Difluoromethyl group and

A peculiar dehydrofluorination occurs when tnfluoromethyl dihydropyndine derivatives are treated with organic bases A double-bond shift and a hydrogen migration convert one tnfluoromethyl group to a difluoromethyl group and aromatize the ring [22] (equation 20)... 

The enzyme is irreversibly inhibited by the difluoromethyl analog of androstendione. The mechanism postulated for the inhibition involves oxidation of the difluoromethyl group and subsequent elimination of hydrofluoric acid. The resulting carbonyl fluoride binds covalently to a nucleophilic group of the enzyme, disabling it permanently [80]. 

The difluoromethyl group in chlorofluoroalkanes can be oxidized into a carboxylic group by a mixture of chlorine and dinitrogen tetroxide at high temperatures [2] (equation 1)... 

The monofluoromethylene group and difluoromethyl group m 1H perfluoro-alkanes and -cycloalkanes are oxidized at the C-H bond to perfluoroalkyl and perfluorocycloalkyl fluorosulfates by anodic oxidation m fluorosulfonic acid [J, 4] Two modifications of the method are used ox idation by fluorosulfonyl peroxide generated pnor to the reaction [J] (equation 2A) and direct electrolysis m the acid [i, 4] (equabons 2B and 3)... 

The a-methoxylated products are highly useful building blocks for the construction of a carbon-carbon bond a to the trifluoromethyl and diflu-oromethyl groups, which is difficult to obtain by other methods, as shown in Scheme 6.15. Thus, a-tri and a-difluoromethylated a-aminonitriles, which are precursors to the corresponding fluorinated a-amino acids, have been prepared in good yields, and flourinated homoallyanilines have been also successfully prepared [44]. in addition, tri- and difluoromethylated tetra- and dihydroquinoline derivatives can be prepared by cationic polar cycloaddition in high yields [45]. 

Difluoroacetic acid and its derivatives (esters, aldehyde) are excellent reagents for introducing a difluoromethyl group. However, because they are expensive, they are used relatively infrequently. Their reactivity is close to that of trifluoroacetic derivatives. ... 

When toluene is fluorinated65 over potassium tetrafluorocobaltate(III), the major products at 330-340cC are notable for being unsaturated and for containing a difluoromethyl group they are also similar in type to those produced in the potassium tetrafluorocobaltate(III)/ben-zene reaction. Over cesium tetrafluorocobaltate(III), toluene and -xylene give66 about 25-30 % of aromatic compounds. 

The methylpyridines over cesium tetrafluorocobaltate(III) at 270-340°C also react to give97 significant quantities (10-37% of the product mixtures) of polyfluoropyridines (4-7 compounds, most of which have the ring fully fluorinated with the methyl groups converted into difluoromethyl or trifluoromethyl groups) and perfluoro(alkylpyrrolidines) (23-58%) in overall yields of about 30-35%. 

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. 

A well-established feature of nucleophilic reactions of fluoroalkenes is that attack occurs exclusively at a difluoromethyl group.61 The order of increasing reactivity is F2C = CF2 < F,C = CFCFj < < F2C = C(CF, )2.61 The primary products of base-catalyzed additions of alcohols to fluoroethenes are saturated ethers 87 however, with higher concentrations of base, unsaturated ethers are formed. Tetrafiuoroethene with sodium methoxide yields a product of substitution, trifluoromethoxyethene (4), and the addition product 1,1,2,2-tetrafluoro-l-methoxyethane (5).62... 

The formulas of l-aryl-4-difluoromethyltetrazole-5-thiones 305, whose preparation and properties have been reported, are shown <2004RJ0601>. These compounds are of interest as useful substrates for functionalization (e.g., by replacing the halogen of the difluoromethyl group in the position 4). 

This bibliographical survey shows the wide range of syntheses of the fluorinated difunctional compounds, whatever the position of the fluorinated substituent in the molecule. However, major efforts were developed, for example, to protect a group from hydrolysis in the case of esters protected by gera-trifluoromethyl groups. Actually, because of the electroattractive effects of the difluoromethyl groups in a position about the functions, the fluorinated polyesters and polyurethanes exhibit weak points which affect the applications of such polymers. 

In general, halodifluoromethanes such as dibromodifluoromethane, difluorodiiodomethane and dichlorodifluoromethane are very poor sources of difluorocarbene for the synthesis of cyclo-propanes.10 13 Cyclic systems 5-8 contain a difluoromethyl group which can be added to multiple bonds. 

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