The reaction of safrole derivatives with aluminum chloride: improved procedures for the preparation of catechols or their mono-O-Methylated Derivatives and a mechanistic interpretation

Abstract

Um procedimento otimizado para a preparação de catecóis através da reação de quebra da ponte metilenodioxílica de derivados do safrol com cloreto de alumínio é descrito. Em substratos com grupos substituintes atraentes de elétrons (carboxaldeído e nitro) observou-se a formação regiosseletiva de éteres clorometílicos facilmente isoláveis. A partir desses intermediários foram sintetizados os fenóis mono O-metilados (3-hidroxi-4-metoxibenzaldeído, 2-bromo-4-metoxi-5-hidroxibenzaldeído, 2-nitro-4-metoxi-5-hidroxibenzaldeído, e 2-metoxi-4-(2-oxoprop-1-il)-5-nitrofenol). Com base nesses dados experimentais e em cálculos semi-empíricos (MNDO) de orbitais moleculares foi proposta uma racionalização mecanística para explicar as regiosseletividades observadas.An improved procedure for the "one-pot" preparation of cathecols from methylenedioxy-ring cleavage reaction of safrole derivatives with aluminum chloride is described. In substrates substituted by conjugated electron-withdrawing groups (carboxyaldehyde or nitro groups) the regioselective formation of the easily isolable chloromethyl ether intermediates was observed. From these intermediates the syntheses of mono-O-methylated phenols (3-hydroxy-4-methoxybenzaldehyde, 2-bromo-4-methoxy-5-hydroxybenzaldehyde, 2-nitro-4-methoxy-5-hydroxybenzaldehyde and 2-methoxy-4-(2-oxoprop-1-yl)-5-nitrophenol) were accomplished. Based on these experimental data and semi-empirical (MNDO) molecular orbital calculations, a mechanistic rationale that explains the observed regioselectivities was also proposed.

Synthesis of Nine Safrole Derivatives and Their Antiproliferative Activity Towards Human Cancer Cells

“…Cleavage of the methylenedioxy ring of nitrosafrol took place during the conversion into the catechol 4 (57.4% yield) using the AlCl 3 /CH 2 Cl 2 /H 2 O method [12][13][14][15] . In the 1 H NMR spectrum, the absence of the methylenedioxy singlet between 5.90-6.05 ppm confirmed the presence of catechol coupled with a broad signal at d=8.99 (brs, 2H).…”

New Catechol Derivatives of Safrole and Their Antiproliferative Activity towards Breast Cancer Cells

“…Oxidative hydroboration of the side chain in both catechols led to a hydroxyl group in C-3’. The side chains of the catechols were oxidized using BH 3 ·DMS/THF/NaBO 3 ·4H 2 O/H 2 O as previously described for other alkenes and alkynes [ 14 , 15 , 16 , 17 , 18 , 19 ]. The primary alcohols 5 and 8 were obtained in 35.1% and 49.3% w/w yields and the secondary alcohol 9 with 6.1% yield ( Scheme 1 ).…”

The Synthesis of Velloziolide via Nicholas Reaction Based γ-Carbonyl Cations

“…The use of BCl 3 in reaction with 17 gave a mixture of velloziolide ( 1 ) and chloromethylated 18 , the latter as evidenced by an additional δ 6.09 singlet in the 1 H NMR spectrum, and presence of m / e 362/364 in the mass spectrum of the crude reaction product. Consequently, the final protocol involved the reaction of 17 with BCl 3 , followed by subjecting the crude reaction product to wet AgNO 3 ; under these conditions, velloziolide could be isolated in 82% yield. Synthetic 1 was found to be identical to natural velloziolide based on a comparison of physical and spectral data, save for the optical activity of the natural product.…”