Base-catalysed Degradation

M. S. Feather and S. J. Eitelman, Synthesis of a derivative of l-deoxy-2,3-D-t/jreo-(D-erythro) hexodiulose, an intermediate in the acid and base catalysed degradation of hexoses, J. Carbohydr. Chem., 7 (1988) 251-262. 

Commercial alumina packing materials for HPLC have lower column efficiency values and lower specific surface areas (typically 100-250 m g ) which leads to a lower sample capacity. Another disadvantage of alumina is that the highly active surface has a tendency to catalyse deterioration reactions, which is particularly important for molecules which undergo base-catalysed degradation, because of the basic nature of the alumina surface. 

The base-catalysed degradation of the ring of isoxazolium salts is particularly easy, requiring only alkali metal carboxylates to achieve it. The mechanism, illustrated for the acetate-initiated degradation of 2-methyl-5-phenylisoxazolium iodide, involves initial 3-deprotonation with cleavage of the N-O bond subsequent rearrangements lead to an enol acetate which rearranges to a final keto-imide. 

The base-catalysed degradation of the ring of isoxazolium salts is particularly easy, requiring only alkali metal carboxylates to achieve it. The mechanism, ... 

Details of the selective cleavage of o-glucuronidic linkages in saponins have been published (see Vol. 10, p. 117). A modified procedure for determining the sites of attachment of hexuronic acid residues in methylated acidic polysaccharides by base-catalysed degradation has been modelled on experiments with the methylated aldobiouronic acid derivative (430), which eliminated methyl 2,3,4-tri-O-methyl-p-D-glucopyranoside (89%) on treatment with sodium methylsulphinyl-methanide in DMSO at room temperature. When this procedure is applied to... 

Tomasz M, Lipman R, Lee M S, Verdine G L, Nakanishi K 1987 Reaction of acid activated mitomycin C with calf thymus DNA and model guanines Elucidation of the base-catalysed degradation of N7-alkylguanine nucleosides. Biochem 26 2010-2027... 

One published stereoselective synthesis uses the base-catalysed cycllsation oi optically active enone (2) with a prolonged reaction time to get cis-(3) which is converted into (1) by degradation of the oxime. 

Epoxides can react with alcohols via acidic or basic catalysed reaction mechanisms. However, since both strong acids and bases will degrade the cell wall polymers of wood, the reaction is usually catalysed via the use of amines, which are more strongly nucleophilic than the OH group. For example, whereas the production of epoxy-phenolic resins requires temperatures in the region of 180-205 °C, reaction between epoxides and primary or secondary amines takes place at 15 °C (Turner, 1967). Reaction of epoxides with wood often involves the use of tertiary amines as catalysts (Sherman etal., 1980). The sapwood is more reactive towards epoxides than heartwood (Ahmad and Harun, 1992). 

Base-catalysed quaternary ammonium salts give alkenes and 3° amines. This reaction is known as Hofmann elimination or Hofmann degradation. Amines can readily be converted to quaternary ammonium salt by the treatment of excess primary alkyl halides, and then Ag20 and H2O. Quaternary ammonium salts undergo E2 elimination, when heated with NaOH to give alkenes and tertiary amines. Thermal decomposition of a quaternary ammonium salt by NaOH to an alkene is known as Hofmann elimination. 

As any of the degradation reactions depends on the presence of a strong base, it is evident that neutralizing the base supports to the stabilization of the polymer. Thus, after having extracted the polymer either by water or by diluted acids, and after having dried the polymer, the decrease of the viscosity is much slower than in the case of non extracted polymer (103) (fig. 4). This makes it possible to apply the base catalysed polymerization for the production of polyamides for extruding and molding purposes. 

We should also note that the oxidative degradation of some dmgs in solution may be pH-dependent for example, the oxidation of prednisolone is base-catalysed. Similarly, the oxidation of morphine occurs more rapidly in alkaline or neutral solution than in acid solution. The reason for this may be the effect of pH on the oxidation-reduction potential, Eq, of the drug. 

Prevention of deamidation If the deamidation occurs by a general acid-base mechanism then the optimum pH for a peptide formulation will usually be about 6, where both rates are at their minimum. If the deamidation occurs through the cyclic imide intermediate it is, in principle, preferable to formulate at a low pH since this type of deamidation is base-catalysed. This may not be feasible in practice, however, since other routes of degradation tend to predominate at lower pH and a compromise must then be sought. It is well established that deamidation rate may be affected markedly by buffer components and hence care must be taken in the choice of buffer used in the control of pH. In general it is found that the phosphate anion is most problematic in its effect on the rates of deamidation. 

The processing of polymers should occur with dry materials and with control of the atmosphere so that oxidative reactions may be either avoided, to maintain the polymer s molar mass, or exploited to maximize scission events (in order to raise the melt-flow index). The previous sections have considered the oxidative degradation of polymers and its control in some detail. What has not been considered are reactions during processing that do not involve oxidation but may lead to scission of the polymer chain. Examples include the thermal scission of aliphatic esters by an intramolecular abstraction (Scheme 1.51) (Billingham et al., 1987) and acid- or base- catalysed hydrolysis of polymers such as polyesters and polyamides (Scheirs, 2000). If a polymer is not dry, the evolution of steam at the processing temperature can lead to physical defects such as voids. However, there can also be chemical changes such as hydrolysis that can occur under these conditions. 

Yang, S.K. Base-catalysed rearrangement of temazepam. J.Pharm.Biomed.Anal., 1994, 12, 209-219 [simultaneous degradation products]... 

The log k-pH profiles indicated specific-acid and specific-base catalyses and there were inflection points near pH 6 and 9 corresponding to the piCa-i P- a-2 values. Arrhenius data showed that the degradation at room temperature was negligible at all pH values studied."... 

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