Eiji Hayashi

The electrochemical fluorination of nitrogen-containing carboxylic acids. Fluorination of dimethylamino- or diethylamino-substituted carboxylic acid derivatives

Abstract The electrochemical fluorination of six derivatives of dimethylamino- or diethylamino-substituted carboxylic acids has been conducted. As the main fluorination products, cyclized and cleaved products as well as the desired N-containing perfluoroacid fluorides were formed, and their ratios depended on the chain length and the structure of the starting carboxylic acids, and the nature of the dialkylamino group. Through this work, perfluoro(dimethylamino-acetyl fluoride), perfluoro(diethylamino- acetyl fluoride), perfluoro(2-dimethylamino-propionyl fluoride), perfluoro(2-dimethylamino-butyryl fluoride) and perfluoro(3-dimethylamino-propionyl fluoride) were prepared. Except for perfluoro(dimethylamino-acetyl fluoride), these acid fluorides were new compounds. The physical properties of new compounds obtained including these acid fluorides are reported together with their spectral ( 19 F nmr, Mass and IR) data.

Mutation Analysis of 2009 Pandemic Influenza A(H1N1) Viruses Collected in Japan during the Peak Phase of the Pandemic

Background Pandemic influenza A(H1N1) virus infection quickly circulated worldwide in 2009. In Japan, the first case was reported in May 2009, one month after its outbreak in Mexico. Thereafter, A(H1N1) infection spread widely throughout the country. It is of great importance to profile and understand the situation regarding viral mutations and their circulation in Japan to accumulate a knowledge base and to prepare clinical response platforms before a second pandemic (pdm) wave emerges. Methodology A total of 253 swab samples were collected from patients with influenza-like illness in the Osaka, Tokyo, and Chiba areas both in May 2009 and between October 2009 and January 2010. We analyzed partial sequences of the hemagglutinin (HA) and neuraminidase (NA) genes of the 2009 pdm influenza virus in the collected clinical samples. By phylogenetic analysis, we identified major variants of the 2009 pdm influenza virus and critical mutations associated with severe cases, including drug-resistance mutations. Results and Conclusions Our sequence analysis has revealed that both HA-S220T and NA-N248D are major non-synonymous mutations that clearly discriminate the 2009 pdm influenza viruses identified in the very early phase (May 2009) from those found in the peak phase (October 2009 to January 2010) in Japan. By phylogenetic analysis, we found 14 micro-clades within the viruses collected during the peak phase. Among them, 12 were new micro-clades, while two were previously reported. Oseltamivir resistance-related mutations, i.e., NA-H275Y and NA-N295S, were also detected in sporadic cases in Osaka and Tokyo.

The electrochemical fluorination of nitrogen-containing carboxylic acids. Fluorination of methyl esters of cyclic amino-group substituted carboxylic acids

Abstract Nine methyl esters of cyclic amino-group substituted carboxylic acids related to glycine, alanine or β-alanine were subjected to electrochemical fluorination. This afforded the corresponding perfluoroacid fluorides together with cleavage products in fair yields. As cyclic amino-substituents, pyrrolidino-, morpholino-, piperidino-, hexamethyleneimino- and N′-methyl-piperazinyl-groups were investigated. The formation of cyclized by-products was not observed, which contrasts with the fluorination of aliphatic dialkylamino-substituted carboxylic acids. From such methyl 2-cyclic amino-propionates [cyclic amino-group: a pyrrolidino, a morpholino or a piperidino-group], the perfluorinated methyl esters were obtained together with the corresponding perfluoroacid fluorides in yields of 1∼2 % and 14∼29 % respectively. The formation of the former compounds is ascribed to the blocking effect of the bulky cyclic amino-groups. The physical properties of the new compounds obtained are reported together with their spectral ( 19 F NMR, Mass and IR) data.

The electrochemical fluorination of nitrogen-containing carboxylic acids. Fluorination of methyl esters of 3-dialkylamino propionic acids

Abstract Six methyl esters of 3-dialkylamino-substituted propionic acids were subjected to electrochemical fluorination to give the corresponding perfluoroacid fluorides. The following dialkylamino substituents were investigated: diethylamino, di- n -propyl-amino, di- n -butylamino, pyrrolidino, morpholino and piperidino groups. These perfluoroacid fluorides, which were obtained in fair yields, are considered to be prospective key precursors for preparing soft-type (degradable) fluorochemicals. The salts show a considerable lowering of surface tension in aqueous solution. The physical properties of all the perfluoroacid fluorides obtained are reported, together with their spectroscopic data ( 19 F NMR, mass and IR spectra).

The electrochemical fluorination of N-containing carboxylic acids (Part 4). Fluorination of methyl 3-dialkylamino-isobutyrates and methyl 3-dialkylamino-n-butyrates☆

Abstract Several methyl esters of 3-dialkylamino-substituted n- and isobutyric acids have been subjected to electrochemical fluorination to give the corresponding perfluoroacid fluorides. Dimethyl, diethyl, pyrrolidino, morpholino, piperidino and N -methylpiperazino groups were investigated as dialkylamino substituents. The structure/yield relationship was evaluated both in terms of the structure of the acid and the kind of amino group, respectively. Better yields of perfluoroacid fluorides were obtained from methyl esters having isobutyric acid skeletons than those having n-butyric acid groups, and from the acids containing cyclic amino groups than those containing acyclic ones.

Synthesis of perfluorobicyclic ethers [1]. The electrochemical fluorination of cycloalkyl-substituted carboxylic acids

Abstract A new synthetic method for making perfluorobicyclic and perfluoromonospiro ethers by fluorinating the cycloalkyl-substituted carboxylic acid electrochemically is presented. Novel perfluoro(2-oxabicyclo[3.3.0]octane) and perfluoro(7-oxabicyclo- [4.3.0]nonane) were obtained by the fluorination of methyl cyclopentylacetate and methyl cyclohexylacetate in yields of 10.5% and 11.8% respectively. The fluorination of methyl 3-cyclopentylpropionate and methyl 3-cyclohexylpropionate afforded the new perfluoro(1-oxaspiro[4.4]nonane) and perfluoro(1-oxaspiro[4.5]- decane) as the main cyclization products in yields of 12.4% and 16.6% respectively. Several kinds of perfluorinated cyclization products having a perfluoroalkyl group at the β-carbon to oxygen were also prepared by the fluorination of α-alkyl-α-cycloalkyl- substituted acetic acids. These new fluorination products, including some perfluorocycloalkanes and perfluoroalkanoyl fluorides, have been characterized by elemental analysis and infrared, mass and 19 F nmr spectra.

Fluorination of 2-alkyl-substituted oxanes. The synthesis and purification of perfluoro(2-alkyl-substituted oxane)s

Abstract Five kinds of 2-alkyl-substituted oxanes like 2-ethyloxane, 2-n-propyloxane, 2-iso-propyloxane, 2-n-butyloxane and 2-n-amyloxane were fluorinated electrochemically to give the corresponding perfluoro(2-alkyloxane)s. The perfluoro(2-alkyloxane)s were obtained in good yields from these starting materials together with isomeric perfluoro(2-alkyloxolane)s, perfluoro(2-alkyl-5-methyloxolane)s and perfluoro(dialkyl ether)s. The purification of the perfluoro(2-alkyloxane)s which contained small amounts of isomeric perfluoro(2-alkyloxolane)s was successfully achieved by recovering the former unreacted after treating these mixture with anhydrous aluminum chloride at 150 /sR 160 °C during /sR 48 hrs in order to convert the latter into the easy-separable perfluoro(2,5,5- trichloro-2-alkyloxolane)s. Small quantities of new perfluoro(5,5-dichloroalkanoyl chloride)s were also among the chlorination products. The spectroscopic data as well as the physical properties of these new fluorination products, and perfluoro(2,5,5-trichloro-2-alkyloxolane)s and perfluoro(5,5-dichloroalkanoyl chloride)s are presented.

One-Step Detection of the 2009 Pandemic Influenza A(H1N1) Virus by the RT-SmartAmp Assay and Its Clinical Validation

Background In 2009, a pandemic (pdm) influenza A(H1N1) virus infection quickly circulated globally resulting in about 18,000 deaths around the world. In Japan, infected patients accounted for 16% of the total population. The possibility of human-to-human transmission of highly pathogenic novel influenza viruses is becoming a fear for human health and society. Methodology To address the clinical need for rapid diagnosis, we have developed a new method, the “RT-SmartAmp assay”, to rapidly detect the 2009 pandemic influenza A(H1N1) virus from patient swab samples. The RT-SmartAmp assay comprises both reverse transcriptase (RT) and isothermal DNA amplification reactions in one step, where RNA extraction and PCR reaction are not required. We used an exciton-controlled hybridization-sensitive fluorescent primer to specifically detect the HA segment of the 2009 pdm influenza A(H1N1) virus within 40 minutes without cross-reacting with the seasonal A(H1N1), A(H3N2), or B-type (Victoria) viruses. Results and Conclusions We evaluated the RT-SmartAmp method in clinical research carried out in Japan during a pandemic period of October 2009 to January 2010. A total of 255 swab samples were collected from outpatients with influenza-like illness at three hospitals and eleven clinics located in the Tokyo and Chiba areas in Japan. The 2009 pdm influenza A(H1N1) virus was detected by the RT-SmartAmp assay, and the detection results were subsequently compared with data of current influenza diagnostic tests (lateral flow immuno-chromatographic tests) and viral genome sequence analysis. In conclusion, by the RT-SmartAmp assay we could detect the 2009 pdm influenza A(H1N1) virus in patients swab samples even in early stages after the initial onset of influenza symptoms. Thus, the RT-SmartAmp assay is considered to provide a simple and practical tool to rapidly detect the 2009 pdm influenza A(H1N1) virus.

Inhibition of Combustion by Bromine-Free Polyfluorocarbons I. Burning Velocities of Methane Flames Containing Polyfluoroalkylamines

Abstract To estimate the inhibition effect of several bromine-free polyfluoroalkylamines such as (CF3CF2)N, (CF3)2NCF2CF3, (CF3)2NCF2,CHF2 and (CF3)2NCF=CF2 on flame propagation, the laminar burning velocity was measured for a mixture of 9.5% methane, 90.0% air, and 0.5% inhibitor, at an initial temperature of 298 ± 2xa0K. and a pressure of 1xa0atm. All of the polyfluoroalkylamines inhibited flame propagation less than CF3Br(Halon 1301), but more than CH3CHFCF3(FM200). Calculations showed that the inhibition effect of polyfluoroalkylamines was caused not only by physical factors, but also by a chemical process in which fluoric species capture chain carriers (H, O, and OH) ofcombustion reactions to form stable HF molecules. The inhibition efficiencies of polyfluoroalkylamines were found to be higher than those of polyfluoroalkanes because of polyfluoroalkylamines decomposition to reactive polyfluoroalkyl radicals in the lower temperature region of each flame. The application of polyfluoralkylamines to fire-ext...

Electrochemical fluorination of N-containing carboxylic acids Part 5. Fluorination of the methyl esters of cis-2,6-dimethylmorpholino-group substituted carboxylic acids

Abstract Cis -2,6-dimethylmorpholine and its derivatives having an ester group were subjected to electrochemical fluorination. The electrochemical fluorination of cis -2,6-dimethylmorpholine afforded only a small quantity of F -( N -fluoro-2,6-dimethyl-morpholine), whereas the N -(methoxycarbonylalkyl)-substituted cis -2,6-dimethyl-morpholines gave the corresponding F -acid fluorides in fair yields. Cis -and trans -isomerization on two methyl substituents of the morpholine ring occurred through electrochemical fluorination of pure cis -2,6-dimethylmorpholine to give a 1:0.25–0.5 mixture of cis - and trans -isomers having a F -2,6-dimethylmorpholino-moiety. The formation of a seven-membered ring expanded product was confirmed as a by-product in the fluorination of methyl cis -2,6-dimethylmorpholino-acetate. Spectroscopic data as well as physical properties of new nitrogen-containing F -carboxylic acids are presented.