Efficient copper-catalyzed coupling of aryl iodides and thiobenzoic acid

A highly efficient copper-catalyzed coupling reaction of aryl iodides and thiobenzoic acid, using 10 mol % of copper iodide, 20 mol % of 1,10-phenanthroline, and ⁱPr₂NEt in toluene, was developed. This methodology is applicable to a variety of aryl iodides.     

Synthesis of functionalized hydroquinones via [Cp*RuCl2]2-catalyzed cocyclization of alkynes, alpha,beta-unsaturated carbonyl compounds, and carbon monoxide

[reaction: see text] Catalytic [2 + 2 + 1 + 1] cocyclization reaction of an alkyne, an alkene, and two molecules of carbon monoxide, leading to functionalized hydroquinones, was studied. Using [Cp*RuCl2]2 as a catalyst, we found that a variety of electron-deficient alkenes, such as alpha,beta-unsaturated ketones, esters, amides, and nitriles, can be employed as an alkene coupling partner to give the corresponding hydroquinones.     

Mercuric triflate-catalyzed synthesis of 2-methylfurans from 1-alkyn-5-ones

[reaction: see text] 2-Methylfurans were prepared by an effective cyclization of 1-alkyn-5-ones in the presence of mercuric triflate as the catalyst under very mild reaction conditions with high catalytic turnover up to 100 times. Benzene, toluene, or dichloromethane was the solvent of choice.     

KINETICS OF ENZYMATIC PHOTOREACTIVATION STUDIED WITH PHAGE T1 AND ESCHERZCHZA COLI Bs-1*

Abstract— The kinetics of enzymatic photoreactivation (PR) of u.v.-induced killing was compared among E. coli B_s-1, phage T1 in B_s-1 and phage T1 in irradiated B_s-1. The PR action spectrum showed no substantial difference between PR of B_s-1 and PR of T1 in B_s-1. The PR D₃₇ (i.e. the PR dose required to reactivate all but 37 per cent of the reactivable lethal lesions) was found to decrease linearly with decreasing U.V. dose whether U.V. was given to produce pyrimidine dimers in B_s-1 DNA, which then compete with irradiated T1 DNA for PR enzyme, or to B_s-1 or T1 DNA to produce dimers serving as substrate for the PR enzyme. A generalized Michaelis-Menten formula was used to analyze the data and the following conclusions were drawn. (1) The number of PR enzyme molecules per cell available for PR of T1 DNA inside the B_s-1 host is only a quarter of the number available for PR of the B_s-1 host itself. (2) The Michaelis constant K_m for reaction of host-DNA-damage and PR-enzyme becomes larger when the host damage acts as competitive inhibitor to PR of T1 DNA than when it is the substrate for PR enzyme. (3) PR enzyme retains almost all its initial catalytic efficiency even after about two-hundred rounds of catalytic functioning. Conclusions (1) and (2) suggest that PR enzyme is concentrated within the nuclear area surrounding the host DNA.     

Bitterness evaluation of medicines for pediatric use by a taste sensor

The purpose of this study was to evaluate the bitterness of 18 different antibiotic and antiviral drug formulations, widely used to treat infectious diseases in children and infants, in human gustatory sensation tests and using an artificial taste sensor. Seven of the formulations were found to have a bitterness intensity exceeding 1.0 in gustatory sensation tests (evaluated against quinine as a standard) and were therefore assumed to have an unpleasant taste to children. The bitterness intensity scores of the medicines were examined using suspensions in water or an acidic sports drink. In the case of three macrolide antibiotic formulations containing erythromycin (ERYTHROCIN dry syrup), clarithromycin (CLARITH dry syrup for pediatric), and azithromycin (ZITHROMAC fine granules for pediatric use), the bitterness intensities of suspensions in acidic sports drinks were dramatically enhanced compared with the corresponding scores of suspensions in water. This enhancement could be predicted using the taste sensor. On the other hand, a reduction of bitterness intensity was observed for an acidic sports drink suspension of an amantadine product (SYMMETREL fine granules) compared with an aqueous suspension. This reduction in bitterness could also be predicted using the taste sensor output value. Thus, the taste sensor could predict whether or not suspension in an acidic sports drink would enhance or reduce the bitterness intensity of pediatric drug formulations, compared with suspensions in water.     

Controllable donor-acceptor neutral [2]rotaxanes

In pursuit of a neutral bistable [2]rotaxane made up of two tetraarylmethane stoppers--both carrying one isopropyl and two tert-butyl groups located at the para positions on each of three of the four aryl rings--known to permit the slippage of the pi-electron-donating 1,5-dinaphtho[38]crown-10 (1/5DNP38C10) at the thermodynamic instigation of pi-electron-accepting recognition sites, in this case, pyromellitic diimide (PmI) and 1,4,5,8-naphthalenetetracarboxylate diimide (NpI) units separated from each other along the rod section of the rotaxane's dumbbell component, and from the para positions of the fourth aryl group of the two stoppers by pentamethylene chains, a modular approach was employed in the synthesis of the dumbbell-shaped compound NpPmD, as well as of its two degenerate counterparts, one (PmPmD) which contains two PmI units and the other (NpNpD) which contains two NpI units. The bistable [2]rotaxane NpPmR, as well as its two degenerate analogues PmPmR and NpNpR, were obtained from the corresponding dumbbell-shaped compounds NpPmD, PmPmD, and NpNpD and 1/5DNP38C10 by slippage. Dynamic 1H NMR spectroscopy in CD2Cl2 revealed that shuttling of the 1/5DNP38C10 ring occurs in NpNpR and PmPmR, with activation barriers of 277 K of 14.0 and 10.9 kcal mol(-1), respectively, reflecting a much more pronounced donor-acceptor stabilizing interaction involving the NpI units over the PmI ones. The photophysical and electrochemical properties of the three neutral [2]rotaxanes and their dumbbell-shaped precursors have also been investigated in CH2Cl2. Interactions between 1/5DNP38C10 and PmI and NpI units located within the rod section of the dumbbell components of the [2]rotaxane give rise to the appearance of charge-transfer bands, the energies of which correlate with the electron-accepting properties of the two diimide moieties. Comparison between the positions of the visible absorption bands in the three [2]rotaxanes shows that, in NpPmR, the major translational isomer is the one in which 1/5DNP38C10 encircles the NpI unit. Correlations of the reduction potentials for all the compounds studied confirm that, in this non-degenerate [2]rotaxane, one of the translational isomers predominates. Furthermore, after deactivation of the NpI unit by one-electron reduction, the 1/5DNP38C10 macrocycle moves to the PmI unit. Li+ ions have been found to strengthen the interaction between the electron-donating crown ether and the electron-accepting diimide units, particularly the PmI one. Titration experiments show that two Li+ ions are involved in the strengthening of the donor-acceptor interaction. Addition of Li+ ions to NpPmR induces the 1/5DNP38C10 macrocycle to move from the NpI to the PmI unit. The Li+-ion-promoted switching of NpPmR in a 4:1 mixture of CD2Cl2 and CD3COCD3 has also been shown by 1H NMR spectroscopy to involve the mechanical movement of the 1/5DNP38C10 macrocycle from the NpI to the PmI unit, a process that can be reversed by adding an excess of [12]crown-4 to sequester the Li+ ions.     

1,2-silyl-migrative cyclization of vinylsilanes bearing a hydroxy group: stereoselective synthesis of multisubstituted tetrahydropyrans and tetrahydrofurans(1)

Acid-catalyzed intramolecular addition of a hydroxy group to alpha-alkylated vinylsilanes has been studied. Treatment of (Z)-5-alkyl-5-silyl-4-penten-1-ols 1 (R = alkyl) with 5 mol % TiCl(4) in CHCl(3) gave trans-2-alkyl-3-silyltetrahydropyrans 2 exclusively (trans/cis = >99/1 to 97/3). The cyclization efficiency and rate strongly depended on the geometry of the C-C double bond and the silyl group. The use of (E)-vinylsilanes resulted in lower yields with poor cis-selectivity. In the cyclization of (Z)-1 (R = Bu), the silyl group used, the reaction time, and the yield of 2 were as follows: SiMe(2)Ph, 9.5 h, 75%; SiMe(3), 7.5 h, 66%; SiMePh(2), 24 h, 58%; SiMe(2)-t-Bu, 0.75 h, 85%; SiMe(2)Bn, 1.5 h, 78%. This 1,2-silyl-migrative cyclization could be applied to stereoselective synthesis of trisubstituted tetrahydropyrans. The acid-catalyzed reaction of 1-, 2-, or 3-substituted (Z)-5-silyl-4-nonen-1-ols 8 gave r-2,t-3,c-6-, r-2,t-3,t-5-, or r-2,t-3,c-4-trisubstituted tetrahydropyrans with high diastereoselectivity, respectively. (Z)-4-Alkyl-4-silyl-3-buten-1-ols 5 as well as 1 underwent the 1,2-silyl-migrative cyclization to give 2-alkyl-3-silyltetrahydrofurans 6 with high trans-selectivity. This silicon-directed cyclization was also available for the stereoselective synthesis of tri- and tetrasubstituted tetrahydrofurans.     

Surface-potential reversibility of an amino-terminated self-assembled monolayer based on nanoprobe chemistry

Nanoprobe chemistry offers a promising approach for the construction of nanostructures consisting of organic molecules by employing the tip of a scanning probe microscope. In a previous report, we demonstrated that a nitroso-terminated surface on an organosilane self-assembled monolayer could be converted into an amino-terminated surface by applying such a nanoprobe electrochemical technique. This paper reports on surface-potential reversibility originating from a reversible chemical reaction between amino and nitroso groups. In addition, we demonstrate surface-potential memory based on this chemical reversibility. Amino-terminated SAMs were prepared from p-aminophenyl-trimethoxysilane through chemical vapor deposition. Surface potentials were acquired by Kelvin force microscopy. When scanning probe lithography was conducted with a gold tip at positive-bias voltages, the surface potential of the scanned area shifted dramatically in the negative direction. Scanning with negative-bias voltages led to positive shift in the surface potential of the scanned area. The surface potential could be recovered even after multiple scannings with positive and negative applied bias voltages. On the basis of this discovery, we also succeeded in demonstrating surface-potential memory via our nanoprobe electrochemical technique.     

"Chiral perturbation factor" approach reveals importance of entropy term in stereocontrol of the 2,4-pentanediol-tethered reaction

The stereocontrol mechanism of the 2,4-pentanediol (PD)-tethered reaction was studied in detail using a reaction system consisting of phenyl and rhodium carbenoid moieties. Different tethers were examined to analyze the effects of the methyl groups on the PD tether. Among the reactions with these tethers, the PD tether achieves an unmeasurably high stereoselectivity in a diastereomeric ratio of >500. Another tether showing a high but measurable stereoselectivity in a ratio of 41 is mostly controlled by the entropy term. To clarify the role of the methyl groups on the chiral tethers, which are the origin of the stereocontrol, the "chiral perturbation factor" is introduced. This parameter is defined as the rate of a chiral reaction relative to that of an achiral reference reaction. By analyzing the temperature dependence of the chiral perturbation factors for different chiral-tethered reactions, high potentials of the PD-tethered reaction in its stereocontrol are concluded to be due to the entropy term.     

Syntheses and Characterization of Polymetallosiloxanes from Silicic Acid and Metal Chlorides

Syntheses and characterization of polymetallosiloxanes by the non-hydrolysis sol-gel process using no metal alkoxides were investigated. The reaction of silicic acid (SA) with MCl₄ (M = Ti, Zr) in the molar ratios SA/MCl₄ = 0.5–3.0 using a tetrahydrofuran-methanol solvent formed polymetallosiloxane (PMS), which was insoluble in organic solvents regardless of the molar ratio. The PMS was isolated as esterified polymetallosiloxane by esterification with isopropyl alcohol for various periods, which were soluble in methanol, acetone, and tetrahydrofuran. The number average molecular weight was 1000–3200 for esterified polytitanosiloxane and 3400–11000 for esterified polyzirconosiloxane. Esterified polymetallosiloxanes had no melting point but decomposition point. The results of analytical data indicated that esterified polymetallosiloxane and/or polymetallosiloxane consisted of the main chain of Si–O–Si and Si–O–M linkage with the pendants of alkoxy, silanol, and chloro group.