Synthesis of 8-Bromo-N-benzylpurines via 8-Lithiated Purines: Scope and Limitations

Abstract

9-Benzylpurines have been lithiated in the 8-position and subsequently brominated when trapped with BrCCl₂CCl₂Br. The 8-bromopurines were isolated in excellent yields when the benzyl group carried an alkoxy or alkyl group in the ortho or para position. Without these substituents, the conversion was generally less, and formation of 8,8′-purinyl dimers was observed. There was also evidence of debenzylation in some instances. Bromination of 7-benzylpurines employing the same set of reaction conditions has also been achieved.

Keywords:

• Bromination
• debenzylation
• dimerization
• lithiation
• purine

ACKNOWLEDGMENTS

The Quota scholarship to T. G. is gratefully acknowledged. The authors also thank the Norwegian Research Council for the partial financing of the Bruker Avance NMR instruments used in this study.

Notes

^a After adding BrCCl₂CCl₂Br.

^b Molecular ratio taken from the ¹H NMR spectra of the crude products.

^c No aldehyde present in the crude product according to ¹H NMR.

^d Based on the presence of a signal at 6.10 ppm in the crude ¹H NMR spectrum, which may be assigned to the CH₂ in the dimer.

^e Not isolated.

^f Molecular ratio 1:2:5.

^g Dimer 5 (Fig. 1) isolated in 4%.

^h A signal was present in the ¹H NMR spectrum of the crude product, which corresponded well with the reported ppm value for the CHO proton in the aldehyde 4.

ⁱ Based on the presence of a signal at 6.27 ppm in the crude ¹H NMR spectrum, which may be assigned to the CH₂ in the dimer.