1. Structure and Synthesis of Alcohols

2. Structure of Alcohols Hydroxyl (OH) functional group
Oxygen is sp3 hybridized =>

3. Classification Primary: carbon with –OH is bonded to one other carbon.
Secondary: carbon with –OH is bonded to two other carbons.
Tertiary: carbon with –OH is bonded to three other carbons.
Aromatic (phenol): -OH is bonded to a benzene ring =>

4. Classify these:
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5. IUPAC Nomenclature
Find the longest carbon chain containing the carbon with the -OH group.
Drop the -e from the alkane name, add -ol.
Number the chain, starting from the end closest to the -OH group.
Number and name all substituents. =>

6. Name these: 2-methyl-1-propanol 2-butanol 2-methyl-2-propanol
3-bromo-3-methylcyclohexanol =>

7. (1997 revision of IUPAC rules) =>
Unsaturated Alcohols
Hydroxyl group takes precedence. Assign that carbon the lowest number.
Use alkene or alkyne name.
4-penten-2-ol (old)
pent-4-ene-2-ol
(1997 revision of IUPAC rules) =>

8. Naming Priority Acids Esters Aldehydes Ketones Alcohols Amines Alkenes
Alkynes
Alkanes
Ethers
Halides =>

9. Hydroxy Substituent
When -OH is part of a higher priority class of compound, it is named as hydroxy.
Example:
also known as GHB =>
4-hydroxybutanoic acid

10. Common Names Alcohol can be named as alkyl alcohol.
Useful only for small alkyl groups.
Examples:
isobutyl alcohol
sec-butyl alcohol
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11. Naming Diols Two numbers are needed to locate the two -OH groups.
Use -diol as suffix instead of -ol.
1,6-hexanediol =>

12. Glycols 1, 2 diols (vicinal diols) are called glycols.
Common names for glycols use the name of the alkene from which they were made.
1,2-ethanediol
1,2-propanediol
ethylene glycol
propylene glycol
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13. Naming Phenols -OH group is assumed to be on carbon 1.
For common names of disubstituted phenols, use ortho- for 1,2; meta- for 1,3; and para- for 1,4.
Methyl phenols are cresols.
4-methylphenol
para-cresol
=>
3-chlorophenol
meta-chlorophenol

14. Physical Properties
Unusually high boiling points due to hydrogen bonding between molecules.
Small alcohols are miscible in water, but solubility decreases as the size of the alkyl group increases =>

15. Boiling Points
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16. Solubility in Water
Solubility decreases as the size of the alkyl group increases =>

17. Methanol “Wood alcohol” Industrial production from synthesis gas
Common industrial solvent
Fuel at Indianapolis 500
Fire can be extinguished with water
High octane rating
Low emissions
But, lower energy content
Invisible flame =>

18. Ethanol Fermentation of sugar and starches in grains
12-15% alcohol, then yeast cells die.
Distillation produces “hard” liquors
Azeotrope: 95% ethanol, constant boiling
Denatured alcohol used as solvent
Gasahol: 10% ethanol in gasoline
Toxic dose: 200 mL ethanol, 100 mL methanol =>

19. 2-Propanol
“Rubbing alcohol”
Catalytic hydration of propene
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20. Acidity of Alcohols pKa range: 15.5-18.0 (water: 15.7)
Acidity decreases as alkyl group increases.
Halogens increase the acidity.
Phenol is 100 million times more acidic than cyclohexanol! =>

21. Table of Ka Values
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22. Formation of Alkoxide Ions
React methanol and ethanol with sodium metal (redox reaction).
React less acidic alcohols with more
reactive potassium.
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23. Synthesis (Review) Nucleophilic substitution of OH- on alkyl halide
Hydration of alkenes
water in acid solution (not very effective)
oxymercuration - demercuration
hydroboration - oxidation =>

24. Organometallic Reagents
Carbon is bonded to a metal (Mg or Li).
Carbon is nucleophilic (partially negative).
It will attack a partially positive carbon.
C - X
C = O
A new carbon-carbon bond forms =>

25. Grignard Reagents Formula R-Mg-X (reacts like R:- +MgX)
Stabilized by anhydrous ether
Iodides most reactive
May be formed from any halide
primary
secondary
tertiary
vinyl
aryl =>

26. Some Grignard Reagents
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27. Organolithium Reagents
Formula R-Li (reacts like R:- +Li)
Can be produced from alkyl, vinyl, or aryl halides, just like Grignard reagents.
Ether not necessary, wide variety of solvents can be used =>

28. Reaction with Carbonyl
R:- attacks the partially positive carbon in the carbonyl.
The intermediate is an alkoxide ion.
Addition of water or dilute acid protonates the alkoxide to produce an alcohol.
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29. Synthesis of 1° Alcohols
Grignard + formaldehyde yields a primary alcohol with one additional carbon.
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30. Synthesis of 2º Alcohols
Grignard + aldehyde yields a secondary alcohol.
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31. Synthesis of 3º Alcohols
Grignard + ketone yields a tertiary alcohol.
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32. How would you synthesize…
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33. Grignard Reactions with Acid Chlorides and Esters
Use two moles of Grignard reagent.
The product is a tertiary alcohol with two identical alkyl groups.
Reaction with one mole of Grignard reagent produces a ketone intermediate, which reacts with the second mole of Grignard reagent =>

34. Grignard + Acid Chloride (1)
Grignard attacks the carbonyl.
Chloride ion leaves.
Ketone intermediate =>

35. Grignard and Ester (1) Grignard attacks the carbonyl.
Alkoxide ion leaves! ? !
Ketone intermediate =>

36. Second step of reaction
Second mole of Grignard reacts with the ketone intermediate to form an alkoxide ion.
Alkoxide ion is protonated with dilute acid.
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37. How would you synthesize...
Using an acid chloride or ester.
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38. Grignard Reagent + Ethylene Oxide
Epoxides are unusually reactive ethers.
Product is a 1º alcohol with 2 additional carbons.
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39. Limitations of Grignard
No water or other acidic protons like O-H, N-H, S-H, or -C—C-H. Grignard reagent is destroyed, becomes an alkane.
No other electrophilic multiple bonds, like C=N, C—N, S=O, or N=O =>

40. Reduction of Carbonyl Reduction of aldehyde yields 1º alcohol.
Reduction of ketone yields 2º alcohol.
Reagents:
Sodium borohydride, NaBH4
Lithium aluminum hydride, LiAlH4
Raney nickel =>

41. Sodium Borohydride
Hydride ion, H-, attacks the carbonyl carbon, forming an alkoxide ion.
Then the alkoxide ion is protonated by dilute acid.
Only reacts with carbonyl of aldehyde or ketone, not with carbonyls of esters or carboxylic acids.

43. Lithium Aluminum Hydride
Stronger reducing agent than sodium borohydride, but dangerous to work with.
Converts esters and acids to 1º alcohols.
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44. Comparison of Reducing Agents
LiAlH4 is stronger.
LiAlH4 reduces more stable compounds which are resistant to reduction =>

45. Catalytic Hydrogenation
Add H2 with Raney nickel catalyst.
Also reduces any C=C bonds.
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46. Thiols (Mercaptans) Sulfur analogues of alcohols, -SH.
Named by adding -thiol to alkane name.
The -SH group is called mercapto.
Complex with heavy metals: Hg, As, Au.
More acidic than alcohols, react with NaOH to form thiolate ion.
Stinks! =>

47. Thiol Synthesis
Use a large excess of sodium hydrosulfide with unhindered alkyl halide to prevent dialkylation to R-S-R.
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48. Thiol Oxidation
Easily oxidized to disulfides, an important feature of protein structure.
Vigorous oxidation with KMnO4, HNO3, or NaOCl, produces sulfonic acids.
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Chapter 10