General anesthetics. 1. Halogenated methyl ethyl ethers as anesthetic agents

Insertion reactions of difluorocarbene generated by pyrolysis of hexafluoropropene oxide to OH bond

“…The fluorinated ether (3) was obtained in about 40 % yield by the reaction with 1a or 1b ( Table 2, entries 1 and 2). However, the reaction with 1c, 1d or 1e afforded only a small amount of the corresponding ether, but a large amount of 4 ( Table 2, entries [3][4][5]. The reaction with the other alcohols or phenols (1f-1k) gave a complex mixture of products without product 3 ( Table 2, entries 6-11).…”

“…ROCHF 2 -type fluorinated ethers have been prepared by the insertion reaction of difluorocarbene to O-H bond of alcohol. In general, CHClF 2 (HCFC-22) was employed as a carbene source [3].…”

Reactions of aliphatic fluoro-alcohols with CHClF2 at atmospheric pressure

“…ROCHF 2 -type fluorinated ethers are usually synthesized by the insertion of difluorocarbene to O-H bond of alcohol. In this reaction, chlorodifluoromethane (CHClF 2 ) [3,4], dibromodifluoromethane (CF 2 Br 2 ) [5], sodium trifluoroacetate (CF 3 COONa) [6], fluorosulfonyldifluoroacetic acid (FO 2 SCF 2-COOH) [7] and hexafluoropropylene oxide [8] could be employed as a difluorocarbene source. CHClF 2 is one of the most convenient and inexpensive difluorocarbene sources, because it is commercially available as an alternative refrigerant R-22.…”

Inhalational Anesthetics Stereochemistry: Optical Resolution of Halothane, Enflurane, and Isoflurane

“…By 1930, it was understood that anesthetics with the desired characteristics of noncombustibility, volatility, potency, low toxicity, and stability would likely be organic fluorides (2). This realization led eventually to the synthesis of halothane (I) in 1951 (3), enflurane (II) in 1963 (4), and isoflurane (III) in 1965 (4). Together with the weaker agent nitrous oxide, these three compounds are the most important agents in use today (5) Although the physiological effects of these drugs have been studied in detail, the definition of a molecular mechanism for general anesthesia has remained an elusive goal (6).…”

“…The apoAI gene is expressed primarily in liver and intestine (3) and is regulated by diet (4,5), estrogen (5,6), thyroid hormone (7), and temporal factors during development (3,5). The -222 to -110 DNA region upstream of the human apoAI gene functions as a liver-specific transcriptional enhancer (8).…”