Hydrosilylation of 3-oxa-1,4-pentadiene and 1,5-hexadiene with silicofunctional alkyhydrosilanes and 1,1,3,3-tetramethyldisiloxane

Conclusions We synthesized some new types of organosilicon monomers based on the hydrosilylation of 3-oxa-1,4-pentadiene and 1,5-hexadiene with silicofunctional alkylsilanes of type R_3–nSiH(OC₂H₅)₅ (n=1–3) and R₂SiHCl. The halogenation of the monoaddition products gave the dibromo and dichloro derivatives.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1368–1370, June, 1976.     

Nitrosation of salts of 1-hydroxyimino-2,2-dinitro-1-R-ethanes,a novel method for the preparation of isomeric 3(4)-nitro-4(3)-R-furoxans

A novel general method for the synthesis of isomeric 3(4)-nitro-4(3)-R-furoxans is developed. 3-Nitro isomers were obtained by reaction of hydroximoyl chlorides with dinitromethane sodium salt followed by conversion of the resulting 1-substituted 1-hydroxyimino-2,2-dinitroethanes into dipotassium (or disodium salts) and their subsequent nitrosation with NaNO₂ in AcOH or with N₂O₄. Thermal isomerization of 3-nitro isomers afforded 4-nitro isomers were prepared in high yields.     

On a preliminary theoretical approach to the investigation of the mercury (3P1) photosensitized internal cycloaddition in 1,4-pentadiene and 1,5-hexadiene

A preliminary theoretical calculation was performed on the photosensitized internal cycloaddition in non-conjugate dienes by using an ab initio SCF MO procedure. The result explains very reasonably the experiments; predominant parallel compound from 1,4-diene, cross compound from 1,5-diene, and the ratios of these parallel/cross products in both cases.     

Acid-promoted reaction of the stilbene antioxidant resveratrol with nitrite ions: mild phenolic oxidation at the 4'-hydroxystiryl sector triggering nitration, dimerization, and aldehyde-forming routes

In 0.1 M phosphate buffer, pH 3.0, and at 37 degrees C, resveratrol ((E)-3,4',5-trihydroxystilbene, 1a), an antioxidant and cancer chemopreventive phytoalexin, reacted smoothly at 25 microM or 1 mM concentration with excess nitrite ions (NO2(-)) to give a complex pattern of products, including two novel regioisomeric alpha-nitro (3a) and 3'-nitro (4) derivatives along with some (E)-3,4',5-trihydroxy-2,3'-dinitrostilbene (5), four oxidative breakdown products, 4-hydroxybenzaldehyde, 4-hydroxy-3-nitrobenzaldehyde, 3,5-dihydroxyphenylnitromethane, and 3,5-dihydroxybenzaldehyde, two dimers, the resveratrol (E)-dehydrodimer 6 and restrytisol B (7), and the partially cleaved dimer 2. The same products were formed in the absence of oxygen. 1H,15N HMBC and LC/MS analysis of the crude mixture obtained by reaction of 1a with Na (15)NO2 suggested the presence of 3,4',5,beta-tetrahydroxy-alpha-nitro-alpha,beta-dihydrostilbene (8) as unstable intermediate which escaped isolation. Under similar conditions, the structurally related catecholic stilbene piceatannol ((E)-3,3',4,5'-tetrahydroxystilbene, 1b) gave, besides (E)-3,3',4,5'-tetrahydroxy-beta-nitrostilbene (3b), 3,4-dihydroxybenzaldehyde and small amounts of 3,5-dihydroxybenzaldehyde. Mechanistic experiments were consistent with the initial generation of the phenoxyl radical of 1a at 4'-OH, which may undergo free radical coupling with NO2 at the alpha- or 3'-position, to give eventually nitrated derivatives and/or oxidative double bond fission products, or self-coupling, to give dimers. The oxygen-independent, NO2(-)-mediated oxidative fission of the double bond under mild, physiologically relevant conditions is unprecedented in stilbene chemistry and is proposed to involve breakdown of hydroxynitro(so) intermediates of the type 8.     

Ring transformation of 4-amino-1H-1,5-benzodiazepine-3-carbonitrile and ethyl 4-amino-1H-1,5-benzodiazepine-3-carboxylate into benzimidazole derivatives with amines

The ring contraction of 4-ammo-1H-1,5-benzodiazepine-3-carbonitrile hydrochloride 1 and ethyl 4-amino-1H-1,5-benzodiazepine-3-carboxylate hydrochloride 2 with aromatic primary amines into benzimidazole derivatives 3 and 4 was readily accomplished by heating in methanol. Benzodiazepine 1 also reacted with methylamine and ethylamine at about 40° to give ring-opened amine adducts 7 which were recyclized to 1 with hydrochloric acid.     

Synthesis and characterization of silyldichloramines, their reactions with F- ions, instability of N2Cl2 and NCl2-, and formation of NCl3

Only two silyldichloramines, (C6H5)3SiNCl2 and (CH3)3SiNCl2, have been reported in the literature. The synthesis of the former was successfully repeated, and its structure was established by single-crystal X-ray diffraction and vibrational spectroscopy. Attempts to prepare (CH3)3SiNCl2 were unsuccessful; however, a new trialkylsilyldichloramine, t-BuMe2Si-NCl2, was prepared and characterized by Raman and multinuclear NMR spectroscopy. The reaction of t-BuMe2SiNCl2 with (CH3)4NF in CHF3 solution at -78 degrees C, followed by removal of all volatile products at -30 degrees C, produced the expected t-BuMe2SiF byproduct and a white solid consisting of NCl3 absorbed on Me4NCl. The NCl3 could be reversibly desorbed from the substrate and was identified as a neat liquid at room temperature by Raman spectroscopy. The observed final reaction products are consistent with the formation of an unstable N(CH3)4+NCl2- intermediate which decomposes to N(CH3)4+Cl- and NCl molecules which can dimerize to N2Cl2. Theoretical calculations confirm that NCl2- can readily lose Cl- and that N2Cl2 also possesses a low barrier toward loss of N2 to give chlorine atoms and, thus, can account for the formation of NCl3.     

Kinetics and mechanisms of aqueous ozone reactions with bromide, sulfite, hydrogen sulfite, iodide, and nitrite ions

Reactions of ozone with Br(-), SO(3)(2-), HSO(3)(-), I(-), and NO(2)(-), studied by stopped-flow and pulsed-accelerated-flow techniques, are first order in the concentration of O(3)(aq) and first order in the concentration of each anion. The rate constants increase by a factor of 5 x 10(6) as the nucleophilicities of the anions increase from Br(-) to SO(3)(2-). Ozone adducts with the nucleophiles are proposed as steady-state intermediates prior to oxygen atom transfer with release of O(2). Ab initio calculations show possible structures for the intermediates. The reaction between Br(-) and O(3) is accelerated by H(+) but exhibits a kinetic saturation effect as the acidity increases. The kinetics indicate formation of BrOOO(-) as a steady-state intermediate with an acid-assisted step to give BrOH and O(2). Temperature dependencies of the reactions of Br(-) and HSO(3)(-) with O(3) in acidic solutions are determined from 1 to 25 degrees C. These kinetics are important in studies of annual ozone depletion in the Arctic troposphere at polar sunrise.     

N-Alkylation of 4-nitro-1,2,3-triazole revisited. Detection and characterization of the N3-ethylation product, 1-ethyl-5-nitro-1,2,3-triazole

The products of the alkylation of sodium 4-nitro-1,2,3-triazolate with ethyl bromide were investigated using ¹H, ¹³C, and ¹⁵N NMR spectroscopy. It was found that alkylation proceeds on the triazole nitrogen atoms giving a mixture of three isomeric N-ethyl-4-nitro-1,2,3-triazoles. The molar ratio of N1, N2, and N3-alkylation products was 4:8:1. The formation of a minor N3-isomer, namely 1-ethyl-5-nitro-1,2,3-triazole was confirmed by X-ray structural analysis of single crystals of its tetranuclear copper(II) complex obtained by reaction of copper(II) chloride dihydrate with a mixture of the N2 and N3-isomers.     

Aromatic nucleophilic substitution—II : Intermediates in the reactions of 2,4-dinitro- or 2,4,5-trinitro-1-naphthyl ethyl ether with secondary amines and preparation of a spiro meisenheimer complex

The intermediates in the reactions of 2,4-dinitro-(2) or 2,4,5-trinitro-1-naphthyl ethyl ether (11) with secondary amines have been studied. In the reaction of 2 with piperidine, the NMR spectrum of the reaction system indicated the coexistence of the three species-starting material, Meisenheimer complex, and substituted product. In the reaction of 11 with piperidine or N-methyl-n-butylamine, the the NMR spectra of the reaction system indicated the presence of a Meisenheimer complex, but did not indicate the formation of a substituted product. In addition, the spiro Meisenheimer complex (9) was prepared from 1-[N-methyl-(2′-hydroxy)ethylamino]-2,4,5-trinitronaphthalene (8) and sodium methoxide.     

Synthesis and characterization of spiro-, ansa-, and spiro-ansa-cyclic derivatives of cyclotetraphosphazene with the reactions of pentane-1,5-diol

The reactions of octachlorocyclotetraphosphazatetraene, N₄P₄Cl₈ (1) with difunctional aliphatic reagent, HO-(CH₂)₅-OH (3) have aroused a good deal of attention, and four types of products have been realized: one 2-open chain-(1′-oxy-5′-hidroxy-pentane)-2,4,4,6,6,8,8-heptachlorocylotetraphosphazatetraene, N₄P₄Cl₇[O(CH₂)₅OH] (4); one 2,2-mono-spiro-(1′,5′-pentanedioxy)-4,4,6,6,8,8-hexachlorocyclotetraphosphazatetraene, N₄P₄Cl₆[O(CH₂)₅O] (5); its isomers 2,4-mono-ansa-((1′,5′-pentanedioxy)-2,4,6,6,8,8- hexachlorocyclotetraphosphazatetraene (6) and 2,6-mono-ansa-(1′,5′-pentanedioxy)-2,4,6,6,8,8-hexachlorocyclotetraphosphazatetraene (7); one 2,2,6,6-dispiro-(1′,5′-pentanedioxy)-4,4,8,8-tetrachlorocyclo- tetraphosphazatetraene, N₄P₄Cl₄[O(CH₂)₅O]₂ (8); two isomeric 2,4,6,8-bisansa-(1′,5′-pentanedioxy)-2,4,6,8-tetrachlorocyclotetraphosphazatetraene (9) and 2,6,4,8-bisansa-(1′,5′-pentanedioxy)-2,4,6,8-tetrachloro-cyclotetraphosphazatetraene (10); one 4,4,8,8-dispiro-2,6-ansa- (1′,5′-pentanedioxy)-2,6-dichlorocyclotetra-phosphazatetraene, N₄P₄Cl₂[O(CH₂)₅O]₃ (11), one 2,2,4,4,6,6-trispiro-(1′,5′-pentanedioxy)-8,8-dichlorocyclo-tetraphosphazatetraene, N₄P₄Cl₂[O(CH₂)₅O]₃ (12); and a 2,2,4,4,6,6,8,8-tetraspiro-(1′,5′-pentanedioxy)-cyclotetraphosphazatetraene derivative, N₄P₄[O(CH₂)₅O]₄, (13). The respective structures were deduced by means of elemental analysis, mass spectrum, and ³¹P, ¹H, and ¹³C nuclear magnetic resonance spectroscopic investigations.     

Preparation,characterization and reactions of novel vicinal dibenzotriazol-1-yl derivatives of benzotriazole and glyoxal

A variety of novel 1,2-disubstituted-1,2-di(benzotriazol-1-yl)ethane and 1,2-di(benzotriazol-1-yl)ethylene derivatives were prepared from the adduct of benzotriazole and glyoxal.     

Photostimulated reactions of 1-iodoadamantane and iodobenzene with thiolate,selenate, and tellurate ions

The photostimulated reaction of 1-iodoadamantane (1-IAd) with benzenethiolate ion gave the substitution product 1-adamantylphenylsulfide. With benzeneselenate ion (PhSe^?) it gave three products: diphenylselenide, 1-adamantylphenylselenide and di(l-adamantyl) selenide. With benzenetellurate ions it gave the substitution product 1-adamantylphenyltelluride and diphenyltelluride, the latter is ascribed to the photodecomposition of the nucleophile. The photostimulated reaction of 1-IAd with 1-naphtaleneselenate ion only gave the substitution product without scrambling of products.The photostimulated reaction of PhI with 1-adamantaneselenate ion gave the same three products as the reaction of 1-IAd and PhSe^? ion, but with different ratios of products. The reaction with 1-adamantanetellurate ion gave mainly diphenyltelluride, together with the substitution product 1-adamantylphenyltelluride.The relationship of the fragmentation rates of AdZ and PhZ bonds in radical anions of structure (1-AdZPh)? were studied, and k_fAdZ/k_fPhZ, being ZS is 3.7, ZSe is 9.5 and ZTe is 13.These results suggest that in the photostimulated reactions the products obtained depend on the energy levels of the antibonding $\text{π}{}^1$ MO and the $\text{σ}{}^1$ MO of the C-Z(Z=S, Se and Te) bonds of the radical anion intermediate.The fragmentation rates of the radical anion intermediates depend on the energy levels of the MO'S involved.     

Kinetics and mechanism of the reactions ofcis-tetraaminediaqua-cobalt(III) with nitrite,azide and salicylate ions in aqueous acidic media

Summary Kinetic studies of the anation of the title complex by NO ₂ ^– show that it occurs in a stepwise manner leading to thecis-dinitro-complex both steps having a common rate equation:-d[complex]/dt = a[NO ₂ ^– ]/{[NO ₂ ^– ] + b}. The variation ofpseudo-first-order rate constant (k_obs) with [NO ₂ ^– ] indicates that the reaction proceeds through ion-pair interchange path. Activation parameters calculated by the Eyring equation are: H ₁ = (65±7) kJ mol^–1 and S ₁ = (–82±11) JK^–1 mol^–1 for the formation of [Co(NH₃)₄(NO₂)(H₂O)]²⁺, and H ₂ = (97±1) kJ mol^–1 and S ₂ = (6±2) JK^–1 mol^–1 for the formation of [Co(NH₃)₄(NO₂)₂]⁺. Anation of the title complex by N ₃ ^– at pH 4.1 also occurs in a stepwise manner ultimately producing thecis-diazido species. At a fixed pH the reaction shows a first-order dependence on [N ₃ ^– ] for each step. pH-variation studies at a fixed [N ₃ ^– ] show that the hydroxoaqua-form of the complex reactsca. 16 times faster than the diaqua form. Evidence is presented for an ion-pair preequilibrium at high ionic strength (I = 2.0 mol dm^–3). Activation parameters obtained from temperature variation studies are: H ₁ = (121±1) kJ mol^–1 and S ₁ = (104±3) JK^–1 mol^–1 (for the first step anation), and H ₂ = (111±2) kJ mol^–1 and S ₂ = (74±9) JK^–1 mol^–1 (for the second step anation). The reaction ofcis-tetraaminediaquacobalt(III) ion with salicylate (HSal^–) has been studied in aqueous acidic medium in the temperature range 39.8–58.2°C. The reaction is biphasic corresponding to the anation of two salicylate ions. The kinetic results for the first phase reaction are compatible with the equation: k_obs = k_IPQ[HSal^–]/(1 + Q[HSal^–]) where Q denotes ion-pair formation constant and k_IP is the first-order rate constant for the interchange reaction. The activation parameters obtained from the temperature dependence of rate are: H = (138±3) kJ mol^–1 and S = (135±4) JK^–1 mol^–1. The reaction seems to take place by a dissociative interchange mechanism.     

New forced degradation products of vildagliptin: Identification and structural elucidation using LC-MS,with proposed formation mechanisms

Abstract

A new and simple RP-HPLC-UV method was developed for well-separation of vildagliptin raw material and its degradation products at different conditions; it uses of ammonium acetate buffer at pH= 7.5 and methanol with Athena C18 -WP (250?mm) column. Results show that six degradants have been identified using LC–MS technique, in addition to the NMR approach in some cases. One degradant at relative retention time (RRT) 1.3 was formed under acidic condition and designated as 2-((1R, 3S, 5R, 7S)-3-hydroxyadamantan-1-yl) hexahydropyrrolo[1,2-a]pyrazine-1,4-dione at m/z = 304. Three degradants were formed under various conditions of basic hydrolysis at RRTs 1.2, 0.6 and 0.4 with following names and molar masses (m/z), respectively: 1-(((1S, 3S, 5S, 7S)-1,3-dihydroxyadamantan-2-yl)glycyl)pyrrolidine-2-carboxamide at m/z = 337.2, 1-(((1R, 3S, 5R, 7S)-3-hydroxyadamantan-1-yl)glycyl)pyrrolidine-2-carboxamide at m/z = 321.1 and (1,4-dioxo-1,4,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-3-yl)glycylproline at m/z = 322.6. Another three degradants were also formed under oxidative oxidations of vildagliptin, one at RRT 0.38 and designated as N-hydroxy-N-((1R, 3S, 5R, 7S)-3-hydroxyadamantan-1-yl) glycinate with m/z 241.1, the second one was identical to that formed under basic hydrolysis at RRT 0.6 and the last one has RRT 0.8 and was identified as (1S, 3R, 5R, 7S)-3-(hydroxyamino)adamantan-1-ol at m/z 183.1. Formation mechanisms for the degradation products were described.     

Reaction of crown ethers with five-membered heterocycles: 1H-imidazole-4,5-dicarbonitrile, 3-nitro-1,2,4-triazole, and 1H-tetrazole

By the reaction of 1H-imidazole-4,5-dicarbonitrile, 3-nitro-1,2,4-triazole, and 1H-tetrazole, containing one proton at each of the two proton-donating atoms separated by one covalent bond, it was shown that uncharged crystalline supramolecular compounds can be obtained on account of the proton-donating characteristics of the aromatic heterocycles. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1302–1305, September, 2006.     

Synthesis and structural characterization of complexes of a DO3A-conjugated triphenylphosphonium cation with diagnostically important metal ions

To understand the coordination chemistry of a DO3A-conjugated triphenylphosphonium (TPP) cation, triphenyl(4-((4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)methyl)benzyl)phosphonium (DO3A-xy-TPP), with diagnostically important metal ions, In(DO3A-xy-TPP)+, Ga(DO3A-xy-TPP)+, and Mn(DO3A-xy-TPP) were prepared by reacting DO3A-xy-TPP with 1 equiv of the respective metal salt. All three complexes have been characterized by elemental analysis, IR, ESI-MS, NMR methods (for In(DO3A-xy-TPP)+ and Ga(DO3A-xy-TPP)+), and X-ray crystallography. Results from HPLC concordance experiments show that (111)In(DO3A-xy-TPP)+ and In(DO3A-xy-TPP)+ have the same composition. The solid-state structures of In(DO3A-xy-TPP)+ and Mn(DO3A-xy-TPP) are very similar with DO3A being heptadentate in bonding to In(III) and Mn(II) in a monocapped octahedral coordination geometry. Because of the smaller size of Ga(III), the DO3A in Ga(DO3A-xy-TPP)+ is only hexadentate with four amine-N and two carboxylate-O atoms bonding to Ga(III). One carboxylic acid group in DO3A is deprotonated to balance the positive charge of Ga(III). The coordination geometry of Ga(DO3A-xy-TPP)+ is best described as a distorted octahedron. The NMR data shows that the coordinated DO3A in In(DO3A-xy-TPP)+ and Ga(DO3A-xy-TPP)+ is symmetrical in aqueous solution. There is no dissociation of the acetate chelating arms in In(DO3A-xy-TPP)+ and Ga(DO3A-xy-TPP)+, providing indirect evidence for the high solution stability of (111)In(DO3A-xy-TPP)+ and (68)Ga(DO3A-xy-TPP)+.     

O-nucleophilicity of hydroxamate ions in reactions with ethyl 4-nitrophenyl ethylphosphonate,diethyl 4-nitrophenyl phosphate,and 4-nitrophenyl 4-toluenesulfonate

The nucleophilicity of hydroxamate ions toward ethyl 4-nitrophenyl ethylphosphonate, diethyl 4-nitrophenyl phosphate, and 4-nitrophenyl 4-toluenesulfonate in water (µ=1, KCl, 25°C) is described by the Brø nsted equation (_N=0.54, 0.70, and 0.59, respectively). In these reactions, hydroxamate ions act as typical -nucleophiles; they are more reactive than phenoxide ions with the same basicity by a factor of 300 to 800. In the series of hydroxamate ions, an anomalously high nucleophilicity was revealed for the anions possessing catalytic centers (in terms of general base catalysis), which are capable of providing anchimeric assistance in the transition state. An equation has been proposed, which relates the efficiency of such assistance in anions derived from aminohydroxamic acids to the pK _a values characterizing their acidic and basic groups.Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 9, 2004, pp. 1384–1396.Original Russian Text Copyright © 2004 by Simanenko, Prokopeva, Popov, Bunton, Karpichev, Savelova, Ghosh.Deceased.This study was performed under financial support by the US Civil Research and Development Foundation (CRDF) (grant no. UC2-2489-DO-03).     

Novel tandem reactions of ethyl acetoacetate with aromatic aldehydes: product- and stereo-selective formation of highly functionalised cyclohexanones

The five-component tandem reaction of ethyl acetoacetate with aromatic aldehydes in the presence of pyrrolidine affords t(3),t(5)-diaryl-t(4)-[(E)-3-aryl-2-propenonyl]-r(2)-ethoxycarbonylcyclohexanones stereoselectively in good yields presumably via a tandem Knoevenagel condensation-Michael addition-condensation via enamine-deethoxycarbonylation-Michael addition sequence. The same reactants in the presence of DBU led to the formation of t(3)-aryl-r(2),c(4)-bisethoxycarbonyl-c(5)-hydroxy-t(5)-methylcyclohexanones in excellent yields via a tandem Knoevenagel condensation-Michael addition-aldol reaction sequence.