Acetolysis

Trifluoroethanol was first prepared by the catalytic reduction of trifluoroacetic anhydride [407-25-0] (58). Other methods iaclude the catalytic hydrogeaatioa of trifluoroacetamide [354-38-1] (59), the lithium aluminum hydride reductioa of trifluoroacetyl chloride [354-32-5] (60) or of trifluoroacetic acid or its esters (61,62), and the acetolysis of 2-chloro-l,l,l-trifluoroethane [75-88-7] followed by hydrolysis (60). More recently, the hydrogenation of... 

Higher perfluoroalkanesulfonates are slightly more reactive than triflates toward nucleophilic displacements. The rate constants for acetolysis of methyl nonafluorobutanesulfonate [6401 -03-2J, methyl trifluoromethanesulfonate [333-27-7] and methyl toluenesulfonate [80-48-8] are 1.49 x, ... 

Thiabicyclo[2.2.1]heptane, 2-emlo-chloro-acetolysis, 4, 857 6-Thiabicyclo[3.1.1 ]heptane synthesis, 7, 434 5-TTiiabicyclo[2.1.1 ]hexane bond angles, 7, 404 ring strain, 7, 419 synthesis, 7, 434 3-Thiabicyclo[3.1.0]heptane... 

In earlier experiments a temperature of 30-40° was maintained during the addition of the cotton (which then required more time), and the acetolysis was allowed to proceed at room temperature for six days. The yield of product melting at 220-222° was 50-56 g., but rose to 62-70 g. when the period of digestion was extended to eight days. 

The preparation of a-cellobiose octaacetate by the acetolysis of cellulose was discovered by Franchimont, and the process has been studied carefully by a number of other investi-... 

Conversely, processes which convert carbons to sfp- carbons are more favorable for five-membered than for six-membered rings. This can be illustrated by the data for acetolysis of cyclopentyl versus cyclohexyl tosylate. The former proceeds with an enthalpy of activation about 3kcal/mol less than the latter." A molecular mechanics analysis found that the difference was largely accounted for by the relief of torsional strain in the cyclopentyl case." Notice that there is an angle-strain effect which is operating in the opposite direction, since there will be some resistance to the expansion of the bond angle at the reaction center to 120° in the cyclopentyl ring. 

Solvolysis rate studies also indicate that there is greater stabilization by a cyclopropyl group in a bisected geomeby. In tosylate 1, the cyclopropane ring is locked into an orientation which affords a perpendicular arrangement. It reacts 300 times more slowly than the model compound 2. Tosylate 3, which corresponds to the bisected geomeby, undergoes acetolysis at least 10 times faster than the model 2-adamantyl tosylate 4. ... 

Trifluoromethanesulfonate (triflate) ion is an exceptionally good leaving grov. It can be used for nucleophilic substitution reactions on unreactive substrates. Acetolysis of cyclopropyl triflate, for example, occurs 10 times faster than acetolysis of cyclopropyl tosylate. Table 5.11 gives a conqiarison of the triftate group with some other common leaving groups. 

The rate of acetolysis of t-butyl bromide relative to that of i-propyl bromide at 25°C is 10 - , whereas the rate of acetolysis of 2-methyl-2-adamantyl bromide relative to that of 2-adamantyl bromide is 10 ... 

This interpretation is supported by results on the acetolysis of the bicyclic tosylates 9 and 10. With 9, after three months in acetic acid at 150°C, 90% of the starting material was recovered. This means that both ionization to a cyclopropyl cation and a concerted ring opening must be extremely slow. The preferred disrotatory ring-opening process would lead to an impossibly strained structure, the /ran -cyclohexenyl cation. In contrast, the stereoisomer 10 reacts at least 2x10 more rapidly because it can proceed to a stable cis-cyclohexenyl cation ... 

On the other hand the acetolysis of the 6y5,19-ether bridge is a useful reaction in the 6a-methyl-6j9,19-ether series ... 

Acetolysis of the 6)5,19-ether can also be achieved in the presence of a A -3-keto group. This reaction affords an entry to 19-oxygenated-A -3-ketones. ° ss. 78... 

Acetolysis of 3/ -methoxy-19-hydroxy-androst-5-en-17-one 19-methane-sulfonate (68b) in the presence of 4 equivalents of potassium acetate at 100° for 16 hr followed by basic hydrolysis gives 3/ -methoxy-7) -hydroxy-B-homo-estr-5(10)-en-17-one (70a) in 77% yield and 8% of 3/ -methoxy-5, 19-... 

Methoxy-7)5-hydroxy-B-homo-estr-5(10)-en-17-one (70a) ° The buffered acetolysis solution is prepared by heating at reflux overnight a solution prepared from anhydrous potassium carbonate (3.5 g), acetic anhydride (5 ml) and glacial acetic acid (250 ml). 

A solution prepared of 19-methanesulfonate (68b 2.45 g) and buffered acetolysis solution (120 ml) is heated at 100° for 16 hr. The product (2.17 g of orange oil) is isolated by ether extraction in the following manner. The reaction mixture is cooled to room temperature and shaken with a mixture of ether (600 ml) and water (1 liter). The aqueous phase is separated and extracted with ether (600 ml). The ether solutions are washed separately with water (two and three 500 ml portions respectively) then combined and... 

For the preparation of 19-nor-B-homosteroids Tadanier s acetolysis procedure appears to be the method of choice. The mild reaction conditions employed with each of these procedures allows the maintainance of a variety of functional groups, e.g., double bonds, ethers, hydroxyls and the like during the homologation process. 

These rate constants are for the acetolysis of exo-2-tosyloxybicyclo[2.2.1]-heptan-7-one ethylene glycol ketal. " ... 

The fact that acetolysis of both 4-methoxy-l-pentyl brosylate (18) and 5-methoxy-2-pentyl brosylate (19) gave the same mixture of products is further evidence for... 

C=C as a neighboring group."° The most striking evidence that C=C can act as a neighboring group is that acetolysis of 29-OTs is 10 times faster... 

C undergoes acetolysis 140,000 times faster than the saturated analog 33. Triple bonds and allenes can also act as neighboring groups. 

TABLE 10.1 Approximate kjks Ratios for Acetolysis of P-ZC6H4CH2CH2OTS at 90°C... 

In the brosylate acetolysis sets, conjugative stabilization of the transition state is geometrically excluded in the syn form, but is anticipated in the anti form (13). That is, on structural grounds, is expected to be the parameter of choice for the syn set and for the anti set. The available data (for the OMe, Me, Cl and NO2 substituents) do indeed conform to this expectation ... 

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