| 95% |
|
1) in a clean 3000L reactor (prior to 2000 kg of water for cooking clean and dry) into the nitrosyl sulfuric acid 950kg, open the stirring, open jacket frozen saline down to 5 ~ 10 , slowly from the aniline tank A mixture of 650 kg of 2,6-dichloro-4-trifluoromethylaniline and 500 kg of acetic acid was added dropwise (previously mixed and sampled in another reaction to analyze the analytical content), and the dropping time was about 8 hours , Evenly dropping, about 200Kg per hour control, after the drop, the temperature to 50 , at this temperature for 3 hours, the diazonium liquid;2) in a clean 6300L reactor (plus 3000kg of water for cooking and cleaning)Adding 2500 kg of water and 535 kg of ethyl 2,3-dicyanopropionate,The temperature of the reaction kettle is not more than 15 C, the dropping time is controlled for about 3 hours, and after the dropwise addition is carried out at 10 to 10 C, the temperature of the reaction vessel is reduced to 10 C, 20 between the insulation reaction after 5 hours, add water 1000kg, temperature to 25 ~ 30 , holding 12 hours, the reaction completely static stratification;3) water each time chlorinated benzene 1000kg extraction twice, the material layer all into the ammoniated kettle;4) in a clean 5000L ammoniated kettle (in advance add 3000kg of water for cooking clean), add to step 2) the wasteThe raw material layer of the step 2) and the step (3) of the obtained chlorinated benzene extract were added to the ammoniation kettle and stirred for 15 minutes to measure the pH value to pH Value ? 9 (if the pH value is less than 9 plus soda ash adjustment until the pH ? 9), continue to cool and stir;5) Control 20 below the drop of ammonia 925kg, drop to 15 ~ 20 in the incubation reaction 3 hours, 20 ~ 30 after 8 hours of thermal reaction after standing stratification, stratified alkaline water applied to step 4 ) (The upper layer of waste water, also known as the application of alkaline water layer, the material layer in the bottom);6) the material layer of water 3000kg washed 2 times, each washing and stirring for 30 minutes after standing 60 minutes stratification, the last one washedAfter the end of the measured layer of pH should be neutral, or to continue to wash to pH to neutral;7) After the last time after washing water, the water will be separated after the liquid into the crystallization kettle, open the mixing, open jacket frozenSalt water down to 20 when centrifugal, rejection material, dried finished products.The synthesis route is simple, the synthesis device is simple (several reactors can be completed synthesis), the synthesis of the originalMaterials and synthetic technology on the environment-friendly, low cost of synthesis, is conducive to enhancing the economic efficiency of enterprises,The resulting 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl)The yield of pyrazole was 95%Purity of 99%. |
| 90% |
|
Experiment 1: (0049) Process of preparation of 5-amino-3-cyano-l-(2,6-dichloro-4-trifluoromethyl phenyl)pyrazole in accordance with present disclosure: (0050) A 4-Neck 2.0 liter capacity glass reactor with an overhead stirrer system was set for the reaction. 150 ml of toluene was added to the reactor. 0.5 gm of sucrose polystearate (SP-20) & 230 gm of 2,6-dichloro-4-trifluoromethylaniline was added to the reactor under stirring. (0051) To this solution, 600 ml 13.9 N spent acid solution having 3.9N sulfuric acid and 10 N HC1 was gradually added over 30 minutes at 30 C to 40 C. The reaction mixture comprised a mixture of 2,6-dichloro-4- trifluoromethylaniline salts, which was stirred for 1 hour at 30 to 40C and then cooled to 15 C to 20 C. (0052) 75.9 gm sodium nitrite was dissolved in 100 ml 0 to get sodium nitrite solution. This sodium nitrite solution was added into the reaction mixture comprising a mixture of 2,6- dichloro-4-trifluoromethylaniline salts, over a period of 3 hours at 15 C to 20 C. The reaction mixture containing diazotized salt was stirred for 1 hour at 15 C to 20 C. After 1 hour, the reaction mixture was poured into 1200 gm chilled ice water while controlling temperature below 20 C. (0053) To this diluted diazo mass at 10 C to 15C, 152 gm of 2,3-dicyanopropionic acid ethyl ester was added with stirring over 30 minutes by maintaining the temperature at 10 C to 15 C. Stirring was continued for 12 hours at 15 C to 25 C to get a biphasic system containing coupled product. After 12 hours, stirring of the reaction mixture was stopped. The organic layer was separated as coupled product and the aqueous layer was extracted with 100 ml toluene. The extracted toluene layer was mixed with the organic layer comprising the cyclized product. The coupled product solution was added into 1000 ml, 2 N sodium hydroxide solutions at temperature 5 C to 25 C and stirred for 4 hours at 20 C to 25 C. The organic phase after addition of sodium hydroxide was further heated to 40 C to 42 C and equilibrated for 1 hour. (0054) The precipitated product slurry was cooled back to 10 C to 15 C and filtered. The filtered cake was washed with water to make it free of alkalinity followed by 50 ml of chilled toluene 5 wash. The isolated product is 5-amino-3-cyano-l-(2,6-dichloro-4- trifluoromethylphenyl)pyrazole (structure II) having 80% yield with 99.0% HPLC purity. (0055) Experiment 2-13 (0056) Process of preparation of 5-amino-3-cyano-l-(2,6-dichloro-4-trifluoromethyl phenyl)pyrazole in accordance with present disclosure: (0057) 10 Similar experiments were carried out (expt 2-13) by varying the normality of spent HCl and spent H2SO4 and mixtures thereof, and by varying the reaction conditions. The results obtained from the process of the present disclosure by such variations are summarized in table 1. (0058) TABLE 1: (0059) 30 to 40 Deg (0060) 1200 ml, (0061) 4.4N 9.8N C over 30 152 gm 2500 gm 99.10% 91% 14.2 N (0062) min (0063) 30 to 40 Deg (0064) 1000 ml, (0065) 4.2N 9.9N C over 30 138 gm 2000 gm 99.50% 90% 14.1 N (0066) min (0067) 30 to 40 Deg (0068) 1000 ml, (0069) 4.1N 9.9N C over 30 152 gm 2000 gm 99.50% 85% 14.1 N (0070) min (0071) 30 to 40 Deg (0072) 1000 ml, (0073) 4.1N IO N C over 30 138 gm 2000 gm 99.20% 89% 14.1 N (0074) min (0075) 30 to 40 Deg (0076) 1000ml, (0077) 4.4N 9.9N C over 30 138 gm 2000 gm 99.30% 86% 14.3N (0078) min (0079) 30 to 40 Deg (0080) 1000ml, (0081) 4.4N 9.9N C over 30 152 gm 2000 gm 99.20% 85% 14.3N (0082) min |
| 22.3% |
|
0.01 mL of 2,6-dichloro-4-trifluoromethylaniline and a small amount of ethanol were placed in a 250 mL round bottom three-necked flask, and 3.0 mL (0.035 mol) of concentrated hydrochloric acid was added dropwise with stirring under ice bath.0.018 mol of sodium nitrite was dissolved in 10 mL of water, and slowly dropped into the flask. After the completion of the dropwise addition, the reaction was carried out for 0.5 h to obtain a yellow diazonium salt solution.Add 0.01 mol of ethyl 2,3-dicyanopropionate to a three-necked flask.The prepared diazonium salt solution was dropped into the flask, and the reaction was added dropwise for 2 hours.Ammonia water was added, the pH was adjusted to 9-10, and the reaction was carried out for 2 h at room temperature.After the reaction was completed, it was extracted with 40 mL of dichloromethane, and the organic layer was washed with water (2×30 mL).Wash with saturated sodium chloride solution (1×40 mL), dry over anhydrous magnesium sulfate.The solvent was crystallized under reduced pressure to obtain 0.72 g of the product, the yield was 22.3%, |
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