Nitrobenzamides, hydrolysis

At lower acidities the iV-nitrobenzamides and /V-methyl-.V-nitrobenzamides have a hydrolysis mechanism that is not acid-catalyzed for these cases plots of log kv - log h2o are linear, as for the acyhmidazoles discussed above. N-Nitroacetamide also hydrolyzes in this way.291 The proposed mechanism is given in Scheme 17, written for TV-nitroacetamide if the hydration shown is a pre-equilibrium (this is a carbonyl compound with a strong electron-withdrawing group attached, so this is likely), only one water molecule will appear in the rate expression (the difference between 3 and 2), as observed.287 Some evidence for hydroxide-catalyzed processes at the very lowest acidities was also found for some of these compounds.287... 

Olsen and co-workers used a solution of nitronium tetrafluoroborate in acetonitrile for the V-nitration of acetamides and urethanes at —30°C. The following nitramides were obtained by this method V-nitroacetamide (13 %), V-nitro-2-chloroacetamide (55 %), V-nitro-n-butylacetamide (40 %), V-nitrobenzamide (53 %), ethyl V-nitro-n-butylcarbamate (91 %) and V-nitrosuccinimide (43 %). The low yield of V-nitroacetamide, a primary nitramide, is attributed to competing hydrolysis due to the release of tetrafluoroboric acid as the reaction progresses. The scope of the reaction is improved by moving to more basic solvents like ethyl acetate, 1,4-dioxane and trimethyl phosphate. ... 

Evidence comes from comparative rate studies.216 Thus 71 was hydrolyzed about 105 times faster than benzamide (PhCONH2) at about the same concentration of hydrogen ions. That this enhancement of rate was not caused by the resonance or field effects of COOH (an electron-withdrawing group) was shown by the fact both o-nitrobenzamide and terephthal-amic acid (the para isomer of 71) were hydrolyzed more slowly than benzamide. Many other examples of neighboring-group participation at a carbonyl carbon have been reported.2 7 It is likely that nucleophilic catalysis is involved in enzyme catalysis of ester hydrolysis. 

An H acidity function scale has been constructed for methoxide ion in methanol and its mixtures with DMSO (10-80%, v/v) using the dissociation of 11 amides (114) as the anchors for the scale.The degradation pathways of the anti-flammatory and analgesic lomoxicam (115), which contains an amide bond, have been examined recently. In acid, cleavage of the amide bond was the main reaction path and in alkaline and neutral solution the proton shift of the enolic hydroxyl initiated the major degradation pathway. The mechanism of hydrolysis of some A-nitrobenzamides (116) in strong acid follow an -1 mechanism with O-protonation but, in more moderate acid, they exhibit a neutral water-catalysed mechanism. /V-Methyl-/V-nitroacetamide (117) shows only the neutral water-catalysed process. Nitrourea follows an, 4-1 acid-catalysed mechanism. ... 

A vast amount of research has shown that the Hammett relationship holds for hundreds of sets of reactions. (Ionization of 40-odd p-substituted benzoic acids, for example, is one set.) By use of just two tables—one of a constants and one of p constants— we can calculate the relative Keq s or relative rates for thousands of individual reactions. For example, from the a value for W-NO2 ( + 0.710) and the p value for ionization of benzoic acids in water at 25" (+1.000), we can calculate that Ka for m-nitrobenzoic acid is 5.13 times as big as the Ka for benzoic acid. Using the same acid-catalyzed hydrolysis of benzamides in 60% ethanol at 80° (-0.298), we can calculate that m-nitrobenzamide will be hydrolyzed only 0.615 as fast as benzamide. 

With aromatic amides, hydrolysis prior to rearrangement may occur to such an extent that the yield is lowered seriously. Amides like p-nitrobenzamide, having a substituent which withdraws electrons from O... 

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