Synthesis of 2-aryl-5,5-dimethyl-5,6-dihydro-1,2,4-triazolo-[3,4-a]isoquinolinium tetrafluoroborates

Abstract

Recently the chemistry of N-heterocyclic carbenes made rapid progress, as seen from a large number of freshly published reviews [1–4] and a monograph [5]. In the modern organic synthesis the N-heterocyclic carbenes are used either directly [1, 2] or in complexes with transition and nontransition metals [3]. N-heterocyclic carbenes known now and their derivatives known now contain metal complexes based on salts of 1,2,4-triazole substituted with chiral functional groups [6] and of 1,2,4-triazole fused with pyrrolidine [7], oxazole [8], oxazine [9], morpholine [10], indeno[2,1-b]morpholine [11], and also with indeno[1,2-b]pyrroline, naphtho[1,2-b]pyrroline, and naphtho[2,1-b]morpholine [2]. Yet the heterocyclic system of triazolo[3,4-a]isoquinoline was notused as a precursor of N-heterocyclic carbenes. The target of the present study was the preparation of 2-aryl-5,5-dimethyl-5,6-dihydro-1,2,4-triazolo[3,4-a]isoquinolinium salts and their 8,9-dimethoxy analogs as precursors N-heterocyclic carbenes. We chose for counterion the tetrafluoroborate anion since unlike chlorides and bromides 2-aryl-5,5-dimethyl-5,6-dihydro-1,2,4-triazolo[3,4-a]isoquinolinium tetrafluoroborates were nonhydroscopic, heat-resistant, and formed well-developed crystals. The developed method of preparation of the target compound consisted in the cyclization of amidrazones IIa–IIe, obtained via methylsulfanyl derivatives Ia and Ib, carried out in excess ethyl orthoformate in the presence of ammonium tetrafluoroborate. Amidrazones IIa–IIe were obtained by heating 1methylsulfanyl-3,4-dihydroisoquinolines Ia and Ib [12] with arylhydrazines in an argon atmosphere at ~170– 180°C for 0.5–1 h. Compounds IIa and IIb have been isolated as yellow oily substances darkening in air and stable at room temperature for several days; amidrazone IIe can be stored at room temperature for 6 months without visible signs of decomposition . The attempts to isolate intermediate amidrazones IIc and IId in pure state failed due to their fast oxidation in air, therefore we further used them direct after the synthesis in the cyclization into the target compounds IIIc and IIId. Amidrazones IIa–IIe may exist in two tautomer forms but 1H NMR spectra detect the form shown in the scheme as indicated by the downfield shift of the signal belonging to proton HC8 [13]. Salts IIIa–IIIe are colorless or light-yellow (IIIb and IIIe) crystalline substances soluble in DMF, DMSO,