Nitro esters, hydrolysis

It is frequently advisable in the routine examination of an ester, and before any derivatives are considered, to determine the saponification equivalent of the ester. In order to ensure that complete hydrolysis takes place in a comparatively short time, the quantitative saponi fication is conducted with a standardised alcoholic solution of caustic alkali—preferably potassium hydroxide since the potassium salts of organic acids are usuaUy more soluble than the sodium salts. A knowledge of the b.p. and the saponification equivalent of the unknown ester would provide the basis for a fairly accurate approximation of the size of the ester molecule. It must, however, be borne in mind that certain structures may effect the values of the equivalent thus aliphatic halo genated esters may consume alkali because of hydrolysis of part of the halogen during the determination, nitro esters may be reduced by the alkaline hydrolysis medium, etc. 

One effective method for synthesis of tryptophan derivatives involves alkylation of formamido- or acetamido- malonate diesters by gramine[l,2]. Conversion to tryptophans is completed by hydrolysis and decarboxylation. These reactions were discussed in Chapter 12. An enolate of an a-nitro ester is an alternative nucleophile. The products can be converted to tryptophans by rcduction[3,4],... 

Serine peptidases can hydrolyze both esters and amides, but there are marked differences in the kinetics of hydrolysis of the two types of substrates as monitored in vitro. Thus, the hydrolysis of 4-nitrophenyl acetate by a-chy-motrypsin occurs in two distinct phases [7] [22-24]. When large amounts of enzyme are used, there is an initial rapid burst in the production of 4-nitro-phenol, followed by its formation at a much slower steady-state rate (Fig. 3.7). It was shown that the initial burst of 4-nitrophenol corresponds to the formation of the acyl-enzyme complex (acylation step). The slower steady-state production of 4-nitrophenol corresponds to the hydrolysis of the acetyl-enzyme complex, regenerating the free enzyme. This second step, called deacylation, is much slower than the first, so that it determines the overall rate of ester hydrolysis. The rate of the deacylation step in ester hydrolysis is pH-dependent and can be slowed to such an extent that, at low pH, the acyl-enzyme complex can be isolated. 

Nitroamide, the simplest of the nitroamines, is formed by the action of dilute acid on potassium nitrocarbamate, which itself results from the nitration of urethane and the subsequent hydrolysis of the nitro ester by means of alcoholic potassium hydroxide. 

Fig. 3. Examples of hydrolysis reactions performed in microemulsions. Scheme 1 alkaline hydrolysis of 4-nitrophenyldiphenyl phosphate. Scheme 2 catalysis of phosphate ester hydrolysis by a iodosobenzoate. Scheme 3 alkali- and lipase-catalysed hydrolysis of 4-nitro-phenyldecanoate...

The Taft analysis has the working disadvantage that it requires two measurements to define a a value, and it also suffers from the problem that the parameters of some substituents cannot be obtained either because the ester decomposes too quickly for measurements to be made or because it would not decompose by ester hydrolysis. Such restrictions apply to the halogen substituents, nitrile or the nitro group, which would require study of such compounds as Hal-CO-OR, NC-CO-OR and O2N-CO-OR. This problem can be solved by use of Taft analysis of esters of the type X-CH2-CO-OR instead of X-CO-OR. In this analysis the similarity coefficient, p, for the substituted acetic acid derivatives is attenuated by 0.41 from the set value of p = 2.48 for the formic acid derivatives (Equations 8 and 9). The a constants based on formic acid derivatives are recorded in Table 1 in Appendix 3. ... 

Similarly, aliphatic a-nitro esters and nitrogen oxides do not give compounds resembling pseudonitrols but lose the nitro group and afford the aliphatic nitroso esters.164,279,280 On nitrosation of ethyl 2-benzoylpropionate the hydrolysis can be avoided and ethyl 2-benzoyl-2-nitrosopropionate can be isolated.281... 

A study has been conducted on the effects that sugar alditols and aminoalditols have on the rate of phosphate ester hydrolysis in the substrates bis(4-nitro-phenyOphosphate and supercoiled DNA, when catalysed by lanthanide cations. See Chapter 23 for the effect of solvents on the relative stabilities of the complexes formed between alditols and lanthanide cations. 

An interesting example describing the asymmetric synthesis of a-methyl L-amino acids is shown in Scheme 2.39. Hydrolysis of the o-a-nitro esters from the D/L-mixture leads to the formation of the corresponding labile a-nitroacids, which readily decarboxylate to yield secondary nitro compounds. The L-configured enantiomers of the unhydrolyzed esters could be recovered in high optical purity and these were further transformed into a-methyl L-amino acid derivatives [259]. 

Reaction of ethyl crotonate and nitroethane in the presence of the basic 1,8-diaza-bicyclo[5.4.0]undec-7-ene (DBU) led to nitro-ester 3.49 in 74% yield.31 Catalytic hydrogenation of the nitro group and acid hydrolysis produced 3-methyl-4-amino-butanoic acid, 3.50. Choosing different conjugated esters as starting materials led to formation of 3-ethyl- (59% overall yield) 3-propyl- (51% overall yield) 3-isopropyl-(62% overall yield) 3-butyl- (56% overall yield) 3-sec-butyl- (60% overall yield) 3-isobutyl- (58% overall yield) and, 3-r-butyl-4-aminobutanoic acid (31% overall yield).31 The yields observed in this study clearly show that conjugate addition of nitro enolates is a synthetically useful process. 

It was shown (Overberger and Sannes, 1974) that the polymeric imidazole was about 10 times as reactive as the monomeric imidazole in the hydrolysis of p-nitrophenyl acetate and certain 3-nitro-4-acyloxybenzoic acids. The increased catalytic activity of the polymeric imidazoles has been attributed to the cooperative interactions of the imidazole moieties anchored on the polymer chain at regular intervals (Scheme 13-3). Although practical applications of polyvinylimidazoles as catalytic nucleophiles in ester hydrolysis have not been made, it appears that they can provide quite effective and reusable solid-phase catalysts for such reactions. 

Nitro-esters. Compounds of this class should be hydrolysed as described on pages 127, 128 and the products of hydrolysis identified in the usual manner (see nitro-acids, above). See also Tables 5 and 8. 

The mother liquors from the washings and recrystallisations are saved for the recovery of the 4-nitrophthalic acid. The combined mother liquors ore concentrated to a small bulk and the acid is extracted with ether. Upon esterification by the Fischer - Speier method, the 3-nitro acid forms only the acid ester and may be removed by shaking the product with sodium carbonate solution, whilst the neutral ester of 4-iiitrophthalic acid remains unaffected. Hydrolysis of the neutral ester gives the pure 4-nltrophthalio acid, m.p. 165°. 

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