Synthesis and Photochemistry of Novel 3,5-Diacetyl-1,4-dihydropyridines

 Some novel 3,5-diacetyl-1,4-dihydropyridine derivatives were synthesized; their photochemical behaviour was studied under oxygen or argon atmosphere. Irradiation of these compounds resulted in the aromatization of the ring and formation of 3,5-diacetylpyridine derivatives. The presence of oxygen plays an important role in the type, rate, or failure of oxidation. Irradiation of these compounds with of 2-furyl or 5-methyl-2-furyl substituents in position 4 under argon resulted in the formation of a pyridine ring with retention of these substituents, whereas loss of these substituents and ring aromatization was observed upon irradiation under oxygen.     

Photoinduced Aromatization of Unsymmetrically Substituted 1,4‐Dihydropyridines

Irradiation of unsymmetrically substituted 1,4‐dihydropyridines ( 1b ‐ 1j ) while bubbling oxygen or argon through the solution resulted in aromatization to the corresponding pyridine derivatives ( 3b ‐ 3j ). Compound 1a with 2‐nitrophenyl substituent in 4‐position undergoes elimination of water upon irradiation under both oxygen and argon atmospheres and formation of 3a with 2‐nitrosophenyl substituent. On the other hand, irradiation of the compounds 1e , 1k and 1l with 4‐hydroxy‐3‐methoxyphenyl, 5‐methyl‐2‐furyl and 2‐furyl substituent in this position, respectively, resulted in the expulsion of these substituents and formation of a pyridine derivative unsubstituted in position 4, namely compound 2 . Chloroform as a solvent causes the photo‐oxidation of these compounds by an electron transfer mechanism which is supported by the formation of dichloromethane according to GC analysis and presence of acid (HCl) in the solution after irradiation.     

Synthesis and Photochemistry of Novel 3,5-Diacetyl-1,4-dihydropyridines. II [1]

Summary. In continuation of previous work some novel 3,5-diacetyl-1,4-dihydropyridine derivatives were synthesized and their photochemical behavior was studied under oxygen and argon atmosphere. Oxidation of the dihydropyridine ring and formation of pyridine derivatives was the result of the reaction. The presence of oxygen affects not only on the rate of oxidation, but also the formation of some unidentified by-products was observed on irradiation under this atmosphere.     

Phenylfurylthieno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridyl-methanes. synthesis and reactions of the furan ring transformation

Triarylmethane derivatives with various substituents, phenyl, 5-methyl-2-furyl, and 3-acylamino-thieno[2,3-b]pyrid-2-yl have been obtained for the first time. The behavior of these compounds under protolytic conditions has been studied. It was shown that the character of the protection of the amino group of the thienopyridine fragment affects the type of transformation of the furan ring.     

Synthesis and Photochemistry of Novel 3,5-Diacetyl-1,4-dihydropyridines. II [1]

In continuation of previous work some novel 3,5-diacetyl-1,4-dihydropyridine derivatives were synthesized and their photochemical behavior was studied under oxygen and argon atmosphere. Oxidation of the dihydropyridine ring and formation of pyridine derivatives was the result of the reaction. The presence of oxygen affects not only on the rate of oxidation, but also the formation of some unidentified by-products was observed on irradiation under this atmosphere.     

Photosensitized oxidation of unsymmetrical 1,4-dihydropyridines

Photosensitized oxidation of unsymmetrically substituted 1,4-dihydropyridines using dye sensitizers methylene blue, rose bengal and tetraphenylporphyrin by taking visible light source resulted in the aromatization of dihydropyridine ring and formation of the corresponding pyridine derivatives. Comparison of the results obtained under photosensitized reaction with those obtained by direct photo-oxidation indicated a very fast and smooth reaction of these compounds and formation of pyridine derivatives using theses dyestuffs.     

Nitration of 2- and 4-[2-(2-furyl)vinyl]thiazole derivatives

Nitration of 4-methyl-2-[2-(nitro-2-furyl)vinyl]thiazole with a mixture of concentrated nitric and sulfuric acids leads to 4-methyl-5-nitro-2-[2-(3,5-dinitro-2-furyl)vinyl]thiazole. Under the same conditions 2-methyl- and 2-acetamido-4-[1-R-2-(5-nitro-2-furyl)vinyl]thiazoles (R=CH₃, Cl) are nitrated in the 3 position of the furan ring, 2-amino-4-[1-chloro-2-(5-nitro-2-furyl)vinyl]thiazole is nitrated in the 5 position of the thiazole ring and 2-acetamido-5-nitro-4-[2-(2-furyl)vinyl]thiazole undergoes profound changes. Under the influence of a mixture of of nitric acid and acetic anhydride the latter compound is converted quantitatively to the 5-nitro derivative (with respect to the furan ring), whereas 4-[2-(5-nitro-2-furyl)vinyl]thiazole derivatives do not undergo reaction.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 314–317, March, 1977.     

姜黄素-N-取代吡唑类衍生物合成及抑菌活性

为了寻求杀菌剂的新的先导化合物,用姜黄素与取代酰肼反应得到13个新的姜黄素-N-取代吡唑类衍生物,其结构经IR,1H NMR,13C NMR,MS和元素分析所表征,初步抑菌实验结果表明,在1×10-4mol/L浓度下,所有衍生物与姜黄素对比,对枯草杆菌、金黄色葡萄球菌、大肠杆菌、青霉、黑霉有较好的抑菌效果.其中,3,5-二(4-羟基-3-甲氧基苯基乙烯基)-N-脒基吡唑(3c),3,5-二(4-羟基-3-甲氧基苯基乙烯基)-N-(苯并噻唑-2-硫基乙酰基)吡唑(3k),3,5-二(4-羟基-3-甲氧基苯基乙烯基)-N-(香豆素-3-甲酰基)吡唑(3m)有优异的抑菌效果(抑菌圈16.34～23.81 mm).这些结果表明含有噻唑环、脒基、香豆素环取代基可能有助于提高姜黄素-N-取代吡唑类衍生物的活性.     

Synthesis and anticonvulsant activity of new fluorinated N-phenyl- and N-benzyl-2-azaspiro[4.4]nonane- and [4.5]decane-1,3-dione derivatives: Part III

A series of N-phenyl- and N-benzyl-2-azaspiro[4.4]nonane- and [4.5]decane-1,3-diones containing a fluoro or trifluoromethyl substituents at the aryl ring was synthesized and tested for their anticonvulsant activity in the maximal electroshock (MES) and subcutaneous metrazole (sc.Met) tests. Among them, the most active were N-benzyl derivatives with fluoro and trifluoromethyl substituents especially at position-2 of the aryl moiety. The introduction of the phenyl ring at the imide nitrogen atom resulted in less active compounds. The results obtained showed that incorporation of fluoro or trifluoromethyl substituents increased the anticonvulsant activity in comparison to respective chloro, methoxy or methyl analogues. Crystallographically obtained conformation for one active and two inactive derivatives with trifluoromethyl substituents at position-2 or -3 of phenyl ring were initially used for molecular electrostatic potentials (MEP) calculation. The MEP distribution at carbonyl oxygen atoms was different for active and inactive molecules.     

MASS SPECTRA OF PERACETYLATED DERIVATIVES OF SUGAR ANALOGUES HAVING PHOSPHORUS IN THE HEMIACETAL RING

Abstract

The first, detailed analysis of the mass spectra of the title compounds having a pyranoid or furanoid ring was carried out. The molecular-ion intensities of these phosphorus sugars were shown to be higher compared to the oxygen analogues, thus permitting accurate mass measurement. The main fragmentation pathway was the consecutive loss of the substituents from ring carbon atoms and C-6 (the A series of fragmentation), leading to the formation of 1,2-dihydro-λ⁵-phosphorin or -phosphole oxide derivatives. Possible degradation pathways of the phosphorus-containing ring to acyclic fragments are also discussed. These findings are considered to be of use in structural analysis of these phosphorus sugars.     

Mass-spectral investigation of pyrrolo[3,2-c]piperidines

The dissociative ionization of derivatives of pyrrolo[3,2-c]piperidines and their deutero analogs was studied. The successive elimination of the substituents in the piperidine ring, which leads to its aromatization, and cleavage of this ring via a retrodiene fragmentation mechanism are the principal pathways of fragmentation of these substances. The principles found make it possible to determine the position and character of the substituents in the piperidine ring of derivatives of pyrrolo[3,2-c]piperidines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 212–215, February, 1988.     

Electrochemical oxidation of 4H-imidazole N-oxides

Electrochemical oxidation of substituted 4H-imidazole N-oxides was studied by cyclic voltammetry and EPR spectroscopy. The oxidation potentials of these compounds depend on the chemical form of the substituents, and also on the number and the position of N-oxide oxygen atoms in the ring. During low-temperature electrochemical oxidation in CH₂Cl₂ the formation of cation radicals of 4H-imidazole N-oxides was established. It was shown that the oxidative methoxylation of 4H-imidazole N-oxides proceeds via a cation-radical mechanism.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2009–2013, September, 1991.     

Rearrangements in the Course of Fluorination by Diethylaminosulfur Trifluoride at C-2 of Glycopyranosides: Some New Parameters

Summary.  Reaction of a series of 21 glycosides unprotected at O-2 and featuring various configurations with DAST (diethylaminosulfur trifluoride) was monitored by ¹⁹F NMR spectroscopy. By means of the diacritical set of data (shift values and coupling constants) thus obtained for each product, identification of the operative mechanisms was possible. By correlation of these findings with stereochemical details from the structure of the educts, new parameters governing the choice of the reaction paths could be deduced. This evaluation led to the result that ring contraction after attack at C-2 of the ring oxygen and entry of the fluoride at C-1 is strongly favoured over all other possibilities. Exceptions are all derivatives of the manno series as well as all members of the trans-decalin type structure as present after 4,6-O-benzylidene acetal formation with educts having their ring substituents at C-4 and C-5 in diequatorial (trans) orientation. From these, α-D-mannopyranosides generally and of the trans-decalin types those with an additional 1,2-trans-configuration are prone to 1,2-aglycon migration and, again, entry of the fluoride at C-1. Additional pathways like alkoxy group migration, substitution under retention of configuration, or orthoester formation, are possible by participation of a suitably located neighbouring group at C-3 inasmuch as an alkoxy group interferes from an antiperiplanar orientation to the leaving group at C-2 and an acyloxy functionality attacks in a diequatorial relationship to the latter. The generally intended nucleophilic substitution by fluoride under inversion of configuration is of minor importance. Received November 26, 2001. Accepted November 28, 2001     

Regiospecifity of acetylene photocycloadditions to fluorosubstituted benzenes

Irradiation of a cyclohexane solution of hexafluorobenzene and 1-phenyl-2-alkylsubstituted acetylenes resulted in the formation of bicyclo ( 4.2.0) octatriene derivatives, the quantum yield of (2+2) photoaddition depending on the structure of the acetylene, the con- centration of hexafluorobenzene, and the solvent polarity. Reaction with phenylacetylene resulted in the formation of two isomeric cyclo- octatetraene derivatives. Regiospecific (2+2) photoaddition of 1- phenyl-2-tert-butylacetylene to position C-3 and C-4 in alkoxysubsti- tuted pentafluorobenzene derivatives was observed. (2+2) photoaddition of 1-phenylpropyne-1 to alkoxysubstituted pentafluorobenzenes resulted in 3-phenyl-4-methyl-7-alkoxy-1,2,5,6,8-pentafluorobicyclo (4.2.0) octa- triene derivatives. Replacement of the fluorine atom in hexafluoro- benzene with alkoxy substituents diminished quantum yields of (2+2) photocycloadditions.     

Base cleavage of substituted [phenyl(2-thienyl)methyl]- and [phenyl(2-furyl)methyl]-trimethylsilane. Stabilization of carbanionic centres by 2-thienyl and 2-furyl groups

Rates of cleavage by NaOMEMeOH at 25°C have been determined for (2-thienyl)₂CHSiMe₃ and for the compounds Ph(2-thienyl)CHSiMe₃ and Ph(2-furyl)CHSiMe₃ and some of their derivatives with a substituent in the m- or p-position of the phenyl group or the 5-position of the heterocyclic group. The results indicate that the 2-thienyl and 2-furyl groups stabilize a carbanionic centre more effectively than a phenyl group, and the following approximate pK_a values can be derived: Ph₂CH₂, 33.4; Ph(2-thienyl)CH₂, 30.0; Ph(2-furyl)CH₂, 29.6; (2-thienyl)₂CH₂, 27.1. The effect of the 2-Cl substituent in the thiophen ring is close to that of the p-Cl substituent in the benzene ring, and the effects of the p-Me substituents on the benzene ring are very close to those of the 2-Me substituents on the thiophen or furan rings. The product and rate isotope effects (determined by use of MeOD) are consistent with separation of the carbanion in the rate-determining step.     

Rearrangement processes in the mass spectra of some 3,5-dimethylisoxazole derivatives

The mass spectra of isoxazole and some 3,5-dimethylisoxazole derivatives were investigated. Schemes for the formation of the principal rearranged ions are proposed on the basis of a study of the dissociative ionization of labeled compounds. Examples of the effect of electronic and steric factors on the probability of the existence of different channels for disintegration of the molecular ion are presented. It is shown that the formation of an ion with mass 82 during the dissociative ionization of a number of the investigated compounds occurs via different mechanisms as a function of the nature of the substituents in the 4 position of the isoxazole ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1336–1340, October, 1972.     

Intramolecular sulphonamidomethylation. Part II. Fused heterocycles from 2-phenylethanesulphonamides

1,2,4,5-Tetrahydro-3,2-benzothiazepine 3,3-dioxides 2 , with a variety of substituents on the nitrogen atom, can be easily obtained by the title reaction. The isomeric compounds 4–6 are also formed from sulphonamides bearing an N-aralkyl group with a chain of two or more carbon atoms. Activation of the ring closure-position or deactivation of the aromatic ring in the substituent can direct the reaction to give compounds 2 . Cyclization results are influenced by the size of the new heterocycle ring and by the predominant formation of derivatives with the SO₂ group outside the ring.     

Preparation of Regioselectively Modified Amylose Derivatives and Their Applications in Chiral HPLC

Four regioselectively modified amylose derivatives with three different substituents at the 2-, 3-, and 6-positions were prepared and their enantioseparations in HPLC were examined. Investigations indicated that the nature as well as the arrangement of the substituents significantly influenced their enantioseparations and each derivative exhibited characteristic chiral recognition. Amylose 2-benzoyl-3-(3,5-dimethylphenylcarbamate or 3,5-dichlorophenylcarbamate)-6-((S)-1-phenylethylcarbamate) exhibited chiral resolving abilities comparable to the commercial available amylose tris(3,5-dimethylphenylcarbamate)-based column, Chiralpak AD and the racemic compounds shown in this study were most effectively resolved on these two derivatives. The influence of mobile phase on chiral resolution was also examined.     

Preparation of Regioselectively Modified Amylose Derivatives and Their Applications in Chiral HPLC

Four regioselectively modified amylose derivatives with three different substituents at the 2-, 3-, and 6-positions were prepared and their enantioseparations in HPLC were examined. Investigations indicated that the nature as well as the arrangement of the substituents significantly influenced their enantioseparations and each derivative exhibited characteristic chiral recognition. Amylose 2-benzoyl-3-(3,5-dimethylphenylcarbamate or 3,5-dichlorophenylcarbamate)-6-((S)-1-phenylethylcarbamate) exhibited chiral resolving abilities comparable to the commercial available amylose tris(3,5-dimethylphenylcarbamate)-based column, Chiralpak AD and the racemic compounds shown in this study were most effectively resolved on these two derivatives. The influence of mobile phase on chiral resolution was also examined.

     

The effect of an N-substituent on the recyclization of (2-aminoaryl)bis(5-tert-butyl-2-furyl)methanes: synthesis of 3-furylindoles and triketoindoles

The recyclization of (2-aminophenyl)bis(5-tert-butyl-2-furyl)methane derivatives has been studied. It was shown that the acid-catalyzed recyclization of N-tosylamides leads to the formation of 2-(3-oxoalkyl)-3-(2-furyl)indoles. In contrast, under the same reaction conditions, acetamides are transformed into indoles containing three keto groups. The acid-catalyzed removal of the acetyl group from these substrates facilitated protolytic furan ring opening. The same triketones can be directly obtained from (2-aminoaryl)bis(5-tert-butyl-2-furyl)methanes.