Mixture Of Rotamers Research Articles

Trifluoromethyl Fluoroformyl Trioxicarbonate, CF3OC(O)OOOC(O)F: The First Nonsymmetric Acyl Trioxide

This paper reports for the first time the synthesis and characterization of trifluoromethyl fluoroformyl trioxicarbonate, CF(3)OC(O)OOOC(O)F. The new trioxide is obtained from the gas-phase photolytic reaction of CF(3)C(O)OC(O)CF(3) and FC(O)C(O)F at 223-228 K. It is a very thermally labile molecule that decomposes at room temperature by rupture of either of the CF(3)OC(O)O-O-OC(O)F bonds. These bonds are nonequivalent, and a branching ratio of 0.8 for fragmentation through the CF(3)OC(O)OO-OC(O)F bond was obtained. Unambiguous identification was possible through reaction of the trioxide with an excess of NO(2). Potential-energy surfaces (PES) of the different rotamers were studied by the B3LYP/6-311+G* method, and analysis of the IR frequency of the possible mixture of rotamers agrees excellently with the experimental IR spectrum. This molecule is the first nonsymmetric acyl trioxide reported in the literature.

Synthesis and reactivity of rhodium(III) pentamethylcyclopentadienyl complexes of N– B–PTA(BH 3): X-ray crystal structures of [Cp ∗RhCl 2{ N– B}–PTA(BH 3)] and [Cp ∗Rh{ N– B–PTA(BH 3)}(η 2-CH 2 = CHPh)

The reaction between 1-boranyl-1,3,5-triaza-7-phosphaadamantane ligand N– B–PTA(BH 3) and [Cp ∗RhCl(μ-Cl)] 2 affords [Cp ∗Rh{ N– B–PTA(BH 3)}Cl 2] ( 3) or [Cp ∗Rh{ N– B–PTA(BH 3)} 2Cl]Cl ( 5) containing one or two P-bonded boronated PTA ligands. The hydride [Cp ∗Rh{ N– B–PTA(BH 3)}H 2] ( 8) was also obtained by reaction of 3 with NaBH 4 and alternatively by direct hydroboration of [Cp ∗Rh(PTA)Cl 2] with excess NaBH 4. Moderately slow hydrolysis of the N-boranyl rhodium complexes affords dihydrogen, H 3BO 3 and the corresponding PTA derivatives, including the water-soluble dihydride [Cp ∗Rh(PTA)H 2] ( 9). Finally, the reaction of 8 with electron poor alkynes gives the alkene complexes [Cp ∗Rh{ N– B–PTA(BH 3)}(η 2-CH 2 = CHR)] (R = Ph, 10; C(O)OEt, 11) as a mixture of rotamers η 2-coordinated to rhodium without affecting the N–BH 3 moiety. The X-ray crystal structures of 3 and 10 were also obtained and are here discussed.

Synthesis, structure, and reactivity of monofunctional platinum(II) and palladium(II) complexes containing the sterically hindered ligand 6-(methylpyridin-2-yl)acetate

Three complexes containing the novel, sterically hindered ligand 6-(methylpyridin-2-yl)acetate (PICAC) have been synthesized and characterized: [Pt(NH 3) 2(PICAC- N, O)]NO 3 ( 1), [Pt(en)(PICAC- N, O)]NO 3 ( 2), and [Pd(en)(PICAC- N, O)]NO 3 ( 3) (en = ethane-1,2-diamine). The crystal structures of 2 and 3 have been determined. The two complexes are isostructural and exhibit a mixed [N 3O] coordination. In both cases, PICAC forms a sterically crowded six-membered chelate. Signal multiplicities in 1H NMR spectra of 1– 3 indicate that the N,O chelates are conformationally rigid on the NMR timescale as a result of the steric bulk of the pyridine derivative. Complex 2 undergoes facile ring opening in 0.1 M NaCl solution at neutral pH, resulting in a zwitterionic species in which carboxylate oxygen has been replaced with chloride. The complex was identified by X-ray crystallography as [PtCl(en)(PICAC- N)] · H 2O ( 4), which contains a “dangling” carboxylate group. In 4, the pyridine moiety adopts an almost perpendicular orientation relative to the platinum coordination plane. Likewise, complex 2 reacts rapidly with 5′-guanosine monophosphate (5′-GMP) to form the monofunctional adduct [Pt(en)(PICAC)(5′-GMP)] ( 5) (NMR, 25 °C, t 1/2 ≈ 24 min). 2-D nuclear Overhauser enhancement spectroscopy (NOESY) and double quantum-filtered correlated spectroscopy (dqf-COSY) experiments (500 MHz) and variable temperature NMR spectroscopy confirm that adduct 5 exists as a 1:1 mixture of rotamers in solution as a result of the mutual repulsion between the cis-oriented pyridine and guanine bases. While 2 readily reacts with DNA nitrogen, its monofunctional adducts show no significant effect on the conformation of native DNA. Circular dichroism (CD) spectra recorded of platinum-modified calf-thymus DNA suggest that the structural damage produced by complex 2 does not mimic that produced by the clinical agent. Both the unusual reactivity and the inability to induce cisplatin-like DNA conformational changes are proposed to be responsible for the marginal biological activity of the new complexes.

Trifluoromethoxycarbonyl Peroxynitrate, CF3OC(O)OONO2

The trioxide, CF(3)OC(O)OOOC(O)OCF(3), reacts with NO(2) at 0 degrees C to yield the new peroxynitrate, CF(3)OC(O)OONO(2), which is stable for hours at room temperature. It is spectroscopically characterized and some thermal properties are reported. From the vapor pressure, ln(p/p(0)) = 14.06 - 4565/T, of the liquid above the melting point of -89 degrees C, the extrapolated boiling point is 52 degrees C. CF(3)OC(O)OONO(2) dissociates at higher temperatures and low pressures into the radicals CF(3)OC(O)OO and NO(2) as demonstrated by matrix isolation experiments. The matrix-isolated peroxy radicals consist in a rotameric mixture of trans,trans,trans-CF(3)OC(O)OO and trans,trans,cis-CF(3)OC(O)OO, where trans and cis denote dihedral angles of ca. 180 degrees and 0 degree, respectively, around beta F-C-O-C, beta C-O-C-O, and beta O-C-O-O, with an equilibrium composition dependent on the thermolysis temperature. The radical trans,trans,cis-CF(3)OC(O)OO is found to be ca. 3 kJ mol(-1) higher in enthalpy than trans,trans,trans-CF(3)OC(O)OO. DFT calculations are performed to support the vibrational assignments and to provide structural information about CF(3)OC(O)OONO(2).

The synthesis and conformation of oxygenated trianglimine macrocycles

The synthesis of series of D(2h) and C(2v) symmetric oxygenated aromatic dicarboxaldehydes, using dilithiation methodology, is described along with their reactivity in the [3+3] cyclocondensation reaction with (1R,2R)-diaminocyclohexane to give oxygenated trianglimine macrocycles. Macrocycles derived from C(2v) symmetric dialdehydes give macrocycles with a stereogenic aromatic plane with complete diastereocontrol, as a mixture of rotamers.

A novel approach toward the synthesis of kendomycin: selective synthesis of a C-aryl glycoside as a single atropisomer.

[reaction: see text] A convergent and concise route to an advanced precursor 2b of kendomycin (1) has been developed by applying a S(N)1 ring cyclization as a key step. The resulting C-aryl glycoside was initially isolated as a rotameric mixture, but after MOM protection of the o-hydroxyl of the phenol, the conformation was frozen to the desired kendomycin-like atropisomer.

Dictyoquinazols A, B, and C, new neuroprotective compounds from the mushroom Dictyophora indusiata.

In an effort to identify neuroprotective compounds against excitatory neurotoxins from edible and medicinal mushrooms, dictyoquinazols A (1), B (2), and C (3) have been isolated from the methanolic extract of the mushroom Dictyophora indusiata. On the basis of NMR studies, their structures have been assigned as unique quinazoline compounds, which are very rare in nature. 2 and 3 existed as mixtures of rotamers (2a, 2b and 3a, 3b) inseparable by HPLC because of fast interconversion. The E/Z isomers of these compounds were assigned by comparison of (1)H NMR, (13)C NMR, and NOESY spectra and by (3)J(C,H) coupling constants. Dictyoquinazols protected primary cultured mouse cortical neurons from glutamate- and NMDA-induced excitotoxicities in a dose-dependent manner.

Characterization of rotameric mixtures in o- and m-substituted benzaldehydes by matrix isolation IR spectroscopy.

The cis and trans conformers of benzaldehydes substituted in the o- or m-positions by Cl or CN can be differentiated by IR spectroscopy in Argon matrices. Partial photochemical rotamerization allows assignment of the IR bands and establishment of their relative intensities in pairs of rotamers, which permits, in turn, quantitation of equilibrium compositions prior to photolysis. The observed spectra and equilibrium compositions are in very good agreement with the predictions of vibrational spectra and free energy differences from B3LYP/6-31G calculations. The present work represents the first attempt to quantitate the small contributions that the cis rotamers make to the room-temperature equilibrium compositions of the two o-substituted benzaldehydes. The results for the m-substituted derivatives are compared to earlier estimates based on other methods.

Synthesis ofN-Acetyl-1,3-dimethyltetrahydroisoquinolines by Intramolecular Amidomercuration: Stereochemical Aspects

Mercury(II)-mediated ring closure of N-[1-(2-allyl-3-benzyloxy-4,6-dimethoxyphenyl)ethyl)acetamide 4 afforded N-acetyl-5-benzyloxy-6,8-dimethoxy-1,3 -trans-dimethyl-1,2,3,4-tetrahydroisoquinoline 3. The product was shown to exist as a mixture of rotamers by NMR spectroscopy, since signals coalesced at higher temperatures. 2-[2-[1-(Acetylamino)ethyl]-6-(benzyloxy)-3,5-dimethoxyphenyl]-1-methylethyl methanesulfonate 8 was also cyclized with sodium hydride to afford rotameric products with the same isoquinoline skeleton, but as a mixture of 1,3-cis-and transdimethyl isomers.

First total syntheses of aeruginosin 298-A and aeruginosin 298-B, based on a stereocontrolled route to the new amino acid 6-hydroxyoctahydroindole-2-carboxylic acid.

The first total syntheses of aeruginosin 298-A (1) and aeruginosin 298-B (3) are described. The syntheses of the alternative putative structures 2 and 4 were also accomplished. The key common strategic element is the stereo-controlled synthesis of (2S,3aS,6R,7aS)-6-hydroxyoctahydroindole-2-carboxylic acid (L-Choi, 5) from L-tyrosine. The synthesis of this new bicyclic alpha-amino acid, which is the core of aeruginosins, involves Birch reduction of O-methyl-L-tyrosine (6) and aminocyclization of the resulting dihydroanisole 7 in acid medium, followed by N-benzylation to give the diastereoisomers 12 and 13. Upon acid treatment with HCl-MeOH, the last two produce an equilibrium mixture in which the endo isomer 13 significantly predominates. Hydrogenation of 13 in the presence of (Boc)2O gives 16, which on reduction with LS-Selectride furnishes the alcohol 22, a protected L-Choi. Successive couplings of 22 with D-leucine, protected (R)-(4-hydroxyphenyl)lactic acid, and L-arginine fragments, followed by reduction to the argininol level and a deprotection end step complete the synthetic sequence to produce aeruginosin 298-A (1). Spectral comparison showed that peptide 2, with the structure previously proposed for aeruginosin 298-A, was different from the natural product. However, synthetic 1 was found to be identical to the isolated natural sample of aeruginosin 298-A. These results unequivocally establish that the absolute stereochemistry of aeruginosin 298-A, formerly assigned incorrectly, is D-Hpla-D-Leu-L-Choi-L-Argol, as shown by structure 1. Aeruginosin 298-B was also synthesized and shown to be a mixture of rotamers of D-Hpla-D-Leu-L-ChoiNH2 (3), rather than an epimeric mixture of 3 and the L-Leu-incorporating 4.

Rotational isomerism and crystal structures of 2,2′-diphenyl-2,2′-bi-1,3-dithianyl and 2,2′-diphenyl-2,2′-bi-1,3-dioxolanyl †

Dipole moments of the compounds 2,2′-diphenyl-2,2′-bi-1,3-dithianyl 1 and 2,2′-diphenyl-2,2′-bi-1,3-dioxolanyl 2 in carbon tetrachloride and benzene have been measured over a range of temperatures. The crystal and molecular structures of the compounds were determined by single-crystal X-ray diffraction methods. Analyses of the crystal structures and relative permittivity data show that the compounds exist in the trans conformation in the solid state and as rotameric mixtures in solution with a predominantly high trans population of 85% and 80% respectively at 25 °C. The experimentally derived values of the energy difference between the gauche and trans rotamers and the gauche/trans population quotients were compared with the values predicted by molecular orbital calculations.

Rotational isomerism and crystal structures of 9,9′-dicyano-9,9′-bifluorenyl and 9,9′-dinitro-9,9′-bifluorenyl

Dipole moments of the compounds 9,9′-dicyano-9,9′-bifluorenyl 1 and 9,9′-dinitro-9,9′-bifluorenyl 2 in 1,4-dioxane and benzene have been measured over a range of temperatures. The crystal and molecular structures of the compounds were determined by single-crystal X-ray diffraction methods. Analyses of the crystal structures and relative permittivity data show that the compounds exist in the polar gauche conformation in the solid state and as rotameric mixtures in solution with a predominantly high gauche population of 94% and 99% respectively at 25 °C. The experimentally derived values of the energy difference between the gauche and trans rotamers and the gauche/trans population quotients were compared with the values predicted by the semiempirical MO programme AMPAC using AM1 parametrization. Dynamic 1H NMR was employed to determine the activation parameters for the barriers to rotation in solution.

Conformational Analysis of Methyl 2,3,4-Tri-O-acetyl-6-deoxy-6-phenylsulfinyl-.ALPHA.-D-glucoside.

Conformational analysis of methyl 2, 3, 4-tri-O-acetyl-6-deoxy-6-(R)-phenylsulfinyl-α-D-glucopyranoside (1), methyl 2, 3, 4-tri-O-acetyl-6-deoxy-6-(S)-phenylsulfinyl-α-D-glucopyranoside (2) and methyl 2, 3, 4-tri-O-acetyl-6-deoxy-6-phenylsulfonyl-α-D-glucopyranoside (3) in solution (CDCl3) and the crystalline state was carried out using 1H-NMR spectra and X-ray crystallographic data. The conformational preference of the C6-S bond in the above mentioned compounds was found to be GT (GT is short for gauche-trans), and as a 1 : 1 mixture of rotamers for the (S)-S-oxide (2) and sulfone (3) but not in the (R)-S-oxide (1) in the solid state.

Carbonyl Hypofluorite-A Density Functional Theoretical Study

Calculations on FOC(O)OF are reported at the B3LYP/6-311+G(2df)//B3LYP/6-31+G(d)+ZPC level of theory. The molecule is predicted to exist as a mixture of rotamers. The lowest-energy rotamer, the syn−anti, is predicted to be planar. The syn−syn rotamer appears to be conformationally floppy; a nonplanar (C2) form, with O−F bonds rotated from the CO3 plane by 16.4°, and a planar (C2v) form are separated by only 0.01 kcal/mol. The anti−anti rotamer is predicted to be nonplanar (C2 symmetry); the O−F bonds are rotated out of the CO3 plane by 27.9°. Calculated barriers for interconversion of rotamers are less than 10 kcal/mol. We also calculate vibrational frequencies for the rotamers. The calculated O−F bond enthalpy is 30.2 kcal/mol.

Rotational isomerism in 1,2-diaminoethane, 1,2-bis(dimethylamino)ethane and 1,2-bis(diethylamino)ethane

IR and Raman spectra as well as dipole moments of the title compounds in solution are reported. Analysis of the dielectric data shows that, at 25°C, the compounds in the series exist as rotameric mixtures in benzene solution containing 84, 72 and 67% respectively of the gauche rotamer. The experimentally derived values of the gauche/trans population quotients are compared with values predicted by semiempirical MO and molecular mechanics calculations.

Rotational isomerism in tetramethyldistibane studied by UV photoelectron spectroscopy

He(I) photoelectron spectroscopic (PE) measurements and ab initio calculations were performed on tetramethyldistibane. The spectroscopic measurements gave clear evidence for the existence of gauche and anti conformers in the gas phase. The composition of the rotameric mixture is 12% gauche and 88% anti conformers, estimated on the basis of the corresponding PE band areas. The Hartree-Fock calculations were performed using both effective core potential and all-electron 3–21 Gaussian basis sets. Full geometry optimizations were applied, resulting in theoretical evidence for the existence of the two rotamers. The calculated ionization energies seem to necessitate further studies on the assignment of the PE bands related to the antimony lone pairs.

Fluoroformyl Hypofluorite, Fluoroformyl Peroxyhypofluorite, and Fluoroformyl Peroxide. A Density Functional Study

Calculations on FC(O)OF, FC(O)OOF, and FC(O)OOC(O)F are reported at the B3LYP/6-31+G(d)//B3LYP/6-31+G(d)+ZPC level of theory. All these molecules are predicted to exist as mixtures of rotamers. For FC(O)OF, the calculations reproduce the known structural parameters, the enthalpy difference between the rotamers, the activation energy for their interconversion, and their vibrational frequencies. They predict an O−F bond dissociation energy of 28.7 kcal/mol in the lowest-energy (trans) rotamer. For FC(O)OOF, the calculations predict nonplanar molecules, with O−F and O−O distances of 1.446 and 1.394 A, respectively, and O−F and O−O bond dissociation energies of 30.8 and 22.3 kcal/mol, respectively, in the trans rotamer. Calculations on FC(O)OOC(O)F reproduce the known structural parameters and vibrational frequencies; they predict an O−O bond dissociation energy of 14.8 kcal/mol. Enthalpy changes for the proposed reactions which lead to the formation of FC(O)OF from FC(O)OOC(O)F and for the proposed decomposi...

Chemistry and occurrence of taxane derivatives. Part 16. Rearranged taxoids from Taxus×media Rehd. cv Hicksii. X-Ray molecular structure of 9-O-benzoyl-9,10-dide-O-acetyl-11(15 → 1)abeo-baccatin VI

The roots of Taxus×media Rehd. cv Hicksii gave four new taxoids of the abeo 11(15 → 1)-type (2–5). Structures were elucidated by spectroscopic techniques, including X-ray analysis for compound 4. Compound 2 is conformationally fixed, whereas compounds 3–5 exist in solution as a mixture of rotamers, whose interconversion was investigated by variable-temperature NMR spectroscopy. Compound 2 has a C-13, C-15 oxygen bridge, and is the first natural taxoid with a β-oxygen function at C-13.

Synthesis, transformations and biological activity of chloro enamines and ynamines derived from chloroalkenyl- and alkynyl-N-substituted purine and pyrimidine bases of nucleic acids

Reactions of nucleic acid bases and related heterocycles 1–5, 18 and 22 with tetra-, tri- and dichloroethylenes 6–9 in hexamethylphosphoric triamide gave the corresponding N-trichloro-, -dichloro- and -chloro- enamines 11–17, 19, 20, 23 and 24 in high regioselectivity (N9 for purines and N1 for pyrimidines). Bases 1, 5, 18, 22 and trichloroethylene 7 gave the respective E-dichloro enamines 15, 16, 20 and 24. Compounds 16 and 20 were identical with the products obtained by addition of bases 1 and 18 to dichloroacetylene. Thymine 18 and compound 7 gave N1,N3-bisdichloro enamine 21 as the major product. The latter exists at room temperature as a mixture of rotamers 28 and 29(ΔG‡≅ 18 kcal mol–1). The reaction of adenine 1 with (Z)-1,2- or 1,1-dichloroethylene 8 or 9 furnished Z-chloro enamine 17 whereas thymine 18 and tetrachloroethylene 6 in dimethyl sulfoxide afforded a reduction product 20. Benzoylation of N9-(trichlorovinyl)adenine 11 gave N6,N6-dibenzoyl derivative 26. The reaction of N1-(dichlorovinyl)cytosine 24 with N,N-dimethylformamide dimethyl acetal afforded amidine 25. Interaction of (E)-N9-(dichlorovinyl)adenine 16 with sodium methoxide gave exclusively E-enamine 27. Trichloro enamines 11–14, 19, 23 and 26 were transformed to ynamines 30–35. Hydrogenation of compounds 30 and 35 furnished N9-ethyladenine 36 and N1-ethylthymine 37. Alkylation of ynamine 30 with acetone 38 gave only carbinol 41 whereas cyclohexanone 39 gave both compound 42 and cyclic ketal 43. The reaction of ynamines 30 and 35 with ketone 40 afforded only ketals 44 and 45. The reaction of compound 30 with N,N-dimethylformamide dimethyl acetal led to N-dimethylaminomethylene derivative 46. Ynamine 30 is a substrate for adenosine deaminase.

Principal-component self-modeling analysis of fluorescence for some trans-diarylethylenes. A comparison with kinetic analysis

A refined version of the “principal-component analysis — self-modeling” (PCA-SM) method was applied to resolve the fluorescence spectra of mixtures of rotamers for two trans-1,2-diarylethylenes. The effect of the excitation wavelength (λ exc) on the fluorescence of 3-styrylphenanthrene allowed the photophysical and thermodynamic parameters of the two rotamers to be obtained. The effect of λ exc and temperature on the emission of 2-styrylanthracene gave similar information for a three-component system (two rotamers, one having a dual fluorescence). Comparison with results previously obtained by the kinetic fluorescence analysis (KFA) method was useful for checking the validity of the statistical and kinetic methods and led to some extensions and some revisions of the already published data.