THEORETICAL MODELING OF SEMIBULLVALENE SYNTHESIS

CHEM260 FALL2016
KEYANG SUN

1. INTRODUCTION

Semibullvalene (SBV) is a synthetically fascinating fluxional molecule that undergoes

rapid cope rearrangement even at -110°C[3] and has prompted many studies exploring its
synthesis. While the principle pathways to semibullvalene all include isomerization of cyclic
precursors such as barrelene, cyclooctatetraene and tricyclo[3.3.0.02.8]octa-3,7-diene,[1] Sauer et.
al. proposed an alternative approach to semibullvalene synthesis using 3,3’-bicyclopropenyl and
1,2,4,5-tetrazinediester in a sequence of cycloaddition-cycloelimination steps accompanied by
dinitrogen extrusions[2]; the mechanism can also introduce structural variations by substitution of
1,2,4,5-tetrazine.
The purpose of this computational study is to elucidate the energetics of the synthesis of
semibullvalene via density functional theory (DFT), specifically, comparing the thermodynamic
states of the aforementioned cyclic precursors, investigating the free energy change of the
mechanism proposed by Sauer et. al., and visualizing the orbital interactions of SBV as it
undergoes rapid [3,3]-sigmatropic rearrangement.

2. RESULTS AND DISCUSSION

2.1 Cope Rearrangement

All calculations were performed using QChem 4.4.1[8] using B3LYP/6-31G** level of
theory; all frequency calculations were computed at 298.15K. The fluxional thermal barrier to
the degenerate cope rearrangement of SBV is computed to be 4.35 kcal/mol (figure 1), which
agrees with the experimental value of 4.8±0.2 kcal/mol.[7]

Figure 1. Enthalpy (298.15K) diagram for the [3,3] sigmatropic rearrangement of SBV

Qualitatively, the facile nature of the pericyclic reaction can be attributed to the benzene-
like six-membered ring transition state (TS), which gives significant aromatic stabilization. The
six-electron reaction follows the Hückel topology in a disrotatory [π2S+σ2S+π2S] reaction. The
reactant and product SBV, which belong to the CS symmetry group, are connected through a TS
structure of C2V symmetry that contains elements of both CS groups; this conservation of
symmetry is consistent with principles of electrocyclization reaction. In the computed wave
function of the lowest unoccupied molecular orbital (LUMO) of SBV, it is possible to delineate
the overlaps visually (figure 2); the LUMO of the π systems in the reactant SBV shows a
constructive supraficial interaction between the LUMO of C3 and C4 (shown in red) to form the
σ-bond in the product SBV. The σ-bond (shown in red) in the reactant SBV mixes with the π
LUMO between C and C in a disrotatory fashion to form the π system between C1 and C2, and
C6 and C5 in the product SBV.

Figure 2. Computed LUMO of SBV

At the transition state, the highest occupied molecular orbital (HOMO) wave function
resembles one of the two degenerate HOMOs of the benzene π system from a simple Frost
diagram analysis (figure 3). The Cope rearrangement TS can also be viewed as constructive
mixing of the nonbonding LUMO of two allyl or propylene systems between C1, C2, C3 and C4,
C5, C6; this is evident in the calculated TS structure: the bond lengths between C1 and C2, C2
and C3, C4 and C5 and, C5 and C6 are all equivalent at 1.39Å.

Figure 3. Computed HOMO of the TS shown in figure 1.

2.2 Semibullvalene Synthesis

The reaction of 1,2,4,5-tetrazine and 3,3’-bicyclopropenyl to SBV was modeled via the
mechanism shown in figure 5 to yield the minimum free energy path shown in figure 4
calculated at the B3LYP/6-31G** level of theory at 298.15K; The intermediates were optimized
individually, each accompanied by a frequency and a single point energy calculation, which
produced enthalpy, entropy values as well as the intrinsic electronic energy of the molecule. TS
were determined via the freezing string method to obtain intermediate structures along the
reaction coordinate for reaction steps 1,2, 3 and 4; a transition state search is performed after,
followed by a frequency and single point energy calculation.

Figure 4. Free-energy (298.15K) diagram of SBV synthesis. The elementary steps are labeled
according to the reaction mechanism shown in figure 5.

An intermolecular Diels-Alder cycloaddition initiates the reaction with a barrier of 22.7

kcal/mol and irreversibly loses nitrogen in a facile cyclic step with a barrier of 2.2 kcal/mol to
form the sterically less hindered diazanorcaradiene stereoisomer C. The equilibrium between C
and the more sterically demanding isomer F requires 13.3 kcal/mol through rotational
conformers D, E of a diazepine intermediate; calculations of the TS of these equilibrium steps
were omitted.

Figure 5. Mechanism of SBV synthesis

 An intramolecular [2+4] cycloaddition involving the diazanorcaradiene stereoisomer F
forms a polycyclic-azo compound G with a barrier of 18.5 kcal/mol. A fast step follows with the
nitrogen extrusion from G to form SBV. The overall change in free energy was calculated to be
extremely favorable at -160.1 kcal/mol. The exergonicity of the reaction is reflected in the
instability of the reactants: specifically, the two highly strained cyclopropene units of 3,3’-
bicyclopropenyl and the large enthalpy of formation of 1,2,4,5-tetrazine.[2]
The initial intermolecular [2+4] cycloaddition is calculated to be the rate-determining
step (RDS), and the apparent activation energy is represented by the initial barrier to form the
adduct B. It is possible to obtain kinetic parameters from this simple second order reaction as
described by Eq.1, where 𝐤 𝐓𝐒𝐓 𝐀𝐁 is the rate constant and 𝐭𝐞𝐭𝐫𝐚𝐳𝐢𝐧𝐞 and [𝐛𝐢𝐜𝐲𝐜𝐥𝐨𝐩𝐫𝐨𝐩𝐞𝐧𝐲𝐥] are
the concentrations of the reactants.

𝐫𝟏 = 𝐤 𝐓𝐒𝐓
𝐀𝐁 𝐭𝐞𝐭𝐫𝐚𝐳𝐢𝐧𝐞 [𝐛𝐢𝐜𝐲𝐜𝐥𝐨𝐩𝐫𝐨𝐩𝐞𝐧𝐲𝐥]

The rate constant can be calculated via transition state theory using the Eyring-Polanyi
equation, where 𝐤 𝐁 is the Boltzmann’s constant, T is the temperature, h is Planck’s constant, R
!
is the gas constant and 𝚫𝐆𝑨𝑩 is the free energy change from state A to state B as shown in Figure
4. From this, 𝐤 𝐓𝐒𝐓
𝐀𝐁 is found to be 1.42e-4 s-1.
!
𝐤𝐁𝐓 𝚫𝐆𝑨𝑩
𝐤 𝐓𝐒𝐓
𝐀𝐁 = 𝐞𝐱 𝐩 − = 𝟏. 𝟒𝟐×𝟏𝟎!𝟒 𝒔!𝟏
𝐡 𝐑𝐓

The rate-determining intermolecular Diels-Alder reaction undergoes an allowed [π4S+π2S]

cycloaddition. In a computed wave function of the HOMO of the TS, we can visualize the
interactions via frontier molecular orbital (FMO) theory. We can delineate the constructive
mixing of the 1,2,4,5-tetrazine LUMO and the HOMO of one of the cyclopropene unit on
bicyclopropenyl as seen in figure 6 (shown in red).

Figure 6. Computed HOMO of A! shown in figure 4

Some of the principle routes to SBV involves the isomerization of several cyclic
precursors (Figure 7): barrelene L, cyclooctatetraene K and tricyclo[3.3.0.02.8]octa-3,7-diene J.
Barrelene is most energetically similar to SBV within 1.4 kcal/mol, while compound J is higher
in energy by 28.2 kcal/mol and compound K is lower by 6.9 kcal/mol. In fact, it is shown by
Martin et. al. that cyclooctatetraene is the primary thermal decomposition product of SBV.[6]
 Figure 7. Relative free-energies of various SBV precursors.

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