Isomeric Adducts Research Articles

A crystallized view of acid-base chemistry.

The structural relationship between Lewis adduct isomers is resolved.

Synthesis and trapping of spiro [bicyclo[4.2.0]octa-2,3-diene-7,2'-[1,3]dioxolane

Spiro[bicyclo[3.2.0]hept-2-ene-6,2'-[1,3]dioxolane] was synthesized by the reaction of bicyclo[3.2.0]hept-2-en-6-one with ethylene glycol in yield of 92%. Addition of dichlorocarbene to Spiro[bicyclo[3.2.0]hept-2-ene-6,2'-[1,3]dioxolane] gave the 3',3'-Dichlorospiro[1,3-dioxolane-2,7'-tricyclo[4.2.0.02,4]octane] in 50 % yields. Finally, the 3',3'-Dichlorospiro[1,3-dioxolane-2,7'-tricyclo[4.2.0.02,4]octane] was submitted to Doering-Moore-Skatebol reaction for the synthesis of allene precursors. The reaction of the 3',3'-Dichlorospiro[1,3-dioxolane-2,7'-tricyclo[4.2.0.02,4] octane] with methyl lithium (MeLi) in the presence of 1,3-diphenylisobenzofuran (DBI) as a trapping reagent under a nitrogen atmosphere at ca. 0 ℃ was started and continued at room temperature for four hours, resulting in the formation of four cyclo adduct isomers of spiro[bicyclo[4.2.0]octa-2,3-diene-7,2'-[1,3]dioxolane].

Structural Analysis of Intracellular Lipid Radicals by LC/MS/MS Using a BODIPY-Based Profluorescent Nitroxide Probe.

Free radical-mediated lipid peroxidation (LPO) induces the formation of numerous lipid radicals, which contribute to the development of several oxidative diseases. To understand the mechanism of LPO in biological systems and the significance of these radicals, identifying the structures of individual lipid radicals is imperative. In this study, we developed an analytical method based on liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) and a profluorescent nitroxide probe, N-(1-oxyl-2,2,6-trimethyl-6-pentylpiperidin-4-yl)-3-(5,5-difluoro-1,3-dimethyl-3H,5H-5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-7-yl)propanamide (BDP-Pen), for the detailed structural analysis of lipid radicals. The MS/MS spectra of BDP-Pen-lipid radical adducts showed product ions and thus allow the prediction of the lipid radical structures and individual detection of isomeric adducts. Using the developed technology, we separately detected the isomers of arachidonic acid (AA)-derived radicals generated in AA-treated HT1080 cells. This analytical system is a powerful tool for elucidating the mechanism of LPO in biological systems.

Reversible Diels-Alder Addition to Fullerenes: A Study of Dimethylanthracene with H2@C60.

The study of isolated atoms or molecules inside a fullerene cavity provides a unique environment. It is likely to control the outer carbon cage and study the isolated species when molecules or atoms are trapped inside a fullerene. We report the Diels–Alder addition reaction of 9,10-dimethyl anthracene (DMA) to H2@C60 while 1H NMR spectroscopy is utilized to characterize the Diels–Alder reaction of the DMA with the fullerene. Through 1H NMR spectroscopy, a series of isomeric adducts are identified. The obtained peaks are sharp, precise, and straightforward. Moreover, in this paper, H2@C60 and its isomers are described for the first time.

Gas-Phase Reaction Kinetics of the Ortho and Ipso Adducts 1,2,4,5-Tetramethylbenzene–OH with O2

The reversible reaction of OH radicals with 1,2,4,5-tetramethylbenzene (1245-TeMB, durene) leads to adducts at the substituted (ipso) and unsubstituted (ortho) positions of the ring. By the use of flash photolysis for production and resonance fluorescence for detection of OH, the gas-phase reactions of O2 with these adducts were investigated over the temperature range of 300–340 K in He at 200 mbar. The decay of OH, generated by pulsed vacuum-UV photolysis of H2O, was monitored under slow-flow conditions in the presence of 1245-TeMB and O2 at concentrations of up to 19 × 1012 cm–3 and 2 × 1016 cm–3, respectively. Triexponential OH decays resulted from the unimolecular decomposition of the two adducts, representing OH reservoirs with different stabilities. In the presence of O2, additional adduct loss pathways exist, leading to faster OH consumption. Triexponential functions fitted to these decays were analyzed to obtain rate constants for the reactions of O2 with both adducts. Rate constants in the range of (4–13) × 10–15 and (0.3–3) × 10–15 cm3 s–1 were obtained for the ortho and the ipso adducts, respectively, depending on temperature and assumptions regarding details of the underlying mechanism of adduct isomer formation and isomerization. At O2 concentrations exceeding about 1 × 1016 cm–3, deviations from a linear dependence of the adduct loss rates on the O2 concentration indicate an even more complex mechanism. The validity of the rate constants is therefore confined to O2 concentrations below 1 × 1016 cm–3. The adduct + O2 rate constants for 1245-TeMB are greater than the corresponding previously obtained rate constants for benzene, toluene, and p- and m-xylene but smaller than those for hexamethylbenzene. The results are discussed in terms of the current knowledge about the mechanism of OH-induced degradation of aromatic compounds in the presence of O2.

Encapsulation and Stabilization of a Donor-Acceptor Stenhouse Adduct Isomer in Water Inside the Blue Box: A Combined Experimental and Theoretical Approach.

We synthesized two types of donor-acceptor Stenhouse adducts (DASAs), a new type of photochromic molecules showing dual color in two different isomeric forms in solution phase, using Meldrum acid (DASA-Mel) and barbituric acid (DASA-Bar), along with a naphthalimide derivative to obtain interesting fluorescence properties. DASA-Mel was found to have fast photochromic conversion in comparison to DASA-Bar, evident from ultraviolet-visible (UV-vis) and fluorescence spectroscopic studies. The colored form of DASA-Mel was encapsulated inside the water-soluble Stoddart's blue box and became soluble in water much faster than DASA-Bar. Interestingly, the competitive encapsulation experiment showed that DASA-Mel was selectively encapsulated inside the blue box in water whereas DASA-Bar was mostly separated out from the solution after centrifugation, and this phenomenon was confirmed by 1H and DOSY NMR and mass spectroscopies. Moreover, we found through density functional theory (DFT) optimization that the open form of DASA-Mel was more stable during the encapsulation reaction in a water medium in comparison to DASA-Bar. The calculated binding energies of encapsulated DASA-Mel and DASA-Bar are -10.2 and -9.9 kcal/mol, respectively, clearly showing that the former is more stable by 0.3 kcal. Consequently, the organic macrocycle selectively separating one kind of DASA from a mixture by encapsulation in water is reported for the first time with experimental and theoretical support in the literature.

Product selectivity of thermal Buchner reaction of methyl 2-(3-arylisoxazol-5-yl)-2-diazoacetates with benzene, naphthalene and mesitylene, and ring-opening/closing reaction of products

Methyl 2-(3-arylisoxazol-5-yl)-2-diazoacetates were synthesized and the product selectivity of their thermal Buchner reaction with benzene, naphthalene and mesitylene was studied. The reaction of the isoxazolyl-substituted diazoacetates with benzene gave a mixture of cycloheptatriene/norcaradiene isomeric adducts, which are in a rapid equilibrium. Heating the same diazo compounds with naphthalene led exclusively to stable norcaradiene adducts. In contrast, their thermal reaction with mesitylene gave only the products of carbene insertion into C–H bond of mesitylene. According to DFT calculations, such a difference in the product selectivity of the thermal Buchner reaction of the diazoacetates with benzene, naphthalene and mesitylene is associated with the fact that the first two reactions proceed under kinetic control, and the last one under thermodynamic control. Isoxazoles synthesized were converted to a new family of functionalized enaminones, ( Z )-methyl 5-amino-2,5-diaryl-3-oxo-2-phenylpent-4-enoates, by reaction with Mo(CO) 6 /H 2 O hydrogenative reagent, wherein Mo(CO) 6 catalyzes also the retro-Buchner reactions of the norcaradiene moiety of the starting compounds. The obtained enaminones are convenient precursors of 3,6-diaryl-4-hydroxy-3-phenylpyridin-2(1 H )-ones, which were prepared from them under thermal conditions in high yields.

Kinetics of C5H4 isomer + H reactions and incorporation of C5H (x = 3 – 5) chemistry into a detailed chemical kinetic model

Abstract Although C5H4 isomers are detected in flames, they are not thoroughly incorporated into detailed chemical kinetics models (DCKMs). Here we use RRKM/ME modelling to simulate C5H4 + H reactions on a C5H5 potential energy surface. Kinetic studies indicate that C3H3 + C2H2 is the main fate but fall-off from the initial adduct isomer back to C5H4 + H cannot be ignored at relevant combustion temperatures of 900 to 2000 K. Calculated rate coefficient expressions were incorporated into a DCKM for a toluene flame, along with updates to other relevant reactions from the recent literature, particularly the open-chain 1-vinylpropargyl radical, l-C5H5. Obtained species mole fractions were found to be in good agreement with published experimental data for a low-pressure toluene flame, with a significant improvement in predicted concentration of the cyclopentadienyl radical. The presented DCKM will allow for further reactions of C5Hx species such as 1-vinylpropargyl to be included in combustion simulations.

Multiple Addition of 2-Cyano-Iso-Propyl Radicals to Fullerene C60

A quantum chemical simulation of the sixfold addition of 2-cyano-iso-propyl radical to fullerene C60 and the formation of a number of isomeric adducts is carried out. The thermodynamic characteristics of the elementary acts and the pattern of the spin density delocalization in fullerene C60 adducts containing an odd number of addends are determined. It is shown that the addition of up to four 2-cyano-iso-propyl radicals to fullerene C60 leads to the attachment of radicals to the tops of the radilene of the fullerenyl part of the adducts. The addition of the fifth 2-cyano-iso-propyl radical proceeds to the atoms more distant from the previously attached addends in the tetrakisadduct.

In vitro reactions of a cyanocobalamin-cisplatin conjugate with nucleoside monophosphates.

Cisplatin (CP) is a widely used anticancer drug characterized by toxic side effects that could be alleviated using novel delivery systems including CP prodrugs. The in vitro incubation of a putative prodrug, obtained from cyanocobalamin (CNCbl) and cis-diamminemonochloroplatinum(II) (mCP), with nucleoside monophosphates (NMPs) was investigated. The in vitro reactions between the putative prodrug CNCbl-mCP and the NMPs of adenosine (AMP), guanosine (GMP), cytidine (CMP) and uridine (UMP) were carried out in slightly acidic water-methanol solutions at 37°C for 24 h. Each sample was examined using reversed-phase liquid chromatography coupled with electrospray ionization in positive ion mode and tandem mass spectrometry (RPLC/ESI-MS/MS) by collision-induced dissociation in a linear ion-trap mass spectrometer. Seven adducts were recognized as formed by substitution reactions of the chloride ligand in planar CP. Comparison between observed and theoretical isotopic patterns together with MS/MS fragmentation pathways revealed the presence of single or multiple binding sites depending on the NMP involved. The CNCbl-mCP conjugate was found to interact with N7 or O4 atoms of GMP and UMP, respectively, generating single adducts, while two isomeric adducts were observed for CMP. Finally, AMP gave rise to three isomeric adducts. In agreement with literature data relevant to the interaction between CP and NMPs, the most reactive nucleotides were AMP and GMP. The present RPLC/ESI-MS/MS approach is very promising for investigation of the reactions of CP conjugates with ribonucleotides not only in vitro but also in vivo.

Catalytic effect of hydroxyl-containing compounds at the propagation step of the chain reaction of thiophenol with quinone imines

Hydroxyl-containing compounds (water, methanol, and phenol) act as efficient catalysts of the chain reactions of thiophenol with quinone imines at their propagation steps as it was found previously for thiols. The results of quantum chemical analysis of isomerization of a radical adduct into phenoxyl radical or corresponding aromatic aminyl radical are considered. The adduct was formed at the rate limiting step of the chain propagation by thiyl radical addition to quinone imine. Enthalpies and activation energies for mono- and bimolecular isomerization of the adduct with participation of hydroxyl-containing compounds were computed and matched. For comparison, analogous reactions with participation of thiols (hydrogen sulfide, metahnthiol and thiophenol) were also studied. In both the cases, the catalytic effect is caused by transforming the four-membered cyclic transition state of the monomolecular isomerization reaction into the energetically favorable six-membered transition state by the O—H or S—H groups of the indicated compounds. This considerably reduces the activation energy.

Diastereospecific and Highly Site-Selective Functionalization of C70 Fullerene by a Reaction with Diethyl N-Arylaziridine-2,3-dicarboxylates.

The diastereospecific and highly site-selective cycloaddition of N-arylazomethine ylides generated in situ from diethyl N-arylaziridine-2,3-dicarboxylates to C70 fullerene is reported. The reaction provides C70 fulleropyrrolidines in up to hundreds on a milligram scale as α- and β-adducts in a 4:1 ratio with a controlled stereochemical outcome: cis-aziridines give exclusively trans-adducts, and trans-aziridines give only cis-adducts. The 1H and 13C{1H} NMR spectra for different isomeric adducts were recorded and analyzed to identify some characteristic features, which permit an easy identification of isomeric adducts of this type.

Thermodynamic functions for the formation of isomeric CF3 adducts of C70 and C84

ABSTRACTGas-phase formation enthalpies and Gibbs energies of formation (ΔfH°m; ΔfG°m) of trifluoromethylderivatives of fullerenes C70 and C84 are calculated at the DFT (density functional theory) level of theory. The approach employs homodesmic (HD) transtrifluoromethylation reactions and experimental thermochemical data on C60, C70, C84 and S6-C60(CF3)12.

Bicyclo[6.3.0]undeca-1(11),2,4,6,8-pentaen-10-ylidene: An Aromatic Carbene with Ambiphilic Properties.

The title carbene (4) was generated as a highly reactive species in solution by photoirradiation of 10-diazobicyclo[6.3.0]undecapentaene (5) using a high-pressure mercury lamp. Carbene 4 reacts with benzene to afford two isomeric adducts, 10-phenylbicyclo[6.3.0]undecapentaene (10) and tricyclo[9.3.03, 10 .0]heptadeca-1,3(10),4,6,8,12,14,16-octaene (11). The reactivity toward benzene is a characteristic of an electrophilic aromatic carbene analogous to cyclopentadienylidene 1. In contrast, the reaction of 4 with methanol produces 7-methoxybicyclo[6.3.0]undeca-1,3,5,8,10-pentaene (15). When [D1 ]methanol was employed as a reactant, the 10-deuterated analogue was formed. The results clearly indicate the formation of bicyclo[6.3.0]undecapentaenyl cation (7) as a novel 10 π-electronic compound by protonation of 4. Theoretical calculations indicate that the 2- and 7-positions of the cation have the largest positive charge in the cation. Moreover, the carbene was generated in the presence of tert-butyl hydroperoxide in aqueous tetrahydrofuran to afford azulene through oxidation of 7, followed by decarbonylation. The nucleophilic property of carbene 3 is similar to that of cycloheptatrienylidene 2. Thus, 4 can be regarded as a novel ambiphilic aromatic carbene.

Supramolecular complexes [M{NH(CH2)4O}{S2CN(C2H5)2 2] ∙ CCl4 (M = Zn or 63Cu(II)): Synthesis, structures, spectral and thermal properties

Solvated adducts of diethyldithiocarbamate complexes of zinc and copper(II) of the formula [M{NH(CH2)4O}{S2CN(C2H5)22] ∙ CCl4 (M = Zn (I) and 63Cu (II)) were obtained. 13C MAS NMR experiments revealed magnetic nonequivalence in the dithiocarbamate moieties of the adduct isomers, the morpholine heterocycles, and the outer-sphere solvate molecules. The rhombic anisotropy of the EPR parameters of magnetically diluted isotope-substituted complex II is due to the copper polyhedron geometry, which is intermediate between a tetragonal pyramid and a trigonal bipyramid, with the ground state of the unpaired electron resulting from the mixing \(3{d_{{x^2} - {y^{2 - }}}}\) of and \(3{d_{{z^{2 - }}}}\) of copper(II). According to X-ray diffraction data, complex I is a supramolecular complex combining structurally nonequivalent adduct molecules (A and B) and “guest” molecules (CCl4). In addition, the crystal lattice has an array of channels occupied by outersphere solvate CCl4 molecules (a structural type of lattice clathrates). An STA study of the thermal properties revealed three main thermolysis steps: desorption of the solvate CCl4 molecules, elimination of coordinated morpholine molecules, and thermolysis of the dithiocarbamate moiety of the adduct.

Substituent Effects on Regioselectivity of the Diels-Alder Reactions: Reactions of 10-Allyl-1,8-dichloroanthracene with 2-Chloroacrylonitrile, 1-Cyanovinyl Acetate and Phenyl Vinyl Sulfone

Diels-Alder reaction of 10-allyl-1,8-dichloroanthracene (3) with 2-chloroacrylonitrile (4) and 1-cyanovinyl acetate (5) gives exclusively theorthoisomer while its reaction with phenyl vinyl sulfone (10) yields a mixture of two isomeric adducts with priority toorthoisomer. The reactions proceeded under microwave condition in xylene. Configurations of these isomers have been assigned with the help of NMR spectra. The results indicated that the steric effect is dominating toward the isomer regioselectivity in the Diels-Alder reaction of the present compounds.

Structure-Reactivity Relationships in Lithiated Evans Enolates: Influence of Aggregation and Solvation on the Stereochemistry and Mechanism of Aldol Additions.

Aldol additions to isobutyraldehyde and cyclohexanone with lithium enolates derived from acylated oxazolidinones (Evans enolates) are described. Previously characterized trisolvated dimeric enolates undergo rapid addition to isobutyraldehyde to give a 12:1 syn:syn selectivity in high yield along with small amounts of one anti isomer. The efficacy of the addition depends critically on aging effects and the reaction quench. Unsolvated tetrameric enolates that form on warming the solutions are unreactive toward isobutyraldehyde and undergo retroaldol reaction under forcing conditions. Additions to cyclohexanone are relatively slow but form a single isomeric adduct in >80% yield. The ketone-derived aldolates are robust. All attempts to control stereoselectivity by controlling aggregation failed. Rate studies of addition to cyclohexanone trace the lack of aggregation-dependent selectivities to a monomer-based mechanism. The synthetic implications and possible utility of lithium enolates in Evans aldol additions are discussed.

Absolute configuration, stability, and interconversion of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine valine adducts and their phenylthiohydantoin derivatives

Pyrrolizidine alkaloid-containing plants are widespread in the world and probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids require metabolic activation to form dehydropyrrolizidine alkaloids that bind to cellular proteins and DNA leading to hepatotoxicity, genotoxicity, and tumorigenicity. At present, it is not clear how dehydropyrrolizidine alkaloids bind to cellular amino acids and proteins to induced toxicity. We previously reported that reaction of dehydromonocrotaline with valine generated four highly unstable 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived valine (DHP-valine) adducts that upon reaction with phenyl isothiocyanate (PITC) formed four DHP-valine-PITC adduct isomers. In this study, we report the absolute configuration and stability of DHP-valine and DHP-valine-PITC adducts, and the mechanism of interconversion between DHP-valine-PITC adducts.

Kinetic and mechanistic study of the reaction of OH radicals with methylated benzenes: 1,4-dimethyl-, 1,3,5-trimethyl-, 1,2,4,5-, 1,2,3,5- and 1,2,3,4-tetramethyl-, pentamethyl-, and hexamethylbenzene.

The reaction of OH radicals with a series of methylated benzenes was studied in a temperature range 300-350 K using a flash-photolysis resonance fluorescence technique. Reversible OH additions led to complex OH decays dependent on the number of distinguishable adducts. Except for hexamethylbenzene, triexponential OH decay curves were obtained, consistent with formation of at least two adduct species. For three compounds that can strictly form two adduct isomers for symmetry reasons (1,4-dimethyl-, 1,3,5-trimethyl-, and 1,2,4,5-tetramethylbenzene) with OH bound ortho or ipso with respect to the methyl groups, OH decay curves were analysed in terms of a reaction mechanism in which the two adducts can be formed directly by OH addition or indirectly by isomerization. In all cases one adduct (add1) is dominating the decomposition back to OH. The other (add2) is more elusive and only detectable at elevated temperatures, similar to the single OH adduct of hexamethylbenzene. Two limiting cases of the general reaction mechanism could be examined quantitatively: reversible formation of add2 exclusively in the OH reaction or by isomerization of add1. Total OH rate constants, adduct loss rate constants and products of forward and reverse rate constants of reversible reactions were determined. From these quantities, adduct yields, equilibrium constants, as well as reaction enthalpies and entropies were derived for the three aromatics. Adduct yields strongly depend on the selected reaction model but generally formation of add1 predominates. For both models equilibrium constants of OH reactions lie between those of OH + benzene from the literature and those obtained for OH + hexamethylbenzene. The corresponding reaction enthalpies of add1 and add2 formations are in a range -87 ± 20 kJ mol(-1), less exothermic than for hexamethylbenzene (-101 kJ mol(-1)). Reaction enthalpies of possible add1 → add2 isomerizations are comparatively small. Because results for 1,3,5-trimethylbenzene are partly inconsistent with a direct formation of add2, we promote the existence of isomerization reactions. Moreover, based on available theoretical work in the literature, add1 and add2 are tentatively identified as ortho and ipso adducts, respectively. Total OH rate constants were obtained for all title compounds. They can be described by Arrhenius equations: kOH = A × exp(-B/T). The parameters ln(A/(cm(3) s(-1))) = -25.6 ± 0.3, -25.3 ± 0.6, -27.3 ± 0.3, -24.6 ± 0.3, -26.2 ± 0.4, -26.2 ± 0.4 and -24.5 ± 0.2, and B/K = -160 ± 90, -550 ± 180, -1120 ± 90, -330 ± 100, -820 ± 100, -980 ± 130, and -570 ± 40 were determined for 1,4-dimethyl-, 1,3,5-trimethyl-, 1,2,4,5-, 1,2,3,5- and 1,2,3,4-tetramethyl-, pentamethyl-, and hexamethylbenzene.

Activation of nitrogen Brønsted acids: synthesis and reactivity of a new class of nitrogen acid complexes.

The nitrogen acids RC(O)NHNO2, N-nitroamide, R = CH3 (1), C2H5 (2) and N-nitrocarbamate, R'OC(O)NHNO2, R' = CH3 (3), C2H5 (4) are a class of primary N-nitrocarboxamide compounds that oxidatively add to trans-Ir((I))(Cl)(N2)(PPh3)2 to give six-coordinate Ir((III))(η(2)-(NO2)-nitrogen acid)(H)(Cl)(PPh3)2 complexes 5-8. Unexpected fluxional behavior of the complexes in solution is observed by (1)H NMR spectroscopy. Reaction intermediates of the oxidative addition reactions were also observed and monitored using (31)P and (1)H NMR and solution IR spectroscopies. Complex 5 reacts with methyl triflate in CH3CN to generate bis(acetonitrile) complex (9) from a net loss of the nitrogen acid anion. P(CH3)2Ph reacts with 5 to give phosphine-substituted and P(CH3)2Ph addition isomers (10). Reactivity studies of 5 with CO gave metastable CO adduct isomer 11, which loses CO on prolonged standing in solution.