Aryl ether synthesis pyridine

The synthesis of the oligomers was carried out by the reaction of various aromatic bis-diols with m-dibromobenzene leading to a series of bromo end-capped, aryl-ether systems. Pyridine was used as the solvent for the reactions, and anhydrous potassium carbonate was utilized to generate the metallic salts of the bis-diols.. In an effort to promote low molecular weight oligomers, the molar ratio of m- dibromobenzene to aromatic bls-diol used in the S3mthesls... 

UUmann ether synthesis. The original Ullmann ether synthesis9 involved melting the salt of a phenol with an aryl bromide in the presence of copper metal. Yields are low. Williams et al.10 found that the reaction can be carried out at lower temperatures by using as solvent pyridine, which forms a complex with copper salts (cuprous chloride preferred), which provides catalysis for the reaction reflux temperature is then sufficient. 

Another well-known process that utilizes a nucleophilic phosphane is the Mit-sunobu reaction, that is, the reaction between an acidic partner and an alcohol, typically facilitated by an azodicarboxylate and a phosphane. Two options are possible, anchoring of the electrophilic part to the solid support, dealt with in the next section, or anchoring of the nucleophilic phosphane. Georg et al. used polystyrene-bound triphenylphosphane and DEAD (diethyl azodicarboxylate) in their synthesis of aryl ethers [31]. Alcohols were reacted successfully with electron-rich and electron-deficient phenols, giving the desired products in good yield and purity. More recently, Wilhite and coworkers disclosed an efficient protocol for the synthesis of pyridine ethers using ADDP [l,l -(azodicarbonyl)dipiperidine] and polymer-supported triphenylphosphane (Scheme 6.9) [32], Both methods eliminate purification problems caused by triphenylphosphane oxide, but chromatography is still needed. 

Activating Agent. Pyridine was found to promote the synthesis of aryl ethers starting from phenols via a 2,4,6-triphenylcyclotriboroxane-pyridine adduct (easily prepared by addition of pyridine to the corresponding 2,4,6-triphenylcyclotriboroxane). When 4-phenylphenol is reacted with 0.66 equiv of the above boroxane adduct in the presence of stoichiometric copper(II) acetate and cesium carbonate, the desired aryl ether is obtained in 99% isolated yield after 24 h at room temperature (eq 40). 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

Inverse type hetero-Diels-Alder reactions between p-acyloxy-a-phenylthio substituted a, p-unsaturated cabonyl compounds as 1-oxa-1,3-dienes, enol ethers, a-alkoxy acrylates, and styrenes, respectively, as hetero-dienophiles result in an efficient one step synthesis of highly functionalized 3,4-dihydro-2H-pyrans (hex-4-enopyranosides). These compounds are diastereospecifically transformed into deoxy and amino-deoxy sugars such as the antibiotic ramulosin, in pyridines having a variety of electron donating substituents, in the important 3-deoxy-2-gly-culosonates, in precursors for macrolide synthesis, and in C.-aryl-glucopyranosides. 

To carry out the similar MCR involving 5-amino-3-methyl-l-phenylpyrazole, aromatic aldehydes, and 3-cyanoacetyl indoles, Zhu et al. [70] used microwave-assisted synthesis in glygol at 150°C. Application of other solvents was less effective and gave either no reaction products (water medium) or led to the sufficient yield decreasing (EtOH, HOAc, DME). Microwave irradiation was also used by Quiroga et al. [71] to synthesize ether 4-aryl-5-cyano-6-phenylpyrazolo[3,4-b]pyridine-3-ones or their dihydroderivatives under argone atmosphere. 

Pyridine synthesis.1 Dihydropyrans (1), formed by cycloaddition of aryl en-ones with vinyl ethers (12,561), can serve as protected 1,5-dicarbonyl compounds and react with hydroxylamine (2 equiv.) to form 2,4-disubstituted pyridines (2). 

The addition of an aryl radical intermediate to a pyridine featured as a key step in a total synthesis of the alkaloid toddaquinoline by Harrowven and Nunn <98TL5875, 00TL6681, 01T4447>. Thus, cyclisation of azastilbene 148 using tributyltin hydride and AIBN, led to both the desired product, toddaquinoline methyl ether 149, and an unwanted regioisomer 150 (Scheme 41). 

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