Cyclohexane disubstituted derivatives

Disubstituted cyclopropanes exemplify one of the simplest cases involving stabil ity differences between stereoisomers A three membered ring has no conformational mobility so the ring cannot therefore reduce the van der Waals strain between cis sub stituents on adjacent carbons without introducing other strain The situation is different m disubstituted derivatives of cyclohexane... 

Terephthalic acid has been obtained from a great many /)-disubstituted derivatives of benzene or cyclohexane by oxidation with permanganate, chromic acid, or nitric acid. The following routes appear to have preparative value from />-toluic acid, />-methylacetophenone,2 or dihydro-/)-tolualdehyde by oxidation with permanganate from f>-cymene by oxidation with sodium dichromate and sulfuric acid from />-dibromobenzene or from /i-chloro- or -bromobenzoic acid by heating at 250° with potassium and cuprous cyanides and from />-dibromo-benzene, butyllithium, and carbon dioxide. ... 

C. Reduced nickel (20% on diatomite) served as the catalyst. Hydrogenation was carried out in a reactor made of copper (20 x 0.6 cm) at 70°C. In the hydrogenation of disubstituted derivatives of benzene and cyclohexane, cis- and fra s-isomers are formed, their ratio depending on the structure of the compounds being hydrogenated and on the hydrogenation conditions. 

Use your answers from Problem 3.44 to complete the following table, showing correlations between cis, trans isomers and axial, equatorial positions for disubstituted derivatives of cyclohexane ... 

The chemoenzymatic synthesis of the analgesic U-(—)-50,488 [41] and new C2-symmetric bisaminoamide ligands derived from N,N-disubstituted trans-cyclohexane, ,2-diamine [41] has been possible by a CALB-catalyzed resolution using ethyl acetate as solvent and acyl donor [42]. 

Table 4.8 The Physical Constants of Cis- and Ttwmx-Disubstituted Cyclohexane Derivatives...

In the ring closures of the 1,2-disubstituted 1,3-difunctional cyclohexane, cycloheptane, and cyclooctane derivatives discussed in Sections II,A,B, and C, no appreciable differences were found in the reactivities of the cis and trans isomers. In contrast, very significant differences were observed in the cyclization reactivities of the cis and trans 1,2-disubstituted 1,3-difunctional cyclopentane derivatives, such as 1,3-amino alcohols, 2-hydroxy-l-carboxamides or /S-amino acids. Whereas the cis isomers reacted readily, their trans counterparts did not undergo ring closure in most cases. This difference was manifested in the formation of both d - and e -fused derivatives. 

Muthusamy et al. (82) prepared a number of oxacyclic ether compounds from the tandem ylide formation-dipolar cycloaddition methodology. Their approach provides a synthetic tactic to compounds such as ambrosic acid, smitopsin, and linearol. Starting with either cyclopentane or cyclohexane templates, they prepared ylide sizes of five or six, which are trapped in an intermolecular cycloaddition reaction by the addition of DMAD. The products are isolated in good overall yield. In a second system, 2,5-disubstituted cyclohexenyl derivatives are utilized to generate the pendent ylide, then, A-phenylmaleimide is added in an intermolecular reaction, accessing highly substituted oxatricyclic derivatives such as 182 (Scheme 4.43). 

Mono- and 1,1-disubstituted cyclohexanes. There are several electron diffraction investigations of mono-substituted cyclohexanes. Cyclohexylfluoride301 exists as 57% e and 43% a which means that the equatorial position is favored by about 710 J/mol. A microwave study302 yielded 1.6+ 1.2 kJ/mol for this energy difference. Cyclohexylchloride303 is very similar to the fluorine derivative in that the gas phase... 

Turova-Polyak and co-workers have carried out extensive studies of naphthene isomerization with AICI3, particularly of the substituted cyclopentanes. The conversion of mono- and disubstituted cyclopentanes to cyclohexanes was reported as an analytical technique for the determination of cyclopentanes in mixture with paraffins (411). Ethyl-cyclopentane at room temperature gave an 18-20% yield of cyclohexane derivatives (412). At 140-145°, an 85% yield of 1,3,5-trimethyl-cyclohexane was obtained. This work was also extended to 1,1-dimethyl-cyclopentane (410), up to 95% of which was converted to methyl-cyclohexane at 115°. Similar conversions of alkylated cyclopentanes were also reported by Shulkin and Plate (375). These researches parallel similar work done in the United States. 

Configurational isomerism is encountered in bi- and polysubstituted cyclic molecules, as well as in fused ring systems. In the simple case of bisubstituted monocyclic systems, cis-trans-isomehsm exists provided that the two substituents are not gemi-nal. Thus, 1,2-, 1,3- and 1,4-disubstituted cyclohexane derivatives (LII) show this... 

A 2,6-disubstituted pyridine derivative was also synthesised and incorporated into an EDMA-based (the porogen was not disclosed) non-covalently imprinted polymer. The resulting polymer was reportedly sensitive to solvent, pH and the presence of organic additives in solution. The example provided shows that cyclohexane suspensions of the polymer exhibit no diminution of fluorescence upon the addition of anisole, but show approximately 15% quenching in the presence of an equivalent concentration of phenol. Approaches such as these, wherein the fluorescent properties of the MIP itself are altered by interaction with the analyte, should prove extremely useful. 

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