Hydrolysis and Related Reactions

Ester hydrolysis is one of the most rudimentary manipulations in organic chemistry. The 1-ester function in a malate can be selectively hydrolyzed to an acid by treatment with one equivalent of potassium hydroxide. In this way 7a is converted to 13 in high yield [3]. 

Hydrolysis can also be accomplished under enzymatic conditions. Dimethyl (5)-malate (2), when incubated with pig liver esterase (400 units per 43 mmol of substrate), is hydrolyzed regioselectively to the optically pure acid 14 [22]. 

L-j -Malamidic acid (16) is the penultimate intermediate in the synthesis of (5)-isoserine (17), an amino acid component of several biologically active peptides. Treatment of 16 with sodium hypochlorite in alkaline solution produces 17 (28% yield) via a Hofmann rearrangement [23]. 

Significantly higher yields can be realized by converting 16 to its 0-acetyl derivative (acetic anhydride, pyridine, acetonitrile) followed by treatment with bis[trifiuoro-acetoxy]-phenyliodine. The resulting 0-acetyl (5)-isoserine is then hydrolyzed to 17 with concentrated 

As we have just seen, hydrolysis of malic acid derivatives at the 1-position is relatively straightforward. But what if a chemist desires a malic acid half ester in which only the 4-carboxyl exists as a free acid Derivatives of this type are also accessible from L-malic acid through C-1 site-selective reactions. 

Hydrolysis and Related Reactions.—Aspects of the hydrolysis of glycosides have been dealt with by Capon in his review of carbonyl compounds  

Tachikawa, K. Ohaku, K. Temi, and K. Matsuzaki, Makromol. Chem., 1977, 178,1929. N. K. Kochedcov and I. V. Obruchnikov. Tetrahedron Letters, 1977, 57. 

Kinetic studies of the hydrolyses of a series of mono- and di-nitrophenyl a-L-arabinopyranosides and p-D-galactopyranosides by E. coli p-D-galactosidase have indicated that the hydroxymethyl-group of the D-galactopyranosides assists only in binding and does not destabilize the substrate-enzyme complex. Other studies with P-D-galactosidase are mentioned in Chapter 9. 

A neat method for cleaving acid-sensitive triterpenoid and steroid aglycones from L-arabinopyranosides and D-galactopyranosides involved oxidation (DMSO-acetic anhydride) of the corresponding 3,4-0-isopropylidene derivative to the glycopyranosidulose, which can be cleaved on u.v.-irradiation in t-but-anol. Photolysis of the model acetals (61) gave, depending on the substituents 

Bernasconi, L. Cottier, and G. Descotes, Bull. Soc. chim. France, 1977,101. 

Hydrolysis and Related Reactions.— The hydrolysis of 2,4-dinitrophenyl jS-D-galactopyranoside at 25 °C has been found to be independent of pH between pH 1.6 and 8.4, whereas specific base-catalysis occurs above pH 8.4. Studies of related glycosides of pentoses, 6-deoxyhexoses, and 6-chloro-6-deoxyhexoses furnished evidence supporting the A-1 mechanism for the hydrolysis of these glycosides with acid. 

The enzymic hydrolysis of some 4-nitrophenyl 2-aroylamino-2-deoxy-jS-D-glucopyranosides has been reported.  

A quantum mechanical study of the distribution of charge in alkyl and aryl hexopyranosides has demonstrated a correlation between the rate of acid-catalysed hydrolysis and either the inductive effects of the alkyl groups or the char on the glycosidic oxygen atoms of aryl glycosides.  

Evidence has been obtained for the formation of a stable glycosyl-enzyme intermediate in the short-term reaction between a-D-glucosidase and methyl a-D-[ C]glucopyranoside the intermediate appears to be covalently linked. Related studies on the enzymic hydrolysis of 2-nitrophenyl )8-D-galactopyranoside at -10 C have also been reported.  

Hydrolysis and Related Reactions. These reactions involve nucleophilic substitution and not electrophilic attack on sulphur. The alkaline decomposition of thiourea and A -ethylthiourea, which is first order in thiourea and NaOH, has 

Cyclization. Formation of heterocycles is the most frequently used reaction of thioureas, and the literature until 1973 has been reviewed. This section deals with the different types of heterocycles derived from thioureas. 

The thiiran groups of thia-tris-a-homobenzenes (37) and (38) are formed from the tris(oxiran) (36) via isothiouronium salts. Interconversion of epoxides into episulphides has also been reported in the carbohydrate series.  

Setaka, H. Yamamoto, and T. Kwan, Chem. and Pharm. Bull. Japan), 1974, 22, 962. 

Cyclization of iS -methylsulphinylmethyl-isothiouronium salts yields azathiets (39).  

The possibility of effecting selective cleavage of glycosidic linkages in partially methylated polysaccharides by oxidation of the unsubstituted hydroxy-groups and base-catalysed /3-elimination from the oxidized product (see Vol. 6, pp. 116 and 157) has been tested with the methylated disaccharide (20). The results 

Additional physical and analytical data for the u.v.(253.7 nm)-photolysis of phenyl /3-D-glucopyranosides in aqueous solution have been provided. The data permit a number of experimental observations to be explained, although it is still not possible to propose a valid mechanism for o-glucosidic bond scission. 

Protection of the anomeric centre of sugars with the trichloroethyl group, which can be removed with zinc and dilute acid, is mentioned in Chapter 20. 

The configuration at the benzylic centre of naturally occurring and synthetic glycosides of mandelonitrile can be assigned by n.m.r. spectroscopy, since the chemical shifts of the methine and anomeric protons depend on the configuration at the benzylic centre. 

The a- and jS-anomers of ethyl 2-amino-2-deoxy-D-glucopyranoside have been separated on cationic resins prior to A-acylation with a series of fatty-acid anhydrides.  

The literature is replete with examples of participation by ionized and un-ionized hydroxyl groups in a variety of hydrolysis reactions. Although a more complete discussion of intramolecular catalysis in hydrolytic reactions is presented in Volume 2, some examples are included here to demonstrate the extent to which this effect is observed. 

Lactonization of hydroxy acids has been used as one means of gaining information on the propensity of the hydroxyl group in a certain configuration to interact with a carboxyl group. The relative rates for the acid-catalyzed lactonization of the hydroxy acids (242)-(246) are 1,3.9, 4.2, 84, and 13,000, respectively (see the third reference in Ref. 133 some of the structures in this reference are incorrect cf. Ref. 134). This variation, which obviously reflects differences in AS (see Chapter 2), may result in part 

Nucleophilic participation by the hydroxyl group has been noted in acid-catalyzed studies of systems other than carboxyl groups. In dilute aqueous acid solution, methyl furanosides [e.g., (248)] were formed by ring closure during hydrolysis of the acetal bonds of the acyclic dimethyl acetals of glucose (247) and galactose.It was estimated that the rates of these cyclizations were faster than the expected unassisted rates of hydrolysis. 

Hydroxyl groups also participate as nucleophiles in a variety of other acid-catalyzed cyclizations of synthetic utility. One example is the Ritter reaction, which normally produces amides upon reaction of olefins or alcohols with nitriles. Cyclization occurs with 1,3-diols, hydroxy alkenes, or epoxides. Examples of each are given in Eqs. (74)-(76). 

0 -7 Participation has been invoked to account for the base-catalyzed hydrolysis of 3-methyluridine (249). The product 2-methylurea riboside (250) was said to result from hydroxyl participation, since methylation of the 5 -hydroxyl group inhibits this reaction. 

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Volume 8 Volume 9 Volume 10 Volume 12 Volume 13 Proton Transfer Addition and Elimination Reactions of Aliphatic Compounds Ester Formation and Hydrolysis and Related Reactions Electrophilic Substitution at a Saturated Carbon Atom Reactions of Aromatic Compounds Section 5. POLYMERISATION REACTIONS (3 volumes)... 

Ester Formation and Hydrolysis and Related Reactions 13 Reactions of Aromatic Compounds... 

Base catalysis, general, of ester hydrolysis and related reactions, 5, 237 Basicity of unsaturated compounds, 4, 195... 

Catalysis, enzymatic, physical organic model systems and the problem of, 11,1 Catalysis, general base and nucleophilic, of ester hydrolysis and related reactions, 5,237 Catalysis, micellar, in organic reactions kinetic and mechanistic implications, 8,271 Catalysis, phase-transfer by quaternary ammonium salts, 15,267 Catalytic antibodies, 31,249... 

Nuclear motion, the principle of least, and the theory of stereoelectronic control, 24, 113 Nucleophiles, partitioning of carbocations between addition and deprotonation. 35, 67 Nucleophilic aromatic photosubstitution, 11,225 Nucleophilic catalysis of ester hydrolysis and related reactions, 5,237 Nucleophilic displacement reactions, gas-phase, 21, 197... 

Gaseous carbonium ions from the decay of tritiated molecules, 8, 79 General base and nucleophilic catalysis of ester hydrolysis and related reactions, 5, The Gomberg Century Free Radicals 1900-2000, 36, 1 Gomberg and the Nobel Prize, 36, 59... 

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