Binary conformers of a flexible, long-chain fluoroalcohol: dispersion controlled selectivity and relative abundances in a jet.

The complex conformational panorama of binary 4,4,4-trifluoro-1-butanol (TFB) aggregates was investigated using chirped-pulse Fourier transform microwave spectroscopy, aided by conformational searches using CREST (Conformer-Rotamer Ensemble Sampling Tool) and quantum chemistry calculations. From nearly 1500 initial dimer geometries, 16 most stable binary candidates were obtained within a relative energy window of ∼4 kJ mol-1. Rotational spectra of five binary conformers were experimentally observed in supersonic expansion and assigned. Interestingly, three out of the five observed binary conformers are composed solely of monomer conformers, which were not observed in their isolated gas phase forms in jet expansion. In addition, an observed dimer that is made exclusively of the most stable TFB monomer subunits does not correspond to the global minimum. The intricate kinetically and thermodynamically controlled dimer formation mechanisms are discussed, and a modified kinetic-thermodynamic model was developed, providing conformational abundances that are in good agreement with the experiment. Subsequent non-covalent interaction analyses reveal that the observed conformers are held together by one primary O-H⋯O hydrogen bond and secondary intermolecular C-H⋯O, C-H⋯F, and/or O-H⋯F interactions, as well as C-H⋯H-C London dispersion interactions between the methylene groups. Further symmetry-adapted perturbation theory analyses of the TFB dimer conformers and related alcohol dimers reveal a considerable rise in dispersion contributions with increasing n-alkyl carbon chain length and highlight the role of dispersion interactions in preferentially stabilizing the global minimum of the TFB dimer.

Rotational Spectrum and Ring Structures of Silacyclohex-2-ene and 1,1-Difluorosilacyclohex-2-ene.

Silacyclohex-2-ene and 1,1-difluorosilacyclohex-2-ene have been synthesized, and the chirped-pulse, Fourier-transform microwave spectra of each have been observed and analyzed from 4.9 to 23.1 GHz. Quantum chemical calculations have been performed at the B3LYP-D3BJ/Def2TZVP level of theory and predict µa to be the largest dipole moment component with a significantly larger value in this component for 1,1-difluorosilacyclohex-2-ene. In accordance with this prediction, the spectra were predominantly a-type with the observation of a few b- and c-type transitions. The signal-to-noise ratio was adequate in both spectra to observe 29Si, 30Si, and all singly substituted 13C isotopologues in natural abundance. All spectra have been fit to a semirigid rotational Hamiltonian and are presented. Analysis of the physical meaning of the fitted parameters is explored and determined to hold for the rotational constants while being more empirical for the centrifugal distortion terms. Experimental structures of both molecules indicate that the quantum chemically calculated structures for the atoms in the ring are a very close depiction of the experimentally determined structures. The structures of each molecule are compared to similar molecules for context, where it is shown that both molecules possess a similar "half-chair" conformation to that of the all-carbon analogue, cyclohexene.

Twins in rotational spectroscopy: Does a rotational spectrum uniquely identify a molecule?

Rotational spectroscopy is the most accurate method for determining structures of molecules in the gas phase. It is often assumed that a rotational spectrum is a unique "fingerprint" of a molecule. The availability of large molecular databases and the development of artificial intelligence methods for spectroscopy make the testing of this assumption timely. In this paper, we pose the determination of molecular structures from rotational spectra as an inverse problem. Within this framework, we adopt a funnel-based approach to search for molecular twins, which are two or more molecules, which have similar rotational spectra but distinctly different molecular structures. We demonstrate that there are twins within standard levels of computational accuracy by generating rotational constants for many molecules from several large molecular databases, indicating that the inverse problem is ill-posed. However, some twins can be distinguished by increasing the accuracy of the theoretical methods or by performing additional experiments.

Computational optimal transport for molecular spectra: The fully continuous case.

Computational optimal transport is used to analyze the difference between pairs of continuous molecular spectra. It is demonstrated that transport distances which are derived from this approach may be a more appropriate measure of the difference between two continuous spectra than more familiar measures of distance under many common circumstances. Associated with the transport distances is the transport map which provides a detailed analysis of the difference between two molecular spectra and is a key component of our study of quantitative differences between two continuous spectra. The use of optimal transport for comparing molecular spectra is developed in detail here with a set of model spectra, so that the discussion is self-contained. The difference between the transport distance and more common definitions of distance is elucidated for some well-chosen examples and it is shown where transport distances may be very useful alternatives to standard definitions of distance. The transport distance between a theoretical and experimental electronic absorption spectrum for SO2 is studied and it is shown how the theoretical spectrum can be modified to fit the experimental spectrum better adjusting the theoretical band origin and the resolution of the theoretical spectrum. This analysis includes the calculation of transport maps between the theoretical and experimental spectra suggesting future applications of the methodology.

Rotational Spectroscopy of the 2,2,3,3,3-Pentafluoropropanol⋠⋠⋠Water Complex: Conformations and Large Amplitude Motions.

The 2,2,3,3,3-pentafluoropropanol (PFP) monomer can exist in five conformations defined by the CCCO and CCOH dihedral angles: four mirror-imaged pairs (G+g+/G-g-, G+g-/G-g+, G+t/G-t, Tg+/Tg-) and an achiral Tt form. We examined the conformational landscape of the PFP⋅⋅⋅water complex using chirped pulsed Fourier transform microwave spectroscopy and theoretical calculations. Rotational spectra of two PFP⋅⋅⋅water conformers, PFPG+g+⋅⋅⋅WH and PFPTg+⋅⋅⋅WH , and seven deuterated isotopologues of each, were assigned. Tunneling splittings were observed for both conformers and are attributed to the exchange of the bonded and non-bonded hydrogen atoms of water. On the other hand, the tunneling splitting associated with the OH flipping motion in PFPTg+/Tg- appears to be quenched upon hydrogen bonding with water. The large amplitude motions associated with the water subunits were examined in detail to explain the very different magnitudes of the experimental and theoretical permanent electric dipole moment components. The study highlights the challenge in correctly identifying the conformers observed when large amplitude motions are involved. Quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) analyses, as well as electrostatic potential (ESP) calculations were carried out to explore the nature of the non-covalent interactions and to appreciate the effects of fluorination.

Structural study of 1- and 2-naphthol: new insights into the non-covalent H-H interaction in cis-1-naphthol.

Previous microwave studies of naphthol monomers were supplemented by measuring spectra of all 13C mono-substituted isotopologues of the cis- and trans-conformers of 1-naphthol and 2-naphthol in their natural abundances. The resulting data were utilized to determine substitution structures and so-called semi-experimental effective structures. Results from electronic structure calculations show that the OH group of cis-1-naphthol points ≈6° out of plane, which is consistent with the inertial defect data of cis- and trans-1-naphthol. The non-planarity of cis-1-naphthol is a result of a close-contact H-atom-H-atom interaction. This type of H-H interaction has been the subject of much controversy in the past and we provide here an in-depth theoretical analysis of it. The naphthol system is particularly well-suited for such analysis as it provides internal standards with its four different isomers. The methods used include quantum theory of atoms in molecules, non-covalent interactions, independent gradient model, local vibrational mode, charge model 5, and natural bond orbital analyses. We demonstrate that the close-contact H-H interaction is neither a purely attractive nor repulsive interaction, but rather a mixture of the two.

2,2,3,3,3-Pentafluoro-1-propanol and its dimer: structural diversity, conformational conversion, and tunnelling motion.

Rotational spectra of 2,2,3,3,3-pentafluoro-1-propanol (PFP) were measured using cavity and chirped pulse Fourier transform microwave spectrometers. Of the nine possible PFP configurations which include four mirror-imaged pairs and an achiral conformer, the two most stable monomeric PFP imaged pairs, i.e., PFPG+g+/G-g- and PFPTg+/Tg- were observed and assigned, along with the 13C, 18O and deuterated isotopologues of PFPG+g+/G-g-. The rotational transitions of PFPTg+/Tg- exhibit large tunnelling splittings and were analyzed in detail. CREST, a recently developed conformational search tool that was used for systematic conformational searches of possible binary PFP conformers and the subsequent DFT calculations at the B3LYP-D3(BJ)/def2-QZVP level produced nearly 80 stable, binary PFP geometries, where ten of them are within a narrow energy window of ∼1 kJ mol-1, highlighting the structural diversity of the system. Rotational spectra of five (PFP)2 conformers were assigned and were identified as the five most stable binary conformers predicted. A closer examination reveals that the assigned binary conformers are made exclusively of the two most stable PFP monomeric subunits observed experimentally. A combined kinetic and thermodynamic model was proposed to explain the observation or non-observation of low energy conformers, and the analysis was further verified by the 'argon test'. The non-covalent intermolecular interactions of PFP and its binary conformers are also discussed with the aid of quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) analyses, as well as the effects of fluorination by comparing with 1-propanol and its dimers.

Examining the gas-phase homodimers of 3,3,3-trifluoro-1,2-epoxypropane using quantum chemistry and microwave spectroscopy.

Gas phase homodimers of 3,3,3-trifluoro-1,2-epoxypropane (TFO), a molecule which has shown promise as an effective chiral tag for determining the absolute stereochemistry and the enantiomeric composition of chiral analytes, are explored using a variety of quantum chemistry models and rotational spectroscopy. The potential surface governing the interaction of the two molecules is rapidly explored using the artificial bee colony algorithm for homodimer candidates that are subsequently optimized by quantum chemistry methods. Although all model chemistries employed agree that the lowest energy form of the heterochiral homodimer of TFO (RS or SR) is lower in energy than that of the homochiral dimer (RR or SS), the energy spacings among the lower energy isomers of each and indeed the absolute energy ordering of the isomers of each are very model dependent. The experimental results suggest that the B3LYP-D3BJ/def2-TZVP model chemistry is the most reliable and provides excellent estimates of spectroscopic constants. In accord with theoretical predictions the non-polar lowest energy form of the heterochiral homodimer is not observed, while two isomers of the homochiral dimer are observed and spectroscopically characterized. Observation and assignment of the spectra for all three unique singly-substituted 13C isotopologues, in addition to that of the most abundant isotopologue for the lowest energy isomer of the homochiral homodimer of TFO, provide structural information that compares very favorably with theoretical predictions, most notably that the presence of three fluorine atoms on the trifluoromethyl group removes their direct participation in the intermolecular interactions, which instead comprise two equivalent pairs of CH⋯O hydrogen bonds between the two epoxide rings augmented by favorable dispersion interactions between the rings themselves.

Alternating 1-Phenyl-2,2,2-Trifluoroethanol Conformational Landscape With the Addition of One Water: Conformations and Large Amplitude Motions.

The 1:1 adduct of 1-phenyl-2,2,2-trifluoroethanol (PhTFE), a chiral fluoroalcohol, with water was investigated using chirped pulse Fourier transform microwave spectroscopy and computational methods. While PhTFE itself was predicted to have three minima, I (gauche+), II (trans), and III (gauche-), only I and II were stable and only I was observed experimentally. A systematic search of the PhTFE···H2O conformational landscape identified 110 stable minima, 14 of which are within a 15 kJ mol-1 energy window. Rotational spectra of the two PhTFE···H2O conformers along with several deuterium and 18O isotopologues were assigned, and the isotopic data were used to verify the corresponding structures. In the two observed monohydrate conformers, one contains PhTFE I where the water subunit is inserted into the existing intramolecular OH···F contact of I, and the binary adduct is stabilized by two intermolecular contacts: OH···OW and HW···F, whereas the other contains PhTFE II where the water subunit interacts with both the alcohol hydrogen and phenyl ring of II, demonstrating that interaction with water sufficiently stabilizes II for its observation in a jet expansion. Interestingly, the predicted electric dipole moment components at the identified minima deviate considerably from the experimental ones. Such deviations were analyzed in terms of dynamic effects associated with the large amplitude motions of the unbound HW. In addition, tunnelling effects associated with the exchange of the bonded and nonbonded HW were also discussed.

Computational optimal transport for molecular spectra: The semi-discrete case.

Comparing a discrete molecular spectrum to a continuous molecular spectrum in a quantitative manner is a challenging problem, for example, when attempting to fit a theoretical stick spectrum to a continuous spectrum. In this paper, the use of computational optimal transport is investigated for such a problem. In the optimal transport literature, the comparison of a discrete and a continuous spectrum is referred to as semi-discrete optimal transport and is a situation where a metric such as least-squares may be difficult to define except under special conditions. The merits of an optimal transport approach for this problem are investigated using the transport distance defined for the semi-discrete case. A tutorial on semi-discrete optimal transport for molecular spectra is included in this paper, and several well-chosen synthetic spectra are investigated to demonstrate the utility of computational optimal transport for the semi-discrete case. Among several types of investigations, we include calculations showing how the frequency resolution of the continuous spectrum affects the transport distance between a discrete and a continuous spectrum. We also use the transport distance to measure the distance between a continuous experimental electronic absorption spectrum of SO2 and a theoretical stick spectrum for the same system. The comparison of the theoretical and experimental SO2 spectra also allows us to suggest a theoretical value for the band origin that is closer to the observed band origin than previous theoretical values.

Substitution Reactions in the Pyrolysis of Acetone Revealed through a Modeling, Experiment, Theory Paradigm.

The development of high-fidelity mechanisms for chemically reactive systems is a challenging process that requires the compilation of rate descriptions for a large and somewhat ill-defined set of reactions. The present unified combination of modeling, experiment, and theory provides a paradigm for improving such mechanism development efforts. Here we combine broadband rotational spectroscopy with detailed chemical modeling based on rate constants obtained from automated ab initio transition state theory-based master equation calculations and high-level thermochemical parametrizations. Broadband rotational spectroscopy offers quantitative and isomer-specific detection by which branching ratios of polar reaction products may be obtained. Using this technique, we observe and characterize products arising from H atom substitution reactions in the flash pyrolysis of acetone (CH3C(O)CH3) at a nominal temperature of 1800 K. The major product observed is ketene (CH2CO). Minor products identified include acetaldehyde (CH3CHO), propyne (CH3CCH), propene (CH2CHCH3), and water (HDO). Literature mechanisms for the pyrolysis of acetone do not adequately describe the minor products. The inclusion of a variety of substitution reactions, with rate constants and thermochemistry obtained from automated ab initio kinetics predictions and Active Thermochemical Tables analyses, demonstrates an important role for such processes. The pathway to acetaldehyde is shown to be a direct result of substitution of acetone's methyl group by a free H atom, while propene formation arises from OH substitution in the enol form of acetone by a free H atom.

Conformational Landscape, Chirality Recognition and Chiral Analyses: Rotational Spectroscopy of Tetrahydro-2-Furoic Acid⋠⋠⋠Propylene Oxide Conformers.

A chiral adduct formed between a chiral carboxylic acid, tetrahydro-2-furoic acid (THFA), and a chiral ester, propylene oxide (PO), was investigated using rotational spectroscopy and DFT calculations. Isolated THFA exists dominantly as three different conformers: I, II, and III in a jet, with I and II taking on the trans-COOH configuration and III having the cis-COOH configuration. We utilized CREST, a conformational ensemble space exploration tool, to identify the possible conformations of the binary adduct, THFA⋅⋅⋅PO. Subsequent DFT geometry optimizations predicted about two hundred homochiral and heterochiral binary structures with 28 low energy structures within an energy window of 15 kJ mol-1 . A rich broadband rotational spectrum was obtained with a mixture of trace amounts of THFA+PO in neon in a supersonic jet expansion. Six THFA⋅⋅⋅PO conformers were identified experimentally. Kinetically favored binary products which contain trans-COOH I dominate among the observed conformers, while thermodynamically more stable adducts were also detected. Detailed analyses of the structures of the observed conformers show interesting chirality-controlled structural preferences. Such non-covalently bound chiral contact pairs are the foundation of chiral-tag rotational spectroscopy, an exciting new analytical application of rotational spectroscopy for determination of enantiomeric excess. Enantiomeric excess analyses were performed and the results are discussed.

Modifying conformational distribution of chiral tetrahydro-2-furoic acid through its interaction with water: a rotational spectroscopic and theoretical investigation.

Rotational spectrum of a binary complex formed between tetrahydro-2-furoic acid (THFA) and water was measured using a chirped pulse Fourier transform microwave spectrometer. A comprehensive theoretical conformational search procedure was carried out using CREST, a conformational searching tool, and DFT calculations to aid the spectral assignment and interpretation. The final conformer ensemble is classified into two structural groups: Type 1 conformers showing a classic carboxylic acid monohydrate structure with two strong hydrogen-bonds formed between the COOH group of cis-THFA and water, and the much less stable Type 2 conformers with trans-THFA and weaker intermolecular interactions with water. The 'cis-' and 'trans-' labels refer to the configurations where the carboxylic C[double bond, length as m-dash]O and OH functional groups are on the same or opposite side, respectively. Only the two most stable Type 2 conformers containing trans-THFA I and II were observed experimentally in a neon jet expansion with an abundance ratio of 1 : 1. This relative abundance observation differs greatly from that of the THFA monomer, i.e. with trans-THFA I : trans-THFA II : cis-THFA III of 10 : 1 : 1 in a neon jet expansion, reported previously. The observation indicates a kinetically controlled formation process of different types of the monohydrates in a jet expansion, whereas a thermodynamically controlled process dominates within each type of structures. The relative stability of the THFA ring conformations is altered by interaction with water, showing a noticeable water induced conformational preference.

Rotational Spectrum and Molecular Structures of the Binary Aggregates of 1,1,1,3,3,3-Hexafluoro-2-propanol with Ne and Ar.

The structures and binding topologies of two binary van der Waals complexes 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)···Ne and ···Ar were investigated. The rotational spectra of these two complexes including several isotopic species containing 20Ne, 22Ne, 40Ar, 13C, and hydroxyl D were measured using a chirped pulse Fourier transform microwave spectrometer and a cavity-based Fourier transform microwave spectrometer. While HFIP was shown to exist in both the gauche and trans configurations based on previous reports, the rare gas atom is predicted to attach to HFIP in several different binding topologies, leading to a total of nine possible structural isomers for each complex. Only one isomer was detected for each species, and it corresponds to the most stable one predicted, based on the comparison of the experimental rotational constants and electric dipole moment components with the theoretical predictions and on the isotopic data. We applied quantum theory of atoms in molecules (QTAIM) and electrostatic potential calculations to examine the different rare gas binding sites and to explore the nature of the interactions in these two complexes and several previously reported alcohol···Ar complexes. The effects of fluorination are also discussed by comparison with the binary complexes of isopropanol···Ne and ···Ar.

Higher-Energy Hexafluoroisopropanol···Water Isomer and Its Large Amplitude Motions: Rotational Spectra and DFT Calculations.

Rotational spectra of the 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)···water complex were measured using a chirped pulse Fourier-transform microwave spectrometer. The spectral analyses, aided by density functional theory calculations, reveal two HFIP···water isomers: one previously reported, trans HFIP (HFIPt)···water (Phys. Chem. Chem. Phys. 2015, 119, 5650-5657), and a new isomer, gauche HFIP (HFIPg)···water. To confirm the identity of the new isomer, rotational spectra of seven of its deuterated species were also measured and analyzed. Both the experimental and theoretical pieces of evidence indicate that the intermolecular interaction with water preferentially stabilizes the HFIPg monomer configuration over the global minimum configuration, HFIPt. The relative energy difference between these monomeric forms is 4.1 kJ mol-1 and decreases to 2.5 kJ mol-1 in the respective monohydrates at the B3LYP-D3(BJ)/def2-QZVP level of theory. Both rigid and relaxed potential energy surface scans were carried out to gain insights into the large-amplitude water motions in HFIPg···water. The nonobservation of a water tunneling splitting in HFIPt···water has been explained to be a result of a barrier-less (after zero-point-energy correction) pathway for the water motion, whereas in HFIPg···water, a relatively large water tunneling barrier was identified as the cause of barely resolved water tunneling splittings. Noncovalent interaction and quantum theory of atoms and molecule analyses were used to evaluate the changes in HFIPg···water when going from the minimum to the transition state in terms of attractive interactions such as the OH···H and OH···F contacts. The effect of fluorination is discussed by comparing the vastly different binding topologies of isopropanol···water and HFIP···water.

Computational optimal transport for molecular spectra: The fully discrete case.

The use of computational optimal transport is investigated as a tool for comparing two molecular spectra. Unlike other techniques for comparing molecular spectra in a pattern-recognition framework, transport distances simultaneously encode information about line positions and intensities. In addition, it is shown that transport distances are a useful alternative to Euclidean distances as Euclidean distances are based on line-by-line comparisons, while transport distances reflect broader features of molecular spectra and adequately compare spectra with different resolutions. This paper includes a tutorial on the use of optimal transport and investigates several well-chosen examples to illustrate the utility of computational optimal transport for comparing molecular spectra.

The Role of Non-Covalent Interactions on Cluster Formation: Pentamer, Hexamers and Heptamer of Difluoromethane.

The role of non-covalent interactions (NCIs) has broadened with the inclusion of new types of interactions and a plethora of weak donor/acceptor partners. This work illustrates the potential of chirped-pulse Fourier transform microwave technique, which has revolutionized the field of rotational spectroscopy. In particular, it has been exploited to reveal the role of NCIs' in the molecular self-aggregation of difluoromethane where a pentamer, two hexamers and a heptamer were detected. The development of a new automated assignment program and a sophisticated computational screening protocol was essential for identifying the homoclusters in conditions of spectral congestion. The major role of dispersion forces leads to less directional interactions and more distorted structures than those found in polar clusters, although a detailed analysis demonstrates that the dominant interaction energy is the pairwise interaction. The tetramer cluster is identified as a structural unit in larger clusters, representing the maximum expression of bond between dimers.

Conformational Panorama and Chirality Controlled Structure-Energy Relationship in a Chiral Carboxylic Acid Dimer.

Chirality recognition in dimers of tetrahydro-2-furoic acid (THFA) was studied in a conformer-specific manner using rotational spectroscopy and theoretical approaches. THFA shows a strong preference for the trans- over the cis-COOH configuration. Two drastically different scenarios are possible for the detectable (THFA)2 : a kinetically preferred dimer bound by feeble interactions between two trans THFAs or a thermodynamically favored dimer with a double hydrogen-bonded ring structure between two cis subunits. To identify the conformers responsible for the extremely dense rotational spectra observed, it was essential not only to locate several hundred homo/heterochiral (THFA)2 minima in ab initio calculations but also to evaluate the energetic connectivities among the minima. The study further reveals an interesting chirality dependent structure-energy ordering relationship. A method for enantiomeric excess (ee) determination of THFA is presented using a recently proposed chiral self-tag approach.

A microwave spectroscopic and ab initio study of keto-enol tautomerism and isomerism in the cyclohexanone-water complex.

Cyclohexanone and water are two important components of secondary organic aerosol (SOA), and understanding the intermolecular interactions between these two species can provide insight to the initial formation mechanism of SOA particles. In this work, we have investigated the keto-enol tautomeric and conformational changes of the cyclohexanone monomer and its monohydrate by Fourier-transform microwave spectroscopy and ab initio calculations. Chirped-pulse and cavity-based FTMW spectrometers in the region of 7-14 GHz were used to measure rotational spectra of the most stable species prepared in a cold molecular beam. The experimental and theoretical results suggest that the chair conformer of the keto tautomer is the most stable structure. We have measured and assigned rotational spectra of ten isotopologues, including all six single 13C substitutions observed in natural abundance and four different isotopic species of water (H2O, D2O, DOH and HOD). The experimental structure of cyclohexanone-water was determined directly using this isotopic information. The analysis reveals the existence of both canonical and secondary hydrogen bonding, which we confirm using QTAIM analyses. To further elucidate the hydrogen bonding characteristics in ketone-water clusters, cyclohexanone-water is compared to a variety of other hydrated ketones, namely formaldehyde, acetone, cyclobutanone, and cyclopentanone, through utilization of the symmetry adapted perturbation theory (SAPT) energy decomposition method. The results of this study shed light on the effects of water on keto-enol tautomerization, and the role of hydrogen bonding in ketone monohydrates and the formation of related SOA particles.

The rich conformational landscape of perillyl alcohol revealed by broadband rotational spectroscopy and theoretical modelling.

The rotational spectrum of perillyl alcohol, a naturally occurring, chiral, dietary monoterpene, was investigated using a chirped pulse Fourier transform microwave spectrometer and a cavity-based Fourier transform microwave spectrometer. To aid the assignment of the dense chirped pulse spectrum obtained, extensive theoretical conformational searches were carried out. In one approach, several one and two-dimensional scans along three dihedral angles associated with the rotational motions of the -OH, -CH2OH, and -C(CH2)CH3 groups were performed. These scans, combined with the equatorial and axial positions of the -C(CH2)CH3 group, resulted in 54 conformers. The same conformers were identified in the second approach where a semi-classical conformational search code was used. The relative stabilities of the conformers and the interconversion barriers among them were explored extensively at the DFT B3LYP-D3(BJ)/def2-TZVP and B3LYP-D3(BJ)/6-311++G(2d,p), as well as local MP2/aug-cc-pVQZ levels of theory, and 12 conformers were ultimately identified as possibly observable candidates in a molecular jet expansion. Rotational spectra of eight out of the 12 candidates were observed experimentally and analyzed. The non-observation of the remaining four conformers may be attributed to their low abundances. The study points out the importance of identifying all conformers of relevant abundance, even those which could not be detected experimentally, in order to properly benchmark the theoretical relative stabilities with the experimental ones. A comprehensive study of the conformational distribution of perillyl alcohol contributes to our understanding of its structural properties which may influence its functions.