Aromatic Compounds - 1 Summary of Class Discussion

(a.)(b.)(c.)(d.)(e.)Chemistry 212 Spring 2013Aromatic Compounds - 1Summary of Class Discussion2. Mechanisms of Reactions of Aromatic Compounds.a. Unsubstituted Compounds (Benzene)(1.) Data:+++++BrBrCCl 4BrClBrClFeBr 3AlCl 3SO 3H 2 SO 4H 2 SO 4No RxnOSBrClONO 2O H+++HBrHClH 2 O(2.) Exploration: Analysis of Reactions of Aromatic Compounds:(a.) What is the overall reaction in each example where a reactionoccurs?The overall reaction in each example is substitution of ahalogen, a nitro group, a sulfone group, an alkyl group or anacyl group for a hydrogen atom on an aromatic ring.(b.) What bonds are made and broken in each reaction? Whatsimilarities are there among bonds made and broken in allreactions? Propose a simple general model for the overallreaction.For most of the reactions, a C-H bond on the benzene andone σ-bond in the reagent are broken and a σ-bond betweenan electrophilic atom of the reagent and the carbon atom ofbenzene is made while a new bond is made between an H-atom and a nucleophilic atom of the reagent.Simple Model for Aromatic SubstitutionHE(f.)(g.)++CH 3CH 3C CH 3CH 3 C ClCH 3AlClCH 33OOCCHC3CH 3 Cl AlCl 3++HClHCl+ E Nu(c.) What type of reagents seem to be most common among theexamples (nucleophilic-basic, electrophilic-acidic, etc.) (FeCl 3 ,AlCl 3 and AlBr 3 are Lewis Acids.)All of the reagents are Brønsted or Lewis Acids --Electrophiles.+HNu(d.) Considering your previous experience with the reactivity of alkenes, use your general model to work your way, step-by-step,through a mechanism for the overall reaction. What should be the first step? How can the final product be formed for the firstintermediate?As with isolated C=C compounds under acidic conditions we would expect the first interaction to be between the π-electronsof the benzene ring with the electrophilic atom of the reagent forming a new σ-bond. In order to get to the resultingproducts, the nucleophilic atom of the reagent needs to remove the H of the benzene as a proton forming the H-Nu σ-bond

2 Aromatic Compoundsand reforming the aromatic system of the ring. This second step is essentially the second step of the E 1 eliminationmechanism. So both steps have precedents in our recent experience.HHE+ E NuE +Nu+HNu(e.) Apply your general mechanism to each of the reactions in the data set. (NOTE: as indicated above, FeCl 3 , AlCl 3 and AlBr 3 areLewis Acids. As illustrated below, their positively charged metal ions associate with the lone pair e - ‘s on one of the halogen oroxygen atoms in the reagent. The nuclear charge of the metal ion lowers the energy of the e - 's of that halogen or oxygen atom. Asshown below for reactions (e.) -> (g.) the reagents combine to form an electrophilic intermediate that reacts with the aromatic ring.Reactions b & c – Illustrated for the reaction of Br 2 .H+!BrBr!FeBr 3Br+FeBr 4HBr+HBrThe electrophile is a complex of the halogen with Ferric halide complex that polarizes the halogen electrons toward the iron.Initial reaction of the electrophile with the benzene π electrons produces a delocalized cation on the ring. The nucleophileproduced is the ferric tetra-halide anion complex that releases the hydrogen halide upon protonation.

Aromatic Compounds 3Reactions dOH+OOSOHOSOOHOS OOH+HOOSOOHSOOHO + H 2 SO 4In this case SO 3 acts as the electrophile and H 2 SO 4 serves as an acid and base catalyst after the first step. (See CGW pp 476-478) In this case the bond broken in the electrophile is a π-bond so the reagent remains a single unit and regains the protonremoved from the ring. So technically, the net reaction is addition, but the mechanism follows the same sequence as thesubstitution reaction and a ring C-H bond is replaced by a C-S. As we discussed in class it is also reasonable to protonateSO 3 before the reaction with the aromatic ring. (See CGW p.476)HHSOOOH+OOSOOH

4 Aromatic CompoundsThe following reagents react to form the actual active electrophile. These reactions are illustrated below. Complete the mechanisms using the activeelectrophile.Reaction e+ONOHOO+ HSO 4 ++HSOH 2 SO 4N4 N+ H 2 O O + H 2 OO + H 2 OHHNO 3 + H 2 SO 4As explained in the question and illustrated in the equations and on p. 476 of CGW, the mixture of HNO 3 and H 2 SO 4 reactto form the electrophile, NO 2+ , water and hydrogen sulfate anion. The after the initial electrophilic addition step, the HEEon HSO 4- remove the proton from the intermediate complex forming the nitro aromatic and reforming sulfuric acid.Reaction fFor 2˚ or 3˚ alkyl halides, the aluminum trihalide complex dissociates to form the free carbocation, which acts as theelectrophile. (See reactions b & c above). (See also CGWW p. 553)CHCH 3H3dd++ C + AlBrCH 43CH 3CHCH 333˚ cation has sufficient e - density that itcan form without a large energy increase.C Br AlBr 3HCH 3CCH 3CH 3CH 3+HBrHCCH 3CH 3AlBr 4

Aromatic Compounds 5Acyl halides (Rxn g) interact with the catalysts to form acylium ions that act as carbon electrophiles toward the aromatic ring.Reaction h.+CH 3COClAlCl 3An Acylium IonCH 3 C OH++ AlCl 4OHCHC3+ AlCl 4CH 3CO+ H-Cl(f.) What problems did you encounter in applying your general mechanism to all of the reactions? Could you modify your mechanismto work for all of the reactions? How or why not? Explain.Explanations above.(g.) Based upon your experience in (2) (a.) -> (f.), your understanding of alkene reactions, and the structure and energy of aromaticcompounds, propose a reason why it is reasonable that aromatic compounds might undergo substitution rather than addition asalkenes do. You should consider (write out) the expected mechanism for addition and compare the energies of the transitionstates for substitution vs. addition in each case.The mechanism proposed in d. above still seems to be appropriate and can account for all of the products in the data set.H+ E Nu!HENu !1 2H!E + NuHENu !E+HNuaromtic partially aromtic non-aromtic partially aromticaromticThe second step differs from that in electrophilic addition to alkenes because the partial aromaticity developing in thesubstitution (loss of the proton makes the substitution lower in energy than the addition (Br adding to the cation)which lacks aromaticity.

6 Aromatic CompoundsTransition States for Substitution vs Addition to BenzeneAromaticSubstitutionHEH+NuHBrH+NuAromaticAddition!BrH! BrHPartially AromaticDelocalized PartialCation!HBrH!NuDelocalized butNOT Aromatic PartialCationE+ HNuOnly Product IsolatedHEHNuNot Formed in Significant Amounts

Aromatic Compounds 7(h,) Considering your answers and mechanisms above, try to suggest a reason why there is no reaction in example (1.) (a.), whilecyclohexene (See below) reacts under identical conditions. A reaction coordinate diagram may be helpful to your analysis.+(a.) +BrBrCCl 4BrBrBr Br No RxnCCl 4+BrBrAlkeneAromaticw/o catalyst!G Aromaticw/ catalystG!G AlkenereactantsAlkeneAromatic!G Aromaticw/o catalystAromaticw/ catalystAromaticw/ catalystRxn CoordinateThere should be no reaction in example (1.) (a.) because the relatively low energy of the aromatic ring e-'s together withthe relatively high energy of the e-'s on the partially negative leaving Br atom in the transition state make the ΔG forformation of the intermediate cation too high to produce a significant rate of reaction. The catalyst decreases theenergy of the partial negative on Br in the transition state. So with the catalyst, the relatively lower energy transitionstate makes the ΔG low enough to allow the reaction to proceed.Because the π-electrons of the alkene have considerably higher energy than those in the aromatic π system, the ΔG for theaddition of halogen to the C=C is low enough to occur even without the FeBr 3 in the transition state.