Conformational Study of Cyclohexanols in Dimethyl Sulfoxide

161

107

The exact analysis of the ABC type absorption due to the -CH20H group of 3j3-acetoxy-5j3,6[3-oxidocholestan-19-01 provides two vicinal HCOH coupling constants for dihedral angles of 80" and 160". A least squares fit of these and previous data in the literature to a "Karplus" relation provides values for the coefficients in such an equation. The theoretical justification for such a relation has been obtained by extended Hiickel molecular orbital calculations for methanol with different dihedral angles. The practical limitations in, and applications of the relation are discussed. An effect of solvent on the vicinal coupling constants is also noted and discussed.

Section: Introductionmentioning

confidence: 84%

Stereochemical dependence of vicinal H—C—O—H coupling constants

Fraser¹,

Kaufman²,

Morand³

et al. 1969

161

107

“…Hydroxyl coupling constants are known to vary with polarity of the solvent (5, 6), electronegativity of neighboring substituent groups (5,8), and the geometry of the molecule (6,7,9,10). Bearing in mind these limitations, the stereochemical dependence of the vicinal H-C-0-H coupling constants has been calculated (1 1) as JHCoH = 10.4 COS' $ -1.5 COS $ -k 0.2 where J is the spin-coupling constant and $ the dihedral angle between vicinal protons.…”

Section: Introductionmentioning

confidence: 99%

Assignment and conformational properties of the sugar-ring hydroxyl protons of the common nucleosides

Davies¹,

Danyluk²

1970

A 60 MHz proton magnetic resonance study has been made of the hydroxyl protons of the ribose and deoxyribose rings for the common nucleosides dissolved in mixtures of dry DMSO-d6 and CsD6. Use of this solvent system permitted the detection and assignment of the exchange-free spin-coupled multiplets for the hydroxyl protons. The assignment was confirmed by spin-decoupling experiments.Based on the magnitudes of the observed coupling constants, it is concluded that the 0-H,, group is freely rotating around the C,,-O,, bond. It is calculated that the O-H,, bond favors a gauche conformation relative to the C3,-H3, bond, consistent with the preferred conformation found in the solid state for the H3,-C3,-0,'-P bonds of the nucleoside 3'-phosphates. The conformation of the 0-H2. bond relative to the C2.-Hz. bond demonstrates no preference for the gaztche rotamer. Such a rotamer might be expected if a hydrogen-bond between the 2'-OH and the purine base exists in this solvent system, as well as in aqueous solutions where such an interaction has been postulated as a stabilizing influence for ribosides.

“…Coupling of this nature is not observed in aminoalcohols except when the basicity of nitrogen is eliminated as in methiodide salts (1 1 ).3 In spectra of isomeric methiodides the trans OH signal (doublet 6 4.96) did not differ significantly in chemical shift from the cis (doublet 6 4.93) but the assignments 3a and 4a are confirmed by the larger values of the trans OH doublet (trans 5.5, cis 4.2 Hz) (10).…”

mentioning

confidence: 98%

Synthesis and Stereochemistry of Diastereoisomeric 1,3-Dimethylpiperidin-4-ols and Related Compounds

Casy¹,

Jeffery²

1972

The synthesis of cis and trans 1.3-dimethylpiperidin-4-01s and derived acetate, benzilate, and diphenylacetate esters is described. Configurations and preferred conformations of these derivatives are assigned on the basis of 4-methine and 4-hydroxyl p.m.r. characteristics. Conformational studies of esters of I-methylpiperidin-3-01 and isomeric 3-tropanols are also described. Epimeric conjugate acids are well defined in 3-acetoxy-I-methylpiperidine hydrochloride as solute in CDCI,.La synthtse des cis et trans dimethyl-1,3 piperidinols-4 et des esters qui en dtrivent, acetates, benzylates, et diphtnylacttates, est dtcrite. Les configurations et les conformations privilegites de ces derives sont attribuees en se fondant sur les caracteristiques p.m.r. du mtthine-4 et de I'hydroxyl-4. Les etudes conformationnelles des esters du methyl-l piptridinol-3 et des tropanols-3 isomeres, sont egalement decrites. Les acides conjugues epimtres sont bien definis dans le chlorhydrate d'acktoxy-3 methyl-l piperidine dissous dans le CDCI,.Canadian Journal of Chemistry, 50,803 (1972) The cis and trans 1,3-dimethyl-4-piperidyl esters described in this paper were prepared as the steric analogs of cholinolytic esters of tropine and pseudotropine for use in structureactivity studies of drugs related to atropine. The parent piperidinols 1 were obtained by reduction of 1,3-dimethyl-4-piperidone (2) under various conditions. These reactions were first reported by Mistryukov ( I ) who separated the two alcohols by g.1.c. and column chromatography. He assigned configurations cis and cis trans 3 4 a R = H b R=COMe trans to the initially and finally displaced isomers respectively, on the assumption of the cis isomer 3a having an axial (hindered), and the trans 4a an equatorial (accessible) hydroxyl function. These assignments are now confirmed by p.m.r. data, as shown later. We sought to achieve separation of the piperidinols 1 in bulk by crystallization of the base hydrochlorides. In this way only the trans salt could be separated from a total base mixture obtained from the piperidone 2 and LAH; treatment of the base recovered from the mother liquors with acetyl chloride in hot ethyl acetate, however, gave the cis acetate 5 hydrochloride from which H OCOMe we Me 5 the alcohol could be derived after treatment of the free ester with LAH. It was later found that the trans ester 5 separated quantitatively during the reaction when the total piperidinols 1 were acetylated leaving the almost pure cis isomer in the mother liquors. Isomeric purity of the products was confirmed from their p.m.r. spectra (see below). This procedure was adopted as the best route to the pure cis and trans piperidinols 1; it also enabled isomer ratios in the total products of various reductions of 2 to be calculated. The translcis ratio after LAH (2.3) was reasonably close to the reported (1) value of 1.7, while that after aluminum isoCan. J. Chem. Downloaded from www.nrcresearchpress.com by 34.210.69.67 on 05/11/18For personal use only.