Structure reactivity relationships

Structure-reactivity relationships can be probed by measurement of rates and equilibrium, as was discussed in Chapter 4. Direct kinetic measurements have been used relatively less often in the study of radical reactions than for heterolytic reactions. Instead, competition methods have been widely used. The basis of the competition method lies in the rate expression for the reaction, and is just as valid a comparison of relative reactivity as individually measured rates, provided the two competing processes are of the same kinetic order. Suppose it is desired to compare the reactivity of two related compounds, B-X and B-Y, in a hypothetical sequence  

The data required are the relative magnitudes of and ky. When both B-X and B-Y are present in the reaction system, they will be consumed at rates that are a function of their reactivity and their concentration  

Integration of this expression with the limits [B-X] = [B-Xlnmai to [B-X], and [B-Y]initiai to [B-Y] where t is a point in time during the course of the reaction, gives 

This relationship permits the measurement of the ratio kx/kY- The initial concentrations [B-X]i and [B-Y]i are known from the conditions of the experiment. The reaction can be stopped when some B-X and B-Y remain unreacted, or an excess of B-X and B-Y can be used, so that neither is completely consumed when the other reagent, A-A, has completely reacted. Anlysis for [B-X] and [B-Y] then provides the information needed to calculate kx/kY- Is it clear why the reactions being compared must be of the same order If they are not, division of the two rate expressions would leave uncanceled concentration terms. 

Another experiment that can be considered to be of the competition type involves the determination of the reactivity of different atoms in the same molecule. For example, gas-phase chlorination of butane can lead to 1- or 2-chlorobutane. The relative reactivity (kp/k/) of the primary and secondary hydrogens is the sort of information that helps to characterize the details of the reaction process  

Entries 4 and 5 point to another important aspect of free radical reactivity. The data given indicate that the observed reactivity of the chlorine atom is strongly influenced by the presence of benzene. Evidently a complex is formed that attenuates the reactivity of the chlorine atom. Another case is chlorination in bromomethene, where the pri sec text selectivity increases to 1 8.8 38. This is probably a general feature of radical chemistry, but there are relatively few data available on solvent effects on either absolute or relative reactivity of radical intermediates. 

The TS for hydrogen atom abstraction is pictured as having the hydrogen partially bonded to the donor carbon and the abstracting radical. Generally, theoretical models of such reactions indicate a linear alignment, although there are exceptions  

The Bell-Evans-Polanyi relationship and the Hammond postulate (see Section 3.3) provide a basic framework within which to discuss structure-reactivity relationships. The Bell-Evans-Polanyi equation implies that there will be a linear relationship between and the C-H BDE. 

We would therefore expect the E to decrease as the reacting C—H bond becomes weaker. The Hammond postulate relates position on the reaction coordinate to TS stmcture. Hydrogen atom abstractions with early TS will be reactant-like and those with late TS will be radical-like. We expect highly exothermic atom transfers to have early TSs and to be less sensitive to radical stability factors. Energy neutral reactions should have later TSs. 

Relative reactivity information such as that in Table 11.5 can be used in interpreting and controlling reactivity. For example, the high selectivity of the CBtj and CClj is the basis for a recently developed halogenation procedure that is especially 

Since the polymerization with aluminum porphyrins takes place at the central aluminum atom, the rate of monomer consumption may be affected by the structure of the 

Other matters that are important include the ability of the electrophile to select among the alternative positions on a substituted aromatic ring. The relative reactivity of different substituted benzenes toward various electrophiles has also been important in developing a firm understanding of electrophilic aromatic substitution. The next section considers some of the structure-reactivity relationships that have proven to be informative. 

Because the substituent groups have a direct resonance interaction with the charge that develops in the a-complex, quantitative substituent effects exhibit a high resonance component. Hammett equations usually correlate best with the r+ substituent constants (see Section 4.3).  

If the transition state resembles the intermediate n-complex, the structure involved is a substituted cyclohexadienyl cation. The electrophile has localized one pair of electrons to form the new a bond. The Hiickel orbitals are those shown for the pentadienyl system in Fig. 10.1. A substituent can stabilize the cation by electron donation. The LUMO is 1/13. This orbital has its highest coefficients at carbons 1, 3, and 5 of the pentadienyl system. These are the positions which are ortho and para to the position occupied by the electrophile. Electron-donor substituents at the 2- and 4-positions will stabilize the system much less because of the nodes at these carbons in the LUMO. 

The effect of the bond dipole associated with electron-withdrawing groups can also be expressed in terms of its interaction with the cationic u-complex. The atoms with the highest coefficients in the LUMO 3 are the most positive. The unfavorable interaction of the bond dipole will therefore be greatest at these positions. This effect operates with substituents such as carbonyl, cyano, and nitro groups. With ether and amino substituents, the unfavorable dipole interaction is overwhelmed by the stabilizing effect of the lone-pair electrons stabilizing 3. 

The effect of substituents has been probed by MO calculations at the STO-3G level. An isodesmic reaction corresponding to transfer of a proton from a substituted 7-complex to an unsubstituted one will indicate the stabilizing or destabilizing effect of the substituent. The results are given in Table 10.1. 

The general mechanistic framework outlined in the preceding paragraphs must be elaborated by other details to fully describe the mechanisms of the individual electrophilic substitutions. The question of the identity of the active electrophile in each reaction is important. We have discussed the case of nitration, in which, under many circumstances, the electrophile is the nitronium ion. Similar questions arise in most of the other substitution processes. Other matters that are important include the ability of the electrophile to select among the alternative positions on a substituted aromatic ring. The relative reactivities of different substituted benzenes toward various electrophiles have also been important in developing a firm understanding of electrophilic aromatic substitution. The next section considers some of the structure-reactivity relationships that have proven to be informative. 

If we consider a 7r-acceptor substituent, we see that such a substituent will strongly destabilize the system when it occupies the 1-, 3-, or 5-position on the pentadienyl cation. The destabilizing effect would be less at the 2- or 4-position. The conclusions drawn from this PMO interpretation are the same as for resonance arguments. Donor substituents will be most stabilizing in the transition state leading to ortho, para substitution. Acceptor substituents will be least destabilizing in the transition state leading to meta substitution. 

The calculated energy differences give a good correlation with r+. The p parameter (p = —17) is larger than that observed experimentally for proton exchange (p —8). A physical interpretation of this is that the theoretical results pertain to the gas phase, where 

Direct resonance interaction with the substituent group cannot occur in the cr-complex for meta substitution. As a result, the transition state leading to this O -complex is relatively less favored than those for the ortho and para cases. Because 

Electron-attracting groups retard electrophilic substitution. Since deactivation of the ortho and para positions is greatest, electrophilic substitution occurs primarily at the meta position  

A few substituent groups, most notably chlorine and bromine, decrease the rate of reaction, but nevertheless direct incoming electrophiles to the ortho and para positions. This is the result of competition between field and resonance effects. The halogens are more electronegative than carbon, and as a result of their electron withdrawal, the electron density in the rings is diminished and reactivity toward 

The ortho-para- versus meta-directing and activating versus deactivating effects of substituents can also be described in terms of PMO theory. The discussion can focus either on the structure of the cr complex or on the aromatic substrate. According to the Hammond postulate, it would be most appropriate to focus on the intermediate in the case of reactions which are relatively endothermic. The transition state should then resemble the a complex in reactions when the initial step has an appreciable activation energy. For more highly reactive electrophiles the transition state may be more reactant-like, in which case consideration of the reactant and application of frontier orbital theory would be more appropriate. Let us examine the effect of substituents from both perspectives. 

An additional factor which would not be directly revealed by Hiickel-type MO calculations has to do with electrostatic effects. Since the electron distribution of the pentadienyl cation is such as to place the positive charge primarily at C-1, C-3, and C-5, there will be an electrostatic repulsion for substituents which have a positive charge on the atom directly bound to the aromatic ring. This factor contributes to the deactivating effect of electron-attracting substituents such as carbonyl, cyano, and nitro groups. 

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The polarity of covalent bonds between carbon and substituents is the basis of important structure-reactivity relationships in organic chemistry. The effects of polar bonds are generally considered to be transmitted in two ways. Successive polarization through bonds is called the inductive fect. It is expected that such an effect would diminish as the number of intervening bonds increases. 

Electrophilic aromatic substitution reactions are important for synthetic purposes and also are one of the most thoroughly studied classes of organic reactions from a mechanistic point of view. The synthetic aspects of these reactions are discussed in Chapter 11 of Part B. The discussion here will emphasize the mechanisms of several of the most completely studied reactions. These mechanistic ideas are the foundation for the structure-reactivity relationships in aromatic electrophilic substitution which will be discussed in Section 10.2... 

A substantial body of data, including reaction kinetics, isotope effects, and structure-reactivity relationships, has permitted a thorough understanding of the steps in aromatic nitration. As anticipated from the general mechanism for electrophilic substitution, there are three distinct steps ... 

As a consequence, it appears to be valid to apply Marcus theory (Section 5.3) to Sn2 reactions. Note that we may expect structure-reactivity relationships in Sn2 reactions to be functions of both the bond formation and bond cleavage processes, just as in acyl transfers. 

STRUCTURE-REACTIVITY RELATIONSHIPS Table 7-15. Examples of Hard-Soft Acid-Bases... 

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