Fluoromethyl group

F]Fluoroiodomethane, a valuable synthetic precursor for the introduction of a fluoromethyl group into radiopharmaceuticals, has been prepared from diiodomethane (Scheme 55) [224]. Its reactivity toward amine, acid, thiol or phenolate functions has also been studied. 

These compounds come from methylenation reactions of the corresponding carbonyl derivative by means of an ylide. Several experimental conditions have been described. In most cases, CF2Br2 and HMPT (hexamethyl phosphorotriamide) are employed. The reaction occurs with aldehydes as well as with ketones in the furanose and pyranose series. The reaction can also be performed with lactones the fluoromethyl group is then introduced in the anomeric position. With these substrates, the Julia olefmation, which uses difluoromethyl sulfone, has also been reported to be an efficient method. Some examples of these reactions are shown in Figure 6.24. 

Fluoromethyl ethers may additionally be attacked by a further alkene molecule under the reaction conditions, which then inserts between the C-F bond of the fluoromethyl group. Thus, 1,1-dihaloethene and the hydrogen fluoride/formaldehyde reagent react to form the symmetrical ether 6. 

A neutral diazo compound can be considered as both a nucleophile and an electrophile. Thus, it can be substituted by the combination of an electrophilic moiety and a nucleophilic moiety (X+ Nu ") (Scheme 8). In practice, the diazomethyl group is transformed to the fluoromethyl group by treatment with hydrogen fluoride/pyridine mixture (70 30 w/w) (X = H Nu = F), or to the halofluoromethyl group by addition of A-halosuccinimide in the same medium (X = Cl, Br, I Nu = F), e.g. formation of l.16 The reaction can be performed on secondary diazo alkanes, diazo ketones or diazo esters.16 90 316... 

Elimination of hydrogen fluoride from cyclohexanes 34A and 34B illustrates the balance between electronic and conformational effects. Anti elimination is possible from cyclohexane 34A to give 1//-nonafluorocyclohexene (35), involving removal of fluorine from a fluoromethyl group rather than from a difluoromethyl group. Here electronic and conformational effects are in accord. 

The outside hydrogens in cyclopentanes 14A and 14B are the most acidic, but exclusive inwards anti elimination occurs from cyclopcntane 14A and largely (86%) inwards syn elimination occurs from cyclopentanc 14B, giving cyclopentene 15. This is further indication that the removal of fluorine from a fluoromethyl group is easier than from a difluoromethyl group. 

In various heterocyclic compounds two types of C F bonds are hydrogenolyzed. In fluoromethyl groups, which are attached to the aromatic heterocyclic ring, the C-F bonds arc activated similarly to benzylic C-F bonds, but the degree of activation is influenced by the position relative to the heteroatom the reactivity of aromatic C-F bonds in six-membered heterocyclcs is strongly influenced by their positions relative to the heteroatom(s). 

Ab initio and semiempirical studies on the transition structure of the Baeyer-Villiger rearrangement of acetone with performic acid have been undertaken,510 and a theoretical investigation has been made511 of the mechanism of the Baeyer-Villiger reaction in non-polar solvents. The effect of fluoromethyl groups on the Baeyer-... 

The electrochemical oxidations of several fluorinated amines have been investigated with a view to synthesizing fluoroorganic compounds [272]. Substitution of the hydrogen on the carbon of amines by chloromethyl and fluoromethyl groups slightly increases their oxidation potential [273]. Anodie oxidation of fluoromethyl... 

The dehydration procedure of this preparation is stated to be imsatisfactory for substituted phenylmethylcarbinols which have a strongly electronegative group, such as the nitro or tri-fluoromethyl group, in the tmta position. 

Fig. 3-28 Orbital interactions between a filled p-orbital and the filled 7t-orbitals of a fluoromethyl group...

For halothane (CFj—CHClBr), the C—Cl and C—Br vibrations are hardly affected by pyridine at room temperature. In accordance with the results of our low temperature study the C—H bond becomes more acidic and the C—Cl and C—Br bonds less associable because of the presence of the fluoromethyl group. 

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