Alcohols are versatile organic compounds since they undergo a wide variety of transformations – the majority of which are either oxidation or reduction type reactions. In this chapter provides knowledge of reactions of alcohols. This chapter presents the following content: Deprotonation, SN1/SN2 via protonation, carbocation rearrangements,.and other contents. | Deprotonation SN1 / SN2 E1 / E2 Oxidation Chapter 9: Reactions of Alcohols pKa (ROH) ~ 15-18. Need base stronger than RO : a. RLi , ., CH3Li [pKa(CH4) ~ 50]; b. Na NH2 ( NH3, 35); LDA [(i-Pr)2NH, 40); K H or Li H (H2, 38); d. (CH3)3CO [(CH3)3COH, 18] - : : : : : - + : : : - : : : - + : - + Deprotonation H2O a. Rprim : : OH : : HX Rprim OH2 : + X SN2 - : : R X : : : b. Rsec/tert OH : : H + : R + SN1 E1 R Nu Alkene OH Br OH I HBr HI Problem: mixtures Dehydration Note: Needs H+ with a good Nu (X) SN1/SN2 Via Protonation : Bad leaving group Good leaving group Best when Rsec Rtert (exothermic), but “degenerate” shifts possible Rsec Rsec, Rtert Rtert There is another general problem with SN1: H shifts - : + + + + + H C C OH H + H2O C C + H C C H + SN1 E1 + Carbocation Rearrangements Hydride shift Mechanism of Hydride Shift 7/30/2015 © Univesity of California 5 1:53 BeachBoys Be true to your scholl The Hydride Shift Transition State Shift Lipsh BeachB CH2CH3 + Br : : H H Br : : : : CH3 + | Deprotonation SN1 / SN2 E1 / E2 Oxidation Chapter 9: Reactions of Alcohols pKa (ROH) ~ 15-18. Need base stronger than RO : a. RLi , ., CH3Li [pKa(CH4) ~ 50]; b. Na NH2 ( NH3, 35); LDA [(i-Pr)2NH, 40); K H or Li H (H2, 38); d. (CH3)3CO [(CH3)3COH, 18] - : : : : : - + : : : - : : : - + : - + Deprotonation H2O a. Rprim : : OH : : HX Rprim OH2 : + X SN2 - : : R X : : : b. Rsec/tert OH : : H + : R + SN1 E1 R Nu Alkene OH Br OH I HBr HI Problem: mixtures Dehydration Note: Needs H+ with a good Nu (X) SN1/SN2 Via Protonation : Bad leaving group Good leaving group Best when Rsec Rtert (exothermic), but “degenerate” shifts possible Rsec Rsec, Rtert Rtert There is another general problem with SN1: H shifts - : + + + + + H C C OH H + H2O C C + H C C H + SN1 E1 + Carbocation Rearrangements Hydride shift Mechanism of Hydride Shift 7/30/2015 © Univesity of California 5 1:53 BeachBoys Be true to your scholl The Hydride Shift Transition State Shift Lipsh BeachB CH2CH3 + Br : : H H Br : : : : CH3 + H Br : : : : - CH3 CH2CH3 CH3 CH2CH3 Br : : : Cis/trans CH2CH3 - H Note: stereospecific; H stays on same side CH3 : Attack from either side Other Carbocation Precursors Example: All steps reversible thermodynamic equilibration possible, but hydride shift is fast, therefore some selectivity at relatively lower temperatures and short reaction times. Bottom line: mixtures to be expected Note: proton loss is reversible, . double bonds can be protonated to carbocations (Chapter 11). + + OH H2SO4 H2O + H- shifts H- shift H+ H + H + More Complications: E1 becomes prevalent at higher temperatures Proton loss Most stable carbocation H C C + R C C R + Best Rsec Rtert + + More Complications: Alkyl Shifts Especially when there are no hydrogens to shift: Slower than H- shifts, but compete. R+sec R+tert Alkyl shifts are fast when they relieve ring strain: OH : : H2O : : + + OH : : H H2O : : + Mechanism Of Alkyl Shift H + By concerted shifts, bypassing cations: H+, needs Δ + C C R C C R + H H H
