Cleavage of Catechol Monoalkyl Ethers by Aluminum Triiodide–Dimethyl Sulfoxide

Abstract

Using eugenol and vanillin as model substrates, a practical method is developed for the cleavage o-hydroxyphenyl alkyl ethers. Aluminum oxide iodide (O=AlI), generated in situ from aluminum triiodide and dimethyl sulfoxide, is the reactive ether cleaving species. The method is applicable to catechol monoalkyl ethers as well as normal phenyl alkyl ethers for the removal of methyl, ethyl, isopropyl, and benzyl groups. A variety of functional groups such as alkenyl, allyl, amide, cyano, formyl, keto, nitro, and halogen are well tolerated under the optimum conditions. Partial hydrodebromination was observed during the demethylation of 4-bromoguaiacol, and was resolved using excess DMSO as an acid scavenger. This convenient and efficient procedure would be a practical tool for the preparation of catechols.

Anchimerically Assisted Selective Cleavage of Acid-Labile Aryl Alkyl Ethers by Aluminum Triiodide and N,N-Dimethylformamide Dimethyl Acetal

“…This protocol was successfully employed in the syntheses of escoparone and esculetin, 20 two natural coumarins of pharmacological importance (Scheme 2). 21 The selective demethylation of 2,4,5-trimethoxybenzaldehyde (10) afforded 4,5-dimethoxysalicylaldehyde (11) in an 81% yield.…”

“…Being similar to the demethylation of eugenol by Al­(O i Pr) 3 -KI, it was not surprising that Al­(OEt) 3 was effective in ether cleavages in the presence of NaI. Thus, vanillin ( 4l ) was subjected to the treatment, which afforded protocatechualdehyde ( 5l ) in a 58% yield (Scheme ).…”

“…2-Hydroxy-4,5-dimethoxybenzaldehyde (11). Off-white solid; yield: 0.738 g (81%); mp 104−105 °C; R f = 0.88 (PE/EA 3:1).…”

“…Although we have used pyridine, dimethyl sulfoxide, CaO, and 1,3-diisopropylcarbodiimide (DIC) to counteract HI, AlI 3 had an impact to various extents. It was thus reasoned that AlI 3 might be tuned for the selective cleavage of ethers upon adequate deactivation by proper additives.…”

An efficient synthesis of Nepetoidin B

“…15 The first step of this approach required a tedious workup and purification to afford tetramethylated nepetoidin B in 40% yield and to recover the starting material. 15 Due to our interest in the synthesis of biological active phenolic compounds, [16][17][18][19][20] we developed an efficient route for the synthesis of nepetoidin B in three steps from the commercially available and inexpensive 3,4dimethoxybenzaldehyde.…”