6 Alcohols And Ethers Oct 31 Notes

Alcohols Order the following compounds from most to least acidic? HO OH OH2

C

1

A) B) C) D) E)

1>2>3 3>2>1 2>1>3 3>1>2 1>3>2

3

2

Which of the following equilibriums would not be shifted to the right? O

OH +

A)

+

CH3O

OH

O +

B)

CH3OH

+

+

CH3O

+

CH3OH

OH

OH2 C)

CH3OH

CH3O

Sec. 6: Alcohols, Ethers

1

Alcohols may be weakly basic as well as being acidic. Molecules that can be both acidic and basic are called amphoteric. strong base

strong acid R

OH2

Alkoxonium ion Strong Acid

R

mild base

OH

Alcohol

R

mild acid

Weak acid and base

O

Alkoxide ion Strong Base

Very strong acids are required to protonate alcohols.

Sec. 6: Alcohols, Ethers

2

Preparation of Alcohols

• •

90 %

SN1 SN2

10 %

O

HMPA – hexanamethylphosphoric triamide

(H3C)2N

(H3C)2N Sec. 6: Alcohols, Ethers

P

N(CH3)2

3

Oxidation States of Carbon A reaction of an organic molecule usually corresponds to increasing its hydrogen content or decreasing its oxygen content. [O]

RCH3 Lowest Oxidation State

RCH2OH

[H]

OH R CH R

O R C H

[O] [H]

[O] [H]

O R C

[O] [H]

O R C OH Highest Oxidation State

R

Oxidation → broad definition → a reaction that increases its content of any element more electronegative than carbon CH3

[O]

CH2Cl

[H]

How to figure out the oxidation state of a carbon atom a bond to hydrogen or anything less electronegative than carbon is electron donating → -1 a bond to nitrogen, oxygen or anything more electronegative than carbon is electron withdrawing → +1 H H a bond to a carbon → 0

H

OS = 4 x -1 =-4

H

C

O

H

C

O

OS = 4 x +1 =+4

H

OS = oxidation state

H

C

C

H

H

OS = (3 x -1) + 0 =-3 Sec. 6: Alcohols, Ethers

OH OS = Hydrogen - (2 x -1)

Oxygen - (1 x 1) Carbon - 0 =-1 4

Oxidation States of Carbon H

H C

C H

H OS = - 2

H2/Pd

H

Reduction

H

H

C

C

H H OS = - 3

H

H

H

H

C

C

H

H

OS = - 1

OH

KMnO4 Oxidation

H

H

O

C

C

OH

H OS = 3

LEO goes GER – Loss of Electrons Oxidation, Gain of Electrons Reduction

Alcohols can form by hydride reduction of the carbonyl group The carbonyl functional group is polarized due to the high electronegativity of the carbonyl oxygen atom:

Sec. 6: Alcohols, Ethers

5

Alcohols by Reduction of Carbonyl Compounds with LiAlH4 and NaBH4 The carbonyl carbon can be attacked by a nucleophilic hydride ion, H¯, furnished by a hydride reagent. Sodium borohydride, NaBH4, and lithium aluminum hydride, LiAlH4, are commonly used for hydride reductions because their solubilities are higher in common organic solvents than LiH and NaH.

The carbonyl group is susceptible to nucleophilic attack.

Nucleophile (base)

Electrophile (acid) These reductions are achieved by the addition of a H¯ ion (nucleophile) to the electropositive carbon and a proton to the electronegative oxygen Sec. 6: Alcohols, Ethers

6

R

Electrophile (acid) Oδ CH3CH2OH C δ+ R solvent

Mechanism with LiAlH4 and NaBH4 R

R H

C

+

O Na

+ BH3

H

C

O BH3 + CH3CH2OH

R

R

+

Na H3B- H Nucleophile (base)

R H

C R

R R H

C R

OH + CH3CH2O BH3 O

This will react three more times

C

CH3CH2OH

R

R OH

+

NaB(OH)3

+ CH3CH2OH

H2O

4 H

C

OH +

(CH3CH2O)4B

R Sec. 6: Alcohols, Ethers

7

The reactivity of LiAlH4 is much greater than that of NaBH4 and is less selective in its reactions. LiAlH4 reacts vigorously with water and ethanol and must be used in an aprotic solvent such as diethyl ether.

Electrophile (acid) Oδ C δ+ R R

H

O R H

C R

+

OAlH3 Li

3 R

R R

C

H

R

Solvent: Et2O

R

O O

R

Al

R O

O R

C

C R

R

R

H

or

H

C R

+

OAl Li 4

H

+

Li H3Al- H Nucleophile (base)

C

C

a tetra-alkyl aluminate R LiOH + Al(OH)3 + H

C

H3O+ OH

work-up

R Sec. 6: Alcohols, Ethers

8

Oxidation of Alcohols Oxidation - loss of electrons or add oxygens OS = +1

OS = -1

CH3CH2CH2OH propanol

KMnO4 / OH¯ / heat

O

CH CH CH

very hard to stop oxidation

3 2 or NaCr2O7 / H2SO4 propanal or H2CrO4 or CrO3  Jones reagent

OH

OH

O H2CrO4

CH3CH2COH

propanoic acid

H2CrO4

No Reaction

acetone

acetone OS = 0

OS = +3 O

OS = +2

can’t break C-C σ bond

can’t break C-C σ bond

Sec. 6: Alcohols, Ethers

9

Oxidation of Alcohols Primary alcohols tend to overoxidize to carboxylic acids when oxidized in aqueous solution:

Overoxidation of primary alcohols is not a problem in the absence of water. The oxidizing agent, pyridinium chlorochromate (pyH+CrO3Cl-) can be used in dichloromethane to successfully oxidize these alcohols:

CH3CH2CH2OH + PCC

CH2Cl2

O Cl

CH3CH2CH stops at aldehyde

H

C

Cl H aprotic solvent

Sec. 6: Alcohols, Ethers

10

Chromic esters are intermediates in alcohol oxidation The mechanism of chromium(VI) oxidations involves two steps: Formation of a chromic ester E2 elimination of a proton and a HCrO3- ion.

Oxidized farther to carboxylic acid If using PCC stops at aldehyde The Cr(IV) species disproportionates into Cr(III) and Cr(V) (redox reaction). The Cr(V) may also function as an oxidizing agent. Eventually all is reduced to Cr(III). Sec. 6: Alcohols, Ethers

11

Examples 1) LiAlH4/Et2O 2) H3O+

O

OS = +1

OS = -1

O

OH

O

OS = +3

OH B)

A)

H

C)

O CH3

NaBH4/H2O

OH

(H3C)2HCO

OH

(H3C)2HCO B)

A)

CH3

CH3

O

O O

O

O

OH

O

O

D)

A)

H

OH

O

OH

OH OS = 0

NaCr2O7 / H2SO4

O

B)

E)

OH

H OH

OS = +3 C)

Sec. 6: Alcohols, Ethers

OH

OS = +2

OS = +3 already oxidized 12

Organometallic Compounds +

C M M = Na+ or K+ Primarily ionic explosive with water

δ+ δ - C M

C

M = Mg or Li polar covalent

M = Pb, Sn, Hg, or Tl Primarily covalent

relative stable in ether

M

much less reactive

CH3Li CH3MgCl Sec. 6: Alcohols, Ethers

13

Organolithium Compounds Br

+ 2 Li

Br

+ 2 Li

ether

Li

ether

Li

+ LiBr

+ LiBr

Grignard Reagents Br

+ Mg

Br + Mg

ether

MgBr

ether

MgBr

General Reactions The actual structure of the Grignard reagents are more complex than the formula 2 RMgX

R2Mg +

MgX2

It also forms a complex with the solvent, ether For convenience we will represent Sec. 6: Alcohols, the Grignard reagent asEthers RMgX

14

Grignard reagents as well as organolithium compounds are very strong bases. They act as if they have free carbanions. Organolithium compounds will react as a Bronsted-Lowry base or as a nucleophile. δ δ+ δ δ+ δ δ+ CH MgBr + CH O-H - 3 3CH2-

CH4

+ CH3CH2O

Mg2+

+

X

weaker base carbon with a negative charge is a stronger base than an oxygen with a negative charge

C

C sp

sp2

δ δ+ H + CH - 3MgBr sp3

C

C

+ MgBrCl

C

CH2

C

SN2 δ+

CH3 CH3

dilute HCl

OMgBr C6H5

+ CH4

weaker base

OH C6H5

δ δ+ δ -C MgBr-

C

C

CH2

C

δ Oδ+

steric interaction

CH3 CH3

Sec. 6: Alcohols, Ethers

15

Alkylhalides into Alkanes

A more direct way of producing an alkane from a haloalkane is by an SN2 displacement of the halide by a hydride ion from LiAlH4.

NaBH4 is not reactive enough to carry out this displacement. A deuterium atom can be introduced into an alkane by the reaction of D2O with an organometallic reagent:

Sec. 6: Alcohols, Ethers

16

Grignard Reagents and Carbonyl Compounds

Step One

Mechanism

R δ δ+ δ δ+ δ -R MgX+ C -O nucleophile R (base) electrophile (acid) Step Two R R

C R

R ether

Mg2+ X

H

C

O

Mg2+ X

R halomagnesium alkoxide

+

O

R

nucleophilic attack on carbonyl carbon

R

H

O

X

R

H

C

OH

+ H2O + MgX2

R alcohol

Order of Reactivity

RI > RBr > RCl

RI and RBr mostly used RCl reacts sluggishly Sec. 6: Alcohols, Ethers

17

General Reactions δ δ+ δ -R1MgBr-

H +

δ+ δ C -O

H ether

R1

H formaldehyde

δ δ+ δ -R1MgBr-

δ+ δ C -O

ether

R1

+

C

OMgBr

a ketone

ether

R1

C

C

OH + MgBr2

R2 R1

C

OH + MgBrCl

H 2° alcohol

R2

R3

HCl (dilute)

H

R2 δ+ δ C -O

R1

H 1° alcohol

R2

H an aldehyde

δ δ+ δ -R1MgBr-

OMgBr

H

H

R2 +

C

HBr (dilute)

OMgBr

HCl (dilute)

R3

R2 R1

C

OH + MgBrCl

R3 3° alcohol

Sec. 6: Alcohols, Ethers

18

General Reactions δ δ+ δ -R1MgBr-

R2

R2 +

δ+ δ C -O

ether

R1

R3O

C R3O

a ester

R2 C

OMgBr R1

δ δ+ -R1MgBr

leaving group

R2 R3OH + MgBrCl +

R1

C

OH

O + R3OMgBr

R2

HCl (dilute)

R1 3° alcohol

R1

C

OMgBr

R1

Grignard Reagent add twice because a ketone is created as an intermediate that can react with the second equivalence of the Grignard Reagent

Sec. 6: Alcohols, Ethers

19

Examples  Because Grignard reagents are very strong bases they can not be made from compounds that have acidic hydrogens → -OH, -NH2, -SH, -CO2H, -SO3H etc.  Limited to alkyl halides or organic compounds containing carbon-carbon double bonds, internal triple bonds, ether linkages and -NR3 groups.  Although we can make acetylenic Grignards through an acid base reaction and use it to our advantage. δ O δ δ+ OH -δ+ δ δ+ 1) CH MgBr CH3CH2C CH - 3 CH3CH2C -CMgBr H ether + CH4(g) 2) H3O+

H3C O δ+ δ -

1)

CH

δ δ+ - 2Li CH

H3 C 2) H3O+

OH

Sec. 6: Alcohols, Ethers

20

Examples Sometimes a Grignard reaction can be completed with a compound containing an acidic hydrogen if two equivalents of the reagent is used δ O δ δ+ OH δ δ+ CH ether - 3MgBr CH HOCH2CH2C CH3 BrMgOCH2CH2CCH3 - 3MgBr + HOCH2CH2CCH3 + δ+ 2) H3O CH3 + CH4(g) Oδ + δ+ C Na O + δ δ+ 1) H3C CH3 Na NH2 CH3CH2C CH CH3CH2C C C CH3 CH3CH2C C - Na 2) NH4Cl, H2O CH3 H O

H OH CH3CH2C C

C

+ NH3 + NaCl

CH3

Sec. 6: Alcohols, Ethers

CH3

N

+

H acid

H Cl

21

Which of the following compounds could be used successfully to prepare a Grignard reagent for alcohol synthesis by subsequent reaction with an aldehyde or ketone? acidic proton Br O

Br Cl

Cl

OH

O

A)

B)

C)

D)

react with itself Cyclopentylmethylmagnesium bromine, shown opposite, is treated in ether with cyclopentanol. The major organic product after a dilute acid work up is:

A)

B)

CH2

C)

CH2 O

D)

CH2

CH2MgBr

HO Sec. 6: Alcohols, Ethers

22

What is the final product 3 formed in the following sequence of reactions? O Mg/ether

1

2) H3O

Br O

HO

Na2Cr2O7/H2SO4

1) H

3

2

+

O

HO

H

O H

A)

B)

C)

Sec. 6: Alcohols, Ethers

D)

E)

23

What is the final product 3 formed in the following sequence of reactions? OH H2CrO4

O

1

1) CH3MgI 2) NH4Cl

1) NaH 2

3

2) CH3I

O

O

O A

B

Sec. 6: Alcohols, Ethers

C

D

24

What is the final product 3 formed in the following sequence of reactions?

CH3CH2Cl

NaOH, H2O

1

PCC, CH2Cl2

Li , Et2O

1)

2

3

2) H3O+

O OH

A)

OH

B)

H C)

Sec. 6: Alcohols, Ethers

Cl D)

OH

25

Vollhardt: Chapter 9

Which of the reagents would not produce the ethoxide ion from ethanol? NaNH2 ? CH CH OH CH3CH2O 3 2 LiN(CH(CH3)2)2 KH NaSCH3 ¯NR2 Stronger base the alkoxide ion Na(s) H¯ Stronger base the alkoxide ion Na or any alkaline metals Li, Na, K, Cs (2H2O + 2M  2M+ ¯ OH + H2(g) Which would react faster with water Li or Cs - why

Order the following carbocations from most stable to least stable? A) B) C) D) E)

1>2>3>4 4>3>2>1 1>2>4>3 3>4>2>1 2>3>1>4

H C

H

H 1)

2)

3)

Free Energy

• • • • •

4)

∆G‡ =

Sec. 6: Alcohols, Ethers

26

Acid-Catalyzed Dehydration of Alcohols? Alcohols undergo elimination reactions via an E1 mechanism. Order the following compounds from the most reactive to least reactive? (CH3)3COH

conc. H2SO4

t-butyl alcohol

60°C

1)

(CH3)2CHOH

2)

3)

2-propanol

100°C

CH3CH2OH

conc. H2SO4

ethanol

180°C

H R

conc. H2SO4

C R

CH2=C(CH2)2

CH2=CHCH3

85% H2SO4

R

OH

O

H

base Mechanism

R

60°C O

acid

S

1>2>3 3 > 2 >1 2 > 1 >3 3>1>2

CH2=CH2

H C

A) B) C) D)

H

H

C

C

R H

O

+

O

H

O S

R

-H2O

O +

OH

R

OH

H

H

C

C

O

O

R

S

OH

O

R

H C

O

Sec. 6: Alcohols, Ethers

R

+

R

C 27

R

What is the product of the following reaction? OH

Br

OH

Na

C)

D)

OSO3H

conc. H2SO4 / NaBr 100°C A)

B)

E)

Explanation:

The conjugate bases of acids such as HBr or HI are also good nucleophiles, Br, I , whereas the conjugate bases of H2SO4 and H3PO4 are not good nucleophiles HSO4 and H2PO4 . Which of the following SN2 reactions would react the fastest. Cl OH HCl A) Br HBr OH B)

Explanation:

The chloride ion is a much poorer nucleophile and reacts very slowly. This is a very poor method to make 1o chloroalkanes but a good way to make simple primary iodo- and bromoalkanes Sec. 6: Alcohols, Ethers

28