Lecture Outline Epoxide Ring Opening by Attack of Nucleophiles

Name ______________________________________ Text section 10.13 covers dehydration of alcohols. There's nothing new here. It's just protonation of the –OH, loss of water to form a carbocation, then loss of an H+ to make a new double bond (E1 chemistry). 1 Draw the products of the following dehydrations. OH H3PO4 ! OH H2SO4 ! 2 Write a mechanism to account for this dehydration. OH H3PO4 ! major product Lecture outline Epoxide ring opening by attack of nucleophiles (a) Basic conditions — direct SN2 attack by good nucleophiles Not surprisingly, backside SN2 attack occurs at the less sterically hindered ring C. O R2C CH3O CH2 CH3OH OH R2C CH2 OCH3 mech: — The reaction above is one that ordinary ethers don't do. For example, nucleophiles do not attack acyclic ethers, nor do they attack cyclic ethers like the one below. What’s the critical difference between the epoxide rxn above and non-rxns like the one below? O OCH3 — other nucleophiles also attack epoxide rings, e.g., O Et–NH2 Ph O Ph 1. LiAlD4 2. H+ O KCN H+ no rxn. Epoxy resins — O + HO base Cl OH catalyst epichlorohydrin bisphenol A O O O O O OH n O pre-polymer "resin" R–NH2 polyamine "hardener" (b) Acidic conditions — attack on protonated epoxide ring by weak nucleophiles After protonation by a strong acid, the epoxide ring is attacked (backside) by weakly basic nucleophiles at the C with the most positive charge. OH O H R2C CH2 EtOH R2C EtO CH2 Eliminations — E2 — Recall that in cases where more than one alkene can be produced, the most stable alkene generally predominates, except with bulky bases — in these cases the most sterically accessible β-H is removed preferentially. We can make use of this in syntheses. For example, how would you carry out the following conversion in the best possible yield? Br Although we may be able to optimize the amount of the desired alkene by the choice of base, we still get a mixture. If we could instead start with the alkyl bromide below, we avoid that problem, but another potential complication needs to be considered. What is it? Br We'll see later that alkenes are extremely valuable as intermediates in synthetic schemes, since there are many reactions involving additions to π-bonds that lead to epoxides, alcohols, halides, and other useful compounds. Alkynes can also be made by E2 chemistry. For example, vinylic halides can be treated with a very strong base, like H2N– (or an alkoxide base, RO–, at high temperature) to form a new triple bond. Anti elimination works better than syn, though both will go under these conditions. NaNH2 Cl Ph And both vicinal dihalides (vicinal means on adjacent Cs), like the one below, and geminal dihalides (geminal means on the same C) undergo two sequential eliminations to make alkynes. Br Ph Br NaNH2 (2 equiv) E1 — Recall that E1 is a minor pathway that accompanies SN1, so it is normally not useful in preparing alkenes. E1 is the exclusive reaction pathway, however, when 2° and 3° alcohols are treated with concentrated sulfuric or phosphoric acid, or a sulfonic acid like p-toluenesulfonic acid ("tosic acid", TsOH). This is just as strong as sulfuric acid but easier to handle. conc H2SO4 (CH3)3C OH or conc H3PO4 (CH3)2C CH2 + H2O or RSO3H mech: Because this reaction goes via a carbocation, it is limited to alcohols that, after protonation, can lose water to form relatively stable carbocations. More examples as time permits.