Difluoromethyl group

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)... 

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)... 

G. Forat, J.-M. Mas, L. Saint-Jalmes (Rhone-Poulenc Chimie). Method for Grafting a Substituted Difluoromethyl Group to a Compound Containing an Electrophilic Group with Microwave Irradiation. PCT International Application WO 5, 609,1998 (FR Application 96/ 9,754, 1 Aug 1996) Chem. Abstr. 1998, 128, 166999u. 

Sulfur tetrafluoride provides an inexpensive method for selectively converting a carbonyl to a difluoromethyl group. However, the reactions involving sulfur tetrafluoride, in general, require pressure equipment constructed of fluorine-resistant material such as Hastelloy-C bombs.8 Phenylsulfur trifluoride may be used to advantage for the same reaction, where small amounts are involved, since the reaction may be run at atmospheric pressure in glass, polyethylene, or metal containers. 

Radical addition of dibromodifluoromethane to alkenes followed by sodium borohydride reduction is a convenient two-step method for the introduction of the difluoromethyl group.5 Either one or both carbon-bromine bonds in the intermediate dibromides may be reduced, depending on the reaction conditions. In the case of acyclic dibromodifluoromethane-alkene adducts, the reduction occurs regioselectively to yield the relatively inaccessible bromodifluoromethyl-substituted alkanes. The latter are potential building blocks for other fluorinated compounds. For example, they may be dehydrohalogenated to 1,1-difluoroalkenes an example of this methodology is illustrated in this synthesis of (3,3-difluoroallyl)trimethylsilane. 

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. ... 

The reactions catalyzed by Lewis acids are conducted for 10-20 hours at — 20 C to give hypochlorites in almost quantitative yield.82 Chlorine monofluoride activated by hydrogen fluoride to enhance its electrophilicity transforms the carbonyl function in esters of carboxylic acids to a difluoromethyl group. The reactions are carried out by passing 2molar equivalents of chlorine monofluoride gas through a solution of the ester in an equal volume of hydrogen fluoride at - 70 to - 30°C.83... 

A shift from allenes to acetylenic products formed from acetylenic alcohols in which trifluoro-methyl groups are replaced by difluoromethyl groups can be explained in terms of lowering the positive character of the terminal acetylenic carbon atom, thus retarding the nucleophilic attack of fluorine at this position.56... 

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. 

Some partially fluorinated tetrazines have been fluorinated28 in the liquid phase, for example, 3,6-bis(l,2,2,2-tetrafluoroethyl)-l,2,4,5-tetrazine (12) gives a number of products, the same product mixture being obtained starting from the compound having an NH-NH rather than an N = N unit. The tetrazine with difluoromethyl groups, instead of 1,2,2,2-tetrafluoroethyl... 

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. 

The synthesis of trifluoromethyl aromatics is also achieved by the fluorination of aromatic tribromoinethyl groups with antimony(III) fluoride, e.g. formation of 12. Similary. aromatic dibromomelhyl groups are converted into the corresponding difluoromethyl group, c. g. formation of 13. in good yield. 

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