Steven Kass, Associate Fellow

Understanding Organic Systems via Molecular Orbital Calculations

Ab initio molecular orbital and density functional calculations were carried out on a variety of organic systems during this research period. Particular attention was paid to reactive intermediates (key intermediates in numerous chemical and industrial processes), antiaromatic compounds (potential substrates for the design of novel materials), and zwitterions (important species in biological processes). These results aided in the design and interpretation of experimental data.

Specific work within this overall research focus produced a number of results. For example, the researchers considered the impact of fusing a strained ring onto benzene. The gasphase acidities of the two aromatic sites in benzocyclobutene were measured in a Fourier transform mass spectrometer using a kinetic technique (i.e., the DePuy method). Fusion of a cyclobutane ring onto benzene was found to have a slight acidifying effect on the α-position (3.2 ± 1.7 kcal mol^-1) and little, if any, influence on the β-site (0.8 ± 1.9 kcal mol^-1). Energetic data (∆H˚acid = 386.2 ± 3.0 kcal mol^-1, EA = 0.84 ± 0.11 eV, and C-H BDE = 92 ± 4 kcal mol^-1) for the benzylic position were obtained via the bracketing technique and application of a thermodynamic cycle. Differences in the reactivities of the three conjugate bases also were explored. Ab initio and density functional theory calculations were carried out to provide geometries, energies, and insights into the carbanions’ electronic structures.

Also in this period, benzocyclobutadienyl diazirine was synthesized and reacted with hydroxide ion in a Fourier transform mass spectrometer to produce the conjugate base of benzocyclobutadiene (1a). Authentication of the ion structure was carried out by a derivatization experiment (i.e., 1a was converted to benzocyclobutenone enolate, which has previously been studied), and its reactivity was explored. Thermochemical data for benzocyclobutadienene were obtained (∆H˚acid (1) = 386 ± 3 kcal mol-1, EA(1r) = 1.8 ± 0.1 eV, and C-H BDE (1) = 114 ± 4 kcal mol^-1), compared to MP2 and B3LYP calculations, and contrasted with a series of model compounds. Cyclobutadienyl radical appears to be quite different from benzocyclobutadienyl radical (1r) and worth further exploration.

In another experiment, dodecahedryl anion (1a) was generated in a Fourier transform mass spectrometer by deprotonation of dodecahedrane (1). Examination of the acid and base behavior of 1 and 1a, respectively, enabled the acidity of 1 to be determined (∆H˚acid = 402 ± 2 kcal/mol). Good agreement is found with the 298 K computed MP2/6-31 + G(d)//HF/6-31 + G(d) value of 405.1 kcal/mol. In a similar manner, the electron affinity of dodecahedryl radical was measured (EA = 4 ± 2 kcal/mol). These results were combined in a thermodynamic cycle to afford the C-H bond dissociation energy of dodecahedrane (BDE = 92 ± 3 kcal/mol), which is reasonably well reproduced (96.7 kcal/mol) at the MP2/HF level but leads to the suggestion that the reported heat of hydrogenation of dodecahedrene is in error. The DePuy kinetic method for measuring the acidity of 1 also was explored. It was found that this approach works well with triphenylsilyldodecahedrane but gives poor results with triethylsilyldodecahedrane. This latter failure is attributed to steric effects, and provides a rationale for several problem cases and a means to overcome these difficulties.

Furthermore, benzocyclobutadiene radical anion (5) was synthesized by the researchers in the gas phase by three independent approaches: collision-induced dissociation (CID) of 1,2- benzocyclobutenedicarboxylate, reaction of 2- trimethylsilyl-1-benzocyclobutenyl anion with neopentyl nitrite followed by CID of the resulting β-nitroso carbanion intermediate, and reaction of the same β-silyl carbanion with molecular fluorine. The proton affinity and electron binding energy of 5 were measured (0.32 ± 0.05 eV and 368 ± 2 kcal mol-1 respectively) and combined in a theromdynamic cycle to obtain the heat of hydrogenation (49 ± 4 kcal mol-1) and the heat of formation (97 ± 4 kcal mol-1) of benzocyclobutadiene (1). These results were compared to model compounds as well as MP2 and B3LYP calculations in order to assess the antiaromatic destabilization energy of 1. Based on this data, a predicted heat of formation of cyclobutadiene (102 kcal mol-1) was obtained. This work demonstrated the utility of dicarboxylates as radical anion precursors and the electron as a protecting group.

In addition to these projects, the research group generated dicarboxylates by electrospray ionization mass spectrometry and found that they lose carbon dioxide and an electron upon collision-induced dissociation to afford distonic ions. These radical anions can also be synthesized via laser desorption, chemical ionization, and electron ionization of dibenzyl esters. Subsequent fragmentation of the remaining CO2 affords new radical anions corresponding to neutral reactive intermediates. By measuring the proton affinities and electron binding energies of these species, quantitative energetic information on carbenes, biradicals, and other transient molecules can be obtained. This approach was demonstrated by measuring the heats of formation of 2,3- and 2,6-dehydronaphthalene; ancillary thermochemical data also were derived, and the results were then compared to either o- or p-benzyne.

Yet another project sought to probe electrostatic effects using the formation and characterization of zwitterionic ions and their “neutral” counterparts in the gas phase. A dipolar ion and its non-zwitterionic counterpart were generated and characterized in the gas phase. A single charge site was found to be sufficient to lower the energy of a zwitterion well below its neutral counterpart. Charge separation in a dipolar anion enables hydrogen–deuterium exchange to take place with acids over an extraordinarily large range. These results provide a basis for studying electrostatic effects and understanding mass spectroscopic processes involving large biological molecules.

Research Group and Collaborator

Victoria M. Bedell, Supercomputing Institute Undergraduate Intern
Jelena Dacres, Research Associate
Zoran Glasovac, Department of Organic Chemistry and
Biochemistry, Ruder Boskovic Institute, Zagreb, Croatia
Lev Lis, Research Associate
Sudha Marimanikkuppam, Research Associate
Dana R. Reed, Graduate Student Researcher
Ashutosh Singh, Graduate Student Researcher