20788-05-0Relevant academic research and scientific papers
Integrating Metal-Catalyzed C-H and C-O Functionalization to Achieve Sterically Controlled Regioselectivity in Arene Acylation
Serratore, Nicholas A.,Anderson, Constance B.,Frost, Grant B.,Hoang, Truong-Giang,Underwood, Steven J.,Gemmel, Philipp M.,Hardy, Melissa A.,Douglas, Christopher J.
supporting information, p. 10025 - 10033 (2018/07/21)
One major goal of organometallic chemists is the direct functionalization of the bonds most recurrent in organic molecules: C-H, C-C, C-O, and C-N. An even grander challenge is C-C bond formation when both precursors are of this category. Parallel to this is the synthetic goal of achieving reaction selectivity that contrasts with conventional methods. Electrophilic aromatic substitution (EAS) via Friedel-Crafts acylation is the most renowned method for the synthesis of aryl ketones, a common structural motif of many pharmaceuticals, agrochemicals, fragrances, dyes, and other commodity chemicals. However, an EAS synthetic strategy is only effective if the desired site for acylation is in accordance with the electronic-controlled regioselectivity of the reaction. Herein we report steric-controlled regioselective arene acylation with salicylate esters via iridium catalysis to access distinctly substituted benzophenones. Experimental and computational data indicate a unique reaction mechanism that integrates C-O activation and C-H activation with a single iridium catalyst without an exogenous oxidant or base. We disclose an extensive exploration of the synthetic scope of both the arene and the ester components, culminating in the concise synthesis of the potent anticancer agent hydroxyphenstatin.
2,6 Dihydroxybenzoic acid derivatives as anthelmintics
Ruschig,Konig,Duwel,Loewe
, p. 1745 - 1758 (2007/10/06)
The 2,6 dihydroxybenzoic acid anilides have marked cesticidal properties when a specific form of substitution by halogen atoms or methyl groups is made in the anilide portion of the molecule. Optimum activity is achieved with 2,6 dihydroxybenzoic acid 4' bromanilide. This compound interferes with the energy metabolism of cestodes, inhibiting the breakdown of glucose and lowering the ATP level. The introduction of halogen atoms in the 3 and 5 position of the benzoic acid portion increases the activity but the toxicity as well. Activity against the liver fluke is also observed and prevails when an electronegative substituent is introduced in the 3 position. The most effective compounds are the 3 nitro 2,6 dihydroxybenzoic acid anilides, followed by the 3 acyl 2,6 dihydroxybenzoic acid anilides. The choice of substituents in the anilide portion is restricted to halogens, methyl groups, tri halogenated methyls, i.e. substituents which improve the lipoid solubility. Optimum efficacy is achieved with 3 nitro 2,6 dihydroxybenzoic acid 3',5' bis trifluoromethyl anilide. A description of the chemical methods of synthesis is given.
