcrH(2), the heterolytic C4-H bond dissociation energies are smaller (by 3.62 kcal mol(-1)) and larger (by 7.4 kcal mol(-1)), respectively, than the corresponding homolytic C4-H bond dissociation energy. However, for HEH, the heterolytic C4-H bond dissociation energy (69.3 kcal mol(-1)) is very close to the corresponding homolytic C4-H bond dissociation energy (69.4 kcal mol(-1)). These results suggests that the hydride is released more easily than the corresponding hydrogen atom from BNAH and vice versa for AcrH(2), and that there are two almost equal possibilities for the hydride and the hydrogen atom transfers from HEH. Examination of the two sets of the (C4-H)(.+) bond dissociation energies shows that the homolytic (C4-H)(.+) bond dissociation energies are much larger than the corresponding heterolytic (C4-H)(.+) bond dissociation energies for the ten NADH models by 23.3-34.4 kcal mol(-1); this suggests that if the hydride transfer from the NADH models is initiated by a one-electron transfer, the proton transfer should be more likely to take place than the corresponding hydrogen atom transfer in the second step. In addition, some elusive structural information about the reaction intermediates of the NADH models was obtained by using Hammett-type linear free-energy analysis.     

Graphite oxide mediated oxidative aromatization of 1,4-dihydropyridines into pyridine derivatives

A new approach utilizing graphite oxide as an oxidizing agent is applied for the oxidative aromatization of 1,4-dihydropyridines. Graphite oxide efficiently aromatized Hantzsch 1,4-dihydropyridines into their corresponding pyridine derivatives in excellent yields. The reaction was carried out in toluene at 100 °C.     

Use of pyridinium ionic liquids as catalysts for the synthesis of 3,5-bis(dodecyloxycarbonyl)-1,4-dihydropyridine derivative

The synthesis of cationic amphiphilic 1,4-dihydropyridine derivative, potential gene delivery agent is achieved via an efficient multi-step sequence. The key step of this approach is a two-component Hantzsch type cyclisation of 3-oxo-2-[1-phenylmethylidene]-butyric acid dodecyl ester and 3-amino-but-2-enoic acid dodecyl ester utilising bis(2-hydroxyethyl)ether as a solvent and 1-butyl-4-methylpyridinium chloride as a catalyst. The 1,4-dihydropyridine derivative with long alkyl ester chains at positions 3 and 5 of the 1,4-DHP ring — 3,5-bis(dodecyloxycarbonyl)-2,6-dimethyl-4-phenyl-1,4-dihydropyridine was obtained in substantially higher yield with respect to classical Hantzsch synthesis. Bromination of this compound followed by nucleophilic substitution of bromine with pyridine gave the desired cationic amphiphilic 1,4-dihydropyridine.      

Synthesis and properties of 1-substituted derivatives of diethyl 4-aryl-1,4-dihydrcpyridine-3,5-dicarboxylic acid esters

1-Unsubstituted 4-aryl-3,5-diethoxycarbonyl-1,4-dihydropyridines in the presence of NaH form anions that react with alkyl halides, acid chlorides, and halo acid esters to form the corresponding 1-substituted derivatives of 1,4-dihydropyridine Hydrolysis of one or both ethoxycarbonyl groups in the 3 and 5 positions, as well as hydrolysis of ethyl 4-phenyl-3,5-diethoxycarbonyl-1,4-dihydropyridinyl-1-acetate, occur upon reaction with alkali, but 1,3,5-triethoxycarbonyl-4-phenyl-l,4-dihydropyridine gives the corresponding unsubstituted 1,4-dihydropyridine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1067–1071, August, 1982.     

Novel Reaction of Nitrosonium(NO~ ) with Hantzsch Dihydropyridines

OurinterestinthereactionofHantzschl,4-dihydropyridinewithnitrosoniumtetrafluoroborate(NO BF#-)wasraisedfromtwoaspects.Thefirstwasbiologicalactivitiesandcytotoxicrolesofnitricoxideandnitrosonium(NO )"2.NO isaredoxpartnerofNO,butitsnatureisinstarkcontrasttoNO2'3.ThesecondwasthatHantzschl,4-dihydropyridinesareanaloguesofNADHcoenZymes.TheoxidationofHantzschl,4-dihydropyridinesisanoldreaction.Ithasbeenattractedmoreattentionofchemistsinrecentyears,essentiallysincethediscoverythattheirmetabol…     

Efficient Oxidation of Hantzsch 1,4-Dihydropyridines with Tetrabutylammonium Peroxomonosulfate Catalyzed by Manganese(III) Schiff Base Complexes: The Effect of Schiff Base Complex on the Product Selectivity

Efficient and rapid oxidation of Hantzsch 1,4-dihydropyridine with tetrabutylammonium peroxomonosulfate (TBAO) is reported. The Mn(salophen)/monopersulfate catalytic system efficiently converts 1,4-dihydropyridines (DHPs) to their corresponding pyridine derivatives under mechanical stirring and microwave irradiation in CH₂Cl₂. The ability of various Schiff base complexes to oxidize DHPs was also investigated. The results showed that in the presence of manganese Schiff complex, no by-product was obtained.     

无溶剂超声辐射下硝酸镱高效催化合成 1,4-二氢吡啶衍生物

在Yb(NO₃)₃催化下, 芳香醛、 5,5-二甲基-1,3-环己二酮、 乙酰乙酸乙酯和醋酸铵在室温无溶剂条件下经超声辐射一锅法合成了一系列1,4-二氢吡啶衍生物, 反应时间为15~35 min, 产率为86%~97%. 该方法具有条件温和、 反应时间短且产率高的优点. 催化剂Yb(NO₃)₃对环境友好且可循环使用, 为此类化合物的合成提供了一种有效的新方法.     

Facile photoreduction of graphene oxide by an NAD(P)H model: Hantzsch 1,4-dihydropyridine

To make "clean" reduced GO sheets in high quality and in large scale, a natural reduced nicotinamine adenine dinucleotide NAD(P)H model, Hantzsch 1,4-dihydropyridine (HEH), is used as a mild organic photoreductant in this work. Benefiting from the intense absorption of HEH in the range of 300-420 nm, the graphene oxide (GO) can be readily reduced by HEH under UV light irradiation (λ > 320 nm) to afford single or few-layer reduced graphene oxide at room temperature. Studies on reduction extent reveal that both irradiation time and concentration ratio of HEH to GO are important for effective reduction of GO under UV light. The as-prepared photochemically reduced graphene oxide (PRGO) dispersion is stable without the need for any polymeric or surfactant stabilizers. Simply by extraction treatment, the "clean" PRGO sheets can be obtained in large quantities, and its conductivity approaches to 4680 S·m(-1) that is the highest value reported by photochemical approaches so far.     

A facile synthesis of (±)-sesbanine via γ-addition of ketene silyl acetal with quaternized methyl nicotinate

Total synthesis of (±)-sesbanine ($\text{1}$) was carried out using γ-addition of ketene silyl acetal of methyl 3-cyclopentenecarboxylate to quaternized methyl nicotinate. The resulting 1,4-dihydropyridine ($\text{7}$) was oxidized with DDQ to give 4-substituted nicotinate ($\text{2}$) and $\text{2}$ was converted to alcohol ($\text{8}$) by stereoselective oxymercuration followed by treatment with ammonia to give $\text{1}$.     

Hantzsch synthesis of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-methoxyphenyl)-1,4-dihydropyridine; a novel cyclisation leading to an unusual formation of 1-amino-2-methoxy-carbonyl-3,5-bis(o-methoxyphenyl)-4-oxa-cyclohexan-1-ene

Hantzsch condensation of two equivalents of methyl-3-aminocrotonate with (m- and p)-methoxybenzaldehyde afforded the expected products 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(m-methoxyphenyl)-1,4-dihydropyridine and 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(p-methoxyphenyl)-1,4-dihydropyridine, whereas o-methoxy-benzaldehyde produced mainly 1-amino-2-methoxycarbonyl-3,5-bis(o-methoxy-phenyl)-4-oxa-cyclohexan-1-ene. The structure of the product, not previously reported in the literature, was determined by 1D and 2D NMR spectra and its MS fragmentation. This is the first example of cyclisation leading to a substituted pyran rather than 1,4-DHP under typical Hantzsch reaction conditions. A plausible mechanism for its formation is postulated.     

A study on the reactions of NADH models with electron-deficient alkenes. A probe for the extreme of concerted electron-hydrogen atom transfer mechanism

The reactions of 9-fluorenylidenemalononitrile (FDCN) and 1,1-diphenyl-2,2-dicyanoethylene (DPCN) with Hantzsch ester (HEH), N-methyl Hantzsch ester (Me-HEH), and 1-benzyl-1,4-dihydronicotinamide (BNAH) in oxygen-saturated acetonitrile have been studied. The aerobic reactions with HEH give solely reduction products. However, reactions with Me-HEH and BNAH not only result in reduction products, but also give varying amounts of oxidation products. The amount of oxidation product appears to be related to the electronic character and bulkiness of reactants. We propose that all these reactions follow a general mechanism of concerted electron-hydrogen atom transfer mechanism. If the electron-transfer complex is very tight, only ‘concerted hydride transfer reaction’ occurs. However, if the electron-transfer complex is not so tight, oxygen can capture the radicaloid intermediate to result in oxidation products.     

Novel Reaction of Nitroxide with Hantzsch Dihydropyridines

Nitroxides have been found to be the intermediate in the in vivo metabolism of hydroxamic acid, a well-known biological molecule1. Structural modification of some antitumor drugs by introducing nitroxides can lower toxicity remarkably with retention or even increase of the antitumor activity2. Furthermore, the use of nitroxides as spin probes makes it possible to get information regarding the microenvironment of the reaction. 4-Substituted Hantzsch 1,4-dihydropyridines (DHP) are analogs …     

Oxidative reactivity of S-nitrosoglutathione with Hantzsch 1,4-dihydropyridine

[formula: see text] S-Nitrosoglutathione oxidized 4-substituted Hantzsch 1,4-dihydropyridines in CH3CN/H2O or CH3CN/phosphate aqueous buffer solution to give aromatic products in various yields.     

Electron ionization mass spectrometric study of 1,4-dihydro-4-substituted 2,6-dimethyl-3,5-bis(alkoxycarbonyl)pyridines

Using the accurate masses obtained from a time-of-flight instrument and the tandem mass spectrometric (MS/MS) data from an ion trap instrument, electron ionization mass spectra of a series of 1,4-dihydro-4-substituted 2,6-dimethyl-3,5-bis(alkoxycarbonyl)pyridines are reported and rationalized. Two sets of fragmentation pathways are proposed. One involves the formation of fragment ions containing the 1,4-dihydropyridine structure, and the other of ions containing a pyridine ring.