6 alcohols and ethers oct 31 notes

Sec. 6: Alcohols, Ethers 1

AlcoholsOrder the following compounds from most to least acidic?

C

OH

OH2

1 2 3

HO A) 1 > 2 > 3B) 3 > 2 > 1C) 2 > 1 > 3D) 3 > 1 > 2E) 1 > 3 > 2

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

OH

A)CH3O

O

CH3OHB)

OH2

CH3OC)

+

+

+

O

CH3OH

OH

CH3O+

OH

CH3OH

+

+


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

R OH2 R OH R O

Alkoxoniumion

Alcohol Alkoxideion

Strong Acid Strong BaseWeak

acid and base

strong acid

mild base

strong base

mild acid

Very strong acids are required to protonate alcohols.


Preparation of Alcohols

90 % 10 %

A) SN1B) SN2

HMPA – hexanamethylphosphoric triamide (H3C)2NP

O

N(CH3)2

(H3C)2N


Oxidation States of Carbon

A reaction of an organic molecule usually corresponds to increasing its hydrogen content or decreasing its oxygen content.

RCH3

[O]

[H]RCH2OH

[O]

[H]R C

O

H[O]

[H]R C

O

OH

LowestOxidation State

HighestOxidationState

R CH ROH

R C R

O[O]

[H]

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

CH3[O]

[H]CH2Cl

How to figure out the oxidation state of a carbon atom

a bond to hydrogen or anything less electronegative than carbon is electron donating → -1a bond to nitrogen, oxygen or anything more electronegative than carbon is electron withdrawing → +1a bond to a carbon → 0

C

H

H

H

HOS = 4 x -1 = - 4

C OO

OS = 4 x +1 = + 4

C

H

H

H

C

H

OH

H

OS = (3 x -1) + 0 = - 3

OS = Hydrogen - (2 x -1) Oxygen - (1 x 1) Carbon - 0 = - 1

OS = oxidation state


Oxidation States of Carbon

C C

H

HH

HH2/Pd

C

H

H

H

C

H

H

HOS = - 2 OS = - 3

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

C

H

H

H

C

H

OH

H

KMnO4C

H

H

H

C

O

OH

OS = - 1 OS = 3

Reduction Oxidation

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:


Alcohols by Reduction of Carbonyl Compoundswith LiAlH4 and NaBH4

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

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.


Mechanism with LiAlH4 and NaBH4

C

O

RR

Na H3B- H+

C O

R

R

H

-

+ Na+

H2O

Nucleophile(base)

Electrophile(acid)

CH3CH2OH

solvent+ BH3

C O

R

R

H BH3

C OH

R

R

H

CH3CH2OH+

CH3CH2O+ BH3

This will reactthree more times

C

O

RR

4 (CH3CH2O)4B+C OH

R

R

H NaB(OH)3

CH3CH2OH

+

+

CH3CH2OH

C OH

R

R

H


C

O

RR

Li H3Al- H+

-

+

Nucleophile(base)

Electrophile(acid)

C OAlH3 Li

R

R

H+

C

O

RR

3C O

R

R

H Al

O

O

O

CR

H

R

C

C

R

R

R R

H

H

a tetra-alkyl aluminate

H3O+

C OH

R

R

H

The reactivity of LiAlH4 is much greater than that of NaBH4 and is less selective in its reactions.

orC OAl Li

R

R

H

4

+

LiOH + Al(OH)3 +work-up

Solvent: Et2O

LiAlH4 reacts vigorously with water and ethanol and must be used in an aprotic solvent such as diethyl ether.


Oxidation of Alcohols

CH3CH2CH2OH CH3CH2CH

OKMnO4 / OH¯ / heat

orNaCr2O7 / H2SO4

orH2CrO4

very hard tostop oxidation

CH3CH2COH

O

propanol propanal propanoic acid

OH

or CrO3 Jones reagent

H2CrO4

acetone

O

can’t break C-C bond

OHH2CrO4

acetoneNo Reaction

can’t break C-C bond

Oxidation - loss of electronsor add oxygens

OS = -1 OS = +1OS = +3

OS = 0 OS = +2


CH3CH2CH2OH + PCCCH2Cl2

CH3CH2CH

O

HC

Cl

Cl

Haprotic solvent

stops at aldehyde

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

Oxidation of Alcohols

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:


Chromic esters are intermediates in alcohol oxidation

The mechanism of chromium(VI) oxidations involves two steps:Formation of a chromic esterE2 elimination of a proton and a HCrO3

- ion.

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).

Oxidized farther to carboxylic acid If using PCC stops at aldehyde


Examples

O

H

1) LiAlH4/Et2O

2) H3O+

OH O O

OH

A) B) C)

OH(H3C)2HCO

CH3

OH(H3C)2HCO

CH3

A) B)

O

O

CH3

NaBH4/H2O

OS = +1

OS = -1

O

OH

OH

OS = 0OS = +3

O

OH

OO

H

OH

OHOH

OHOO

H

O

A)

B)

C)

D)

E)

OS = +2 OS = +3alreadyoxidized

NaCr2O7 / H2SO4

OS = +3

O


Organometallic Compounds

C M+

C M- +

C M

M = Na+ or K+

Primarily ionic

explosive with water

M = Mg or Lipolar covalent

relative stable in ether

M = Pb, Sn, Hg, or TlPrimarily covalent

much less reactive

CH3Li

CH3MgCl


Grignard Reagents

Br

Br

+ Mg

+ Mg MgBr

MgBrether

ether

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 the Grignard reagent as RMgX

Organolithium Compounds

Br

Br

+ 2 Li

+ 2 Li Li

Li + LiBr

+ LiBr

ether

ether


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.

CH3MgBr + CH3CH2O-H- + - +-+

CH4 + CH3CH2O Mg2+ + X

weaker base

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

C C H CH3MgBr- +

+ C C MgBr- + -

+ CH4

spsp2

sp3

O-

+ +

weaker base

SN2

steric interactionC6H5 C C CH2 C

OMgBr

CH3

CH3dilute HCl

C6H5 C C CH2 C

OH

CH3

CH3

+ MgBrCl


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:


Grignard Reagents and Carbonyl Compounds

Mechanism

R MgX- + -

nucleophile(base)

R

C O

R

+ -

electrophile(acid)

+

nucleophilic attackon carbonyl carbon

Step One

R

C O

R

R Mg2+ X

halomagnesium alkoxide

Step Two

R

C O

R

R Mg2+ X

ether

H O

H

H

+

X

R

C OH

R

R + H2O + MgX2

alcohol

Order of Reactivity RI > RBr > RCl

RI and RBr mostly used RCl reacts sluggishly


General Reactions

R1MgBr- + - H

C O

H

+ -+

H

C OMgBr

H

R1

ether

formaldehyde

HBr(dilute)

H

C OH

H

R1 + MgBr2

1° alcohol

R1MgBr- + -

C O

H

+ -+ C OMgBr

H

R1

ether

an aldehyde

HCl(dilute)

C OH

H

R1 + MgBrCl

2° alcohol

R2R2 R2

R1MgBr- + -

C O+ -

+ C OMgBrR1

ether

a ketone

HCl(dilute)

C OHR1 + MgBrCl

3° alcohol

R2R2 R2

R3 R3 R3


General Reactions

R1MgBr- + -

C O+ -

+ C OMgBrR1

ether

a ester

HCl(dilute)

C O

R1

R3OH + MgBrCl +

3° alcohol

R2R2 R2

R3O R3O leavinggroup

+ R3OMgBr

R1MgBr- +

C OMgBrR1

R2

R1

C OHR1

R2

R1

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


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.

Examples

CH3CH2C CHCH3MgBr

CH3CH2C CMgBr

O

H

+- +-

ether

+

-

1)

2) H3O+

OH

O

+ CH4(g)

H3C

CH

H3C

CH2Li+-

+ -1)

2) H3O+ OH


Examples

Sometimes a Grignard reaction can be completed with a compound containing an acidic hydrogen if two equivalents of the reagent is used

CH3MgBr ++- ether

HOCH2CH2CCH3

O

BrMgOCH2CH2CCH3

OCH3MgBr

+-

2) H3O+

HOCH2CH2C

CH3

OH

CH3+

-

+ CH4(g)

CH3CH2C CH Na NH2

+

CH3CH2C C-

Na+

O

CCH3H3C

+

-

1)

2) NH4Cl, H2O

CH3CH2C C C

OH

CH3

CH3

CH3CH2C C C

O

CH3

CH3

+

Na

N

H

H

H

H+

Cl

acid

+ NH3 + NaCl


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?

O

Cl O

Br

Br OH Cl

A) B) C) D)

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

CH2MgBr

A)

B)

C)

D)CH2

CH2 O

CH2

HO

react with itself

acidic proton


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

A) B) C) D)

Br

Mg/ether

2) H3O+1

1) H

O

2

Na2Cr2O7/H2SO4

3

OOHOHO H O

H

E)


OHH2CrO4 1 2

1) CH3MgI2) NH4Cl

1) NaH

2) CH3I3

A B C D

O

O

O O




CH3CH2ClLi

OHA) B) C) D)

2) H3O+

11)

2 3NaOH, H2O PCC, CH2Cl2 , Et2O

OHH

O

OH

Cl


Which of the reagents would not produce the ethoxide ion from ethanol?

CH3CH2OH CH3CH2OA) NaNH2

B) LiN(CH(CH3)2)2

C) KHD) NaSCH3

E) Na(s)

Vollhardt: Chapter 9

?

¯NR2 Stronger base the alkoxide ionH¯ Stronger base the alkoxide ionNa 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?

H

C H

H

1) 2) 3) 4)

A) 1 > 2 > 3 > 4B) 4 > 3 > 2 > 1C) 1 > 2 > 4 > 3D) 3 > 4 > 2 > 1E) 2 > 3 > 1 > 4

G‡ =

Fre

e E

ne

rgy


Alcohols undergo elimination reactions via an E1 mechanism. Order the following compounds from the most reactive to least reactive?

(CH3)3COH

(CH3)2CHOH

CH3CH2OH

t-butyl alcohol

2-propanol

ethanol

conc. H2SO4

conc. H2SO4

conc. H2SO4

60°C

100°C

180°C

CH2=C(CH2)2

CH2=CHCH3

CH2=CH2

1)

2)

3)

A) 1 > 2 > 3B) 3 > 2 >1C) 2 > 1 >3D) 3 > 1 > 2

Mechanism

85% H2SO4

+

+60°C

C

H

R

R

C

H

R

OH

S

O

OH

O

OH

base

C

H

R

R

C

H

R

O

H H

+

-H2OC

H

R

R

C

H

R

S

O

OH

O

O

C

R

R

C

H

R

S

O

OH

O

O

Acid-Catalyzed Dehydration of Alcohols?

acid


What is the product of the following reaction?

OH

OH

Cl

BrHCl

HBr

Br OH Na

A) B) C) D)

OSO3H

E)

conc. H2SO4

100°C

/ NaBr

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 .

Explanation:

Which of the following SN2 reactions would react the fastest.

OH

A)

B)

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

Explanation:

6 alcohols and ethers oct 31 notes

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