For a long time, fluorine has been used in medicinal chemistry to optimise pharmaceutical drug properties. There have been many studies on the effect of fluorine on lipophilicity and it is known that fluorination will decrease the lipophilicity. However, there has been less research on the effect of other substituents on the lipophilicity of fluorinated aromatic compounds. This research aims to investigate the effect of replacing a methyl group with monofluorinated, difluorinated and trifluorinated groups and the effect of substitution of electron withdrawing and electron donating groups on the measured lipophilicity.
Two aromatic compounds containing a CFH2 group were synthesised, one having a nitro group and the other having a methoxy group in the para position. One aromatic compound containing a CF2H group with a para substituted methoxy group was also synthesised. These were all synthesised by deoxofluorination using Deoxofluor.
1HNMR, 19FNMR and 13CNMR spectroscopy were used to analyse the synthesised products and it was concluded that the desired products had been successfully synthesised.
The retention times of the products and seven standard compounds with known log P values were measured by HPLC. This data was used to estimate the log P values for the three products. The lipophilicity data for the monofluorinated compounds showed a decrease in log P for the compound with a methoxy group compared to the compound with the nitro group. The data showed an overall trend of the trifluorinated and non-fluorinated compounds having increased lipophilicity compared to the difluorinated and monofluorinated compounds for both the nitro and methoxy compounds. The data suggested that electron donating groups increase the lipophilicity of the monofluorinated compound compared to the difluorinated compound and electron withdrawing groups decrease the log P of the monofluorinated compound compared to the difluorinated compound.
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