Abstract
In substituted cyclohexanes, such as cyclohexanol or its methyl ether, the substituent will preferably assume the equatorial position as opposed to the axial one, due to fewer nonbonded interactions with other ligands (in this case the C3 and the C5 hydrogen atoms) on the cyclohexane ring [1–5]. Thus, the conformational mixture of cyclohexanol or its methyl ether contains, at equilibrium, 89% of the conformer with equatorially oriented hydroxyl or methoxy group and 11% of the conformer with axially oriented hydroxyl or methoxy group, indicating clear preference for the equatorial conformer (Fig. 3.1).
Keywords
- Axial Orientation
- Anomeric Effect
- Conformational Equilibrium
- Unshared Electron Pair
- Equatorial Orientation
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Szarek, W. A.; Horton, D., Eds. “Anomeric Effect, Origin and Consequences”, ACS Symposium Series 87, American Chemical Society, Washington, DC, 1979
Kirby, A. J., “The Anomeric Effect and Related Stereoelectronic Effects at Oxygen”, Springer-Verlag, Berlin, 1983
Deslongchamps, P., “Stereoelectronic Effects in Organic Chemistry”, Pergamon Press, Oxford, 1983
Thatcher, G. R. J., Eds., “The Anomeric Effect and Associated Stereoelectronic Effects”, ACS Symposium Series 539, American Chemical Society, Washington, DC, 1993
Juaristi, E.; Cuevas, G., “The Anomeric Effect”, CRC Press, Boca Raton, 1995
Bates, F. J. and Associates, “Polarimetry, Saccharimetry, and the Sugars”, United States Government Printing Office, Washington, DC, 1942, p.455
Angyal, S. J., “Conformational analysis in carbohydrate chemistry. I. Conformational free energies. The conformations and α:β ratios of aldopyranoses in aqueous solution”, Aust. J. Chem. (1968) 21, 2737–2746
Angyal, S. J., “The composition and conformation of sugars in solution”, Angew. Chem. Intern. Ed. (1969) 8, 157–166
Bonner, W. A., “The acid-catalyzed anomerization of Acetylated Aldopyranoses”, J. Am. Chem. Soc. (1959) 81, 1448–1452
Lemieux, R. U., “Molecular Rearrangements”, Vol. 2, p 709, de Mayo, P., Ed., Interscience, New York, 1963
Lemieux, R. U.; Hayami, J-Y., “The mechanism of the Anomerization of the Tetra-O-acetyl-D-glucopyranosyl chlorides” Can. J. Chem. (1965) 43, 2162173
Pacsu, E., “Über die Einwirkung von Titan (IV)-chlorid auf Zucker-Derivate, I.: Neue Methode zur Darstellung der α β Aceto-chlor-zucker und Umlagerung des β-Methyl-glucosids in seine α-Form”, Chem. Ber. (1928) 61, 1508–1513
Lindberg, B., “The Zempl.acte.en glucoside synthesis”, Arkiv Kemi, Mineral., Geol., Ser. B (1944), 18, No. 9, 1–7
Lindberg, B., “Action of strong acids on acetylated glycosides. I. Transformation of some aliphatic tetraacetyl- β -glucosides to the α-form”, Acta Chem. Scand. (1948) 2, 426–429
Lindberg, B., “Action of strong acids on acetylated glucosides. III. Strong acids and aliphatic glucoside tetraacetates in acetic anhydride-acetic acid solutions”, Acta Chem. Scand. (1949) 3, 1153–1169
Chü, N. J., Ph. D. thesis, Department of Chemistry, University of Ottawa, 1959
Lemieux, R. U.; Chü, N. J., “Conformation and relative stabilities of acetylated sugars as determined by nuclear magnetic resonance spectroscopy and anomerization equilibria”, Abstracts of Papers, Am. Chem. Soc. 133, 31 N (1958)
Edward, J. T., “Stability of glycosides to acid hydrolysis”, Chemistry & Industry (London) (1955) 1102–1104
Corey, E. J., “The Stereochemistry of α-Haloketones. I. The molecular configurations of some Monocyclic α-Haloketones”, J. Am. Chem. Soc. (1953) 75, 2301–2304
Lemieux, R. U., “Effects of unshared pairs of electrons and their Solvation Conformational Equilibria”, Pure Appl. Chem. (1971) 27, 527–548
Winstein, S.; Holness, N. J., “Neighboring Carbon and Hydrogen. XIX. t-Butylcyclo hexyl Derivatives. Quantitative Conformational Analysis”, J. Am. Chem. Soc. (1955) 77, 5562–5578
Eliel, E.L., Stereochemistry of Carbon Compounds, McGraw Hill, New York, 1962, p.236
Andersen, C.B.; Sepp, D. T., “Conformation and the anomeric effect in 2-oxy-substituted tetrahydropyrans”, Tetrahedron (1968) 24, 1707
Isbell, H. S.; Pigman, W. W., “Bromine oxidation and mutarotation measurements of the α- and β-aldoses”, J. Res. Natl. Bur. Std. (1937) 18, 141–194
Angyal, S. J., “Conformational analysis in carbohydrate chemistry. I. Conformational free energies. The conformations and α: ® ratios of aldopyranoses in aqueous solution”, Aust. J. Chem. (1968) 21, 2737–2746
Angyal, S. J., “The composition and conformation of sugars in solution” Angew. Chem. Intern. Ed. (1969) 8, 157–166
Reeves, R. E., “Cuprammonium–Glycoside Complexes. II. The Angle Between Hydroxyl Groups on Adjacent Carbon Atoms”, J. Am. Chem. Soc. (1949) 71, 212–214
Reeves, R. E., “The shape of pyranoside rings”, J. Am. Chem. Soc. (1950) 72, 1499–1506
Reeves, R. E., “Cuprammonium-Glycoside complexes”, Adv. Carbohydr. Chem. (1951) 6, 107–134
Hageman, H. J. , PhD Thesis, Leiden (1965)
Eliel, E. L.; Allinger, N.L.; Angyal, S. J.; Morrison, G. A., Conformational Analysis, Interscience, New York, 1965, p. 44
Planje, M. C., PhD Thesis, Leiden (1964)
Booth, G. E.; Ouellette, R. J., “Conformational Analysis. V.1, 2 2-Chloro- and 2-Bromotetrahydropyran”, J. Org. Chem. (1966) 31, 544–546
Anderson, C. B.; Sepp, D. T., “Conformation and the anomeric effect in 2-halotetrahydropyrans”, J. Org. Chem. (1967) 32, 607–611
Akishin, P. A.; Vilkov, L. V.; Sokolova, N. P., “Electronographic study of the structure of the molecules of monochloro- and monobromodimethyl ethers”, Izvest. Sibir. Otdel. Akad. Nauk S.S.S.R. (1960) 5, 59–60
Planje, M. C.; Toneman, L. H.; Dallinga, G., Rec. Trav. Chim. (1965) 84, 232
Bishop, C. T.; Cooper, F. P., “Glycosidation of sugars. II. Methanolysis of D-Xylose. D-Arabinose, D-Lyxose, and D-Ribose”, Can. J. Chem. (1963) 41, 2743–2758
Eliel, E. L.; Giza, C. A., “Conformational analysis. XVII. 2-Alkoxy- and 2-alkylthio- tetrahydropyrans and 2-alkoxy-1,3-dioxanes. Anomeric effect”, J. Org. Chem. (1968) 33, 3754–3758
Pierson, G. O.; Runquist, O. A., “Conformational analysis of some 2-alkoxytetra- hydropyrans”, J. Org. Chem. (1968) 33, 2572–2574
Sweet, F.; Brown, R. K., “Cis- and trans-2,4-dimethoxytetrahydropyran. Models for the study of the anomeric effect”, Canad. J. Chem. (1968) 46, 1543–1548
de Hoog, A. J.; Buys, H. R.; Altona, C.; Havinga, E., “Conformation of non- aromatic ring compounds—LII: NMR spectra and dipole moments of 2-alkoxytetrahydropyrans”, Tetrahedron (1969) 25, 3365–3375
Altona, C.; Havinga, E. cited as unpublished in Romers, C.; Altona, C.; Buys, H. R.; Havinga, E. Topics in Stereochemistry, Eliel, E. L.; Allinger, N. L., Eds., Vol. 4, Wiley-Interscience, New York1969, pp. 39–97
Altona, C.; Romers, C.; Havinga, E., “Molecular structure and conformation of some dihalogenodioxanes”, Tetrahedron Lett. (1959) 1, 16–20
Romers, C.; Altona, C.; Buys, H. R., Havinga, E., “The Anomeric Effect”, in Topics in Stereochemistry, Eliel, E. L.; Allinger, N. L., Eds., Vol. 4, Wiley- Interscience, New York1969, pp. 39–97
Altona, C., Ph. D. Thesis, Leiden, (1964)
Altona, C.; Romers, C, “The conformation of non-aromatic ring compounds. VIII. The crystal structure of cis-2,3-dichloro-1,4-dioxane at -l40°C”, Acta Cryst. (1963) 16, 12251232
Altona, C.; Knobler, C.; Romers, C., “The conformation of non-aromatic ring compounds. VII. Crystal structure of trans-2,5-dichloro-1,4-dioxane at 125°C”, Acta Cryst. (1963) 16,1217–1225
de Wolf, N.; Romers, C.; Altona, C., “The conformation of non-aromatic ring compounds. XXXIV. The crystal structure of trans-2,3-dichloro-1,4-thioxane at -185°C”. Acta. Cryst. (1967) 22, 715–719
Lemieux, R. U.; Koto, S.; Voisin, D., “The Exo-Anomeric Effect”, in Szarek, W. A.; Horton, D., Eds., “The Anomeric Effect: Origin and Consequences”, Am. Chem. Soc. Symposium Series, Vol. 87, Washington 1979, pp 17–29
Hutchins, R. O.; Kopp, L. D.; Eliel, E. L., “Repulsion of syn-axial electron pairs. The rabbit-ear effect”, J. Am. Chem. Soc. (1968) 90, 7174–7175
Kubo, M., Sci. Papers Inst. Phys. Chem. Res. (Tokyo) (1936) 29, 179
Aoki, K., J. Chem. Soc. (Japan), Pure Chem. Sect. (1953) 74, 110; Chem. Abstr. (1953) 47, 5191
Astrup, E. E., “Molecular structure of dimethoxy-methane, MeOCH 2 OMe”, Acta Chemica Scand. (1971) 25, 1494–1495
Booth, H.; Lemieux, R. U., “Anomeric effect: the conformational equilibriums of tetrahydro-1,3-oxazines and 1-methyl-1,3-diazane”, Can. J. Chem. (1971) 49, 777–788
Zefirov, N. S., “The problem of conformational effects”, Tetrahedron (1977) 33, 3192
Eliel, E, L.; Allinger, N. L.; Angyal, S. J.; Morrison, G. A., Conformational Anal., p. 460, Wiley-Interscience, 1965
Horton, D.; Turner, W. N., “Conformational and configurational studies on some Acetylated Aldopyranosyl Halides”, J. Org. Chem. (1965) 30, 3387–3394
Lemieux, R. U.; Morgan, A. R., “The abnormal conformations of Pyridinium α-glycopyranosides”, Can. J. Chem. (1965) 43, 2205–2213
James, M. N. G., Proc. Can. Fed. Biol. Soc. (1969) 13, 71
Lemieux, R. U.; Koto, S., “The conformational properties of glycosidic linkages”, Tetrahedron (1974) 30, 1933–1944
Lemieux, R. U.; Hendriks, K. B.; Stick, R. V.; James, K. “Halide ion catalyzed glycosidation reactions. Syntheses of α-linked disaccharides”, J. Am. Chem. Soc. (1975) 97, 4056–4062
Saluja, S. S., Ph. D. Thesis, University of Alberta, 1971
Paulsen, H.; Györgdeák, Z.; Friedmann, M., “Konformationsanalyse, V. Einfluß des anomeren und inversen anomeren Effektes auf Konformationsgleichgewichte von N-substituierten N-Pentopyranosiden”, Chem. Ber. (1974) 107, 1590–1613
Grein, F.; Deslongchamps, P., “The anomeric and reverse anomeric effect. A simple energy decomposition model for acetals and protonated acetals, Can. J. Chem. (1992) 70, 1562–1572
Grein, F., “Anomeric and Reverse Anomeric Effect in Acetals and Related Functions” in “The Anomeric Effect and Associated Stereoelectronic Effects”, Thatcher, G. R. J., Ed. ACS Symposium Series No. 539, 205–226, ACS, Washington, DC, 1993
Finch, P.; Nagpurkar, A. G., “The reverse anomeric effect: further observations on N-glycosylimidazoles”, Carbohydr. Res. (1976) 49, 275–287
Ratcliffe, A. J.; Fraser-Reid, B., “Generation of -D-glucopyranosylacetonitrilium ions. Concerning the reverse anomeric effect”, J. Chem. Soc. Perkin 1(1990) 747–750
Batchelor, J. G., “Conformational analysis of cyclic amines using carbon-13 chemical shift measurements: dependence of conformation upon ionisation state and solvent”, J. Soc., Perkin Trans. 2 (1976) 1585–1590
Booth, H.; Jozefowicz, M. L., “The application of low temperature 13C nuclear magnetic resonance spectroscopy to the determination of the A values of amino-, methylamino-, and dimethylamino-substituents in cyclohexane” J. Chem. Soc. Perkin Trans. 2 (1976) 895–901
Sicher, J.; Jonás, J.; Tichý, M., “The a-values of the amino acid and dimethylamino groups”, Tetrahedron Lett. (1963) 4, 825–830
Eliel, E. L.; Della, E. W.; Williams, T. H., “The conformational equilibrium of the amino group”, Tetrahedron Lett. (1963) 4, 831–835
Ford, R. A.; Allinger, N. L., “Conformational analysis. LXVII. Effect of solvent on the conformational energy of the carbethoxy group”, J. Org. Chem. (1970) 35, 3178–3181
Perrin, C. L.; Armstrong, K. B., “Conformational analysis of glucopyranosylammonium ions: does the reverse anomeric effect exist?”, J. Am. Chem. Soc. (1993) 115, 6825–6834
Isbell, H. S.; Frush, H. L., “Mutarotation, Hydrolysis, and Rearrangement Reactions of Glycosylamines”, J. Org. Chem. (1958) 23, 1309–1319
Pinto, B. M.; Leung, Y. N., “The Anomeric Effect and Associated Stereoelectronic Effects”, Thatcher, G. R. J., Ed. ACS Symposium Series No. 539, 126–155, ACS, Washington, DC, 1993
Cramer, C. J., “Anomeric and reverse anomeric effects in the gas phase and aqueous solution”, J. Org. Chem. (1992) 57, 7034–7043
Salzner, U; Schleyer, P. v. R., “Ab initio examination of anomeric effects in Tetra-hydropyrans, 1,3-Dioxanes, and Glucose”, J. Org. Chem. (1994) 59, 2138–2155
Chan, S. S. C.; Szarek, W. A.; Thatcher, G. R. J., “The reverse anomeric effect in N-pyranosylimidazolides: a molecular orbital study”, J. Chem. Soc. Perkin Trans. 2, (1995) 45–60
Vaino, A. R.; S. S. C. Chan; Szarek, W. A.; Thatcher, G. R. J., “An experimental re-examination of the reverse anomeric effect in N-Glycosylimidazoles”, J. Org. Chem. (1996) 61, 4514–4515
Fabian, M. A.; Perrin, C. L.; Sinnott, M. L., “Absence of reverse anomeric effect: Conformational analysis of Glucosylimidazolium and Glucosylimidazole” J. Am. Chem. Soc. (1994) 116, 8398–8399
Juaristi, E.; Cuevas, G, “Recent studies of the anomeric effect”, Tetrahedron, (1992) 48, 5019–5087
Mikolajczyk, M.; Graczyk, P.; Wieczorek, M. W.; Bujacz, G “Conformational preference of 2-Triphenylphosphonio-1,3-Dithianes: Competition between steric and anomeric effects”, Angew. Chem. Int. Ed. Engl.(1991) 30, 578–580
Graczyk, P. P.; Mikolajczyk, M.; Phosphorus, Sulfur Silicon Relat. Elem. (1993) 78, 313
Juaristi, E.; Cuevas, G., “Conformational analysis of 1,3-dithian-2-yltrimethylphosphonium chloride. Origin of the S-C-P anomeric effect”, J. Am. Chem. Soc. (1993) 115, 1313– 1316
Thibaudeau, C.; Plavec, J.; Watanabe, K. A.; Chattopadhyaya, J., “How do the aglycons drive the pseudorotational equilibrium of the pentofuranose moiety in C-nucleosides?”, J. Chem Soc., Chem. Commun. (1994) 537–540
Jones, P. G.; Komarov, I. V.; Wothers, P. D.,“A test for the reverse anomeric effect”, Chem. Commun., 1998, 1695–1696
Kennedy, J.; Wu, J.; Drew, K.; Carmichael, I.; Serianni, A. S., “Carbohydrate reaction intermediates: Effect of ring-oxygen protonation on the structure and conformation of Aldofuranosyl rings”, J. Am. Chem. Soc. (1997) 119, 8933–8945
Alder, R. W.; Carniero, T. M. G.; Mowlam, R. W.; Orpen, A. G.; Petillo, P. A.; Vachon, D. J.; Weisman, G. R.; White, J. M., “Evidence for hydrogen-bond enhanced structural anomeric effects from the protonation of two aminals, 5-methyl-1,5,9-triazabicyclo[7.3.1]tridecane and 1,4,8,11-tetraazatricyclo[9.3.1.14,8]hexadecane”, J. Chem. Soc., Perkin Trans. 2 (1999) 589–599
Cramer, C. J., “Hyperconjugation as it affects conformational analysis”, J. Mol. Struct. (THEOCHEM) (1996) 370, 135–146
Ganguly, B.; Fuchs, B., “Stereoelectronic Effects in Negatively and Positively (Protonated) Charged Species. Ab Initio Studies of the Anomeric Effect in 1,3-Dioxa Systems”, J. Org. Chem.(1997) 62, 8892–8901
Cloran, F.; Zhu, Y.; Osborn, J.; Carmichael, I.; Serianni, A. S., “2-Deoxy-D- ribofuranosylamine: Quantum mechanical calculations of molecular structure and NMR spin–spin coupling constants in nitrogen-containing Saccharides”, J. Am. Chem. Soc. (2000) 122, 6435–6448
Randell, K. D.; Johnston, B. D.; Green, D. F.; Pinto, B. M., “Is there a generalized reverse anomeric effect? Substituent and solvent effects on the configurational equilibria of neutral and protonated N-Arylglucopyranosylamines and N-Aryl-5- thioglucopyranosylamines”, J. Org. Chem. (2000) 65, 220–226
Guthrie, J. P., “Hydrolysis of esters of oxy acids: pKa values for strong acids; Brønsted relationship for attack of water at methyl; free energies of hydrolysis of esters of oxy acids; and a linear relationship between free energy of hydrolysis and pKa holding over a range of 20 pK units”, Can. J. Chem. (1978) 56, 2342–2354
Booth, H.; Lemieux, R. U., “Anomeric effect: the conformational equilibriums of tetrahydro-1,3-oxazines and 1-methyl-1,3-diazane” Can. J. Chem. (1971) 49, 777–788
Allingham, Y.; Cookson, R. C.; Crabb, T. A.; Vary, S., “The NMR spectra and conformations of some tetrahydro-1, 3-oxazines”, Tetrahedron (1968) 24, 4625–4630
Allingham, Y.; Cookson, R. C.; Crabb, T. A.; Vary, S., “The NMR spectra and conformations of some tetrahydro-1, 3-oxazines”, Tetrahedron (1968) 24, 4625–4630
Booth, H.; Khedhair, K. A., “Endo-anomeric and exo-anomeric effects in 2-substituted tetrahydropyrans”, J. Chem. Soc., Chem. Commun. (1985) 467–468
Kirby, A. J.; Wothers, P. D., “Conformational equilibria involving 2-amino-1, 3-dioxanes: steric control of the anomeric effect”, ARKIVOC (2001) XII, 58–71
Booth, H.; Readshaw, S. A., “Experimental studies of the anomeric effect. Part IV. Conformational equilibria due to ring inversion in tetrahydropyrans substituted at position 2 by the groups ethoxy, 2'-fluoroethoxy, 2,'2'-difluoroethoxy, and 2',2',2'-trifluoroethoxy”, Tetrahedron (1990) 46, 2097–2110
Booth, H.; Khedhair, K. A.; Readshaw, S. A., “Experimental studies of the anomeric effect. I. 2-Substituted tetrahydropyrans”, Tetrahedron (1987), 43(20), 4699–4723
Kilpatrick, J. E.; Pitzer, K. S.; Spitzer, R., “The thermodynamics and molecular structure of cyclopentane”, J. Am. C hem. Soc. (1947) 69, 2483–2488
Plavec, J.; Tong, W.; Chattopadhyaya, J., “How do the gauche and anomeric effects drive the pseudorotational equilibrium of the pentofuranose moiety of nucleosides?”, J. Am. Chem. Soc. (1993) 115, 9734–9746
Plavec, J.; Garg, N.; Chattopadhyaya, J., “How does the steric effect drive the sugar conformation in the 3-C-branched nucleosides?”, J. Chem. Soc. Chem. Commun. (1993), 1011–1014
Plavec, J.; Koole, L. H.; Chattopadhyaya, J., “Structural analysis of 2',3'-dideoxyinosine, 2',3'-dideoxyadenosine, 2',3'-dideoxyguanosine, and 2',3'-dideoxycytidine by 500-MHz proton-NMR spectroscopy and ab-initio molecular orbital calculations”, J. Biochem. Biophys. Methods (1992) 25, 253–272
Altona, C.; Sundaralingam, M., “Conformational analysis of the sugar ring in nucleosides and nucleotides. New description using the concept of pseudorotation”, J. Am. Chem. Soc. (1972) 94, 8205–8212
Altona, C.; Sundaralingam, M., “Conformational analysis of the sugar ring in nucleosides and nucleotides. Improved method for the interpretation of proton magnetic resonance coupling constants”, J. Am. Chem. Soc. (1973) 95, 2333–2344
Saenger, W., “Principles of Nucleic Acid Structure”, Springer-Verlag, Berlin, 1988
Olson, W. K.; Sussman, J. L., “How flexible is the furanose ring? 1. A comparison of experimental and theoretical studies”, J. Am. Chem. Soc. (1982) 104, 270–278
Olson, W. K., “How flexible is the furanose ring? 2. An updated potential energy estimate”, J. Am. Chem. Soc. (1982) 104, 278–286
Plavec, J.; Tong, W.; Chattopadhyaya, J., “How do the gauche and anomeric effects drive the pseudorotational equilibrium of the pentofuranose moiety of nucleosides?”, J. Am. Chem. Soc. (1993) 115, 9734–9746
Plavec, J.; Thibaudeau, C.; Chattopadhyaya, J., “How do the energetics of the stereoelectronic gauche and anomeric effects modulate the conformation of nucleos(t)ides”, Pure. Appl. Chem. (1996) 68, 2137–2144
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Miljković, M. (2010). Anomeric Effect. In: Carbohydrates. Springer, New York, NY. https://doi.org/10.1007/978-0-387-92265-2_3
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