Ester hydrolysis, partial

Macrocyclic model lipids for the formation of vesicles often contain four ester bonds— two on each head group. It has been found that these ester bonds are exceptionally stable against acid-catalyzed hydrolysis in water. The reasons probably lie in the partial hydrophobicity of the ester group s environment, the macrocycle s order, and the reversibility of ester hydrolysis. Partially hydrolyzed tetraesters are presumably immediately reformed in vesicular membrane structures before the second, third, and fourth ester group reacts (Scheme 2.4.9). 

Three general methods exist for the resolution of enantiomers by Hquid chromatography (qv) (47,48). Conversion of the enantiomers to diastereomers and subsequent column chromatography on an achiral stationary phase with an achiral eluant represents a classical method of resolution (49). Diastereomeric derivatization is problematic in that conversion back to the desired enantiomers can result in partial racemization. For example, (lR,23, 5R)-menthol (R)-mandelate (31) is readily separated from its diastereomer but ester hydrolysis under numerous reaction conditions produces (R)-(-)-mandehc acid (32) which is contaminated with (3)-(+)-mandehc acid (33). 

Expect some product contamination if feed components can react with water, eg, ester will be partially hydrolyzed to acid and alcohol fate of reaction product species depends on above rules, eg, methanol from methyl ester hydrolysis probably not stripped out of bottoms stream. 

Oae found that for both base- and acid-catalyzed hydrolysis of phenyl benzenesul-fonate, there was no incorporation of 0 from solvent into the sulfonate ester after partial hydrolysis. This was interpreted as ruling out a stepwise mechanism, but in fact it could be stepwise with slow pseudorotation. In fact this nonexchange can be explained by Westheimer s rules for pseudorotation, assuming the same rules apply to pentacoordinate sulfur. For the acid-catalyzed reaction, the likely intermediate would be 8 for which pseudorotation would be disfavored because it would put a carbon at an apical position. Further protonation to the cationic intermediate is unlikely even in lOM HCl (the medium for Oae s experiments) because of the high acidity of this species a Branch and Calvin calculation (See Appendix), supplemented by allowance for the effect of the phenyl groups (taken as the difference in between sulfuric acid and benzenesulfonic acid ), leads to a pA, of -7 for the first pisTa of this cation about -2 for the second p/sTa. and about 3 for the third Thus, protonation by aqueous HCl to give the neutral intermediate is likely but further protonation to give cation 9 would be very unlikely. 

When 1,2-diols are subjected to the same reaction conditions required for the formation of sulphonic esters, oxiranes are produced [27]. Presumably, the mono ester is initially formed and, under the basic conditions, intramolecular elimination occurs to produce the oxirane. Partial hydrolysis and ring-closure of a,p-di(tosyloxy) compounds under basic phase-transfer catalytic conditions provides a convenient route to carbohydrate oxiranes [e.g. 28, 29]. Oxiranes have been produced by an analogous method via carbonate esters from partially protected carbohydrates [30],... 

The acid-catalyzed hydrolysis of orthoesters is very much faster than that of esters. The second-order rate coefficient for the hydrolysis of ethyl acetate is of the order of 10"4 1-mole-1-sec1 at 25°C, whereas that for the hydrolysis of ethyl orthoacetate103 is of the order of 104 l-mole-1-sec 1, and that for the breakdown of a monoalkyl orthoester must be faster still. If the breakdown of the tetrahedral intermediate is partially rate-determining in acid-catalyzed ester hydrolysis, therefore, its concentration must be very small that is, the equilibrium for its formation must be highly unfavourable. This... 

The broad outline of the mechanism of catalysis of ester hydrolysis by hydroxide ion is not in doubt. The reaction is well known to involve acyl-oxygen cleavage, and seems invariably to be of the second order, being first order in both ester and hydroxide anion. General base catalysis in the usual sense is not a possibility, the partial removal of a proton from water cannot generate a species more reactive than hydroxide ion, so direct nucleophilic attack must be involved. (However, if it is accepted that the high ionic nobility of the hydroxide ion in water is explained by a Grotthus-type mechanism... 

The principles outlined above were allied by Marckwald and McKenzie 18 for the partial resolution of a racemic acid with an active alcohol. Thus When df-mandelic acid was heated with less than one equivalent of 1-menthol, the resulting ester contained somewhat more J-menthyl-d-mandelate than f-menthyl-L-mandelate and the unesterified acid contained a corresponding excess of i-mandelic acid. Also, when a mixture of equal amounts of the two diastereoisomeric esters was partially hydrolyzed, the regenerated acid and that still combined in the residual ester contained unequal amounts of the two antipodes. The process has been extended to the resolution of acids and amines through the formation and hydrolysis of amides.89... 

On the other hand, the substrate may undergo nucleophilic attack by base, either in the rate-determining step — with or without formation of an intermediate — or in a fast pre-equilibrium step which is followed by rate-determining breakdown of the intermediate. These three possibilities are included in the B2 mechanism according to Ingold s nomenclature [14]. Examples of one-step B2 reactions (SN2 mechanisms) are the alkaline hydrolyses of sulfonic esters [14] and 2,4,6,-tri-f-butylbenzoic esters [18]. Intermediates are formed by carbonyl addition of hydroxide ion in the alkaline hydrolyses of (unhindered) carboxylic esters and amides. Addition of OH is partially or completely rate-determining in ester hydrolysis [4, 15], but probably not in amide hydrolysis [15]. 

Angustmycin A (decoyinine, 68, R = adenin-9-yl, R = CH2OH) has been prepared from psicofuranine (71a) by way of the 1, 3, -ortho-formate. Standard elimination, and removal of the ester by partial hydrolysis with acid, gave a product which was identical with the natural antibiotic. In the course of the work, compound 68 (R = adeni-nyl, R = H) was again prepared.1298... 

An alternative method of synthesis of (IV.91) from 2,4-diamino-6-bromo-methylpteridine was described in 1980 by Piper and Montgomery [120]. The bromo compound was treated with triphenylphosphine in DMA (60-63 °C, 1.5 h), and the resultant ylide was condensed with diethyl N- 4-formylbenzoyl)-L-glutamate to obtain diester (IV.97) in 78% yield. Catalytic reduction of the 9,10 double bond resulted in partial reduction of the pteridine ring to a 7,8-dihydro derivative. Reoxidation of ring B with HjOj followed by ester hydrolysis with NaOH afforded (IV.91) (62%). 

The partial hydrolysis of 4a with methanolic potassium hydroxide followed by selective carboxylic acid reduction with excess borane and treatment of the resulting monoalcohol with methanesulfonyl chloride affords methyl 4-0-methanesulfonyl-2,3-0-isopropylidene-L-threonate (43). Facile displacement of the mesylate with azide followed by ester hydrolysis and catalytic reduction to an amine provides 4-amino-4-deoxy-2,3-0-isopropylidene-L-threonic acid (44). Mild acidic deprotection and ion-exchange desalting of 44 yields (2i ,3 S)-4-amino-4-deoxy-L-threonic acid (45), which has been utilized for the preparation of anthopleurine 46, the alarm pheromone of the sea anemone Anthopleura elegantissima [4] (Scheme 11). 

Reports on the transformation of 1,2,3,4-tetra-O-acetyl-p-D-glucopyranuro-nic acid with trimethylsilyl azide under SnC catalysis are ambiguous. According to Murphy et al. the a-azide 64 was obtained, however Toth et reported the product to be the p derivative 65. However, the first report describes a partial ester hydrolysis of 61 with LiOH to give 65, but the authors did not cite the earlier paper. 

The most prominent cellulose ester produced on the industrial scale is cellulose acetate. The reaction is usually performed with acetic anhydride and with sulfuric acid as a catalyst. To minimize heterogeneities, acetylation is allowed to run nearly to completion, and subsequently partial ester hydrolysis is initiated by the addition of water until a desirable solubility is achieved that corresponds to a DS of about 2.5. Such higher acyl homologues as propanoyl or butanoyl exhibit more thermoplastic properties. Many specialized esters such as chiral (-)-menthyloxyacetates, furan-2-carboxylates, or crown-ether-containing acylates have been prepared on the laboratory scale and characterized by NMR spectroscopy. Various procedures have been applied, using anhydrides and acyl chlorides as acylating agents in combination with such bases as pyridine, 4-dimethylaminopyridine (DMAP), or iV,iV -carbonyldi-imidazole. The substitution pattern of cellulose acetates has also been modified by postchemical enzymatic deacetylation. Cellulose 6-tosylates have been used as activated intermediates for nucleophihc substitution to afford 6-amino-6-deoxy, 6-deoxy, or 6-deoxy-6-halo-celluloses. ... 

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