Organic Chemistry Reviews Chapter 11

1. Organic Chemistry ReviewsChapter 11 Cindy Boulton February 8, 2009

2. Alcohol vs Ethers • Alcohol • CH3OH • IUPAC: methanol • Radiofuntional name: methyl alchol • Ether • CH3OCH3 • IUPAC: methoxymethane • Radiofunctional name: dimethyl ether

3. Alcohol Chemistry and Properties • Determined by –OH group • -OH is a polar covalent bond • Cable of hydrogen bond • Raises boiling point • Strong dipole • Hydrogen has a pKa = 17 • Readily removed by a strong base • Dissolves polar and ionic compounds

4. Ether Chemistry and Properties • Oxygen has a partial negative charge • Two Carbons attached have a partial positive charge • Charges partially cancelled each other out • Not as polar or reactive • Used as a solvent • Inert: not as reactive

5. Synthesis of Alcohols • Hydration of alkenes • By aqueous Sulfuric Acid (H+) • Regiochemistry: Markovinkov, incoming hydrogen goes to carbon with more hydrogen’s and forms a stable carbon cation • Stereochemistry: Racemic, an equal amount of new stereocenters (R and S) are formed • Pros: • Sulfuric Acid is cheap • Eliminate multiple steps (easy) • Cons: • Primary R-OH is difficult to make • Skeletal rearrangement is possible, carbocation will rearrange to a higher order

6. Synthesis of Alcohols • Oxymercuration/Demercuration • Alkene reacts with 1) Hg(OAc)2 2) NaBH4, OH- • Hg has multiple bonds and partial bonds with carbocation • Blocks alkanide migration/skeletal rearrangement • Regiochemistry: Markovinkov • Stereochemistry: Racemic • Pros: • Skeletal rearrangement is blocked • Cons: • Hg is toxic and expensive • 2 Steps and multiple clean up steps • Lower overall yield • Primary Alcohols not likely formed

7. Synthesis of Alcohols • Hydroboration-oxidation • Alkene reacts with 1) BH3 2) H2O2, OH- • Tranistion State: Boron and Hydrogen bonds to both Carbons, forms a trialkylborane • Regiochemistry: Antimarkovinkov-incoming Hydrogen goes to Carbon with less Hydrogen, Sterics • Stereochemistry: Racemic, Syn addition • Pros: • Can make Primary Alcohol • No Skeletal rearrangement • Cons: • 2 Steps • Costly • Needs clean up

8. Sulfonates • Good leaving group for SN1, SN2, E1, and E2 reactions • Stable ions and unreactive • Resonance Structure • Strong inductive effect • Alcohol is a bad leaving group but is changed to a have a sulfonate • Triflate (Tf): best • Tosylate (Tf) • Mesylate : worst

9. Conversion of Alcohols to Alkyl Halides • Alcohol is a poor leaving group, but a halide is a good leaving group for another reaction • Conversion by HX (X = Cl, Br, I), PBr3, and SOCl2 • 1o Alcohol Mechanism • “SN2”- retains stereochemistry, no carbocation intermediate • 3o Alcohol Mechanism • “SN1”- sterics from the –R groups block SN2 reaction • A stable carbocation intermediate is fromed • Product is a racemic mixture with Optical Rotation = 0o • 2o Alcohol Mechanism • Either “SN1” or “SN2” depending on the –R groups • Identified by optical rotation

10. Synthesis of Ethers • Dehydration of alcohol • An alcohol reacts with H+ to protonate the –OH • Second alcohol acts as a nucleophile and H2O acts as a good leaving group • Oxygen is protonated and removed by water of something else forming symmetric or asymmetric ethers. • Reacts at an optimal temperature for the alcohol • At different temperature can form an alkene

11. Synthesis of Ethers • Williamson Synthesis • Alcohol reacts with a sulfonate and base to form a good leaving group • The smaller of the two alcohols • If the larger alcohol had been used, sterics would have prevented the small nucleophile from attacking and an alkene would have been formed in an E2 reaction • A second alcohol reacts with a strong base to remove the proton on the hydroxyl forming an alkoxide, a good nucleophile • The larger of the two alcohols • Control synthesis forming the ether using an SN2 reaction

12. Reaction of Ethers • Cleaved by strong acids at high temperature • The ether becomes protonated by the acid forming an oxonium (O+) • The acid acts as a nucleophile attacking one of the Carbon groups • An acid and alcohol is formed • A second acid reacts with the alcohol, protonating the hydroxyl group • The acid acts as a nucleophile reacting with the carbon group • Overall products: 2 alkyl halides and H2O

13. Epoxides • Oxiranes or cyclooxapropanes • Cyclic ether • 2 Carbons and 1 Oxygen in a ring shape • Strained and reactive • Synthesis of Epoxides • Alkene reacts with a peroxy acid • Oxygen connected to the –H reacts with the alkene • Forms enantiomers and racemic mixture

14. Epoxides • Base Catalyzed Ring Opening • Hydroxyl attacks the carbon that is less crowded due to sterics • Oxygen remains bound to more crowded Carbon and is protonated • Forms a trans-alcohol due to anti addition • Acid Catalyzed Ring Opening • Oxygen is protonated forming an oxonium • Incoming H2O molecule attacks more substituted carbon which forms a more stable carbocation due to electronics • H2O molecule is deprotonated by a water molecule • Forms a trans-alcohol due to anti addition • Give enantiomers of same original molecule • Different from Syn Hydroxylation