Self-Associating Behavior of Acetone in Liquid Krypton

Acetone molecules are inclined to self-associate through dipole–dipole interactions because of their large dipole moment. Infrared spectroscopy of compounds dissolved in liquid noble gases supported by high level <i>ab initio</i> calculations allows investigating the self-associating behavior and determining the thermodynamical properties. In this study, infrared spectra of various concentrations of acetone dissolved in liquid krypton are recorded at constant temperature. Overlapping monomer and dimer spectra are separated by analyzing the obtained data sets with numerical methods based on least-squares fitting. Although acetone is known to self-associate, only a few spectral features have been presented in literature before. In this study, the application of new numerical approaches succeeds in resolving overlapping spectra and allows observing isolated acetone dimer absorption bands for the complete mid infrared spectrum. By use of data sets of spectra recorded at temperatures between 134 and 142 K, the experimental standard dimerization enthalpy was determined to be −10.8 kJ mol^–1. MP2/aug-cc-pVDZ calculations predicted a stacked and planar dimer geometry of which the stacked geometry is more stable. Combining MP2 energies and single point corrections involving CCSD­(T) calculations and complete basis set extrapolations based on the MP2/aug-cc-pVDZ equilibrium geometry lead to complexation energy of −28.4 kJ mol^–1 for the stacked geometry and −15.1 kJ mol^–1 for the planar geometry. The corresponding values for the complexation enthalpies in solution, obtained by combining these values with corrections for thermal and solvent influences are −13.7 and −5.8 kJ mol^–1

Effect of Fluorination on the Competition of Halogen Bonding and Hydrogen Bonding: Complexes of Fluoroiodomethane with Dimethyl Ether and Trimethylamine

To further rationalize the competition between halogen and hydrogen bonding, a combined experimental and theoretical study on the weakly bound molecular complexes formed between the combined halogen bond/hydrogen bond donor fluoroiodomethane and the Lewis bases dimethyl ether and trimethylamine (in standard and fully deuterated form) is presented. The experimental data are obtained by recording infrared and Raman spectra of mixtures of the compounds in liquid krypton, at temperatures between 120 and 156 K. The experiments are supported by <i>ab initio</i> calculations at the MP2/aug-cc-pVDZ-PP level, statistical thermodynamics and Monte Carlo free energy perturbation calculations. For the mixtures containing fluoroiodomethane and dimethyl ether a hydrogen-bonded complex with an experimental complexation enthalpy of −7.0(2) kJ mol^–1 is identified. Only a single weak spectral feature is observed which can be tentatively assigned to the halogen-bonded complex. For the mixtures involving trimethylamine, both halogen- and hydrogen-bonded complexes are observed, the experimental complexation enthalpies being −12.5(1) and −9.6(2) kJ mol^–1 respectively. To evaluate the influence of fluorination on the competition between halogen and hydrogen bonding, the results obtained for fluoroiodomethane are compared with those of a previous study involving difluoroiodomethane

Expanding Lone Pair···π Interactions to Nonaromatic Systems and Nitrogen Bases: Complexes of C₂F₃X (X = F, Cl, Br, I) and TMA‑<i>d</i> ₉

The molecular electrostatic potential surface of unsaturated, locally electron-deficient molecules shows a positive region perpendicular to (a part of) the molecular framework. In recent years it has been shown both theoretically and experimentally that molecules are able to form noncovalent interactions with Lewis bases through this π-hole. When studying unsaturated perfluorohalogenated molecules containing a higher halogen atom, a second electropositive region is also observed near the halogen atom. This region, often denoted as a σ-hole, allows the molecules to interact with Lewis bases and form a halogen bond. To experimentally characterize the competition between both these noncovalent interactions, Fourier transform infrared and Raman spectra of liquefied noble gas solutions containing perfluorohalogenated ethylene derivatives (C₂F₃X; X = F, Cl, Br, or I) and trimethylamine­(-<i>d</i> ₉) were investigated. Analysis of the spectra shows that in mixed solutions of trimethylamine­(-<i>d</i> ₉) and C₂F₄ or C₂F₃Cl lone pair···π complex is present, while evidence for halogen-bonded complex is found in solutions containing trimethylamine­(-<i>d</i> ₉) and C₂F₃Cl, C₂F₃Br, or C₂F₃I. For all species observed, complexation enthalpies were determined, the values varying between −4.9(1) and −24.4 kJ mol^–1

Statistical Validation of Absolute Configuration Assignment in Vibrational Optical Activity

Chiroptical spectroscopy usually requires theoretically computed spectra to assist in the elucidation of the absolute configuration of samples for which experimental spectra have been recorded. Due to the inherently different nature of these two types of spectra, perfect agreement is quasi impossible. Several methods exist to quantify the degree of similarity between the two spectra, but rather limited work has been done to evaluate the robustness of the similarity between theory and experiment. In this work, a novel method is described to determine the statistical significance of the numerical degree of similarity between experimental and calculated vibrational circular dichroism spectra and to offer valuable support for performing absolute configuration assignments. The approach is successfully applied to a number of quinolizidine alkaloids

Competition of C(sp²)–X···O Halogen Bonding and Lone Pair···π Interactions: Cryospectroscopic Study of the Complexes of C₂F₃X (X = F, Cl, Br, and I) and Dimethyl Ether

Inspection of the electrostatic potential of C₂F₃X (X = F, Cl, Br, and I) revealed a second electropositive region in the immediate vicinity of the CC double bond apart from the σ hole of chlorine, bromine, and iodine, leading to C­(sp²)–X···Y halogen bonding, through which complexes stabilized by so-called lone pair···π interactions can be formed. Consequently, the experimental studies for the complexes of dimethyl ether with C₂F₃X (X = F, Cl, Br, and I) not only allowed one to experimentally characterize and rationalize the effects of hybridization on halogen bonding but, for the first time, also allowed the competition of C–X···Y halogen bonding and lone pair···π interactions to be studied at thermodynamic equilibrium. Analysis of the infrared and Raman spectra reveals that in the cryosolutions of dimethyl ether and C₂F₃I, solely the halogen-bonded complex is present, whereas C₂F₃Br and C₂F₃Cl give rise to a lone pair···π bonded complex as well as a halogen-bonded complex. Mixtures of dimethyl ether with C₂F₄ solely yield a lone pair···π bonded complex. The experimentally derived complexation enthalpies for the halogen bonded complexes are found to be −14.2(5) kJ mol^–1 for C₂F₃I·DME and −9.3(5) kJ mol^–1 for C₂F₃Br·DME. For the complexes of C₂F₃Cl with dimethyl ether, no experimental complexation enthalpy could be obtained, whereas the C₂F₄·DME complex has a complexation enthalpy of −5.5(3) kJ mol^–1. The observed trends have been rationalized with the aid of an interaction energy decomposition analysis (EDA) coupled to a Natural Orbital for Chemical Valence (NOCV) analysis and also using the noncovalent interaction index method

Mechanistic and chiroptical studies on the desulfurization of epidithiodioxopiperazines reveal universal retention of configuration at the bridgehead carbon atoms.

<p>2,3,10,10-Tetramethyl-2,3-dihydro-1H-3,10a-epithiopyrazino[1,2-a]indole-1,4(10H)-dione (<strong>8</strong>). To a solution of gliotoxin analogue (7, 33 mg, 0.10 mmol) in dioxane (8 mL) was added PPh3 (33 mg, 0.16 mmol) and the resulting mixture was stirred overnight at room temperature. The solvent was then re-moved under reduced pressure and the pink residue was purified by column chromatography [PEEtOAc (100:0 to 95:5)] to afford a colorless oil (19 mg, 64%) which was recrystallized from CH2Cl2 to give a white solid: m.p. 58 60 C; IR (neat) 1720, 1456, 1387, 1288, 1134 cm-1; 1H NMR (400 MHz, CDCl3) 8.54 (app-d, J = 7.8 Hz, 1H), 7.25 (td, J = 7.8, 1.0 Hz, 1H), 7.20 (dd, J = 7.8, 1.0 Hz, 1H), 7.13 (td, J = 7.8, 1.0 Hz, 1H), 2.96 (s, 3H), 1.83 (s, 3H), 1.75 (s, 3H), 1.48 (s, 3H); 13C NMR (100 MHz, CDCl3) 172.5, 172.0, 139.7, 138.1, 128.1, 124.7, 122.4, 113.6, 86.6, 75.1, 43.5, 27.2, 26.3, 25.7, 13.3; MS (CI) m/z 289 (M+H)+, 306 (M+NH4)+; HRMS (CI) m/z calcd for C15H17N2O2S [(M+H)+] 289.1011, found: 289.1026. The obtained enantiomers could be separated by chiral HPLC (OD+ semiprep column, Hexane : Isopropanol, 90:10): First peak: [α]25D -47.5 (c 1.12, CH2Cl2), Second peak: [α]25D +34.4 (c 1.12, CH2Cl2).</p

Mechanistic and Chiroptical Studies on the Desulfurization of Epidithiodioxopiperazines Reveal Universal Retention of Configuration at the Bridgehead Carbon Atoms

The stereochemistry of the desulfurization products of chiral natural and synthetic 3,6-epidithiodiketopiperazines (ETPs) is specified inconsistently in the literature. Qualitative mechanisms have been put forward to explain apparently divergent stereochemical pathways, but the quantitative feasibility of such mechanistic pathways has not been assessed. We report a computational study revealing that desulfurization of ETPs should occur universally with retention of configuration. While the majority of stereochemically assigned and reassigned cases fit this model, until now desulfurization of the synthetic gliotoxin analogue shown has remained assigned as proceeding via inversion of configuration. Through detailed chiroptical studies comparing experimentally obtained optical rotation values, electronic circular dichroism spectra, and vibrational circular dichroism spectra to their computationally simulated counterparts as well as chemical derivatization studies, we have unambiguously demonstrated that contrary to its current assignment in the literature, the desulfurization of this synthetic ETP also proceeds with retention of configuration

Zn-Catalyzed <i>tert</i>-Butyl Nicotinate-Directed Amide Cleavage as a Biomimic of Metallo-Exopeptidase Activity

A two-step catalytic amide-to-ester transformation of primary amides under mild reaction conditions has been developed. A <i>tert</i>-butyl nicotinate (<i>t</i>Bu <i>nic</i>) directing group is easily introduced onto primary amides via Pd-catalyzed amidation with <i>tert</i>-butyl 2-chloronicotinate. A weak base (Cs₂CO₃ or K₂CO₃) at 40–50 °C can be used provided that 1,1′-bis­(dicyclohexylphosphino)­ferrocene is selected as ligand. The <i>t</i>Bu <i>nic</i> activated amides subsequently allow Zn­(OAc)₂-catalyzed nonsolvolytic alcoholysis in <i>t</i>BuOAc at 40–60 °C under neutral reaction conditions. The activation mechanism is biomimetic: the C3-ester substituent of the pyridine in the directing group populates the <i>trans</i>-conformer suitable for Zn-chelation, CO_amide–Zn–N_{directing group}, and Zn-coordinated alcohol is additionally activated as a nucleophile by hydrogen bonding with the acetate ligand of the catalyst. Additionally, the acetate ligand assists in intramolecular O-to-N proton transfer. The chemoselectivity versus other functional groups and compatibility with challenging reaction partners, such as peptides, sugars, and sterols, illustrates the synthetic applicability of this two-step amide cleavage method. The <i>t</i>Bu <i>nic</i> amides do not require purification before cleavage. Preliminary experiments also indicate that other weak nucleophiles can be used such as (hetero)­arylamines (transamidation) as exemplified by 8-aminoquinoline