Formolysis and Acetolysis

Formolysis and acetolysis are not common methods for cleavage of glycosidic linkages. They do have some unique applications, however. For instance, methylated polysaccharides are not generally soluble in hot water, and consequently, hydrolysis is best preceded by formolysis under these circumstances. For example, 5 mg of methylated polysaccharide is dissolved in 3 mL of 90% formic acid, and the solution is kept for 2 h at 100°. The formic acid is removed by evaporation at 40°. The residue is dissolved in 1 mL of 250 mM sulfuric acid and the solution is heated for 12 h at 100°, cooled, the acid neutralized with barium carbonate, the 

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Chuchani and coworkers160 examined the participation by a more remote benzene ring in co-phenylalkyl chlorides. Analysis of the data of Table 16 indicated that participation of C6H5 at the 2-, 4- and 5-positions is more favored than in the 3-position which seems unimportant. The relative sequence found in this work is somewhat similar to that found in the formolysis and acetolysis of co-phenylalkyl / -bromobenzenesulfonates by Heck and Winstein161 ... 

High secondary a-deuterium kinetic isotope effects for the primary carhon-oxygen cleavage in formolysis and acetolysis of dideuterioferrocenylmethyl henzoate... 

The mentioned results of Kevill et who found that the rates of fer-rocenylmethyl acetate solvolyses increase with increasing the solvent ionizing power, and the observation of close similarity in reaction rates of formolysis and acetolysis of ferrocenylmethyl benzoate, despite the large difference in ionization power of these two acids, ° prompted a reinvestigation of the mentioned kinetic data. The new measurements fully support the earlier results. 

Cram and Singer also noted a remarkable difference in the solvolysis of the systems 100b and 101 b. On acetolysis of the a-C deuterated model compound 101c the deuterium was found to be scrambled with 46% D recovered in the position (on hydrolysis 26% D was recovered the / position), whereas in the acetolysis and formolysis of 100c the deuterium remained totally undisturbed in the a position. 

Recent studies on the solvolysis of the diastereomeric tosylates 107 support this hypothesis. The acetolysis and formolysis of these compounds proceed with high retention of configuration 90> while in ordinary simple acetolysis of tosyl esters of secondary alcohols containing no neighboring groups, inversion predominates. 

Glycosidic linkages may also be cleaved in other solvents, such as methanol. In this case, water is rigorously excluded, so that the elements of a molecule of methanol are added across the glycosidic linkage to afford the methyl glycosides. Methanolysis is usually catalyzed by the addition of dry hydrogen chloride to the methanol. Other solvents, such as acetic anhydride-acetic acid (acetolysis) and formic acid (formolysis), are occasionally used for special purposes. 

Various techniques have been utilized for sequencing the glycosyl residues of polysaccharides and oligosaccharides. These techniques are elaborations of the commonplace procedure of converting polysaccharides, by partial hydrolysis, into structurally analyzable oligosaccharides. This conversion is generally achieved by partial hydrolysis with acid, by acetolysis,131 or by formolysis.62 These reagents may differ in the... 

In contrast to Sfj2 reactions, rates of reactions involving TSs with cationic character increase with substitution. The relative rates of formolysis of alkyl bromides at 100°C are methyl, 0.58 ethyl, 1.00 i-propyl, 26.1 and r-butyl 10. This order is clearly dominated by carbocation stability. The effect of substituting a methyl group for hydrogen depends on the extent of nucleophilic participation in the TS. A high CHj/H rate ratio is expected if nucleophilic participation is weak and stabilization of the cationic nature of the TS is important. A low ratio is expected when nucleophilic participation is strong. The relative rate of acetolysis of r-butyl bromide to... 

The rates of solvolysis in ethanol, formic acid, and acetic acid of l-(p-methoxyphenyl)ethyl toluene-p-sulfonate (65) are approximately the same as those of its para isomer (66). Because of the lack of product analyses and therefore quantitative knowledge of the importance of aryl participation " and the pathway,it is not possible to determine the extent of o-MeO-5 participation. However, o-MeO-6 participation occurs extensively in the acetolysis and formolysis of the analogous 3-(o-methoxyphenyl)-l-propyl p-bromobenzenesulfonate (73) and 3-(o-methoxyphenyl)-3-methyl-l-butyl toluene-p-sulfonate (74) (see Table 6). Any competing aryl participation would be Ari-4 participation and, as shown by the reaction rates for the para isomers, is unimportant. The reaction products (Table 6) contain large amounts of the pyran derivatives (75) and (76) and of the methyl arenesulfonates, and the reactions may therefore be formulated as shown in... 

As already pointed out, the acetolysis and formolysis of dideuterioferro-cenylmethyl benzoate exhibit large secondary a-D KIEs, and an abnormal temperature dependence has also been observed. In the presence of LiC104 ca. 0.1 moldm ), which prevents reversion from solvent-separated to contact ion pairs, 25 °C amounted to 1.53 0.02 (acetolysis) and 1.48 ... 

These effects, determined with tertiary chlorides, unquestionably refer to 8n1 reactions so also do Lewis and Boozer s effects on acetolysis and formolysis—-if we can rely on the constancy of the effect of a-deuteration (Table VIII). The /3-effects then suggest that formolysis of the secondary bromide and solvolysis in aqueous ethanol of the tosylate are also SnI—or nearly so, unless bimolecular displacement reactions are also subject to similar isotope effects. Shiner (117) had however already shown that this was not so, since deuteration in the two methyl groups of isopropyl bromide did not lead to an experimentally significant effect on the displacement reaction with ethoxide ion in ethanol. It is thus also reasonable to interpret the very small effect (AAF" = 6 cal.) cited by Lewis (74f) for acetolysis of ethyl-2d8 brosylate as evidence that acetolysis of primary sulfonate esters is borderline if not Sn2. This conclusion, already suggested by the abnormally low a-effect for unassisted acetolysis of phenylethyl tosylate [Table VIII and text of Sec. VA, 2(b) 1 is supported by a similarly... 

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