95420-79-4

Upstream product

• 860562-50-1 4-mercapto-3-methoxy-benzoic acid 
• 77-78-1 dimethyl sulfate 
• 624-92-0 Dimethyldisulphide 
• 586-38-9 3-Methoxybenzoic acid 
• 320583-54-8 4-chlorosulfonyl-3-methoxybenzoyl chloride 
• 503446-60-4 4-chlorosulfonyl-3-methoxy-benzoic acid 

Downstream Products

• 89075-37-6 2-(3-Methoxy-4-methylsulfanyl-phenyl)-3H-imidazo[4,5-c]pyridine; hydrochloride 

Relevant academic research and scientific papers

First general, direct, and regioselective synthesis of substituted methoxybenzoic acids by ortho metalation

(Chemical Equation Presented) New general methodology of value in aromatic chemistry based on ortho-metalation sites in o-, m-, and p-anisic acids (1-3) (Scheme 1) is described. The metalation can be selectively directed to either of the ortho positions by varying the base, metalation temperature, and exposure times. Metalation of o-anisic acid (1) with s-BuLi/TMEDA in THF at -78°C occurs exclusively in the position adjacente to the carboxylate. On the other hand, a reversal of regioselectivity is observed with n-BuLi/t-BuOK. With LTMP at 0°C, the two directors of m-anisic acid (2) function in concert to direct introduction of the metal between them while n-BuLi/t-BuOK removes preferentially the proton located ortho to the methoxy and para to the carboxylate (H-4). s-BuLi/TMEDA reacts with p-anisic acid (3) exclusively in the vicinity of the carboxylate. According to these methodologies, routes to very simple methoxybenzoic acids with a variety of functionalities that are not easily accessible by other means have been developed (Table 1).

Toward a better understanding on the mechanism of ortholithiation. Tuning of selectivities in the metalation of meta-anisic acid by an appropriate choice of base

(Chemical Equation Presented) If employed in THF at 0°C, LTMP metalates meta-anisic acid at the doubly activated position. In contrast, n-BuLi/t-BuOK deprotonates position C-4 preferentially at low temperature. Functionalization at C-6 requires protection of the C-2 site beforehand. As a result of these findings, a new mechanism is proposed for the heteroatom-directed ortholithiation of aromatic compounds.