Hydrolysis in Alkali

The main disadvantage of alkaline hydrolysis is that much more destruction of amino acids occurs than with acid. The chief amino acids to be affected are cysteine, serine, threonine and arginine. Wieland and Wirth (1949) have used paper chromatography to study the effect of strong alkali on certain amino acids. They found that serine broke down to give appreciable quantities of glycine and alanine, threonine 

Sanger and Tuppy (1951a) studied an alkaline hydrolyzate of an oxidized insulin fraction. Although the conditions used would not have been expected to cause any destruction of free serine or threonine, it was evident that most of these residues in the protein had been broken down. Thus, for instance, Gly.Pro was found in the alkaline hydrolyzate whereas Thr.Pro was present in the acid hydrolyzate. The arginine residues were also converted to ornithine (or citrulline). 

Extensive racemization of the amino acids also occurs in the presence of alkali, which may complicate the results of a partial hydrolysis experiment (Levene and Bass, 1928, 1929). 

Alkaline hydrolysis offers a possible advantage for the investigation of tryptophan peptides since tryptophan itself is more stable in alkali than in acid (Lugg, 1938 Brand and Kassell, 1939). 

The possibility that long chain bases, such as hexyl trimethyl ammo- 

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R = H) is made similarly from its ester (789 R = Et), itself prepared by several obvious steps (see (i) below) from the pyrimidine (788) which can be made by primary synthesis (66AP362). 4-Aminopyrimidine-5-carbonitrile (790 R = CN), which may be made by primary synthesis, undergoes hydrolysis in alkali to the amino acid (790 R = C02H) it may be made similarly from the amide (790 R = CONH2) (53JCS331). 

The evidence obtained by Evans16 64 66 is based largely on the formation of lactic acid by the action of hot alkali on reducing disaccharides. Free D-glucose may be converted by alkali to lactic acid, in a yield of 60% (1.2 moles/mole). If a disaccharide such as cellobiose underwent direct hydrolysis in alkali to two moles of D-glucose, the yield of lactic acid would presumably be 2.4 moles/mole. However, the maximum yield from cellobiose is 1.2 moles/mole, or that which would be expected from half of the D-glucose present in the molecule. 

Scheme 3 Carbamate hydrolysis in alkali. Subscript Lg refers to substituent change in the leaving group (-OAr) subscript Nuc refers to substituent change in the nucleophile. / sc refers to change in effective charge...

When colchicine is heated with acetic anhydride it gives the enol acetate (444, R=Ac), which is partially hydrolysed by acid-washed alumina to the iv-acetyl compound (444, R=H). This, on mild hydrolysis in alkalis, yields the ketone (445),... 

The hydrolysis by alkali is illustrated by the following experimental details for benzamido. Place 3 g. of benzamide and 50 ml. of 10 per cent, sodium hydroxide solution in a 150 ml. conical or round-bottomed flask equipped with a reflux condenser. Boil the mixture gently for 30 minutes ammonia is freely evolved. Detach the condenser and continue the boiling in the open flask for 3-4 minutes to expel the residual ammonia. Cool the solution in ice, and add concentrated hydrochloric acid until the mixture is strongly acidic benzoic acid separates immediately. Leave the mixture in ice until cold, filter at the pump, wash with a little cold water and drain well. RecrystaUise the benzoic acid from hot water. Determine the m.p., and confirm its identity by a mixed m.p. test. 

The acetyl group in aconitine may be eliminated in two other ways (a) by heating aconitine in sealed tubes with methyl alcohol, when methylbenzoylaconine, m.p. 210-1°, is formed, or (b) by heating the alkaloid at its melting-point, when pyraconitine, C32H43O9N, m.p. 167-5° (171°, Schulze), [a] ° — 112-2° (EtOH), is formed. The latter yields crystalline, laevorotatory salts, and on hydrolysis by alkalis affords benzoic acid and pyraconine, C2sH3gOgN, amorphous, [a]n — 91° (HgO), but yields a crystalline hydrochloride, B. HCl. 2-5H20, m.p. 154° (135°, Schulze), Md - 102° (HgO) (- 124-6°, Schulze). ... 

Acylglycerols can be hydrolyzed by heating with acid or base or by treatment with lipases. Hydrolysis with alkali is called saponification and yields salts of free fatty acids and glycerol. This is how soap (a metal salt of an acid derived from fat) was made by our ancestors. One method used potassium hydroxide potash) leached from wood ashes to hydrolyze animal fat (mostly triacylglycerols). (The tendency of such soaps to be precipitated by Mg and Ca ions in hard water makes them less useful than modern detergents.) When the fatty acids esterified at the first and third carbons of glycerol are different, the sec-... 

Nucleosides are much more water-soluble than the free bases because of the hydrophilicity of the sugar moiety. Like glycosides (see Chapter 7), nucleosides are relatively stable in alkali. Pyrimidine nucleosides are also resistant to acid hydrolysis, but purine nucleosides are easily hydrolyzed in acid to yield the free base and pentose. 

Dilute aqueous solutions of sulfamic acid are stable for many months at room temperature but at higher temperatures hydrolysis to NH4[HS04] sets in. Alkali metal salts are stable in neutral and... 

As the free acids present in essential oils consist in the main of acetic acid, they are, when necessary, calculated in terms of acetic acid in the same way the esters are conventionally calculated from the alkali required for their hydrolysis, in terms of the principal ester present, for example, linalyl acetate in the case of lavender and bergamot oUs, and geranyl tiglate in the case of geranium oil. 

It has been found that the tris(tert-butyloxycarbonyl) protected hydantoin of 4-piperidone 2, selectively hydrolyses in alkali to yield the N-tert-butyloxycarbonylated piperidine amino acid 3. The hydrolysis, which is performed in a biphasic mixture of THF and 2.0M KOH at room temperature, cleanly partitions the deprotonated 4-amino-N -(tert-butyloxycarbonyl)piperidine-4-carboxylic acid into the aqueous phase of the reaction with minimal contamination of the hydrolysis product, di-tert-butyl iminodicarboxylate, which partitions into the THF layer. Upon neutralization of the aqueous phase with aqueous hydrochloric acid, the zwitterion of the amino acid is isolated. The Bolin procedure to introduce the 9-fluorenylmethyloxycarbonyl protecting group efficiently produces 4.8 This synthesis is a significant improvement over the previously described method9 where the final protection step was complicated by contamination of the hydrolysis side-product, di-tert-butyl iminodicarboxylate, which is very difficult to separate from 4, even by chromatographic means. 

Sucrose degrades in acid far more easily than in alkali, and invert sugar (the product of acid hydrolysis) is far more reactive in alkali than in acid. 

PETP flakes produced from used soft drinks bottles were subjected to alkaline hydrolysis in aqueous sodium hydroxide. A phase transfer catalyst (trioctylmethylammonium bromide) was used to enable the depolymerisation reaction to take place at room temperature and under mild conditions. The effects of temperature, alkali concentration, PETP particle size, PETP concentration and catalyst to PETP ratio on the reaction kinetics were studied. The disodium terephthalate produced was treated with sulphuric to give terephthalic acid of high purity. A simple theoretical model was developed to describe the hydrolysis rate. 17 refs. 

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