8 8-1 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Introduction to Organic Chemistry 2 ed William H. Brown

8 8-2 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Alcohols, Ethers, and Thiols Chapter 8

8 8-3 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Structure - Alcohols The functional group of an alcohol is an -OH group bonded to an sp 3 hybridized carbon bond angles about the hydroxyl oxygen atom are approximately 109.5° Oxygen is also sp 3 hybridized two sp 3 hybrid orbitals form sigma bonds to carbon and hydrogen the remaining two sp 3 hybrid orbitals each contain an unshared pair of electrons

8 8-4 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Structure - Ethers The functional group of an ether is an oxygen atom bonded to two carbon atoms Oxygen is sp 3 hybridized with bond angles of approximately 109.5°. In dimethyl ether, the C-O- C bond angle is 110.3°

8 8-5 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Structure - Thiols The functional group of a thiol is an -SH (sulfhydryl) group bonded to an sp 3 hybridized carbon The bond angle about sulfur in methanethiol is 100.3°, which indicates that there is considerably more p character to the bonding orbitals of divalent sulfur than there is to oxygen

8 8-6 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature-Alcohols IUPAC names the longest chain that contains the -OH group is taken as the parent. the parent chain is numbered to give the -OH group the lowest possible number eol the suffix -e is changed to -ol Common names alcohol the alkyl group bonded to oxygen is named followed by the word alcohol

8 8-7 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature - Alcohols

8 8-8 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature - Alcohols Problem: write IUPAC names for these alcohols

8 8-9 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature - Alcohols Compounds containing more than one -OH group are named diols, triols, etc.

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature - Alcohols Unsaturated alcohols en the double bond is shown by the infix -en- ol the hydroxyl group is shown by the suffix -ol number the chain to give OH the lower number

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature - Ethers IUPAC: the longest carbon chain is the parent. Name the OR group as an alkoxy substituent ether Common names: name the groups attached to oxygen followed by the word ether

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature - Ethers Although cyclic ethers have IUPAC names, their common names are more widely used

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature - Thiols IUPAC names: the parent is the longest chain that contains the -SH group ethiol change the suffix -e to -thiol Common names: mercaptan name the alkyl group bonded to sulfur followed by the word mercaptan

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Physical Prop - Alcohols Alcohols are polar compounds Alcohols are associated in the liquid state by hydrogen bonding

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Physical Prop - Alcohols Hydrogen bonding Hydrogen bonding: the attractive force between a partial positive charge on hydrogen and a partial negative charge on a nearby oxygen, nitrogen, or fluorine atom the strength of hydrogen bonding in water is approximately 5 kcal/mol hydrogen bonds are considerably weaker than covalent bonds nonetheless, they can have a significant effect on physical properties

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Physical Prop - Alcohols Ethanol and dimethyl ether are constitutional isomers. Their boiling points are dramatically different ethanol forms intermolecular hydrogen bonds which increases attractive forces between its molecules, which results in a higher boiling point

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Physical Prop. - Alcohols In relation to alkanes of comparable size and molecular weight, alcohols have higher boiling points are more soluble in water The presence of additional -OH groups in a molecule further increases boiling points and solubility in water

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Physical Prop. - Alcohols

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Physical Prop. - Ethers Ethers are polar molecules; the difference in electronegativity between oxygen (3.5) and carbon (2.5) is 1.0 each C-O bond is polar covalent oxygen bears a partial negative charge and each carbon a partial positive charge

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Physical Prop. - Ethers Ethers are polar molecules, but because of steric hindrance, only weak attractive forces exist between their molecules in the pure liquid state Boiling points of ethers are lower than alcohols of comparable MW and close to those of hydrocarbons of comparable MW Ethers hydrogen bond with H 2 O and are more soluble in H 2 O than are hydrocarbons

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Physical Prop. - Thiols STENCH Low-molecular-weight thiols have a STENCH the scent of skunks is due primarily to these two thiols

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Physical Prop. - Thiols The difference in electronegativity between S (2.5) and H (2.1) is 0.4. Because of the low polarity of the S-H bond, thiols show little association by hydrogen bonding have lower boiling points and are less soluble in water than alcohols of comparable MW

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Acidity of Alcohols In dilute aqueous solution, alcohols are weakly acidic

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Acidity of Alcohols

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Basicity of Alcohols In the presence of strong acids, the oxygen atom of an alcohol behaves as a weak base proton transfer from the strong acid forms an oxonium ion

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Reaction with Metals Alcohols react with Li, Na, K, and other active metals to liberate hydrogen gas and form metal alkoxides

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Conversion of ROH to RX Conversion of an alcohol to an alkyl halide involves substitution of halogen for -OH at a saturated carbon the most common reagents for this purpose are the halogen acids, HX, and thionyl chloride, SOCl 2

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Reaction with HX Water-soluble 3° alcohols react very rapidly with HCl, HBr, and HI. Low-molecular-weight 1° and 2° alcohols are unreactive under these conditions

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Reaction with HX Water-insoluble 3° alcohols react by bubbling gaseous HX through a solution of the alcohol dissolved in diethyl ether or THF

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Reaction with HX 1° and 2° alcohols require concentrated HBr and HI to form alkyl bromides and iodides

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Mechanism: 3° ROH + HCl An S N 1 reaction Step 1: rapid, reversible acid-base reaction that transfers a proton to the OH group

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Mechanism: 3° ROH + HCl Step 2: loss of H 2 O to give a carbocation intermediate

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Mechanism: 3° ROH + HCl Step 3: reaction of the carbocation intermediate (a Lewis acid) with halide ion (a Lewis base)

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Mechanism: 1°ROH + HBr An S N 2 reaction Step 1: rapid and reversible proton transfer

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Mechanism: 1° ROH + HX Step 2: displacement of HOH by halide ion

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Mechanisms: S N 1 vs S N 2 Reactivities of alcohols for S N 1 and S N 2 are in opposite directions

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Reaction with SOCl 2 Thionyl chloride is the most widely used reagent for the conversion of 1° and 2° alcohols to alkyl chlorides a base, most commonly pyridine or triethylamine, is added to neutralize the HCl

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Dehydration of ROH An alcohol can be converted to an alkene by elimination of H and OH from adjacent carbons (a  -elimination) 1° alcohols must be heated at high temperature in the presence of an acid catalyst, such as H 2 SO 4 or H 3 PO 4 2° alcohols undergo dehydration at somewhat lower temperatures 3° alcohols often require temperatures only at or slightly above room temperature

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Dehydration of ROH

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Dehydration of ROH Where isomeric alkenes are possible, the alkene having the greater number of substituents on the double bond generally predominates (Zaitsev rule)

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Dehydration of ROH A three-step mechanism Step 1: proton transfer from H 3 O + to the -OH group to form an oxonium ion

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Dehydration of ROH Step 2: the C-O bond is broken and water is lost, giving a carbocation intermediate

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Dehydration of ROH Step 3: proton transfer of H + from a carbon adjacent to the positively charged carbon to water. The sigma electrons of the C-H bond become the pi electrons of the carbon-carbon double bond

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Dehydration of ROH Acid-catalyzed alcohol dehydration and alkene hydration are competing processes large amounts of water favor alcohol formation scarcity of water or experimental conditions where water is removed favor alkene formation

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Oxidation: 1° ROH A primary alcohol can be oxidized to an aldehyde or a carboxylic acid, depending on the oxidizing agent and experimental conditions

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Oxidation: chromic acid Chromic acid is prepared by dissolving chromium(VI) oxide or potassium dichromate in aqueous sulfuric acid

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Oxidation: 1° ROH Oxidation of 1-octanol by chromic acid gives octanoic acid the aldehyde intermediate is not isolated

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. PCC Pyridinium chlorochromate (PCC) Pyridinium chlorochromate (PCC): a form of Cr(VI) prepared by dissolving CrO 3 in aqueous HCl and adding pyridine to precipitate PCC PCC is selective for the oxidation of 1° alcohols to aldehydes; it does not oxidize aldehydes further to carboxylic acids

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Oxidation: 1° ROH PCC oxidation of a 1° alcohol to an aldehyde

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Oxidation: 2° ROH 2° alcohols are oxidized to ketones by both chromic acid and and PCC

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Reactions of ethers Ethers, R-O-R, resemble hydrocarbons in their resistance to chemical reaction they do not react with strong oxidizing agents such as chromic acid, H 2 CrO 4 they are not affected by most acids and bases at moderate temperatures Because of their good solvent properties and general inertness to chemical reaction, ethers are excellent solvents in which to carry out organic reactions

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Epoxides Epoxide Epoxide: a cyclic ether in which oxygen is one atom of a three-membered ring Common names are derived from the name of the alkene from which the epoxide is formally derived

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Synthesis of Epoxides-1 Ethylene oxide, one of the few epoxides manufactured on an industrial scale, is prepared by air oxidation of ethylene

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Synthesis of Epoxides-2 The most common laboratory method for the synthesis of epoxides is oxidation of an alkene using a peroxycarboxylic acid (a peracid) such as peroxyacetic acid

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Synthesis of Epoxides-2 Epoxidation of cyclohexene

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Hydrolysis of Epoxides In the presence of an acid catalyst, an epoxide is hydrolyzed to a glycol

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Hydrolysis of Epoxides Step 1: proton transfer to the epoxide to form a bridged oxonium ion intermediate

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Hydrolysis of Epoxides Step 2: attack of H 2 O from the side opposite the oxonium ion bridge

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Hydrolysis of Epoxides Step 3: proton transfer to solvent to complete the hydrolysis

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Hydrolysis of Epoxides Attack of the nucleophile on the protonated epoxide shows anti stereoselectivity hydrolysis of an epoxycycloalkane gives a trans-diol

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Hydrolysis of Epoxides Compare the stereochemistry of the glycols formed by these two methods

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Thiols Thiols are stronger acids than alcohols

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Thiols When dissolved an aqueous NaOH, they are converted completely to alkylsulfide salts

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Thiols Thiols are oxidized to disulfides by a variety of oxidizing agents, including O 2. they are so susceptible to this oxidation that they must be protected from air during storage The most common reaction of thiols in biological systems in interconversion between thiols and disulfides, -S-S-

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Alcohols, Ethers, and Thiols End of Chapter 8