CH-1Organic Chemistry-2

Prepared By

Prof Dr. Abdelfattah Haikal & Dr. Khalid Ahmad Shadid

Islamic University in Madinah

Department of Chemistry

AlcoholsAlcohols from Carbonyl CompoundsOxidation-Reduction & Organometallic Compounds

OH OH OH

Structure & Nomenclature Alcohols have a hydroxyl (–OH) group

bonded to a saturated carbon atom (sp3 hybridized)

1o 2o 3o

Ethanol 2-Propanol(isopropylalcohol)

2-Methyl-2-propanol

(tert-butyl alcohol)

OHOH

OH

2-Propenol(allyl alcohol)

2-Propynol(propargyl alcohol)

Benzyl alcohol

Phenols

• Compounds that have a hydroxyl group attached directly to a benzene ring

OH

Phenol

OH

4-Methylphenol

OH

3-Chlorophenol

Cl

H3C

Ethers

• The oxygen atom of an ether is bonded to two carbon atoms

Diethyl ether tert-Butyl methyl ether

Divinyl ether

OO

CH3

O O

Ethyl phenyl ether

Physical Properties ofAlcohols and Ethers

Ethers have boiling points that are roughly comparable with those of hydrocarbons of the same molecular weight (MW)

Alcohols have much higher boiling points than comparable ethers or hydrocarbons

For example

O

Diethyl ether

(MW = 74)

b.p. = 34.6oC

Pentane

(MW = 72)

b.p. = 36oC

OH

1-Butanol

(MW = 74)

b.p. = 117.7oC

Alcohol molecules can associate with each other through hydrogen bonding, whereas those of ethers and hydrocarbons cannot

Water solubility of ethers and alcohols

• Both ethers and alcohols are able to form hydrogen bonds with water

• Ethers have solubilities in water that are similar to those of alcohols of the same molecular weight and that are very different from those of hydrocarbons

• The solubility of alcohols in water gradually decreases as the hydrocarbon portion of the molecule lengthens; long-chain alcohols are more “alkane-like” and are, therefore, less like water

Physical Properties of Ethers

Dimethyl ether

Diethyl ether

Diisopropyl ether

1,2-Dimethoxyethane

CH3OCH3

CH3CH2OCH2CH3

(CH3)2CHOCH(CH3)2

CH3OCH2CH2OCH3

-138

-116

-86

-68

-24.9

34.6

68

83

O

O

(DME)

Oxirane

Tetrahydrofuran (THF)

-112

-108

12

65.4

Name Formula mp(oC)

bp (oC)(1 atm)

Physical Properties of Alcohols

Methanol

Ethanol

Isopropyl alcohol

tert-Butyl alcohol

Hexyl alcohol

Cyclohexanol

Ethylene glycol

CH3OH

CH3CH2OH

CH3CH(OH)CH3(CH3)3COH

CH3(CH2)4CH2OH

-97

-117

-88

25

-52

24

-12.6

64.7

78.3

82.3

82.5

156.5

161.5

197

inf.

inf.

inf.

inf.

0.6

3.6

inf.

OH

HOOH

Name Formula mp(oC)

bp (oC)(1 atm)

*

* Water solubility (g/100 mL H2O)

Diethyl EtherDiethyl Ether

Diethyl ether is a very low boiling, highly flammable liquid

Most ethers react slowly with oxygen by a radical process called autoxidation to form hydroperoxides and peroxides

Step 1

O O C OR'

H

O O H+ COR'

+

Step 2

C OR'

OO

COR'

+ O2

Hydrogen abstractionadjacent to the ether oxygen

occurs readily

Step 3a

C OR'

H

+ COR'

+C OR'

OO

C OR'

OOH

orStep 3b

+ COR'

C OR'

OO

R'O C OO C OR'

Hydroperoxides and peroxidescan be explosive

A hydroperoxide

A peroxide

Synthesis of Alcohols from Alkenes

Acid-catalyzed Hydration of Alkenes

C CH

H2OC C

OHH

C C

OH

H

H

C C

H

H⊕

H2O

H2O

Reactions of Alcohols The reactions of alcohols have mainly to do

with the following:• The oxygen atom of the –OH group is

nucleophilic and weakly basic• The hydrogen atom of the –OH group is

weakly acidic• The –OH group can be converted to a

leaving group so as to allow substitution or elimination reactions

OH

C–O & O–H bonds of an

alcohol are polarized

Protonation of the alcohol converts a poor leaving group (HO⊖) into a good one (H2O)

C O+ H

H

C O H H A A+

alcohol strongacid

protonatedalcohol

Once the alcohol is protonated substitution reactions become possible

C O H

H

Nu + CNu + O H

H

protonatedalcohol

SN2

The protonated –OHgroup is a good leavinggroup (H2O)

Alcohols as Acids

Alcohols have acidities similar to that of water

pKa Values for Some Weak Acids

Acid pKa

CH3OH 15.5

H2O 15.74

CH3CH2OH 15.9

(CH3)3COH 18.0

Relative Acidity

H2O > ROH > > H2 > NH3 > RHRC CH

H2O & alcohols are thestrongest acids in this series

Increasing acidity

Relative Basicity

R > NH2 > H > > RO > HORC C

HO⊖ is the weakestacid in this series

Increasing basicity

Conversion of Alcohols into Alkyl Halides

• HX (X = Cl, Br, I)• PBr3

• SOCl2

R OH R X

OH Clconc. HCl

25oC+ HOH

(94%)

Examples

OH Br

(63%)

PBr3

Alkyl Halides from the Reactionof Alcohols with HydrogenHalides

The order of reactivity of alcohols• 3o

The order of reactivity of the hydrogen halides

• HI > HBr > HCl (HF is generally unreactive)

R OH R XHX+ + H2O

> 2o > 1o < methyl

Mechanisms of the Reactions ofAlcohols with HX

Secondary, tertiary, allylic, and benzylic alcohols appear to react by a mechanism that involves the formation of a carbocation

Step 1

H O H

HO

H + O H

HO

H +

Hfast

Step 2

OH

H

O H

H

+

slow

Step 3

+ ClClfast

Primary alcohols and methanol react to form alkyl halides under acidic conditions by an SN2 mechanism

+X R C O H

H

H

H

protonated 1o alcohol

or methanol

RC

H

H

X O H

H

+

(a goodleaving group)

Reaction of alcohols with SOCl2

• SOCl2 converts 1o and 2o alcohols to alkyl chlorides

• As with PBr3, the reaction does not involve the formation of a carbocation and usually occurs without rearrangement of the carbon skeleton (especially if the temperature is kept below 0°C)

• Pyridine (C5H5N) is often included to promote the reaction

O

Structure of the Carbonyl Group

Carbonyl compounds

O

R HAldehyde Ketone

O

R R'

Carboxylic acid

O

R OH

Ester

O

R OR'

Amide

O

R NR'

R"

StructureStructureThe carbonyl carbon atom is sp2 hybridized; thus it and the three groups attached to it lie in the same plane. The bond angles between the three attached atoms are what we would expect of a trigonal planar structure; they are approximately 120o.

The bonding molecular orbital of formaldehyde (HCHO). The electron pair of the bond occupies both lobes.

Polarization and resonance structure

O

C

O

C

The more electronegative oxygen atom strongly attracts the electrons of both

the bond and the bond, causing the carbonyl group to be highly polarized;

the carbon atom bears a substantial positive charge and the oxygen atom bears

a substantial negative charge.

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Reactions of Carbonyl Compounds with Reactions of Carbonyl Compounds with NucleophilesNucleophiles

Nu

O

C

nucleophilic

addition

O

CNu

One of the most important reactions of carbonyl compounds is one in which the carbonyl compound undergoes nucleophilic addition. The carbonyl group is susceptible to nucleophilic attack because, the carbonyl carbon bears a partial positive charge.

As the reaction takes place, the carbon atom undergoes a change in its geometry and its hybridization state. It goes from a trigonal planar geometry and sp2 hybridization to a tetrahedral geometry and sp3 hybridization.

Two important nucleophiles:●Hydride ions (from NaBH4 and

LiAlH4)●Carbanions (from RLi and RMgX)

O

CR H

OH

R HH

oxidation

reduction

1o alcohol aldehyde

[O]

[H]

Primary alcohols can be oxidized to aldehydes, and aldehydes can be reduced to alcohols.

Oxidation-Reduction Reactions in Organic Chemistry

Reduction of an organic molecule usually corresponds to increasing its hydrogen content or decreasing its oxygen content

carboxylicacid

reduction

[H] O

R H

O

R OHaldehyde

oxygen contentdecreases

reduction

[H] OH

R H

O

R HH

hydrogen contentincreases

The opposite reaction of reduction is oxidation.

Oxidation involves Increasing the oxygen content of an organic

molecule or decreasing its hydrogen content is oxidation

OH

R HH

O

R OH

O

R H

[O]RCH3

[H]

[O]

[H]

[O]

[H]

lowestoxidation

state

highestoxidation

state

Oxidation of an organic compound may be more broadly defined as a reaction that increases its content of any element more electronegative than carbon

[O]

[H]

[O]

[H]

[O]

[H]Ar CH3 Ar CH2Cl Ar CHCl2 Ar CCl3

Alcohols by Reduction of Carbonyl Compounds

R OH

H H(1o alcohol)

[H]

R R'

O

R R'

HO H

H

R O

[H]

[H]OH

R O

[H]OR'

R O

Primary and secondary alcohols can be synthesized by the reduction of a variety of com pounds that contain the carbonyl group.

(2o alcohol)

Carboxylic acid

Ester

Aldehyde

Ketone

Lithium Aluminum Hydride

LiAlH4 (LAH)● Not only nucleophilic, but also very basic● Reacts violently with H2O or acidic

protons (e.g. ROH)● Usually reactions run in ethereal solvents

(e.g. Et2O, THF)● Reduces all carbonyl groups

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Reductions of carboxylic acids are the most difficult, but they can be accomplished with the powerful reducing agent lithium aluminum hydride (LiAlH4, abbreviated LAH). It reduces carboxylic acids to primary alcohols in excellent yields.

Examples

O

R OH

OH

R HH

1. LiAlH4, Et2O

2. H+, H2O(1)

O

R OR'

1. LiAlH4, Et2O

2. H+, H2O(2)

OH

R HH

+ HOR'

O

R H

OH

R HH

1. LiAlH4, Et2O

2. H+, H2O(3)

Mechanism

O

R OR'

H

Al HH

H

+

O

OR'R

HO

R HR'O +

H

Al HH

HO

RH

H

OH H

OH

RH

H

Esters are reduced to 1o alcohols

Sodium BorohydrideSodium Borohydride

NaBH4

● less reactive and less basic than LiAlH4

● can use protic solvent (e.g. ROH)● reduces only more reactive carbonyl

groups (i.e. aldehydes and ketones) but not reactive towards esters or carboxylic acids

Aldehydes and ketones can also be reduced to alcohols by hydrogen and a metal catalyst, by sodium borohydride (NaBH4)

Examples

Mechanism (Animation)

O

R R'

H

B HH

H

+

O

R'R

H

OH HOH

RH

R'

Aldehydes are reduced to 1° alcohols & ketones are reduced to 2° alcohols

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A Mechanism for the A Mechanism for the ReactionReaction

Overall Summary of LiAlH4 and NaBH4 Reactivity

O

R O<

O

R OR'

O

R R'<

O

R H<

ease of reduction

Reduced by NaBH4

Reduced by LiAlH4

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Which reducing agent, LiAIH4 or NaBH4 would you use to carry out the following transformations?

ProblemProblem

5. Organometallic Compounds Compounds that contain carbon-metal bonds

are called organometallic compounds

C M

primarily ionic(M = Na or K)

C : M

(M = Mg or Li)

C M

primarily covalent(M = Pb, Sn, Hg or Tl)

Organometallic compounds of lithium and magnesium are of great importance in organic synthesis. Their carbon-metal bonds have considerable ionic character. The carbon atoms that is bonded to the metal atom of an organolithium or organomagnesiurn compound is a strong base and powerful nucleophile.

Preparation of Organomagnesium Compounds

Organomagnesium halides were discovered by the French chemist Victor Grignard in 1900. Grignard received the Nobel Prize for his discovery in 1912, and they are now called Grignard reagents in his honor. Grignard reagents have great use in organic synthesis.

Grignard reagents are usually prepared by the reaction of an organic halide and magnesium metal in an ether solvent.

Order of reactivity of RX● RI > RBr > RCl

THF+ Mg

Br MgBr

Example

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Reactions with Compounds Containing Acidic Hydrogen Atoms

Grignard reagents and Organolithium compounds are very strong bases. They react with any compound that has a hydrogen attached to an electronegative atom such as oxygen, nitrogen, or sulfur.

Preparation of Organomagnesium Compounds

Reactions of Organolithium andOrganomagnesium Compounds

Reactions with Compounds Reactions with Compounds Containing Acidic HydrogenContaining Acidic HydrogenAtomsAtoms

RMgX ~ R:MgX RLi ~ R:Li

Grignard reagents are very strong bases

R MgX H Y+

(or RLi) (Y = O, N or S)

++ XR H Y Mg2+ +

Examples● As base

CH3OH+

MgBr

+ Mg2+ + Br

+ CH3O(2)

CH3MgBr + H2O + HOH3C H(1)

+ Mg2+ + Br

Examples● As base

CH3OH+

MgBr

+ Mg2+ + Br

+ CH3O(2)

CH3MgBr + H2O + HOH3C H(1)

+ Mg2+ + Br

Examples● As base

(3) H + H3C MgBr

MgBr H CH3+

A good method for the preparationof alkynylmagnesium halides

Reactions of Grignard Reagents with Epoxides (Oxiranes)

Not only are Grignard reagents strong bases, they are also powerful nucleophiles. They attack at a saturated carbon when they react with oxiranes to give primary alcohols.

The nucleophilic alkyl group of the Grignard reagent attacks the partially positive carbon of the oxirane ring. Because it is highly strained, the ring opens, and the reaction leads to the salt of a primary alcohol.

Via SN2 reaction

OR RO

H , H2O

ROH

(1o alcohol)

Alcohols from Grignard Reagents

Grignard additions to carbonyl compounds are especially useful because they can be used to prepare primary, secondary, or tertiary alcohols.

1. Grignard Reagents React with Formaldehyde to Give a Primary Alcohol.

2. Grignard Reagents React with All Other Aldehydes to Give Secondary Alcohols

3. Grignard Reagents React with Ketones to Give Tertiary Alcohols

4. Esters React with Two Molar Equivalents of a Grignard Reagent to Form Tertiary Alcohols.

The product is a tertiary alcohol with two identical alkyl groups, groups that correspond to the alkyl portion of the Grignard reagent

R = alkyl, R’ = H (higher aldehydes) (Animation) ● 2o alcohol

O

R' HMgXR +

higheraldehyde

O MgX

RH

R'

OH

RH

R'

H3O+

2o alcohol

R, R’ = alkyl (ketone)● 3o alcohol

O

R' R"MgXR +

ketone

O MgX

RR"

R'

OH

RR"

R'

NH3ClH2O

3o alcohol

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GOOD GOOD LUCKLUCK

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