Development of diversified methods for chemical modification of the 5,6-double bond of uracil derivatives depending on active methylene compounds

The reaction of 5-halogenouracil and uridine derivatives 1 and 7 with active methylene compounds under basic conditions produced diverse and selective C-C bond formation products by virtue of the nature of the carbanions. Three different types of reactions such as the regioselective C-C bond formation at the 5- and 6-positions of uracil and uridine derivatives (products 2, 5, 8, 17, 20 and 21), and the formation of fused heterocycle derivatives 2,4-diazabicyclo[4.1.0]heptane (15) and 2,4-diazabicyclo-[4.1.0]nonane (16) via dual C-C bond formations at both the 5- and 6-positions were due to the different active methylene compounds used as reagents.     

Application of aminopropyltriethoxysilane and <Emphasis Type="Italic">N</Emphasis>-[2-(aminoethyl)-<Emphasis Type="Italic">N</Emphasis>-3-(trimethoxysilyl)propyl]amine to the synthesis of linear and heterocyclic compounds

Reaction of 3-aminopropyltriethoxysilane and N-[2-(aminoethyl)-N-3-(trimethoxysilyl)propyl]-amine and their derivatives with diethylcarbamic acid trimethylsilyl ether and trimetisilylisocyanate proceeds through the stage of formation of intermediate products which under conditions of the synthesis undergo intramolecular (in the case of formation O-silylcarbamates) and intermolecular (in the case of the formation of carbamide trimethylsilyl derivatives) desilylation leading to the cyclic and linear products respectively.     

Synthesis of derivatives of 2-(o-nitrobenzyl)pyridine

Diazotization of 2-(o-nitro-p-aminobenzyl)pyridine (I) in concentrated H₂SO₄ and subsequent diazo-reaction lead to the formation of 2-(o-nitro-p-halogenbenzyl)pyridines. During the acylation reaction with acetic anhydride and benzoyl chloride, the corresponding derivatives are readily formed. Compound I reacts with benzyl chloride with the formation of the corresponding monoand dibenzyl derivatives and with p-nitrobenzaldehyde with the formation of the corresponding azomethine.     

Application of sec-butanol to the derivatization of hydroxyfuranones.

This paper reports the use of sec-butanol for the derivatization of chlorinated hydroxyfuranones. The following hydroxyfuranones were investigated: 3,4-dichloro-5-hydroxy-2(5H)-furanone, 3,4-dibromo-5-hydroxy-2(5H)-furanone, 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone, and 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone. Their derivatization products were analyzed by gas chromatography/mass spectrometry. The sec-butyl derivatives of the hydroxyfuranones investigated yield ions that are less abundant than those obtained for the corresponding isopropyl derivatives. However, sec-butyl derivatives are easily detectable in especially dirty matrixes because they produce double peaks in the chromatogram. The ion intensity of the first peak in the pair is lower than that of the second peak, but both are characterized by the same spectrum. The formation of multiple peaks is related to the formation of diastereoisomers during derivatization.     

Formamidopyrimidines as major products in the low- and high-intensity UV irradiation of guanine derivatives

Two major UV-induced transformation products of guanosine (Guo) in oxygen-free aqueous solution were isolated and characterized using reverse-phase HPLC-ESI-MS and UV absorption spectrophotometric techniques. These products were identified as two different sugar isomers of 2,6-diamino-4-hydroxy-5-formamidopyrimidine ribonucleosides, FapyGuo. A formation quantum yield of the order of 10(-3) for these products was obtained at a 75 microM concentration of Guo, while an increase in the ground state concentration of Guo from 10(-5) to 10(-4) M decreased their formation yield by a factor of ten. The formation of FapydGuo was also observed in the 254 nm photolysis of 2'-deoxyguanosine. In addition, the formation FapyGua was identified in the UV photolysis of all the guanine derivatives investigated. A formation quantum yield of the order of 10(-4) was obtained for the latter product, except in the photolysis of Gua in which a higher formation yield (10(-3)) was determined. These results suggest that hydration of the radical cation of guanine, followed by opening of the imidazole ring to form Fapy products, is one of the main low-intensity UV radiation-induced photo-transformation pathway of the guanine derivatives in oxygen-free aqueous solutions. Furthermore, the formation of the Fapy products and base release occurs through a similar photo-transformation pathways using a high-intensity UV radiation source.     

Synthesis of Dehydro Derivatives of Cycloheximide and Inactone

Catalytic hydrogenation of 3-chloro-2-(2,6-dioxopiperidin- 4-ylacetyl)-2-cyclohexenones over palladium catalyst leads to formation of dehydrocycloheximide derivatives. Reduction of the same compounds with Zn-Ag yields dehydroinactone derivatives.     

Spectrophotometric methods for the determination of certain catecholamine derivatives in pharmaceutical preparations

Two simple, rapid and sensitive spectrophotometric methods for the determination of catecholamine derivatives (pyrocatechol, dopamine, levodopa and methyldopa) are developed. The first method involves the oxidation of o-dihydroxybenzene derivatives by N-bromosuccinimide followed by oxidative coupling with isoniazid leading to the formation of a red-coloured products of maximum absorbance (lambda(max)=480-490 nm). The second method is based on the formation of green to blue complex (lambda(max)=635-660 nm) between o- dihydroxybenzene derivatives and sodium nitroprusside in the presence of hydroxylamine hydrochloride. All measurements of the two procedures are carried out in an alkaline medium at room temperature. The two methods are successfully applied for the determination of dopamine hydrochloride, levodopa and methyldopa in injections and tablets of pharmaceutical preparation. The common excipients used as additives in pharmaceuticals do not interfere in the proposed methods. The reliability of these methods are established by parallel determination with the reported and official methods.     

Substituent effects on the reversibility of furan-maleimide cycloadditions

The effects of furan and maleimide substitution on the dynamic reversibility of their Diels-Alder reactivity have been investigated computationally and by (1)H NMR spectroscopy. Furan and furan derivatives bearing methoxy, methyl, or formyl groups at their 2- or 3-positions were investigated with maleimide and maleimide derivatives bearing N-methyl, N-allyl, and N-phenyl substituents. Computational predictions indicate that electronic and regiochemical effects of furan substitution significantly influence their Diels-Alder reactivity with maleimide, with reaction free energies of exo adduct formation ranging from ΔG = -9.4 to 0.9 kcal/mol and transition state barriers to exo adduct formation ranging from ΔG(?) = 18.9 to 25.6 kcal/mol. Much less variation was observed for the reactivity of N-substituted maleimide derivatives and furan, with reaction and transition state free energies each falling within a range of 1.1 kcal/mol. Dynamic exchange experiments monitored by (1)H NMR spectroscopy support computational predictions. The results indicate the reactivity and reversibility of furan-maleimide cycloadditions can be tuned significantly through the addition of appropriate substituents and have implications in the use of furan and maleimide derivatives in the construction of thermally responsive organic materials.     

One-pot synthesis of adamantane derivatives by domino Michael reactions from ethyl 2,4-dioxocyclohexanecarboxylate

Adamantane derivatives were constructed by the one-pot reaction of ethyl 2,4-dioxocyclohexanecarboxylate with 2-phenylethyl 2-(acetoxymethyl)acrylate or 2-(acetoxymethyl)-1-phenyl-2-propen-1-one via domino Michael reactions and a Dieckmann condensation or an aldol-type reaction (four-bond formation). This is the first one-pot construction of adamantane derivatives from cyclohexanone derivatives not involving enamines.     

Transformations of (1E,3E)-1-(benzoylamino)-4-(dimethylamino)buta-1,3-diene-1,2,3-tricarboxylates into pyridine and pyrrole derivatives

New, highly functionalised (1E,3E)-1-(benzoylamino)-4-(dimethylamino)buta-1,3-diene-1,2,3-tricarboxylates proved to be useful and versatile reagents in the formation of highly substituted pyridine, N-aminopyridine, pyrrole and pyrido[3,4-c]pyridazine derivatives. The formation of the particular type heterocyclic system is dependent on the starting (1E,3E)-1-(benzoylamino)-4-(dimethylamino)buta-1,3-diene-1,2,3-tricarboxylate. By an appropriate choice of different ester groups it is possible to drive the reactions towards the formation of either pyridine or pyrrole derivatives.     

Research of benzimidazole derivatives. XXXVI. Synthesis and transformations of N-propargyl-substituted 2-aminobenzimidazoles

1-(2′-Propynyl)-2-aminobenzimidazole and 1,3-di(2′-propynyl)-2-iminobenzimidazoline, which are cyclized by the action of bases to imidazo[1,2-a]benzimidazole derivatives, were obtained by alkylation of 2-aminobenzimidazole with propargyl bromide. The cyclization proceeds with the formation of intermediate N-propadienyl derivatives.     

Thienopyrrolizines: New condensed triheterocyclic systems

Cyclization of 3-(1-pyrrolyl)thiophene-2-carboxamide derivatives of methyl 3-(1-pyrrolyl)-2-thiophenecarboxylate afforded imminium salts and resulted in the formation of thieno[2,3-b]pyrrolizine derivatives.     

Ethynyl ketene-S,S-acetals: the highly reactive electron-rich dienophiles and applications in the synthesis of 4-functionalized quinolines via a one-pot three-component reaction

An efficient synthetic method for 4-functionalized quinoline derivatives, 4-((1,3-dithian-2-ylidene)methyl)quinolines, has been developed. Mediated by trifluoromethanesulfonic acid, ethynyl ketene-S,S-acetals can react in a one-pot procedure with various arylamines and aldehydes under mild conditions to give the corresponding quinoline derivatives in good to high yields via a consecutive arylimine formation, regiospecific aza-Diels-Alder (Povarov) reaction, and reductive amination.     

A convenient procedure for the synthesis of fused fluoro isoquinolines

A base-promoted conversion of ortho-trifluoromethyl benzyl derivatives of NH-heterocycles into a respective fluorinated isoquinolines (38-57% isolated yields) is reported. The reaction is general for the benzylated derivatives of the electron-rich NH-heterocycles and the respective derivatives of pyrazole. The outcome of the reaction could be explained by an intermediate formation of a highly reactive quinone methide species.     

Specific Sequestering Agents for the Actinides. 29. Stability of the Thorium(IV) Complexes of Desferrioxamine B (DFO) and Three Octadentate Catecholate or Hydroxypyridinonate DFO Derivatives: DFOMTA, DFOCAMC, and DFO-1,2-HOPO. Comparative Stability of the Plutonium(IV) DFOMTA Complex(1)

The metal complex stability constants of Th(IV) with desferrioxamine B (DFO) and three octadentate derivatives [N-(2,3-dihydroxy-4-carboxybenzoyl)desferrioxamine B (DFOCAMC), N-(1,2-dihydro-1-hydroxy-2-oxopyridin-6-yl)carbonyl)desferrioxamine B (DFO-1,2-HOPO) and N-(2,3-dihydroxy-4-(methylamido)benzoyl)desferrioxamine B (DFOMTA)] have been determined. The formation constant of the Pu(IV)/DFOMTA complex has also been determined, and the formation constants have been estimated for the other Pu(IV) complexes of octadentate DFO derivatives. The DFO derivatives form 1:1 complexes with Th(IV) in aqueous solution. The solution chemistry of the Th(IV) complexes has been studied by spectrophotometric, potentiometric and proton NMR titrations. The Th(IV) formation constants are as follows (log K(f) values and esd's): DFO, 26.6(1); DFOMTA, 38.55(5); DFOCAMC, 37.2(3); DFO-1,2-HOPO, 33.7(4). The Pu(IV)/DFOMTA formation constant, determined by competitive spectrophotometric titration is (log K(f) value) 41.7(2). The estimation of the other Pu(IV) formation constants are as follows (log K(f) values): DFOCAMC, 40.4; DFO-1,2-HOPO, 36.9. The selectivity of DFO and the three derivatives for actinide(IV) ions is discussed.     

Preparation of novel synthons, uniquely functionalized tetrahydrofuran and tetrahydropyran derivatives

The dianion of the acetoacetic ester reacts with epibromohydrin derivatives to afford a mixture of (Z)-2-alkoxycarbonylmethylidenetetrahydrofuran derivative and (E)-2-alkoxycarbonylmethylidenetetrahydropyran derivative. The selective formation of the tetrahydrofuran derivative is achieved by the use of LiClO4 as the additive. The preparation of the optically active tetrahydrofuran derivatives and tetrahydropyran derivatives is also examined, and the optical purity and absolute configuration of the products is elucidated.     

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.     

Rearrangements in the haloalkoxy(mercapto,amino)-sym-triazine series

It is shown by means of an O¹⁸ label that the thermolysis of 2-methoxy-4-(2-chloroethoxy)-6-dialkylamino-sym-triazines to give oxazolo-sym-triazines in an inert medium proceeds without the formation of intermediate N-2-chloroethyl derivatives. In contrast to this, the thermolysis of 2-ethoxy(propoxy)-4-(2-chloroethoxy) derivatives gives N-2-chloroethyl derivatives, which upon prolonged heating are converted to oxazolo-sym-triazines. Triazinium salts are formed when both 2-chloroethoxy and N-2-chloroethyl derivatives are heated in water. The triazinium salts undergo rearrangement to N-2-chloroethyl derivatives when the water is removed. On the basis of the data obtained it is assumed that the thermolysis of 2-chloroethoxy-sym-triazines in an inert medium proceeds via a concerted mechanism, whereas thermolysis proceeds via an ionic mechanism in water. Data from the UV, IR, and PMR spectra are presented.See [1] for communication 3.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 124–127, January, 1979.     

2-(取代苯亚氨次甲基)吲哚衍生物的质谱研究

报道了由吲哚-2-甲醛和取代苯胺进行亲核加成反应合成了22个2-(取代苯亚氨次甲基)吲哚衍生物,主要对本类化合物的两种质谱特殊裂解过程进行了分析研究。     

Intramolecular iminium ene reaction with Cu(I) catalysts: facile formation of 4-amino-3-methylenechromans from O-propargyl salicylaldehydes and dialkylamines

Reaction of O-propargyl salicylaldehyde and related compounds with dialkylamines in the presence of copper(I) iodide gave 4-(alkylamino)-3-methylenechroman derivatives in good yields through the loss of one alkyl group of the dialkylamine. The reaction also worked well by employing 2-amino benzaldehyde derivatives to afford 4-(alkylamino)-3-methylene-1,2,3,4-tetrahydroquinolines. A deuterium-labeling experiment suggested that the α-hydrogen of the dialkylamine was transferred intramolecularly into the terminal methylene. This result indicated the reaction mechanism, which involved the formation of iminium ion between the aldehyde and the dialkylamine followed by ene-type C-C bond formation with inverse electron demand and hydrolysis.