Organic Chemistry Reviews Chapter 11 Cindy Boulton February 8, 2009

Alcohol vs Ethers  Alcohol  CH 3 OH  IUPAC: methanol  Radiofuntional name: methyl alchol  Ether  CH 3 OCH 3  IUPAC: methoxymethane  Radiofunctional name: dimethyl ether

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

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

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

Synthesis of Alcohols  Oxymercuration/Demercuration  Alkene reacts with 1) Hg(OAc) 2 2) NaBH 4, 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

Synthesis of Alcohols  Hydroboration-oxidation  Alkene reacts with 1) BH 3 2) H 2 O 2, OH -  Tranistion State: Boron and Hydrogen bonds to both Carbons, forms a trialkyl borane  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

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

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), PBr 3, and SOCl 2  1 o Alcohol Mechanism  “SN2”- retains stereochemistry, no carbocation intermediate  3 o 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 = 0 o  2 o Alcohol Mechanism  Either “SN1” or “SN2” depending on the –R groups  Identified by optical rotation

Synthesis of Ethers  Dehydration of alcohol  An alcohol reacts with H + to protonate the –OH  Second alcohol acts as a nucleophile and H 2 O 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

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

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 H 2 O

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

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 H 2 O molecule attacks more substituted carbon which forms a more stable carbocation due to electronics  H 2 O 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