Alcohols and Phenols.pdf

7/27/2019 Alcohols and Phenols.pdf

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alcohols & phenols 1

Alcohols and Phenols

R-OH and Ar-OH

In alcohols C(sp3)-OHIn phenols C(sp2)-OH


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Complex alcohols

cholesterol


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most steroids function as hormones

(chemical messengers)

cholesterol

Hydrocortisone

(control inflammation)

progesterone

(fertility control)

progesterone (developmentof male sexual characteristics)


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More complex alcohols

glucose

cellulose

Amylose

(a form of starch)


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Carbolic acid (phenol) was one of the first

Antiseptics used in surgery

Lord Lister in surgery

a chemical burn


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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 near1200 cm-1,

IR of phenol also shows aromatic absorptionO-H at 3300 3600 cm-1, C=C at 1600 cm-1


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1H NMR


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IR: 3500 cm-1

51H 1H

3H

C8H10O


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NomenclatureUse 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 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) oxidizesRCH2OH RCHO only, R2CHOH R2C=O


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More rigorous oxidizing agents

oxidize to RCOOH2. CrO3/H+ (Jones reagent)

orNa2Cr2O7/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 acidin a manner similar to the mechanism shown

Tertiary alcohols are not oxidized, because thereis 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 groupsmay interfere with the

reactivity of others elsewhere in the molecule.

Protecting groups are used to avoid this kind ofinterference

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 tetrahydro-

pyranyl ether (THP) (remove with H3O+

)

The TMS and THP protecting groups areinsensitive 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 10

pKa 16


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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

[increased electronic delocalization (can draw

more resonance forms) see Fig. McM p. 663

pKa 10 pKa 7.2 pKa 0.6

more acidic than mostcarboxylic acids


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Electron donating groups decrease

aciditybecause

the donated

electron density

destabilizes thephenoxide

anion, so less

delocalization

occurspKa 10pKa 10.46


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Preparation of Phenols


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Reactions of Phenols


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Kolbe-Schmitt carboxylation puts aCOOH group ortho to OH on phenol


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Oxidation of phenols

phenols are oxidized to quinones, (biologicallyimportant for energy production by electron transferprocesses 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 andsolvents, 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 anefficient, 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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Alcohols and Phenols.pdf