Chemical Properties
colorless to light yellow liqui
Uses
2,4-Difluorotoluene was used in the synthesis of new hydrophobic isosteres of pyrimidines and purine nucleosides.
General Description
2,4-Difluorotoluene was synthesized as a nucleotide analog and was incorporated into DNA and undergoes replication by DNA polymerase enzymes.
Synthesis
The general procedure for the synthesis of p-fluorotoluene, 2-fluorotoluene, 3-fluorotoluene, 2,4-difluorotoluene, 2,5-difluorotoluene, and 1,2-difluoro-4-methylbenzene from toluene is as follows: to a glass reactor fitted with a PTFE-lined magnetic stirring bar attached to a gas scrubbing flask were added toluene derivative (0.95-1.14 mmol), acetonitrile (1-2.5 mL/mmol of toluene derivative), and boron trifluoride ethyl ether complex (1.3-1.6 mmol/mmol of toluene derivative). mmol toluene derivative), acetonitrile (1-2.5 mL/mmol toluene derivative) and boron trifluoride ethyl ether complex (1.3-1.6 mmol/mmol toluene derivative). The reaction mixture was stirred at -25 °C for 10-15 min, followed by the addition of xenon difluoride (1.2-1.3 mmol/mmol toluene derivative) in batches. The reaction system was slowly warmed to 22 °C over 1 h and stirring was continued for 40-60 min. Upon completion of the reaction, hexafluorobenzene was added as an internal standard and samples were taken for 19F NMR analysis (Method B). The reaction mixture was quenched with saturated aqueous sodium bicarbonate and extracted with dichloromethane (1-2 mL). The combined organic phases were dried with anhydrous magnesium sulfate and subsequently analyzed by 19F NMR and GC/MS (Procedure C). The major products are listed in the table and others are shown below (GC/MS data).
References
[1] Russian Journal of Organic Chemistry, 2016, vol. 52, # 10, p. 1400 - 1407
[2] Zh. Org. Khim., 2016, vol. 52, # 10, p. 1412 - 1419,8
