1-Chloro-6,6-dimethyl-2-hepten-4-yne: Uses; Preparation

Fig 1. Chemical structure formula of 1-Chloro-6,6-dimethyl-2-hepten-4-yne

1-Chloro-6,6-dimethyl-2-hepten-4-yne(CAS:NO.287471-30-1) is the allylamine antifungal agents terbinafine intermediate.1-Chloro-6,6-dimethyl-2-hepten-4-yne choose to inhibit COX-fungal squalene, so that reduction of membrane ergosterol, thus inhibiting the growth of fungi play an inhibitory role; right ergosterol synthesis of precursors and no inhibitory effect on other stages.

1-Chloro-6,6-dimethyl-2-hepten-4-yne mainly due to keratin aggregation produce squalene, was squalene cyclooxygenase inhibition, squalene in the cells of a large number gathered in the form of lipid droplets penetrate fungal cell membrane, destruction of the membrane lipid composition, resulting in fungal death. A typical procedure for preparing of 1-chloro-6,6-dimethyl-2-hepten-4-yne using boron trichloride is as follows: Compound 1 (53 g, 0.38 mol) in 2800 mL of n-hexane was cooled to 10～15℃. Boron trichloride (1 M in hexane, 480 mL, 0.48 mol) was added to the mixture at 15～20℃ over a 10 min period. After 10 min of stirring at 20℃, the mixture was quenched with 1000 mL of water and stirred for 10 min. The separated organic phase was washed with 20% NaCl, dried (MgSO4), and evaporated to afford the title compound 2 (57.1 g, 95%) in 9:1 E:Z ratio.

Fig 2. Preparation process of 1-Chloro-6,6-dimethyl-2-hepten-4-yne

In conclusion, a boron trichloride mediated synthesis of 1-chloro-6,6-dimethyl-2-hepten-4-yne from the enyne alcohol 1 has been developed. By judicious choice of the reaction conditions, the chloride can be obtained in excellent stereoselectivity and isolated yield. The obtained E:Zmax (9:1) is the maximum value among those reported[1,2].

References

[1] Stutz, A. Eur. Pat. Appl. 24,587, 1981.
[2] Meki, N.; Nishida, K. U.S. Patent 5,021,446, 1991.