Facile N9-Alkylation of Xanthine Derivatives and Their Use as Precursors for N-Heterocyclic Carbene Complexes.

Moloud Mokfi,Jörg Rust,Christian W Lehmann,Fabian Mohr

doi:10.3390/molecules26123705

Moloud Mokfi, Jörg Rust + Show 2 more

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https://doi.org/10.3390/molecules26123705

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Abstract

The xanthine-derivatives 1,3,7-trimethylxanthine, 1,3-dimethyl-7-benzylxanthine and 1,3-dimethyl-7-(4-chlorobenzyl)xanthine are readily ethylated at N9 using the cheap alkylating agents ethyl tosylate or diethyl sulfate. The resulting xanthinium tosylate or ethyl sulfate salts can be converted into the corresponding PF6− and chloride salts. The reaction of these xanthinium salts with silver(I) oxide results in the formation of different silver(I) carbene-complexes. In the presence of ammonia, ammine complexes [Ag(NHC)(NH3)]PF6 are formed, whilst with Et2NH, the bis(carbene) salts [Ag(NHC)2]PF6 were isolated. Using the xanthinium chloride salts neutral silver(I) carbenes [Ag(NHC)Cl] were prepared. These silver complexes were used in a variety of transmetallation reactions to give the corresponding gold(I), ruthenium(II) as well as rhodium(I) and rhodium(III) complexes. The compounds were characterized by various spectroscopic methods as well as X-ray diffraction.

Highlights

Metal complexes containing N-heterocyclic carbenes (NHCs) are today considered a common class of ligands in organometallic chemistry
As an alternative to these reagents, methyl tosylate or dimethyl sulfate have been successfully used for N9-methylation in xanthines, affording the respective xanthinium tosylate or methyl sulfate salts in high yields and short reaction times (90 min at 170 ◦C without additional solvent) [16,46,47,48]
We examined the feasibility of introducing ethyl groups in position 9 of different xanthine derivatives with ethyl tosylate or diethyl sulfate

Summary

Introduction

Metal complexes containing N-heterocyclic carbenes (NHCs) are today considered a common class of ligands in organometallic chemistry. Their seemingly endless structural variety combined with a very stable metal-carbon-bond makes carbene complexes so important in homogeneous catalysis and for biomedical applications [1,2,3,4,5,6,7,8,9,10,11,12,13,14]. Given our interest in NHC-complexes of various metals and their biological activity and reactivity [39,40,41,42,43,44], we wished to develop more efficient methods to access a greater variety of xanthinium salts as well as their corresponding metal carbene-complexes

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