Isomers diaxial

Some instances of incomplete debromination of 5,6-dibromo compounds may be due to the presence of 5j5,6a-isomer of wrong stereochemistry for anti-coplanar elimination. The higher temperature afforded by replacing acetone with refluxing cyclohexanone has proved advantageous in some cases. There is evidence that both the zinc and lithium aluminum hydride reductions of vicinal dihalides also proceed faster with diaxial isomers (ref. 266, cf. ref. 215, p. 136, ref. 265). The chromous reduction of vicinal dihalides appears to involve free radical intermediates produced by one electron transfer, and is not stereospecific but favors tra 5-elimination in the case of vic-di-bromides. Chromous ion complexed with ethylene diamine is more reactive than the uncomplexed ion in reduction of -substituted halides and epoxides to olefins. ... 

The case is interesting in 1,2 dibromocyclohexane. The moment for the diaxial isomer is assumed to be zero, while the calculated and observed values for the diequatorial form are respectively 3.09 D and 3.12 D. The trans diaxial form is more stable than the trans diequatorial, although the latter is favoured sterically. The reason for the lesser stability of the trans diequatorial form is that it is destabilized by dipole repulsion. 

Arguing as before, we conclude that the ae conformation will be the most stable cis conformation. A comparison of the sigma conjugative interactions which obtain in the most stable tram conformation, the aa conformation, and the most stable cis conformation, the ae conformation, leads to the conclusion that the tram diaxial isomer is the most stable conformation of this molecule. 

Stereoisomers of the trans-decahydro-quinoline (228) (273) and the trans-decalin (229) (88) displayed extremely low orders of muscarinic effect, with the 2,3-ira/is-diaxial isomer of (229) being the most potent of the four stereoisomers of this structure (0.06%the potency of acetylcholine). 

These are represented by 25 and 26, which are the two chair conformations of ra-l,4-dimethylcyclohexane, so called (1) because the bonds between the ring carbons and the attached methyl groups in 25 and 26 are both inclined toward the plane defined above, or (2) because 25 (or 26) is derived from the trans diaxial isomer 17 by a change in configuration at one carbon. 

The need for coplanarity of the eliminating halogens in the transition state is confirmed by studies with cyclohexyl derivatives. In the rigid cumbersome triterpenoid series, 11,12-diequatorial dibromides are inert but the diaxial isomers undergo a/iri-elimination with iodide ion - . In the cyclohexyl system, /ra 5-l, 2-dihalides (or halide-sulphonate esters) undergo rapid... 

The Fiirst Plattner rule can be used only for predicting the regioselectivity of kinetically controlled cleavage reactions. If thermodynamic control takes place and the initially formed diaxial isomer is able reversibly to close back to the aziridine ring, the diequatorial isomer can begin to accumulate in the reaction mixture and is isolated either as the sole product or in a mixture " with the diaxial isomer. 

The diaxial isomer 189 was the main product at short times of reaction, whereas the diequatorial product 190 was formed exclusively after prolonged heating. Application of the same conditions to the diaxial isomer alone led to its conversion into the diequatorial isomer through the equilibrium between the diaxial isomer and the epimine. Rate constants for each reaction involved in the cleavage have been estimated. ... 

Exclusive formation of the diequatorial isomers 193 194 has been observed in the reactions of l,6-anhydro-4-0-benzyl-2,3-(A-benzylepimino)-2,3-dideoxy-p-D-allopyranose 160 with a mixture of ammonium and tetrabutylammonium bromide or iodide on heating in toluene at high temperature. In these instances, the corresponding diaxial isomers 191-192 were unstable and were formed only in situ (see Table X for details). ... 

The configuration of the starting epimine can have a strong influence on feasibility of back-formation of the aziridine ring from the diaxial isomer of the cleavage product. This is particularly true for the reactions of D-manno epimine 199. It has been reported in the literature (cf. Refs. 102, 135), that the cyclization of an oxirane or an aziridine ring in the 2,3-endo position on a 6, 8-dioxabicyclo[3.2.1]octane skeleton proceeds rather slowly as compared to 2,... 

The observed ratio of diaxial/diequatorial isomers is very little influenced by the presence of ammonium chloride in the reaction mixture in contrast to the marked effect of the A -substituent. The diaxial isomers predominate in most reactions, although the amounts of diequatorial isomers are sometimes significant. In the... 

Only the diaxial isomer 240 was formed in the reaction of quaternized epimine 239 with sodium azide in A, A -dimethylformamide. ... 

Free epimino derivative 44 afforded products of trara-diequatorial cleavage only, whereas A-substitution with an electron-withdrawing group led to the formation of mixtures of both stereoisomers, with the diaxial isomer predominant. In the cleavage of benzyl glycosides 53 and 255, the authors proved the existence of an equilibrium between the diaxial isomer and the starting epimine, which led to preponderant formation of the diequatorial isomer. 

The A-benzoyl derivative 45 afforded a mixture of both isomers when treated with tetrabutylammonium fluoride. In the mixture, the diaxial isomer 265 preponderated, but its abundance depended on the solvent and slightly on the amount of the reagent (Table VII). 

All cleavage reactions of the epimines having the D-manno configuration afforded solely the diaxial isomers of the products, except for the reaction of N-benzyl derivative 199 with a mixture of Bu4NBr and NH4Br in toluene, wherein which 2-bromo derivative 202 of the opposite configuration on carbon C-2 was... 

Cleavage of the A-benzyl-, A-o-nitrobenzenesulfonyl, and A-tosyl-2,3-D-a//o-epimines 160, 195, and 288, with nucleophiles (azide anion and HBr) proceeds according to the Fiirst-Plattner rule and only diaxial isomers are formed. 

All reactions mentioned in Table XII produced only diaxial isomers of the cleavage products, except for the reaction of V-benzylepimine 163 with a Bu4NBr + NH4Br mixture, which gave the diequatorial bromo derivative 308. Again, its formation is evidently the result of an equilibrium existing between diaxial isomer and the epimine, as already reported for the 2,3-D-allo epimine... 

In the reactions of V-benzylepimine 161 with a mixture BU4NX + NH4X (X = Br, I) in toluene, the equilibrium between the diaxial isomer and the epimine was established and thus the diequatorial halo derivatives 319-320... 

The experimental [82] and theoretical [83] evidence indicates that the equatorial sulfoxide oxygen is at least Skcalmol lower in energy than the axial counterpart in (38). An axial orientation of the sulfinyl oxygen is also unstable in the corresponding 1,5-dioxide, where the sulfinyl oxygens in the diaxial isomer repel each other sterically and electrostatically [84]. 

Dimethylcyclohexanes. Using a cyclohexane template, construct cis(a,a)-1,3-dimethylcyclohexane, cis(e,e)-l,3-dimethylcylohexane, and frdistance between the two methyl groups. What do you conclude Explain the result. 

The final example in Table 7.13 shows that two elimination reactions can occur on the same substrate. Although it appears that elimination occurs from the 1,2-diequatorial isomer, it is almost certainly true that conformational change to the diaxial isomer (prepared, e.g.,by addition of bromine [Br2] to cyclohexene) precedes the elimination as shown in Scheme 7.41. 

FIGURE 5.41 Diequatorial trans-1,2-dimethylcyclohexane is more stable than the diaxial isomer. 

In the diaxial isomer, the two methyl groups occupy anti positions, and therefore their interaction with one another is not destabilizing. However, for each axial methyl group we still have the two gauche interactions with the ring methylene groups (see p. 199), and this will cost the molecule 2 X 1.74 kcal/mol = 3.48 kcal/mol. We can predict that the diequatorial isomer should be (3.48 — 0.6) kcal/mol = 2.88 kcal/mol more stable than the diaxial isomer. In turn, this calculation predicts that at 25 °C there will be more than 99% of the diequatorial form present. 

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