Synthesis
The general procedure for the synthesis of 3,5-dimethylfluorobenzene from 1-amino-3,5-xylene is as follows:
1. Continuous diazotization step:
- Preparatory material A: 1-amino-3,5-xylene (100 mmol), fluoboric acid (120 mmol) and hydrochloric acid (180 mmol) were dissolved in 50 mL of water.
- Prepare Material B: Dissolve sodium nitrite (105 mmol) in 50 mL of water.
- Material A and Material B were each pumped through a T-fitting into a reaction tube at a flow rate of 4 mL/min at 25 °C. The mixture flowed through the outlet and was collected in a cooling vessel. Vigorous stirring was maintained.
- The reaction mixture was cooled to -5 °C and the solid was collected by filtration. The solid was washed with methanol and subsequently dried under vacuum to give diazonium tetrafluoroborate.
2. Continuous fluorination step:
- The diazonium tetrafluoroborate prepared above was suspended in 300 mL of co-solvent and introduced continuously into the reaction tube at a flow rate of 4 mL/min.
- The reaction was maintained at the set temperature for 1 min, followed by cooling in the tandem tube.
- The reaction solution was collected and washed with aqueous NaOH and water to give an almost colorless liquid of 3,5-dimethylfluorobenzene.
References
[1] Tetrahedron Letters, 2013, vol. 54, # 10, p. 1261 - 1263
[2] Chemistry - A European Journal, 2008, vol. 14, # 18, p. 5465 - 5481
[3] Journal of the American Chemical Society, 1994, vol. 116, # 4, p. 1324 - 1336
[4] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1986, p. 169 - 174
[5] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1984, # 3, p. 529 - 532
