Acetals methanolysis

C3-hydroxy benzylation, through alkylation of the intermediate 2,3-0-dibutylstannylene of mannose acetal 24, gives 25 (Scheme 5). Hydroboration of the exocyclic 5-alkene derived from this material provides 26, in which the C5 stereochemistry is inverted. Benzylation and acetate methanolysis leads to the suitable glycosyl acceptor 27. 

Fig. 4 (a) Reactivity profiling of the hydroxyl groups of erythromycin imder NMI-catalyzed conditions, (b) Hit peptide 46. (c) 4" 11-Acylation ratios, following 2 -acetate methanolysis, for different acylating reagemts under NMI and peptide-catalyzed conditions [87]. Note all reactions were tun at a concentration of 0.1 M 40 in CHCI3 solvent with 5 equiv. EtsN at 25 °C fin 24-72 h [87]... 

We shall describe a specific synthetic example for each protective group given above. Regiosdective proteaion is generally only possible if there are hydroxyl groups of different sterical hindrance (prim < sec < tert equatorial < axial). Acetylation has usually been effected with acetic anhydride. The acetylation of less reactive hydroxyl groups is catalyzed by DMAP (see p.l44f.). Acetates are stable toward oxidation with chromium trioxide in pyridine and have been used, for example, for protection of steroids (H.J.E. Loewenthal, 1959), carbohydrates (M.L. Wolfrom, 1963 J.M. Williams, 1967), and nucleosides (A.M. Micbelson, 1963). The most common deacetylation procedures are ammonolysis with NH in CH OH and methanolysis with KjCO, or sodium methoxide. 

Raw Material. PVA is synthesized from acetjiene [74-86-2] or ethylene [74-85-1] by reaction with acetic acid (and oxygen in the case of ethylene), in the presence of a catalyst such as zinc acetate, to form vinyl acetate [108-05-4] which is then polymerized in methanol. The polymer obtained is subjected to methanolysis with sodium hydroxide, whereby PVA precipitates from the methanol solution. 

Coe et al. reported an efficient modification for the preparation of /-substituted indole analogs for biology screening in good yield. The intermediate P-nitrostyrene 44, prepared from the condensation of 43 with DMFDMA, underwent methanolysis and reduction to provide the aniline acetal intermediate 45. Alkylation of amine 45 was carried out employing standard conditions of reductive alkylation to provide A-alkyl analogs represented by 46. The indole 47 was generated by formation of the oxonium ion (from 46) under acidic conditions, followed by cyclization, accompanied by loss of methanol. 

PET methanolysis involves the reaction of PET with methanol at high temperatures and pressures in the presence of transesterification catalysts such as magnesium acetate, cobalt acetate, and lead dioxide. 

Alkyl esters are efficiently dealkylated to trimethylsilyl esters with high concentrations of iodotrimethylsilane either in chloroform or sulfolane solutions at 25-80° or without solvent at 100-110°.Hydrolysis of the trimethylsilyl esters serves to release the carboxylic acid. Amines may be recovered from O-methyl, O-ethyl, and O-benzyl carbamates after reaction with iodotrimethylsilane in chloroform or sulfolane at 50—60° and subsequent methanolysis. The conversion of dimethyl, diethyl, and ethylene acetals and ketals to the parent aldehydes and ketones under aprotic conditions has been accomplished with this reagent. The reactions of alcohols (or the corresponding trimethylsilyl ethers) and aldehydes with iodotrimethylsilane give alkyl iodides and a-iodosilyl ethers,respectively. lodomethyl methyl ether is obtained from cleavage of dimethoxymethane with iodotrimethylsilane. 

Qualitative analysis of selected fractions was based on GLC separation of alditol acetates (5). Alditol acetates from uronosyl residues were prepared by methanolysis followed by reduction (4). 

To obtain this compound the key step consisted in the epimerization of the C-5 in compound 6. This was acomplished by triflation of the alcohol 6 and nucleophilic substitution of the triflate by a large excess of tetrabutylammonium acetate in dichloromethane. A controlled (4 °C, 3 h) basic methanolysis of the enol benzoate led to the keto-ester 11" whose hydroxyl functions at C-4 and C-6 were simultaneously deprotected under acidic conditions to furnish 12. Finally a Zemplen deprotection of the 5-acetoxy group led to 13 obtained in five steps and 11% overall yield from 6 (figure 4). 

Two competing chain-transfer mechanisms in copolymerization of CO and ethene catalyzed by Pd11 acetate/dppp complexes were found. One involves termination via an isomerization into the enolate followed by protonation with methanol the rate of this reaction should be independent of the concentration of the protic species. The second chain-transfer mechanism comprises termination via methanolysis of the acylpalladium species, and subsequent initiation by insertion of ethene into the palladium hydride bond.501... 

If the alkoxy group at the C-6 atom in nitroso acetals (475) is absent, silyl derivatives (476) are generated instead of nitroso ketones A, and methanolysis of compounds (476) gives rise to y-hydroxy oximes (479). 

Fig. 2 Speciation diagram for 2.0 x 10" 3 M La3+ in methanol as a function of pH. Data superimposed on the figure as ( ) are second-order rate constants for La3 +-catalyzed methanolysis of p-nitrophenyl acetate (2) as a function of pH.

Having established the speciation, we now have a very powerful tool for analyzing the kinetic data for the pH dependence of the La3 + catalysis of the alcoholysis of various substrates. Included in the Figs 1 and 2 plots are the second-order rate constants for La3 + -catalysis of the ethanolysis of paraoxon (1) and the methanolysis of /xnitrophenyl acetate (PNPA, 2) as a function of pH in ethanol and methanol, respectively. The kinetic data mainly follow the rise/fall behavior of the Lal+( OR)2 species with some involvement of the other species, La2 + ( OR)i, La2 1 ( OR)3 and Lal+(-OR)4. 

Fits for the La3 +-catalyzed methanolysis of /xnitrophenyl acetate (2),7 paraoxon (1), its thio derivative, 0,0-Diethyl. S -p-nitrophcnyl phosphorothioate (3)10b and IV-p-nitrophenyl /1-lactam (4)32 have also been computed, with the various ky" the values being given in Table 4. 

The initial study of the La3 +-catalyzed methanolysis of carboxylate esters163 reported the apparent second-order rate constant for La2 + ( OCH3)2-catalyzed methanolysis of some representative examples of aryl esters (2, 5 and 2,4-dinitrophenyl acetate (14)), phenyl benzoate (15) and three aliphatic esters, ethyl acetate, isopropyl acetate (16) and tert-butyl acetate (17). Given in Table 6 are the rate constants for the La3+ and methoxide-catalyzed methanolysis of these esters along with... 

Methanolysis rates for esters 2, 14, 5, 15 determined by UV kinetics in CH3OH ethyl acetate, 16, 17 determined by [H NMR in d4-methanol. 

Fig. 4 A Bronsted plot of log pKz phenol in methanol vs. log fcaa fn( OCH3-) for methanolysis of aryl acetates promoted by 9 Zn2 + ( OCH3), T = 25°C, data in Table 7. Dashed line corresponds to NLLSQ fit of data to Equation (15) encompassing all esters with Pi = -0.023 0.03 and f 2 = -0.690 0.005 with a breakpoint of pJTa H = 14.8. Reproduced from ref. 16f with permission.

The partially methylated monosaccharides obtained on depolymerization of the permethylated sample are preferably analyzed as acetates by g.l.c.-m.s., as shown by Bjomdal and coworkers.41,42 The neutral sugars and the amino sugars obtained in acetolysis-acid hydrolysis are reduced, and acetylated for the analysis, and the amino-hexitol and the neuraminic acid residues are acetylated after methanolysis. Identification with the aid of g.l.c.-m.s. has been described for all of the common components of protein- and lipid-linked glycans and oligosaccharides from animal cells, namely, the neutral sugars,41-43 hexitols,44 hexosamines,29,43,45,46 aminohexitols,31,32 and neuraminic acids.33,34,47... 

The Pyoc group is stable to acids and bases, but may be selectively removed after conversion into the jV-methylpyridinium form and subsequent treatment with morpholine, to give 146. Treatment of 146 with acetic anhydride in pyridine gave 147. Hydrogenolysis of the benzyl ester group of 147 followed by methanolysis catalyzed by hydrazine afforded (44,73) the de-protected derivative 148. 

In contrast, the results obtained in the methanolysis, acetolysis, and trifluoroacetolysis of the tosylate 91 were not the expected ones. Cram obtained the methyl ether 93, the acetate 94 and the trifluoro-acetate 95 with the same configuration and optical purity as in the direct synthesis from the alcohol 92. These solvolyses at the bridge carbon atom of [2.2]paracyclophane therefore proceed with complete retention of configuration. The rate of acetolysis of the tosylate 91 also deviates considerably from that of aliphatic secondary tosylates it is some 100 times faster than that of 2-butyl tosylate and about the same as that of a-phenylneopentyl tosylate, acetolysis of which is only slightly stereospecific. 

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. 

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