Alcohols Hydrogen Bonding Three ethanol molecules. Hydrogen Bonding & boiling point Increases boiling point, higher temperature needed to separate the molecules. Hexane 69 deg. 1-pentanol 138 1,4-butanediol 230 Ethanol 78 deg Dimethyl ether 24 Earlier Discussion of Acidity RO-H RO – (solvated) + H + (solvated) Alkoxide ion, base Increasing Hinderance of Solvation Methanol Ethanol 2-Propanol 2-Methyl-2-propanol Increasing Basicity of Alkoxide Anion, the conjugate base Increasing Acidity of the alcohol Alkoxides can be produced in several ways… Recall: H2O + Na Na+ + OH- + ½ H2(g) Alcohols behave similarly ROH + Na Na+ + OR- + ½ H2(g) Also: ROH + NaH Na+ + OR- + ½ H2(g) Alkoxide, strong base, strong nucleophile (unless sterically hindered) -OH as a Leaving Group Poor leaving group, hydroxide ion. R-OH + H+ R-OH2+ Protonation of the alcohol sets-up a good leaving group, water. Another way to turn the –OH into a leaving group… Conversion to Alkyl Halide, HX + ROH RX + H2O When a carbocation can be formed (Tertiary, Secondary alcohols) beware of rearangement. SN1 H+ R3COH XR3COH2 R3C + + H2O R3CX Expect both configurations. When a carbocation cannot be formed. Methanol, primary. SN2 H RCH2OH X- + RCH2OH2 RCH2X But sometimes experiment does not agree with our ideas… X HX CH2OH Observed reaction CH2X The problem: •Rearrangement of carbon skeleton which usually indicates carbocations. •Reacting alcohol is primary; do not expect carbocation. •Time to adjust our thinking a bit…. H3C H CH2OH + X H3 C H3C CH2OH2+ CH3 CH2.......OH2 H2O Not a primary carbocation X- Other ways to convert: ROH RX We have used acid to convert OH into a good leaving group H+ XR3C + + H2O R3COH2 R3COH R3CX There are other ways to accomplish the conversion to the halide. primary, secondary Br - PBr3 RCH2-O(H)PBr2 RCH2-OH RCH2Br + HOPBr2 Leaving group. primary, secondary, tertiary Cl - SOCl2 RCH2-OS(O)Cl RCH2-OH RCH2Cl + SO2 amine Leaving group. Next, a very useful alternative to halide… An alternative to making the halide: ROH ROTs CH3 CH3 Preparation from alcohols. ROH + O S O O S O Cl p-toluenesulfonyl chloride Tosyl chloride TsCl The configuration of the R group is unchanged. O R Tosylate group, -OTs, good leaving group, including the oxygen. Example CH3 CH3 TsCl H H OTs C3H7 CH3 OH C3H7 CH3 C2H5 Preparation of tosylate. Retention of configuration C2H5 Substitution on a tosylate The –OTs group is an excellent leaving group Acid Catalyzed Dehydration of an Alcohol, discussed earlier as reverse of hydration Secondary and tertiary alcohols, carbocations Protonation, establishing of good leaving group. Elimination of water to yield carbocation in rate determining step. Expect tertiary faster than secondary. Rearrangements can occur. Elimination of H+ from carbocation to yield alkene. Zaitsev Rule followed. Primary alcohols Problem: primary carbocations are not observed. Need a modified, non-carbocation mechanism. Recall these concepts: 1. Nucleophilic substitution on tertiary halides invokes the carbocation but nucleophilic substitution on primary RX avoids the carbocation by requiring the nucleophile to become involved immediately. 2. The E2 reaction requires the strong base to become involved immediately. Note that secondary and tertiary protonated alcohols eliminate the water to yield a carbocation because the carbocation is relatively stable. The carbocation then undergoes a second step: removal of the H+. The primary carbocation is too unstable for our liking so we combine the departure of the water with the removal of the H+. What would the mechanism be??? Here is the mechanism for acid catalyzed dehydration of Primary alcohols 1. protonation 2. The carbocation is avoided by removing the H at the same time as H2O departs (like E2). As before, rearrangements can be done while avoiding the primary carbocation. Principle of Microscopic Reversibility Same mechanism in either direction. Pinacol Rearrangement: an example of stabilization of a carbocation by an adjacent lone pair. Overall: Mechanism Reversible protonation. Elimination of water to yield tertiary carbocation. 1,2 rearrangement to yield resonance stabilized cation. Deprotonation. This is a protonated ketone! Oxidation Primary alcohol RCH2OH Na2Cr2O7 Na2Cr2O7 RCH=O RCO2H Na2Cr2O7 (orange) Cr3+ (green) Actual reagent is H2CrO4, chromic acid. Secondary Na2Cr2O7 R2CHOH R2C=O KMnO4 (basic) can also be used. MnO2 is produced. Tertiary R3COH NR The failure of an attempted oxidation (no color change) is evidence for a tertiary alcohol. Example… OH OH Na2Cr2O7 acid HO CH2OH O CO2H Oxidation using PCC Primary alcohol PCC RCH2OH RCH=O Secondary PCC R2CHOH R2C=O Stops here, is not oxidized to carboxylic acid Periodic Acid Oxidation OH O OH HIO4 glycol O + HIO3 two aldehydes OH O O HIO4 HO O + aldehydes carboxylic acid O O O HO HIO4 O + OH carboxylic acid HIO3 carboxylic acid OH O O 2 HIO4 + 2 HIO3 HO O OH OH O HIO3 Mechanistic Notes Cyclic structure is formed during the reaction. Evidence of cyclic intermediate. Sulfur Analogs, Thiols Preparation RI + HS- RSH SN2 reaction. Best for primary, ok secondary, not tertiary (E2 instead) Oxidation Acidity H2S pKa = 7.0 RSH pKa = 8.5