FULL PAPER DOI: 10.1002/ejoc.200700132 Design of Brønsted Neutral Organic Bases and Superbases by Computational DFT Methods: Cyclic and Polycyclic Quinones and [3]Carbonylradialenes Ines Despotovic ´, [a] Zvonimir B. Maksic ´, [a,b] and Robert Vianello* [a] Keywords: Proton affinity / Basicity / Aromaticity / Cationic resonance / Relaxation effects The gas-phase proton affinities and basicities of a large number of extended polycyclic π systems possessing a car- bonyl oxygen head serving as a basic proton scavenger are explored by using DFT at the B3LYP/6-311+G(d,p)//B3LYP/ 6-31+G(d) level of theory. Some of these neutral organic superbases exhibit proton affinities in the range of 264– 284 kcal mol –1 . In constructing these systems it turned out that a =C(NMe 2 ) 2 fragment attached to a quinoid six-mem- bered ring enhanced the basicity to a considerable extent. There is abundant and convincing evidence that protonation Introduction Notwithstanding its size, the proton plays a gargantuan role in many chemical phenomena being in particular of paramount importance in acid–base chemistry and bio- chemistry. [1–3] It is pivotal in the very definition of Brønsted acids and bases, which in turn are fundamental concepts in chemistry. In this paper we shall focus on neutral organic (super)bases which are very useful auxiliaries in chemical synthesis [4] as they have some distinct advantages over their inorganic ionic counterparts. The latter exhibit some un- favourable features, such as poor solubility in most organic solvents and pronounced sensitivity to moisture and CO 2 . On the other hand, neutral organic (super)bases permit the use of mild reaction conditions. [5] They show very good sta- bility at low temperatures [6] and exhibit an enhanced reac- tivity towards naked anions forming poorly associated ion pairs upon deprotonation. [7] Finally, it should be stressed that they are efficient catalysts particularly if immobilized on appropriate surfaces [8–11] being recyclable and conse- quently desirable and acceptable in green chemistry. Last but not least, neutral organic (super)bases have found use- ful applications in both catalytic and stoichiometric asym- metric syntheses. [12] In recent years, the work on proton af- finities and proton transfer reactions has been reviewed in several review articles. [13–18] [a] Quantum Organic Chemistry Group, Division of Organic Chemistry and Biochemistry, Rudjer Bos ˇkovic ´ Institute, Bijenic ˇka 54, 10000 Zagreb, Croatia Fax: +385-1-4561118 E-mail: vianello@spider.irb.hr [b] Faculty of Science, Department of Physical Chemistry, The University of Zagreb, Horvatovac 102A, 10000 Zagreb, Croatia Supporting information for this article is available on the WWW under http://www.eurjoc.org or from the author. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Eur. J. Org. Chem. 2007, 3402–3413 3402 triggers strong aromatization of the quinoid rings. Moreover, sequential quinoid rings undergo the aromatic domino effect upon protonation if linearly aligned. Triadic analysis has re- vealed that highly pronounced basicity in some studied sys- tems is a result of the synergistic action of Koopmans’ frozen neutral base ionization energy contribution and subsequent relaxation of the radical cation. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) It is, therefore, not unexpected that a lot of effort has been devoted over several decades to the design of new neu- tral organic bases with pronounced basicities both in the gas phase and in organic solvents. Examples include amides and imidates, [19] cyclic and acyclic guanidines, [20–23] phos- phazenes, [24–26] quinoimines and related systems, [27] quinol- ylboranes, [28] extended 2,5-dihydropyrrolimines [29] and C 2 diamines. [30] The extensive theoretical and experimental work carried out by Koppel, Leito and co-workers should be singled out as it includes both the theoretical design and the synthesis of organic bases and superbases as well as measurements of their pK a values in various solvents. [31–35] The intramolecular hydrogen bonding (IMHB) motif proved very useful for this purpose too, [36,37] being particu- larly effective if utilized in a cooperative way by including multiple hydrogen bonds. [38–40] A lot of attention has been focused on neutral organic bases known as “proton sponges” possessing chelating proton-acceptor functionali- ties. The archetypal proton sponge is Alder’s DMAN [1,8- bis(dimethylamino)naphthalene] synthesized some 35 years ago. [41] The design of proton sponges more basic than DMAN has received unabated interest ever since. [42–52] Alder’s seminal idea materialized in DMAN was advan- tageously extended recently through the preparation of TMGN [1,8-bis(tetramethylguanidino)naphthalene] [53,54] and HMPN [1,8-bis(hexamethyltriaminophosphazenyl)- naphthalene] [55] in which the NMe 2 groups in DMAN were replaced by the guanidino and phosphazeno functionalities, respectively. Although all of these compounds offer a wide variety of superbases, there is a need for new alternative systems exhibiting different physical and chemical properties occu-