Transition State Search

Computing transition states generally not being a straightforward task, it reveals its own challenges for the interconversion of two non-covalent dimer complexes. There are multiple ways to obtain barrier heights.¹⁰² When regarding the interconversion of monomer conformations scanning of a dihedral angle is commonly used.⁴⁹ But normally there is no such distinct reaction coordinate to scan for the interconversion of two dimer conformations. Alternatively, Quasi-Newton algorithms can be used.

However, they only succeed if the initial guess is sufficiently close to the transition state geometry. Thus, finding a suitable initial guess is the true challenge.

For finding an initial geometry, two different methods have been used. In favorable cases a pseudo reaction coordinate can be defined and a relaxed surface scan of this coordinate applied. ORCAcan combine these two steps, but this has not been tested in this thesis. For the hydrogen bonded clusters studied in this thesis one can try scanning the H–O distance, when changing from one binding type to the other, preferably starting from the less defined binding type (OH–π) to the well defined (OH–O). For the flexible acceptor molecule diphenyl ether, a relaxed scan of the conversion from one monomeric enantiomer to the other has been successful.

If no suitable pseudo reaction coordinate to scan was apparent, the woelfling module of Turbomole has proven to be a useful tool. It creates an initial guess of the reaction path by a modified linear synchronous transition (LST) method¹⁰³ before optimizing it assuming a quadratic potential with the constraint of equal spacing of structures along the path.¹⁰⁴ Thorough attention has to be paid to the atom labeling. Therefore, running a test stopping after the LST step and checking for a reasonable first path is always worthwhile. Although, woelfling has a key-word for aligning the input structures, the use of pre-aligned input structures (and possibly disable the automatic alignment) might help. Furthermore, symmetry of the monomer molecules has to be taken into consideration. Starting from the same

’educt’ geometry, the lowest energy path is generally different for the conversion into two enantiomeric ’product’ structures. Thereby, the atom numbering can also be used to force woelfling to try another pathway. Additionally, a stepwise reaction path, including a local minimum as an intermediate structure should be considered, especially when determining the reaction path for other than the two lowest energy structures.⁸³Having obtained a plausible reaction path, the maximum energy struc-ture can be taken as the initial guess transition state.

Since ORCA was used as the standard method for geometry optimization in this thesis, if not stated otherwise, the final transition states have also been obtained by this program at B3LYP-D3(BJ, abc)/def2-TZVP level. It utilizes a quasi-Newton like Hessian mode following algorithm.¹⁰⁵ The same keywords stated previously have been used, with ’OptTS’ added to specify the optimization to a transition state. This includes the ’FREQ’ keyword for the frequency calculation to verify that

the obtained geometry has exactly one imaginary frequency, its mode connecting the two equilibrium structures. Additionally, plotting an overlay of the start, end and transition state geometries helps to check for plausibility. A second run of woelfling’s LST step for an initial path might also help to visualize the reaction pathvia the determined transition state. Recalculation of the Hessian matrix every 5 steps improved the geometry convergence.

Furthermore, the transition state search methods of the Gaussian program⁹⁶ have been tested. Gaussian offers the QST (quadratic synchronous transit) met-hods, which combine an initial quadratic synchronous transit approach followed by a quasi-Newton optimization. Two variants can be used, QST2 and QST3, depen-ding if an initial guess for the transition state is available. For the tested conformer interconversions only the QST3 method with an initial guess fromwoelfling was able to provide a transition state. Besides, the TS option is available to optimize to a transition state instead of an equilibrium structure using the Berny algorithm.

A more general guide on which method to apply for finding transition states can be found in Ref. 102. Further approaches mentioned therein potentially suitable for dimer complexes are a normal symmetry-constrained geometry optimization if the transition state can be defined by symmetry or the use of a transition state obtained for a related cluster as the initial guess.

As a heterocycle, furan offers two acceptor sites for hydrogen bonding with a protic solvent. Theπsystem would usually be regarded inferior to an oxygen atom acceptor for an OH hydrogen bond, but as the latter is part of the π system, the situation is at level, since the electron density of the oxygen atom is also distributed. Furans are therefore well suited as molecular balances for these two different hydrogen bond types.37,38,106,107 Furthermore, their rigidity allows for only a small amount of conformers and thus simplifies the IR spectrum. Linear FTIR spectroscopy is especially suited for measuring this class of compounds as it is not affected by the ultrafast photodynamics of the electronically excited state.¹⁰⁸

Furan and its derivatives have been studied thoroughly for their complexation behavior. The furan dimer itself presents a molecular balance between weak CH–O and CH–πinteractions. In a theoretical study using DFT methods, the combination of two CH–O contacts has been found superior. However, dispersion corrections were not applied.¹⁰⁹Microwave spectroscopy has been used to study van-der-Waals clusters of furan. As can be expected, the argon(2) cluster^110–112 as well as the CO cluster¹¹³ exhibit binding to the πface. Line splitting indicated a hindered internal rotation of CO above the furan plane. SO2 is also bound to the π face of furan.¹¹⁴ Furthermore, excited complexes of furan derivatives with aromatic hydrocarbons in solution have been investigated using fluorescence spectroscopy.^115,116

The most systematically studied class of complexes are those of hydrogen hali-des and their analogues with furan and its derivatives. They have been investiga-ted both theoretically^36,117–120 and experimentally¹²¹. An early study recorded IR band shifts and formation enthalpies of HF with furan and 2,5-dimethylfuran in solution.¹²² Later studies confirmed the proposed binding to the oxygen site using microwave spectroscopy¹²³, although the structure assignment is more ambiguous when going down the halogen group. For furan–HCl, an oxygen-bound conformer was identified using microwave spectroscopy¹²⁴, while both docking variants were found by FTIR spectroscopy.¹²⁵ The rotational spectrum of furan–HBr revealed a

face-on conformation, but the hydrogen is pointed towards the oxygen atom.¹²¹ An evenly balanced case has also been found for the furan–acetylene dimer prepared by helium nanodroplets spectroscopy experiments,¹²⁶ while the preparation in argon matrix was found to favor the oxygen-bound species.^36,127 As theπ system of this donor forms secondary interactions with theortho CH group breaking theC2v sym-metry, these types of complexes have been the subject of a theoretical study.³⁶ The furan–ethylene dimer has also been studied by microwave spectroscopy, revealing a T-shaped dimer structure, that compromises CH–O and CH–π interactions.¹²⁸

Hydrogen bonded complexes with NH donors have also shown to form complexes with the oxygen as an acceptor as well as π-bound complexes,^37,106 whereas only oxygen-bound conformers have been identified for the OH donor formic acid me-asured in argon matrix¹⁰⁷. A very recent matrix isolation study¹²⁹ also found a single oxygen-bound conformer for furan–water, which was already predicted by theory.^130,131 The same holds true for methanol as reported by a matrix isolation study, that was published during this project.¹³² However, the band assignment was based on DFT calculations without dispersion correction, whose inclusion reverses the predicted stability sequence. Furthermore, the applied argon matrix might influ-ence the band shifts, as indicated by the offset of 20 cm⁻¹of the methanol monomer band¹³³ compared to gas phase as well as the relative cluster abundance. This emp-hasizes the relevance of an independent study of this cluster using supersonic jet FTIR spectroscopy.

The competition between oxygen andπbinding in furan has also been investigated for clusters with metal cations.^134–136 π binding is preferred throughout all metals under study, while the hapticity varies from η⁵ to η² and η¹. The experimental binding energies range from 113 kJ mol⁻¹ to 255 kJ mol⁻¹ and are lower than for benzene. Larger M:furan clusters have been investigated for Mn and Zn.¹³⁷

Moreover, furans can serve as dienes for Diels-Alder cycloadditions. In favorable cases, transition metal catalysts promote these reactions by disrupting the aroma-ticity. However, the reaction is strongly dependent on the equilibrium of 3,4-η² and 4,5-η² isomers, which is most favorable for the 2,5-dimethylated furan.¹³⁸

In this chapter furan and several alkylated as well as polycyclic derivatives are studied for their complexation behavior with small alkyl alcohols, namely methanol and tert-butyl alcohol. The latter are chosen as they are among the most simple

OH-hydrogen bond donors and their rigidity reduces the complexity of the confor-mational space. At first, the overarching geometry patterns are introduced and the corresponding nomenclature is defined. The smallest clusters, furan and its methy-lated derivatives with methanol, form the starting point. To possibly increase the relevance of π binding, the alkyl moieties are then enlarged in Sec. 3.3. A slightly different approach to favorπ binding is attempted in Sec. 3.4, where the size of the πsystem is enhanced by annulating one or two benzene rings to furan.