Fluorinated methyl

Annelation of enamines or enolates with fluorinated methyl vinyl ketones gives the corresponding cyclohexenones [116, 117] (equation 101)... 

The 4-triflates 277, 279, and 281 of benzyl 2,3-anhydro-o -D- and -) -L-ri-bopyranosides and -a-D-lyxopyranoside gave, - readily, on reaction with BU4NF [CgHg (24 h) or MeCN (5-8 h), r.t.], the respective 2,3-anhydro-4-deoxy-4-fluoro derivatives 278,280, and 282 in good yields. The conformation ( //s) of the starting compounds remained the same after fluorination. Methyl 2,3-anhydro-4-deoxy-4-fluoro-a-L-lyxopyranoside (284, 86%) was prepared from the 4-triflate 283 by treatment with EtjN- 3HF (CH2CI2-EtjN, 40°, 5 h). 

This indirect proof of the appearance of CF3SF leads to the conclusion that fluorination of sulfenyl chlorides of the series CF Cl3 SCl (n = 0, 1, 2) with alkali metal fluorides follows the mechanism observed in the formation of sulfenyl fluorides the initial chlorine-fluorine exchange at the sulfur atom is followed by isomerization to the sulfenyl chloride containing the corresponding more highly fluorinated methyl group. 

Sevoflurane is a fluorinated methyl isopropyl ether (Figure 3.2). It was first released for clinical use in Japan in 1990 and it is now available in many other countries worldwide. Being relatively insoluble (blood/gas solubility coefficient, 0.68) it has the potential to provide rapid anaesthetic induction and recovery. Unlike isoflurane it is non-irritant to the airway and can be given in high concentrations for anaesthetic induction. Its MAC ranges from 3.3 in infants to 2.5 in older children and 1.8 in adults. 

Desflurane is a fluorinated methyl ethyl ether identical to isoflurane except for the substitution of a chlorine by a fluorine atom (Figure 3.2). It is the least soluble of all the volatile anaesthetics with a similar blood/gas solubility to nitrous oxide (0.42). It is non-flammable under all clinical conditions. The vapour pressure of desflurane approaches 1 atm at 23°C making controlled administration impossible with a conventional vaporiser. A desflurane vaporiser is an electronically controlled pressurised device that delivers an accurately metered dose of vaporised desflurane into a stream of fresh gases passing through it. The MAC of desflurane (6.5% in adults) is the highest of any modern fluorinated agent but in common with these the value decreases in the elderly and in other circumstances (see below). 

Enflurane is a fluorinated methyl ethyl ether and is a structural isomer of isoflurane (Figure 3.2). It was synthesised in 1963 and introduced into clinical practice in 1966 at a time when concern was growing about the hepatotoxicity of halothane. Its main advantage over halothane was its resistance to biotransformation (2.5% compared to some 20%). For that reason it was widely used as an alternative to halothane, particularly for multiple administration. 

When R = Me, first one or two hydrogen atoms of the methyl group are substituted by fluorine. Methyl groups attached to the C = C bond in the cyclohexadiene or cyclohexene are almost unreactive towards vanadium(V) fluoride under the indicated conditions, but at 25 C a mixture of products from C = C bond fluorination and substitution of hydrogen in the methyl group is formed.117... 

Under milder fluorination conditions a range of partially fluorinated methyl-germanium compounds is produced (see Tables Vila and VHb). 

Table 9. ESR Hyperfine Splitting Constants (a) for Methyl. Fluorinated Methyl, and Fluorinated Alkyl Radicals90 9 100...

Table 1. ESR hyperfine splitting constants for fluorinated methyl radicals [4]...

The limited data available for partially fluorinated methyl radicals is consistent with the above data in that CH2F- and CHF2- appear to have reactivities roughly comparable to those of RCH2CHF- and RCH2CF2, respectively. For example, for their additions to pentafluorostyrene in acetonitrile kM (CH2F ) = 3.5 x 105 M1 s 1, and kM (CHF2 )=5.5 x 106 M 1 s 1 [70],... 

The structure and reactivity of perfluoroalkyl radicals is determined by the complex interplay between the strong (7-acceptor effect and the w-donating effect of fluorine. Whereas the methyl radical is planar, fluorinated methyl radicals are pyramidal [9]. The pyramidalization and inversion barriers increase with increasing fluorination [10]. The calculated inversion barriers are 1, 7, and 25 kcal mol for CHjF, CHFj-, and CF,-, respectively [11]. 

By-products. The presence in the products of small quantities of compounds which would arise from combination of free radical intermediates can provide evidence for a free radical process. For example, the explosive reaction of methane with fluorine gives mainly hydrogen fluoride and a mixture of mono-, di-, tri- and tetrafluoromethanes, but small quantities of fluorinated ethanes, including C2F6, are also produced. These two-carbon products cannot be readily explained on the basis of possible molecular reactions (see reaction 6.16), but would arise naturally as combination products of the fluorinated methyl radicals produced in a radical chain reaction sequence (reaction 6.17). 

Fluorinated methyl aryl ethers. The facile rearrangement of oxygenated benzyl derivatives effected by XeFa to give fluorinated methyl ethers, i.e., benzyl alcohols to fluoromethyl aryl ethers and benzaldehydes to difluoromethyl aryl ethers, may involve the formation of fluoroxy intermediates and thence oxaspirobenzenium ions. 

Scheme 2.8 Preparation of fluorinated methyl propyl carbonates...

Sasaki, Y. Satake, H. Tsukimori, N. Nanbu, N. Takehara, M. Ue, M., Physical and electrolytic properties of partially fluorinated methyl propyl carbonate and its application to lithium batteries. Electrochemistry 2010, 78,467 70. 

This rearrangement process often involves hydrogen but species as diverse as fluorine, methyl, ethyl, met-hoxy, and phenyl or hydroxy may be involved, leading to products of enhanced stability. For a rearrangement reaction to produce observable quantities of product, the unfavorable entropy of the reaction must be more than balanced by particularly favorable activation energy. 

In the synthesis of ( )-fluorobotryodiplodin, the thermal rearrangement of vinyl substituted fluorinated methyl ether with the (Z,Z) geometry proceeded in a highly stereoselective manner, giving a ketone with syn geometry in 92% yield (Eq. 3.1.25) [33]. 

C, indicate that the mesomeric effect e.g. MejC- -F Me2C=F ) of the halogens involved decreases in the order F > Cl > Br. All this and related work by Olah s group on fluorinated carbocations has been reviewed, and the results of MO studies of fluorinated methyl, allyl, or trans-2 vinylcyclopropylmethyP cations and radicals have been presented in detail. The electronic structure of difluoromethane and the partial double-bond character of C— F bonds in CHjF, CHjFj, and CHF, have received attention at the hands of MO pundits. 

Anteunis and Dirinck have investigated some fluorinated methyl-1,3-dioxans by n.m.r. techniques. A 4-trifluoromethyl or -difluoromethyl group appears to prefer the axial position, although, possibly for entropy reasons, a 4-fluoromethyl group has an equatorial preference. When the fluorinated methyl is in the 5-position as in 5-difluoromethyl- or 5-fluoro-methyl-5-methyl-l,3-dioxan (7) the polar substituent seems to prefer the equatorial position. ... 

Specifically-fluorinated methyl yft-glycosides of (1- 6)- -D-galacto-oligosaccharides have been synthesized by use of 3-fluoro sugar units... 

R = naphthalene, quinoline, or pyridine, have allowed examination of the inductive effect on electron transfer reactivity. Where the substituent R is methyl or a fluorinated methyl derivative, estimated precursor association constants vary little and thus provide a direct comparison A linear dependence of et on the Taft CT inductive parameter was found for acetato and formato complexes. Although redox potentials for these systems are not readily available, it is thought that they may be correlated with the inductive parameter. Thus —CF3, the most electron-withdrawing of the groups, increases the potential most. 

In attempts to establish information about the relative heats of formation of various fluorinated methyl ions, studies (33,34, 38,39) have been carried out examining the directions of fluoride and hydride transfer reactions between fluoromethyl ions and various fluorinated methanes. Some studies (38,39) have also included ions and molecules containing chlorine atoms. Although the more quantitative aspects of this work will be covered in detail later in our discussion of the thermochemistry of fluorinated ions, it is interesting to examine here the relative Importances of competing reaction channels, shown in Table III. It should be pointed out that at sufficiently high pressures, stabilization of the dimethyl fluoronium Ion intermediates of the reactions is observed ( ). 

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