P-Nitrophenyl salicylate

The rate of alkaline ethanolysis of p-nitrophenyl salicylate by alkali metal ethox-ides (EtOM M = K, Na, Li) decreased as the concentration of EtOM increased. This inhibitory effect was attributed to a stabilization of the oxyanion of the substrate (9 ) through formation of a six-membered cyclic complex with M+ (i.e. 10) (Scheme 4). Kinetic data pointed to a unimolecular mechanism that favoured, on the basis of theoretical calculations, the formation of an intermediate ketene (11) from (9-) (Scheme 5). ... 

Although metal-promoted hydrolysis of phosphate esters is a topic of very current interest (Section 61.4.4), little work has been published dealing with the effects of metal ions on the hydrolysis of sulfate esters. The acid-catalyzed hydrolysis of aryl sulfates has been shown to occur by an A-l mechanism (Scheme 34).434 Nucleophilic catalysis by amines has been observed in the hydrolysis of p-nitrophenyl sulfate435 and intramolecular carboxyl group catalysis occurs with salicyl sulfate436 as with salicyl phosphate. 

The effects of [1-CD on the kinetics of hydrolysis of salicylic acid esters (199 R = Me, m-nitrophenyl and p-nitrophenyl) have been examined, as has the Smiles rearrangement of (199 R = Me). The latter was accelerated by [1-CD but its hydrolysis was not affected. Various other effects are reported for the other esters.169... 

On the other hand, phosphorane intermediates are not expected to be involved in the hydrolysis of phosphate monoesters, so the effective observed catalysis by the carboxyl group of salicyl phosphate 3.21 [51] (Scheme 2.26) is presumed to be concerted vith nucleophilic attack. (The hydrolysis reaction involves the less abundant tautomer 3.22 of the dianion 3.21, and the acceleration is >10 -fold relative to the expected rate for the pH-independent hydrolysis of the phosphate monoester dianion of a phenol of pK 8.52.) However, this system differs from the methoxy-methyl acetals discussed above, in that there is a clear distinction between neutral nucleophiles, which react through an extended transition structure similar to 3.16 in Scheme 2.23, and anions, which do not react at a significant rate, presumably because of electrostatic repulsion. This distinction is well-established for the dianions of phosphate monoesters with good leaving groups (p-nitrophenyl [52] and... 

Most of the quantitative work in this area has been done with putative models for lysozyme action. Thus, synchronous acetamido group participation and intramolecular general acid catalysis was held to be responsible for the modest rate enhancement of compound LXI compared with the p-nitrophenyl compound or salicyl glucoside... 

It is therefore clear that any intramolecular catalysis of the hydrolysis of the ionized form of the mixed acetic salicylic anhydride can produce only a small rate enhancement. This is reasonable since the ratio in the rates of hydrolysis of the ionized to un-ionized forms of p-nitrophenyl 5-nitrosalicylate is about 30 [28], and a reduced catalytic effect would be expected with a less basic dinitrophenolate ion. It has recently been claimed, on the basis of the variation of fc(ionized) with atom fraction of deuterium for hydrolysis in HjO—D2O mixtures, that the acetic salicylic anhydride reacts with 39 per cent attack at salicyl carbon and 61 per cent attack at acetyl carbon [86]. This conclusion does, however, depend on several unproven assumptions. 

Hydroxy-5-[(4-nitrophenyl)azo]benzoic acid, 9CI. 5-[(p-Nitrophenyl)azo]salicylic acid. 4 -Nitro-4-oxyazobenzene-3-carboxylic acid. Alizarine orange 2GN. C.I. Mordant orange 1. Azochromol orange R. Brasilon chrome orange R. Kenachrome orange. C.I. 14030. Numerous other proprietary names [2243-76-7]... 

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