2-Chloro-5-(trifluoroMethoxy)nitrobenzene

Synthesis, separation and purification of 1-chloro-2-nitro-4-trifluoromethoxybenzene:3-Nitro-4-chloro-phenyldiazonium tetrafluoroborate (1 mmol, 1.0 eq) was added to a 50 mL round bottom flask under N2.After sealing with a rubber stopper, 4 ml of deaerated anhydrous acetonitrile was added to the round bottom flask with a syringe, and the reaction flask was stirred under a dry ice bath at -40 C.Then 0.5 M of AgOCF3 acetonitrile solution (6 ml, 3 mmol, 3.0 eq) was added to the reaction flask with a syringe.The reaction was continued at -40 C for 2 hours, and then naturally warmed to room temperature for 13 hours.After completion of the reaction, the reaction solution was extracted twice with 20 ml of dichloromethane, and then the obtained organic phase was dried over anhydrous sodium sulfate.Filtration and rotary distillation under reduced pressure gave a crude product with a small solvent.The crude product is then separated on a silica gel column using a mixture of low boiling petroleum ether: dichloromethane = 50:1.The final product was obtained: 1-benzyloxy-3-trifluoromethoxybenzene as a colorless oily liquid, yield 41%.EXAMPLE 3 2-[[4-[4-(trifluoromethoxy)-2-nitrophenoxy]phenoxy]]propanoic acid, methyl ester To a mixture of 10.01 g. of 4-(benzyloxy)phenol and 3.51 g. (0.05 mole) of potassium methoxide in 75 ml. of DMF is added 12.08 g. (0.05 mole) of 1. Synthesis of 4-chloro-2(-3)-nitrotrifluoro-methoxybenzene 1207.0 g of 4-chlorotrifluoromethoxybenzene are added over one hour to a stock of 1640 g of 96.8%-sulphuric acid and 680.4 g of 100% nitric acid, preheated to 40 C. The reaction mass is then heated to 50 C. and maintained at this temperature for four hours. After stopping the stirring, the upper organic phase is decanted off at 40 C. and then poured into 638.2 g of 18.2% caustic soda. After a further decantation, the organic phase is washed with 250 ml of water. The crude reaction mass contains a 50/50 mixture of 4-chloro-2-nitrotrifluoromethoxybenzene and Further, synthesis of the halogenated alkoxy substituents can be performed using by starting with commercially available l-chloro-4-fluoromethoxybenzene. This on nitration with HNO3 and H2SO4 at 500C about 3 h. The yield (2 isomers) obtained in 98% (scheme-1). 2-Chloro-4-trifluoromethoxy nitrobenzene is readily synthesized according to the following scheme from Michel Dury, U.S. Patent 6, 121, 492, which is incorporated by reference.A. 4-Chloro-2-nitro-1 -trifluoromethoxy-benzene and 1 -Chloro-2-nitro-4- trifluoronnethoxy-benzeneTo a mixture of i-chloro-4-trifluoromethoxy-benzene (9.24 g, 47 mol) in cone. H2SO4 (30 ml_) at 00C is added cone. HNO3 (10 ml_) dropwise over a 5 min period. After the mixture is stirred at 0 0C for 1 h, it was poured into ice. More H2O is added, and the resulting mixture is extracted with EtOAc. The organic extract is washed with H2O (3X) and brine, dried over MgSO4, filtered, and concentrated in vacuo to yield 10.87 g (95%) of the product as a mixture of 1 -chloro-2-nitro-4-trifluoromethoxy-benzene and 4-chloro-2-nitro-1-trifluoromethoxy-benzene (-50/50, based upon 19F NMR). 1H NMR (CDCI3): delta 8.05-7.95 and 7.85-7.70 (m, 1 H), 7.70-7.55 and 7.50-7.35 (m, 2H); 19 F NMR (CDCI3) delta -57.32 and -57.84 (s, 3F), -109.07 and -117.90 (t, J = 6.2Hz and d, J = 6.2 Hz, 1 F).

Molecular Weight:241.55
XLogP3:3.5
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:1
Exact Mass:240.9753551
Monoisotopic Mass:240.9753551
Topological Polar Surface Area:55
Heavy Atom Count:15
Complexity:243
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes