Chapter 8 Reactions of Alcohols

1. Chapter 8 Reactions of Alcohols • Oxidation and Reduction of Alcohols • Inorganic Oxidation and Reduction • Oxidation = loss of electrons: Cu+ Cu3+ • Reduction = gain of electrons: Zn2+ Zn0 • Organic Oxidation and Reduction • Oxidation = addition of electronegative atoms (O, Cl, N) = removal of H • Reduction = removal of electronegative atoms (O, Cl, N) = addition of H • Relationship between alcohols and carbonyl groups • C==O = carbonyl -2 e- +2 e-

2. Aldehyde is an oxidized Primary Alcohol (reduced aldehyde) • Ketone is an oxidized Secondary Alcohol (reduced ketone) • Alcohol Synthesis by Reduction of Aldehydes and Ketones • Hydrogenation = adding H2 to a double bond • Catalyst = reactant that doesn’t get destroyed; it speeds up the reaction by lowering the Ea for the reaction • Heterogeneous Catalyst = insoluble, reaction occurs at its surface • Fine powder increases surface area (put cat. on fine charcoal) • Pd/C or Pt metal or Ni metal work as hydrogenation cat.’s • Homogeneous Catalyst = soluble, reaction occurs in solution • Hydrogenation of Carbonyls gives Alcohols aldehyde 1o ROH ketone 2o ROH

3. Alcohol Synthesis by Hydride Reduction of Carbonyl’s • Carbonyl groups are polar • Hydride = has several efficient sources for Organic Synthesis • Na+H- or Li+H- M+ + H- (not very organic soluble) • NaBH4 Na+ + B(solvent) + 4 H- • LiAlH4 Li+ + Al(solvent) + 4 H- • Reduction of Carbonyl’s to Alcohols • NaBH4 Mechanism

4. LiAlH4 is too reactive to use in Protic Solvents • LiAlH4 in Aprotic Organic Solvent • Oxidation of Alcohols to Carbonyls • Reduction reactions can be reversed to give the aldehydes or ketones • Oxidizing Reagent is Cr(VI) • (Na2Cr2O7 or K2Cr2O7 or CrO3) and H2SO4 and H2O • Primary alcohols can be overoxidized to carboxylic acids

5. Do Primary alcohol oxidation without water • PCC = pyridinium chlorochromate = • Anhydrous conditions and PCC don’t overoxidize primary alcohol 4) Mechanism involves Chromic Ester

6. Organometallic Reagents = carbon-metal bonds • Nucleophilic Carbon • H- is a nucleophilic hydrogen that gives new C—H bonds • Formation of new C—C bonds is the key requirement in organic synthesis • Alkylmetal Reagents • Haloalkanes can be transformed into organometallic compounds • Alkyllithium Synthesis (I > Br > Cl reactivity) • Alkylmagnesium Synthesis (Grignard Reagent)

7. Alkylmetals are very strong Nucleophiles • Use them as soon as you make them (…made in situ…) • Air and water sensitive, must do reaction under N2 or Ar • True structure involves coordinated solvent—require ether or THF • Very polar bond, metal is very electropositive • Opposite of usual situation for carbon, as in Haloalkanes • Treat the molecule like R- = Carbanion • Resonance forms • Alkylmetals are very basic • Basicity: RCH2- > RNH- > RO- (electronegativity) • Acidity: RCH3 < H2NR < ROH • Leads to fast hydrolysis (see above) in protic solvents Hydrolysis

8. Making Alkanes from Haloalkanes a) Use alkyl metal hydrolysis • Use hydride nucleophile • Useful for Deuterating compounds (D = deuterium = 2H) • Alkylmetal reagents in Alkanol Synthesis • Formation of new C—C bond by using C Nucleophile • Nucleophilic attack of Haloalkane by alkylmetal reagent is too slow

9. Must use Carbonyl electrophile (Cd+==Od-) • Ketone gives tertiary alcohol product • Aldehyde gives a secondary alcohol product • Formaldehyde (CH2O) gives primary alcohol product

10. Synthetic Strategies • Use Mechanisms to predict the products of a reaction • Know all of the tools (reactions) you can use

11. C. Synthesis of Complex Alcohols Using Alkylmetal Reagents 1. Useful Reaction Sequence 2. Retrosynthetic Analysis = Work Backwards from Target a) Complex molecules are made from simple parts b) Look for C—C bonds to break (form)

12. Avoid Synthetic Pitfalls • Use fewest possible steps • 2 steps at 90% yield = (0.9)(0.9) = 81% total yield • 4 steps at 95% yield = (0.95)(0.95)(0.95)(0.95)= 81% total yield • Convergent Synthesis is better than Linear Synthesis A B C D (50% yield at each step) E F D G H • Don’t use functional groups that would interfere in the reaction • Remember mechanistic limitations • Br2 is very selective form tertiary H • SN2 can’t happen for tertiary electrophile 80g 40g 20g 10g 20g 10g 10g 20g 10g