Converting Caffeine to Electronically Different N-Heterocyclic Carbenes with a Hypoxanthine Backbone

Abstract

The synthesis of the new mixed amino–amido N-heterocyclic carbene 2, featuring a hypoxanthine structural unit, starting from caffeine via the hypoxanthinium precursor 4 is described. NHC 2 forms adducts with group 6 elements, coordinates to L2ClRh fragments (L2 = COD, (CO)2), or dimerizes to yield olefin 8. The donor properties of NHC 2 were evaluated by IR spectroscopic assessment of its TEP value (2058 cm–1), which is typical for an amino–amido NHC. Dicarbenes are also easily obtained by converting the imidazole moieties of the hypoxanthinium cation 4 or the olefin 8 into NHC functions. X-ray structure determinations of a Rh complex of carbene 2 and the olefinic dicarbene precursor 13 are presented.

Determining the Ligand Properties of N‐Heterocyclic Carbenes from 77Se NMR Parameters

“…Sodium bis(trimethylsilyl)amide (2 M in thf; Acros Organics, CAS: 1070‐89‐9), selenium powder (Strem Chemicals, 99.5 %; CAS: 7782‐49‐2), and methyl trifluoromethanesulfonate (Acros Organics, CAS: 333‐27‐7) were purchased and used as received. Compounds 4· Se, 5· Se, 9· Se, 13· Se, 18· Se, 20· Se, 22· Se,9 7· Se,10b 11· Se,17c 15· Se,17e 17· Se, and 19· Se17g are known in the literature. N , N′ ‐1,4‐Bis(4‐fluorophenyl)‐1,4‐diaza‐1,3‐butadiene,28 1· HBr, 4· HBr,29 2· HI,30 3· HCl, 5· HCl,31 6· HCl,32 7· HCl,33 10· HPF 6 ,34 11· HBr,17c 13· HBr,35 1,3‐dimesityl‐4‐hydroxyimidazolium chloride,36 16· HClO 4 ,17f 17· HNO 3 , 19· (HOTf) 2 ,17g 18· HCl,17h and 21· HOTf4i were prepared according to the literature.…”

Xanthine Scaffold: Available Synthesis Routes to Deliver Diversity by Derivatization

“…As we have described earlier for xanthine-NHC complexes, the literature mainly reports the use of caffeine as starting material for the synthesis of the corresponding NHC (N-heterocyclic carbene) metal complexes, after its transformation into the corresponding caffeinium salt and deprotonation at the C 2 atom of the imidazolium ring [56,51]. Nonetheless, a few papers report the use of caffeine as a starting material in organic synthesis [81,82].…”

Caffeine gold complex supported on magnetic nanoparticles as a green and high turnover frequency catalyst for room temperature A3 coupling reaction in water

“…Therefore, a loading of 0.007 mol% of catalyst, room temperature and water were selected as the optimized reaction conditions. To study whether cationic gold species are working as actual catalysts using Fe 3 O 4 @Caff-Au, 15) with piperidine and phenylacetylene proceeded very well affording 91% and 90% isolated yields, respectively. In addition, reaction of heterocyclic 3-thiophenecarbaldehyde with piperidine and 2thiophenecarbaldehyde with morpholine and phenylacetylene were performed efficiently giving 95% and 91% yields, respectively ( Table 2, entries 16 and 17).…”

“…Caffeine is a natural precursor widely consumed in beverages, the most commonly used drug in the world, and its analogues have recently drawn attention for their possible therapeutic applications as anticancer agents . Recently, the imidazole ring of caffeine has been used as a N‐heterocyclic carbene precursor for the preparation of gold (I), silver, Rh or Ir, and Pt complexes, which showed interesting anticancer and biological properties. Also, Pd complex of caffeine has been employed in Suzuki, Heck and Sonogashira reactions under homogeneous conditions in aqueous media .…”