Alcohols and Ethers

Question 1

What makes a hydroxyl group more acidic?

Answer 1

When the negative charge can be distributed through resonance or electron withdrawing groups are nearby to share the negative charge.

Question 2

What are the three key reactions for creating alcohols?

Answer 2

1) Nucleophilic substitution via SN1 and SN2
2) Electrophilic addition to a double bond
3) Nucleophilic addition to a carbonyl

Question 3

Common reducing agents for creating alcohols and their limitations?

Answer 3

LiAlH4 (LAH) and NaBH4. LAH reduces everything including esters, amides, and carboxylic acids, all the way to alcohol. NaBH4 is weaker and cannot reduce esters, carboxylic acids, or amides.

Question 4

Explain phenol synthesis via the hydrolysis of diazonium salt

Answer 4

Way to synthesize Phenol. Benzene with NH2 and Br is reacted with HNO2 in H2SO4 which creates the diazonium salt, benzene with Br and N2+. The N2+ group then leaves and is replaced with OH.

Question 5

How to coax alcohols to participate in SN1/SN2 reactions?

Answer 5

Make the OH a good leaving group by

1) Protonating it
2) Converting it to a tosylate
3) Form an inorganic ester

Question 6

What’s a milder way to eliminate a hydroxyl group than H2SO4 + heat?

Answer 6

POCl3, through an E2 mechanism.

Question 7

Name a couple compounds that can be used to make OH a good leaving group?

Answer 7

Tosyl chloride, thionyl chloride (SOCl2), PBr3 in pyridine

Question 8

What is a mild oxidizing agent and what’s an example?

Answer 8

PCC will only oxidize an OH to an aldehyde because it lacks the water to hydrate the aldehyde.

Question 9

What is another reagent used to fully oxidize primary and secondary alcohols? What’s an even stronger oxidant?

Answer 9

Sodium or potassium dichromate salt (in acid). Even stronger is CrO3 (with dilute sulfuric acid in acetone). Called Jone’s oxidation.

Question 10

How would you create an alcohol from an aldehyde or ketone?

Answer 10

Add NaBH4 or LiAlH4 in acid.

Question 11

How would you create an alcohol from a carboxylic acid or ester or amide?

Answer 11

LiAlH4 in acid. NaBH4 is not strong enough to reduce an ester or carboxylic acid or amide.

Question 12

How would you create an alcohol from a haloalkane?

Answer 12

Through SN1 or SN2 mechanism with OH- (from NaOH).

Question 13

How would you create an alcohol from a double bond?

Answer 13

Add water and acid (sulfuric) at low temperature. The electrons in the double bond attack the free H+, creating a carbocation. Water attacks that carbocation and sheds a proton back into solution.

Question 14

Describe Williamson ether synthesis

Answer 14

Metal alkoxide combined with primary alkyl halide or tosylate. Alkoxide attacks alkyl halide through SN2 rxn. Competes with E2. Also works with phenols in mild basic conditions because the hydrogen is relatively acidic.

Question 15

What’s a common way to produce cyclic ethers with a haloalcohol?

Answer 15

Strong base and intramolecular SN2.

Question 16

How to make a cyclic ether with an alkene?

Answer 16

Oxidation with a peroxy acid (ROOOH) such as mCPBA.

Question 17

What happens to ethers when reacted with oxygen in air?

Answer 17

They form highly explosive peroxides.

Question 18

Explain how to cleave an ether

Answer 18

Takes place only under vigorous conditions, at high temps in the presence of HBr or HI. The ether oxygen is protonated and then a SN1 or SN2 reaction proceeds.

Question 19

How do epoxides react when attacked under acidic conditions (HBr) vs basic conditions (Br-)?

Answer 19

In acidic, the epoxide is cleaved in an SN1-like way, so the nucleophile ends up on the more highly substituted carbon. In basic conditions, the nucleophile attacks the less substituted carbon in an SN2 rxn.