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.     

Capillary electrochromatographic analysis of barbiturates in serum

A capillary electrochromatographic method was developed for the separation of barbiturates. The separation was optimized in a 75 microm ID capillary, packed with 3-(1,8-naphthalimido)propyl-modified silyl silica gel (NAIP), studying the effect of buffer pH, buffer concentration, and mobile phase composition. Using an applied voltage of 20 kV and the short-end injection method (9 cm capillary effective length), the mobile phase of 1.0 mM citrate buffer (pH 5.0) containing 40% methanol provided the baseline separation of barbital, phenobarbital, secobarbital, and thiopental (internal standard) in less than 4.5 min. The method was successfully applied to the analysis of barbiturates in human serum. Under the optimal conditions, good repeatability and linearity were obtained in the range of 2.90-43.29 microg/mL for barbital, phenobarbital, and secobarbital.     

An efficient photoinduced iodoperfluoroalkylation of carbon-carbon unsaturated compounds with perfluoroalkyl iodides

Dependent on the selection of the light sources employed, the photoinduced iodoperfluoroalkylation of a variety of unsaturated compounds takes place efficiently via a radical mechanism. Upon irradiation with a xenon lamp through Pyrex (hnu >300 nm), terminal alkenes (R-CH=CH2) and alkynes (R-C triple bond CH) undergo iodoperfluoroalkylation with perfluoroalkyl iodides (RF-I) regioselectively, providing R-CH(I)-CH2-RF and R-C(I)=CH-RF, respectively. In the case of terminal allenes (R-CH=C=CH2), the photoinduced iodoperfluoroalkylation occurs selectively at the terminal double bond, giving the corresponding beta-perfluoroalkylated vinylic iodides (R-CH=C(I)-CH2-RF) in good yields. The photoinitiated reaction of vinylcyclopropanes (c-C3H5-C(R)=CH2) with RF-I proceeds via the rearrangement of cyclopropylcarbinyl radical intermediates to the homoallylic radical intermediates, and the corresponding 1,5-iodoperfluoroalkylated products (I-(CH2)2CH=C(R)-CH2-RF) are obtained in high yields. Isocyanides (R-NC), as C-N unsaturated compounds, also undergo the xenon-lamp-irradiated iodoperfluoroalkylation to provide the corresponding 1,1-adducts (R-N=C(I)-RF) in good yields. Furthermore, the present photoinitiation procedure can be applied to the iodotrifluoromethylation of unsaturated compounds, when the xenon-lamp-irradiated reactions are conducted under the refluxing conditions of excess CF3-I.     

Investigation of the novel mixed-mode stationary phase for capillary electrochromatography. I. Preparation and characterization of sulfonated naphthalimido-modified silyl silica gel

A novel packing material, 3-(4-sulfo-1,8-naphthalimido)propyl-modified silyl silica gel (SNAIP), was prepared for the use as a stationary phase of capillary electrochromatography (CEC). The sulfonic acid groups on SNAIP stationary phase contributed to the generation of electroosmotic flow (EOF) at low pH and served as a strong cation-exchanger. In CEC with SNAIP, a mixed-mode separation was predicted, comprising hydrophobic and electrostatic interactions as well as electrophoretic migration process. In order to understand the retention mechanism on SNAIP, effects of buffer pH, concentration, and mobile phase composition on EOF mobility and the retention factors of barbiturates and benzodiazepines were systematically investigated. Moreover, the retention behavior of barbiturates on SNAIP was investigated and compared with those on octadecyl silica (ODS), phenyl-bonded silica, and 3-(1,8-naphthalimido)propyl-modified silyl silica gel to confirm the presence of pi-pi interaction on its retention mechanism. It was observed that a column efficiency was more than 85,000 N/m for retained compounds and the relative standard deviations for the retention times of EOF marker, thiourea, and five barbiturates were below 2.5% (n = 4). Under an applied voltage of 20 kV and a mobile phase consisted of 5 mM phosphate (pH 3.8) and 40% methanol, the baseline separation of five barbiturates was achieved within 3 min.     

Photoswitching of single association force between a pair of photoionizable spirobenzopyrans

We have measured the single intermolecular force of a typical photoionizable molecule, spirobenzopyran, by means of atomic force microscopy, which has proven to be useful in measuring directly single molecular forces. The spirobenzopyran moiety was immobilized covalently on both Au-coated probe tips and substrates by use of a self-assembled monolayer of a hexanethiol derivative incorporating a terminal spirobenzopyran moiety, 1'-(6'-mercaptohexyl)-3',3'-dimethylindolino-6-nitrospiro-(2H-1-benzopyran-2,2'-indoline). Force curve measurements were carried out using the spirobenzopyran-modified probe tip and substrate under dark conditions and in situ UV light irradiation. The adhesion force observed in a polar solvent (i.e., ethanol) was increased substantially under in situ UV light irradiation, which caused photoisomerization of the spirobenzopyran moiety bound to both tip and substrate from its electrically neutral spiropyran form to the corresponding zwitterionic merocyanine one. Statistical analyses of the observed force by autocorrelation technique have revealed that the photoionization enhanced by UV light caused a remarkable increase in the single intermolecular force of the photochromic compound.     

Rapid separation of barbiturates and benzodiazepines by capillary electrochromatography with 3-(1,8-naphthalimido)propyl-modified silyl silica gel

A capillary electrochromatographic (CEC) method was applied to the simultaneous separation of barbiturates (barbital, phenobarbital, secobarbital and thiopental) and benzodiazepines (nitrazepam, diazepam and triazolam). The separation was performed in a 75 microm i.d. capillary, packed with 3-(1,8-naphthalimido)propyl-modified silyl silica gel (NAIP), studying the effects of buffer pH and mobile phase composition. Using an applied voltage of 20 kV and the short-end injection method (9 cm capillary effective length), the mobile phase of 1.0 mM citrate buffer (pH 5.0) containing 45% methanol provided the baseline separation of seven toxic drugs in less than 9 min. In CEC with NAIP, the benzodiazepines were separated by the combination of hydrophobic and pi-pi interactions, whereas the separation of the barbiturates was based on the hydrophobic interaction.     

Diastereoselective addition of alcohol to diastereotopic silylenes

The successful example of diastereoselective addition of alcohol to diastereotopic silylenes is reported.     

A novel glycosidation of glycosyl fluoride using a designed ionic liquid and its effect on the stereoselectivity

The glycosidations of glucopyranosyl fluoride and alcohols using an ionic liquid containing a protic acid effectively proceeded under mild conditions to afford the corresponding glycosides in good to high yields. The stereoselectivity of the glycosidation was significantly affected by the ionic liquid solvent. 1-n-Hexyl-3-methylimidazolium trifluoromethanesulfonate (C₆mim[OTf]), containing a trifluoromethanesulfonate anion, and 1-(3-cyanopropyl)-3-methylimidazolium trifluoromethanesulfonimidide (CNC₃mim[NTf₂]), possessing a cyano group at the side chain of the imidazolium cation, gave the β-stereoselectivity.     

Photoelectrochemical reduction products of carbon dioxide at metal coated p-GaP photocathodes in non-aqueous electrolytes

Photoelectrochemical reduction of CO₂ was carried out using metal-coated p-GaP photocathodes in non-aqueous electrolytes prepared from tetraalkylammonium salts and propylene carbonate as an aprotic solvent. In non-aqueous electrolytes, the coating of Au, In and Pb increased the cathodic photocurrents and the stability of the electrodes, while Zn coating did not show such significant effects. Photoelectrochemical reduction products at a bare p-GaP in non-aqueous electrolytes were (COOH)₂, HCOOH, CO and H₂, and the faradaic efficiency for CO formation became 50%, in contrast to that in the aqueous electrolytes where it was only a few %. The Photoelectrochemical reduction products at metal-coated p-GaP photocathodes depended greatly on the catalytic properties of the coated metal, i.e. the catalytic effect on the electrochemical reduction of CO₂. By Pb coating, the faradaic efficiency for (COOH)₂ formation became ca. 50%, and by Au, In or Zn coating, that for CO became almost 100%. The water content in non-aqueous electrolytes affected the faradaic efficiency of each product significantly.     

Highly selective double chalcogenation of isocyanides with disulfide-diselenide mixed systems

A highly selective method for introducing thio and seleno groups into a variety of isocyanides has been developed based on the elucidation of the relative reactivities of organic dichalcogenides and chalcogen-centered free radicals. When the reactions of aromatic isocyanides (ArNC) with organic disulfides (R'SSR') and diselenides (R'SeSeR') are conducted upon irradiation with a tungsten lamp through Pyrex (hnu>300 nm), simultaneous introduction of both thio and seleno groups into the isocyanides takes place to provide the corresponding thioselenation products (R'S-C(=NAr)-SeR') in good yields with excellent selectivity. In the cases of aliphatic isocyanides (RCN), a novel diselenide-assisted bisthiolation of RNC with diaryl disulfides (Ar'SSAr') proceeds successfully to give the corresponding bisthiolation products (Ar'S-C(=NR)-SAr'), although the same photoirradiated reaction of RNC with diaryl disulfides does not occur in the absence of diselenide. These double chalcogenation reactions are assumed to proceed via the formation of imidoyl radical intermediates by the reaction of isocyanides with relatively reactive thio radicals (compared with seleno radicals). The obtained thioselenation products can be employed as useful precursors for the construction of beta-lactam framework by the formal [2+2] cyclization with ketene equivalents.