Synthesis Of 2-(2-chlorophenyl) Methyl-4, 4-dimethyl-3-isoxazolidinone

The herbicide is one important part of agricultural chemicals. Now sales of herbicides is 46.7% of sales of agricultural chemicals, and it is 50% of agricultural chemicals sales in developed countries, for example U.S.A.. There are about 50,000 kinds of weed in the world in which 1,800 kinds of weed have resulted in economic loss. There are 200 kinds of weed in the field of crops which cause about 15% reduction of output every year. Along with development of industry and advancement of society, chemistry prevention has been the main measure for preventing weed. At present, there are about 300 kinds of herbicides used to prevent the growth of broad-leaved and gramineous weed.Since 1940s', sales of herbicides has been growing, and the percent of sales in agricultural chemicals market varies from 20% to 47%. In 1960, sales of herbicide was about 170 million dollars in the world that it was 20% sales of the agricultural chemicals; in 1980, 4.891 billion dollars, 43%; in 1990, 11.625 billion dollars; in 1995, 13.3 billion dollars, 47.1%. In 1990s', the speed of sales growing sharply decelerated.In addition to high activity, today the characteristic of herbicides developed is safe enough to ensure the safety of unaimed life, human being, and environment. Clomazone was synthesized for this reason.Clomazone (2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone), a soil-applied herbicide, was reported to interfere with chloroplast development and reduce or prevent accumulation of plastid pigments in susceptible species. It is an inhibitor of photosynthesis and carotenoid biosynthesis in higher plants. Clomazone has the characteristics which are high efficiency, low toxicity, broad applicability, good effects on weeds, extensive scale to weed, long range of effect, excellent miscibility, safety for environment, etc.The synthesis routes of clomazone comprise two methods, viz.ο-chlorobenzaldehyde method and 3-chloro-2,2-dimethyl propionyl chloride method.ο-chlorobenzaldehyde method is a route thatο-chlorobenzaldehyde is used as raw material. Through oximation, reduction, acylation, and cyclization, clomazone is synthesized. This route has many disadvantages such as using a great deal of solvent, complex purification process, using expensive reductant, competition reaction between amino and hydroxyl in N-(2-chlorobenzyl)hydr- oxylamine acylation, and low yields. Therefore this route has a high cost and can not be industrialized.3-chloro-2,2-dimethyl propionyl chloride method uses 3-chloro-2,2-di- methyl propionyl chloride as raw material. Through ammonolysis, cyclization, and benzylation, clomazone is synthesized. This route is short. The reaction condition is mild. Reaction process is easily handled. Raw materials are facile. Purification is easy. Thereby this route is popular. In this paper, we use this route to synthesize clomazone. We are going to optimize reaction conditions in order to reduce cost, simplify operation, and industrialize the route. In the synthesis of 3-chloro-N-hydroxy-2,2-dimethyl propionyl amine, we substitute methanol for water as solvent to avoid hydrolysis of 3-chloro-2,2-dimethyl propionyl chloride and solve the problems that hydrolysis of raw material results in low yield and the separation of hydolysates. As we substitute methanol for water, inorganic base is not easily dissolved in methanol. Therefore we substitute base A for NaOH to make the reaction in homogeneous phase. By changing solvents and bases, the yield of 2,2-dimethyl-3-isoxazolidinone is improved evidently. This reaction does not need to separate product. So it simplifies operational process. The base A and methanol can be recovered and the cost of 2,2-dimethyl-3-isoxazolidinone can be reduced.In the synthesis of 2,2-dimethyl-3-isoxazolidinone, all of yields reported in references are over 90%. Thereby we investigated the synthesis of 2,2-dimethyl-3-isoxazolidinone according to references. The total yield of the first step and the second step is 91.71%, it is 7.59% more than 84.12% which is the highest yield in references.In the synthesis of 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-is- oxazolidinone, some effects of reaction conditions on reaction are investigated, such as dosage of base, basicity, dosage of catalyst, and temperature. As a result, a appropriate condition for this reaction is obtained, namely 90℃and 4,4-dimethyl-3-isoxazolidinone:NaHCO3:PTC=1:1:0.01. We find that yield obviously declines when temperature drops. K2CO3, Na2CO3, and NaHCO3 are used as bases in this reaction in order to reduce cost and decrease isomerization. Not only does the cost be reduced, but also the yield is improved. When Na2CO3 and NaHCO3 are used as bases, the conversion of 4,4-dimethyl-3-isoxazolidinone is quantitative. In 90℃, the conversion of 4,4-dimethyl-3-isoxazolid- inone is also quantitative when catalyst is reduced. At the same time, the yield is higher, and isomerization is lower. By carrying out a series of experiment, we find the suitable condition for the reaction in which yield can reach 94.11% that it is 6.42% more than 87.69%, the highest yield is reported in references.By investigating the synthesis route of 2-[(2-chlorophenyl)methyl]-4,4- dimethyl-3-isoxazolidinone, we get a suitable condition in which the total yield is up to 86.31%. We also calculate cost of raw materials and analyze economy profit. If the route was industrialized, the cost would be from 36112.39Yuan/ton to 39659.42Yuan/ton. However, the price of clomazone is 128000 Yuan/ton. So there is huge profit for producing clomazone, and the route is suitable for industrialization.