Chemoselective Chlorination And Etherification Of Benzyl Alcohols Using 2,4,6-Trichloro-1,3,5-triazine And DMSO

Chemoselective chlorination and etherification of benzyl alcohols using TCT (2,4,6-trichloro-1,3,5-triazine) and DMSO have been reported in this dissertation.An efficient chlorination of benzyl alcohols using 0.55 equiv of TCT in DMSO has been reported in the first part of this dissertation. Various benzyl alcohols were converted into the corresponding chlorides in the yields of 80-100% within 10 to 40 min at room temperature (16 examples). The reaction conditions are mild and compatible with substrates bearing acid-labile founctional groups, such as acetal, ester, olefin and silyl ether. Both competitive intramolecular and intermolecular reactions for benzyl alcohols in the presence of aliphatic alcohols indicate high selectivity (8 examples). The procedure has been successfully used in the selective chlorination of gastrodin, the active ingredient of Tianma. Furthermore, a possible mechanism for the selective chlorination of benzyl alcohols is proposed.An efficient transformation of benzyl alcohols into their methyl or ethyl ethers using 1.2 equiv of TCT and 1 equiv of DMSO in methanol or ethanol has been reported in the second part of this dissertation. Benzyl alcohols were transformed into their methyl or ethyl ethers in the yields of 40-94% within 15 min to 18 h (12 examples). Competitive intramolecular reactions indicate that the etherification is chemoselective for benzylic hydroxyls in the presence of aliphatic and phenolic hydroxyls (7 examples). This procedure has been successfully used in the synthesis of 2-methoxymethylestradiol. Compared with the current synthetic route, the new route is shortened, without protection and deprotection steps. Moreover, a plausible mechanism for the selective etherification of benzyl alcohols is proposed.In conclusion, the chemoselective chlorination and etherification of benzyl alcohols reported herein are operationally simple, and require inexpensive and commercially available reagents, which represent new useful tools in organic and medicinal chemistry.