Selective hydrolysis position

Selective hydrolysis of the 3-carboxylate with 6N-HCl/AcOH was unsuccessful and instead the 4-carboxylate hydrolyzed to the corresponding acid, however, heating of 432 at 50 °C caused its hydrolysis and decarboxylation in one step. Subsequent reaction with either MnO or DDQ gave 433. The fluorine atom at 8-position could be replaced by cyclic amines to give the 8-pyrrolyl or 8-[l-methyl-4-piperazinyl] derivatives 436 which upon hydrolysis using either acidic or basic conditions afforded the... 

The synthesis of deoxysepiapterin (82) has been recently achieved by homo-lytic nucleophilic substitution of the pteridine nucleus by acyl radicals (505). Since this substitution arises preferentially at the most electron-deficient 7 position, protection at 7 position is necessary for nucleophilic attack at the 6 position. 2,4-Diamino-7-methylthiopteridine (597) and 2-amino-4- -pentyloxy-7-n-pro-pylthiopteridine (600), protected by the thio function, can be used as starting materials. Homolytic acylation of 597 with the system propionalde-hyde/Fe2+//ert-butylhydroperoxide afforded 6-propionylpteridine (598) in good yields, which could be transformed to deoxysepiapterin (82) by selective hydrolysis followed by deprotection of the thio function (Scheme 75). Deoxysepiapterin (82) can also be prepared by a similar procedure from 600. 

Hydroxyl groups can be introduced by hydrolytic reactions in the electrophilic 2-, 4-and 6-positions, and direct hydrolysis of halopyrimidines can be effected under both acidic and alkaline conditions <1994HC(52)1>. Normally 4-halopyrimidines hydrolyze faster than 2-halo derivatives, but in the case of 2-chloro, 6-di(pyrrolidinyl)pyrimidine 163 and 4-chloro-2,6-di(pyrrolidinyl)pyrimidine 164, the 2-chloro isomer 163 was found to hydrolyze 350 times faster (to 165) than the 6-chloro isomer 164 in 6N HCl, and 1750 times faster in 12N HCl <20060PD921>. This result was interpreted as being due to the transition state for hydrolysis of the 4-chloro isomer involving two more molecules of water (each acting as a base) than the transition state for hydrolysis of the 2-chloro isomer. As the concentration of HCl increases from 6 N to 12 N, there are fewer unprotonated water molecules and thus, hydrolysis of the 4-isomer is less favored. This difference in reactivity was able to be exploited to perform a selective hydrolysis on a production scale <20060PD921>. 

Hydrolysis of pyrimidinamines generally requires more vigorous conditions, although selective hydrolysis can often be achieved. Thus, the acid-catalyzed hydrolysis of 2,4,6-triaminopyrimidine 170 occurred in the 2-position to give 4,6-diamino-2(l//)-pyrimidinone 171 <2001JOC192>. Examples of selective diazotization of diamines are also known <2005JOC1612>. 

The preparation of -substituted derivatives is more difficult and different methods have been used in the various series. 2-Tritylpyrrole undergoes electrophilic substitution selectively at the 3-position (Section 3.3.1.4.3) and the trityl group can then be removed. Again, in the pyrrole series the selective hydrolysis of a-C02Et in alkali and of (3-C02Et in acid, followed by decarboxylation, allows the introduction of (3-substituents into compounds such as 2,4-dialkylpyrrole-3,5-dicarboxylic esters to afford 3-substituted 2,4-dialkylpyrroles (Section 33.3.3.1). 

It has been shown that thiophene-2,3-dicarboxyIic acid is preferentially esterified in the 2-position also, selective hydrolysis of the 2,3-diester results in the formation of the 2-carboxylic acid. Decarboxylation during electrophilic substitution is a well-recognized... 

Selective hydrolysis can be used to remove the 0-6 protecting group of methyl 2,3,4,6-tetrakis-0-(trimethylsilyl)-a-D-glucopyranoside [403, 404]. Under properly controlled conditions, selective cleavage at one or both of the primary positions of pertrimethyl-silylated a,a-trehalose has been achieved [405]. The simple heteronuclear 1H29Si chemical shift correlated two-dimensional NMR spectroscopy enables the assignment of positions of trimethylsilyl substituents [406]. Interestingly, octakis-0-(tri-methylsilyl)sucrose is a stable, crystalline material which has been even proposed as an internal standard for GLC [407]. 

The homochiral prostaglandin precursor (15,3fi)-330.1 was prepared [Scheme 4.330] by selective hydrolysis of the /weso-diacetate of cw-4-cyclopentene-13-diol 330 2 using pig liver esterase (PLE),617 whereas the enantiomer (1/ ,35)-330 3 was the product of electric eel cholinesterase (EECE) hydrolysis,618 Since enzyme-catalysed reactions are reversible, transesterification can also be used to prepare esters. In the case at hand, ciy-4-cydopentene-l,3-diol (330.4) was enan-tioselectively transesterified using pig pancreatic lipase (PPL) and trichloroethyl acetate.619 The trichloroethyl ester is used in order to influence the position of equilibrium since trichloroethanol is a better leaving group and weaker nucleophile than cyclopentenediol.620... 

After library cleavage, screening, and selection of positives (steps a-c. Fig. 7.28), the positive beads, such as 7.46, are decoded simply by strong aqueous acid hydrolysis, neutralization, and dansylation of the residual amines to give the dansyl derivatives 7.47 (steps d-g), which are all distinct in an HPLC spectrum. Several recent reports have provided optimized HPLC/fluorescence decoding protocols (198), which shortened the average decoding procedure from 1 h to around 6 min, and also alternative... 

A different type of assisted hydrolysis occurs when a 17 a,-2i-diacetoxypregnan-20-one is treated with mild alkali [ig]. Instead of selective hydrolysis of the primary C(2i) ester, only complete hydrolysis occurs. It was shown by partial hydrolysis of a 17-acetate 2i-propionate that the reaction proceeds through rapid migration of the tertiary I7a-acetate to the C(2i) position, presumably through a iya,2x-oHho ester cf. p. 61), The actual hydrolysis then occurs twice at the primary position. 

The selective hydrolysis of acetyl groups, led in methanol in presence of concentrated sulphuric acid, gives the a,P unsaturated methyl ester 13e. Therefore the two hydroxyls at C-3 and at C-4, in sin position each other, are protected by means of formation of isopropylidene function, doing react the methyl ester 13e with 2,2-dimetiioxypropane in acetone in presence of catalj tic quantity of strongly acidic resin, so obtain the 3,4-O-isopropylidene derivative 13f. 

Other reactions may also be affected by the presence of complexing cations. Methyl furanosides that complex readily are hydrolyzed by acids at a lower rate in the presence of calcium chloride than those which do not. The first step of the hydrolysis, protonation by the acid, is impeded by the positive charge of the glycoside-cation complex. This retardation may be useful for the selective hydrolysis of polysaccharides. 

The structural elucidation of these sesquiterpenes, given the difficulty in determining the linking sites of the respective ester groups when more than three kinds of acid are involved as esters in the molecule, necessitates the use of nmr experiments (selective INEPT [10], Coloc [11] or HMBC 2D [12]), selective hydrolysis processes or X-ray crystallographic methods [13], From comparison of the chemical shifts of similar compounds, it is not easy to establish the exact position of each ester. 

This section focuses on the chemistry associated with the carboxyl group in the 1-position of malic acid derivatives. Manipulations such as selective hydrolysis, reduction, or cyclization... 

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