Alcohols and Phenols

R-OH and Ar-OH In alcohols C(sp3)-OH In phenols C(sp2)-OH

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Complex alcohols

cholesterol

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most steroids function as hormones (chemical messengers)

cholesterol

progesterone (development
of male sexual characteristics)

Hydrocortisone (control inflammation)

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progesterone (fertility control)

More complex alcohols

cellulose

Amylose (a form of starch) glucose

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Carbolic acid (phenol) was one of the first Antiseptics used in surgery

a chemical burn

Lord Lister in surgery

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Physical properties of alcohols

Hydrogen bonding strong intermolecular attractive force, (H-bond ~ 20 kJ/mol) leads to higher boiling points, melting points than alkanes of similar molecular weight

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hydride (H:-), amide (-:NH2) can remove alcohol H pKa CH3CH2OH = 15.9; (pka H2O = 15.7) Basicity R-O-H + HCl R-OH2 + Cl+

(alcohols are amphoteric)

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Influence of chemical structure on acid strength

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IR Spectrum of an Alcohol

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IR Spectrum of a Phenol

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Spectroscopy of Alcohols
IR Characteristic broad, strong stretch 3300 3600 cm-1 C-O near 1200 cm-1, IR of phenol also shows aromatic absorption O-H at 3300 3600 cm-1, C=C at 1600 cm-1
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1H

NMR

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C8H10O
IR: 3500 cm-1

3H 5 1H 1H

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Nomenclature
Use suffix OL, name as alcohol if highest priority functional group on molecule
(S)-3-chloro-1-pentanol

(E)-(S)-5-ethyl-3-hepten-2-ol (E/Z) listed before (R/S)

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Preparation of Alcohols

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Reactions of Carbonyl & Like Cmpds with Grignard Reagent

1o alcohol

2o alcohol

epoxide

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1o alcohol

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Reduction of Carbonyl Compounds (will be doing this in lab V)

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Must use more reactive LiAlH4 to reduce esters and carboxylic acids

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Dehydration of alcohols

works best on 3o alcohols, requires concentrated acid, heat

phosphorus oxychloride works on 2o or 3o alcohols, needs mild (low temp.) and basic conditions
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Mechanism of POCl3 Dehydration

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Alkyl halide formation

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Oxidation

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Selective oxidation
PCC (pyridinium chlorochromate) oxidizes RCH2OH RCHO only, R2CHOH R2C=O

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More rigorous oxidizing agents oxidize to RCOOH

2. CrO3/H+ (Jones reagent) or Na2Cr2O7/H+ (chromic acid reagent) or 1. KMnO4, HO- 2. H3O+ will oxidize 1o ROH to carboxylic acid oxidize 2o ROH to ketone

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select all that could have been oxidized from alcohol with PCC

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Mechanism of Cr(VI) oxidation of a 10 alcohol

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In H3O+ the aldehyde is in equilibrium with its hydrate

So the hydrate is oxidized to the carboxylic acid in a manner similar to the mechanism shown Tertiary alcohols are not oxidized, because there is no H on the alcohol carbon (to remove)
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Williamson ether synthesis McM 18.3

Relies on the fact that alcohols are weakly acidic Goes by an SN2 mechanism, so halide must be methyl or primary

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Esterification
Alcohols are converted to esters by reaction with (a) carboxylic acids (lab L), (b) acid chlorides

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Tosylate formation

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Use tosylate to control stereochemistry

Formation of tosylate does not affect stereochemistry Therefore the SN2 reaction that forms the product causes inversion

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Convert OH to CN without tosylate

two inversions, so original stereochem retained We can form either R or S enantiomer in the product by choosing reactions carefully
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Protection of alcohols
When a compound has more than one functional group, the different groups may interfere with the reactivity of others elsewhere in the molecule. Protecting groups are used to avoid this kind of interference Characteristics of a good protecting group:
Easily added Remains unaltered by desired reaction Easily removable
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Protect ROH as trimethylsilyl ether(TMS)

(remove with H3O+or F-)

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Alcohol protected as tetrahydropyranyl ether (THP) (remove with H3O+)

The TMS and THP protecting groups are insensitive to basic conditions, Grignard reagents, oxidizing and reducing agents, etc.
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which of the following resonance structure best justifies the orientation of the THP ether?

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Phenols (aromatic alcohols)

Act like aliphatic alcohols in many ways There are some significant differences Phenols are more acidic than aliphatic alcohols
The phenolic H can be removed with NaOH or KOH

pKa 16 pKa 10

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Increased acidity of phenols

due to resonance stabilization of phenoxide anion, so phenol dissociates more readily than ethanol

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Electron withdrawing groups increase the acidity

pKa 10

pKa 7.2

pKa 0.6 more acidic than most carboxylic acids

[increased electronic delocalization (can draw more resonance forms) see Fig. McM p. 663
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Electron donating groups decrease acidity

because the donated electron density destabilizes the phenoxide anion, so less delocalization occurs
pKa 10.46
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pKa 10

Preparation of Phenols

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Reactions of Phenols

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Kolbe-Schmitt carboxylation puts a

COOH group ortho to OH on phenol

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Oxidation of phenols
phenols are oxidized to quinones, (biologically important for energy production by electron transfer processes in the body) in vitro use Na2Cr2O7/H+ or Fremys salt (KSO3)2NO (potassium nitrosodisulfonate) to oxidize Use NaBH4 or SnCl2 to reduce quinone

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test prep task 1

using alkenes and cycloalkenes as sources of carbon, and any other necessary reagents and solvents, give an efficient, step-wise synthesis for

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test prep task 2

using compounds of 6 carbons or less, and any other necessary reagents and solvents, give an efficient, step-wise synthesis for

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test prep task 3

write a detailed reaction mechanism to explain all products indicated in the following reaction

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test prep task 4

classify as aromatic, antiaromatic or non-aromatic

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