Synthesis,conformational preferences in gas and solution,and molecular gear rotation in 1-(dimethylamino)-1-phenyl-1-silacyclohexane by gas phase electron diffraction (GED), LT NMR and theoretical calculations

1-(Dimethylamino)-1-phenyl-1-silacyclohexane 1, was synthesized, and its molecular structure and conformational properties studied by gas-phase electron diffraction (GED), low temperature ¹³C NMR spectroscopy and quantum-chemical calculations. The predominance of the 1-Ph_ax conformer (1-Ph_eq:1-Ph_ax ratio of 20:80%, ΔG°(317?K)?=??0.87?kcal/mol) in the gas phase is close to the theoretically estimated conformational equilibrium. In solution, low temperature NMR spectroscopy showed analyzable decoalescence of C_ipso and C(1,5) carbon signals in ¹³C NMR spectra at 103?K. Opposite to the gas state in the freon solution employed (CD₂Cl₂/CHFCl₂/CHFCl₂?=?1:1:3), which is still liquid at 100?K, the 1-Ph_eq conformer was found to be the preferred one [(1-Ph_eq: 1-Ph_ax?=?77%: 23%, K?=?77/23?=?2.8; ?ΔG°?=??RT ln K (at 103?K)?=?0.44?±?0.1?kcal/mol]. When comparing 1 with 1-phenyl-1-(X)silacylohexanes (X?=?H, Me, OMe, F, Cl), studied so far, the trend of predominance of the Ph_ax conformer in the gas phase and of the Ph_eq conformer in solution is confirmed.     

First-principle studies of intermolecular and intramolecular catalysis of protonated cocaine

We have performed a series of first-principles electronic structure calculations to examine the reaction pathways and the corresponding free energy barriers for the ester hydrolysis of protonated cocaine in its chair and boat conformations. The calculated free energy barriers for the benzoyl ester hydrolysis of protonated chair cocaine are close to the corresponding barriers calculated for the benzoyl ester hydrolysis of neutral cocaine. However, the free energy barrier calculated for the methyl ester hydrolysis of protonated cocaine in its chair conformation is significantly lower than for the methyl ester hydrolysis of neutral cocaine and for the dominant pathway of the benzoyl ester hydrolysis of protonated cocaine. The significant decrease of the free energy barrier, approximately 4 kcal/mol, is attributed to the intramolecular acid catalysis of the methyl ester hydrolysis of protonated cocaine, because the transition state structure is stabilized by the strong hydrogen bond between the carbonyl oxygen of the methyl ester moiety and the protonated tropane N. The relative magnitudes of the free energy barriers calculated for different pathways of the ester hydrolysis of protonated chair cocaine are consistent with the experimental kinetic data for cocaine hydrolysis under physiologic conditions. Similar intramolecular acid catalysis also occurs for the benzoyl ester hydrolysis of (protonated) boat cocaine in the physiologic condition, although the contribution of the intramolecular hydrogen bonding to transition state stabilization is negligible. Nonetheless, the predictability of the intramolecular hydrogen bonding could be useful in generating antibody-based catalysts that recruit cocaine to the boat conformation and an analog that elicited antibodies to approximate the protonated tropane N and the benzoyl O more closely than the natural boat conformer might increase the contribution from hydrogen bonding. Such a stable analog of the transition state for intramolecular catalysis of cocaine benzoyl-ester hydrolysis was synthesized and used to successfully elicit a number of anticocaine catalytic antibodies.     

Comparative Studies on Mass Spectrometric Fragmentation of Linear Chiral Secondary Alcohols （ R ） -1-（4-Alkylphenyl） and （ R ） -1- （ 4-Alkoxyphenyl/Alkylthiophenyl ） Alcohols

Introduction Chiralsecondaryalcoholsareveryimportantinter mediatesinorganicsynthesis.Theyaregenerallypre paredviachemicalorenzymaticresolutionofracemic secondaryalcohols[1—4],chemicalorenzymaticasym metricreductionofprochiralketones[5—7],andasym metrica…     

Thermodynamic conformational analysis and structural stability of the nicotinic analgesic ABT-594

This work presents a theoretical study of the nicotinic analgesic ABT-594. We describe its neutral (precursor) and protonated (active) forms in vacuum and aqueous solution at the MP2/cc-pVDZ level. A conformational analysis is performed on the two torsional angles describing the orientation of the azetidinyl group and the azetidinylmethoxy moiety. To account for entropic effects, a thermostatistical study of conformational populations at physiological temperature is carried out. In the neutral form, conformer I is found as the most populated in vacuum and solution. Here, the nitrogen of the azetidinyl group is far from the electron pairs of the oxygen and the pyridinic nitrogen. In the protonated form, conformer VIII is the most stable in vacuum and solution. Now, the additional proton on the azetidinyl group is oriented toward the electron lone pairs of oxygen. The structural stability of conformers I and VIII is considered through the atoms in molecules theory. The conformer I, in the neutral forms, is stabilized by an intramolecular hydrogen bond. The preference of conformer VIII in the protonated forms is explained by the higher strength of its intramolecular hydrogen bond over the cation-pi interaction found in conformer I. The effect of the interaction energy with the receptor on the conformational preferences of protonated ABT-594 is simulated. The result is that the population of conformers associated to the rotation of the azetidinyl group increases. So, the molecule can easily adopt the optimal internitrogen separation for interaction with the receptor.     

Photochemical Properties of 1-(9-Phehanthryl)-2-(2-Quinolyl)ethylene

Spectral and photochemical properties of 1-(9-phehanthryl)-2-(2-quinolyl)ethylene (9Ph2QE) in neutral and protonated forms have been investigated. It has been found that both isomers of 9Ph2QE are photoactive. The quantum yield of trans–cis photoisomerization (? _tc = 0.47) in the neutral form is typical of the diabatic photoisomerization; on passing to the protonated form, ? _tc increases up to 0.70. Thus, the double annelation of the 2-styrylquinoline phenyl group to form 9Ph2QE makes it possible to conserve the α-effect, which consists in an increase in the quantum yield to ? _tc > 0.5 on passing from the neutral to protonated form, whereas the effect disappears for other types of annelation (naphthylquinolylethylenes, 1-(9-anthryl)-2-(2-quinolyl)ethylene).     

Photoisomerization of 2-styrylquinoline in neutral and protonated forms

The quantum yields of the trans-cis and cis-trans photoisomerization of 2-styrylquinoline (2SQ) and its several derivatives were measured in neutral, protonated, and quaternized forms. It was shown that electron-donor substituents in the styryl moiety increase the quantum yield of trans-cis photoisometization ?_tc in the neutral form as a result of stabilization of the intermediate zwitterionic perpendicular conformer. On passing from the neutral to the positively charged forms (protonated or quaternized), an increase in the quantum yields to ?_tc > 0.5 was observed, thus suggesting in terms of the classical diabatic mechanism of photoisomerization via the perpendicular conformer the shift of the minimum on the potential energy surface (PES) of the S ₁ state relative to the maximum of the S ₀ state PES to the cis-isomer or a possible contribution of the adiabatic route to the photoisomerization of the 2SQ cations.     

Conformational and structural studies of 1-chloropropane and 1-bromopropane from temperature-dependant FT-IR spectra of rare gas solutions and ab initio calculations

Variable temperature (−55 to −150°C) studies of the infrared spectra (3500–400 cm⁻¹) of 1-chloropropane (CH₃CH₂CH₂Cl) and 1-bromopropane (CH₃CH₂CH₂Br) dissolved in liquid krypton and xenon, respectively, have been recorded. Utilizing two conformer pairs in krypton solution for chloride and three conformer pairs in xenon solution for bromide, enthalpy differences of 52±3 cm⁻¹ (0.62±0.06 kJ/mol) and 72±7 cm⁻¹ (0.86±0.08 kJ/mol) were obtained for the chloride and bromide, respectively, with the gauche form being the more stable conformer for both molecules. From these data, it is estimated that 28 and 26% of trans form are present at ambient temperature for the chloride and bromide, respectively. The conformation stabilities, harmonic force constants, fundamental frequencies, infrared intensities and Raman activities have been obtained from RHF/6-31G(d) and/or MP2/6-31G(d) ab initio calculations for both halopropanes and these quantities have been compared to the experimental values when appropriate. The optimized geometries have also been obtained with several different ab initio basis sets with full electron correlation by the perturbation method up to MP2/6-311+G(2d,2p). The r₀ structural parameters of both halopropanes have been obtained by combining the ab initio data with the previously reported microwave rotational constants for both conformers. The quantities are compared to the corresponding results for some similar molecules.     

Photochemical properties of 1-(9-Anthryl)-2-(2-Quinolyl)ethylene

Spectral and photochemical properties of 1-(9-anthryl)-2-(2-quinolyl)ethylene (9A2QE) in neutral and protonated forms have been studied experimentally and by quantum-chemical methods. It has been found that the quantum yield of trans-cis photoisomerization (φ_tc) has values of φ_tc < 0.5 typical of the diabatic photoisomerization for both forms of 9A2QE. A comparison of this data with the results of the study of other aza-diarylethylenes containing the 2-styrylquinoline (2SQ) moiety has led to the general conclusion that the increase in the π-system in 2SQ upon fusion of the benzene rings results in the disappearance of the α-effect, which lies in the fact that the quantum yield increases upon going from the neutral to protonated form up to the values φ_tc > 0.5, which exceeds the limiting value for the diabatic photoisomerization.     

Infrared spectroscopy of Li(+)(CH4)1Ar(n), n = 1-6, clusters

Infrared predissociation (IRPD) spectra of Li(+)(CH(4))(1)Ar(n), n = 1-6, clusters are reported in the C-H stretching region from 2800 to 3100 cm(-1). The Li(+) electric field perturbs CH(4) lifting its tetrahedral symmetry and gives rise to multiple IR active modes. The observed bands arise from the totally symmetric vibrational mode, v(1), and the triple degenerate vibrational mode, v(3). Each band is shifted to lower frequency relative to the unperturbed CH(4) values. As the number of argon atoms is increased, the C-H red shift becomes less pronounced until the bands are essentially unchanged from n = 5 to n = 6. For n = 6, additional vibrational features were observed which suggested the presence of an additional conformer. By monitoring different photodissociation loss channels (loss of three Ar or loss of CH(4)), one conformer was uniquely associated with the CH(4) loss channel, with two bands at 2914 and 3017 cm(-1), values nearly identical to the neutral CH(4) gas-phase v(1) and v(3) frequencies. With supporting ab initio calculations, the two conformers were identified, both with a first solvent shell size of six. The major conformer had CH(4) in the first shell, while the conformer exclusively present in the CH(4) loss channel had six argons in the first shell and CH(4) in the second shell. This conformer is +11.89 kJ/mol higher in energy than the minimum energy conformer at the MP2/aug-cc-pVDZ level. B3LYP/6-31+G* level vibrational frequencies and MP2/aug-cc-pVDZ level single-point binding energies, D(e) (kJ/mol), are reported to support the interpretation of the experimental data.     

Retention of bioactive ligand conformation in a gaseous protein-trisaccharide complex

Arrhenius parameters, obtained with the blackbody infrared radiative dissociation technique, are reported for the dissociation of gaseous protonated complexes of a single-chain variable fragment (scFv) of the monoclonal antibody Se155-4 with structurally constrained trisaccharide ligands that resemble the bioactive conformer. The similarity in the dissociation activation energies measured for the +10 charge-state complexes of the constrained ligands and the native trisaccharide is evidence that the bioactive conformation of the native ligand is retained in the gas phase.     

2,4,6-三甲氧基苯-1-O-D葡萄糖苷的核磁共振谱的理论研究

The 1H and 13C-NMR of 2,4,6-trimethoxyphenol-1-O-D-glucopyranoside(Compound 1) isolated from Celastrus angulatus (Celastraceae) was calculated theoretically at the both levels HF/6-311+G(2d,p)//B3LYP/6-31G(d) and HF/6-311+G(2d,p)//B3LYP/6-31G(d,p) using the GIAO (gauge-independent atomic orbital) method. Statistical error analysis for theoretically predicted δH and δC values versus those experimentally observed for compound 1 was discussed. The results show that the theoretically predicted δH and δC values of β conformer of compound 1 are more close to the experimentally observed values than α conformer, and the β conformer of compound 1 is more stable than α conformer according to molecular energy theoretically calculated. So compound 1 is assigned to be 2,4,6-trimethoxyphenol-1-O-β-D-glucopyranoside, which is in good consistence with the conclusion deduced by the anomeric proton signal (δH=4.80, J=7.3 Hz) experimentally observed.     

1-(2-Quinoxalyl)-, 1-[3,5-Di(trifluoromethyl)phenyl]-, 1-(2-Carboxyphenyl)-, and 1-Ethoxycarbonyl-4-oxo-4,5,6,7-tetrahydroindazoles

The corresponding 1-(2-quinoxalyl)-, 1-[3,5-di(trifluoromethyl)phenyl]-, and 1-ethoxycarbonyl-3-methyl-4-oxo-4,5,6,7-tetrahydroindazoles have been obtained from reactions of 2-acetyl-1,3-cyclohexanedione, its 5,5-dimethyl and 5-(2-furyl) derivatives, with 2-hydrazinoquinoxaline, 3,5-di(trifluoromethyl)phenylhydrazine, and ethoxycarbonylhydrazine. On interaction with ethoxycarbonylhydrazine the intermediate 2-[1-(-ethoxycarbonyl)hydrazino]ethylidene-1,3-cyclohexanediones were also isolated. From the potassium salt of 2-formyldimedone and 2-carboxyphenylhydrazine hydrochloride, 2-(2-carboxyphenyl)hydrazinomethylene-5,5-dimethyl-1,3-cyclohexanedione was obtained, the cyclization of which in ethanol in the presence of HCl led to 1-(2-carboxyphenyl)- and 1-(2-ethoxycarbonylphenyl)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazole.     

Absolute configuration and conformation analysis of 1-phenylethanol by matrix-isolation infrared and vibrational circular dichroism spectroscopy combined with density functional theory calculation

The absolute configuration and conformation of 1-phenylethanol (1-PhEtOH) have been determined by matrix-isolation infrared (IR) and vibrational circular dichroism (VCD) spectroscopy combined with quantum chemical calculations. Quantum chemical calculations have identified that there are three conformers, namely, I, II, and III, in which characteristic intramolecular interactions are found. The IR spectrum-conformation correlation for 1-PhEtOH has been developed by the Ar matrix-isolation IR measurement and used for the assignments of the observed IR bands. In a dilute CCl(4) solution, 1-PhEtOH exists predominantly as conformer I along with a trace amount of conformer II. By considering conformations and intermolecular hydrogen-bonding in the spectral simulation for (S)-1-PhEtOH, we have successfully reproduced the VCD spectrum of (-)-1-PhEtOH observed in a dilute CS(2) solution. Thus, (-)-1-PhEtOH is of S-configuration and conformer I in the dilute solution. The same method has been applied to analyze the VCD spectra measured in the liquid state of (-)-1-PhEtOH. The absolute configuration of 1-PhEtOH in the condensed phase is enabled by identifying VCD bands that are insensitive to conformational changes and intermolecular interactions. The present work provides a combinatorial procedure for determination of both the absolute configuration and the conformation of chiral molecules in a dilute solution and condensed phase.     

An ab initio study of the geometries and rotational barriers of 1-, 2-, and 5-phenylimidazole

The torsional barrier was calculated in the 3-21G basis set for 1-, 2-, and 5-phenylimidazole. Full geometry optimization was carried out at inter-ring torsional angles of 0°, 30°, 60°, 90°, 120°, 150°, 180°, and additional intermediate angles. All torsional potential energies were found to be symmetric with respect to the 90° conformation. The 2-phenylimidazole torsional energy exhibits a minimum at 0° (and 180°) and a maximum at 90° with a barrier height of 5.83 kcal/mol relative to the 0° conformation. The minima in the 1- and 5-phenylimidazole torsional potential energies correspond to non-planar conformations, resulting in a double-well potential with maxima at 0° (180°) and 90°. The 1-phenylimidazole minima are located at 46.5 and 133.5°; the 5-phenylimidazole minima, at 35.3 and 144.7°. In the 0° (180°) and 90° conformations, 1-phenylimidazole exhibits torsional barriers of 1.84 and 0.75 kcal/mol, respectively, relative to the energy of the 46.5° conformation. For 5-phenylimidazole, these barriers are 0.94 and 1.89 kcal/mol, relative to the energy of the 35.3° conformation. The energy of 5-phenylimidazole in the 35.3° conformation corresponds to a relative tautomeric energy difference of 1.80 kcal/mol compared to the 0° conformer of the 4-phenylimidazole tautomer.     

Synthesis and properties of 2-(2-furyl)-1-methyl-1H-acenaphtho[9,10-d]imidazole

2-(2-Furyl)-1-methyl-1H-acenaphtho[9,10-d]imidazole was obtained by the condensation of 9,1-acenaphthenequinone with furfural in the presence of ammonium acetate followed by N-methylation of the obtained 2-(2-furyl)-1H-acenaphtho[9,10-d]imidazole with methyl iodide in N-methylpyrrolid-2-one in the presence of potassium hydroxide. It was established that its electrophilic substitution in an acidic medium only takes place at position 2 of the furan ring while in a neutral medium both position 2 and position 7 of the aromatic part of the molecule undergo electrophilic attack. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 191–196, February, 2006.     

On the structural and spectroscopic properties of the thienyl chalcone derivative: 3-(5-Bromo-2-thienyl)-1-(4-nitrophenyl)-prop-2-en-1-one

In this study, we investigate the structural and spectroscopic properties of the thienyl chalcone derivative 3-(5-Bromo-2-thienyl)-1-(4-nitrophenyl)-prop-2-en-1-one, C₁₃H₈BrNO₃S, using nuclear magnetic resonance (¹H and ¹³C NMR), UV–vis and Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy at room conditions combined with density functional theory (DFT) and time-dependent DFT (TD-DFT) augmented with B3LYP/6-311G(d,p) and CAM-B3LYP/6-311G(d,p) basis sets, yielding valuable information on the molecular conformational preferences, vibrational assignments, optical properties and electronic transitions. The vibrational mode assignments of the most stable conformer of C₁₃H₈BrNO₃S are discussed based on potential energy distribution (PED) analysis and establishing a comparison with a similar chemical structure. The temperature dependence on the Raman spectra of the C₁₃H₈BrNO₃S shows a reversible phase transition in the range 443–443 K pointed out by the discontinuity in the dω/dT of bands in the external and internal modes region. The UV–vis spectrum of the C₁₃H₈BrNO₃S indicates a semiconductor behavior with an optical band gap of 2.6 eV, corresponding to the predicted value of 3.42 eV assigned as the electronic transition from the highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO). TD-DFT calculations reveal that the electron donor and acceptor group substitution on the 1-phenyl-3-(thiophen-2-yl)prop-2-en-1-one affects its absorption and nonlinear activity.     

Synthesis of 1-(alkylamino)- and 1-(dialkylamino)benzimidazoline-2-thiones

Unlike 1-aminobenzimidazoles, 1-alkylaminobenzimidazoles are thiolated on fusing with sulfur without elimination of theN-amino group, yielding the previously unknown 1-(alkylamino)benzimidazoline-2-thiones. These compounds can be more conveniently obtained on a preparative scale by thiolation of 1-alkylacetamidobenzimidazoles with subsequent hydrolytic elimination of the acetyl group. When 1-(dialkylamino)benzimidazoles are fused with sulfur, they are converted into 1-(dialkylamino)benzimidazoline-2-thiones. By alkylation of 1-(methylamino)- and 1-(diethylamino)benzimidazoline-2-thiones with methyl iodide in alkaline media the corresponding 2-(methylthio)benzimidazoles were prepared.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2231–2235, November, 1995.The authors are grateful to the Contest Center of Basic Natural Science at St. Petersburg University for financial support of this study.     

1H and 13C NMR spectra of N-substituted morpholines

(1)H and (13)C NMR data for N-substituted morpholines 1-20 were measured using 1D (DEPT, 1D NOE difference) and 2D NMR spectroscopic methods including (1)H-(1)H COSY, long-range (1)H-(1)H COSY, NOESY, gHMBC and gHMQC experiments. At room temperature the (1)H NMR spectra of protonated compounds 2 and 9 show the chair conformation for the morpholine ring. Spin-spin coupling constants were deduced from the resolution-enhanced proton spectra.     

A quantum-chemical study of aza derivatives of (<Emphasis Type="Italic">E</Emphasis>)-1-styrylnaphthalene in the ground and lowest electronically excited states

The structures of (E)-1-styrylnaphthalene (1SN) and its aza derivatives 1-styrylisoquinoline (1SiQ) and 4- and 8-styrylquinolines (4SQ and 8SQ, respectively) in the neutral and protonated forms were calculated by the semiempirical (PM3) and DFT (B3LYP/6-31G*) methods. It follows from the DFT data that, in the ground state (S0), 1SiQ and 8SQ are planar, whereas 1SN, neutral 4SQ, and all protonated azastyrylnaphthalenes are nonplanar with aromatic cores twisted by 5 to 40° out of the plane of the double bond and with linear correlation between the torsion angles of the two cores. The calculated adiabatic excitation energy (E _ad) varies within 61–64 kcal mol^?1 for the neutral compounds and decreases for the protonated forms to 48, 45, and 33 kcal mol^?1 for 1SiQH⁺, 4SQH⁺, and 8SQH⁺, respectively. The lower E _ad value for 8SQH⁺ is in qualitative agreement with a lower photoisomerization quantum yield for this compound as compared with that for other protonated azastyrylnaphthalenes.     

Synthesis, Crystal Structure and Antidepressant Activity of 5-[4-(Benzyloxy)phenyl]-9-(n-propyl)-4,6-dioxa-1-azabicyclo[3.3.1]nonane Hydrochloride 0.5Hydrate

The title compound 2(C22H28N+O3)·H2O·2Cl-was synthesized by the reaction of 2-bromo-1-[4-(benzyloxy)phenyl]-1-pentone with 2,2'-azanediyldiethanol. The crystal determined by X-ray diffraction analysis belongs to the monoclinic system, space group Pc with a = 18.312(3), b = 14.838(3), c = 7.6227(14) , β = 97.981(4)°, Z = 2, Mr = 797.82, V = 2051.1(6) 3, Dc = 1.292 g/cm3, S = 0.956, μ = 0.21 mm-1, F(000) = 852, the final R = 0.0625 and wR = 0.1428 for 5683 observed reflections (Ⅰ > 2σ(Ⅰ)). Flack parameter is 0.10(9). The title compound is composed by four non-coplanar ring systems, two benzenes and two morpholines. One morpholine ring (C(3)-C(4)-N(1)-C(1)-C(2)-O(1)) forms a chair conformation, while the other (C(4)-C(3)-O(2)-C(6)-C(5)-N(1)) assumes a boat conformation. X-ray crystal structure displays extensive N-H…Cl and O-H…Cl intermolecular hydrogen bonds. The preliminary antidepressant activity test indicates that the inhibition ratio of SERT (5-HT Transporter) was 35.9% at the dosage of 10.0 mg/L.