Alcohol cyclohexyl secondary

In analogy with primary allylic alcohols, a secondary allylic alcohol bearing a bulky E-substituent (R ) is a good substrate for kinetic resolution. For example, the k ei for (E)-l-cyclohexyl-2-buten-l-ol is 104 and that for l-cyclohexyl-4,4-dimethyl-2-penten-l-olis 300 [59]. Best substrates are those in which the -sub-stituent is trimethylsilyl, iodo, or trimethylstannyl. The relative rate constant for (E)-l-trimethylsilyl-l-octen-3-ol is 700 and, at 50% conversion,both the imre-acted alcohol and the anti-epoxy alcohol have more than 99% ee (Scheme 12)... 

Yields of the primary alkyl acrylates vary somewhat, owing to occasional losses through formation of polymer, but are usually in the range of 85-99%. Some secondary alcohols react very slowly, others readily. The method has been applied to more than fifty alcohols, some of which (with percentage yields) are listed below ethyl, 99% isopropyl, 37% -amyl, 87% isoamyl, 95% -hexyl, 99% 4-methyl-2-pentyl, 95% 2-ethylhexyl, 95% capryl, 80% lauryl, 92% myristyl, 90% allyl, 70% fur-furyl, 86% citronellyl, 91% cyclohexyl, 93% benzyl, 81% (3-ethoxyethyl, 99% /S-(/3-phenoxyethoxy) ethyl (from diethylene glycol monophenyl ether), 88%. 

In addition to simple halides, the method was used to prepare chol-esteryl iodide (30%) and cyclohexyl iodide (34%) from the corresponding alcohols, thus demonstrating the applicability of the reaction to cyclic secondary alcohols. An early adaptation to carbohydrates was reported by Lee and El Sawi (75). They claimed that treatment of l,2 5,6-di-0-isopropylidene-D-glucofuranose (49) with triphenylphosphite methiodide... 

Secondary alcohols such as cyclohexanol or 2-butanol also react on heating for 20-120 min at 80 °C with TCS 14 in the presence of BiCl3 to give the chloro compounds cyclohexyl chloride 784 and 2-chlorobutane in 93 and 90% yield, respectively, HCl, and HMDSO 7 [11, 12]. Benzyl alcohol is transformed likewise by Me3SiCl 14 after 120 min. at 80 °C into benzyl chloride in quantitative yield. Analogously, esters such as 2-acetoxypropane 785 are also converted by TCS 14 in 100% yield into chloro compounds such as 786 and trimethylsilyl acetate 142. The yS-lactone 787 gives rise to 788... 

Finally, reaction of primary, secondary, or tertiary alcohols 11 with Me3SiCl 14 in the presence of equivalent amounts of DMSO leads via 789 and 790 to the chloro compounds 791 [13]. n-Pentanol, benzyl alcohol, yS-phenylefhanol or tert-butanol are readily converted, after 10 min reaction time, into their chloro compounds, in 89-95% yield, yet cyclohexanol affords after reflux for 4 h cyclohexyl chloride 784 in only 6% yield [13] (Scheme 6.5). 1,4-Butanediol is cyclized to tetrahydrofuran (THF) [13a], whereas other primary alcohols are converted in 90-95% yield into formaldehyde acetals on heating with TCS 14 and DMSO in benzene [13b] (cf also the preparation of formaldehyde di(n-butyl)acetal 1280 in Section 8.2.1). 

Aluminum chloride, used either as a stoichiometric reagent or as a catalyst with gaseous hydrogen chloride, may be used to promote silane reductions of secondary alkyl alcohols that otherwise resist reduction by the action of weaker acids.136 For example, cyclohexanol is not reduced by organosilicon hydrides in the presence of trifluoroacetic acid in dichloromethane, presumably because of the relative instability and difficult formation of the secondary cyclohexyl carbocation. By contrast, treatment of cyclohexanol with an excess of hydrogen chloride gas in the presence of a three-to-four-fold excess of triethylsilane and 1.5 equivalents of aluminum chloride in anhydrous dichloromethane produces 70% of cyclohexane and 7% of methylcyclopentane after a reaction time of 3.5 hours at... 

The reduction is believed to be preceded by an acid-catalyzed reversible cleavage of the ketals to alcohols and unsaturated ethers which are subsequently hydrogenated. Mineral acid is essential. Best yields and fastest reductions are found with ketals of secondary alcohols. The hydrogenation proceeds at 2.5-4 atm at room temperature with ketals of secondary alcohols, and at 50-80° with ketals of primary alcohols. Acetone and cyclohexanone diisopropyl ketals gave 75% and 90% yields of diisopropyl and cyclohexyl isopropyl ether at room temperature after 1 and 2.5 hours, respectively [933]. 

Aliphatic Ketones The asymmetric hydrogenation of simple aliphatic ketones remains a challenging problem. This may be attributed to the difficulty with which the chiral catalyst differentiates between the two-alkyl substituents of the ketone. Promising results have been obtained in asymmetric hydrogenation of aliphatic ketones using the PennPhos-Rh complex in combinahon with 2,6-lutidine and potassium bromide (Tab. 1.11) [36]. For example, the asymmetric hydrogenation of tert-butyl methyl ketone affords the requisite secondary alcohol in 94% ee. Similarly, isopropyl, Butyl, and cyclohexyl methyl ketones have been reduced to the corresponding secondary alcohols with 85% ee, 75% ee, and 92% ee respectively. 

For reaction 3 to replace an oxygen with a methylene group to form a primary alcohol, there are enthalpies of formation for only seven alcohols to compare with the nineteen hydroperoxides, almost all of them only for the liquid phase. The enthalpies of the formal reaction are nearly identical, —104.8 1.1 kJmol, for R= 1-hexyl, cyclohexyl and ferf-butyl, while we acknowledge the experimental uncertainties of 8.4 and 16.7 kJmol, respectively, for the enthalpies of formation of the secondary and tertiary alcohols. We accept this mean value as representative of the reaction. For R = 1- and 2-heptyl, the enthalpies of reaction are the disparate —83.5 and —86.0 kJmol, respectively. From the consensus enthalpy of reaction and the enthalpy of formation of 1-octanol, the enthalpy of formation of 1-heptyl hydroperoxide is calculated to be ca —322 kJ mol, nearly identical to that derived earlier from the linear regression equation. The similarly derived enthalpy of formation of 3-heptyl hydroperoxide is ca —328 kJmol. The enthalpy of reaction for R = i-Pr is only ca —91 kJmol, and also suggests that there might be some inaccuracy in its previously derived enthalpy of formation. Using the consensus enthalpy of reaction, a new estimate of the liquid enthalpy of formation of i-PrOOH is ca —230 kJmoU. ... 

For the formal deoxygenation (decomposition) reaction 5, there is an enthalpy of formation value for every alcohol that matches a hydroperoxide . Using our exemplary groups, R = 1-hexyl, cyclohexyl and ferf-butyl, the liquid enthalpies of reaction are —77.9, —75.0 and —65.6 kJmoR, respectively (there is no liquid phase enthalpy of formation reported for f-butyl peroxide from Reference 4). The secondary hydroperoxides enthalpies of reaction average —77 7 kJmoR. For the three instances where there are also gas phase enthalpies of formation, the enthalpies of reaction are almost identical in the gas and liquid phases. The 1-heptyl (—60.3 kJmoR ) and 1-methylcyclohexyl (—50.6 kJmoR ) enthalpies of reaction are again disparate from the 1-hexyl and tert-butyl. If the enthalpy of reaction 5 for 1-hexyl hydroperoxide is used to calculate an enthalpy of formation of 1-heptyl hydroperoxide, it is —325 kJmoR, almost identical to values derived for it above. The enthalpies of reaction for the liquid and gaseous phases for the tertiary 2-hydroperoxy-2-methylhex-5-en-3-yne are —78.2 and —80.9 kJmoR, respectively. For gaseous cumyl hydroperoxide, the enthalpy of reaction is —84.5 kJmoR. ... 

Kotsuki et al.203 have reported high yields of alkylated products formed in the presence of triflic acid using cyclohexyl methanesulfonate [Eq. (5.79)]. Similar performance was found for mesitylene, durene, and naphthalene, as well as for other secondary alcohol methanesulfonates. 

Alcohol inversion. Elimination competes with S, 2 substitution in the inversion of secondary alcohols by the Mitsunobu reaction or by reaction of mesylates with cesium propionate or cesium acetate. Elimination in the inversion of cyclopentyl and cyclohexyl alcohols can be largely suppressed by reaction of the mesylate with cesium acetate (excess) and a catalytic amount of l8-crown-6 in refluxing benzene. Even inversion of an ally lie alcohol can be effected in moderate yield under these conditions (equation I). ... 

Reductive ozonolysis of the double bond of the appropriate epimer of 36, followed by selective silylation of the diol produced, and radical deoxygenation of the secondary alcohol function, lead to 37, which is a derivative of the cyclohexyl unit of the immunosuppressive agent tacrolimus [20]. 

There is much additional evidence to support the postulate that the effect of neighboring sulfur is due to anchimeric assistance. Cyclohexyl chloride undergoes solvolysis in ethanol-water to yield a mixture of alcohol and ether. As usual for secondary alkyl substrates, reaction is SnI with nucleophilic assistance from the solvent (see Sec. 14.17). A C5H5S— group on the adjacent carbon can speed... 

ROM—>RBr. In the cyclohexane series reaction of diols with PBr is attended with rearrangements. Thus treatment of the 1,3- and 1,4-cyclohexanediols with PBrj affords mixtures of cis- and trans-1,3- and l,4-dibromides. Eliel and Haber found that cu-d-i-butylcyclohexanol reacts with PBr to give trani-4-/-butylcyclo-hexyl bromide, together with a small amount of olefin and a mixture of dibromides. Thus PBr, is evidently superior to PBr, for conversion of secondary alcohols into bromides. However, the Hunsdiecker reaction seems to be the method of choice for preparation of cyclohexyl bromides. ... 

Esters, prepared by reaction of the reagent with a primary or secondary alcohol in benzene containing pyridine, are highly colored ( 297-320 ca. 30,000), crystalline, and high melting methyl ester, 187°, ethyl ester 163°, cetyl ester, 11° cyclohexyl ester, 165° crotyl ester, 136°. A study of model esters showed that mixtures are easily separated by countercurrent distribution and chromatography."... 

The reaction of phenol with secondary alkyl halides, such as 2-bromoadamantane, cyclohexyl bromide and exc -2-bromonorbomane, also proceeds noncatalytically to give the corresponding ortho- and para-alkylated phenols . The Friedel-Crafts alkylations using primary alcohols, however, require catalysts. 

The HF-SbFs system works well in the Gattermann-Koch formylatlon of arenes and the Koch carbonylation of alkanes [54]. For instance, biphenyl is diformylated in HF-SbFs-CO to afford 4,4 -diformylbiphenyl as a major isomer (Scheme 14.20). The carbonylation of alkanes with C5-C9 carbon atoms in the HF-SbFs-CO system affords mixtures of C3-C8 carboxylic acids after hydrolysis of the generated secondary carbenium ions [55]. Successive treatment of methylcyclopentane with CO in HF-SbF and with water produces cyclohexanecarboxylic acid as a major product (Scheme 14.21) [56]. It seems that a tertiary methylcyclopentyl cation readily isomerizes to the more stable cyclohexyl cation before being trapped by CO. Bicyclic a, -unsaturated ketones are functionahzed by HF-SbF or FSOsH-SbFs under a CO atmosphere to give saturated keto esters after methanolysis (Scheme 14.22) [57]. Alcohols with short carbon chains also react with CO in HF-SbFs to give the corresponding methyl esters [58]. y-Butyrolactones are carboxy-lated under the same conditions to afford 1,5-dicarboxyhc acids [59]. 

A new polymer-bound reagent system for the efficient oxidation of primary alcohols to aldehydes and of secondary alcohols to ketones in the presence of a catalytic amount of 2,2,6,6-tetramethyl-l-piperidonoxyl (TEMPO) has been described [102]. Work-up of this heavy metal free oxidation is achieved by simple filtration followed by removal of the solvent. Benzyl alcohol was oxidized in 94% yield. The more demanding cyclohexyl alcohol was converted into cyclohexanone in 96 % yield. 

Asymmetric epoxidation of racemic secondary allyl alcohols 3.17 takes place with kinetic resolution [127], The presence of a substituent on the same face as the reagent at transition state induces a decrease in rate due to steric hindrance. Therefore, according to the (Ry or (S)-absolute configuration of the substrate, the rate of epoxidation with a given catalyst will be different (Figure 7.33). The ratio of rates in a kinetic resolution depends upon the nature of the R substituent, the temperature, and the structure of the tartrate 2.69 (R = Me, Et, /-Pr). Cyclohexyl tartrates have been recommended for kinetic resolutions because bulkier esters give higher relative rate ratios [808]. A few examples of resolutions are shown in Fig-... 

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