Alcohol Synthesis and Reactions

Question 1

Oxymercuration: Reactants

Answer 1

1. Hg(OAc)₂ , H₂O
—————————————————>
2. NaBH₄, NaOH

Question 2

Oxymercuration Mechanism

Answer 2

1) Alkene electrons attack Hg ==> Hg bound by 2 carbons

2) H₂O attacks the MOST SUB carbon attached to HG
==> Backside attack to give inversion at the attacked carbon

3) NaBH₄ and NaOH replace Hg on other carbon with an H

4) OH- deprotonates the H₂O to give the alcohol

Question 3

Oxymercuration Properties

Answer 3

1) Stereochem inversion where OH adds

2) ANTI addition

3) Markovnikov (OH on most sub carbon of the alkene)

Question 4

Hydroboration: Reactants

Answer 4

1. BH₃
———————–>
2. H₂O₂, OH-

Question 5

Hydroboration Mechanism

Answer 5

1) Alkene attacks BH₃
==> Forms bond between alkene carbons and H and BH₂ SIMULTANEOUSLY (Syn)

2) BH₂ adds to the LEAST sub. carbon

3) H₂O₂ and OH- oxidize the BH₂ and swaps it with an OH forming the alcohol

Question 6

Hydroboration Properties

Answer 6

1) NO stereochem. selectivity

2) SYN addition

3) ANTI-Markovnikov (OH adds to the LEAST substituted carbon)

Question 7

Acid Catalyzed Hydration: Reactants

Answer 7

H₃O⁺
———————–>
H₂O

Question 8

Acid-Catalyzed Hydration Mechanism

Answer 8

1) Alkene attacks H₃O⁺, deprotonating it

2) Carbocation forms! (the stolen H adds to the least sub side)

3) Carbocat rearrangement occurs if needed/possible

4) H₂O attacks the carbocation adding to it

5) H₂O deprotonates the water added to the carbocation
==> H₃O⁺ reforms and an alcohol is created

Question 9

Acid-Catalyzed Hydration Properties

Answer 9

1) No stereoselectivity (stereochem is lost by making carbocation)

2) OH goes on the carbon that forms the most stable carbocation

3) Subject to carbocation rearrangment!

Question 10

Osmium Tetroxide

Answer 10

1. OsO₄
————————->
2. (CH₃)₃ Na⁺O^-, H₂O

Question 11

Osmium Tetroxide Products and Properties

Answer 11

Produces a 1,2-DIOL with IDENTICAL stereochem of the OH grps!

1) SYN addition

2) No steroselectivity (can attack from any side)

Question 12

Organolithium Alcohol Synthesis: Reactants

Answer 12

1°R-Li + Ketone or Aldehyde
——————————————>
H₃O⁺

Question 13

Organolithium Alcohol Synthesis: process and properties

Answer 13

1) Lithium carbon attacks the carbonyl carbon on the ketone/aldehyde (attaching the R group to the carbonyl carbon)

2) Double bond gets pushed up to the oxygen creating a (-) oxygen

3) (-) Oxygen attacks and deprotonates H₃O⁺ to create the alcohol

Question 14

Grignard Alcohol Synthesis: Reactants

Answer 14

1°R-MgX + Ketone or Aldehyde
——————————————>
H₃O⁺

Question 15

Grignard Alcohol Synthesis: process and properties

Answer 15

1) MgX carbon attacks the carbonyl carbon on the ketone/aldehyde (attaching the R group to the carbonyl carbon)

2) Double bond gets pushed up to the oxygen creating a (-) oxygen

3) (-) Oxygen attacks and deprotonates H₃O⁺ to create the alcohol

Question 16

NaBH₄ (Reductive Alcohol Synthesis): Reactants

Answer 16

NaBH₄ + Ketone or Aldehyde
————————————–>
EtOH

Question 17

NaBH₄ (Reductive Alcohol Synthesis): Process

Answer 17

1) NaBH₄ provides an H^- that reduces the acyl group
–>(adds an H and removes the double bond from oxygen creating a (-) charge on oxygen)

2) Negatively charged oxygen deprotonates EtOH to produce the alcohol

Question 18

In the reductive synthesis of alcohols, what is the purpose of NaBH₄ and EtOH

Answer 18

NaBH₄ = Reducing agent (Source of H-)

EtOH = Proton source (source of H+ to form OH)

Question 19

LiAlH₄ (Reductive Alcohol Synthesis): Reactants

Answer 19

LiAlH₄ + Ketone/Aldehyde/Carboxy Acid/Ester
————————————————————————————–>
H₃O⁺

Question 20

LiAlH₄ (Reductive Alcohol Synthesis): Process with CARBOXY ACID

Answer 20

1) LiAlH₄ removes the carbonyl oxygen from the molecule and replaces with 2H

2) Alcohol is formed with the OH from the COOH remaining!

Question 21

LiAlH₄ (Reductive Alcohol Synthesis): Process with ESTER

Answer 21

1) LiAlH₄ reduces the carbonyl oxygen and forms an OH with it

2) The O-R bond is cleaved (by replacing with an H), releasing the O-R group from the now alcohol

3) The released O-R group gets protonated by acid and forms an alcohol

–> TWO alcohols are formed here! –> One with the carbonyl oxygen and one from the O-R grp of the ester

Question 22

What are the three methods of turning an alcohol into an alkyl halide?

Answer 22

1) 3°ROH + HX

2) 1°/2° ROH + PBR₃

3) 1°/2° ROH + SOCl₂

Question 23

3° Alcohol to Alkyl Halide: Reactants + Process

Answer 23

3°ROH + HX
———————>

1) ROH attacks HX and “steals” an H

2) ROH₂ spontaneously loses water producing a carbocation

3) Carbocation rearrangement if needed/possible

4) X^- attacks the carbocation forming the alkyl halide

(SN1 Mechanism!)

Question 24

1°/2° Alcohol to Alkyl Halide: Reactants + Process

Answer 24

1°/2° ROH + PBr₃ or SOCl₂
————————————————————–>

1) PBr₃ or SOCl₂ attacks the OH carbon ==> BACKSIDE ATTACK, pushing off the OH group

2) Backside attack causes stereochemistry inversion!

(SN2 Mechanism!)

Question 24

Tosylation and Mesylation: Reactants, Process, Properties

Answer 24

**TsCl or MsCl -------------------> Pyridine** 1) Chlorine deprotonates the alcohol to form HCl 2) Tosylate or mesylate grp. attaches to (-) oxygen 3) Forms OTs or OMs ------> Can then go on to react with a nucleophile for an SN2 reaction OR an E2 reaction under basic conditions!

Question 25

What is the purpose of tosylation?

Answer 25

To convert alcohol into a good leaving group so that it can then undergo nucleophilic substitution reaction

Question 26

What is the difference in nucleophilic substitutions if a 3° alcohol is tosylated vs a 1°/2/° alcohol is tosylated?

Answer 26

1°/2° ROH --> Tosylation will create an LG that can undergo SN2 nucleophilic substitution 3° ROH --> Tosylation will create an LG that will favor an E2 elimination reaction!

Question 27

Ester Synthesis: Reactants (2 methods)

Answer 27

Carboxy Acid +1°/2°ROH -----------------------------------> Carboxy Acid + SOCl₂ -------------------------------> 1°/2°ROH

Question 28

Ester Synthesis: Carboxy Acid + ROH Process

Answer 28

1) Carboxy acid OH grp deprotonates ROH to create an H₂O group ==> Alkoxide ion (R-O^-) 2) H₂O group leaves spontaneously to form a carbonyl carbocation 3) Carbonyl carbocation reacts with alkoxide ion to form an ester!

Question 29

Ester Synthesis: Carboxy Acid + SOCl₂ + ROH process

Answer 29

1) SOCl₂ backside attacks the OH group on the carboxy acid ==>Forms an acyl chloride (Carbonyl group attached to a chlorine) 2) Chlorine of the acyl chloride deprotonates the ROH and releases from the carbonyl group as HCl ==> Carbonyl carbocation + alkoxide (from the ROH) 3) Carbonyl carbocation + alkoxide react with each other to form the ester!

Question 30

In ester synthesis with an alcohol, what degree does the alcohol need to be?

Answer 30

Technically it can be primary, secondary, or tertiary BUT 1°ROH will react the fastest AND 2°ROH will definitively undergo the substitution process as well 3°ROH however has the potential to undergo an elimination reaction instead of producing the ester!

Question 31

Alcohol Dehydration: Reactants + Process

Answer 31

**ROH + H₂SO₄ ----------------------------->** 1) ROH deprotonaates H₂SO₄ to turn OH into a better H₂O LG ==> ROH₂ + HSO₄ ^- 2) H₂O spontaneously leaves forming a carbocation 3) Carbocation rearrangement occurs if possible 4) HSO₄ ^- abstracts an H on a carbon adjacent to the carbocat to form the most stable ALKENE

Question 32

What are the methods of alcohol oxidation?

Answer 32

1) Chromium (IV) reagents == carboxy acids and ketones 2) KMnO₄ reagent == carboxy acids and ketones 3) PCC == Ketones and aldehydes 4) Dess-martin == Ketones and aldehydes

Question 33

Alcohol oxidation with chromium reagent: Reactants

Answer 33

Na₂Cr₂O₇ or CrO₃ ------------------------------> H₂SO₄, acetone

Question 34

Alcohol oxidation with potassium permanganate: Reactants

Answer 34

**KMnO₄ ------------------------> NaOH, H₂O**

Question 35

Alcohol oxidation with PCC: Reactants

Answer 35

**PCC ---------> CH₂Cl₂**

Question 36

Alcohol oxidation with Dess-martin: Reactants

Answer 36

**Dess-martin ------------------------> CH₂Cl₂**

Question 37

Alcohol oxidation with KMnO₄ or Cr(IV) Reagents: Products

Answer 37

1°ROH --> Does TWO oxidation steps!! ==> CARBOXY ACID 2°ROH --> Does ONE oxidation step==> KETONE

Question 38

For 1°ROH: Why does PCC and Dess-Martin oxidation produce aldehyde whereas KMnO₄ and Cr(IV) reagents produce carboxy acid?

Answer 38

Due to the reaction conditions! --> PCC and Dess-Martin occur in ORGANIC solvents (not an aqueous reaction mixture) --> KMnO₄ and Cr(IV) reagents occur in AQUEOUS solvents (promotes the second oxidation step that converts an aldehyde to carboxy acid!)

Question 39

Alcohol oxidation with PCC or Dess-Martin: Products

Answer 39

1°ROH --> Does ONE oxidation step ==> Aldehyde 2°ROH --> Done ONE oxidation step ==> KETONE