Bromodifluoromethyl groups

The conversion of the bromodifluoromethyl group to a trifluoromethyl group is only possible after cleavage of one ester group. The direct SN2 displacement of bromide ion by fluoride ion is prevented by electronic and steric factors. 

Hydroxy group of 8-hyd oxy-2-cycloalkyl-2,3,4,6,ll,lla-hexahydro-l//-pyrazino[l,2-i]isoquinoline-l,4-diones was alkylated with allyl bromide, 2-(bromodifluoromethyl)pyridines, l-(bromodifluoromethyl)- and l-(bro-momethyl)benzenes, halomethyl derivatives of different heterocycles (pyridine, pyrazine, pyrazole, pyrrole, thiazole, thiophene) in the presence of CS2CO3 or K2CO3 (98MIP7). Hydroxy group of 8-hydroxy-2-cyclopentyl-... 

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. 

Bromine trifluoride, neat or dissolved in liquid bromine, has found application for the selective substitution of fluorine for bromine (Table 3).108,109 The reactions are carried out at temperatures of no more than 60 C. Under these conditions no hydrogen substitution is observed. As established for bromofluoroethanes. the relative ease of replacement of bromine in various groups decreases in the order tribromomethyl > dibromofluoromethyl > dibromomethyl > bromofluoromethyl > bromomethyl. The presence of fluorine at either the same or an adjacent carbon tends to retard the substitution. Bromine trifluoride is more effeetive than antimony fluorides as it replaces bromine in bromodifluoromethyl and bromomethyl groups. 

The reaction of 5-bromo-2-furoic acid with the sulfur tetrafluoridc/hydrogen fluoride system proceeds under mild conditions and results not only in conversion of the carboxylic acid group but also in addition of two fluorines and replacement or migration of bromine a 1 3.5 mixture of 2,2,5-trifluoro-5-(trifluoromethyl)-2.5-dihydrofuran (10) and 2-(bromodifluoromethyl)-2,5.5-trifluoro-2,5-dihydrofuran (11) is obtained.153... 

Decarboxylation of (bromodifluoromethyl)malonates (9) reminiscent of Krapcho s deal-koxycarbonylation process, is observed on treatment with potassium fluoride in dimethyl sulfoxide at 170 °C to give 2-(trifluoromethyl)-substituted esters 10.43 The precursors are prepared by reacting diethyl malonates 8 with dibromodifluoromethane in the presence of sodium hydride. The exchange of bromine for fluorine in 9 followed by decarboxylation is an excellent method of introducing a trifluoromethyl group a- to an ester group. 

Similarly, trihalo-substituted methyl groups, e. g. bromodifluoromethyl, can be converted into the corresponding nitriles.50... 

Compounds with Two Different Heteroatom Groups Attached to CF2 Including Chloro- and Bromodifluoromethyl Ethers... 

Interestingly, the bromomethyl group and not the bromodifluoromethyl moiety of the allylic compound 6 reacts when treated with triethyl phosphite. Obviously steric factors play an important part in this reaction. 

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