4-broMo-3-(difluoroMethyl)-1-Methyl-1H-pyrazole

1.3 Preparation of 4-bromo-3-difluoromethyl-1-methylpyrazole1.3.a) Halogenation with BromineAt 25° C., bromine (Br1.7 g (30 mmol) iron powder was added to 6.1 g (57 mmol) of the compound of formula VII in a 250ml 3-necked round bottom flask fitted with condenser (which was vented to a caustic scrubber system), thermometer and syringe pump feed. The first charge of carbon tetrachloride (25ml) was made to the flask and the flask contents agitated. Bromine (6.8g) was dissolved in furhter carbon tetrachloride (35ml). Coolant was applied to the condenser, and the bromine solution was fed to the reactor over 1 hr. During the addition the temperature of the reaction rose to ~29°C. GC analysis showed that the reaction was incomplete. A second charge of bromine (8.6g) in carbon tetrachloride (25ml) was then made to the reactor over a further 1 hr and the reaction mass was allowed to stand overnight. GC analysis showed that the reaction wasn't complete but additional impurities were forming at significant levels. The reaction mass was therefore quenched by treating with sodium bisulphite solution (100ml) - a small exotherm occurred to 26°C and the system was decolourised. The two phases were separated and the organic phase was then washed with further sodium bisulphite solution (50ml). The organic phase was separated from the aqueous phase and dried over magnesium sulphate. The solvent was removed by distillation to give an orange oil (7.5gm ~77percent yield on actual weight and GC areapercent strength). The oil was distilled on a kugelrohr short path distillation system at 50 to 96°C (9 to 6 mbar). The compound of formula VI was obtained in the form of a yellow oil over 88 to 96°C (7mbar). The main fraction from the distillation was 5.97g (80percent recovery or 62percent through yield). Crude and distilled products were analysed by GC, GCMS and NMR (27. Selective bromination of 3-difluoromethyl-N-methylpyrazole over 5-difluoro-methyl-N-methylpyrazoleAt a temperature of 25° C., bromine (3.2 g, about 1 eq.) is added dropwise to a solution of an isomer mixture of 3-difluoromethyl-N-methylpyrazole and 5-difluoromethyl-N-methylpyrazole (2.8 g; ratio according to GC analysis: 10:1) in methylene chloride (20 ml). The reaction mixture is stirred at 25° C. for a total of 5 h. According to GC analysis, 67percent of the 3-difluoromethyl-N-methylpyrazole had been converted, whereas most of the 5-difluoromethyl-N-methylpyrazole was present in unreacted form in the reaction mixture. After further addition of bromine (1.6 g, about 0.5 eq.), the reaction mixture was stirred at 25° C. for a further 22 h. According to GC analysis, 96percent of the 3-difluoromethyl-N-methylpyrazole had been converted, whereas most of the 5-difluoromethyl-N-methylpyrazole was present in unreacted form in the reaction mixture. The reaction mixture was diluted with methylene chloride (20 ml) and washed with an aqueous solution of sodium thiosulfate (0.1 M, 70 ml). The organic phase thus obtained contained, in addition to 4-bromo-3-difluoromethyl-N-methylpyrazole, the unreacted 5-difluoromethyl-N-methylpyrazole. The 4-bromo-3-difluoromethyl-N-methylpyrazole was isolated in high purity by fractional distillation.

Molecular Weight:211.01
XLogP3:1.6
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:209.96042
Monoisotopic Mass:209.96042
Topological Polar Surface Area:17.8
Heavy Atom Count:10
Complexity:122
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes