- Structure, conformations, and internal hydrogen bonding in gaseous 4-fluorobutan-1-ol. Gas-phase electron diffraction and Ab initio study
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Excluding enantiomers, there are 14 possible rotomeric conformations of 4-fluorobutan-1-ol, of which two are capable of forming an internal O-H...F hydrogen bond. The composition of the gaseous system is of special interest because it is determined by the energies of the conformers which reflect the energies of the hydrogen bonds. We have investigated the conformational composition of the gaseous system and the molecular structures of the conformers at 83 °C by gas-phase electron diffraction (GED) augmented by molecular orbital calculations. Because of the complexity of the 4-fluorobutan-1-ol system, the parameters of the several models tested were simplified by various constraints taken from the theoretical work. With these constraints, the best agreement with the GED data was obtained with a model consisting of about equal amounts of hydrogen-bonded and non-hydrogen-bonded conformers. Because the curled-up shape of the two forms capable, in principle, of forming internal hydrogen bonds is expected to be energetically unfavorable in the absence of such bonding, the experimental results are interpreted as strong evidence for its existence. Weighted average values, with estimated 2σ uncertainties, of the more important bond distances (ra/A) and bond angles (∠a/deg) for the preferred model are r(Co-C) = 1.529(2), r(CC-CC) = 1.537(2), r(C-CF) = 1.520(2), r(C-O) = 1.430(5), r(C-F) = 1.401(5), ∠(Co-C-C) = 112.5(33), ∠(C-C-O)H bond = 112.3(55), ∠(C-C-O)no H bond = 108.2(45), and ∠(C-C-CF) = 109.8(12). The two hydrogen-bonded conformers comprise 48.5% of the mixture with an estimated 2σ uncertainty of 14.0%. A rough estimate of the energy of the O-H...F hydrogen bond is 3 kcal mol-1. The average O...F separation in this bond for the H-bonded conformers is 2.46(4) A, about 0.3 A less than the sum of the van der Waals radii.
- Traetteberg, Marit,Richardson, Alan D.,Hedberg, Kenneth,Winter, Rolf W.,Gard, Gary L.
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- Effect of Partially Fluorinated N-Alkyl-Substituted Piperidine-2-carboxamides on Pharmacologically Relevant Properties
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The modulation of pharmacologically relevant properties of N-alkyl-piperidine-2-carboxamides was studied by selective introduction of 1–3 fluorine atoms into the n-propyl and n-butyl side chains of the local anesthetics ropivacaine and levobupivacaine. The basicity modulation by nearby fluorine substituents is essentially additive and exhibits an exponential attenuation as a function of topological distance between fluorine and the basic center. The intrinsic lipophilicity of the neutral piperidine derivatives displays the characteristic response noted for partially fluorinated alkyl groups attached to neutral heteroaryl systems. However, basicity decrease by nearby fluorine substituents affects lipophilicities at neutral pH, so that all partially fluorinated derivatives are of similar or higher lipophilicity than their non-fluorinated parents. Aqueous solubilities were found to correlate inversely with lipophilicity with a significant contribution from crystal packing energies, as indicated by variations in melting point temperatures. All fluorinated derivatives were found to be somewhat more readily oxidized in human liver microsomes, the rates of degradation correlating with increasing lipophilicity. Because the piperidine-2-carboxamide core is chiral, pairs with enantiomeric N-alkyl groups are diastereomeric. While little response to such stereoisomerism was observed for basicity or lipophilicity, more pronounced variations were observed for melting point temperatures and oxidative degradation.
- Vorberg, Raffael,Trapp, Nils,Zimmerli, Daniel,Wagner, Bj?rn,Fischer, Holger,Kratochwil, Nicole A.,Kansy, Manfred,Carreira, Erick M.,Müller, Klaus
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p. 2216 - 2239
(2016/10/19)
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- A novel fluorinated erythromycin antibiotic
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A novel fluorinated erythromycin (16-fluoroerythromycin A) has been produced by Saccharopolyspora erythraea ERMD1, using precursor-directed biosynthesis. The Royal Society of Chemistry 2005.
- Goss, Rebecca J. M.,Hong, Hui
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p. 3983 - 3985
(2007/10/03)
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- REACTION OF HYDROXY AND CARBONYL COMPOUNDS WITH SULFUR TETRAFLUORIDE IX. REACTIONS OF GLYCOLS WITH SULFUR TETRAFLUORIDE
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Selective substitution of one of the hydroxyl groups by a fluorine atom occurs in the reactions of 1,2-, 1,3-, and 1,4-glycols with sulfur tetrafluoride under mild conditions.The regioselectivity of substitution in the case of unsymmetrical glycols depends on the electronic nature of the groups present in the molecules of the initial compounds.
- Hassanein, Salah Mohamed,Burmakov, A. I.,Bloshchitsa, F. A.,Yagupol'skii, L. M.
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p. 1473 - 1477
(2007/10/02)
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