Semicarbazone formation

Not all reactions can be fitted by the Hammett equations or the multiparameter variants. There can be several reasons for this. The most common is that the mechanism of the reaction depends on the nature of the substituent. In a multistep reaction, for example, one step may be rate-determining in the case of electron-withdrawing substituents, but a different step may become rate-limiting when the substituent is electron-releasing. The rate of semicarbazone formation of benzaldehydes, for example, shows a nonlinear Hammett... 

We consider data for two reactions to illustrate the method. They are the first and second steps in the following sequence of semicarbazone formation and acid-catalyzed dehydration.4 The use of different pH ranges allowed the study of each of the steps [R = NHC(0)NH2]. 

A Hammett plot (a) of the apparent first-order rate constants for semicarbazone formation at pH 3.9, where a change in the RCS occurs, and (b) of the denitrosation of A-methyl-A-nitrosoanilines, where the mechanism changes. Data are from Refs. 9 and 10. 

Semicarbazone formation from aldehyde 50 with hydrazine... 

It is of interest to mention that in the presence of small amounts of sodium phosphate or arsenate the formation of 69 becomes the dominant reaction at pH 6.0 and 50°C the ratio 69/68 is 90/10. The strong catalytic effect of the phosphate and arsenate anions on the rate of formation of the ethano derivative 69 bears some analogy to the semicarbazone formation between ketone and amine, which is also found to be effectively catalyzed by these anions (68JA4319). 

Anilinium ion, < NH3 +, catalyzes semicarbazone formation from benzaldehyde much more effectively than would be expected on the basis of its strength as an acid. Explain. 

The role of entropy in determining the order of reactivity within a reaction series has been demonstrated for several other reaction systems. A classic example of a reaction in which relative rates are largely determined by TAS terms is semicarbazone formation in phosphate buffers (Price and Hammett, 1941). The differential thermodynamic parameters of activation, with acetone taken as the standard reactant, are given in Table 14. The ninety-fold decrease in reaction... 

Relative Entropies and Energies of Activation for Semicarbazone Formation at 12.5°... 

Because of the complex nature of semicarbazone formation, it is difficult to say with certainty at what stage in the reaction the entropy variations originate. Recent work on the mechanism of the reaction bears on this point. Jencks and Carriuolo (1960) have shown that above pH 4 the reaction involves a fast preequilibrium between carbonyl and semicarbazide, followed by a rate-controlling, acid-catalyzed dehydration of the addition compound. 

Figure 2 Demonstration of a stepwise mechanism for aromatic semicarbazone formation ...

Which step of the mechanism for semicarbazone formation occurs at a reduced rate when the solution pH is... 

Figure 2. A. Second-order rate constants for nitrobenzaldehyde semi-J carbazone formation as a function of formic acid concentration at pH 3-27. r B. Second-order rate constants for acetophenone semicarbazone formation as a function of propionic acid concentration at pH 4-10. (The dashed line is the rate of carbinolamine dehydration at pH 4-10 . )...

Investigation of the effect of substituents on the overall rate of benzaldehyde semicarbazone formation shows that there is a change in rate-determining step with a change in hydrogen ion concentration. At neutraUty, where the overall rate should depend upon both the equiUbrium constant for addition compound formation and the rate constant for its dehydration, the two substituent effects effectively... 

Linear Hammett correlations, however, will not be obtained if the rates of the two steps are comparable so that no single step is rate determining, or if there is a shift in rate-determining step since. 1 different p values will be obtained before and after the shift. This was found to be the case in semicarbazone formation. When the reaction was studied at pH 3-9 a sharp break occurred at a = 0 (Figure 4) By using a steady-state approximation and solving for... 

The rates of reaction of carbonyl compounds with nitrogen bcises are dependent upon the structure of the carbonyl compound, being affected by inductive, resonance and steric effects. It must be remembered that fiictors governing reactivity are distinct firom those governing stability. For example, the rate of cyclohexanone semi-carbazone formation is about fifty times greater than the rate of furfural semicarbazone formation, although the equilibrium constant for the latter is almost three hundred times as favorable . ... 

Figure 3. Logarithmic plot of the effect of substituents on benzaldehyde semicarbazone formation at neutral pH in 25% ethanol. (Equilibrium constant for carbinolamine formation, rate constant for carbinolamine dehydration, A2 rate constant for the overall reaction, Aovereu -)...

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