Chapter 11: Alcohols and Ethers

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1 Chapter 11: Alcohols and Ethers Alcohols and Ethers: Structure and Properties (Sections ) Important Alcohols and Ethers (Section 11.3) Synthesis of Alcohols from Alkenes (Section 11.4; Chapter 8) Reactions of Alcohols (Section 11.5) ld Acid Base Stuff (Section 11.6, Chapter 3) Alcohols into Alkyl alides (Section 11.7) Alcohol Reactions w/ X (Section 11.8) Alcohol Reactions w/ PBr 3, SCl 2 (Section 11.9) Alcohol Derivatives as Leaving Groups (Section 11.10) Synthesis of Ethers (Section 11.11) Reactions of Ethers (Section 11.12) Epoxides: Synthesis and pening (Sections and 11.14) Anti 1,2 Dihydroxylation of Alkenes (Section 11.15)

2 Alcohols: General Nomenclature Methanol Ethanol 2-Propanol 2-methyl-2-propanol 2-Propenol 2-Propynol Benzyl alcohol t Bu Phenol m-ethylphenol p-tert-butylphenol

3 Substitution in Benzene Rings X X X X X X para meta ortho Use para/meta/ortho Designations to Describe Substituent rientation in Disubstituted Benzene Rings, Just as in the Phenol Examples from Previous Slide

4 Ethers: General Nomenclature ethyl methyl ether diethyl ether tert-butyl phenyl ether 2-Methoxypentane Dimethoxymethane 1,2Dimethoxyethane 3 C 2 C C 3 3 C C 3 1-Ethoxy-4-methylbenzene 1-methoxy-4-methylbenzene (para-methylanisole)

5 Naming Cyclic Ethers xacyclopropane (oxirane, ethylene oxide) xacyclopentane (tetrahydrofuran) xacyclobutane (oxetane) 1,4-Dioxacyclohexane (1,4-dioxane) xacyclohexane (tetrahydropyran) Can Use Replacement Nomenclature (oxa replaces C 2 ) Also Many Common Name (Acceptable to Use)

6 Alcohols and Ethers: Physical Properties Properties of Ethers Similar to Alkanes of Like Masses Diethyl ether (MW=74); Pentane (MW=72) Diethyl ether (BP=34.6 C); Pentane (BP=36 C) Alcohols Boil Much igher than Comparable Ethers/Alkanes Related to ydrogen Bonding of Alcohols (See Chapter 4) Alcohols form ydrogen Bonding Networks w/ one Another Ethers Cannot ydrogen Bond w/ one Another Ethers CAN -Bond w/ 2 and Alcohols (Soluble in These) Properties of Some Alcohols/Ethers in Tables 11.1 and 11.2

7 Important Alcohols and Ethers Methanol (C 3 ) ften Called Wood Alcohol (Distilled From Wood) Prepared Now via Catalytic ydrogenation Reactions Ethanol (C 3 C 2 ) Made Through Fermentation of Sugars, in Alcoholic Drinks Common Solvent in rganic Labs (Absolute Ethanol) Ethylene Glycol (C 2 C 2 ) Good Antifreeze: Low MW, igh Boiling Point (197 C) Diethyl Ether (C 3 C 2 C 2 C 3 ) Low Boiling Point, Volatile, ighly Flammable Liquid ne of First Uses was as Surgical Anesthetic Watch ut for ld Ether Containers (Peroxides!!)

8 Synthesizing Alcohols from Alkenes We ve Looked at Several Synthesis Reactions in Ch. 8 Acid-Catalyzed ydration (Markovnikov) 3 + / 2 R warm, dilute 2 S 4, 2 xymercuration/demercuration (Markovnikov) 1. g(ac) 2 TF/ 2 2. NaB 4, Na ydroboration/xidation (Anti-Markovnikov) 1. B 3 : TF , Na Now Let s Consider Some Reactions of Alcohols

9 Reactions of Alcohols A + A Alcohol (Lewis Base, Nucleophile) Strong Acid Protonated Alcohol Lone Pairs on Alcohols: Lewis Bases, Nucleophiles Note Bond Polarizations: C, are δ + and is δ Alcohol Carbon Not Particularly Electrophilic ( Bad LG) Protonation of Alcohol 2 ; Good Leaving Group

10 Reactions of Alcohols Nu Protonated Alcohol S N 2 Reaction Nu + 2 Protonation of Alcohol 2 ; Good Leaving Group Presence of Good Leaving Group Makes C Electrophilic 2+ More Electron Withdrawing than ; More Polarized Can bserve S N 1 or S N 2 Reactions (Depends on Alcohol Class)

11 Reactions of Alcohols Alcohol (Lewis Base, Nucleophile) Protonated Alcohol S N 2 Reaction Protonated Ether + 2 Protonation of Alcohol 2 ; Good Leaving Group Another Alcohol Moleculae Can React, Get Protonated Ether Subsequent Deprotonation Ether Product (Symmetric ere) Reaction is CNDENSATIN of Two Alcohols

12 Converting Alcohols into Alkyl alides conc. Cl 25 o C Cl + 2 conc. Br Reflux Br 3 PBr to 0 o C Br + 3 P 3 Cl SCl 2 pyridine + S 2 + Cl C 3 C 3

13 X Reactions with Alcohols (3, 2 ) Step Step Step 3 Cl Cl

14 X Reactions with Alcohols (1, Me) Br 2 Br + 2 As Seen Previously, Protonation Makes Good Leaving Group Presence of Nucleophile (Br) Allows for Substitution Reaction Can also Add Lewis Acid to elp (esp. ZnCl 2 w/ Cl )

15 Alcohol Reactions w/ PBr 3, SCl 2 P and S Atoms are Electrophilic Sites, acts as Nucleophile Low Temperatures w/ PBr 3 Prevent C Skeleton Rearrangement PBr 3 Reaction Choice Reagent for 1, 2 1, 2 Br SCl 2 Good Reagent for 1, 2 1, 2 Cl Reaction Usually Run with Added Amine Base (Consume Cl) SCl 2 Reactions Also Typically Don t Involve Rearrangements Will Later See SCl 2 Replaces of Carboxylic Acid with Cl

16 Leaving Groups: Derivatives 3 C S 3 C S F 3 C S Mesyl Group (Ms) Tosyl Group (Ts) Trifyl (Tf) Make Better as Leaving Group (Replace, Bond to ) This General Class is Called the Sulfonate Ester Class Prepared By Reacting Alcohol w/ a Sulfonyl Chloride and Base Formation of Derivatives does not Alter C Stereochemistry

17 Leaving Groups: Derivatives 3 C S Cl Pyridine Ts Ts Tf F 3 C S Cl + Pyridine Tf Sample Derivatizations. Note Retention of Stereochemistry in 2 nd

18 Synthesis of Ethers We ve Already Seen Ether Synthesis by Alcohol Dehydration: Alcohol (Lewis Base, Nucleophile) Protonated Alcohol S N 2 Reaction Protonated Ether + 2 Utility of this Reaction is Limited in its Scope: Mixture of Ether/Alkenes with 2 Alkyl Groups Exclusively Alkenes with 3 Alkyl Groups nly Useful for Synthesis of Symmetric Ethers R + R RR + R R + R R

19 Williamson Synthesis of Ethers Unsymmetrical Ethers From RNa + alide, Sulfonate, etc. Na LG Asymmetric Ether Utility of this Reaction is Much Greater Than Condensation: Works with 1 and 2 alides, Sulfonates, etc. Still Exclusively Alkenes with 3 Alkyl Groups Lower Temperatures Favor Substitution over Elimination S N 2 Conditions Apply Prefer Unhindered Substrate

20 Alkoxymercuration-Demercuration This Reaction is Analogous to xymercuration-demercuration 1. g(tf) 2, t Bu 2. NaB 4, Na t Bu Using New g Salt ere (Triflate) Can Use g(ac) 2 Also Instead of 2 in First Step, We Use an Alcohol Carbocation is Captured by Alcohol Molecule After Loss of Proton, Alkoxide is Added Instead of Alcohol See Chapter 8 for Mechanistic Details (Completely Parallel)

21 Protecting Groups: Alcohol Alkylation 2 S 4 + Alcohol Groups do not Survive Many rganic Reactions Alkylation (Ether Formation) Protects s During Synthesis Can Remove the Protecting Group w/ Dilute Aqueous Acid Generally Dissolve Alcohol in Acid, TEN add Isobutylene Addition in this Manner Minimizes Isobutylene Dimerization Let s See Why We Might Want to Use a Protecting Group

22 Target Molecule: Protecting Groups: ow They Work Reagents: Na and Br We can't simply mix the reagents here: deprotonation occurs faster than alkylation (acid base reaction, think about pk a differences) Na + Br + Br Na So, we protect the alcohol as an ether first, and we can successfully alkylate: Br 1. 2 S 4 2. C 2 =C(C 3 ) 2 Br t Bu Na t Bu 3 + / 2 + t Bu

23 Protecting Groups: Silyl Ethers Me Me + Cl Si t Bu Pyridine DMF Si t Bu Me Me tert-butylchlorodimethylsilane -TBDMS Silyl Ethers Stable ver a 4-12 p Range (Acidic and Basic) Can Survive Conditions of Many rganic Reactions Typically Removed w/ Flouride Source (NBu 4 F; aka TBAF) Silyl Ethers More Volatile Than Alcohols (GC Applications)

24 Ether Reactions w/ Strong Acids + Br + Br Ether (Lewis Base) Strong Acid Protonated Ether (xonium ion) + 2Br 2 Br + 2 Ether (Lewis Base) Strong Acid Ethers Can be Protonated by Strong Acids (xonium Ions) w/ 2 Equivalents of Acid (X), Cleaved to 2 Eq. Alkyl alide Protonation, S N 2, Protonation, S N 2

25 Ether Cleavage by Br: Mechanism Br Br - Br Br Br Br Two Equivalents of Ethyl bromide Produced (+ 2 )

26 Synthesis of Epoxides Peroxy Acid Cl (MCPBA) Three-Membered xygen Containing Ring; Use Peroxy Acid

27 Some Peroxyacids Cl Mg 2+ C 2 (MCPBA) (MMPP) 2 3 C Peroxyacetic acid (paracetic acid) Peroxyformic acid (performic acid) Peroxybenzoic acid (perbenzoic acid) Reactive, ften Unstable Species: Chemists use More Stable

28 Epoxide pening: Acid-Catalyzed Trans 1,2 Diol Epoxides Are Reactive to pening Due to Ring Strain After Protonation, pening is S N 2 Like Reaction (Anti) Desire to Relieve Ring Strain Good Electrophiles

29 Epoxide pening: Base-Catalyzed R Trans 1,2 Diol Epoxides Are Ethers That Can be Attacked by Bases Reactivity is Due to Ring Strain (Increases Electrophilicity) As in Acid Case, pening is an S N 2 Reaction Can pen With Strong Base, ydroxide and Alkoxide Usual

But in organic terms: Oxidation: loss of H 2 ; addition of O or O 2 ; addition of X 2 (halogens).

But in organic terms: Oxidation: loss of H 2 ; addition of O or O 2 ; addition of X 2 (halogens). Reactions of Alcohols Alcohols are versatile organic compounds since they undergo a wide variety of transformations the majority of which are either oxidation or reduction type reactions. Normally: Oxidation