DOI: 10.1002/chem.201103628 Reactivity of the 4,5-Didehydroisoquinolinium Cation Nelson R. Vinueza, [a] Enada F. Archibold, [a] Bartłomiej J. Jankiewicz, [a, b] Vanessa A. Gallardo, [a] Steven C. Habicht, [a] Mohammad Sabir Aqueel, [a] John J. Nash, [a] and Hilkka I. Kenttämaa* [a] Introduction Didehydroarenes and their derivatives are reaction inter- mediates that have been known for more than 60 years. [1] Two decades of studies have identified the crucial role of di- dehydroarenes in the biological action of certain antitumor antibiotics, which has led to a renewed interest in the prop- erties of these aromatic carbon-centered s,s-biradicals. [2] However, condensed-phase studies of organic biradicals are challenging due to the difficulty in generating them cleanly in solution. In fact, condensed-phase studies have led to an in-depth understanding of the chemical behavior of only one of the didehydroarenes, 1,2-didehydrobenzene (ortho- benzyne) and its derivatives. [1] Many of the issues that com- plicate the studies of highly reactive species in condensed phases are less problematic in the gas phase. One way to study reaction intermediates in the gas phase involves the well-known distonic ion approach [3] wherein a chemically inert charged group is attached to the reactive intermediate of interest so that it can be manipulated in a mass spectrom- eter. Previous studies carried out by using this approach have demonstrated that the reactivity of charged 1,2-didehy- droarenes in the gas phase is analogous to that reported for their neutral analogs in solution. [4] A comparison of the re- activity [3a,b, 5] of charged 1,2-didehydroarenes to that of 1,3- didehydroarenes in the gas phase has revealed drastic differ- ences that partially reflect the differences in their singlet– triplet gaps (DE ST ). The magnitude of DE ST for singlet birad- icals is thought to affect their ability to undergo radical reac- tions due to the requirement for partial uncoupling of the biradical electrons in the transition state. [6] Consequently, a higher DE ST is expected to lead to higher barriers and slower radical reactions. Indeed, 1,2-didehydroarenes (with large DE ST ) have been found to react like activated alkynes and rapidly undergo nucleophilic or electrophilic addition reactions rather than radical reactions. [4, 5b] However, gas- eous 1,3-didehydroarenes (often with just slightly lower DE ST than 1,2-didehydroarenes) have been demonstrated to undergo both radical and nonradical reactions, depending on their dehydrocarbon atom separation. [5a] A greater dehy- drocarbon atom separation facilitates radical reactions for 1,3-didehydroarenes. Didehydroarenes with more than one heavy atom between the dehydrocarbon atoms (and lower DE ST ), such as the 4,6-didehydroisoquinolinium cation, have been demonstrated to react exclusively via radical mecha- nisms. [7] The 1,8-didehydronaphthalene (1) has been a focus of at- tention for some time. Based on the computational studies of Squires and Cramer, [8] the 1,8-isomer is an especially in- teresting 1,3-didehydroarene since the lowest lying singlet and triplet states are calculated to be nearly degenerate (DE ST = À0.9 kcal mol À1 ) due to the parallel orientation of the formally singly occupied nonbonding molecular orbitals. Abstract: The chemical properties of a 1,8-didehydronaphthalene derivative, the 4,5-didehydroisoquinolinium cation, were examined in the gas phase in a dual-cell Fourier-transform ion cy- clotron resonance (FT-ICR) mass spec- trometer. This is an interesting biradi- cal because it has two radical sites in close proximity, yet their coupling is very weak. In fact, the biradical is cal- culated to have approximately degener- ate singlet and triplet states. This birad- ical was found to exclusively undergo radical reactions, as opposed to other related biradicals with nearby radical sites. The first bond formation occurs at the radical site in the 4-position, fol- lowed by that in the 5-position. The proximity of the radical sites leads to reactions that have not been observed for related mono- or biradicals. Inter- estingly, some ortho-benzynes have been found to yield similar products. Since ortho-benzynes do not react via radical mechanisms, these products must be especially favorable thermody- namically. Keywords: biradicals · didehydro- naphthalene · FT-ICR · ion–mole- cule reactions · reactive intermedi- ates [a] Dr. N. R. Vinueza, E. F. Archibold, Dr. B.J. Jankiewicz, V.A. Gallardo, Dr. S. C. Habicht, M. S. Aqueel, Dr. J. J. Nash, Prof. H. I. Kenttämaa Department of Chemistry, Purdue University 560 Oval Drive, West Lafayette, IN 47907-2084 (USA) Fax: (+ 1) 765-494-0359 E-mail: hilkka@purdue.edu [b] Dr. B. J. Jankiewicz Current Address: Institute of Optoelectronics Military University of Technology Gen. Sylwestra Kaliskiego 2, 00-908 Warsaw (Poland) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201103628.  2012 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim Chem. Eur. J. 2012, 18, 8692 – 8698 8692