Chapter 11 Alcohols & Ethers

1.Structure & Nomenclature  Alcohols have a hydroxyl (–OH) group bonded to a saturated carbon atom (sp 3 hybridized) 1o1o 2o2o 3o3o Ethanol2-Propanol (isopropyl alcohol) 2-Methyl- 2-propanol (tert-butyl alcohol) © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Phenols Compounds that have a hydroxyl group attached directly to a benzene ring © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Ethers The oxygen atom of an ether is bonded to two carbon atoms © 2014 by John Wiley & Sons, Inc. All rights reserved.

1A.Nomenclature of Alcohols  Rules of naming alcohols Identify the longest carbon chain that includes the carbon to which the –OH group is attached Use the lowest number for the carbon to which the –OH group is attached Alcohol as parent (suffix)  ending with “ol” © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Examples © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Example or wrong 3-Propyl-2-heptanol © 2014 by John Wiley & Sons, Inc. All rights reserved.

1B.Nomenclature of Ethers  Rules of naming ethers Similar to those with alkyl halides  CH 3 O–Methoxy  CH 3 CH 2 O–Ethoxy  Example © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Cyclic ethers © 2014 by John Wiley & Sons, Inc. All rights reserved.

2.Physical Properties of Alcohols and Ethers  Ethers have boiling points that are roughly comparable with those of hydrocarbons of the same molecular weight (MW)  Alcohols have much higher boiling points than comparable ethers or hydrocarbons © 2014 by John Wiley & Sons, Inc. All rights reserved.

 For example  Alcohol molecules can associate with each other through hydrogen bonding, whereas those of ethers and hydrocarbons cannot © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Water solubility of ethers and alcohols Both ethers and alcohols are able to form hydrogen bonds with water Ethers have solubilities in water that are similar to those of alcohols of the same molecular weight and that are very different from those of hydrocarbons The solubility of alcohols in water gradually decreases as the hydrocarbon portion of the molecule lengthens; long- chain alcohols are more “alkane-like” and are, therefore, less like water © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Physical Properties of Ethers NameFormulamp ( o C) bp ( o C) (1 atm) © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Physical Properties of Alcohols NameFormulamp ( o C) bp ( o C) (1 atm) * * Water solubility (g/100 mL H 2 O) © 2014 by John Wiley & Sons, Inc. All rights reserved.

3.Important Alcohols & Ethers 3A.Methanol  Methanol is highly toxic  Ingestion of even small quantities of methanol can cause blindness  Large quantities cause death  Methanol poisoning can also occur by inhalation of the vapors or by prolonged exposure to the skin © 2014 by John Wiley & Sons, Inc. All rights reserved.

3B.Ethanol  Ethanol can be produced by Fermentation Acid-catalyzed hydration of ethene © 2014 by John Wiley & Sons, Inc. All rights reserved.

3D.Diethyl Ether  Diethyl ether is a very low boiling, highly flammable liquid  Most ethers react slowly with oxygen by a radical process called autoxidation to form hydroperoxides and peroxides © 2014 by John Wiley & Sons, Inc. All rights reserved.

4.Synthesis of Alcohols from Alkenes  Acid-catalyzed Hydration of Alkenes H⊕H⊕ © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Acid-Catalyzed Hydration of Alkenes Markovnikov regioselectivity Free carbocation intermediate Rearrangement of carbocation possible © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Oxymercuration–Demercuration Markovnikov regioselectivity Anti stereoselectivity Generally takes place without the complication of rearrangements Mechanism  Discussed in Section 8.5 © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Hydroboration–Oxidation Anti-Markovnikov regioselectivity Syn-stereoselectivity Mechanism  Discussed in Section 8.7 © 2014 by John Wiley & Sons, Inc. All rights reserved.

H +, H 2 O or 1. Hg(OAc) 2, H 2 O, THF 2. NaBH 4, NaOH 1. BH 3 THF 2. H 2 O 2, NaOH Markovnikov regioselectivity Anti-Markovnikov regioselectivity © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Example © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Synthesis (1) Need anti-Markovnikov addition of H–OH Use hydroboration-oxidation 1. BH 3 THF 2. H 2 O 2, NaOH © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Synthesis (2) Need Markovnikov addition of H–OH Thus, could potentially use either  acid-catalyzed hydration or  oxymercuration-demercuration However, acid-catalyzed hydration is NOT reasonable here due to likely rearrangement of carbocation © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Oxymercuration-demercuration © 2014 by John Wiley & Sons, Inc. All rights reserved.

5.Reactions of Alcohols  The reactions of alcohols have mainly to do with the following: The oxygen atom of the –OH group is nucleophilic and weakly basic The hydrogen atom of the –OH group is weakly acidic The –OH group can be converted to a leaving group so as to allow substitution or elimination reactions © 2014 by John Wiley & Sons, Inc. All rights reserved.

C–O & O–H bonds of an alcohol are polarized  Protonation of the alcohol converts a poor leaving group (HO ⊖ ) into a good one (H 2 O) © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Once the alcohol is protonated substitution reactions become possible The protonated –OH group is a good leaving group (H 2 O) © 2014 by John Wiley & Sons, Inc. All rights reserved.

6.Alcohols as Acids  Alcohols have acidities similar to that of water pK a Values for Some Weak Acids AcidpKapKa CH 3 OH15.5 H2OH2O15.74 CH 3 CH 2 OH15.9 (CH 3 ) 3 COH18.0 © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Relative Acidity H 2 O & alcohols are the strongest acids in this series Increasing acidity  Relative Basicity HO ⊖ is the weakest acid in this series Increasing basicity © 2014 by John Wiley & Sons, Inc. All rights reserved.

7.Conversion of Alcohols into Alkyl Halides HX (X = Cl, Br, I) PBr 3 SOCl 2 © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Examples © 2014 by John Wiley & Sons, Inc. All rights reserved.

8.Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides  The order of reactivity of alcohols 3 o  The order of reactivity of the hydrogen halides HI > HBr > HCl (HF is generally unreactive) > 2 o > 1 o < methyl © 2014 by John Wiley & Sons, Inc. All rights reserved.

HO ⊖ is a poor leaving group H 3 O ⊕ is a good leaving group © 2014 by John Wiley & Sons, Inc. All rights reserved.

11.Synthesis of Ethers 11A. Ethers by Intermolecular Dehydration of Alcohols © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Mechanism This method is only good for the synthesis of symmetrical ethers © 2014 by John Wiley & Sons, Inc. All rights reserved.

 For unsymmetrical ethers Mixture of ethers 1 o alcohols © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Exception © 2014 by John Wiley & Sons, Inc. All rights reserved.

11B. The Williamson Ether Synthesis  Via S N 2 reaction, thus R is limited to 1 o and some 2 o (but R ' can be 1 o, 2 o or 3 o ) © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Example 1 © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Example 2 © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Example 3  However © 2014 by John Wiley & Sons, Inc. All rights reserved.

11C. Synthesis of Ethers by Alkoxy- mercuration – Demercuration Markovnikov regioselectivity © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Example © 2014 by John Wiley & Sons, Inc. All rights reserved.

12.Reactions of Ethers  Dialkyl ethers react with very few reagents other than acids © 2014 by John Wiley & Sons, Inc. All rights reserved.

12A. Cleavage of Ethers  Heating dialkyl ethers with very strong acids (HI, HBr, and H 2 SO 4 ) causes them to undergo reactions in which the carbon–oxygen bond breaks Cleavage of an ether © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Mechanism © 2014 by John Wiley & Sons, Inc. All rights reserved.

13.Epoxides  Epoxide (oxirane) A 3-membered ring containing an oxygen © 2014 by John Wiley & Sons, Inc. All rights reserved.

13A. Synthesis of Epoxides: Epoxidation  Electrophilic epoxidation © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Peroxy acids (peracids) Common peracids © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Mechanism peroxy acid alkene concerted transition state carboxylic acid epoxide © 2014 by John Wiley & Sons, Inc. All rights reserved.

14.Reactions of Epoxides  The highly strained three-membered ring of epoxides makes them much more reactive toward nucleophilic substitution than other ethers © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Acid-catalyzed ring opening of epoxide © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Base-catalyzed ring opening of epoxide © 2014 by John Wiley & Sons, Inc. All rights reserved.

 If the epoxide is unsymmetrical, in the base-catalyzed ring opening, attack by the alkoxide ion occurs primarily at the less substituted carbon atom 1 o carbon atom is less hindered © 2014 by John Wiley & Sons, Inc. All rights reserved.

 In the acid-catalyzed ring opening of an unsymmetrical epoxide the nucleophile attacks primarily at the more substituted carbon atom This carbon resembles a 3 o carbocation © 2014 by John Wiley & Sons, Inc. All rights reserved.

15.Anti 1,2-Dihydroxylation of Alkenes via Epoxides  Synthesis of 1,2-diols © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Anti-Dihydroxylation A 2-step procedure via ring-opening of epoxides © 2014 by John Wiley & Sons, Inc. All rights reserved.

17.Summary of Reactions of Alkenes, Alcohols, and Ethers  Synthesis of alcohols © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Synthesis of alcohols © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Synthesis of alcohols © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Reaction of alcohols © 2014 by John Wiley & Sons, Inc. All rights reserved.

 Synthesis of ethers  Cleavage reaction of ethers © 2014 by John Wiley & Sons, Inc. All rights reserved.

END OF CHAPTER 11 © 2014 by John Wiley & Sons, Inc. All rights reserved.