Kong, Jianshe, Tao Meng, and Jing Su. Organic Process Research & Development 19.6 (2015): 681-683.
A significantly improved synthesis method for 5,8-difluoro-2H-cycloheptene using silicone oil as the reaction solvent is described. The new method eliminates the cumbersome post-treatment and large amounts of waste generated by traditional methods.
Experimental Procedure: Under a nitrogen atmosphere, 710 g of compound 6 (4.22 mol) was dissolved in 7.5 L of silicone oil in a 12 L three-neck flask equipped with a mechanical stirrer. The solution was heated to 195 °C (internal temperature) for 18 hours using a heating mantle. After cooling the crude product, a sample was taken for 1H NMR analysis. The NMR spectrum showed 8% of the starting material. The crude product was then distilled through a 15 cm Vigreux column under 3-4 mmHg pressure into a receiver cooled to room temperature. The first fraction was collected at 75 °C (internal temperature, 115 °C external temperature, 4 mmHg), yielding 61 g of compound 1 (purity 91%, with 9% of the starting material based on 1H NMR). The main fraction of compound 1 was obtained at the same temperature (444 g, purity 94%, with 6% of the starting material). The third and final fraction (40 g of compound 1, purity 97%, with 3% of the starting material) was collected and combined with the main fraction. Except for the first fraction (recovered for the next round of reaction), 484 g of the desired product 1 was obtained as a colorless oily substance, with a yield of 68% and purity of 94%. The silicone oil was filtered through a 1 kg silica gel pad.
Seo, Kwangseok, Minyoung Kim, and Seunghwan Seok. Colloids and Surfaces A: Physicochemical and Engineering Aspects 492 (2016): 110-118.
Seok, Eunjeong, et al. Journal of Alloys and Compounds 969 (2023): 172386.
