Synthesis of stable class 5 mesoionic benzo[c]tetrazolo[2,3-a]cinnolinium thiolate, dicyanomethylide, and amides.

Although class 5 mesoionic compounds show interesting electrical behaviour, they are generally unstable, readily undergoing ring-opening reactions. We designed and synthesized a bridged mesoionic derivative, benzo[c]tetrazolo[2,3-a]cinolinium (BTC), as a stable class 5 mesoionic compound, which was further transformed to the corresponding thiolate, cicyanomethylide, and amide. The intramolecular bridging imparted stability to the BTC thiolates and amides: the BTC thiolates were unsusceptible to ring-opening at high temperatures, and the BTC amides were stable in the absence of electron-withdrawing groups on the amide nitrogen. The properties of the BTC thiolate were compared with those of 2,3-diphenyltetrazolium derivatives based on UV-Vis absorption spectroscopy, single-crystal X-ray diffraction and quantum calculations.

Indium-Mediated Allylation of Carbonyl Compounds in Ionic Liquids: Effect of Salts in Ionic Liquids.

The In-mediated allylation of carbonyl compounds can be performed in various types of solvents including ionic liquids. However, we have found that in [bmim][BF4] (where bmim = 1-butyl-3-methylimidazolium), the In-mediated coupling of crotyl bromide with benzaldehyde gives a complex mixture, and some additives, such as halides and amines, are crucial for the successful conversion to the corresponding γ-adduct. Instead, the addition of alcohols or water promotes the formation of the α-adduct. An asymmetric induction with up to 62% enantiomeric excess (ee) was observed employing cinchonidine as an additive in a binary solvent consisting of an ionic liquid and dichloromethane.

Synthesis of 3-(phenylazo)-1,2,4-triazoles by a nucleophilic reaction of primary amines with 5-chloro-2,3-diphenyltetrazolium salt via mesoionic 2,3-diphenyltetrazolium-5-aminides.

The reactions of a 5-chloro-2,3-diphenyltetrazolium salt with amines have been examined. In the presence of an inorganic base such as NaHCO(3), primary and secondary amines undergo a nucleophilic substitution to give the corresponding 5-aminotetrazolium salts. When triethylamine is used as a base, primary amines give 3-phenylazo-1,2,4-triazoles. A plausible dual-path mechanism is proposed for the formation of the triazoles via Type B mesoionic tetrazolium-5-aminides.

Cis double allylation of cyclopropenes using cyclopropylindium reagents.

The successive double allylation of cyclopropenes with allylindium sesquiiodide and allyl iodide proceeded with a cis-addition mode in the presence of other organometallics (e.g. Grignard reagent, cuprate, Et(2)Zn and Et(3)Al), giving the corresponding cis-diallylcyclopropanes in high yields.

Nickel-catalyzed indium(I)-mediated double addition of aldehydes to 1,3-dienes.

In the presence of InI, Ni(acac)2 and PPh3, several 1,3-dienes were reacted with two molecules of aldehyde to give the corresponding 1,4- and 1,6-diols. The regioselectivity of the 1,4-/1,6-diol was efficiently regulated by the addition of water; the 1,6-diol was obtained selectively in dry THF, whereas the 1,4-diol was obtained predominantly in DMI containing a small amount of water.

Nickel-catalysed bis-allylation of internal alkynes with triallylindium.

The Ni-catalysed reaction of triallylindium with internal alkynes underwent bis-allylation to afford octa-1,4,7-trienes in high yield.

Instrumentation of high temperature and pressure reaction system with continuous flow and its hyphenation to a liquid chromatograph.

A continuous flow-type hydrothermal reaction system, in which both temperature and pressure were rapidly and dynamically controlled, was constructed. It is called a real time high temperature and pressure reaction system (RT-HighTP). The RT-HighTP was hyphenated with liquid chromatograph (RT-HighTP-LC) to achieve prompt analysis of the reaction products. The RT-HighTP system produced stable pressure under the supercritical and subcritical phases (%RSD < 3%). The RT-HighTP-LC was able to change the hydrothermal condition rapidly. The hydrothermal products under four conditions were analyzed within 70 min. Further, the hydrothermal products of lignin was easily taken out using the sample collecting loop and analyzed by an external instrument of GC/MS.

Retention behavior of neutral solutes in pressurized flow-driven capillary electrochromatography using an ODS column.

Several alkyl benzenes are separated by pressurized flow-driven capillary electrochromatography using a temperature-controlled capillary column packed with octadecyl siloxane-modified silica gel, and the effect of applied voltage on the retention is investigated. The van't Hoff plot shows good linearity at the column temperature between 305 and 330 K under applications from -6 to +6 kV. The applied voltage causes a relatively large variation in the enthalpy and the entropy of transfer of the solute from the mobile phase to the stationary phase (> 20%). However, the direction of variation in the enthalpy is almost opposite to that in the entropy, both of which might compensate each other. Therefore, the retention factor is not significantly varied (< 4%) by the application of voltage.

Identification of ammonia in gas emanated from human skin and its correlation with that in blood.

Identifying and measuring the ammonia gas that emanates from human skin, which we called skin gas, has been achieved using a modified gas chromatographic system with a nitrogen-selective detector (flame-thermoionic detector: FTD). The skin gas is collected with a home-made sampling probe or bag, which is used to cover the skin surface of a subject's wrist, or a finger, for 5 min. It was proved that ammonia was present in skin gas for healthy persons and patients with hepatic disease. The average amounts of ammonia were 1.7 +/- 0.4 and 2.7 +/- 0.8 ng/cm2; furthermore, there was a significant difference between them (p < 0.05). In addition, the ammonia levels present in skin gas were correlated with that in blood (r = 0.64, p < 0.05).

Direct preparation of allylic indium(III) reagents from allylic alcohols via a reductive transmetalation of pi-allylnickel(II) with indium(I) iodide.

InI-mediated direct allylation of carbonyl compounds with allylic alcohols proceeded smoothly with catalytic amounts of Ni(acac)(2) and PPh(3) to give the corresponding homoallylic alcohols in high yields. Allylindium compounds were shown to be the real allylating agents in the present system. Substituted allylic alcohols gave branched homoallylic alcohols with syn-selectivity irrespective of the geometry of the starting allylic alcohols, whereas high anti-selectivity was observed when a bulky substituent is present in the allylic alcohols. The outcome of the diastereoselectivity is discussed on the basis of the reaction mechanism, comparing with the corresponding Pd-catalyzed version. Another distinct behavior between the Ni- and Pd-catalyzed allylation was demonstrated in the reaction of hex-1,5-diene-3,4-diol derivatives: the Pd catalyst did not give any coupling product, whereas the Ni-catalyzed InI-mediated reaction with benzaldehyde afforded the 1:1 and 1:2 adduct diols selectively depending on the reaction conditions.

A new synthesis of pyrroles by the condensation of cyclopropenes and nitriles mediated by gallium(III) and indium(III) salts.

Gallium(III) and indium(III) halides were found to mediate the condensation of cyclopropenes and nitriles to give pyrrole derivatives in moderate yields. When excess nitrile was present, diazepine was also formed.

Control of diastereoselectivity in the crotylation and cinnamylation of aldehydes by the selection of ligands on allylic indium reagents.

Diastereoselective couplings of salicylaldehyde, anisaldehyde and 2-pyridylaldehyde with crotyl- and cinnamylindium reagents were studied. The syl/anti selectivity was found to depend largely on the ligands on the indium atom of the allylic indium reagents. A syn-selective cinnamylation of salicylaldehyde was realized by the combination of cinnamyl acetate and indium(I) iodide, whereas an anti-selective coupling with salicylaldehyde was achieved by the indium trichloride/aluminium-mediated cinnamylation.

Reaction cascades initiated by nucleophilic attack of heteropentalene mesomeric betaine and nitrogen-rich mesoionic tetrazolium-5-amides on electron-deficient unsaturated compounds. Synthesis of novel heterocyclic systems.

The reactions of heteropentalene mesomeric betaine 1 and nitrogen-rich mesoionic tetrazolium-5-amides 4, 11 and 16-18 with electron-deficient unsaturated compounds have been studied. Novel heterocyclic systems, tetrazolo[4,5-a][1,7]benzodiazonine inner salt 2 and 3-oxo-3,7-dihydro-2H-pyrazolo[3,4-b]pyridine 5, have been synthesized by the reactions of dimethyl acetylenedicarboxylate with 1 and tetrazolium-5-anilide 4, respectively, and fully characterized by X-ray crystallography. It has been found that the reactions of other tetrazolium-5-amides are also initiated by the nucleophilic addition of the electron-rich amide nitrogen to the electron-deficient unsaturated compounds.

Allylic-type diindium reagents. Reactivity toward electrophiles and cascade coupling reactions with imines.

The allylic-type diindium reagents A and B were prepared from 3-bromo-1-iodopropene (1a) and 4-bromo-2-iodobut-2-ene (1b), respectively, and their reactions with electrophiles were investigated. The diindium reagents A and B were initially reacted with imines and the resulting vinylindium compounds were then treated with organic halides in the presence of Pd(PPh(3))(4) to give linear N-aryl and N-tosyl homoallylic amines. Diindium A is stable in a small amount of water in solvent, whereas B is easily protonated to give a crotylindium reagent. The reaction of B with benzaldehyde gives mainly the 1,3- and 1,5-diols via a spontaneous coupling with two molecules of the aldehyde, in contrast to A, which reacts with one molecule of carbonyl compounds to give the vinylindium compounds.

Stereochemistry of protected ornithine side chains of gramicidin S derivatives: X-ray crystal structure of the bis-Boc-tetra-N-methyl derivative of gramicidin S.

An X-ray crystallographic analysis of the bis-Ndelta-Boc-tetra-Nalpha-methyl derivative of gramicidin S, cyclo(-Val-MeOrn(Boc)-Leu-d-MePhe-Pro-)2, was undertaken successfully (R-factor = 0.088). As expected, the main chain adopts an antiparallel pleated beta-sheet conformation, but the pleated sheet is slightly twisted, and the sense of twisting is opposite to that found in the reported crystal structures of the gramicidin S-urea complex and the bis-Ndelta-(trichloroacetyl) and bis-Ndelta-(m-bromobenzoyl) derivatives of gramicidin S. In agreement with the observed resistance toward N-methylation, the urethane NH groups of the protected Orn side chains are hydrogen bonded to the carbonyl groups of the d-Phe residues. However, the side-chain-main-chain hydrogen bonding is in the i --> i - 3 mode, although hydrogen bonding in the i --> i + 2 mode was deduced from a 1H NMR study of protected gramicidin S derivatives and was actually found in the crystal structures of the diacylated gramicidin S.

Preparation of gamma-Heterosubstituted Allylindium and Diindium Reagents and Their Reactions with Carbonyl Compounds.

Various gamma-heteroatom-substituted allylindium reagents were prepared, and their reactions with carbonyl compounds were examined. The reaction of 1,3-dibromopropene with metallic indium gave two types of organoindium species, gamma-bromoallylindium and allylic diindium reagents. While the former gave 2-phenyl-3-vinyloxirane upon the coupling with benzaldehyde, the latter gave 1-phenylbut-3-en-1-ol. 1-Iodo-3-bromopropene gave the homoallylic alcohol exclusively. gamma-Alkoxyallylindium reagents were prepared by treating the corresponding gamma-alkoxyallyllithium with indium trichloride and reacted with benzaldehyde to give vic-diol mono ethers in high yields with good syn selectivity. gamma-(Trimethylsilyl)allylindium and alpha,gamma-disubstituted allylindium reagents were also prepared via transmetalation with the corresponding allyllithium.