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CHEM 12
ARMSTRONG
FOOTHILL COLLEGE
OUTLINE KLEIN CHAPTER THIRTEEN: ALCOHOLS
1. Structure/ Properties
a. Relative Boiling points, solubility: hydrogen bonding
b. Acid/Base behavior
i. pKa of MeOH ≈ 16
ii. Acidity trends with branching near C-OH: branching hinders anion
solvation
iii. Basicity of neutral alcohol (pKb(A-) = 14.0 - pKa(HA))
iv. Basicity of alkoxide ion
v. Formation of alkoxide ion by reaction of alcohols with strong base,
Na° or K°
2. Preparation of Alcohols
a. Via SN2 with 1° RLG and hydroxide
b. From alkenes via addition reactions (review)
i. Hg(OAc)2, H2O then NaBH4
ii. BH3•THF then H2O2, OHiii. Vicinal Diols
o from anti-addition of water to Epoxides (with acid or base
catalyst)
o from OsO4 with NMO
c. Via reduction of carbonyls or epoxides with Hydride Reducing reagents
i. Reduction of Ketones, Aldehydes and Epoxides with either NaBH4 or
LiAlH4
ii. Reduction of Esters and Carboxylic Acids with LiAlH4 only
d. Via Grignard RMgX or RLi
i. Formation of Grignard or Alkyl Lithium from alkyl halides
ii. reaction with Ketones and Aldehydes
iii. reaction with acid chlorides or esters (double addition)
iv. reaction with epoxides (Anti stereoselective; SN2-like regioselectivity)
v. Side reactions with acidic compounds
3. Reactivity of Alcohols
a. Reaction of Alkoxides with 1° RLG (Williamson Ether Syn)
b. Formation of alkenes via Elimination with strong mineral acids (H2SO4,
H3PO4)
i. Via E1 for 2° and 3° alcohols
ii. Carbocation rearrangement likely w -branch
iii. Concerted loss of LG and rearrangement for 1° alcohols
iv. Via E2 for 1° alcohols in absence of rearrangement
v. With POCl3 to form alkenes (not in text)
o E2 mechanism/No rearrangement
c. Pinacol rearrangement to form Ketones in vicinal diols
d. Formation of alkyl halides
i. Rxn with HX
o 2° and 3° via SN1 Mechanism: hydronium as leaving group
o Carbocation Rearrangement
CHEM 12
ARMSTRONG
FOOTHILL COLLEGE
OUTLINE KLEIN CHAPTER THIRTEEN: ALCOHOLS
o 1° via SN2 Mechanism with ZnCl2 as catalyst
ii. rxn w Thionyl chloride SOCl2 to form alkyl chlorides
o SN2 and SN1 Mechanisms compete/ no rearrangement/
inversion of configuration incomplete
iii. SN2 reaction With phosphorus trihalides PBr3 or PCl3 or PCl5 or P°
and I2 to form alkyl halides
o Mechanism/ no rearrangement/ inversion of configuration
e. Alkyl tosylates (sulfonate esters) by reaction of ROH with sulfonyl chlorides
i. Mechanism/ retention of configuration
ii. Subsequent reaction of alkyl tosylates with nucleophiles/bases
f. Reduction of Alcohols (Indirect 2 step reactions)
i. Via alkene with hydrogenation (review)
ii. Via tosylate or alkylhalide with LAH
g. Oxidation to form carbonyl compounds
i. NAD+/NADH: cofactors in biosynthesis
ii. Oxidation of 2° alcohols to ketones with chromic acid H2CrO4
iii. Oxidation of 1° alcohols to carboxylic acids with chromic acid
iv. Oxidation of 1° alcohols to aldehydes with Pyridinium
Chlorochromate (PCC)
v. Oxidation of alcohols to Ketones or aldehydes using DMSO in
(COCl)2, Et3N in CH2Cl2: “Swern Oxidation”
vi. Cleavage of vicinal diols with HIO4
LEARNING OUTCOMES
 Propose a reaction or sequence of reactions to produce a target alcohol in high yield.
 Predict the stereochemistry and optical activity of a product from an understanding of
its mechanism of formation.
 Predict the acidity of alcohols relative to one another and relative to other functional
groups
 Recognize structural features of a molecule that are key to its stability and reactivity.
 Predict the reagents needed to produce a given product from an alcohol in one or
more steps.
 Propose the mechanism of a chemical reaction involving alcohols consistent with
known data.
SAMPLE PROBLEMS
1. Propose a reaction/ sequence of reactions to effect the following stereoselective
reaction in high yield:
2. Consider the reaction below and tell why it DOES NOT provide high yields of the
products shown. Draw alternative products, if any are formed.
CHEM 12
FOOTHILL COLLEGE
OUTLINE KLEIN CHAPTER THIRTEEN: ALCOHOLS
ARMSTRONG
3. Consider the reaction below and answer the following:
a. Why doesn’t it provide high yields of the product shown?
b. Propose an alternative synthesis of the product (i.e How might the product
be synthesized in high yield via a different reaction).