Acid-catalyzed solvolysis

The removal of the carbohydrate auxiliary group and the hydrolysis of the amino nitriles is achieved by acidolytic cleavage of the hemiaminal /V-glycosidic bond and the concomitant acid-catalyzed solvolysis of the nitrile using either hydrogen chloride in formic acid or hydrogen bromide in acetic acid56 57. 

Acid-catalyzed solvolysis of hydroxylactams to (m)ethoxylactams has already been discussed. Secondary or tertiary alcohols can also be used, though in the latter case yields are lower. The reverse reaction, viz. hydrolysis of the alkoxy compounds, is generally performed in aqueous acid. 

Scheme 12.15 gives some examples of both acid-catalyzed and nucleophilic ring openings of epoxides. Entries 1 and 2 are cases in which epoxidation and solvolysis are carried out without isolation of the epoxide. Both cases also illustrate the preference for anti stereochemistry. The regioselectivity in Entry 3 is indicative of dominant bond cleavage in the TS. The reaction in Entry 4 was studied in a number of solvents. The product results from net syn addition as a result of phenonium ion participation. The ds-epoxide also gives mainly the syn product, presumably via isomerization to the... 

This synthetic approach involves rearrangement of the incipient carbonium ion derived from the readily available six-membered ring compounds. Acid catalyzed 15,16) and solvolysis 17) reactions of 17a and 17b, respectively, afforded dibenzo[6/]-thiepin (9) which was also obtained by reaction of thioxanthylium ion (18) with diazomethane 18,19). 

An extension of this methodology was used In another approach (16) to the octosyl acids and ezomyclns (Figure 10). In this sequence, D-galactose was transformed Into the 2-0-acetyl derivative 57. Transformation to the acyclic nucleoside derivative and selective oxidation then gave sulfoxide 58. Elimination afforded the trans olefin 59 whereupon solvolysis followed by epoxldatlon and acid-catalyzed cycllzatlon produced and In a 1 2 ratio respectively. The H-NMR spectra showed each to contain a l, 2 -trans configuration, and that the minor Isomer was the required 6-D-nucleoslde, while the major product was the a-D-nucleoslde. 

A series of flavan-4-ols, e.g., 108, was conveniently prepared by metal hydride reduction of the corresponding flavanone. The flavan-4-ols were converted into the 4-methoxyflavans, e.g., 109, by acid-catalyzed solvolysis in methanol. Both these classes of compounds are currently evaluated as anticancer drugs. Enantiomerically enriched cA-flavan-4-ols have been prepared by lipase-catalyzed kinetic resolution of racemic counterparts. ... 

Oxetanes are much less susceptible to cleavage by nucleophiles than oxiranes, except in the presence of acids. Several types of acid-catalyzed nucleophilic reactions are described in the previous section, such as reaction of hydrogen halides to give 3-halogeno-1-propanols and various acid-catalyzed solvolysis reactions. Another example of this type is the reaction of thiourea with 2-alkyloxetanes in the presence of hydrochloric or perchloric acid to give excellent yields of 3-alkyl-3-hydroxybutylisothiouronium salts (equation 39) <67CR(C)(264)1309>. 

In contrast, the acid-catalyzed hydrolysis of alkyl selenates is A-2158. The actual species which undergoes decomposition to alcohol and sulfur trioxide is probably the zwitterion as in the case of phosphate monoester monoanions. Evidence for sulfur trioxide as the reactive initial product of the A-1 solvolysis is obtained from the product compositions arising with mixed alcohol-water solvents. The product distribution is identical to that found for sulfur trioxide solvolysis, with the latter exhibiting a three-fold selectivity for methanol. Although the above entropies of activation and solvent deuterium isotope effects do not distinguish between the conventional A-l mechanism and one involving rate-limiting proton transfer, a simple calculation, based on the pKa of the sulfate moiety and the fact that its deprotonation is diffusion controlled. 

In an acid-catalyzed solvolysis reaction three species are of primary kinetic... 

Some acid-catalyzed solvolysis reactions of oxacyclopropanes appear to proceed by SN1 mechanisms involving carbocation intermediates. Evidence for the SN1 mechanism is available from the reactions of unsymmetrically substituted oxacyclopropanes. For example, we would expect the conjugate acid of 2,2-dimethyloxacyclopropane to be attacked by methanol at the primary carbon by an SN2 reaction and at the tertiary carbon by an SN1 reaction ... 

The acid-catalyzed hypobromous acid bromination is the only direct substitution reaction extended to very deactivated substituted benzenes. The available results are illustrated in Fig. 15. de la Mare and Hilton (1962) evaluated the slope as — 6.2. They also point out that the serious discrepancy exhibited by the m-trimethylamino substituent is not readily identified with an error in the c7+-value. It was suggested (Brown and Okamoto, 1958) that the entropies of activation (Table 19) for the solvolysis of the m- andp-trimethylaminophenyldimethylcarbinyl... 

The hydrolysis and solvolysis of esters can occur through acid-catalyzed, pH-independent, and base-catalyzed mechanisms. These reactions can be classified further according to the type of bond fission and the molecularity of the rate determining step. It is important to realize, however, that there are borderline cases in which classification of the molecularity of the reaction is merely a matter of its academic... 

Lactonization of a b,i-unsaturaled ester/ In a projected synthesis of quassinoid diterpenes, the final step involves lactonization of the unsaturated ester 1. Acid-catalyzed solvolysis (HCl in THE) or treatment with an arvlsulfonic acid in toluene results mainly... 

Various authors have studied the effects of substituents at the aromatic rings of diphenyldiazomethane and 9-diazofluorene on the rate of acid catalyzed solvolysis [218, 219]. Hammett p values for these examples are collected in Table 20. Furthermore a wealth of data can be found in the literature concerned with the effects of substituents in a weak acid, HA,... 

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