Guaiacol → Diphenyl Ether

A toluene para-sulfonyl derivative of compound 14 was transformed with methoxyphenol in pyridine to give the diphenylether (compound 15) at 75% yield. Catalytic reduction of the nitro groups was carried out quantitatively in ethanol in order to allow the diamino derivative (compound 16) to be tetrazotized at 0° C. The resulting tetrazolium salt was reacted with sodium iodide to give the 3,5-diiodo compound in good yield (compound 17). Due to difficulties with hydrolysis, complete acidolysis of the ester was done under reflux using hydriodic acid (HI) as a strong cleaving agent, which removed both the ester and the O-methyl groups. Acetic acid was added to this reaction instead of H2SO4 to avoid decomposition of HI into I2. Tetrac (compound 8) was then obtained by two displacements of a proton from the aromatic nucleus of the di-iodoacid (compound 18) by an iodide. In that reaction, the iodo-deprotonation was carried out using I2 in methanolic NH3 in 91% yield. Of note, complete acidolysis of compound 17 revealed some advantage; thereafter aminolysis of the ethyl ester and formation of an amide during the iodination reaction was avoided. Also, selective iodination on the outer ring benefited from the transformation of the methyl ether group into an alcohol. This was done to allow activation of the ortho position by oxygen through inductive and resonance effects.

ORD record

ord-25387dcc0f084a228dbcbe9f437c837f

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859539B2