A New Cyclization to Fused Pyrazoles Tunable for Pericyclic or Pseudopericyclic Route: An Experimental and Theoretical Study

• Published in: Journal of organic chemistry Vol. 73; no. 10; pp. 3900 - 3906
• Main Authors: Filák, László, Rokob, Tibor András, Vaskó, Gyöngyvér Ágnes, Egyed, Orsolya, Gömöry, Ágnes, Riedl, Zsuzsanna, Hajós, György
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 16.05.2008; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Computer Simulation; Cyclization; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Kinetics and mechanisms; Models, Molecular; Molecular Structure; Organic chemistry; Physical Sciences; Preparations and properties; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Quantum Theory; Reactivity and mechanisms; Science & Technology; Stereoisomerism; ENERGY; AROMATICITY; AZOLIUM SALTS; MOLECULAR-ORBITAL METHODS; AB-INITIO; GAUSSIAN-TYPE BASIS; BASIS-SETS; DERIVATIVES; INDEPENDENT CHEMICAL-SHIFTS; Aromaticity; Quantum chemistry; Nitrogen heterocycle; Pyrazine derivatives; Theoretical study; Experimental study; Ketone; Cyclization; Pyrazole derivatives; Reaction mechanism; Pyridazine derivatives; Basic medium; Pericyclic reaction; Hydrazone; Chemical synthesis; Acid medium; Magnetic properties
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo800483a

2-Pyrazinyl (2) and 3-pyridazinylketone arylhydrazones (6) and their benzologues undergo a ring closure reaction to yield pyrazolo[3,4-b]pyrazines (4) and pyrazolo[4,3-c]pyridazines (7), respectively, in acceptable to good yields. The reaction was found to be accelerated by using acidic or basic conditions. Quantum chemical calculations suggest the key step of the mechanism to be a direct cyclization; analysis of aromaticity based on computed magnetic properties revealed its medium-dependent pericyclic or pseudopericyclic character. The cyclization reaction has also been extended for the synthesis of related ring systems (9, 12, 14).