A method for fully continuous-flow preparation of a nitroimidazole antimicrobial agent using a fully continuous-flow system, the fully continuous-flow system comprising a first micromixer, a second micromixer, a third micromixer, a fourth micromixer, a fifth micromixer, a sixth micromixer, a first microreactor, a second microreactor, a third microreactor, a fourth microreactor, a fifth microreactor, a sixth microreactor, a seventh microreactor, a first back pressure valve, a second back pressure valve, a third back pressure valve, a fourth back pressure valve, a fifth back pressure valve, a first gas-liquid separator, a second gas-liquid separator, a third gas-liquid separator, a fourth gas-liquid separator, a first online solvent switching unit, a second online solvent switching unit, a third online solvent switching unit and a feed unit, and the method comprising:
- (1) mixing a first glyoxal aqueous solution, a first acetaldehyde aqueous solution and a first ammonia solution in the first micromixer to obtain a first mixed solution;
- feeding the first mixed solution to the first microreactor followed by reaction to generate a first reaction product containing 2-methylimidazole;
- removing unreacted glyoxal, acetaldehyde, ammonia and water from the first reaction product in the first online solvent switching unit to collect 2-methylimidazole;
- and mixing 2-methylimidazole with a sulfuric acid solution to give a mixture A;
- (2) mixing the mixture A with a first nitric acid aqueous solution in the second micromixer to give a second mixed solution;
- transporting the second mixed solution to the second microreactor for reaction to produce a second reaction product;
- allowing the second reaction product to flow through the first back pressure valve and the first gas-liquid separator for gas removal to enter the third microreactor for reaction to give a third reaction product;
- and allowing the third reaction product to flow through the second back pressure valve and the second gas-liquid separator for gas removal to give a mixture B;
- (3) mixing a second glyoxal aqueous solution, a second acetaldehyde aqueous solution and a second ammonia solution in the third micromixer to obtain a third mixed solution;
- feeding the third mixed solution to the fourth microreactor followed by reaction to obtain a fourth reaction product containing 2-methylimidazole;
- removing unreacted glyoxal, acetaldehyde, ammonia and water from the fourth reaction product in the second online solvent switching unit to collect 2-methylimidazole;
- and mixing 2-methylimidazole with the mixture B to give a mixture C;
- (4) mixing the mixture C with a second nitric acid aqueous solution in the fourth micromixer to give a fourth mixed solution;
- transporting the fourth mixed solution to the fifth microreactor for reaction to produce a fifth reaction product;
- allowing the fifth reaction product to flow through the third back pressure valve and the third gas-liquid separator for gas removal to enter the sixth microreactor for reaction to give a sixth reaction product;
- and allowing the sixth reaction product to flow through the fourth back pressure valve and the fourth gas-liquid separator for gas removal to give a mixture D;
- (5) mixing the mixture D with a formic acid solution in the fifth micromixer to obtain a fifth mixed solution;
- feeding a reagent to the sixth micromixer via the feed unit, wherein the reagent is selected from the group consisting of ethylene oxide, propylene oxide, epichlorohydrin and 2-(ethylsulfonyl)ethanol;
- mixing the fifth mixed solution with the reagent in the sixth micromixer to give a sixth mixed solution;
- feeding the sixth mixed solution to the seventh microreactor followed by reaction to obtain a seventh reaction product containing nitroimidazole;
- allowing the seventh reaction product to flow through the fifth back pressure valve to enter the third online solvent switching unit for removal and recovery of formic acid to give a crude nitroimidazole product;
- and
- (6) adjusting the crude nitroimidazole product to pH 1-6 in a stirring vessel of the third online solvent switching unit followed by filtration to give a crude 2-methyl-5-nitroimidazole product;
- and adjusting the crude 2-methyl-5-nitroimidazole product to pH 7-13 followed by filtration, decolorization, filtration, concentration, recrystallization, filtration and drying to yield the nitroimidazole antimicrobial agent with a purity of greater than 99.9%.