HYDROXYL COMPOUNDS*

Alcohols and PhenolsAlcohols contain an OH group connected to a a saturated C (sp3)They are important solvents and synthesis intermediatesMethanol, CH3OH, called methyl alcohol, is a common solvent, a fuel additive, produced in large quantitiesEthanol, CH3CH2OH, called ethyl alcohol, is a solvent, fuel, beveragePhenols contain an OH group connected to a carbon in a benzene ringPhenol, C6H5OH (phenyl alcohol) has diverse uses - it gives its name to the general class of compounds*

Naming AlcoholsGeneral classifications of alcohols based on substitution on C to which OH is attachedMethyl (C has 3 Hs), Primary (1) (C has two Hs, one R), secondary (2) (C has one H, two Rs), tertiary (3) (C has no H, 3 Rs), *

IUPAC Rules for Naming AlcoholsSelect the longest carbon chain containing the hydroxyl group, and derive the parent name by replacing the -e ending of the corresponding alkane with -ol Number the chain from the end nearer the hydroxyl groupNumber substituents according to position on chain, listing the substituents in alphabetical order *

Properties of Alcohols and Phenols: Hydrogen BondingThe structure around O of the alcohol or phenol is similar to that in water, sp3 hybridizedAlcohols and phenols have much higher boiling points than similar alkanes and alkyl halides*

Alcohols Form Hydrogen BondsA positively polarized OH hydrogen atom from one molecule is attracted to a lone pair of electrons on a negatively polarized oxygen atom of another moleculeThis produces a force that holds the two molecules togetherThese intermolecular attractions are present in solution but not in the gas phase, thus elevating the boiling point of the solution*

Properties of Alcohols and Phenols: Acidity and Basicity Weakly basic and weakly acidicAlcohols are weak Brnsted basesProtonated by strong acids to yield oxonium ions, ROH2+ *

Alcohols and Phenols are Weak Brnsted AcidsCan transfer a proton to water to a very small extentProduces H3O+ and an alkoxide ion, RO, or a phenoxide ion, ArO

*

pKa Values for Typical OH Compounds *

Generating Alkoxides from AlcoholsAlcohols are weak acids requires a strong base to form an alkoxide such as NaH, sodium amide NaNH2, and Grignard reagents (RMgX)Alkoxides are bases used as reagents in organic chemistry *

Phenol AcidityPhenols (pKa ~10) are much more acidic than alcohols (pKa ~ 16) due to resonance stabilization of the phenoxide ionPhenols react with NaOH solutions (but alcohols do not), forming soluble salts that are soluble in dilute aqueousA phenolic component can be separated from an organic solution by extraction into basic aqueous solution and is isolated after acid is added to the solution*

Nitro-PhenolsPhenols with nitro groups at the ortho and para positions are much stronger acidsThe pKa of 2,4,6-trinitrophenol is 0.6, a very strong acid*

Preparation of AlcoholsAlcohols are derived from many types of compoundsThe alcohol hydroxyl can be converted to many other functional groupsThis makes alcohols useful in synthesis*

Preparation of Alcohols by Regiospecific Hydration of AlkenesHydroboration/oxidation: syn, non-Markovnikov hydration Oxymercuration/reduction: Markovnikov hydration*

Alcohols from Reduction of Carbonyl Compounds Reduction of a carbonyl compound in general gives an alcoholNote that organic reduction reactions add the equivalent of H2 to a molecule *

Reduction of Aldehydes and Ketones Aldehydes gives primary alcoholsKetones gives secondary alcohols *

Reduction Reagent: Sodium BorohydrideNaBH4 is not sensitive to moisture and it does not reduce other common functional groupsLithium aluminum hydride (LiAlH4) is more powerful, less specific, and very reactive with waterBoth add the equivalent of H *

Mechanism of ReductionThe reagent adds the equivalent of hydride to the carbon of C=O and polarizes the group as well*

Reduction of Carboxylic Acids and Esters Carboxylic acids and esters are reduced to give primary alcoholsLiAlH4 is used because NaBH4 is not effective*

Alcohols from Reaction of Carbonyl Compounds with Grignard Reagents Alkyl, aryl, and vinylic halides react with magnesium in ether or tetrahydrofuran to generate Grignard reagents, RMgXGrignard reagents react with carbonyl compounds to yield alcohols*

Examples of Reactions of Grignard Reagents with Carbonyl Compounds*

Mechanism of the Addition of a Grignard ReagentGrignard reagents act as nucleophilic carbon anions (carbanions, : R) in adding to a carbonyl groupThe intermediate alkoxide is then protonated to produce the alcohol *

Reactions of Alcohols Two general classes of reactionAt the carbon of the CO bondAt the proton of the OH bond *

REACTION OF ALCOHOLS WITH SODIUM METAL (Acidic reaction)*

REACTION OF ALCOHOLS WITH ACID (basic reaction)The oxygen center can donate electron density and this causes the alcohols basic nature. Acts as Lewis bases especially for tertiary alcohols*

Dehydration of Alcohols to Alkenes The general reaction: forming an alkene from an alcohol through loss of O-H and H (hence dehydration) of the neighboring CH to give bondSpecific reagents are needed*

Acid- Catalyzed DehydrationTertiary alcohols are readily dehydrated with acidSecondary alcohols require severe conditions (75% H2SO4, 100C) - sensitive molecules don't survivePrimary alcohols require very harsh conditions impracticalReactivity is the result of the nature of the carbocation intermediate*

Conversion of Alcohols into Alkyl Halides 3 alcohols are converted by HCl or HBr at low temperature1 and alcohols are resistant to acid use SOCl2 or PBr3 by an SN2 mechanism*

Oxidation of Alcohols Can be accomplished by inorganic reagents, such as KMnO4, CrO3, and Na2Cr2O7 or by more selective, expensive reagents *

Oxidation of Primary AlcoholsTo aldehyde: pyridinium chlorochromate (PCC, C5H6NCrO3Cl) in dichloromethaneOther reagents produce carboxylic acids*

Oxidation of Secondary AlcoholsEffective with inexpensive reagents such as Na2Cr2O7 in acetic acidPCC is used for sensitive alcohols at lower temperatures*

Mechanism of Chromic Acid OxidationAlcohol forms a chromate ester followed by elimination with electron transfer to give ketone.*

ESTERIFICATION Alcohols react with carboxylic acids/acid chlorides to form esters*

PHENOLSNot exactly the same as alcohols because the lone pair on oxygen and the ring p system are in conjugationIncreases the electron density in the ring activating it towards electrophilic substitution (ortho and para positions)Also decreases the bond strength of O-H making it more acidic than alcohols*

Synthesis of phenolFrom diazonium salts

*

Synthesis of phenolsHydrolysis of chlorobenzene

*

Reactions of PhenolsOH group is acidicO is nucleophilic O-acylation and O-alkylationCan be oxidised to quinonesElectrophloic substitution at the ring*

Reactions of phenolsO-alkylation and O-acylation; formation of ethers and esters*

Reaction with diazomethane-formation of methyl estersDiazomethane can be used to methylate phenolsThe acidic OH proton is first removed to give diazomethane to give methyl diazonium ion which is then attacked by the phenoxide ion*

Electrophilic substitutionsPhenols react very rapidly with electrophiles at the ring because the oxygen atom can donate electron density to the ring making it electron rich. This activates the ring towards electrophilic substitutionSubstitutions occur at the ortho and para positions*

Examples*

Oxidation of phenolsPhenols can be oxidised to give 1,4-quinone (para-quinone)*

Oxidation of phenolsOxidation of dihydroxyarenes*

Riemer-Tiemann ReactionConversion from phenol to 2-hydroxybenzaldehyde using chloroform and base*

Ethers*

Ethers and Their RelativesAn ether has two organic groups (alkyl, aryl, or vinyl) bonded to the same oxygen atom, ROR

Diethyl ether is used industrially as a solvent

Tetrahydrofuran (THF) is a solvent that is a cyclic ether

Epoxides contain a C-O-C unit which make-up a three membered ring

Thiols (RSH) and sulfides (RSR) are sulfur (for oxygen) analogs of alcohols and ethers*

*

Naming Ethers Ethers are named two ways:

As alkoxy derivatives of alkanes

Derived by listing the two alkyl groups in the general structure of ROR in alphabetical order as separate words and adding the word etherWhen both alkyl groups are the same, the prefix di- precedes the name of the alkyl group(Ethers can be described as symmetrical or unsymmetrical) *

Naming Ethers*

Naming EthersEpoxides (oxiranes)epoxy always preceeds the name of the alkane*

Example 1: Name*

Example 2: DrawIsopropyl methyl ether

4-t-butoxy-1-cyclohexene

Phenyl propyl ether

O- nitro anisole

*

Structure, Properties and Sources of Ethers ROR ~ tetrahedral bond angle (112 in dimethyl ether)

Oxygen is sp3-hybridized

Oxygen atom gives ethers a slight dipole moment (diethyl ether 1.2 D)*

Structure, Properties, and Sources of Ethers (comparative boiling points)*

Preparation of EthersAcid catalyzed synthesis of ethersLimited to symmetrical ethers*

Mechanism 1: Acid catalyzed synthesis of ethers *

Preparation of EthersWilliamson ether synthesis Metal alkoxides react with primary alkyl halides by an SN2 pathway to yield ethers.

Secondary and tertiary substrates react following an E2 mechanism

*

Mechanism 2: Williamson Ether Synthesis*

Example 3: Williamson ether synthesis*

Example 4How would you prepare the following compounds using a Williamson synthesis?

Methyl propyl ether

Anisole (methyl phenyl ether)

*

Example 5: Predict the product*

Preparation of EthersAlkoxymercuration of alkenes

React alkene with an alcohol and mercuric acetate or trifluoroacetate

Demercuration with NaBH4 yields an ether

Overall Markovnikov addition of alcohol to alkene *

*

*

Reactions of Ethers: Acidic Cleavage Ethers are generally unreactive

Strong acid will cleave an ether at elevated temperature

HI, HBr produce an alkyl halide from less hindered component by SN2 (tertiary ethers undergo SN1)*

*

Mechanism 3: Acidic Cleavage*Note that the halide attacks the protonated ether at the less highly substituted site

Example 6*

Reactions of Ethers: Claisen Rearrangement Specific to allyl aryl ethers, ArOCH2CH=CH2Heating to 200250C leads to an o-allylphenolResult is alkylation of the phenol in an ortho position *

Mechanism 4: Claisen RearrangementConcerted pericyclic 6-electron, 6-membered ring transition stateMechanism consistent with 14C labeling*