Chapter 17: Alcohols and Phenols
1 Alcohols and Phenols
Alcohols contain an OH group connected to a saturated C (sp3) They are important solvents and synthesis intermediates
Methanol, CH3OH, called methyl alcohol, is a common solvent, a fuel additive, produced in large quantities
Ethanol, CH3CH2OH, called ethyl alcohol, is a solvent, fuel, beverage Phenols contain an OH group connected to a carbon in a benzene ring. Phenol, C6H5OH (“phenyl alcohol”) has diverse uses - it gives its name to the general class of compounds Enol, contains both a double bond and OH, they do not have to be adjacent, note that the priority goes to OH, the last name.
alcohol (ROH) phenol enol 2 Industrial method for making ROH
Methanol (methyl alcohol, wood alcohol) causes blindness in low doses (15 mL), and death in larger doses (100 – 250 mL). Catalytic reduction:
Ethanol (ethyl alcohol, grain alcohol): Non-beverage use obtained by acid-catalyzed hydration of ethylene:
3 17.1 Naming Alcohols
General classifications of alcohols based on C to which OH is attached
CH3OH RCH2OH R2CHOH R3COH
methyl primary 1o secondary 2o tertiary 3o
4 IUPAC Rules for Naming 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 substituents according to position on chain, listing the substituents in alphabetical order
Examples of primary alcohols:
CH3CH2OH ethanol (grain alcohol) CH3CH2CH2OH 1-propanol (n-propanol) CH3CH2CH2CH2OH 1-butanol (n-butanol) CH2(OH)CH2CH(CH3)2 3-methyl-1-butanol 5 Secondary Alcohols
2-propanol 2-butanol (isopropyl or rubbing alcohol)
3-pentanol cyclopentanol
6 Tertiary Alcohols
2-methyl-2-pentanol 2-methyl-2-propanol tert-butyl alcohol
1-cyclopentenol phenol
7 Give the Structure or IUPAC Name for the following: 2-chloro-3-pentanol
H OH
2-phenyl-2-propanol
H
CH3
OH
H
3-ethyl-3-hexanol
OH
H2C CH(CH3)2 8 Give the Structure or IUPAC Name for the following: ROH with a multiple bond 2-propen-1-ol 2-cyclohexenol (Allyl alcohol) OH
H2C C C CH2CH3
More than one ROH in a compound 1,3-pentanediol
OH OH OH
H2C CH CH CH2
CH3
9 Naming Phenols
The word phenol is used both as the name of a specific substance (hydroxybenzene) and as a family name for hydroxy-substituted aromatic compounds. Phenols are named as substituted aromatic compounds according to the rules of naming aromatic compounds. Note that –phenol is used as the parent name rather than benzene.
p-methylphenol 2,4-dinitrophenol
10 Naming Phenols
Problems: Write the structure for the following: m-chlorophenol 2,4,6-tribromophenol
The hydroxyl group is named as a substituent when it occurs in the same molecule with carboxylic acid, aldehyde, or ketone functional groups, which have priority in naming.
m-hydroxybenzoic acid p-hydroxybenzaldehyde
11 17.2 Properties of Alcohols and Phenols: Hydrogen Bonding 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
12 Common alcohols are liquids. Lower molecular weight alcohols (R-OH) are miscible (soluble) in water. As the R-group increases in size, the solubility decreases. Branching tends to increase solubility over linear alcohols of the same molecular weight (isomers). The R-groups tend to make for decreased water solubility, as they are hydrophobic. The OH group tends to increase water solubility, as it is hydrophilic. Flammability: Lower molecular weight alcohols are more flammable, have a lower flash point than higher molecular weight alcohols. However, all alcohols tend to be flammable. Acidity of Alcohols and Phenols. Alcohols are about as acidic as water. Alcohols can undergo slight dissociation reaction with water forming an alkoxide ion (RO-)and + hydronium ion (H3O ). 13 17.3 Properties of Alcohols and Phenols: Acidity and Basicity
Weakly basic and weakly acidic Alcohols are weak Brønsted bases, protonated by + strong acids to yield oxonium ions, ROH2
14 Alchols and Phenols are Weak Brønsted Acids Can transfer a proton to water to a very small extent + Produces H3O and an alkoxide ion, RO , or a phenoxide ion, ArO
15 Brønsted Acidity Measurements
The acidity constant, Ka, measure the extent to which a Brønsted acid transfers a proton to water + [A ] [H3O ] Ka = ————— and pKa = log Ka [HA] Relative acidities are more conveniently presented on a logarithmic scale, pKa, which is directly proportional to the free energy of the equilibrium
Differences in pKa correspond to differences in free energy
Compounds with small Ka (or large pKa) are less acidic.
16 pKa Values for Typical OH Compounds
17 Relative Acidities of Alcohols
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 formation is energetically favored Steric effects are important
18 Inductive Effects
Electron-withdrawing groups make an alcohol a stronger acid by stabilizing the conjugate base
(alkoxide) and lower pKa
19 Generating Alkoxides from Alcohols
Alcohols are weak acids – requires a strong base to form an alkoxide such as NaH, sodium amide
NaNH3, and Grignard reagents (RMgX) Alkoxides are bases used as reagents in organic chemistry
- + CH3OH + NaH CH3O Na + H2 - + CH3CH2OH + NaNH3 CH3CH2O Na + NH3 - + CH3CH2OH + CH3MgBr CH3CH2O MgBr + CH4 + - + 2ROH + 2Na 2RO Na + H2
20 Phenol Acidity
Phenols are about a million times more acidic than alcohols because the phenoxide anion is resonance stabilized. They are soluble in dilute aqueous NaOH and can often be separated from a mixture by basic extraction. Substituted Phenols can be more or less acidic than phenol itself An electron-withdrawing substituent makes a phenol more acidic by delocalizing the negative charge Phenols with an electron-donating substituent are less acidic because these substituents concentrate the charge
21 17.4 Preparation of Alcohols: an Overview Alcohols are derived from many types of compounds The alcohol hydroxyl can be converted to many other functional groups This makes alcohols useful in synthesis
Nucleophilic Substitution of alkyl halide by hydroxide
R-X + OH- R-OH + X- X( = Br, Cl, I)
- - CH3CH2I + OH CH3CH2OH + I
22 Review: Preparation of Alcohols by Regiospecific Hydration of Alkenes
Hydration of Alkenes Hydroboration/oxidation yields syn addition non- Markovnikov products. (7.5)
H OH 1. BH3 H3C CH2 CH CH2 CH3 CH2 CH CH2 2. NaOH, H2O2
23 Review: Preparation of Alcohols by Regiospecific Hydration of Alkenes
Hydration of Alkenes Oxymercuration/reduction yields Markovnikov product. (7.4)
HO H 1. Hg(AcO)2, H2O H C CH CH CH 3 2 2 CH3 CH2 CH CH2 2. NaBH4
24 Preparation of 1,2-Diols
1,2 diols (glycol) can be prepared by OsO4 hydroxylation followed by reduction. The product has syn stereochemistry. (7.8) HO OH 1. OsO4, Pyridine H C CH CH CH 3 2 2 CH3 CH2 CH CH2 2. NaHSO3, H2O
Problem: Predict the product. OOHH HH 1.1. OsO OsO4,4 ,Pyridine Pyridine
2.2. NaHSO NaHSO, ,H HOO 3 3 2 2 HH
OOHH 25 Hydroxylation of alkenes to Form Glycol
KMnO4 will produce a gycol under these mild conditions (syn addition): cold C C C C + KMnO4 + H2O + MnO2 + KOH brown purple OH OH glycol (1,2-diol)
Recall from 7.8: These conditions produce a cleavage
reaction (heat, higher conc. KMnO4, acidic conditions):
H H KMnO O Terminal alkene 4 C C + CO2 + C H H3O OH
O O KMnO4
Internal alkene + + 26 H3O OH HO 17.5 Alcohols from Reduction of Carbonyl Compounds
Reduction of a carbonyl O [H] OH compound in general gives an alcohol C C H Note that organic reduction [H] is the generalized reactions add the equivalent reduction agent of H2 to a molecule
Mechanism of Reduction
- - + O : H O H3O OH C C C H H
alkoxide ion intermediate
27 Reduction of Carbonyl Compounds
Aldehydes produce 1o ROH
Either NaBH4 (milder) or LiAlH4 (more reactive) can be used Ketones produce 2o ROH to reduce aldehydes or
ketones. Only LiAlH4 for carboxylic acids and esters.
Carboxylic acids or esters produce 1o ROH
28 Problem: What carbonyl compound would you reduce to obtain the following?
[H] O OH
O OH
O HO
29 17.6 Alcohols from Reaction of Carbonyl Compounds with Grignard Reagents
Alkyl, aryl, and vinylic halides react with magnesium in ether or tetrahydrofuran (THF) to generate Grignard reagents, RMgX Grignard reagents react with carbonyl compounds to yield alcohols
Grignard Formation R = 1,2,3,alkyl, aryl, or vinylic ether R-X + Mg R-Mg-X X = Cl, Br, I
O 1. RMgX, ether OH
C + C + HOMgX 2. H3O R 30 Mechanism of the Addition of a Grignard Reagent 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
alkoxide ion intermediate
Formaldehyde 1o ROH Aldehyde 2o ROH Ketone 3o ROH o o Ester 3 ROH + 1 ROH 31 Examples of Reactions of Grignard Reagents with Carbonyl Compounds
O 1. CH3MgCl, ether OH C + C HOMgCl 2. H3O + H H H CH3 H
O OH 1. CH3CH2CH2MgBr, ether C H C + HOMgBr + CH2CH2CH3 H CH3 2. H3O H3C
OO HHOO 1.1. CH CH33CHCH22MgBr,MgBr, ether ether CC CC CHCH CHCH HOMgBrHOMgBr 2.2. H HOO++ 22 33 ++ HH33CC CCHH33 33 HH33CC CCHH33 32 Reactions of Esters and Grignard Reagents
Yields tertiary alcohols in which two of the substituents carbon come from the Grignard reagent Grignard reagents do not add to carboxylic acids
O OH 1. 2 CH3MgBr, ether H3C C O CH2CH3 H3C C CH3 HO CH2CH3 + + 2. H3O CH3
Grignard Reaction Limitations: Grignard reagent can’t be prepared from reagents containing other
reactive functional groups, (-CHO, -CN, -NO2, etc.) or from compounds with acidic hydrogens. (-OH, -NH, -SH, -COOH) 33 Problem: Prepare 3-pentanol from propanal (note 2 new carbons needed)
Show the reaction to prepare the Grignard reagent first.
Would the same product be formed if ethanal where used instead? Show reaction
OH O 1. CH3CH2CH2MgBr, ether CH CH CH CH CH HC CH3 + 3 2 2 3 + HOMgBr 2. H3O 34 17.7 Some Reactions of Alcohols
Two general classes of reaction At the carbon of the C–O bond At the proton of the O–H bond
O-H reactions H O
C C-O reactions
35 Dehydration of Alcohols to Yield Alkenes The general reaction: forming an alkene from an alcohol through loss of O-H and H (hence dehydration) of the neighboring C–H to give bond
H OH + + H3OH, THF C C C C H-OH 25 °C +
Alcohol Reactivity Order: 3 > 2 >> 1 (NR) .3o ROH: are readily dehydrated with acid .(E1, carbocation formed) o .2 ROH: require severe conditions (75% H2SO4, 100°C) - sensitive molecules don't survive (E2) .1o ROH: require very harsh conditions – impractical 36 The number of elimination products depends on the starting alcohol. Look for H’s on adjacent carbons, and for different “R” groups. Zero to 3 products may be possible.
OH CH3CH CH3 OH C C(CH ) Alcohol CH3CH2C CH2CH2 CH3 3 3
OH C(CH3)3
Number of Alkene products
37 Acid- Catalyzed Dehydration
Acid catalyzed dehydrations usually follow Zaitsev’s rule to yield the more highly substituted alkene as the major product. + CH3 CH3 CH3 H3O , THF H C C CH CH H C C CH CH H C C CH CH 3 2 3 25 °C 3 3 + 2 2 3 OH Major Product Minor Product + H2O
Problem: What product(s) would you expect from a dehydration reaction of the following? Which is the major product?
+ CH CH CH3 3 2 H3O , THF CH + CH CH H C CH C CH 3CH H O , THFH3C CH C CH3 2 CH3 H3C CH2 C2 CH2 CH3 3 2 2 3 25 3 °C + H C CH C CH CH H C CH C CH CH H C CH C CH CH 3 OH2 2 3 25 °C 3 2 2 3 3 2 2 3 + H O OH Major Product + 2 Minor Product 38 Problem: What product(s) would you expect from a dehydration reaction of the following? Which is the major product? 2-methyl-3-hexanol
CH3 + CH3 CH3 H3O , THF H3C CH CH CH2CH2CH3 H3C C CH CH2CH2CH3 + H3C CH CH CHCH2CH3 25 °C OH Major Product Minor Product
+ H2O
2,3,3-trimethyl-2-butanol
OH CH + CH 3 H3O , THF 3
H3C C C CH3 H C C C CH H O 25 °C 2 3 + 2 CH3 CH3 CH3 CH3 Only Product
39 Dehydration with POCl3
Phosphorus oxychloride in the amine solvent pyridine can lead to dehydration of secondary and tertiary alcohols at low temperatures
An E2 via an intermediate ester of POCl3
H OH POCl3 C C C C Pyridine, 0 °C
CH3 CH CH POCl3 3 2 OH Pyridine, 0 °C + H
40 Conversion of Alcohols into Alkyl Halides R OH + HX R X + H2O o 1° and 2 ROH are resistant to acid – use SOCl2 or R OH + SOCl2 R Cl + HCl + SO2 PX3 by an SN2 mechanism 3 R OH + PX3 3 R X + H3PO3 (X = Cl or Br)
HOR OHCH + HX R XBr C+H H2O 3 + PBr3 3 + HOPBr2
R OH + SOCl2 R Cl + HCl + SO2
33 R° ROHOH are+ PconvertedX3 by3 HClR X or+ HBrH3 PatO 3low (X = Cl or Br) temperature , SN1 (carbocation intermediate)
R OH + HX R X + H2O
ProblemsR OH: Convert+ S ROHOCl2 to alkyl halideR Cl + HCl + SO2
A. CH3CH2CHOHCH3 + SOCl2 CH3CH2CHClCH3 + SO2 + HCl 3 R OH + PX3 3 R X + H3PO3 (X = Cl or Br)
B. (CH3)3COH + HBr (CH3)3CBr + HOH
41 C. 3 CH3CH2OH + PBr3 3 CH3CH2Br + H3PO3 17.8 Oxidation of Alcohols
Can be accomplished by inorganic reagents, such as
PCC or CrO3,
42 Biochemical Oxidation of Ethanol NAD+ (Nicotinamide Adenine Dinucleotide) is an oxidizing agent that will react with ethyl alcohol and form a build-up of acetaldehyde. It is used as an aversion treatment for alcoholism. A build-up of acetaldehyde results in extreme nausea, hypotension, flushing and vomiting.
Metabolism of alcohol. ADH = alcohol dehydrogenase, ALDH = aldehyde dehydrogenase, NAD+ = nicotinamide adenosine dinucleotide, NADH = reduced NAD+. 43 Oxidation of Primary Alcohols
To aldehyde: pyridinium chlorochromate
(PCC, C5H6NCrO3Cl) in dichloromethane
Other reagents produce carboxylic acids
Jones’ Reagent: CrO3 dissolved in aqueous H2SO4 with acetone solvent.
O CrO3 RCH OH C 2 +, H3O acetone R OH
Jones' H3CCH2CH2CH2OH H3CCH2CH2COOH 44 Mechanism of Chromic Acid Oxidation (Jones’ reagent) Alcohol forms a chromate ester followed by elimination with electron transfer to give carbonyl product 1o ROH carboxylic acid 2o ROH ketone The mechanism was determined by observing the effects of isotopes on rates
45 Oxidation of Secondary Alcohols
Effective with inexpensive reagents such as
Na2Cr2O7 in acetic acid
PCC is used for sensitive alcohols (steroids) at lower temperatures Jones’ reagent produces ketone from 2o ROH Problem: Predict Reactant: OH Jones' O H C CH CH CH 3 2 3 H3C C CH2CH3 46 Bordwell-Wellman Oxidation
Qualitative test for determining 1o, 2o, 3o ROH Primary alcohols are oxidized to their respective aldehyde. Secondary alcohols are oxidized to their respective ketone. Tertiary alcohols do not react.
The reactant H2CrO4 is orange, if a reaction occurs it is converted to Cr3+ which is green. O + 3+ RCH2OH + 2 H2CrO4 + 10 H R C H + 2 Cr + 8 H2O
O + 3+ R2CHOH + 2 H2CrO4 + 10 H R C R + 2 Cr + 8 H2O
R3COH + H2CrO4 No Reaction 47 Lucas Reagent
The Lucas Test is used identify an alcohol as primary, secondary or tertiary. The Lucas Reagent is a mixture of zinc chloride and concentrated hydrochloric acid. The alkyl chloride, R-Cl, is insoluble and forms a lower layer or a cloudy solution. ZnCl2 R-OH + HCl R-Cl + HOH Lucas ROH RCl + HOH The rate of the reaction depends on whether the alcohol is primary, secondary, or tertiary. Primary alcohols do not react. Secondary alcohols react after 4-5 minutes. Tertiary alcohols react immediately (SN1). The basis of this rate trend is due to the stability of the intermediate carbocation. The tertiary carbocation is the most stable and the primary is the least stable. 48 Complete the following reactions
OH Jones'
PCC
CH2Cl2
Lucas
Boardwell-Wellman
49 Complete the following reactions
OH Jones'
NaCr2O7
H2O, CH3COOH,
Lucas
Boardwell-Wellman
50 Complete the following reactions
OH Jones'
NaCr2O7
H2O, CH3COOH,
Lucas
Boardwell-Wellman
51 17.9 Protection of Alcohols
It is sometimes necessary to protect an alcohol when it can interfere with a reaction involving a functional group in another part of a molecule
Protection involves three steps: 1. Protect alcohol with formation of TMS (trimethylsilyl ether). This ether is very unreactive. R-OH R-O-TMS
2. Carry out reaction 3. Remove protecting group by aqueous acid or F-.
52 17.10 Preparation and Uses of Phenols
Phenols are used in resins, adhesives, as a starting material to make wood & food preserves (BHT & BHA) and as antiseptics.
Industrial process: Cumene reacts with O2 to from cumene hydroperoxide, then treated with acid to make phenol and acetone.
H OOH
H C C CH H3C C CH3 OH 3 3 + O O2 H3O + H C C CH heat 3 3
53 Laboratory Preparation of Phenols
From aromatic sulfonic acids by melting with NaOH at high temperature Limited to the preparation of alkyl-substituted phenols
54 17.11 Oxidation of Phenols: Quinones
Strong oxidizing agents yields a 2,5-cyclohexadiene-1,4-dione, or
quinone. OH O
(KSO3)2NO Fremy’s salt (KSO3)2NO gives
reasonable yields under mild H2O conditions. Quinones are a valuable class of O compounds because of their O OH oxidation/reduction (redox) SnCl2, H2O properties. They can be easily reduced to hydroquinones using Fremy's salt O OH NaBH4, and SnCl2. Fremy’s salt can re-oxidize back to quinones. 55 17.12 Spectroscopy of Alcohols and Phenols IR Spectroscopy Both ROH and ArOH show an –OH stretch in region 3300-3600 cm-1. ROH shows a C-O stretch near 1500 cm-1.
56 17.12 Spectroscopy of Alcohols and Phenols IR Spectroscopy Both ROH and ArOH show an –OH stretch in region 3300-3600 cm-1. ArOH show aromatic bands at 1500 – 1600 cm-1 and monosubstituted bands at 690 – 760 cm-1.
57 Nuclear Magnetic Resonance Spectroscopy NMR 13C NMR carbons bonded to –OH group absorb in 50 – 80 range. 1H NMR hydrogens on carbons bearing –OH group absorb in 3.5 – 4.5 range. ArOH shows aromatic ring absorption near 7 – 8 , and –OH in 3 –8 range.
58 Mass Spectrometry
Alcohols undergo alpha cleavage, a C–C bond nearest the hydroxyl group is broken, yielding a neutral radical plus a charged oxygen-containing fragment
Alcohols undergo dehydration to yield an alkene radical anion
59 18: Ethers and Epoxides; Thiols and Sulfides Ethers and Their Relatives
An ether has two organic groups (alkyl, aryl, or vinyl) bonded to the same oxygen atom, R–O–R Diethyl ether is used industrially as a solvent Tetrahydrofuran (THF) is a solvent that is a cyclic ether O
R C C R
R R
epoxide
Thiols (R–S–H) and sulfides (R–S–R) are sulfur analogs of alcohols and ethers
61 Ethers: ( R-O-R’ ) Structural Characteristics
Unsymmetrical ethers Symmetrical ethers have identical R groups have different R groups dimethyl ether diethyl ether ethyl methyl ether (solvent, anesthetic)
B.P. -24.5 C B.P. 34.5 C B.P. 10.8 C
62 18.1 Naming Ethers Simple ethers are named by identifying the two organic substituents and adding the word ether
O CH CH 2 3 O
If other functional groups are present, the ether part is considered an alkoxy substituent An alkoxy group (-O-R or –OR) is an alkyl group to which an oxygen atom has been added. Simple alkoxy groups include the following. methoxy ethoxy 1-propoxy 2-propoxy
63 Naming Ethers The smaller hydrocarbon attachment and the oxygen atom are called an alkoxy group, and this group is considered a substituent on the larger hydrocarbon group. 2-methoxypentane 1-methoxypropane
Alcohol has priority over ether and gets to give the compound the last name.
methoxymethanol 4-methoxy-2-butanol
64 Problem: Give the name or structure for the following:
OH
CH3CH CH CH3 CH3CH2CH2CH2OCH3 O CH3 1-ethoxy-1-methylcyclohexane 1-propoxybenzene
2-methoxybutane
CH3CH2 O CH2 CH (CH3)2
65 18.2 Structure, Properties, and Sources of Ethers R–O–R ~ tetrahedral bond angle (112° in dimethyl ether, BP -24.5 oC) Oxygen is sp3-hybridized and gives ethers a slight dipole moment Diethyl ether (BP 34.5oC) prepared industrially by sulfuric acid–catalyzed dehydration of ethanol. Ethers have much lower boiling points than the corresponding isomeric alcohols because ethers cannot form hydrogen bonds with themselves. Ethers are relatively stable and unreactive. Some can react slowly with air to form peroxide (-O-O-) bonds. Ethers are excellent solvents for organic compounds. Their relative inertness makes them good solvents in which to carry out organic reactions.
66 Preparation of Ethers
Symmetrical ethers can be synthesized by acid-catalyzed dehydration of 1 alcohols.
H2SO4 2 ROH + ROR + H2O 140oC
(best for primary alcohols; gives symmetric ethers)
This reaction takes place by SN2 displacement. This method is not practical for the laboratory but used in industry.
67 18.3 The Williamson Ether Synthesis
Best method for the preparation of ethers Reaction of metal alkoxides and primary alkyl halides, (2o RX o OK but never 3 RX, goes by SN2 mechanism). Alkoxides prepared by reaction of an alcohol with a strong base such as sodium hydride, NaH. Note that the O is still covalently bonded to carbon, then Na+ is an ionic attraction next to O. You will need to make alkyl halide R-X from an alcohol (sec. 17.7) as a first step in the synthesis.
ROH + PBr3 RBr + HOPBr2
R’-OH + NaH R’-ONa + H2(g)
R’-ONa + RBr R’-O-R + NaBr 68 List the alcohols need to synthesize the following ethers:
CH CH 2CH3 CH 3 O 3 CH3 CH2 O CH2CH CH3 CH3 CH3 CH O CH3
69 18.3 The Williamson Ether Synthesis
Example with 3o vs 1o ROH starting alcohols
CH3CH2-O-C(CH3)3
70 Problems: Prepare the following ether using Williamson synthesis, starting from alcohol.
A. CH3 H3C CH O CH3
71 Problems: Prepare the following ether using Williamson synthesis, starting from alcohol.
CH3
B. O CH2CH3
72 Silver Oxide-Catalyzed Ether Formation Variation of Williamson synthesis using the reaction
of alcohols with Ag2O directly with alkyl halide that forms ether in one step
CH3I HO CH CH3 H3C O CH CH3 OH Ag2O O
CH3
73 18.4 Alkoxymercuration of Alkenes
Ethers can be formed from the reaction of alcohols with alkenes. The reaction is catalyzed by mercuric trifluoracetate. The product follows Markovnikov’s rule. H OR 1. ROH, (CF3CO2)2Hg C C C C 2. NaBH4 Example
1.1. CH CH3CH3CH2OH,2OH, (CF (CF3CO3CO2)22)Hg2Hg CCHH 2.2. NaBH NaBH 3 3 CCHH3 3 4 4 OCHOCH2CH2CH3 3 74 18.5 Reactions of Ethers: Acidic Cleavage
Ethers are generally unreactive, they only undergo one reaction of general use – strong acids cleave them. HX R O R' R X + R' O H H2O
Where X = Br or I HCl does not cleave ethers
1, 2 alkyl ethers react by SN2 mechanism, where the halide attacks the ether at the less hindered site, producing one halide and one alcohol.
75 18.5 Reactions of Ethers: Acidic Cleavage
more hindered less hindered H H I H + I CH H3C O 3 H3C O CH3 H3C O CH3 CH CH2 CH CH2 S 2 CH CH2 N + CH3 CH3 CH3 I-
Complete the following reaction
HBr,HBr, HH22OO OO HOHO HH3CC BrBr + H C 3 + H33C RefluxReflux
76 18.5 Reactions of Ethers: Acidic Cleavage
3, benzylic and allylic ethers can react by either
SN1, or E1 because a stable carbocation intermediate is formed. The reaction is fast and takes place at moderate temperatures.
CH3 CH3 CH3 CH3 CF3COOH H3C C O C CH3 H3C C OH + C CH3 0 °C CH3 CH3 CH3 CH2
77 18.6 Reactions of Ethers: Claisen Rearrangement (mechanism on next side)
Specific to allyl aryl ethers, ArOCH2CH=CH2 Heating to 200–250°C leads to an o-allylphenol Result is alkylation of the phenol in an ortho position
CH CH OH 2 2 ONa O CH
THF BrCH2CH=CH2 + NaH solution
CH2 O OH CH Claisen Rearrangement CH2 CH2 CH2 250 °C CH
78 Claisen Rearrangement Mechanism
Concerted pericyclic 6-electron, 6-membered ring transition state Mechanism consistent with 14C labeling
79