3,4,5-Trimethoxytoluene (TMT) was synthesized, starting from p-cresol, through bromination followed by methylation to give 3,5-dibromo-4-methoxytoluene (DBMT). The methoxylation of the latter with sodium methoxide in methanol was studied under pressure and by continuous distillation of the solvent, methanol. The O-methylation reaction preceding the methoxylation was advantageous from the point of view of separation, purification, and isolation of the desired product and also in reducing the tar formation. The residue obtained was minimized to 0.6−0.7 wt % of the DBMT. The methoxylation reaction with distillative removal of methanol gave a conversion of 98% of DBMT to the mixture of methoxylated products, and the conversion to TMT was 86.5% as compared to 93% and 70.81%, respectively, when the reaction was carried out under pressure in a sealed reactor. However, the overall conversion to TMT based on p-cresol is 64.27% for the methoxylation reaction under pressure and 78.46% for the reaction by continuous removal of methanol calculated as isolated yield. The advantages of the methoxylation of the DBMT over the published literature procedures involving direct methoxylation of 3,5-dibromo-p-cresol followed by methylation of the dimethoxy-p-cresol are the ease of separation, purification, and isolation by vacuum fractionation of the desired product TMT.

中文翻译：

---

3,4,5-三甲氧基甲苯的合成方法开发

从对位开始合成3,4,5-三甲氧基甲苯（TMT）-甲酚，通过溴化然后甲基化得到3,5-二溴-4-甲氧基甲苯（DBMT）。在压力下并通过连续蒸馏溶剂甲醇来研究后者用甲醇钠在甲醇中的甲氧基化。从所需产物的分离，纯化和分离以及减少焦油形成的观点来看，在甲氧基化之前的O-甲基化反应是有利的。将获得的残留物减至DBMT的0.6-0.7 wt％。通过蒸馏除去甲醇进行的甲氧基化反应使98％的DBMT转化为甲氧基化产物的混合物，而在压力下进行反应时，TMT的转化率为86.5％，而分别为93％和70.81％在密封的反应器中 但是，基于对压力下的甲氧基化反应，对甲酚为64.27％，对于连续分离的甲醇计算，对甲酚的反应率为78.46％，以分离后的收率计算。相对于3,5-二溴对甲酚的直接甲氧基化然后二甲氧基对甲酚的甲基化，DBMT进行甲氧基化的优势在于其易于分离，纯化和真空分级分离的优点。所需的产品TMT。