Pendimethalin (6) is a well-known selective herbicide useful for pre-emergence control of annual broad-leaved weeds and grasses in cotton, soybeans, rice, barley, beans, alliums, vines, ornamentals and orchards of fruit and nut trees.1 It is also utilized to control suckers of tobacco. Several procedures have been reported for the preparation of pendimethalin2,3 and it is currently manufactured from o-xylene (1), by nitration, catalytic hydrogenation, condensation and dinitration4 (Scheme 1). One problem of this process is that the selectivity of the nitration of o-xylene is poor, giving only about 60% yield of 3,4-dimethylnitrobenzene along with 40% of 2,3-dimethylnitrobenzene.5 Another difficulty is that the final dinitration step may produce the potentially carcinogenic N-nitroso compound 7.4 We report a new approach for the synthesis of pendimethalin (6) in a cost-effective, efficient and environmentally friendly manner. As shown in Scheme 2, 3,4-dimethylbromobenzene (8) was prepared6 in 91% yield by bromination of o-xylene (1) at -5-0◦. Methoxylation of 8 with sodium methoxide in the presence of cuprous bromide gave 3,4-dimethoxyanisole in 96% yield.7–9 Monoand dinitration carried out in a stepwise fashion afforded 3,4-dimethyl-2,6-dinitroanisole (10) in 90% yield.10–12 Finally, treatment of 10 with 1-ethylpropylamine led to the title product 6 in 93% yield.2,3 This new synthesis of pendimethalin provided a higher yield under milder conditions and especially avoids the generation of the N-nitroso by-product 7 (the content of N-nitroso compound may be controlled to under 10 mg/kg) thus making this route suitable for industrial production of high quality pendimethalin.

中文翻译：

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二甲戊灵的新合成

Pendimethalin (6) 是一种众所周知的选择性除草剂，可用于棉花、大豆、水稻、大麦、豆类、葱属、藤本植物、观赏植物以及果园和坚果树中的一年生阔叶杂草和禾本科植物的出苗前防治。 1它还用于控制烟草吸盘。已经报道了几种制备二甲戊灵 2,3 的程序，目前它是由邻二甲苯 (1) 通过硝化、催化氢化、缩合和二硝化 4 制造的（方案 1）。该工艺的一个问题是邻二甲苯硝化的选择性差，3,4-二甲基硝基苯的产率只有60%左右，2,3-二甲基硝基苯的产率只有40%。 5另一个难点是最终的二硝化步骤可能会产生潜在致癌的 N-亚硝基化合物 7。4 我们报告了一种以具有成本效益、高效和环保的方式合成二甲戊灵 (6) 的新方法。如方案 2 所示，3,4-二甲基溴苯 (8) 通过邻二甲苯 (1) 在 -5-0° 的溴化以 91% 的产率制备。在溴化亚铜存在下，8 与甲醇钠的甲氧基化得到 3,4-二甲氧基苯甲醚，产率为 96%。7-9 以逐步方式进行单和二硝化得到 3,4-二甲基-2,6-二硝基苯甲醚 (10) 90% 的产率。10–12 最后，用 1-乙基丙胺处理 10 得到了产率为 93% 的标题产物 6。2，