Unexpected products via singlet oxygen oxygenation of functionalized 5,6-dihydro-1,4-oxathiins

[formula: see text] Single oxygen oxygenation of 5,6-dihydro-1,4-oxathiins substituted at C-3 with an electron-withdrawing group leads stereoselectively to ketosulfoxides 5 and 6, instead of the expected dicarbonyl compounds 3. A mechanism involving an unprecedented intramolecular rearrangement of the corresponding dioxetanes 2 is proposed.     

Synthesis of 5,6-dihydro-2H-thiins and 2,3-dihydro-1,4-oxathiins based on 1-benzylsulfonyl-1,1-dihydropolyfluoroalkan-2-ones

1-Benzylsulfonyl-1,1-dihydropolyfluoroalkan-2-ones react with phthalimidosulfenyl chloride or succinimidosulfenyl chloride to form the sulfenylated products on the active methylene group, 1-benzylsulfonyl-1-phthalimido(succinimido)thiopolyfluoroalkan-2-ones. Decomposition of the latter leads to formation of 1-benzylsulfonyl-1-thioxopolyfluoroalkan-2-ones. These compounds easily undergo the hetero Diels-Alder reaction with electron-rich 1,3-dienes as dienophiles and with electron-rich olefins as hetero-1,3-dienes. Polyfluoroalkyl substituted derivatives of six-membered sulfur-containing heterocycles, 5,6-dihydro-2H-thiins and 2,3-dihydro-1,4-oxathiins, are obtained as a result of these reactions.     

Structure and Dynamics of Intramolecular Hydrogen Bonds in Radicals: Substituent,steric and solvent effects

The temperature and solvent dependence of the ESR. spectra of a number of semiquinone- and semidione-type radicals have been investigated with the aim of obtaining structural and kinetic information about intramolecular hydrogen bonding. Systematic variation of the chemical structure of the radicals indicates that in many cases formation and/or exchange of intramolecular H-bonds is disturbed or even precluded by steric hindrance or concomitant dynamic processes, such as internal rotation and/or intermolecular proton exchange.     

New insight into the reaction of singlet oxygen with sulfur-containing cyclic alkenes: dye-sensitized photooxygenation of 5,6-dihydro-1,4-dithiins

The reaction of 3-methyl-5,6-dihydro-1,4-dithiins with singlet oxygen affords dicarbonyl compounds and/or ring-contracted ketosulfoxides, the latter regio- and stereoselectively, depending on the nature of the substituent at C-2 and on the reaction conditions. In competition with normal fragmentation, the intermediate dioxetanes, derived from [2 + 2] cycloaddition of singlet oxygen to the double bond, undergo an intramolecular oxygen transfer to the sulfur-1 atom, leading to labile epoxide intermediates. The latter convert to cis- and trans-ketosulfoxides through a non-concerted S-4 migration. This pathway is promoted by the electron-withdrawing group at C-2 and, for monosubstituted amide, by the solvent basicity. S-Oxidation of dithiins is insignificant, except for the monosubstituted amide derivative or in the presence of protic species, and occurs selectively at the S-1 atom.     

Substituent and solvent effects on the beta-heterolysis reaction of beta-hydroxy arylethyl radicals

Time-resolved conversion of a series of beta-hydroxy arylethyl radicals with electron-donating and -withdrawing aromatic substituents to their corresponding styrene radical cation via heterolytic loss of the beta-hydroxy leaving group was examined with nanosecond laser flash photolysis. In all cases, the reaction was catalyzed by added perchloric acid. Radicals 2a-d reacted via a pre-equilibrium protonation mechanism in acidic 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), and measuring rate constants for radical cation formation as a function of acid content allowed for the determination of absolute rate constants ranging from 3.6 x 10(6) to 3.8 x 10(7) s(-1) for the loss of water from the protonated beta-hydroxy arylethyl radicals 2a-d, as well as the acidity constants, pKa approximately 1.5 (in HFIP), for the protonated radicals. The 4-methoxy-substituted beta-hydroxy arylethyl radical 2e reacted by rate determining protonation in HFIP with a second-order rate constant of k(H+) = 7.8 x 10(8) M(-1) s(-1). However, in acetonitrile, 2,2,2-trifluoroethanol, and mixtures of these two solvents, 2e reacted by pre-equilibrium protonation, allowing for solvent effects on the rate constant for loss of water from the protonated radical 2e to be determined. With use of these data, substituent electronic effects on the kinetics of the beta-heterolysis reaction are discussed. Differences in the effect of solvent on the rate constant for loss of water from the protonated beta-hydroxy arylethyl radicals and other beta-substituted arylethyl radicals are also discussed.     

1,2-dioxetanes as chemiluminescent intermediates in the triplet oxygen oxygenation of olefins.

Several enol ethers react in the dark at elevated temperatures with triplet oxygen, producing ketones and chemiluminescene. Other electron-rich olefins were investigated.     

Substituent,solvent and steric effects on the electrochemical reduction of aziridinium salts

The polarographic behavior of a series of N,N-dimethyl-2-arylaziridinium fluorosulfonates was investigated as another example of ring-opening reactions of this important class of compounds. Half-wave potentials showed that in water reduction was facilitated by electron-donating groups. This unusual result was explained in terms of electron transfer to an aminocarbonium ion-like species. In methylene chloride, however, two one-electron waves were observed, with the first showing a normal substituent effect (? = 0.17 ± 0.03 V). This result indicated direct electron transfer to the aziridinium ion itself to form a radical species which was detected by cyclic voltammetry. Reasons for the change in mechanism are presented, and E_1/2 values for selected aziridinium salts illustrate the importance of steric effects on the reduction process.     

Substituent and solvent effects on electronic spectra of some substituted phenoxyacetic acids

The effects of substituents and solvents have been studied through the absorption spectra of nearly 19 para- and ortho-substituted phenoxyacetic acids in the range of 200-400 nm. The effects of substituent on the absorption spectra of compounds under present investigation are interpreted by correlation of absorption frequencies with simple and extended Hammett equations. Effect of solvent polarity and hydrogen bonding on the absorption spectra are interpreted by means of Kamlet equation and the results are discussed.     

Reactivity of homoallylic substituted adamantylideneadamantanes with bromine. Substituent effects on the stability of the ionic and nonionic intermediates

Sterically congested adamantylideneadamantanes (1b-g) (X = Br, Cl, F, OH, OEt, OCOCH(3)), homoallylically substituted with equatorial groups (X), react with bromine in 1,2-dichloroethane to give a stable bromonium ion intermediate or a substitution product depending on the nature of the substituent and on the bromine concentration. The nature of the substituent markedly affects the formation constant of the 1:1 pi-complexes, as well as of the formation constant and reactivity of bromonium ion intermediates. The different reactivity of the ionic intermediates, which depends on the nature of substituents, is attributed to bromonium or bromocarbenium character of the intermediate, with the support of theoretical investigations. Ab initio calculations on 1:1 adamatylideneadamantane-Br(2) complexes (2a-f) show that the substituent affects the stability of these species through electrostatic and dispersion effects. Solvent effects may also contribute to modulate the relative stability of these species.     

Permanganate oxidation of alkenes. Substituent and solvent effects. Difficulties with MP2 calculations

The permanganate oxidation of alkenes has been studied both experimentally and computationally. Transition state structures were located for the reaction of permanganate ion with a variety of monosubstituted alkenes at the B3LYP/6-311++G** level. Although the calculated activation energy for the reaction with ethene was reasonable, the calculated effect of substituents, based on the energies of the reactants, was much larger than that experimentally found. This was shown to be due to the formation of an intermediate charge-dipole complex which led to the transition state. Reaction field calculations found the complex to disappear in a high dielectric constant medium, and the range of activation energies for the reaction in solution became quite small. MP2 calculations were carried out in order to have a comparison with the DFT results. MP2-MP4 gave unusual results for calculations on permanganate ion as well as chromate ion and iron tetraoxide. They also gave markedly unreasonable results for the activation energy of the reaction of permanganate with ethane. CCSD/6-311++G** calculations gave satisfactory results for permanganate ion and chromate ion. At this level of theory, the reaction of permanganate with ethene was found to have a very early transition state, when the bond lengths of the reactants just began to change. The reaction was calculated to be very exothermic (-69 kcal/mol), and this was confirmed via calorimetry. The rates of permanganate oxidation of allyl alcohol and acrylonitrile were determined, and they had similar reactivities. The kinetics and the products of the reaction of permanganate with crotonate ion were examined in some detail.     

Intramolecular diels-alder reactions of the furan diene: substituent and solvent effects

An internal Diels-Alder reaction, using furan as the diene component, formed a highly functionalized 5-membered carbocyclic ring in excellent yield. Solvent and substituent effects of this reaction were examined.     

Substituent effects on the intramolecular charge transfer and fluorescence of bimetallic platinum complexes

An investigation of a series of platinum-containing organometallic complexes for the study of fluorescence phenomena in organometallic chromophores controlled by the intramolecular charge transfer (ICT) is presented in this work. We report steady-state and time-resolved spectroscopic experiments as well as quantum chemistry calculations to investigate the substituent effects on the ICT and fluorescence emission. We demonstrate that the fluorescence maximum and lifetimes greatly depend on different substituents and the presence of bimetallic platinum donor. This work paves the way for an understanding of the fluorescence phenomena controlled by molecular ICT characters of these kinds of platinum-containing organometallic complexes.     

Substituent effect on the acid-promoted hydrolysis of 2-aryloxazolin-5-one: normal vs reverse

Computational investigations on the acid-promoted hydrolysis of 2-aryl-4,4-dimethyloxazolin-5-one (AMO) and its seven para- and meta-substituted derivatives (with electron-donating groups R = OH, OCH(3), CH(3) and electron-withdrawing groups R = Cl, m-Cl, CF(3), NO(2)) were presented by the density functional theory (B3LYP) method. Two types of reaction mechanism, N-path and O-path, are taken into account, in which the attacks by water molecules at the C2 and C5 are accelerated after the protonation on N3 and carbonyl oxygen atoms, respectively. Our computational results clearly manifest that the hydrolysis of AMOs has an obvious substituent effect at the para and meta positions of the benzene ring by correlating the barrier heights with the Hammett constants of substituents. Furthermore, the N-path shows a normal substituent effect, while the favorable O-path shows a reverse substituent effect. The observed reverse substituent effect in experiment actually springs from the reverse substituent effect of the O-path, not the N-path. The substituent effect of the N-path and O-path can be explained by the electrostatic potential at nuclei (EPN) values and Fukui function, respectively. Our theoretical data provided will allow for a better understanding of the acid-promoted hydrolysis mechanism and the observed reverse substituent effect of the AMOs, in nice agreement with the available experimental conclusion.     

稳定同位素标记1,4-二氢吡啶类药剂的5,6-位及其取代基碳的合成

l,4-二氢吡啶结构是许多生物活性物以及药物分子的重要骨架,同时也是非常重要的有机合成中间体.当前并没有一种适用的方法用于13C标记1,4-二氢吡啶的合成.提供了一种13C标记1,4-二氢吡啶的合成方法以13C2-乙酸钠为标记原料,经磷酸酸化得到13C2-乙酸,羰基二咪唑酰化13C2-乙酸得到13C2-N-乙酰咪唑,随...     

Substituent and solvent effects on tautomeric equilibria of barbituric acid derivatives and isoterically related compounds

N-Mono and N,N-dialkyl/diarylbarbituric acids exist in solution as a single tautomer. The ¹³C nmr spectroscopy shows that they are present in the triketo form in a number of polar and non-polar solvents. 2-Thiobarbituric acid derivatives, however, show extensive tautomerization. Their ¹³C chemical shift assignments were achieved by utilizing models 11a , 11c , 12b and 12d and from which relative tautomer distribution ratios were determined. These ratios were correlated with the dielectric constant of the various solvents (?). Thio-barbituric acids also formed adducts with solvents having carbonyl groups, characteristic observed only with barbiturates possessing the thione or thiophenolic group. 6-Amino and 6-methyluracils and thiouracils exist in DMSO solution as stable “ene” forms as do orotic acid, 24 , and its thio analogue 25. Compound 25 undergoes disproportionantion and tautomerization when heated or on prolonged standing in solution. Literature contradictions regarding the structure of “4,6-dihydroxypyrimidine,” 26 , were resolved and its tautomers in solution correctly assigned by ¹³C nmr. Anions of barbiturics and related systems exist in one of the two possible types A and B, depending on whether ring nitrogens are substituted (type A), or not (type B). Rapid H/D exchange at C₅ was evident from C-deuterium coupling. The redistribution of charge through C₄(C₆) carbonyl groups shown by ¹³C shifts of carbonyl carbon atoms of up to 10 ppm as compared to the CO carbons of the neutral species was evident.     

Photoreactions of 1,4-Naphthoquinones: effects of substituents and water on the intermediates and reactivity

The photochemistry of lapachol and other 1,4-naphthoquinone (NQ) derivatives, e.g. 2-methoxy-1,4-naphthoquinone (MeONQ), 2-hydroxy-1,4-naphthoquinone (2-HONQ) or 5-hydroxy-1,4-naphthoquinone (5-HONQ) and 2-methyl-5-hydroxy-1,4-naphthoquinone (P-NQ) in solution at room temperature was studied by ultraviolet-visible spectroscopy after nanosecond laser pulses at 248 nm. The triplet state and semiquinone radicals were observed for MeONQ, HONQ and P-NQ, whereas for lapachol, intramolecular H-atom and charge transfer processes take place, as in the case of vitamin K1. The photoinduced reaction of NQ into HONQ is initiated by nucleophilic water addition to the triplet state, and for the secondary reactions, a modified mechanism is proposed.     

Substituent effects in carbon-nitrogen cleavage of thiamin derivatives. Fragmentation pathways and enzymic avoidance of cofactor destruction

The combination of thiamin and benzaldehyde can produce benzoin but also destroys thiamin. The destruction comes from fragmentation of the conjugate of thiamin and benzaldehyde undergoing a process that produces a phenyl thiazole ketone and pyrimidine. The key step in this process is cleavage of the C-N bond between the heterocycles, which occurs by an unknown mechanism. Enzymes that utilize similar intermediates do not fragment the cofactor although fragmentation is inherent to the structure. To analyze the nature of the C-N cleavage step, the rates of fragmentation of a series of phenyl-substituted N1'-methyl-2-(1-hydroxybenzyl)thiamin derivatives were determined under two sets of conditions: (1) where proton transfer in the step prior to C-N bond breaking is rate-determining and (2) where C-N bond breaking is rate-determining. The resulting rho values are 1.6 and 1.8, respectively, leading to the conclusion that C-N cleavage is insensitive to substituent effects. On the basis of these results, we conclude that cleavage occurs by a facile process that resembles the outcome of a [1,5] sigmatropic rearrangement. An enzyme may avoid the fragmentation by holding the intermediate in a conformation that prevents such a process, allowing the normal catalytic process to proceed.     

Geometry optimizations of the dioxetane,perepoxide and 1,4-diradicals for the ethylene plus molecular oxygen system: mechanism of photooxygenation of olefins

Geometry optimization of perepoxide, 1,4-diradicals and dioxetane for the ethylene plus molecular oxygen system is performed using the energy gradients of the HF 4-31G and STO-3G solutions. Perepoxide is less stable than the singlet (σπ) diradical by ≈24 k cal/mole at the 4-31G level, incompatible with the GVB CI plus thermochemical estimations. The rotational barrier of the terminal methylene group around the C-C bond is small.