Resonance effects basicity

As an example, experimental kinetic data on the hydrolysis of amides under basic conditions as well as under acid catalysis were correlated with quantitative data on charge distribution and the resonance effect [13]. Thus, the values on the free energy of activation, AG , for the acid catalyzed hydrolysis of amides could be modeled quite well by Eq. (5)... 

Clearly, the nex.t step will be to investigate the physicochemical effects, such as charge distribution and inductive and resonance effects, at the reaction center to obtain a deeper insight into the mechanisms of these biochemical reactions and the finer details of similar reactions. Here, it should be emphasized that biochemical reactions arc ruled and driven basically by the same effects as organic reactions. Figure 10.3-22 compares the Claisen condensation of acetic esters to acctoacctic esters with the analogous biochemical reaction in the human body. 

The mobility of the proton in position 2 of a quaternized molecule and the kinetics of exchange with deuterium has been studied extensively (18-20) it is increased in a basic medium (21-23). The rate of exchange is close to that obtained with the base itself, and the protonated form is supposed to be the active intermediate (236, 664). The remarkable lability of 2-H has been ascribed to a number of factors, including a possible stabilizing resonance effect with contributions of both carbene and ylid structure. This latter may result from the interaction of a d orbital at the sulfur atom with the cr orbital out of the ring at C-2 (21). 

Another example of enhanced sensitivity to substituent effects in the gas phase can be seen in a comparison of the gas-phase basicity for a series of substituted acetophenones and methyl benzoates. It was foimd that scnsitivtiy of the free energy to substituent changes was about four times that in solution, as measured by the comparison of A( for each substituent. The gas-phase data for both series were correlated by the Yukawa-Tsuno equation. For both series, the p value was about 12. However, the parameter r" ", which reflects the contribution of extra resonance effects, was greater in the acetophenone series than in the methyl benzoate series. This can be attributed to the substantial resonance stabilization provided by the methoxy group in the esters, which diminishes the extent of conjugation with the substituents. 

Carbonates, like esters, can be cleaved by basic hydrolysis, but generally are much less susceptible to hydrolysis because of the resonance effect of the second oxygen. In general, carbonates are cleaved by taking advantage of the properties of the second alkyl substituent (e.g., zinc reduction of the 2,2,2-trichloroethyl carbonate). The reagents used to introduce the carbonate onto alcohols react readily with amines as well. As expected, basic hydrolysis of the resulting carbamate is considerably more difficult than basic hydrolysis of a carbonate. 

Resonance effects are also important in aromatic amines. m-Nitroaniline is a weaker base than aniline, a fact that can be accounted for by the —7 effect of the nitro group. But p-nitroaniline is weaker still, though the —I effect should be less because of the greater distance. We can explain this result by taking into account the canonical form A. Because A contributes to the resonance hybrid, " the electron density of the unshared pair is lower in p-nitroaniline than in m-nitroaniline, where a canonical form such as Ais impossible. The basicity is lower in the para compound for two reasons, both... 

In general, resonance effects lead to the same result as field effects. That is, here too, electron-withdrawing groups increase acidity and decrease basicity, and electron-donating groups act in the opposite manner. As a result of both resonance and field effects, charge dispersal leads to greater stability. 

The propenyl group can then supply electrons to the cobalt atom by a resonance effect. This basic mechanism may also be applied to explain the marked accelerating effect of the aroyl group. Except in cases where ortho substitution sterically hinders formation of a cyclic transition state substitution on the aromatic ring has relatively little effect on the rate of decomposition. 

In the two systems so far discussed it is impossible to obtain a quantitative idea of the relative importance of the inductive and resonance effects because it is impossible to achieve the operation of one of the effects without the other. When nitrogen is the basic centre, this becomes possible by steric fixation of the nitrogen lone pair orbital in the plane of the benzene ring, which virtually eliminates its overlap with the 7r-electron orbital of the ring carbon and hence also the mesomerism. So the enhanced acidity of the anilinium ion (pAT = 4-62) as compared with methylammonium (pAfg = 10-67) has been shown (Wepster, 1952) to be half inductive and half mesomeric in origin by a consideration of the following systems ([10]-[12]) ... 

Conversely, we can reason that the formation of conjugate acids from bases will be favoured by electron-donating substituents and inhibited by electron-withdrawing groups. However, the feature of bases is that they have a lone pair of electrons that are able to coordinate with a proton. Sometimes, this lone pair may feed into the molecule via a resonance effect, and this can stabilize the free base and inhibit conjugate acid formation. With bases, therefore, we normally consider two approaches, either stabilization of the conjugate acid, which increases basicity, or stabilization of the free base, which decreases basicity. 

As we move to A-methylaniline, we see only a modest change in pK ,. This is undoubtedly due to the electron-donating effect of the methyl group, and this would be expected to stabilized the conjugate acid, increasing observed basicity. There is a modest increase in basicity, but it is apparent that the resonance effect, as in aniline, is also paramount here, and this compound is also a weak base. However, diphenylamine (A-phenylaniline) is an extremely weak base this can be ascribed to the resonance effect allowing electron delocalization into two rings. 

A series of studies have been reported on the basicities and nucleo-philicities of 4-substituted and 4,4 -disubstituted piperidines, together with related work on decahydroquinolines.211-215 Substituent effects on pKa values determined in methanol of 4,4 -disubstituted A-methyl-piperidines216,217 and 1,2,5-trimethylpiperidines (25)218 were found to be dependent on o i.e., as expected, resonance effects are absent, the hydroxyl substituent where present taking the axial conformation (24),216 owing to a bridging molecule of methanol. 

The bands show significant bathochromic shifts in base solution (Fig. 5.2C) relative to neutral (Fig. 5.2A) or acidic (Fig. 5.2B) solutions. This may be due to tautomeric [39] and resonance effects taking place in basic medium. Interactions occurred between the nonbonded electrons on the nitrogens and the n electrons of the fused rings as evidenced by the blurring of the bands. Furthermore, the enolic configuration... 

The propagation of the wavepacket is thereby reduced to the solution of coupled first-order differential equations for the parameters representing the Gaussian wavepacket, with the true potential being expanded about the instantaneous center of the wavepacket [i2(<),f(<)]. This propagation scheme is very appealing and efficient provided the basic assumptions are fulfilled. The essential prerequisite is that the locally quadratic approximation of the PES is valid over the spread of the wavepacket. This rules out bifurcation of the wavepacket, resonance effects, or strong an-harmonicities. 

Now consider the case of an amide. The same effects are operating. The nitrogen is an inductive electron withdrawer and a resonance electron donor. As we saw in Chapter 17, the resonance effect is stronger in this case. Also, amide ion is quite basic. Overall, amides are much less reactive than acyl halides and are much more favored at equilibrium. 

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