Alcohols’and’Phenols’and’Their’ Reac1ons’ Alcohols.pdf•...
Transcript of Alcohols’and’Phenols’and’Their’ Reac1ons’ Alcohols.pdf•...
More About the Families in Group II
The families in Group II all have an electronega1ve atom or group that is a>ached to an sp3 carbon.
• Alcohols contain an OH group connected to a saturated C (sp3) • They are important solvents and synthesis intermediates • Phenols contain an OH group connected to a carbon in a benzene ring • Methanol, CH3OH, called methyl alcohol, is a common solvent, a fuel
addi1ve, produced in large quan11es • Ethanol, CH3CH2OH, called ethyl alcohol, is a solvent, fuel, beverage • Phenol, C6H5OH (“phenyl alcohol”) has diverse uses -‐ it gives its name to the
general class of compounds • OH groups bonded to vinylic sp2-‐hybridized carbons are called enols
Alcohols and Phenols
• To begin to study oxygen-‐containing func1onal groups
• These groups lie at the heart of biological chemistry
Why this Chapter?
• General classifica1ons of alcohols based on subs1tu1on on C to which OH is a>ached
• Methyl (C has 3 H’s), Primary (1°) (C has two H’s, one R), secondary (2°) (C has one H, two R’s), ter1ary (3°) (C has no H, 3 R’s)
Classifica1on of Alcohols
• Select 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 group • Number subs1tuents according to posi1on on chain, lis1ng the
subs1tuents in alphabe1cal order
IUPAC Rules for Naming Alcohols
• Use “phenol” (the French name for benzene) as the parent hydrocarbon name, not benzene
• Name subs1tuents on aroma1c ring by their posi1on from OH
Naming Phenols
• The structure around O of the alcohol or phenol is similar to that in water, sp3 hybridized. • Alcohols and phenols have much higher boiling points than similar alkanes and alkyl
halides. • A posi1vely polarized ⎯OH hydrogen atom from one molecule is a>racted to a lone pair
of electrons on a nega1vely polarized oxygen atom of another molecule. • This produces a force that holds the two molecules together • These intermolecular a>rac1ons are present in solu1on but not in the gas phase, thus
eleva1ng the boiling point of the solu1on.
Proper1es of Alcohols and Phenols
• Weakly basic and weakly acidic • Alcohols are weak Brønsted bases • Protonated by strong acids to yield oxonium ions, ROH2
+
Proper1es of Alcohols and Phenols: Acidity and Basicity
• Can transfer a proton to water to a very small extent • Produces H3O+ and an alkoxide ion, RO-‐, or a phenoxide ion,
ArO-‐
Alcohols and Phenols are Weak Brønsted Acids
• The acidity constant, Ka, measures the extent to which a Brønsted acid transfers a proton to water
[A-‐] [H3O+] Ka = ————— and pKa = -‐log Ka
[HA] • Rela1ve acidi1es are more conveniently presented on a
logarithmic scale, pKa, which is directly propor1onal to the free energy of the equilibrium
• Differences in pKa correspond to differences in free energy • Table 17.1 presents a range of acids and their pKa values
Acidity Measurements
• Simple alcohols are about as acidic as water • Alkyl groups make an alcohol a weaker acid • The more easily the alkoxide ion is solvated by water the more
its forma1on is energe1cally favored • Steric effects are important
Rela1ve Acidi1es of Alcohols
• Electron-‐withdrawing groups make an alcohol a stronger acid by stabilizing the conjugate base (alkoxide)
Induc1ve Effects Also Important in Determining Acidity of Alcohols
• Alcohols 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
Genera1ng Alkoxides from Alcohols
• Phenols (pKa ~10) are much more acidic than alcohols (pKa ~ 16) because of resonance stabiliza1on of the phenoxide ion
• Phenols react with NaOH solu1ons (but alcohols do not), forming salts that are soluble in dilute aqueous solu1on
• A phenolic component can be separated from an organic solu1on by extrac1on into basic aqueous solu1on and is isolated amer acid is added to the solu1on
Phenol Acidity
• Alcohols are derived from many types of compounds • The alcohol hydroxyl can be converted to many other
func1onal groups • This makes alcohols useful in synthesis
Prepara1on of Alcohols
• Hydrobora1on/oxida1on: syn, an0-‐Markovnikov hydra1on • Oxymercura1on/reduc1on: Markovnikov hydra1on
Review: Prepara1on of Alcohols by Regiospecific Hydra1on of Alkenes
• Review: Cis-‐1,2-‐diols from hydroxyla1on of an alkene with OsO4 followed by reduc1on with NaHSO3
• Trans-‐1,2-‐diols from acid-‐catalyzed hydrolysis of epoxides
1,2-‐Diols
• Reduc1on of a carbonyl compound in general gives an alcohol • Note that organic reduc1on reac1ons add the equivalent of H2
to a molecule
Alcohols from Carbonyl Compounds: Reduc1on
• Aldehydes gives primary alcohols
• Ketones gives secondary alcohols
Reduc1on of Aldehydes and Ketones
• NaBH4 is not sensi1ve to moisture and it does not reduce other common func1onal groups
• Lithium aluminum hydride (LiAlH4) is more powerful, less specific, and very reac1ve with water
• Both add the equivalent of “H-‐”
Reduc1on Reagent: Sodium Borohydride
• The reagent adds the equivalent of hydride to the carbon of C=O and polarizes the group as well
Mechanism of Reduc1on
• Carboxylic acids and esters are reduced to give primary alcohols
• LiAlH4 is used because NaBH4 is not effec1ve
Reduc1on of Carboxylic Acids and Esters
• Alkyl, aryl, and vinylic halides react with magnesium in ether or tetrahydrofuran to generate Grignard reagents, RMgX
• Grignard reagents react with carbonyl compounds to yield alcohols
Alcohols from Carbonyl Compounds: Grignard Reagents
• Yields ter1ary alcohols in which two of the carbon subs1tuents come from the Grignard reagent
• Grignard reagents do not add to carboxylic acids – they undergo an acid-‐base reac1on, genera1ng the hydrocarbon of the Grignard reagent
Reac1ons of Esters and Grignard Reagents
• Cannot be prepared if there are reac1ve func1onal groups in the same molecule, including proton donors
Grignard Reagents and Other Func1onal Groups in the Same Molecule
• Grignard reagents act as nucleophilic carbon anions (carbanions = : R-‐) in adding to a carbonyl group
• The intermediate alkoxide is then protonated to produce the alcohol
Mechanism of the Addi1on of a Grignard Reagent
Acid Converts the Poor Leaving Group into a Good Leaving Group
Alcohols have to be “ac1vated” before they can react.
Only weakly basic nucleophiles can be used. Strongly basic nucleophiles would react with the proton.
• Conversion of alcohols into alkyl halides: -‐ 3˚ alcohols react with HCl or HBr by SN1 through carboca1on intermediate -‐ 1˚ and 2˚ alcohols converted into halides by treatment with HCl, HBr, or HI -‐ 1˚ and 2˚ alcohols converted into halides by treatment with SOCl2 or PBr3 via
SN2 mechanism
Reac1ons of Alcohols
Conver1ng Alcohols to Alkyl Halides
Primary and Secondary alcohols require heat; ter1ary alcohols do not.
The Reac1ons of Primary Alcohols with Hydrogen Halides are SN2 Reac1ons
Recall that Br– is a good nucleophile in a pro1c solvent.
Alcohols undergo SN1 reac1ons unless they would have to form a primary carboca1on.
Cl– is the Poorest Nucleophile of the Halide Ions
ZnCl2 increases the rate of the reac1on by crea1ng a be>er leaving group than water.
The Mechanism for the Reac1on with PBr3 or PCl3
A bromophosphite (chlorophosphite) group is a be>er leaving group than a halide ion.
Pyridine is the solvent and acts as a base.
The Mechanism for the Reac1on with SOCl2
A chlorosulfite group is a be>er leaving group than a halide ion.
Pyridine is the solvent and acts as a base.
Why is It Important to Be Able to Convert Alcohols to Alkyl Halides?
Alcohols are readily available but unreac1ve. Alkyl halides are less available but reac1ve and can be used to synthesized a wide variety of compounds.
• Reac1on with p-‐toluenesulfonyl chloride (tosyl chloride, p-‐TosCl) in pyridine yields alkyl tosylates, ROTos
• Forma1on of the tosylate does not involve the C–O bond so configura1on at a chirality center is maintained
• Alkyl tosylates react like alkyl halides
Conversion of Alcohols into Tosylates
• The SN2 reac1on of an alcohol via an alkyl halide proceeds with two inversions, giving product with same arrangement as star1ng alcohol
• The SN2 reac1on of an alcohol via a tosylate, produces inversion at the chirality center
Stereochemical Uses of Tosylates
• The general reac1on: forming an alkene from an alcohol through loss of O-‐H and H (hence dehydra1on) of the neighboring C–H to give π bond
• Specific reagents are needed
Dehydra1on of Alcohols to Yield Alkenes
• Ter1ary alcohols are readily dehydrated with acid • Secondary alcohols require severe condi1ons (75% H2SO4,
100°C) -‐ sensi1ve molecules do not survive • Primary alcohols require very harsh condi1ons – imprac1cal • Reac1vity is the result of the nature of the carboca1on
intermediate
Acid-‐ Catalyzed Dehydra1on
Dehydra1on is a Reversible Reac1on
To prevent the alkene from adding water and reforming the alcohol, the water is removed as it is formed.
Ter1ary Alcohols are the Easiest to Dehydrate
The rate of dehydra1on reflects the ease of carboca1on forma1on.
Dehydra1on of a Primary Alcohol is an E2 Reac1on
Both E2 and SN2 products are obtained.
Alcohols undergo E1 reac1ons unless they would have to form a primary carboca1on.
Dehydra1on is Stereoselec1ve
The major product is the stereoisomer with the largest groups on opposite sides of the double bond.
• Phosphorus oxychloride in the amine solvent pyridine can lead to dehydra1on of secondary and ter1ary alcohols at low temperatures
• An E2 reac1on via an intermediate ester of POCl2
Dehydra1on (at milder condi1on) with POCl3
• Can be accomplished by inorganic reagents, such as KMnO4, CrO3, and Na2Cr2O7 or by more selec1ve, expensive reagents
Oxida1on of Alcohols
• To aldehyde: pyridinium chlorochromate (PCC, C5H6NCrO3Cl) in dichloromethane
• Other reagents produce carboxylic acids
Oxida1on of Primary Alcohols
• Effec1ve with inexpensive reagents such as Na2Cr2O7 in ace1c acid
• PCC is used for sensi1ve alcohols at lower temperatures
Oxida1on of Secondary Alcohols
• Alcohol forms a chromate ester followed by elimina1on with electron transfer to give ketone
• The mechanism was determined by observing the effects of isotopes on rates
Mechanism of Chromic Acid Oxida1on
• Hydroxyl groups can easily transfer their proton to a basic reagent
• This can prevent desired reac1ons • Conver1ng the hydroxyl to a (removable) func1onal group
without an acidic proton protects the alcohol
Protec1on of Alcohols
• Reac1on with chlorotrimethylsilane in the presence of base yields an unreac1ve trimethylsilyl (TMS) ether
• The ether can be cleaved with acid or with fluoride ion to regenerate the alcohol
Methods to Protect Alcohols
• Industrial process from readily available cumene • Forms cumene hydroperoxide with oxygen at high temperature
• Converted into phenol and acetone by acid
Phenols and Their Uses
• The hydroxyl group is a strongly ac1va1ng, making phenols substrates for electrophilic halogena1on, nitra1on, sulfona1on, and Friedel–Crams reac1ons
• Reac1on of a phenol with strong oxidizing agents yields a quinone
• Fremy's salt [(KSO3)2NO] works under mild condi1ons through a radical mechanism
Reac1ons of Phenols