Difluoromethoxy group

In fluorinated agrochemicals, the difluoromethoxy group is less commonly encountered than the trifluoromethoxy group. The difluoromethoxy group is readily available from the reaction of a phenoxy group and difluorocarbene, generated from chlorodifluoromethane and a base (Fig. 27) [6,107-109]. 

We have earlier discussed the pyrethroid area of insecticides. A number of ester and non-ester pyrethroid insecticides have incorporated the difluoromethoxy group as a means of widening their biological activity to the control of mites [115], Flucythrinate (Cybolt , Cythrin , Pay-Off ) [116] provides control of a variety of sucking insects, beetles, and lepidoptera in cotton and pome fruits. Later, a close analog, flubrocythrinate, was commercialized [117]. 

In some instances, chlorine is successfully replaced with a difluoromethoxy group while retaining desirable properties. Flucythrinate was introduced after fenvalerate by two different companies the only difference was the replacement of the 4-chloro group of fenvalerate with a difluoromethoxy group in flucythrinate. These two molecules have similar insecticidal properties, and though the chemical groups chlorine and difluoromethoxy are chemically different, their Hammet electronic values a and their hydrophobic parameters n lie relatively close to each other in parameter space (Fig. 29) [118]. 

Compounds carrying a difluoromethoxy group as a substituent play an important role in pharmaceutical chemistry [1] and in liquid crystals for display applications [2], Although most of these substances have an aromatic difluoromethoxy group, aliphatic difluoromethyl ethers also have important applications, e. g. as anesthetics [3]. 

Primisulfuron-methyl (99) [191] is a maize-selective herbicide. Comparison with the unfluorinated triazine counterpart metsulfuron-methyl (94) indicates that crop safety for maize is achieved by replacement of the triazine methoxy (R ) and methyl (R" ) group in ring B with two difluoromethoxy groups (R, R" ). 

Primisulfuron-methyl is a selective herbicide for the control of grasses in maize. Comparison [81] with its unfluorinated triazine counterpart methsulfuron-methyl indicates that crop safety for maize is achieved by the replacanent of the triazine methoxy and methyl substituents with two difluoromethoxy groups. It has been shown that primisulfuron-methyl is deactivated in maize by hydroxylation of the phenyl and pyrimidyl moieties followed by hydrolysis or conjugation [82]. 

The electron-donating group required in position 8 can bear fluorine atoms (difluoromethoxy), such as in caderofloxacin, garefloxacin, and BMS-284756 (Figure 8.18). 

Fig. 29. Comparison of physico-chemical parameters of chlorine and difluoromethoxy chemical groups in fenvalerate and flucythrinate.

Nowadays, fluorine, the most electronegative element, plays a key role in pharmaceutical, agrochanical and material sciences. About 20 % of all pharmaceuticals and about 30 % of agrochanicals imder development or recently introduced on the market contain fluorine. Although mainly single fluorine atoms or a trifluoromethyl group have been introduced in various molecitles, the introduction of (difluoromethoxy)- or (trifluoromethoxy) aryl fragments into CTop production products was also realized [1]. 

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