98752-37-5

Upstream product

• 624-92-0 Dimethyldisulphide 
• 22921-68-2 2-bromo-5-methoxy-benzoic acid 
• 77-78-1 dimethyl sulfate 
• 852623-20-2 3-methoxy-6-methylthio-2-(trimethylsilyl)benzoic acid 
• 852623-12-2 3-methoxy-2-(trimethylsilyl)benzoic acid 
• 586-38-9 3-Methoxybenzoic acid 

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.

Synthesis and Biological Activity of the Putative Metabolites of the Atypical Antipsychotic Agent Tiospirone

Putative oxidative metabolites of the lead antipsychotic agent tiospirone (1) were synthesized to assist in the identification of the authentic metabolic products found in human urine samples.Thus far, six authentic metabolites have been correlated to the synthetic species.The putative metabolites were further examined in vitro to assess their central nervous system therapeutic potential.SAR analysis of these derivatives indicates that hydroxyl substitution, particularly in the azaspirodecanedione region of the molecule, diminishes the dopamine D-2 affinity of the species without significantly altering the serotonin type-1A and type-2 interactions.In addition, an increase in α1-adrenergic affinity appears to be linked to the attenuation of effects at the dopamine receptors.The biological profile of the 6-hydroxytiospirone metabolite 42 was exemplary in these respects and the in vivo actions of this compound suggest potent antipsychotic potential with a minimal liability for extrapyramidal side effects (EPS).While compound 42 has been unambiguously characterized as an actual human metabolite of tiospirone, the role of 42 in the observed antipsychotic activity of the parent drug, if any, has not yet been determined.