Hydrolysis sensitizing side groups

Amino acid ester side groups are not the only units that sensitize the system to hydrolysis. The imidazolyl group has an even greater effect.197-198-219 For example, polymer 3.86, prepared by the reaction of poly(dichlorophosphazene) with imidazole, is so unstable hydrolytically that it decomposes in moist air to imidazole, phosphate, and ammonia. This is too high a sensitivity for most biomedical applications. Hence, an emphasis has been placed on the study of polymers such as 3.87 in which a hydrophobic cosubstituent group, such as aryloxy, is present to reduce the rate of erosion. 

The use of an appropriate hydrolytic procedure for the conversion of diethyl 2,2-diethoxyeth-ylphosphonate into diethyl 1-formylmethylphosphonate is an important step in the reaction sequence. A high concentration and a large excess of acid should be avoided to prevent hydrolysis of the acid-sensitive ester groups attached at phosphorus. The use of drastic conditions may provoke undesired side reactions, resulting in loss of the expected product. In the case of diethyl 1-fonnyhnethylphosphonate, a variety of acids have been used H2SO4, H2SO4-... 

Crommen et al. (1992) pi epared poly[(organo)phosphazenes] bearing side groups with hydrolysis sensitive ester functions the so called depsipeptide-esters (Kgtoiir . ... 

Polyester-based PUs are more sensitive to hydrolytic cleavage than polyether-based PUs. However, the introduction of bulky alkyl side groups into a hydroxyl-terminated polyester (e.g., poly(2,4-diethyl-l,5-pentamethyleneadipate) yields PUs that are more hydrolytically stable with regard to hydrolysis [16]. Polyethylene oxide-based PUs exhibit water sensitivity due to their hydrophihcity and the water-absorbing capacity... 

An acylation reaction occurs on the amine terminal functions and, possibly, on some side groups (e.g., the hydroxyls) and thus leaves the carboxyl groups free, which must be neutralized. Because these surfactants contain amide functions, they are sensitive to hydrolysis. Also, they are prone to microbial degradation if they are contaminated and not appropriately preserved. They are rather tolerant to water hardness. 

Weikel, A.L., Krogman, N.R., Nguyen, N.Q., Nair, L.S., Laurencin, C.T., AUcock, H.R. Polyphosphazenes that contain dipeptide side groups synthesis, characterization, and sensitivity to hydrolysis. Macromolecides 42(3), 636-639 (2009). doi 10.1021/ma802423c... 

Many functional groups are stable to alkaline hydrogen peroxide. Acetate esters are usually hydrolyzed under the reaction conditions although methods have been developed to prevent hydrolysis.For the preparation of the 4,5-oxiranes of desoxycorticosterone, hydrocortisone, and cortisone, the alkali-sensitive ketol side chains must be protected with a base-resistant group, e.g., the tetrahydropyranyl ether or the ethylene ketal derivative. Sodium carbonate has been used successfully as a base with unprotected ketol side chains, but it should be noted that some ketols are sensitive to sodium carbonate in the absence of hydrogen peroxide. The spiroketal side chain of the sapogenins is stable to the basic reaction conditions. 

Maleic acid is a linear four carbon molecule with carboxylate groups on both ends and a double bond between the central carbon atoms. The anhydride of maleic acid is a cyclic molecule containing five atoms. Although the reactivity of maleic anhydride is similar to other cyclic anhydrides, the products of maleylation are much more unstable toward hydrolysis, and the site of unsaturation lends itself to additional side reactions. Acylation products of amino groups with maleic anhydride are stable at neutral pH and above, but they readily hydrolyze at acid pH values around pH 3.5 (Butler et al., 1967). Maleylation of sulfhydryls and the phe-nolate of tyrosine are even more sensitive to hydrolysis. Thus, maleic anhydride is an excellent reversible blocker of amino groups to temporarily mask them from reactivity while another... 

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