ORGANIC CHEMISTRY REACTIONS

Preparations of Alkyl Halides

Organic Halogen Compounds

1. Electrophilic Addition of Halogens or Hydrogen Halides to Alkenes

R

R

R

R+ X2 R

R

XR

R

X

R

R

R

R+ R

R

HR

R

XHX

H

CH3

H

H3C+ Cl2 H3C

H

ClCH3

H

Cl

HClH

CH3

H

H3C+ H3C

H

HCH3

H

Cl

Examples:

Examples:

1.

2.

2. Nucleophilic Substitution of Alcohols

General equation:

X = Cl, Br, I (Reagents: HCl, HBr, HI, SOCl2, PCl3, PBr3

H3PO3

OH+ HCl

Cl+ H2O

Examples:

OH + SOCl2 Cl + SO2

OH + PBr3Br +

HCl+

)

3. Preparation of Aryl Halides

+ X2FeX3

X+ HX

X = Cl, Br

+ Cl2FeCl3

Cl+ HCl

Example

Reaction of Alkyl Halides

H

XR

H

+ Nu-

H

NuR

H

+ X-

X = Cl, Br, I

Examples of nucleophiles: OH-, H2O, RO-, RCOO-, H2S, RSH, NHR2, NH2R, NH3

RX + HO- ROH + X-

alcohol

RX + H2O ROH + HXalcohol

RX + RO-Na ROR + X-

ether

RX + RCOO- + X-RCOORester

Br + NaOH OH + NaBr

ClH2O+

OH+ HX

Br++ O-Na+ O NaBr

Br ++ O-Na+ O NaBr

O

O

1.

2.

3.

4.

.

R'-X (excess)+ RNH2 R-N(R')3X+ -

RX + H2S RSH (thiol) + HX

Cl + H2S SH HCl+

R'X + RNH2 (excess) RNHR' + HX

CH3CH2NH2 + CH3Br CH3CH2NHCH3 + HBr

CH3CH2N+(CH3)3Br-CH3CH2NH2 + CH3Br

(excess)

(excess)

5.

6.

7.

Reaction Mechanism of Nucleophilic Substitutions

(i) SN

2 Reaction Mechanism

Example: Reaction of OH- with bromomethane (methyl bromide)

(ii) SN

1 Reaction Mechanism

C

Carbocation

+ XC X

CCNu Nu Enantiomer A

CC Nu Enantiomer BNu

Example: Reaction of water with (S)-3-bromo-2,3-dimethylpentane

Amines

Preparations of Amines

1. Reduction of Amides

Amides can be reduced to amines by using lithium aluminium hydride (LiAlH4

R NH2

O LiAlH4

AmideR NH2

then H2O

).

Example:

NH2

O

NH2Butanamide

LiAlH4then H2O

2. Reduction of Nitriles

Nitriles are compounds that contain group. Nitriles can be reduced to primary amines by using hydrogen in the presence of Ni catalyst.

RNitrile

R NH2C N

H2/ Ni

Example:

CNH2

NH2/ Ni

C N

3. Reduction of Aromatic Nitro Compounds to Aromatic Amines

Aromatic nitro compounds can be reduced to aromatic amines by using hydrogen/Pt or Sn/HCl.

NO2

H2/ Ptor

Sn/ HCl, then NaOHNH2

Reactions of Amines

1. Neutralisation with Acids As amines are basic, they can react with acids to form salts which are soluble in water.

R-NH2 + HCl RNH3+Cl-

Amine Alkyl ammonium chloride,

Example:

CH3NH2 + HCl CH3NH3+Cl

2. Reaction of Alkyl Halides

-

R'-X (excess)+RNH2 R-N(R')3X+ -

RNH2 (excess) + R'X RNHR' + HX

CH3CH2NH2 + CH3Br CH3CH2NHCH3 + HBr

CH3CH2N+(CH3)3Br-CH3CH2NH2 + CH3Br

(excess)

(excess)

3. Formation and Reaction of Diazonium Salts

NH2 N NCl

aniline diazonium salt

NaNO2, HCl

0 oC

The diazonium salt can undergo a coupling reaction with phenols or aromatic amines to give azodye compounds, which are highly coloured.

N NCl

diazonium salt

R

R = OH, NH2, NHR, NR2

+ NN

R

Azodye

Example:

N NCl

diazonium salt

N+ NN

N

AzodyeN.N-dimethylaniline

Preparations of Alcohols

Alcohols, Phenols and Ethers

1. Hydration of Alkenes

Example: Hydration of trans-but-2-ene

2. Nucleophilic substitution of alkyl halides

R X + OH- R OH + X-

OH- can be obtained from H2

Example:

CH3CH2Br NaOH CH3CH2OH + NaBr+

O, NaOH, KOH and X = Br, Cl, I

+ H2O

H OH

H+

+ H2O

H

OHH+ H

H

3. Reduction of Aldehydes and Ketones

(i) Catalytic hydrogenation

R R'

OH2+

R R'

HO HNi catalyst

Reaction conditions: hydrogen + nickel catalyst

Example:

OH2+

HO HNi catalyst

(ii) Reduction by lithium aluminium hydride (LiAlH4

)

R' R"

O

R' R"

OHHthen H2O

LiAlH4

then H2OLiAlH4

Example:

H

O

H

OHH

(iii) Synthesis using Grignard reagents

R' R

O

R' R

OHR"+ R"MgX

Grignardreagent

then H2O

R = alkyl or aryl X = Cl, Br, I

Examples:

H

O

H

OHCH3+ CH3MgBr

CH3

O

CH3

OHCH3

+ CH3MgBr

then H2O

then H2O

Reactions of Alcohols

1. Reaction with Hydrogen Halides R-OH + HX R-X + H2

Alcohol Alkyl halide

O

Reactivity of R-OH: Tertiary OH > Secondary OH > Primary OH

Example:

H3C CH3

H OH

H3C CH3

H Cl+ HCl + H2O

2. Dehydration to Alkenes

OH

RR

R

HR H2SO4 (concentrated)

Concentrated H2SO4 is a dehydrating reagent

alcoholR

R

R

R+ H2O

alkene

3. Oxidation to Carbonyl Compounds

(i) Oxidation of primary alcohol

Primary alcohol Aldehyde Carboxylic acid

Oxidation of primary alcohol with PCC

R OH

HH

Primary alcohol

PCCR O

H

Aldehyde

OH

Primary alcohol

PCCO

H

Aldehyde

1-Propanol Propanal

Example

HR

H

OH[O]

R

H

Ofurther [O]

R

HO

O

Oxidation of primary alcohol with CrO

3

R OH

HH

Primary alcohol

CrO3

R O

H

Oxidation doesnot stop here!

R O

OH

Carboxylicacid

Example

OHOH

OCrO3

OH OH

O

CrO3

(ii) Oxidation of secondary alcohol

Secondary alcohol Ketone

OH

Secondary alcohol

PCCO

Ketone2-Pentanol Pentan-2-one

R OH

HR'

Secondary alcohol

PCC or CrO3

R O

R'

Ketone

PCC = Pyridinium chlorochromate

CrO3 = Chromic acid

Example

(iii) Oxidation of tertiary alcohol

Tertiary alcohol

R'R

H

OH[O]

R

R'

O

no further [O]

R'R

R''

OH[O]

no reaction

Preparation of Phenol SO3H OH

H2SO4 NaOH

300 oCbenzene benzenesulfonic

acidphenol

concentrated

Reactions of Phenols

1. Neutralisation OH

phenol

+ NaOH

O-Na+

sodiumphenoxide

+ H2O

2. Electrophilic Substitution with Halogens

OH

phenol

+ Br2 (aq)

OH

2,4,6-Tribromophenol

Br Br

Br

Preparation of Ethers

Ethers can be prepared by Williamson synthesis.

2 ROH + 2 Na 2 RO-Na+ + H

RO

2

-Na+

Example:

+ R’-Br ROR’ + NaBr

2 CH3OH + 2 Na 2 CH3O-Na+ + H2

CH

3O-Na+ + CH3CH2Br CH3OCH2CH3

+ NaBr

Preparations of Aldehydes

Aldehydes and Ketones

R OH

HH

Primary alcohol

PCCR O

H

Aldehyde

OH

Primary alcohol

PCCO

H

Aldehyde

1-Propanol Propanal

Example

Preparations of Ketone

OH

Secondary alcohol

O

Ketone2-Pentanol Pentan-2-one

R OH

HR'

Secondary alcohol

PCC or CrO3

R O

R'

Ketone

PCC = Pyridinium chlorochromate

CrO3 = Chromic acid

Example

PCC or CrO3

Reactions of Aldehydes and Ketones

1. Oxidation of Aldehydes to Form Carboxylic Acids

R H

O

Aldehyde

R OH

OCrO3 orTollen's reagent

Carboxylic acid

Example:

H

O

OH

O+ Ag

Tollen's reagent

Tollen’s reagent (AgNO3 + NH3 (aq)

2. Reduction to Alcohols

) is used as a test to distinguish aldehydes from ketones. Upon treatment with Tollen’s reagent, only aldehydes will give a silver mirror. No silver mirror is formed for ketones.

R' R"

O

R' R"

OHH

Aldehydes

Ketones

Primary alcohols

Secondary alcohols

then H2OLiAlH4

then H2OLiAlH4

then H2OLiAlH4

H

OOH

Butanal 1-Butanol

O

3-Methylpentan-2-one

OH

aldehyde

ketone

primary alcohol

3-Methylpentan-2-olsecondary alcohol

then H2OLiAlH4

then H2OLiAlH4

Example

Reaction mechanism of carbonyl compounds with LiAlH

R R

O

H

O-

RR H

O

RR

HH-OH

H-

4

3. Reaction with Grignard Reagents

Aldehydes Secondary alcoholsthen H2OR"MgX

H

O+ CH3MgBr

Butanal Methyl magnesiumbromide

HOH

CH3

Pentan-2-ol

then H2O

Example

then H2OKetones Tertiary alcoholsR"MgX

O

+ CH3MgBrPentan-2-one Methyl magnesium

bromide

CH3

OH

CH3

2-Methylpentan-2-ol

then H2O

Example

Reaction mechanism of carbonyl compound with Grignard reagent

H-OHR R

O

R'

OMgX

RR R

O

RR

H

R'MgX

4. Reaction with Amines or Hydrazines

Reaction of aldehydes and ketones with 2,4-dinitrophenylhydrazine

H3C

HO + NH2N

O2N

NO2

H

H3C

HNN

O2N

NO2

H

+ H2O

H3C

H3CO + NH2N

O2N

NO2

H

H3C

H3CNN

O2N

NO2

H

+ H2O

Aldehydes and ketones react with 2,4-dinitrophenylhydrazine to produce 2,4-dinitrophenylhydrazone (orange precipitate). This reaction used as a test for aldehydes and ketones.

Reaction mechanism of ketones with primary hydrazines:

R R

O

NH2NHR'

O-

RR

Tetrahedralintermediate

NHNHR'

O-

RR

H- H2O

R R

N

R'NHNH2

Protontransfer

NHR'

5. Iodoform Reaction

A chemical test for aldehyde and ketone with a CH3CO- group will gives CHI3

H3C R

O

+ 3I2 + NaOH CHI3 + RCOO-Na+ + 3HIwarm

yellow ppt

(iodoform), a yellow ppt.

General properties of carboxylic acids

Carboxylic Acids and Their Derivatives

1. Carboxylic acids can react with sodium to form salts and water.

2 RCOOH + 2 Na 2 RCOO-Na+ + H

O

OH +2 2NaO

O-Na+ + H22

2

2. Carboxylic acids can react with inorganic bases to form salts and water.

RCOOH + NaOH RCOO-Na+ + H2

O

OH + NaOH

O

O-Na+ + H2O

O

3. Carboxylic acids can react with carbonate to form salts, carbon dioxide and water.

2 RCOOH + Na2CO3 2 RCOO-Na+ + CO2 + H2

O

OH +2 Na2CO3

O

O-Na+ + CO2 + H2O2

O

Preparations of Carboxylic Acids

1. Oxidation of Primary Alcohols

R OH

HH

Primary alcohol

CrO3

R O

H

Oxidation doesnot stop here!

R O

OH

Carboxylicacid

Example:

OHOH

OCrO3

OH OH

O

CrO3

2. Oxidation of Alkylbenzenes

R COOHKMnO4

Alkylbenzene Benzoic acid

Examples:

COOHKMnO4

Benzoic acid

OH COOHKMnO4

3. Carboxylation of Grignard Reagents

RMgX + CO2 RCOOHthen H2O

Examples:

+ CO2

MgBr

MgBr

+ CO2

COOH

COOH

then H2O

then H2O

Reactions of Carboxylic Acids

1. Reduction to Form Alcohols

LiAlH4,

then H2OR OH

Oheat

R OH

Example:

LiAlH4,

then H2O

heatOH

OOH

Propanoic acid 1-Propanol

2. Formation of Acid Chlorides

R OH

O SOCl2R Cl

O

Example:

OH

O SOCl2Cl

O

Propanoic acid Propanoyl chloride

3. Formation of Acid Anhydrides

R OH

O

R O

O

R

O

acid anhydride

H2ORHO

O+

heat+

4. Formation of Esters

Carboxylic acids can react with alcohols to give esters. This process is called Fishcher esterification. The esterification is catalysed by dilute sulphuric acid. One water molecule is also formed: OH from carboxylic acid, H from alcohol.

R OH

O

R O

OR'

Ester

H2OHO+heat

+R'

Carboxylicacid

Alcohol

H+

Example:

Benzoic acid

O

OH

O

O

Ethyl benzoate

OH+ + H2Oheat

H+

Preparation of Acid Chlorides

Acid Chlorides

Acid chlorides can be prepared by reacting carboxylic acids with thionyl chloride (SOCl2

).

R OH

O SOCl2R Cl

O

Example:

OH

O SOCl2Cl

O

Propanoic acid Propanoyl chloride

Reactions of Acid Chlorides

1. Acid chlorides can react with water to form carboxylic acids. This reaction with water is called hydrolysis of acid chlorides.

R Cl

O

Acid chlorideR OH

O

Carboxylic Acid

H2O

Example:

Cl

O

OH

OH2O

Propanoylchloride

Propanoic acid

2. Acid chlorides can also react with alcohols to form esters.

R Cl

O

Acid chlorideR OR'

O

Ester

R'OH+

Alcohol

Example:

Cl

O

O

OOH+

3. Acid chlorides can react with ammonia/amines to form amides.

R Cl

O

Acid chloride

R N

O

Secondary amide

2 R'NH2+ R'

H

R Cl

O

Acid chlorideR N

O2 NH3+ H

HAmmonia

NH4+Cl-+

R'NH3+Cl-+

Primary amide

Primaryamine

R Cl

O

Acid chloride

R N

O

Tertiary amide

2 R'NHR"+ R'

R"

R'NR"H2+Cl-+

Secondaryamine

Examples:

Cl

O

N

OCH3NH2+ CH3

H

Cl

O

N

ONH3+ H

H

NH4+Cl-+

CH3NH3+Cl-+

Preparation of Acid Anhydrides

Acid Anhydrides

The most general method for preparing acid anhydrides is by reacting sodium salt of carboxylic acids (sodium alkanoates) with acid chlorides.

R' Cl

O

Acidchloride

R O

O

Acid anhydride

R O-Na+

O

Sodium alkanoate

+R'

O

Example:

Cl

O

Ethanoyl chloride(acetyl chloride)

O

O

Acetic anhydride

O-Na+

O

Sodium ethanoate(sodium acetate)

+O

Reactions of Acid Anhydrides

1. Acid anhydrides can be hydrolysed by water to form carboxylic acid.

R O

O

Acid anhydrideR OH

OH2OR'

O

R' OH

O+

Example:

O

O

OH

OH2OO

OH

O+

2. Acid anhydrides can also react with alcohols to form esters. This reaction requires a base (eg. pyridine)

R OR'

O

Ester

R'OH+R O

O

Acid anhydrideR

O pyridine

Example:

O

O O

O

O

OH+pyridine

3. Acid anhydrides can react with ammonia/amines to form amides.

R N

O 2R''NH2+ R''

H

R N

O2 NH3+ H

HR O

O

R'

O

R O

O

R'

O

Ammonia

Primary amide

Primaryamine Secondary amide

+R O

O

R'

O

R N

O

Tertiary amide

2R''NHR"' R''

R"'Secondaryamine

R' O-NH4+

O+

R' O-N

O+

R''

R' O-NH2

O

R''

R'''+

+

+

Examples:

O

O O

N

O

2CH3NH2+

H

H

N

O

2NH3+

CH3

HO

O O

O-NH4+

O

+

O-NH3CH3

O+ +

Preparations of Esters

Esters

1. Fishcher esterification

R OH

O

R O

OR'

Ester

H2OHO+heat +R'

Carboxylicacid

Alcohol

H+

Example:

Benzoic acid

O

OH

O

O

Ethyl benzoate

OH+ + H2Oheat

H+

2. Esters can also be synthesized from acid chlorides and alcohols. Pyridine is used as a base to remove HCl that is formed during the reaction

R Cl

O

Acid chlorideR OR'

O

Ester

R'OH+Alcohol

pyridine

Reactions of Esters

1. Esters can be hydrolysed by water under acidic condition to form carboxylic acid and alcohols.

R OH

O

Carboxylic acid

Ester

R O

OR' R'OH+

Alcohol

+ H2OH+

Example:

OH

OO

O

++ H2O

Methyl benzoate

CH3OHH+

2. Esters can also react with base (NaOH) to carboxylic acid salts and alcohols. The basic hydrolysis is called saponification.

R O-Na+

O

Carboxylic salt

Ester

R O

OR' R'OH+

Alcohol

+ NaOH

Example:

O-Na+

O

O

O

++ NaOH

Methyl benzoate

CH3OH

Sodium benzoate

3. Esters can react with ammonia/amines to form amide and alcohols.

R N

O R"NH2+ R"

H

R N

O NH3+ H

H

R O

OR'

R O

OR'

R'OH+

R'OH+

Examples:

N

O CH3NH2+ CH3

H

N

O

NH3+ H

HO

O

O

O

+

+

OH

OH

4. Esters can be reduced with lithium aluminium hydrides (LiAlH4

R OH

Ester

R O

OR' R'OH+

AlcoholAlcoholthen H2O

LiAlH4

) to form alcohol.

Example:

then H2OLiAlH4 OHO

O+

Methyl benzoate

CH3OH

Benzylalcohol

Methanol