Lecture 9 Saturday January 23 2016 10 55 AM What is the effect of substituents on the electrophilic aromatic substitution Here are two examples How do we understand the outcomes of these reactions and can we learn enough from these reactions to make some general predictions about other substituted arenes First as the starting point let s remember that when arene reacts with an electrophile such as NO2 positivelly charged intermediate sigma complex is formed As a result of the resonance structures of the intermediate the positive charge is delocalized between two ortho positions and the para position as shown below 3 resonance structures of the sigma complex This is an important thing to remember It shows that ortho and para positions from the electrophile are going to be the most sensitive to the presence of the substituents Another thing to remember is that electrophilic aromatic substitutions are mostly irreversible sulfination being notable exception and are under kinetic control So product that forms the fastest will be the major product So in the nitration of the methyl benzene also known as toluene shown below the question is really which product will form the fastest To figure that out we need to remember that the formation of the sigma complex is the slow step while the deprotonation is fast that allows us to conclude that the formation of the sigma complex is irreversible and rate limiting step of the reaction This means that once one sigma complex is formed there is no going back and that determies which product is going to be formed So product distribution in this case and in all other electrophilic aromatic substitutions that are under kinetic control is really about which sigma complex is formed in the reaction For export Page 1 For export Page 2 So which sigma complex is formed fastest Here it is useful to remember Hammond postulate that says that for endotermic reaction such as going from starting materials to the sigma intermediate the transition state TS will look like the product Based on that we can conclude that we can assess the energy of 3 TS s for the formation of 3 sigma complexes by considering the stabilities of the sigma complexes them selfes In other words Hammond postulate tells us that more stable sigma complex is going to be formed faster For export Page 3 For export Page 4 Lecture 9 Saturday January 23 2016 10 55 AM Overall conclusion is that which product are going to be the major product in electrophilic aromatic substitution comes down to which sigma complex is the most stable This seems like an intuitive conclusion but it is correct only because of all of the following things are true 1 Reaction is under kinetic control 2 First step of the reaction formation of the sigma complex is the first irreversible step rate limiting step of the reaction 3 The formation of the sigma complex is highly endothermic Based on this analysis Methyl substituent can donate electrons to the intermediate and all 3 sigma complexes are more stable than sigma complex of the simple benzene So all 3 products will be formed faster than the benchmark nitration of the benzene What about the 3 sigma complexes in the nitration of toluene In ortho and para sigma complexes there is a resonance structure of the sigma complex where the charge is at the carbon bearing the substituent Me The Me group can donate electrons and that way can stabilize charge As a result these two sigma complexes are more stable than the meta sigma complex In meta sigma complex there is no resonance structure that places charge right next to the Me group Even in meta complex Me group can donate electron density by an inductive effect through sigma bonds so meta complex is more stable than the one formed in the reaction of benzene However this effect is smaller than in ortho amd para complexes because the charge is further away from the Me group So orto and para sigma complexes are more stable than meta and the orto and para substituted products will be formed as major products Meta products will be by far the manor one Minor point Para sigma complex is most stable because of the absence of any steric interactions which are present in the ortho complex That s why activation barrier for the formation of the para complex is smallest However there are 2 ortho positions and only one para position That s why ortho product can be the major one even when the para sigma complex is the most stable one Can we make a general conclusion about electrophilic aromatic substitution based on this analysis Any substituent that can stabilize a positive charge will have fundamentally the same effect as the methyl substituent In general electron donating substituent will make the reaction faster than the reaction with benzene and the major products will be ortho and para isomers For export Page 5 Lecture 9 Saturday January 23 2016 10 55 AM Reaction with trifluoromethyl benzene Fluorine is more electronegative than carbon and that puts shared electron pair from the C F bond closer to the F than to C The result is that the C is partially positivelly charged This polarization is propagated through sigma bonds to the other parts of the molecule The overall result is that CF3 group is electron withdrawing based on this inductive effect How does that effect electrophilic aromatic substitution The presence of the electron withdrawing group EWG will generally destabilize the sigma complexes relative to the sigma complex formed in the reaction of benzene our reference So the reaction will be slower than the reaction with benzene Within the 3 sigma complexes possible in the reaction of trifluoromethyl benzene the effect of the CF3 group will not be the same In para and ortho sigma complexes the charge is placed right next to the CF3 group which significantly destabilizes the intermediate In the meta sigma complex there is no resonance structure that puts charge right next to the CF3 As a result the effect of the CF3 group is smaller CF3 still destabilizes the cation through the inductive effect but the overall effect is smaller So this complex is the least destabilizes and the meta product is the major product of the reaction So in general EWGs deactivate benzene towards electrophilic aromatic substitution and direct the reaction to the formation of the meta products These general conclusion about the effects of electron donating D and electronwithdrawing groups EWG can be summarized as D groups make the reaction faster than with