alcohols and phenols - university of toronto · pdf filestructure and properties alcohols are...
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AlcoholsAlcoholsAlcohols Alcohols andandand and
PhenolsPhenolsPhenolsPhenols
McMurryMcMurry: Chapter: Chapter 1717McMurryMcMurry: Chapter : Chapter 17171
Structure and PropertiesAlcohols are –OH groups attached to sp3‐hybridized carbons, while enols and phenols are –OH groups attached to sp2 carbons:
p
All –OH groups undergo hydrogen bonding:
2
Alcohols and Phenols
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Alcohol Nomenclature
• Alcohols are indicated with the suffix –ol. • Phenol (common name) can be used as the parent namePhenol (common name) can be used as the parent name.• Numbering begins closest to the alcohol and groups are
named in alphabetical order:
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Take‐Home ActivityyDraw the following compounds:
Draw the following compounds:OHOH
Draw the following compounds:
RS E
OHBrDraw the following compounds:
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Properties: Weak Acids and Basesp
Alcohols and phenols act as weak bases in the presence of idstrong acids:
But also act as weak acids in the presence of base:
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Properties: Relative Acidity• Simple alcohols are about as acidic as water (pKa ~16) Compound pKa Acidity
p y
• Bulky alcohols are weaker acids (sterically hindered H+ and low solvation of anion):
5Strong
solvation of anion):
1616
• Induction by EWGs polarize the Weak18
y pO‐H bond and increase acidity
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Properties: Relative Acidity
• Phenol is more acidic than simple alcohols because it
Compound pKa Acidity
p y
simple alcohols because it dissociates more easily due to resonance:
7Strong
10
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• EWGs increase acidity 16 y• EDGs decrease acidity Weak
16
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What Can Deprotonate an Alcohol/Phenol?Alcohols are deprotonated by strong bases. Phenols (pka 10) are more acidic than alcohols (pka 16), so they are
p /
(p ), ydeprotonated more easily:
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IR and NMR Spectroscopy of Alcohols13C NMR: C‐OH: 50‐80 ppm1H NMR: ROH: 1.0‐5.0 ppm (broad singlet), R2CHOH: 3.4‐4.5 ppm
p py
IR: O‐H: 3300‐3600 cm‐1,C‐O: 1000‐1250 cm‐1
H3C
H2C
OH O
H HH
HH
H
H
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Take Home ActivityySolve for the following structure:
C5H12O5 12
IR: strong/broad absorption band at
3300 cm‐1
*Note: bs = broad singlet, s = singlet,
lt = triplet, q = quartet
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Review: Alkene ReactivityConverting alkenes into alcohols can be performed through hydroboration, oxymercuration‐demercuration, or
y
y , y ,dihydroxylation procedures:
M k iknon‐Markovnikov
Markovnikov
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cis 1,2‐diol
Reduction of Aldehydes and KetonesReduction of aldehydes → 1° alcohols while ketones → 2° alcohols:
NaBH4• Mild reducing agent
LiAlH4St d i t th N BH
g g• Alcohols are used as solvents
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• Stronger reducing agent than NaBH4 • Reacts violently with H2O, so Et2O or THF is used as a solvent
Reduction of Carboxylic Acids and EstersyReduction of carboxylic acids give and esters give 1° alcohols:
• Only strong reducing agents (LiAlH ) can be used since carboxylicOnly strong reducing agents (LiAlH4) can be used since carboxylic acids and esters are less electrophilic than aldehydes and ketones
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Carbonyl Reduction Selectivityy y
Carbonyl NaBH4 LiAlH4 Product Complete the following scheme:y 4 4 Complete the following scheme:
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Grignard Addition to Aldehydes and Ketonesg y
Addition of Grignard reagent to an aldehyde or ketone gives alcohol products:alcohol products:
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Grignard Addition to Esters
Addition of Grignard reagent to an ester gives alcohol products:
g
Why can’t carboxylic acids be used with Grignard reagents? 17
In‐Class ActivityIn Class Activity
Predict the product of the following reaction:
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Take‐Home ActivityTake Home Activity
How could you make the following compounds from a Grignard addition to a carbonyl?addition to a carbonyl?
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Take‐Home Activity
Design a synthesis of this product, using at least one Grignard addition:
Take Home Activity
addition:
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Generating Alkyl Halides from 3° AlcoholsGenerating Alkyl Halides from 3 Alcohols
Tertiary (3°) alcohols can be converted into alkyl halides in the presence of HCl or HBr:in the presence of HCl or HBr:
SN1 Mechanism:
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Generating Alkyl Halides from 1°/2° AlcoholsGenerating Alkyl Halides from 1 /2 Alcohols
1° and 2° alcohols are converted using SOCl2 or PBr3:
SN2 Mechanisms:
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Alkenes via Alcohol DehydrationAlkenes via Alcohol Dehydration3° Alcohols undergo elimination with acid and heat (E1):
ΔΔ
Elimination of alcohols can be achieved using milder conditions with phosphorus oxychloride (E2):
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Oxidation of AlcoholsOxidation of AlcoholsAlcohols (1°/2°) can be easily oxidized to carbonyl groups:
1° alcohol aldehyde carboxylic acid1 alcohol aldehyde carboxylic acid
2° alcohol ketone
3° alcohol
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Strong Oxidizing ReagentsStrong Oxidizing Reagents
• Jones Reagent: CrO3 in aq. H2SO4/acetone
• Sodium Chromate: Na2Cr2O7/H+
• Potassium Permanganate: KMnO4/H+
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Mild Oxidizing ReagentsMild Oxidizing Reagents
Dess‐Martin Periodinane (DMP) Collins Reagent: CrO3∙pyr2
Pyridinium Chlorochromate (PCC) Pyridinium Dichromate (PDC) C O / idi /HCl C O / idi /H OCrO3/pyridine/HCl CrO3/pyridine/H2O
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Alcohol Oxidation Selectivity
It is important to identify the different oxidation outcomes in order to properly Complete the
following scheme:p p yexecute a synthetic goal:
Alcohol Carbonyl Reagent(s)
following scheme:
OHPh
O O
Collins reagent, DMP, PCC, PDC
Jones reagent, Na2Cr2O7/H+, KMnO4
C lli
OHPh
OH
Collins reagent, DMP, PCC, PDC,Jones reagent,
Na2Cr2O7/H+, KMnO4O O
2 2 7/ , 4HPh
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Chemistry ConnectionsBiological Oxidation of Alcohols
• Primary alcohols (like ethanol) are oxidized twice in our bodies:
• A build‐up of acetaldehyde and acetic acid causes nausea, vomiting, headache and fatigue (aka: a hang‐over).
• Ethylene glycol (antifreeze) is metabolized into oxalic acid (highly toxic). An overdose is treated with EtOH, which has a 100x greater affinity to the enzyme, blocking its production.
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Preparing and Using PhenolsRecall: phenol synthesis via benzyne intermediate (Dow Process)
p g g
high P, high Δ
R ll S A R i i h Ph l (OH i EDG)Recall: SEAr Reactions with Phenol (OH is strong EDG)
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Phenol Oxidation to QuinonesQ
• Phenols can be oxidized to give benzoquinones, but not in the same way as alcohols Why?but not in the same way as alcohols. Why?
• Benzoquinones can then undergo reversible redox with hydroquinones (reversibility is important for energy y q ( y p gyproduction in cells):
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Chemistry ConnectionsBombardier Beetle: Biological Oxidation
• Powerful defense mechanism where the beetle ejects a noxious spray.
h b l h d ( h l) d h d d• The beetle stores hydroquinone (a phenol) and hydrogen peroxide (oxidant) in separate abdominal chambers. When it feels threatened, the reactants are combined allowing a powerful reaction to occur and the solution is expelled explosively out of its abdomen:solution is expelled explosively out of its abdomen:
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Take Home ActivityPropose a synthesis for the following compounds, using benzaldehyde as the starting material:
y
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Take Home ActivityMatch the following 1H spectra with one of the products in the previous question:
y
*Note: s = singlet, t = triplet, l lp = pentet, m = multiplet
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