chapter 12 study guide.pdf

7/25/2019 Chapter 12 Study Guide.pdf

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Chapter 12

Introduction to Carbonyl Reactions:

Carbonylsinclude aldehydes, ketones, acids and esters

Carbonylshave a sp2hybridized carbon attached to a oxygen

Carbonylshave resonance contributers which show the reactivity of the carbon of the

carbonyl. The carbon of the carbonyl is an electrophile and susceptible to

nucleophilic addition.

O O

+

Nu Oxidation/Reduction Reactions:

Organic chemicals have 4 stages of oxidation

alkane to alcoholto aldehyde/ketone to ester/acid

R(H)R(H) R(H)

OH[O]

OR(

O O

Esters/acids and aldehydes all come from the oxidation of primary alcohols.

Esters/acids and aldehydes all can be reduced to primary alcohols.

OH O

HOR(H)

O

[O][O]

PRIMARY ALCOHOLS

[R] [R]

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Ketones are formed from secondary alcohols. Ketones can be reduced to secondary alcohols.

Tertiary alcohols can not be oxidized.

Reduction Reactions:

To reduce carbonyls hydride reagents are used. The 2 most common are Lithium Aluminum

Hydride(LAH) and Sodium borohydride(NaBH4). LAH can reduce anything. NaBH4 can

reduce aldehydes and ketones only. LAH reacts violently with water so is used in ether

solutions such as THF or diethyl ether. NaBH4 can be run inalcohol solutions or water.

Sodium in methanol, Hydrogen with metal catalyst can also be used to reduce aldehydes and

ketone(but not esters or acids).

R(H)

O

1) NaBH4or

H2/Pd or

Na/Methanol

LAH

2) H3O+ R(H)

OH

OR(H)

O1) LAH

2) H3O+

H

OH

OH

SECONDARY ALCOHOLS

[O]

[R]O

[O]

[R]

NO

REACTION

OH

SECONDARY ALCOHOLS

[O]

[R]NO REACTION

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Mechanism for Reduction:

R(H)

O1) NaBH4

2) H3O+ R(H)

OH

H3B H

R(H)

O

H OH2

Oxidation Reactions:

Primary alcohols can be oxidized to aldehydes or acids. PCC is a special reagent that

stops at the aldehyde level. Potassium permanganate or chromic acid oxidize primary

alcohols all the way to acids(Esters are created from acids).

OHPCC

H

O

OH

H2CrO4

or

KMnO4

OH-

/H20Heat

OH

O

PCC =N H CrO3Cl

-

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Secondary alcohols can be oxidized to ketones by PCC, chromic acid, potassiumpermanganate or Jones reagent.

O

H 2CrO 4

or KMnO 4/OH-/H 20/Heat

or PCCor Jones Reagent

OH

JONES REAGENT = CrO 3/Acetone

Mechanism for Oxidation Reactions:

R(H) R(H)

OOH

[Cr]

Cr

O

O

OOH

H O H

H

R(H)

O

Cr

O

O

HO

HO

H

H2O

H O H

H

R(H)

O

Cr

O

HO

H2O O

R(H)

O

Cr

O

OHO

H

H2O

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Tertiary alcohols do not have a proton to remove in the final step so tertiary alcohols can

not be oxidized.

A test for primary and secondary alcohols is to add the alcohol to a chromic acid(orange)

solution. The solution turns green as the alcohol is oxidized and the chromium is

reduced. In the reduced state chromium is green. Ethyl alcohol is a primary alcohol.

What other test can this chemistry be used for?

Organometallic reactions:

Carbon compounds that contain metals such as lithium, copper and magnesium are called

organometallic reagents. Organometallics are very good nucleophiles and bases.

Organolithium reagents

Alkyl halides in the presence of solid lithium in an ethereal solution produce

organolithium reagents. These reagents are used the same day they are made usually.

During long exposure organolithium reagents will react with ether to form elimination

products. Organolithium reagents can be stored in hydrocarbon solvents.

Br 2 Li/etherLi

The order of reactivity of alkyl halides is:

RI > RBr > RCl

Organolithium reagents will react with any acidic proton in an acid/base reaction. The

acidic proton could be an OH, SH, NH, COOH, CH of a triple bond to name some.

Organolithium reagents will react with carbonyls, leaving groups, epoxidesin a

substitution/addition reaction.

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LiOH

NH2

SH

COOH

Br

OMs

OTs

R(H)

O

Li

Li

Li

Li

Li

Li

Li

Li

H3O+

O

NH

S

COO

R(H)

OH

1)

2)

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Organomagnesium reagents(Grignard)

Alkyl halides react with magnesium in ether to form Grignard reagents. Grignard

reagents are less reactive and basic than organolithium reagents. Grignards have the

same limitations of organolithium reagents. They can not be prepared in the presence of

an acidic hydrogen or a very electrophilic functional group. See page 54.

Br

Mg/diethyl ether

MgBr

In the presence of acids, Grignard reagents will deprotonate the acidic proton.

MgBrOH

NH 2

SH

COOH

Br

OMs

OTs

MgBr

MgBr

MgBr

MgBr

MgBr

MgBr

MgBr

O

NH

S

COO

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In the presence of an electrophilic center, Grignards will substitute or or add.

Grignards since they are less reactive can react to open up epoxides(Organolithium can

also open epoxides but there is chance for acid/base reactions).

H

OMgBr

H3O+

OH

1)

2)

OMgBr

H3O+

OH

1)

2)

OH

OMgBr

H3O+ O

O

1)

2)

OR

OMgBr

H3O

+

OH

1)

2)

O

MgBr

H3O+

1)

2)

OHGrignard's attack less-substituted carbon

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NOTE: Alkynides can also react with carbonyls.

Corey-Posner/Whitesides-House Synthesis:

The Corey/House synthesis are methods for creating carbon carbon single bonds. An

organolithium reacts with copper iodide to form a lithium dialkyl cuprate. The lithium

dialkyl cuprate will then react with another alkyl halide to form a carbon-carbon single

bond. The alkyl groups on the dialkyl cuprate may be methyl, primary, secondary or

tertiary. The alkyl groups on the alkyl halide may be methyl, primary, secondary, phenyl

or vinylic.

H

O

H3O

+

OH

1)

2)

O

H3O+

OH

1)

2)

OH

O

H3O+ O

O

1)

2)

OR

O

H3O+

O1)

2)

OH3O

+

1)

2)

OHAlkynide's attack less-substituted carbon

H

O

H3O

+

OH

1)

2)

O

H3O+

OH

1)

2)

OH

O

H3O+ O

O

1)

2)

OR

O

H3O+

O1)

2)

OH3O

+

1)

2)


H

O

H3O

+

OH

1)

2)

O

H3O+

OH

1)

2)

OH

O

H3O+ O

O

1)

2)

OR

O

H3O+

O1)

2)

OH3O

+

1)

2)


H

O

H3O

+

OH

1)

2)

O

H3O+

OH

1)

2)

OH

O

H3O+ O

O

1)

2)

OR

O

H3O+

O1)

2)

OH3O

+

1)

2)


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Br

1) 2 Li/ether2) CuI

CuLi

CuLi

Br

Br

Br

NOTE: If an acidic proton is in a molecule you need to react with a Grignard,

organolithium you can protect it with TBDMS-Cl.

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H

O

CH3CH2Li

CH3CH2MgBr

O

CH3CH2Li

CH3CH2MgBr HO H2C CH3

HO

H2C

CH3

OH

OH

OCH3

O

CH3CH2Li

CH3CH2MgBr

H2C

CH3

HO CH2

CH3

O

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Corey-House synthesis--can couple any two halogen containing compounds. One of the

halogen containing compounds is turned into a dialkyl lithium cuprate, the other reacts with

that cuprate. The cuprate halogen compound can be 1o, 2

oor 3

o, the other halogen must be

1o

or 2oor vinylic. Br

Br

Br CuLi

2

1) 2 Li/Ether2) CuI

6

5

4

3

2

1

Br

1 2

3 4

5 6

Cl

1) 2 Li/ether

2) CuI3) 2-bromopentane

2

13

4

5

For Ex.

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OH

OH

OHKMnO 4/O H

-/H2O/heat

or CrO3/H 2O

CrO3/Acetone

PCC

A

B

C

B

C

A

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OH

H

O

OH

OH

O

O

O

O

PCC

Jones Reagent

KMnO4, OH-, H2O/heat

1) LAH

2) H+

1) LAH

2) H+

1) LAH

2) H+

1) LAH

2) H+

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O

O

LAH

NaBH4

O

O

OHLAH

NaBH4

LAH

NaBH4

H

O

LAH

NaBH4

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H

O

Et

O OH

O

1) LAH

2) H3O+

1) NaBH4

2) H3O+

1) NaBH4

2) H3O+

3) 2 eq. TBDMS-Cl

imidazole/DMF

4) 1 eq. CH3MgBr

1) NaBH4

2) H3O+

3) 2 eq. TBDMS-Cl

imidazole/DMF

4) 2 eq. CH3MgBr

OCH2CH3 OCH3

OH

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Show how to form each of the following products using Corey-House synthesis, break the molecule

at the shown point and show the reaction to make the product. Then break it at a different point and

show those reactions.

I

II

III IV

For Example

Br

Br

Br

A

1) 2 Li/ether2) CuI

3)Br

A

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OH

OH

OHKMnO4/OH

-/H2O/heat

or CrO3/H2O

CrO3/Acetone

PCC

A

B

C

B

C

A

OH

O

O

OH

O

OH

OH

O

O

OH

H

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OH

H

O

OH

OH

O

O

O

O

PCC

Jones Reagent


1) LAH

2) H+

1) LAH

2) H+

1) LAH

2) H+

1) LAH

2) H+

O

OH

O

OH

OH

OH

OH

O

H

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O

O

LAH

NaBH4

O

O

OH

LAH

NaBH4

LAH

NaBH4

H

O

LAH

NaBH4

OH

NO

REACTION

OH

OH

OH

OH

OH

NO REACTION

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At indicated break point

II

III

Br

1) 2 Li/ether

2) CuI

3) C5H11Br

ORBr

1) 2 Li/ether

2) CuLi

3) Br

I


Br

1) 2 Li/ether

2) CuI

3) C6H13Br

Br

1) 2 Li/ether2) CuI

3)Br


Br

1) 2 Li/ether

2) CuI

3)

Br

OR

OR

Br

1) 2 Li/ether2) CuI

3)Br

IV At indicated break point

OR

Br

1) 2 Li/ether

2) CuI

3)

Br

Br

1) 2 Li/ether

2) CuI

3) Br

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Show how to accomplish the following synthesis problems.

O

Cl OH

O

O

O

H

?

?

OH

OH

O

?

Br

?

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O

Cl OH

O

O

O

H

1) O3, CH2Cl2-78o

2) Zn, AcOHH

O

1) C9H19MgBr or

C9H19Li

2) H3O+

OHJones or PCC

or Chromic Acid...

1) TBDMS-Cl, base

2) BH3: THF

3) H2O2, OH-

Cl OTBDMS

OH

Jones or PCC

or chromic acid..

Cl OTBDMS

O

1) TBAF2) NaH, TfCl

3)

OK

Cl

O

1) BH3:THF

2) H2O2, OH-

3) PCC

O O

H

Cl

1) NaOCH3/CH3OH2) MMPP

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OH

OH O

H

1) C4H9MgBr or C4H9Li

2) H3O+

1) TBDMS-Cl

2) BH3:THF

3) H2O2, OH-

OP

OH

1) PCC or Jones...

2) TBAF

OH

O

PCC

B r

1 ) 2 L i /e t h e r 3 ) C u I3 )

B r O P

O P1 ) H g ( A c e ta t e )2 , H 2O

2 ) N a B H 4, O H-

3 ) P B r 3

B r

O P

1 ) 2 L i /e t h e r

2 ) C u I

3) C 5 H 1 1B r

O P1 ) T B A F2 ) N a H , T f C l

3 ) N aO M e , M e O H

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Name:

OH

PBr3

Br

1) NaH, TsCl

2) NaSH/acetone

1) NaOH

2)

Br2/heat

HBr/H2O2

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1) MMPP

2) H+

2) HCN

2) NaI

1) MMPP

1) MMPP

1) MMPP

1) Hg(Triflate), isopropanol

2) NaBH4, NaOH

OH

Cl

O

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Br

Br

OH OH

Br

Br

OH Br

Br

Br

OH

O

OH

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Name:

OH

PBr3

Br

1) NaH, TsCl

2) NaSH/acetone

1) NaOH

2)

SH

Br

O

Br2/heat

HBr/H2O2

Br

Br

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O

OH

OH

OH

CN

I

OH

O

1) MMPP

2) H

+

2) HCN

2) NaI

1) MMPP

1) MMPP

1) MMPP

1) Hg(Triflate), isopropanol

2) NaBH4, NaOH

OH

SOCl2

Cl

O

1) NaH 2) isopropyl bromide

1) NaH, TfCl 2) NaOMe

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Br

Br

OH OH

Br

Br

OH Br

Br

Br

OH

O

OH

1) NaOMe2) HBr/H2O2

1) PBr3

2) MMPP

3) NaBr

1) MMPP

2) NaBr

3) PBr3

1) TBDMS-Cl, NaH2) BH3:THF3) H2O2/OH

-

4) NaH, Ethyl chloride

5) TBAF/THF

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Name:

OH

H

O

OH

OH

O

O

O

O

PCC

Jones Reagent


1) LAH

2) H+

1) LAH

2) H+

1) LAH

2) H+

1) LAH

2) H+

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Name:

OH

H

O

OH

OH

O

O

O

O

PCC

Jones Reagent


1) LAH

2) H+

1) LAH

2) H+

1) LAH

2) H+

1) LAH

2) H+

O

OH

O

OH

OH

OH

OH

O

H

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