Nitration of 3,5-dicarbonyl derivatives of 4-phenyl-1,4-dihydropyridine

The nitration of the phenyl ring of 4-phenyl-1,4-dihydropyridines with retention of the 1,4-dihydropyridine structure was accomplished.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 68–69, January, 1987.     

Structure of 4-phenyl-4-oxo-1,4-oxaphosphorinane

Conclusions The six-membered heterocycle in the crystal structure of 4-phenyl-4-oxo-1,4-oxaphos-phorinane has the chair conformation with equatorial position of the phenyl substituent.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2625–2627, November, 1988.     

Structure of 3-phenyl-4-hydroxyisoquinoline

It was shown by UV spectroscopy that 3-phenyl-4-hydroxy-isoquinoline exists in neutral, dipolar, cationic, and anionic forms, depending on the medium. The angle of rotation between the planes of the phenyl ring and the hetero-ring, the length of the “single” C-C bond connecting these rings, and its degree of double bond character in neutral, acidic, and alkaline media were calculated by means of perturbation theory within the framework of the Hückel MO method. On the basis of a study of the π-electron structure of 3-phenyl-4-hydroxyisoquinoline, it was concluded that its various forms have aromatic character. The energy of conjugation of the phenyl group with the π system of 4-hydroxyisoquinoline was calculated. A method for the calculation of the coulombic and resonance parameters for the heteroatoms from experimental UV spectroscopic data and the ionization potentials of the molecules by means of perturbation theory is presented.     

Synthesis and sedative-hypnotic activity of helicid derivatives containing a 1,4-dihydropyridine moiety

Reactions of natural helicid with a number of 1,3-dicarbonyl compounds or β-ketoester in the presence of ammonium acetate or 1-naphthylamine gave a series of helicid derivatives containing a 1,4-dihydropyridine fragment (2a–2h). Eight novel helicid derivatives were structurally confirmed by IR, ¹H NMR, ¹³C NMR, and HR-MS spectroscopy and evaluated for their sedative-hypnotic activities on mice. The results demonstrated that two compounds had higher sedative-hypnotic activity compared with helicid.     

3-氰基-1,4-二氢吡啶衍生物的合成

1,4-二氢吡啶类化合物具有多种生物活性,在临床上受到广泛应用,普遍用于各类心脑血管疾病的治疗。以3-氰基吡啶和含不同取代基的溴化苄为原料在加热回流15h的条件下合成中间体盐;以硼氢化钾(KBH₄)作为还原剂,在冰水浴搅拌的情况下,与中间体盐反应,合成了15个结构新颖的1,4-二氢吡啶衍生物(a～o),产率可达85%～90%,其结构经¹H NMR、¹³C NMR和质谱进行表征。该方法具有成本低、环境友好、操作简单、产率高的特点。     

Intramolecular cyclization of 4-aryl-1,4-dihydropyridine acetals

The synthesis of 4-aryl-1,4-dihydropyridines possessing a protected aldehyde functionality at the ortho position is described. These compounds undergo iminium ion mediated cyclization when treated with titanium tetrachloride or gaseous hydrogen chloride. Mechanistically, cyclization utilizes attack of C-3 of the dihydropyridine on the electrophilic species generated from complexation of the acetal. This methodology highlights opportunities for the construction of novel conformationally constrained dihydropyridine analogs.     

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.     

Rapid synthesis and biological evaluation of 1,4-dihydropyridine derivatives containing a benzothiazolyl moiety

A series of N-(6-methylbenzothiazolyl)-2,3,5,6-tetrasubstituted-4-(aryl)-1,4-dihydropyridines were synthesized by reaction of 2-amino-6-methylbenzothiazole, aromatic aldehyde and active methylene compound in methanol by conventional, as well as, microwave irradiation (solvent free and solid support) methods. The microwave irradiation technique gives better yield and shorter reaction time. Among solid supported microwave irradiation better yields are obtained in acidic alumina as compared to silica, neutral alumina, and basic alumina. All compounds were tested for antibacterial and antifungal activities and results have been compared with standard drugs. Entomological activities were also tested. The results showed that a change in the substitution pattern in 1,4-dihydropyridine derivatives may cause a marked effect on their antimicrobial activity.     

Selective fluorescent sensor for mercury ions in aqueous media using a 1,4-dihydropyridine derivative

Novel 1,4-dihydropyridine (DHP) derivatives containing 3 carboxylic acid units are synthesized via cyclotrimerization of N-substituted β-aminoacrylates followed by basic hydrolysis of the triester. These DHP derivatives are readily soluble in aqueous media buffered at pH 8.0 and the solutions give blue fluorescent signals with quantum yields of 7–23%. One of these compounds, bearing a p-methoxyphenyl N-substituted group, shows specific fluorescent quenching with the mercuric ion (Hg²⁺). The fluorescent signal of the DHP derivative decays over a period of minutes to hours depending on the Hg²⁺ concentration, which implies that the sensing mechanism involves chemical reaction between the Hg²⁺ ion and the DHP compound. The ¹H NMR and MS data suggest that Hg²⁺ mediates the oxidation of the DHP ring into a pyridinium ring. The event is useful for fluorescent detection of Hg²⁺ at the micromolar level within 30 min, with a detection limit of 0.2 μM in aqueous medium.     

Synthesis of 2-methyl-3-nitro-4-phenyl-1,4-dihydroquinoline

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, p. 1696, December, 1989.     

Synthesis of a new 1,4-dihydropyridine containing the imidazo[1,5-α]pyridine nucleus

The synthesis of the new dihydropyridine diethyl 1,4-dihydro-4-(imidazo[1,5-α]pyridin-8-yl)-2,6-dimethyl-pyridine-3,5-dicarboxylate ( 1 ) is described. After many attempts to prepare the key intermediate aldehyde 2a by different approaches, this compound has been obtained in good yields from methyl 2-cyano-3-pyridinecar-boxylate ( 10 ). A three-step procedure involving reduction to the amine, formylation with concomitant cyclization and reduction of the ester group was used.     

Structure and absorption sepctra of 3-phenyl-4-hydroxyisoquinoline

It was shown by IR spectroscopy that 3-phenyl-4-hydroxyisoquinoline exists in the hydroxy form in solution in organic nonpolar solvents. The splitting of the ^vOH band in the IR absorption spectra was assigned to the S-cis and S-trans orientations of the OH group relative to the phenyl ring. An intramolecular hydrogen bond is formed in the cis form of 3-phenyl-4-hydroxyisoquinoline due to interaction of the hydroxyl hydrogen atom with the -electron system of the phenyl ring. An interpretation of the first two absorption maxima in the electronic spectra of the neutral and ionic forms of the 4-hydroxyisoquinoline and 3-phenyl-4-hydroxyisoquinoline molecules is given within the framework of the MO method and the Pariser-Parr-Pople approximation. It is shown that the introduction of a phenyl group in the 3 position of 4-hydroxyisoquinoline, protonation of the ring nitrogen atom, the ionization of the exocyclic -hydroxyl group affect the energy of the upper occupied molecular orbital, leaving the lower vacant molecular orbital of 4-hydroxyisoquinoline almost unchanged.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 805–809, June. 1977.     

Regioselective synthesis of 4-alkylpyridines via 1,4-dihydropyridine derivatives from pyridine

N-Ethoxycarbonylpyridinium chloride ($\text{1}$) reacted with RCu·BF₃ at 4-position with almost complete regioselectivity (better than 99%) to afford the corresponding 1,4-dihydropyridine derivatives ($\text{2}$) in high yields (81≈94%). The dihydropyridines were readily oxidized by oxygen to give 4-alkylpyridines ($\text{4}$: 38≈68% yields).