63635-22-3

Upstream product

• 124-38-9 carbon dioxide 
• 2388-74-1 1-methoxy-3-methylsulfanyl-benzene 
• 624-92-0 Dimethyldisulphide 
• 579-75-9 2-Methoxybenzoic acid 
• 15570-12-4 3-methoxybenzenethiol 

Relevant academic research and scientific papers

GlyT1 RECEPTOR ANTAGONISTS

The present invention relates to a compound of formula I wherein R1, R2, X, Ar1 and Ar2 are as defined herein and to pharmaceutically acceptable acid addition salts, to a racemic mixtures, or to their correspond

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).

Directed ortho-metalation of unprotected benzoic acids. Methodology and regioselective synthesis of useful contiguously 3- and 6-substituted 2-methoxybenzoic acid building blocks

By treatment with s-BuLi/TMEDA at -78 °C, unprotected 2-methoxybenzoic acid is deprotonated exclusively in the position ortho to the carboxylate. A reversal of regioselectivity is observed when the acid is treated with n-BuLi/t-BuOK. These results are of general utility for the one-pot preparation of a variety of very simple 3- and 6-substituted 2-methoxybenzoic acids that are not easily accessible by conventional means. The potential usefulness of the method is demonstrated by the expedient synthesis of lunularic acid.

METALATION REACTIONS. VI. STERIC LIMITS IN THE PREPARATION OF 1,2,3-TRI-SUBSTITUTED BENZENE DERIVATIVES

Metalation of 1,3-dialkoxy-, 1-alkoxy-3-(alkylthio)- and 1,3-bis-(alkylthio)-benzenes with n-butyllithium has been examined to verify the possibility of preparing 1,2,3-tri-substituted benzene derivatives.The reaction is affected by steric hindrance.The yields of the metalation in the position ortho to both the substituents decrease as steric requirement increases becoming zero when the bulk of both the alkyl substituent and the hetero-atom is increased.It has been shown that synthesis of 1,2,3-tri-substituted derivatives by this route is feasible only with small substituents.