A New, Convenient, Highly Selective Free-Radical Hydroxymethylation of Heteroaromatic Bases by Persulfate Oxidation of Ethylene Glycol and Glycerol, Catalysed by AgNO3

Francesco Minisci; Ombretta Porta; Francesco Recupero; Carlo Punta; Cristian Gambarotti; Barbara Pruna; Monica Pierini; Francesca Fontana

doi:10.1055/s-2004-820013

LETTER

A New, Convenient, Highly Selective Free-Radical Hydroxymethylation of Heteroaromatic Bases by Persulfate Oxidation of Ethylene Glycol and Glycerol, Catalysed by AgNO₃

Francesco Minisci*^a, Ombretta Porta^a, Francesco Recupero^a, Carlo Punta^a, Cristian Gambarotti^a, Barbara Pruna^a, Monica Pierini^a, Francesca Fontana^b
^a Dipartimento di Chimica, Materiali e Ingegneria Chimica G. Natta, Politecnico di Milano, via Mancinelli, 7, 20133 Milano, Italy
e-Mail: francesco.minisci@polimi.it;
^b Dipartimento di Ingegneria Industriale, Università di Bergamo, viale Marconi 5, 24044 Dalmine BG, Italy

Abstract

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Abstract

A new, convenient and selective source of hydroxymethyl (^•CH₂OH) radical has been developed by persulfate oxidation of ethylene glycol with AgNO₃ catalysis. The ^•CH₂OH radical is selectively trapped by protonated heteroaromatic bases, providing a new, general process of hydroxymethylation; the importance of the β-scission of the alkoxyl radical intermediate is emphasised.

Key words

hydroxymethylation - heterocycles - free-radicals - diols - persulfate

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References

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<A NAME="RG36003ST-3A">3a</A> Cowden CJ. Org. Lett. 2003, 5: 4497

<A NAME="RG36003ST-3B">3b</A> Minisci F. Recupero F. Punta C. Gambarotti C. Pedulli GF. Fontana F. Chem. Commun. 2002, 2496

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Typical Experimental Procedure: Lepidine (20 mmol), CF₃COOH (20 mmol), (NH₄)₂S₂O₈ (80 mmol) and AgNO₃ (2 mmol) were refluxed in H₂O (75 mL) and ethylene glycol (75 mL) for 3 h. The solution was made basic by NaOH and extracted with CH₂Cl₂. GC analysis (quinoline as internal standard) revealed the presence of 2-hydroxymethyllepidine (18.5 mmol) and lepidine (1.3 mmol). The CH₂Cl₂ solution was evaporated and the residue gave, by flash chromato-graphy (hexane-EtOAc, 2:1) pure 2-hydroxymethyllepidine (17.1 mmol), identified by comparison with an authentic sample. The results in the Table 1 refer to GC analyses.