Chapter 10: Structure and Synthesis of Alcohols
100 Physical Properties
Alcohols can be: OH
CH3 CH3 CH CH2CH3 * CH3 CH CH2OH * Secondary alcohol Primary alcohol
CH3 * CH3 C OH
CH3 Tertiary alcohol
101 • Most alcohols (C 1-C12 ) are liquids at room temperature • Bp much higher than alkanes of similar molecular weights (H-bonding)
102 Acidity : the H of the hydroxyl group is weakly acidic:
103 This hydroxyl proton can be removed with suitable bases. Bases such as KOH or NaOH are not strong enough.
NaH, KH or Na (s) , K (s) are usually used.
104 In the case of phenols, the pKa of the hydroxyl group is around 10 and weaker bases can be used (NaOH, KOH, etc…)
105 Synthesis of Alcohols (Review) § Hydration (a) Direct (8.4)
106 Mechanism of Direct Hydration of Alkenes
107 (b) Indirect (4.8) (1) Oxymercuration/Demercuration (8.5)
(2) Hydroboration/Oxidation (8.7)
108 § Hydroxylation (8.14)
109 New Synthesis of Alcohols (Nu attack on carbonyl compounds) An excellent method to make alcohols. Depending on the type of carbonyl used, primary, secondary and tertiary alcohols are all available from this reaction.
110 2 types of reagents can deliver nucleophilic carbons to C=O:
◦ Grignard reagent: R-Mg-X ◦ Alkyl Lithium: R-Li
δ− δ+ δ− δ+
R M gX R Li
111 § Synthesis of Grignard Reagents (10.8)
Br ether MgBr + Mg
Cl MgCl ether CH3CHCH2CH3 + Mg CH3CHCH2CH3
112 Alkyl Lithium can be prepared in a similar way:
113 § Synthesis of 1 o Alcohols (10.9) Grignards or alkyl lithium react with formaldehyde to produce primary alcohols. The carbon chain increases by one carbon from the original organometallic reagent.
114 § Synthesis of 2 o Alcohols (10.9) other aldehydes react to give secondary alcohols with either Grignard reagents or alkyl lithiums to produce secondary alcohols
115 § Synthesis of 3 o Alcohols (10.9) reaction of ketones with RLi or RMgX will produce tertiary alcohols
116 § 3o Alcohols by Acyl Substitution (10.9) acid chlorides and esters react with either Grignard reagents or alkyl lithiums via the acyl substitution mechanism. Since the resulting product is a ketone, the reaction will continue and eventually produce the corresponding tertiary alcohol.
117 Mechanism of Acyl Substitution In the presence of a Grignard or alkyl lithium the reaction will first produce a ketone which will continue to react to produce the corresponding 3 o alcohol.
118 Here is an example of this reaction using two equivalent of grignard reagent with an ester.
119 1o Alcohols With 2 Extra Carbons on the Alkyl Chain. (10.9) These compounds are generated by the reaction of RLi or RMgX with epoxides. ◦ Epoxides are electrophilic due to the ring strain. ◦ 2 extra carbons will be added to the alkyl chain.
120 Limitations of Grignard Reagents
Grignards are good nucleophiles but in the presence of acidic protons it will acts as a strong base. ◦ No water or other acidic protons like O—H, N—H, S—H, or terminal alkynes. No other electrophilic multiple bonds, like C ═N, C ≡≡≡N, S ═O, or N═O.
121 Practice Question What is the major organic product of the following reactions. Disregard stereoisomers.
122 3-Methyl-3-hexanol can be prepared from the reaction of 2-pentanone and ethylmagnesium bromide as shown below. What other combination or grignards and ketones can be used to prepare
this compound? O 1) CH3CH2M gBr OH
2) H3O+
123 Reduction of Carbonyl Compounds (10.11)
Reduction of the carbonyl group also produces alcohol by nucleophilic attack to the carbon of the carbonyl. In this case the nucleophile is the hydride ion. Protonation of the resulting alkoxide ion gives the alcohol.
124 2 common reagents to carry out this transformation are :
LiAlH 4 : lithium aluminum hydride
NaBH 4 : sodium borohydride
125 NaBH 4 is selective only for ketones, aldehydes and acid chlorides. LiAlH 4 will reduce all carbonyl compounds.
126 This selectivity can be used in synthesis to control which functional group reacts.
127 Mechanism of Hydride Reduction of Carbonyls (Ketones and Aldehydes)
128 Mechanism of Acid Chloride/Ester Reduction
In the case of esters and acid chlorides, two equivalents of the hydride are transferred since the first product is a ketone. 1 o alcohols are produced.
129 Catalytic Hydrogenation (10.11)
Similar to the hydrogenation of alkene
seen in CHEM201, addition of H 2 to the carbonyl of ketones and aldehydes is possible resulting in the formation of alcohols.
130 This reaction is also complementary to the reduction using metal hydrides as it allow for other reduction to take place.
131 Practice Questions
Complete the following reactions.
NaBH4 COOCH3 MeOH
132