5-substituted cyclohexanols

An antibody, originally generated against a diaryl substituted cyclohexanol derivative, has been employed to catalyze the oxy-Cope rearrangement of hexadiene 100 to aldehyde 101 (equation 55)80,81. A rate enhancement of 5300-fold over the uncatalyzed reaction was achieved. 

Substituted cyclohexanols containing a 1-perfluorophenyl substituent are surprisingly, when compared with 1-alkylpentafluorobenzenes (vide supra), reduced at the ortho C F bond in the aromatic ring by lithium aluminum hydride.87 Substituted phenols with a trifluoromethyl group in the ortho or para positions are reduced with lithium aluminum hydride66 (Table 3), in contrast to 3-(trifluoromethyl)phenol. 

Arenols can be reduced successfully with hydrogen over nickel catalysts to the corresponding cyclohexanols. A variety of alkyl-substituted cyclohexanols can be prepared in this way ... 

Shine and co-workers239,240 have reported the synthesis and full NMR characterization of a series of alkoxysulfonium ion perchlorates including ions 85 derived from cis- and fraws-substituted cyclohexanols. The X-ray structural study of four salts showed that the orientation of the S O bond is always pseudoaxial. The optically active (—)-86 ion and similar systems have been synthesized.241 1H and 13C NMR measurements indicate that sulfur has a trigonal bipyramidal geometry due to the S—O intramolecular interaction in the axial position. 

J. Baratti, and C. Triantaphylides, lipase-catalyzed ester formation in organic solvents. An easy preparative resolution of a-substituted cyclohexanols, Tetrahedron Lett. 1985, 26, 1857-1860. 

The oxidation of a secondary alcohol to a ketone is usually accomplished with a solution of the alcohol and aqueous acidic chromic acid in either acetone or acetic acid, with a solution of sodium dichromate in acetic acid, or by reaction of the alcohol with aqueous acidic chromic acid as a heterogeneous system. An example is the oxidation of the substituted cyclohexanol below (Reaction XXXV) with sodium dichromate in sulfuric acid (55). 

Other work in which migratory aptitudes have been compared has involved the formation of the azide (or its conjugate acid) in situ from the corresponding alcohol or olefin, and its decomposition without isolation (the Schmidt reaction). For example, 1-substituted cyclohexanols underwent predominantly ring expansion when the 1-substituent was methyl, ethyl or cyclohexyT. A series of tertiary carbinols were studied in which it was found that the migration tendency was in the order Ph i-Pr CgHii Et The products of... 

Dutler and Branden (11, 12) have studied the interaction of the ADH-NAD complex with alkyl-substituted cyclohexanols to determine productive substrate orientations in the active site. Some of their findings were that 1) cyclohexanol fits best in a chair conformation with axial-reacting hydroxyl oxygen and equatorial-reacting hydrogen atoms on Cl, 2) that substitutions at Ck (para) have little effect on the reaction rate due to hydrophobic bonding with the residues in the hydrophobic "barrel region of the active site, 3) substitutions at C2,... 

The HPLC separation data of diastereomeric esters prepared from other racemic alcohols 24, 36, 38, 39, and 57-63 with MaNP acid (.S)-(+)-3 are listed in Table 9.3. It should be emphasized that for most alcohols, their diastereomeric MaNP esters are clearly separated with a values of 1.10-1.88. Phenylacetylene alcohol 57 was separable as the MaNP esters 65a/65b (a = 1.30, entry 3). Substituted cyclohexanols 58 and 59 were also effectively separated as MaNP esters (entries 4 and 5). Especially, the a value of trans-2-isopropylcyclohexanol MaNP esters 66a/66b is as large as 1.88, which is comparable to that of fhe menthol case. On the ofher hand, in the case of trans-2-methylcyclohexanol MaNP esters 67a/67b, the a value is relatively small, a = 1.21. These results indicate that the combination of a longer and larger alkyl group on one side and a smaller alkyl group on fhe ofher side leads to better separation of two diastereomers, as seen in 2-hexadecanol esters 54a/54b (see Fig. 9.15) and tro s-2-isopropylcyclohexanol MaNP esters 66a/66b. 

The enzyme responsible for this bioconversion, catalyzed by wild-type cells of Rhodococcus erythropolis DCL14, is carveol dehydrogenase11911. A high enantiose-lectivity and no further conversion of (-)-carvone was obtained. Carveol dehydrogenase has a broad substrate specificity and prefers substituted cyclohexanols as substrates11911. The regeneration of the cofactor NAD+ was accomplished by the use of living cells. 

Table 8. Alkyl-Substituted Cyclohexanols by Reduction of the Corresponding Cyclohexanones with Lithium Aluminum Hydride (Selective Axial Attack)...

By this means cfj-l,2-disubstituted cyclohexanes can be prepared from trans-2-substituted cyclohexanols ... 

Use as chiral auxiliary. Whitesell has reviewed use of this chiral alcohol (1), particularly as compared with that of (—)-menthol and (lR)-(+)-8-phenylmenthol. One advantage is that both enantiomers of 1 are available by resolution of trans-2-phenyl-cyclohexanol by means of enzymatic hydrolysis of the esters and that 2-substituted cyclohexanols are readily available. Although this chiral auxiliary was used originally for control of ene reactions of glyoxylates, it is also useful for asymmetric alkylation of enolates, and for control of various cycloaddition reactions. 

Cole and Macritchie (1959) have used intensity measurements of the hydroxyl stretching absorption band at various temperatures to determine the energy of the hydrogen bond formed between a substituted cyclohexanol, frans-dihydrocryptol (XI), and a cyclic ether, dioxane (XII) in tetrachloroethylene solutions. The methods... 

A highly enantioselective photoredox catalysis involving proton-coupled electron transfer has been developed to achieve the asymmetric aza-pinacol cyclization of (17), which leads to the corresponding 2-amino substituted cyclohexanols." Likewise, a photocatalyst/enzyme system has been applied to the asymmetric reduction of acetophenones with solar light, to afford the corresponding secondary alcohols with excellent enantioselectivity. ... 

Substituted cyclohexanols 87 and 88 were effectively separated as MaNP esters (entries 1 and 2). Significantly, the a-value of 7ra i-2-isopropylcyclohexanol MaNP esters lOSa/lOSb is as large as 1.88, while in the case of 7ra i -2-methylcyclohexanol MaNP esters 83a/83b, the a-value is relatively small, a =1.21. The result indicates that a sterically larger alkyl group on one side leads to better separation of the two diastereomers. The ACs of the first-eluted MaNP esters 104a and 105a was established by H NMR anisotropy and X-ray... 

Secondary alcohols, such as isopropyl alcohol, j -butyl alcohol, 2-pentanol, 3-pentanol, cyclopentanol, and cyclohexanol, have been autoxidized to hydroxyaLkyl hydroperoxides (1, X = OH R = H) (10,44). These autoxidations usually are carried out at ca 20°C with uv radiation in the presence of a photosensitizer, eg, benzophenone. a-Oxygen-substituted dialkyl peroxides (2, X = Y = OH and X = Y = OOH), also are formed and sometimes they are the exclusive products (10). 

Methanethiol (eq. 6) and cyclohexanethiol (eq. 7) are the only commercially important thiols prepared using alcohol substitution. In most cases, when the alcohol is utilized, less control over the substitution patterns is obtained. Only one isomer is obtainable in the case of methanol and cyclohexanol. 

Habid and Malek49 who studied the activity of metal derivatives in the catalyzed esterification of aromatic carboxylic acids with aliphatic glycols found a reaction order of 0.5 relative to the catalyst for Ti(OBu)4, tin(II) oxalate and lead(II) oxide. As we have already mentioned in connection with other examples, it appears that the activation enthalpies of the esterifications carried out in the presence of Ti, Sn and Pb derivatives are very close to those reported by Hartman et al.207,208 for the acid-catalyzed esterification of benzoic and substituted benzoic acids with cyclohexanol. These enthalpies also approach those reported by Matsuzaki and Mitani268 for the esterification of benzoic acids with 1,2-ethanediol in the absence of a catalyst. On the other hand, when activation entropies are considered, a difference exists between the esterification of benzoic acid with 1,2-ethanediol catalyzed by Ti, Sn and Pb derivatives and the non-catalyzed reaction268. Thus, activation enthalpies are nearly the same for metal ion-catalyzed and non-catalyzed reactions whereas the activation entropy of the metal ion-catalyzed reaction is much lower than that of the non-catalyzed reaction. 

The Co(ni) perchlorate oxidation of substituted and unsubstituted benzal-dehydes has kinetics and a low isotope effect (2.3 at 10 °C) in complete analogy with cyclohexanol and formaldehyde . Ring-substitution by electronegative groups accelerates reaction. 

Cells of Acinetobacter sp. NCIB 9871 grown with cyclohexanol carried out enantiomeri-cally specific degradation of a racemic substituted norbomanone to a single ketone having >95% enantiomeric excess (Levitt et al. 1990). 

Several approaches have been undertaken to construct redox active polymermodified electrodes containing such rhodium complexes as mediators. Beley [70] and Cosnier [71] used the electropolymerization of pyrrole-linked rhodium complexes for their fixation at the electrode surface. An effective system for the formation of 1,4-NADH from NAD+ applied a poly-Rh(terpy-py)2 + (terpy = terpyridine py = pyrrole) modified reticulated vitreous carbon electrode [70]. In the presence of liver alcohol dehydrogenase as production enzyme, cyclohexanone was transformed to cyclohexanol with a turnover number of 113 in 31 h. However, the current efficiency was rather small. The films which are obtained by electropolymerization of the pyrrole-linked rhodium complexes do not swell. Therefore, the reaction between the substrate, for example NAD+, and the reduced redox catalyst mostly takes place at the film/solution interface. To obtain a water-swellable film, which allows the easy penetration of the substrate into the film and thus renders the reaction layer larger, we used a different approach. Water-soluble copolymers of substituted vinylbipyridine rhodium complexes with N-vinylpyrrolidone, like 11 and 12, were synthesized chemically and then fixed to the surface of a graphite electrode by /-irradiation. The polymer films obtained swell very well in aqueous... 

A further attempt has been made to develop a predictive model for chirality transfer achieved through alkylation reactions of ester enolates which feature chiral auxiliaries. " Hippurate esters (30) derived from (lI , 25 )-trani-2-(p-substituted phenyl)cyclohexanols were found, on reaction with benzyl bromide, to give (31) with predominantly the S configuration at the alkylation centre but with no correlation between the degree of stereoselectivity (20-98%) and the electron density on the aromatic ring. 

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