Aromatic sulfonation. 90. Sulfonation of three symmetrical 2,6-dialkylphenols, 2,6-dimethylanisole. Sulfation and sulfonation product distributions and mechanisms

Cerfontain, H.; Koeberg-Telder, Ankie; Lambrechts, Hans J. A.; Wit, Peter de

doi:10.1021/jo00199a034

Cited by 27 publications

(5 citation statements)

References 3 publications

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“…These results are in accordance with early works performed by Cerfontain et al in the 1980s. 37,38 They observed that the initial reaction of 1naphthol, 2,6-dialkylphenols, 2,6-dichlorophenol, phenol, and 2,6-dimethylanisole with SO 3 in an aprotic solvent was sulfation with formation of hydrogen sulfates. However, by increasing the temperature, the initial phenyl hydrogen sulfate was slowly converted into the phenolsulfonic acids via O-desulfonation and subsequent C-sulfonation if the phenol was in excess and via C-sulfonation and subsequent O-desulfonation if the SO 3 was in excess.…”

Section: Journal Of Agricultural and Food Chemistrymentioning

confidence: 99%

A Convenient Synthesis of Hydroxytyrosol Monosulfate Metabolites

Gomes

Torres

Rodríguez‐Borges

et al. 2015

J. Agric. Food Chem.

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The growing interest in the bioactivity of natural polyphenols and of their metabolites requires metabolites to be used in bioassays and as standards in research protocols. We report here on the synthesis of several hydroxytyrosol metabolite monosulfates achieved using a simplified protocol with improved yields. A synthetic solution based on avoidance of high temperature conditions during the synthesis and of low pressure conditions during purification has been established. Monosulfates of several phenolic compounds, namely, hydroxytyrosol, hydroxytyrosol acetate, homovanillyl alcohol, homovanillyl alcohol acetate, homovanillic acid, ferulic acid, and 3,4-dihydroxyphenylethanoic acid, were efficiently synthesized in 1-2 steps in good yield and isolated using simple procedures. The proposed protocol was shown to be relatively rapid, efficient, cheap, and widely applicable to a number of catechol scaffolds.

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Section: Journal Of Agricultural and Food Chemistrymentioning

confidence: 99%

A Convenient Synthesis of Hydroxytyrosol Monosulfate Metabolites

Gomes

Torres

Rodríguez‐Borges

et al. 2015

J. Agric. Food Chem.

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“…The sulfonation of halogenoarenes with chlorosulfuric acid and with concentrated aqueous and fuming sulfuric acid has been studied extensively (2)(3)(4)(5)(6)(7). In aromatic substitution, the directing effect of a halogeno substituent is determined by three factors.…”

Section: Introductionmentioning

confidence: 99%

On the positional reactivity order in the sulfur trioxide sulfonation of benzene, halogenobenzenes, halogenonaphthalenes, and chloroanthracenes

Cerfontain¹,

Zou²,

Bakker³

et al. 1994

Can. J. Chem.

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The reaction of sulfur trioxide with benzene, the four halogenobenzenes, and six halogenonaphthalenes in dichloromethane as solvent, and with four chlorinated anthracenes in nitromethane as solvent, has been studied by analysis of the resulting mixture of the sulfo derivatives with 1H NMR. The sulfonation of benzene yields initially benzenesulfonic acid and subsequently the 1,3-disulfonic acid (1,3-S2). The initial sulfonation of the four halogenobenzenes yields ≥ 98% of the 4-S. Their subsequent sulfonation gives the 2,4-S2 and in the case of fluoro- and iodobenzene also the 2,4,6-S3. Monosulfonation of 1-fluoronaphthalene yields only the 4-S, whereas the three other 1-halogenonaphthalenese yield in addition some 5-S. Further sulfonation on any of the four 1-halogenonaphthalene-4-sulfonic acids yields a mixture of the 2,4-S2 and 4,7-S2, and eventually also some 2,4,7-S3, whereas the 1-halogeno-5-sulfonic acids give the corresponding 5,7-S2. Sulfonation of 2-chloro- and 2-bromonaphthalene yields initially 85% 8-S and 15% 4-S, which are subsequently converted into the 6,8-S2 and 4,7-S2, respectively. On reaction with 1.0 mol-equiv. of SO3, 2-chloroanthracene gives the 9-S, and 9-chloroanthracene gives an 18:82 mixture of the 4-S and 10-S. Both 1,5- and 1,8-dichloroanthracene yield initially the 4-S and subsequently the 4,8-S2 and 4,5-S2, respectively.

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“…A careful analysis of the literature [24,25,26,27,28,29] shows how obtaining the sulfation product could be a challenging target, due to the concurrent formation of the sulfonation product. In particular, Cerfontain and Koeberg-Telder [28] reported a detailed study of the sulfonation of 4-methylphenol in H 2 SO 4 ranging in concentration from 81.6–112.2% and noted that the 2- to 3-sulfonic acid ratio increases strongly upon increasing the H 2 SO 4 concentration.…”

Section: Resultsmentioning

confidence: 99%

Unambiguous Characterization of p-Cresyl Sulfate, a Protein-Bound Uremic Toxin, as Biomarker of Heart and Kidney Disease

et al. 2019

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p-Cresyl sulfate is one of the bound uremic toxins whose level increases in the sera of patients with the severity of chronic kidney disease and is therefore used as a standard for clinical investigations. Our first attempts to obtain p-cresyl sulfate led exclusively to the product of sulfonation of the aromatic ring instead of sulfation on the OH moiety. Nevertheless, this initial discouraging result allowed us to handle both p-cresyl sulfate and 2-hydroxy-5-methylbenzenesulfonic acid obtained by different synthetic pathways. Interestingly, the comparison between the two isomers pointed out that the two molecules show the same fragmentation pattern and are indistinguishable by mass spectrometry. They cannot be separated on several commercially available columns. The only difference between the two compounds is a 10-fold higher ionization yield under negative ion electrospray ionization. NMR spectral studies definitely confirmed the different molecular structures. We present here an unambiguous biomimetic synthetic route for p-cresyl sulfate and the spectroscopic characterization of both the compounds by nuclear magnetic resonance and mass spectrometry.

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Aromatic sulfonation. 90. Sulfonation of three symmetrical 2,6-dialkylphenols, 2,6-dimethylanisole. Sulfation and sulfonation product distributions and mechanisms

Cited by 27 publications

References 3 publications

A Convenient Synthesis of Hydroxytyrosol Monosulfate Metabolites

A Convenient Synthesis of Hydroxytyrosol Monosulfate Metabolites

On the positional reactivity order in the sulfur trioxide sulfonation of benzene, halogenobenzenes, halogenonaphthalenes, and chloroanthracenes

Unambiguous Characterization of p-Cresyl Sulfate, a Protein-Bound Uremic Toxin, as Biomarker of Heart and Kidney Disease

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