2-Methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]benzenamine

Add 107.1 g of o-methylaniline to1000ml pressure reactor, Add 300 ml of water and 300 ml of methyl tert-butyl ether.Then initiator  sodium dithionite was added, and a catalytic amount of tetrabutylammonium sulfate and equimolar sodium carbonate was added., The system slowly warmed to 50 ° C with stirring.Then, an equimolar amount of 2-bromoheptafluoropropane was introduced into the pressure-resistant reactor, and it was completed in about 2 hours.The reaction is continued in the heat preservation, and is followed by a liquid chromatograph. After the conversion of the raw materials is completed, the reaction system is cooled.The reaction pressure is reduced to normal pressure, the organic phase is separated, the organic phase is washed with water, diluted with hydrochloric acid, and dried.Evaporating the organic solvent to obtain 95percent of the intermediate 2-methyl-4-heptafluoroisopropylaniline (B-1).No purification is required for the next reaction.Add to the closed reactor200 ml of water and 200 ml of methyl t-butyl ether, A further 10 g of o-methylaniline (93 mmol)31 g of heptafluoroisopropyl bromide (125 mmol, 1.3 equivalents)23 g sodium hydrosulfite (125mmol, 1.3 equiv.), 11 g of sodium bicarbonate (130 mmol, 1.4 equiv) And 4 g of tetrabutylammonium hydrogen sulfate (12 mmol, 0.13 equiv)The resulting mixture was stirred at room temperature for 2 hours.Separate the organic layer, The aqueous layer was extracted with 200 ml of ethyl acetate, The extract was combined with the organic layer, And thus with 2N hydrochloric acid aqueous solution, 5percent sodium carbonate and saturated sodium chloride solution, The organic layer was dried over sodium sulfate, After filtration, the organic solvent was distilled off under reduced pressure to obtain 25 g of a pale yellow liquid in 97percent yield.The product was subjected to gas phase analysis of the organic layer prior to acid treatment, The results are as follows:O-methyl aniline 0.5percent;2-methyl-4-heptafluoroisopropylaniline 94.5percent;2-methyl-6-heptafluoroisopropylaniline 1.1percent;2-methyl-4-hexafluoroisopropylaniline 3.2percent.Distillation under reduced pressure gave 23 g of product in 90percent yield. Summary:Other by-products (2-methyl-4-hexafluoroisopropylaniline) mentioned in the patent CN 102731317A, With a content of 1.9percent (3.2percent in our repeat test).And we test, through the catalyst control, Its content <0.1percent.The patent gives the crude yield, After distillation, The actual yield is 90percent.From the above can be seen:Our catalyst can effectively control the formation of impurities, At the same time can effectively improve the yield.First 324.96 g (1.87 mol) of sodium dithionite and then 100 g (0.93 mol) of otoluidine (2-methylaniline) were added at room temperature to a mixture of 1200 ml of water, 250 ml of tert-butyl methyl ether, 156.79 g (1.87 mol) of sodiumhydrogen carbonate and 22.18 g of tetra-n-butylammonium hydrogensulphate. Subsequently, a solution of 489.06 g of 2-bromo-1, 1, 1, 2, 3, 3, 3-heptafluoropropane in 200 ml of tert-butyl methyl ether was added dropwise and, on completion of addition, the mixture was stirred at 30° C. overnight. If necessary, sodium carbonate was used to adjust to a pH of 5 and the organic phase was removed, dried and concentrated. [0137] In this way, 250 g (90percent of theory) of the product having a purity of 93percent were obtained.A toluidine (0.717g), NaToluidine (0.717 g), Na 2 S 2 O 4 (1.75 g), NaHCO 3 (0.84 g) and DMSO (7 ml) were charged in a stainless steel autoclave having an internal volume of 30 ml. The lid of the autoclave was closed, 0.5 MPa airtight with N 2, and no leakage was confirmed. After confirmation, depressurization, connecting Rf-Br cylinder and reaction apparatus, 2 g of Rf-Br was charged. The temperature was adjusted so that the internal temperature was 70 ° C., and the mixture was stirred for 4 h. After stirring for 4 h, by-product CO 2 was purged and the autoclave was opened. AcOEt (30 ml) was introduced and stirred for 15 min to precipitate salt. The precipitated salt was filtered under reduced pressure, and AcOEt was distilled off the filtrate by an evaporator. Thereafter, 0.2 g of K 2 CO 3 was added, and DMSO was distilled off at 80 ° C./10 mmHg. AcOEt (30 ml) and H 2 O (30 ml) were introduced, stirred for 30 min, and separated into two layers. After removal of the aqueous layer, the mixture was washed with 5percent aqueous hydrochloric acid (30 ml) and separated into two layers. After further removing the aqueous layer, it was washed with water (30 ml), after separating the two layers, the aqueous layer was removed. AcOEt was distilled off from the obtained organic layer, and then the desired product (RFA) was subjected to simple distillation (100 ° C./10 mm Hg). The yield was 1.36 g and the isolated yield was 75percent.method 1:107.1 g of o-methylaniline was added to a 1000 ml three-necked flask.Add 300 ml of water and 300 ml of methyl tert-butyl ether.Then initiator  sodium dithionite was added, and a catalytic amount of tetrabutylammonium sulfate and equimolar sodium carbonate was added., The system was slowly heated to 50 ° C under stirring, and then an equimolar amount of 2-iodoheptafluoropropane was added dropwise, and the addition was completed in about 1 h.The system was traced by liquid chromatograph, and the reaction was completed after 3 hours. The system was allowed to stand for stratification.The organic phase is washed with dilute hydrochloric acid, The organic phase is dried over anhydrous sodium sulfate.The solvent was evaporated to give 97percent of the intermediate 2-methyl-4-heptafluoroisopropylaniline (B-1).No purification is required for the next reaction.A three-necked flask was charged with 10 g of o-methylaniline (93 mmol) and 200 ml of water and stirred. (11.5 g) of sodium carbonate (111 mmol, 1.2 equivalents), 3.15 g of tetrabutylammonium bisulfate (9.3 mmol, 0.1 equivalents), 2.5 g of p-nitrotoluene (18.6 mmol, 0.2 equivalents) and heptafluoroisopropyl bromide (10 mmol) and 200 ml of methyl tert-butyl ether were pre-stored at 0 ° C. After stirring for 2 minutes, 17.5 g of a suspension (111 mmol, 1.2 equivalent). React overnight. The organic phase was separated and the aqueous layer was extracted with 20 ml of methyl tert-butyl ether and the organic layers were combined. Followed by washing with 5percent sodium carbonate. The organic phase was dried over anhydrous sodium sulfate, filtered and the organic solvent was evaporated to give 30 g of crude product, the crude yield was & gt; 100percent. Distillation under reduced pressure gave 25.1 g of product in 96.5percent yield. The results were as follows: o-methylaniline 0.9percent; 2-methyl-4-heptafluoroisopropylaniline 98.1percent; 2-methyl-6-hexafluoroisopropylaniline 0.8percent; 2- Methyl-4-hexafluoroisopropylaniline 0.1percent.A three-necked flask was charged with 10 g of o-methylaniline (93 mmol) and 200 ml of water, Stir. 11.8 g of sodium carbonate (111 mmol, 1.2 equivalents) was added successively, 3.15 g of tetrabutylammonium bisulfate (9.3 mmol, 0.1 equiv)2.5 g p-nitrotoluene (18.6 mmol, 0.2 equiv)withHeptafluoroisopropylchloromethyl tert-butyl ether solution[Containing 20.8 g of heptafluoroisopropyl chloride (102 mmol, 1.1 equivalents) and 200 ml of methyl tert-butyl ether, Pre-stored at 0 ° C]After stirring for 2 minutes, 17.5 g of the insured powder (111 mmol, 1.2 equiv) was added.React overnight. The organic phase is separated, The aqueous layer was extracted with 20 ml of methyl t-butyl ether, Combine the organic layer.Followed by washing with 5percent sodium carbonate.The organic phase was dried over anhydrous sodium sulfate, Filtration and evaporation of the organic solvent gave 30 g of crude product, Crude yield> 100percent.Distillation under reduced pressure to give 25.1 g of product, Yield 96.5percent. The product is analyzed by gas phase, The results are as follows:O-methylaniline 0.8percent;2-methyl-4-heptafluoroisopropylaniline 98.2percent;2-methyl-6-heptafluoroisopropylaniline 0.8percent;2-methyl-4-hexafluoroisopropylaniline 0.1percent.(12-2). (12-2). Example 27 To a three-necked reaction flask equipped with a thermometer and a dropping funnel, 100.0 g (0.25 mol) of 3-iodo-N-(1, 1-dimethyl-2-methylthioethyl)-o-carbamoylbenzoic acid was added. 800g of dichloromethane, then add In a 100 mL three-necked flask, the reaction product of the previous step and trifluoroacetic anhydride (6.3 g, 30 mmol) were dissolved in 50 mL of dry toluene, and the mixture was stirred at room temperature (25 ° C) for 3 hours, and then stirred and dissolved. Add 40 mL of dichloromethane to the residue, Then

Molecular Weight:275.17
XLogP3:3.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:8
Rotatable Bond Count:1
Exact Mass:275.05449639
Monoisotopic Mass:275.05449639
Topological Polar Surface Area:26
Heavy Atom Count:18
Complexity:282
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes