Takashi Okazoe

Carbonyl methylenation of easily enolizable ketones

Abstract An organometallic reagent prepared from CH 2 I 2 , Zn, and TiCl 4 is effective for methylenation of the title ketones.

Chemoselective methylenation with a methylenedianion synthon

Abstract The combination of CH 2 I 2 -ZN-Ti(O i Pr) 4 or CH 2 I 2 -ZN-Me 3 Al is effective for the selective methylenation of aldehydes. Seletive methylenation of a ketone group is performed by pretreatment of a substrate with Ti(NET 2 ) 4 .

Stereoselective synthesis of (E)-alkenylsilanes from aldehydes with a reagent prepared by chromium(II) reduction of Me3SiCHBr2

Abstract Aldehydes are converted to the corresponding (E)-alkenylsilanes with one carbon homologation by means of a gemdichromium reagent prepared by CrCl 2 reduction of Me 3 SiCHBr 2 in THF. Transformation of aldehydes into alkenyl sulfides is also achieved with a combination of PhSCHCl 2 and CrCl 2 .

Regio- and stereoselective preparation of silyl enol ethers by alkylidenation of silyl esters

Abstract Treatment of trimethylsilyl esters with a reagent for alkylidenation of carbonyl groups derived from 1,1-dibromoalkane, zinc, TiCl4, and TMEDA in THF gives Z-trimethylsilyl enol ethers in a regio- and stereoselective manner.

Overview on the history of organofluorine chemistry from the viewpoint of material industry

Fluorine (from “le fluor”, meaning “to flow”) is a second row element of Group 17 in the periodic table. When bound to carbon it forms the strongest bond in organic chemistry to give organofluorine compounds. The scientific field treating them, organofluorine chemistry, started before elemental fluorine itself was isolated. Applying the fruits in academia, industrial organofluorine chemistry has developed over 80 years via dramatic changes during World War II. Nowadays, it provides various materials essential for our society. Recently, it utilizes elemental fluorine itself as a reagent for the introduction of fluorine atoms to organic molecules in leading-edge industries. This paper overviews the historical development of organofluorine chemistry especially from the viewpoint of material industry.

A new route to perfluorinated vinyl ether monomers: synthesis of perfluoro(alkoxyalkanoyl) fluorides from non-fluorinated compounds

Abstract A new synthetic procedure for the preparation of various perfluoro(alkoxyalkanoyl) fluorides, which are precursors to perfluorinated vinyl ether monomers, from non-fluorinated alkoxyalcohols has been developed. Available perfluoro(alkoxyalkanoyl) fluorides such as perfluoro(2-propoxypropionyl) fluoride, so-called HFPO dimer, can be multiplied by the use of the hydrocarbon counterpart alcohols and fluorine gas as raw materials. In the case that the desired perfluoro(alkoxyalkanoyl) fluoride is not readily available, it can be obtained from its hydrocarbon counterpart alcohol and an available perfluoroacyl fluoride.

Pharmacologic profiles of GA0113, a novel quinoline derivative angiotensin II AT1-receptor antagonist.

GA0113 is a newly developed angiotensin II (Ang II) AT1-receptor antagonist having a quinoline moiety. This study was undertaken to clarify the pharmacologic profile of GA0113. In vitro profiles of GA0113 for Ang II receptors were examined in a receptor-binding assay and an Ang II-induced vasoconstriction study. Antihypertensive effects after single or repeated oral administrations were examined in conscious renal hypertensive (RH) or spontaneous hypertensive (SH) rats. Blood pressure (BP) and heart rate were measured by the tail-cuff method. GA0113 interacted with AT1 receptors in a competitive manner, but showed an insurmountable antagonistic action in Ang II-induced vasoconstriction. In RH rats, GA0113 (0.01-1 mg/kg) reduced BP with ED25 values of 0.015 mg/kg, and required 0.1 mg/kg for 24-h BP control. Repeated administration of GA0113 in SH rats (0.03-0.1 mg/kg) showed moderate onset and gradually potentiated reduction of BP, which reached a plateau after day 4 of treatment without alteration in heart rate. There was no tolerance of the hypotensive action or rebound phenomenon after cessation of the treatment. In pharmacokinetic studies, GA0113 shows excellent oral bioavailability (94%) and a long circulating half-life (12 h) in rats. These findings indicate that GA013 may serve as a highly potent and effective antihypertensive agent in humans. GA0113, with its unique chemical structure and pharmacologic and pharmacokinetic profiles may provide new possibilities in hypertension therapy.

A New Route to Perfluoro(Propyl Vinyl Ether) Monomer: Synthesis of Perfluoro(2-propoxypropionyl) Fluoride from Non-Fluorinated Compounds

Perfluoro(2-propoxypropionyl) fluoride (1a), which is the precursor of the perfluorinated propyl vinyl ether (PPVE) monomer of an industrially important perfluoroalkoxy copolymer (PFA), was synthesized by utilizing direct fluorination of the non-fluorinated counterpart for the first time. The partially-fluorinated ester 7 synthesized from the desired perfluorinated acid fluoride 1a itself and the non-fluorinated alcohol 5, which has a carbon skeleton corresponding to the desired compound 1a, was perfluorinated by liquid-phase direct fluorination with elemental fluorine. Degradation of the resulting perfluorinated ester 8 gave 2 mols of the desired acid fluoride 1a. In a sense, this process can be called self-multiplication of a perfluorinated acid fluoride from a non-fluorinated alcohol.

The modeling of immersion liquid by using quantum chemical calculation

For realizing next generation 193nm immersion lithography, developing suitable high refractive index liquid is an very important issue. To overcome the trade off relationship between high refractive index (optimally more than 1.6 ) and low absorbance (similar degree with H2O 0.0036cm-1), the molecular modeling based on quantum chemical ab-initio calculation was performed. We have successfully developed the predictive method of frequency-dependent refractive index for liquid and its absorbance. Then, we tried to estimate these properties to search for optimal candidates. In this paper, we report on the estimated results of the refractive index n and the absorbance at 193nm for some candidate compounds. We believe we could demonstrate the usefulness of the predictive method by using the quantum chemical calculation for developing new liquids, even if there were some degree of errors in the absolute values. We have found the -SO2- (like sulfone, sulfonate, sulfate) containing five- and six-membered ring compounds such as sulfolane and sultone etc. would achieve both high refractive index around 1.6 and relatively low absorbance. XeF4O and Bi(CF3)3 ,unfortunately, had absorption at 193nm due to the weak binding outer valence electrons. In the case of alkyl Si and Ge, Si(CH2CH3)4 might have a good balance of refractive index 1.59 and relatively low absorbance. Si(CH3)3CH2CH2OH and Ge(CH2CH3)4 were estimated to have refractive index of over 1.6, but have been estimated these might have sightly stronger absorption.