The Benzocaine Ointment green prep work process has the adhering to actions:
① Add 80g of commercially readily available outright ethanol (1.74 mol) as well as 50g of p-nitrobenzoic acid (0.30 mol) into the reaction gadget under stirring, then gradually add 10g of dried concentrated sulfuric acid (0.10 mol) dropwise, After 15 minutes of dripping, the temperature was raised to 80 ± 2 ° C with stirring, and the reaction was refluxed for 6 hrs.
After the reaction mores than, ethanol is first distilled out under typical pressure, and when the temperature gets to 100 ± 2 ° C, the home heating is stopped, the layers are allowed to stand, and also the upper layer (concentrated sulfuric acid layer) is related to the following batch.
Amazing the material in the lower layer to 60 ± 2 ° C, adjust the pH worth to 8 with 5wt% sodium carbonate aqueous service, retest the pH after stirring for 0.5 h, and allow stand to different layers.
② Control the temperature level of the lower layer product (concerning 58g) at 60 ± 2 ° C, after that include it into 290g of water with mixing, then add 1g, 5wt% of Pd/C stimulant, replace it with nitrogen three times after including, and after that pass hydrogen to 0.6 MPa, as well as the catalytic hydrogenation reaction is carried out at a temperature level of 98 ± 2 ° C. When the stress no more goes down, after the catalytic hydrogenation reaction is finished, maintain it warm for 2 hrs, filter it while it is hot, and also cool the filtrate to 40 ° C. Suction filtration, centrifugation, The filter cake was dried at 60-70 ° C to acquire 48.5 g of white powdered benzocaine with a pureness of 99.6% (HPLC) as well as a two-step yield of 98.2%.
Add 500g of ethyl p-nitrobenzoate into a 1L autoclave, control the temperature level at 120 ° C, keep it cozy for 1h, then include 5g of activated Raney nickel catalyst, replace it with nitrogen three times, after that hydrogen 3 times, and then mix Pass hydrogen to 0.4 MPa, and also perform the hydrogenation response at a temperature level of 120 ° C. When the pressure no more goes down, after the hydrogenation reaction is finished, keep the temperature level for 4 hours, and also discharge the hydrogen gas to stop the response.
The GC analysis outcome of sampling evaluation: Benzocaine Ointment has a pureness of 99.98%, ethyl p-nitrobenzoate is not detected, et cetera are unidentified elements. Filter the material through a precision filter, press right into 500g of water for formation, stir till the temperature reaches 25 ° C, centrifuge to obtain a wet item, as well as vacuum cleaner dry for 12 hours to get 418.8 g of the final product with a yield of 98.99%.
The very first step, the synthesis of p-nitrobenzoic acid, in 250mL three-necked flask, include the p-nitrotoluene of 0.05 mol and also be 5% tetramethylammonium bromide and also 50mL distilled water about the molar fraction of p-nitrotoluene, Set up a reflux condenser, a thermostat, as well as a stirrer, start stirring, as well as after the temperature rises to 90 levels, include 0.125 mol KMnO4 in sets, the reaction temperature is 90-95 levels, and also mix for 2.5 hours;
In the second step, cool down the reaction liquid to room temperature level, remove the solid, clean the filter cake two times with hot water, combine the filtrates, acidify to pH= 2-3, precipitate the solid, filter, clean the filter cake with cold water, as well as dry to acquire light yellow Crystal p-nitrobenzoic acid;
The 3rd step is the synthesis of ethyl p-nitrobenzoate, add 0.015 mol p-nitrobenzoic acid, 25mL outright ethanol, and 2.5 mL focused sulfuric acid to a completely dry 100 mL single-neck round bottom flask, warm and stir on a water bathroom Reflux reaction for 1.5 h, put the reaction option right into a beaker with 100mL of ice water, precipitate crystals, filter with suction, clean the filter cake two times with water, after that move to a small beaker, add 10 mL of water to saturate, include mass portion under stirring It is 5% sodium carbonate remedy, as well as the pH of the solution is adjusted to 8 to acquire light yellow solid ethyl p-nitrobenzoate;
The fourth step, the synthesis of Benzocaine Ointment, in a 250mL round bottom flask, include an option constructed from 1.95 grams of ethyl p-nitrobenzoate as well as 100mL of ethanol, after that add 0.02 grams of Pd/C driver, feed hydrogen to mix the response, tender loving care tracking React up until the end of the response, filter with diatomaceous planet to remove the catalyst, spin dry to remove ethanol, as well as obtain white ethyl p-aminobenzoate.