Org Chem

ORGANIC CHEMISTRY REACTION SCHEME AN OVERVIEW ALKANES Preparation of Alkanes 1. Hydrogenation of Alkenes H2 + Ni, Pd or Pt CnH2n   CnH2n+2

2. Reduction of Alkyl Halides a. Hydrolysis of Grignard Reagent dry ethyl ether water RX + Mg   RMgX   RH + Mg(OH)X *Note: RMgX is the Grignard reagent, alkylmagnesium halide. The alkyl group is covalently bonded to magnesium; + – and magnesium-halogen bond is ionic ie. [R:Mg] [X] . In the second step of the reaction, it is a displacement reaction in which water (the stronger acid) displacing the weaker acid (R–H) from its salt (RMgX).

b. Reduction by Metal and Acid +

–

Zn + H RX   RH + Zn + X

2+

Reactions of Alkanes 1. Halogenation [Free Radical Substitution] heat, or UV CnH2n+1H + X2   CnH2n+1X + HX 2. Combustion heat CnH2n+2 + excess O2   nCO2 + (n+1)H2O 3. Pyrolysis Cracking 400-600 C   H2 + smaller alkanes + alkenes alkane  with or w/o catalyst

ALKENES Preparation of Alkenes 1. Dehydrohalogenation of Alkyl Halides H H H

C

C

H

X

alcoholic KOH  H  OH  reflux

H

H

H

C

C

2. Dehydration of Alcohols H H H

C

C

excess conc H2SO 4 , 170 C H   H or Al2 O3 , 400 C

H+ KX + H2O

H

H

C

C

H + H2O

or H3PO4 , 200-250 C

H

OH

3. Dehalogenation of Vicinal Dihalides H H H

C

C

X

X

Zn H  H

H

H

C

C

H + ZnX2

Reactions of Alkenes 1. Addition of Hydrogen. Catalytic Hydrogenation H2 + Ni, Pd or Pt  CnH2n+2 CnH2n  Heat

1

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

SCHEM E

–

AN

OVERVIEW

2. Addition of Halogens [Electrophilic Addition using bromine/ethene] H H H H H

C

X2 /CCl4 H   dark, room temperature

C

3. Addition of Aqueous Halogen. Formation of Halohydrin H H H H

C

X2 /H2 O H   H

C

H

C

C

X

X

H

H H + HX

C

C

X

OH

Dark, room temp

4. Addition of Hydrogen Halides H H

H

C

HX  H H 

C

5. Addition of Water. Hydration a) Industrial Method H H H

C

C

H2 O(g)   conc H3PO4

H

H

H

H

C

C

X

H

H

H

H

C

C

H

OH

H

300C, 60atm

b) Laboratory Method H H

H

C

C

H

conc H2 SO4   cold

H

H

H

C

C

H

OSO3H

H

H2 O, heat    H (hydrolysis)

6. Oxidation a) Cold, alkaline KMnO4 Solution H H H

C

C

alkaline KMnO 4  H cold

H

H

H

C

C

H

H

C

C

H

OH

H + H2SO4

H

OH OH

b) Hot, acidic KMnO4 Solution H H H

C

C

H

H 

MnO4 /H2 SO4 H  hot

C

H O

+

O

C

H

*Note: Terminal carbons will be oxidized into carbon dioxide. *Note: Under such oxidizing conditions, the aldehydes will be oxidized to carboxylic acid very quickly. To extract the aldehyde only, we must use immediate distillation.

7. Combustion

ARENES Reactions of Benzenes 1. Nitration [Electrophilic Substitution in mononitration of benzene] NO 2 conc. HNO3   conc. H2 SO4

o

55 C

2

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

SCHEM E

–

AN

OVERVIEW

2. Sulphonation

OSO2H H2 SO4 ( l )   reflux

+ H2O

3. Halogenation

X + X2

cold, dark   FeX3 , or AlX3

+ HX

Or Fe 4. Friedel-Crafts Alkylation

R FeX3 , or AlX3 + RX   Lewis Acid

+ HX

5. Friedel-Crafts Acylation

COR Note: acyl group

+ RCOCl / [(RCO) 2O]

 FeX3 , or AlX3

O

+ HX R

C H

6. Hydrogenation

+ 3H 2

Ni   150C

Preparation of Alkylbenzenes 1. Attachment of Alkyl Group. Friedal-Crafts Alkylation

R FeX3 , or AlX3 + RX   Lewis Acid

2. Conversion of side chain R

+ HX

H H C

C O

Zn(Hg), HCl, heat   or N2H4 , base, heat

R

+ HX N2 + H2O

Or H2/Pd, ethanol *Note: This is known as the Clemmensen or Wolff-Kishner Reduction

3

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

–

SCHEM E

AN

OVERVIEW

Reactions of Alkylbenzenes 1. Hydrogenation

R

R + 3H2

Ni, Pt, Pd   150C

2. Oxidation a. Mild Oxidation

CHO

R MnO2   oxidation

b. Strong Oxidation R

COOH 

MnO4 /H2 SO4   or acidified K 2Cr2O7

white crystals

3. Free Radical Aliphatic Halogenation RCH3

RCH2X

  X2 UV, light or heat

*Note: Reaction above is only a generic reaction. Actual position of the halogen is dependent on the stability of the carbocation intermediate.

4. Electrophillic Aromatic Halogenation by Electrophillic Addition R R

R

X X2   FeX3 , FeX5

+

X 5. Electrophillic Aromatic Nitration by Electrophillic Addition R R

R NO 2

conc HNO3   conc H2 SO4

+

o

30 C

NO 2 6. Electrophillic Aromatic Friedal-Crafts Alkylation by Electrophillic Addition R R R

R1 R1X   AlX3

+

R1 4

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

SCHEM E

–

AN

7. Electrophillic Aromatic Sulphonation by Electrophillic Addition R R

OVERVIEW

R

OSO2H H2 SO4 ( l )  

+

OSO2H 8. Electrophillic Aromatic Friedal-Crafts Acylation by Electrophillic Addition R R

R

COR1 + R1COCl / [(R1CO)2O]

+

FeX3 , or AlX3  

COR1 Alkylbenzenes clearly offers two main areas to attack by halogens: the ring and the side chain. We can control the position of the attack simply by choosing the proper reaction conditions. Refer to Appendix for more details.

HALOGEN DERIVATIVES Preparation of Halogenoalkanes 1. Substitution in Alcohols a. Using HX (suitable for 3° alcohols) dry HX, ZnX2 (catalyst)   R–X + H2O R–OH  Reflux b. Using PX3/PX5 (suitable for 1°, 2° alcohols) PX3 /PX 5  R–X + POX3 + HX R–OH  Reflux c.

Using SOCl2 (sulphonyl chloride) SOCl2 , Pyridine(C5H5N)  R–Cl + SO2 + HCl R–OH  Reflux *Note: This is the best method because it is very clean. SO 2 can be bubbled off and HCl, being an acid, will react with pyridine.

2. Electrophillic Addition to Alkenes a) Addition of Hydrogen Halides H H H

C

C

HX  H H 

H

H

C

C

X

H

b) Addition of Halogens H H H

C

C

X2 /CCl4 H   dark, room temperature

H

H

H

H

C

C

X

X

H

3. Free Radical Substitution of Alkanes heat, or UV CnH2n+1H + X2   CnH2n+1X + HX

5

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

–

SCHEM E

AN

OVERVIEW

Reactions of Halogenoalkanes 1. Alkaline Hydrolysis of Alcohols [Nucleophilic Substitution] – aqueous KOH R–X + OH–   R–OH + X reflux *Note: Mechanism is S N2 for 1° halogenoalkane and S N1 for 3° halogenoalkane

2. Nitrile Synthesis aqueous ethanol R–X + NaCN   R–C≡N + NaBr reflux o

*Note: Nitriles are useful because they can be used to synthesize 1 amines and carboxylic acids. Reduction to Amine: LiAlH4 , dry ether R–C≡N   RCH2NH2 or 2H2 , Ni, heat Acidic Hydrolysis: HCl ( aq ) R–C≡N   RCOOH + NH4 reflux

+

Basic Hydrolysis: NaOH ( aq ) R–C≡N   RCOO Na + NH3 reflux

–

+

3. Formation of Amines δ+

δ–

–

NH3 ethanol, reflux R–X + excess conc NH3   RNH2 + NH4 X  [H3N---R---X]  sealed tube

+

*Note: NH3 acts as the nucleophile and the base. *Note: In the presence of excess RX, there will be polyalkylation of the halogenoalkane and 1°, 2°, 3° and even 4° ammonium salt will be formed. + –

RX RX RX RX NH3    RNH2    R2NH    R3N    R4 N X

4. Williamson Synthesis (Formation of Ether) Conc H2SO4, 140oC R–X + R'O–Na+   R–O–R' + NaX *Note: The sodium or potassium alkoxide (anion of alcohol) is prepared by dissolving sodium and potassium in appropriate – + alcohol. ROH + Na   RO Na + ½H2

5. Dehydrohalogenation (Elimination) H H

H

C

C

H

X

 alcoholic KOH  H H  OH (aq )  reflux

H

H

C

C

H + KX + H2O

Preparation of Halogenoarenes (Aryl Halides) 1. Electrophilic Aromatic Halogenation by Substitution

X + X2

cold, dark   FeX3 , or AlX3

+ HX

Reactions of Halogenoarenes 1. Industrial Hydrolysis (Replacement of Halogen Atom, difficult due to strong C–X bond) + X O Na 2NaOH   350C, 150atm

+ NaX + H2O

-

+ O Na

OH 

+ Na+

H ( aq )  

2. Williamson Synthesis (Formation of Ether) – + R–X + ArO Na   R–O–Ar + NaX o

Conc H2SO4, 140 C

6

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

SCHEM E

–

AN

OVERVIEW

HYDROXY COMPOUNDS Preparation of Alcohols 1. Alkene Hydration. Addition of Water. H H

H

C

C

H

conc H2 SO4   cold

H

H

H

C

C

H

OSO3H

H2 O, heat    H (hydrolysis)

H

H

H

C

C

H

OH

H + H2SO4

2. Alkaline Hydrolysis of Halogenoalkanes – – aqueous KOH R–X + OH   R–OH + X reflux 3. Reduction of Carboxylic Acids, Aldehydes and Ketones a. Carboxylic Acids and Aldehydes are reduced to their primary alcohols. H R +

C

O

+

1. LiAlH4 (ethoxyethane), reflux 2.H /H2 0   or H2 , Ni

4[H]

R

C

HO

OH

+ H2O

H H

R +

C

+

O

4[H]

1. LiAlH4 (ethoxyethane), reflux 2.H /H 2 0   or H2 , Ni

R

H

C

OH

H

b. Ketones are reduced to their secondary alcohols. R

R +

C

+

O

4[H]

1. LiAlH4 (ethoxyethane), reflux 2.H /H 2 0   or H2 , Ni

R1

C

R1

OH

H

*Note: Lithium aluminium hydride (or Lithium tetrahydridoaluminate(III)), LiAlH4, is one of the few reagents that can reduce an acid to an alcohol; the initial product is an alkoxide which the alcohol is liberated by hydrolysis. –

The H ion acts as a nucleophile, and can attack the carbon atom of the carbonyl group. The intermediate then reacts with water to give the alcohol. -

R

O C

H3C

O

C –

OH

H3C

H2O

C

H

H

H H H2O Carboxylic Acid: 4RCOOH + 3LiAlH4   4H2 + 2LiAlO2 + (RCH2O)4AlLi   4RCH2OH H

H

H2O Ketones: 4R2C=O + LiAlH4   (R2CHO)4AlLi   4R2CHOH + LiOH + Al(OH)3

Reactions of Alcohols 1. Substitution in Alcohols a. Using HX (suitable for 3° alcohols) dry HX, ZnX2 (catalyst)   R–X + H2O R–OH  Reflux b. Using PX3/PX5 (suitable for 1°, 2° alcohols) PX3 /PX 5  R–X + POX3 + HX R–OH  Reflux c. Using SOCl2 (sulphonyl chloride) SOCl2 , Pyridine(C5H5N)  R–Cl + SO2 + HCl R–OH  Reflux *Note: This is the best method because it is very clean. SO 2 can be bubbled off and HCl, being an acid, will react with pyridine.

2. Reaction with Sodium/Potassium H

H

C

O

H

H Sodium/Potassium  H

H

C

-

+

O Na

+

1 H2 2

H

*Note: Alcohols are too weak to react with hydroxides and carbonates.

7

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

SCHEM E

–

AN

OVERVIEW

3. Oxidation to Carbonyl Compounds and Carboxylic Acids a. Primary Alcohols are oxidized to aldehydes first, then carboxylic acids. R R R OH K 2 Cr2 O7 /H2 SO4 K 2 Cr2 O7 /H2 SO4 C O C   C   immediate or KMnO4 /H2SO4 distillation H H HO H

O

*Note: MnO2 is also a milder oxidizing agent.

b. Secondary Alcohols are oxidized to ketones. R R OH K 2 Cr2 O7 /H2 SO4 C C   or KMnO4 /H2SO4 R1 R1 H c.

O

Tertiary alcohols are not readily oxidized.

4. Dehydration to Alkenes a. Excess conc H2SO4 H H H

C

excess conc H2SO 4 , 170 C H   H or Al2 O3 , 400 C

C

H

H

C

C

H + H2O

or H3PO4 , 200-250 C

H

OH

b. Excess alcohol 140C R–CH2OH + conc H2SO4  R–CH2–O– CH2–R excess alcohol 5. Esterification

O R

O

R1

C

(can use acid or alkaline as catalyst)

H

OH

C

conc H2 SO4         heat 

O

+

R1

R

H2O

+

O

6. Acylation a. Acid Chloride R

C

+

Cl

Note: acyl group

R1



OH

R

room temperature

C

O

R1

O

+ HCl R

O

C

O

H

b. Acid Anhydride R

C

O

O

C

R

room temperature  

+ R1 OH

R

C

O

O

R1

+

R

C

O

OH

O H

7. Tri-Iodomethane (Iodoform) Formation *Note: Reaction is only positive for alcohol containing a methyl group and a hydrogen atom attached to the carbon at which the hydroxyl group is also attached. H R

C

OH

I2 , NaOH ( aq )   warm

H

CH3

CHI 3

CH3

a. Step 1: Oxidation of Alcohol to the corresponding carbonyl compound by iodine.

R

CH

OH

+

-

I2 + 2 HO

R

CH3

C

O

+ 2 H2 O

+ 2I

-

CH3

8

C

nh05

OH

ORG ANIC

CHEM IST RY

RE ACT ION

SCHEM E

–

AN

OVERVIEW

b. Step 2: Further oxidation to carboxylate salt and formation of iodoform

R

C

O

-

+ 3 I2 + 4HO

R

O

+ CHI 3 + 3 I

O

+ CHI 3 + 5 I

-

+ 3 H2 O

-

O

CH3 c.

C

Overall Equation:

H R

C

-

OH + 4 I2 + 6HO

R

C O

CH3 Preparations of Phenols – 1. Replacement of OH group in diazonium salts N + N O

NH2

-

+ 5 H2O

-

O -

S

OH

OH

O 

 

water, H , heat  

NaNO2 , H2 SO4

Reactions of Phenols 1. Reaction with Reactive Metals (e.g. Na or Mg) +

-

O Na

OH

+

Na

+

1 H 2 2

2. Reaction with NaOH -

OH

+

O Na

+ NaOH

+

1 H O 2 2

*Note: Phenols have no reactions with carbonates

3. Esterifications -

OH

+

O Na NaOH  

RCOCl 

O

O C R

*Note: Phenols do not react with carboxylic acids but their acid chlorides to form phenyl esters. *Note: Esterification is particularly effective in NaOH(aq) as the alkali first reacts with phenol to form phenoxide ion which is a stronger nucleophile than phenol.

9

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

SCHEM E

–

AN

OVERVIEW

4. Halogenation a. With bromine(aq)

OH OH

Br

Br

+ 3HBr

3Br2 ( aq )  

Br *Note: 2,4,6-tribromophenol is a white ppt.

b. With bromine(CCl4) OH

OH

Br2 (CCl4 )  

OH

+ Br

Br 5. Nitration a. With conc nitric acid

OH

OH O 2N

NO 2

conc HNO3  

NO 2 b. With dilute nitric acid OH

OH

dil HNO3  

OH

+ NO 2

O 2N

6. Reaction with FeCl3(aq) *Note: This is a test for phenol. Violet complex upon adding iron(III) chloride will confirm presence of phenol. Colour may vary depending on the substitution on the ring. 3--

O

OH 3+

Fe  

Fe 6

10

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

SCHEM E

–

AN

OVERVIEW

CARBONYL COMPOUNDS Preparation of Aldehydes 1. Oxidation of Primary Alcohols R OH K 2 Cr2 O7 /H2 SO4   C immediate distillation H H

R C H

Preparations of Ketones 1. Oxidation of Secondary Alcohols R R OH K 2 Cr2 O7 /H2 SO4 C C   or KMnO4 /H2 SO4 R1 R1 H 2. Oxidative Cleavage of Alkenes R2 R3

C R1

+ H2O

O

R2

R3



MnO4 /H2 SO4  hot

C

H2 O

+

O

R1

R4

+

C

C

O

O

R4

Reactions of Carbonyl Compounds 1. Addition of Cyanide. Cyanohydrin formation. [Nucleophilic Addition of Hydrogen Cyanide to Aldehyde and Ketone] H H H C HCN, small amount of base + CN  C CN  H O

OH

*Note: Cyanohydrins can be hydrolysed to form 2-hydroxy acids. Acidic Hydrolysis R H

C

R CN

water, HCl (aq)    heat

H

OH

C

+ NH 4Cl

COOH

OH

Basic Hydrolysis R H

C

R water, NaOH ( aq )   H heat

CN

OH

C

-

COO Na

+

+

NH 3

OH

*Note: Cyanohydrins can undergo reduction. R H

C

R CN

LiAlH4 in dry ether  or H2 , Ni, heat

H

OH

R2

C

CH2NH 2

OH

2. Reaction with 2,4-Dinitrophenylhydrazine (Brady’s Reagent). Condensation Reaction. R2 C

O + H2N

NH

NO 2

C

N

NH

NO 2 +

H2 O

R1

R1

O 2N O 2N *Note: 2,4-dinitrophenylhydrazones formed are orange or yellow crystalline solids with characteristic melting points. They are useful for identifying individual aldehydes and ketones.

11

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

SCHEM E

–

AN

OVERVIEW

3. Oxidation Reactions *Note: Aldehydes are easily oxidized to carboxylic acids. Ketone are not.

a. Oxidation of Aldehydes using hot, acidified potassium dichromate(VI) *Note: K2Cr2O7 turned from orange to green if test is positive.

R

H

R

C

OH C

K 2 Cr2 O7 /H2SO4   heat

O

O O

O K 2 Cr2 O7 /H2 SO4   heat

C

C

H R1

R

OH

C

K 2 Cr2 O7 /H2 SO4   No Reaction heat

O b. Oxidation of Aldehydes using hot, acidified potassium manganate(VII) *Note: KMnO4 turned from purple to colourless if test is positive.

R

H

R

C

OH C

  K 2MnO4 /H2 SO4 heat

O

O O

O C

C

K 2MnO4 /H2 SO4   heat

H

c.

OH

Oxidation of Aliphatic Aldehydes using Fehling’s Solution (Fehling’s Test)

R

H C

-

R

O C

Fehling's Solution   warm

O

+

Cu2O (s)

O O Fehling's Solution   No Reaction warm

C H

R

R1 C

Fehling's Solution   No Reaction warm

O *Note: Aliphatic aldehydes reduce the copper(II) in Fehling’s solution to the reddish-brown copper(I) oxide. 2+ – – R–CHO + 2Cu + 5OH   R–COO + Cu2O (s) + 3H2O *Note: Methanal (strongest aldehyde reducing agent) produces metallic copper as well as copper( I) oxide. – – HCHO + Cu2O + OH   HCOO + 2Cu (s) + H2O

d. Oxidation of Aldehydes using Tollen’s Reagent (Silver Mirror Test)

R

H C

-

R Tollen's Reagent   warm

O

O C

Ag (s)

+

O

O

O Tollen's Reagent   warm

C

C

+ Ag (s) -

H

O

12

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

SCHEM E

–

AN

OVERVIEW

d. Oxidation of Aldehydes using Tollen’s Reagent (Silver Mirror Test) (Cont’d) R R1 Tollen's Reagent C   No Reaction warm

O *Note: Aldehydes redyce the Ag(I) in Tollen’s reagent to Ag, forming a silver mirror. + – – heat RCHO + 2[NH3AgNH3] + 3OH   RCOO + 2Ag (s) + 4NH3 + 2H2 O

4. Reduction Reactions a. Reduction of Aldehydes to Primary Alcohols LiAlH4 in dry ether R–CHO + 2[H]  R–CH2OH or NaBH4 ( aq ) Ni catalyst R–CHO + H2   R–CH2OH heat b. Reduction of Ketones to Secondary Alcohols

R

H

R1 C

+

H2

LiAlH4 in dry ether  or NaBH4 ( aq )

R

C

O R

OH H

R1 C

R1

+

H2

R

Ni catalyst   heat

C

O

R1

OH

5. Reaction with Alkaline Aqueous Iodine (Tri-Iodomethane (Iodoform) Formation)

H

*Note: Reaction is only positive for alcohol containing a methyl group attached to the carbon at which the carbonyl group is also attached i.e. methyl carbonyl compounds. For aldehydes, only ethanal will form iodoform. All methyl ketones will form iodoform. NaOH, warm R C O + CHI 3 + 3I + 3H2O R C O + 3 I2 + 4HO  

-

O

CH3 6. Chlorination using Phosphorus Pentachloride (PCl5)

*Note: Aldehydes and ketones react with phosphorus pentachloride to give geminal-dichloro (cf. vicinal) compounds. The oxygen atom in the carbonyl group is replaced by two chlorine atoms.

CH3CHO + PCl5   CH3CHCl2 + POCl3 CH3COCH3 + PCl5   CH3CCl2CH3 + POCl3

CARBOXYLIC ACIDS & DERIVATIVES Preparation of Carboxylic Acids 1. Oxidation a. Oxidation of Primary Alcohols and Aldehydes R R R OH K 2 Cr2 O7 /H2 SO4 K 2 Cr2 O7 /H2 SO4 C O C   C   immediate or KMnO4 /H2SO4 distillation H H HO H b. Oxidative Cleavage of Alkenes H H C H

H

KMnO4 /H2 SO4 , heat  

C

O C OH

H

13

O

+

O

H C OH

nh05

C CH3

O

ORG ANIC

c.

CHEM IST RY

RE ACT ION

SCHEM E

–

AN

OVERVIEW

Oxidation of an Alkylbenzene (Formation of Benzoic Acid)

O CH3

C + 3[O]

OH

KMnO4/H2SO4 , heat  

+ H2O

2. Hydrolysis a. Hydrolysis of Nitriles (R–C≡N) Acidic Hydrolysis HCl ( aq ) R–C≡N   RCOOH + NH4 reflux

+

Basic Hydrolysis – + NaOH ( aq ) R–C≡N    RCOO Na + NH3 reflux

b. Hydrolysis of Esters (RCOOR’) Acidic Hydrolysis HCl ( aq ), reflux    RCOOH + R’OH RCOOR’ + H2O   conc   H2SO 4

Basic Hydrolysis –

NaOH (aq ) RCOOR’ + H2O    RCOO Na + R’OH reflux

+

H RCOO–Na+   RCOOH reflux +

Reactions of Carboxylic Acids 1. Salt Formation a. Reaction with Metal – + RCOOH + Na   RCOO Na + ½H2 b. Reaction with Bases – + RCOOH + NaOH   RCOO Na + H2O c. Reaction with Carbonates – + 2RCOOH + Na2CO3   2RCOO Na + H2O + CO2 2. Esterification

O R

O C

R1

+

OH

C

conc H2 SO4         heat 

O H

(can use acid or alkaline as catalyst)

R

R1

+

H2O

O

3. Conversion into Acyl Chlorides (RCOCl) RCOOH + PCl5   RCOCl + POCl3 + HCl 3RCOOH + PCl3   3RCOCl + H3PO3 RCOOH + SOCl2   RCOCl + HCl + SO2 4. Reduction to Alcohols 1. LiAlH4 in dry ether RCOOH + 4[H]   RCH2OH + H2O 2. H2SO4 ( aq ) Preparation of Acyl Chlorides 1. From Carboxylic Acid RCOOH + PCl5   RCOCl + POCl3 + HCl 3RCOOH + PCl3   3RCOCl + H3PO3 RCOOH + SOCl2   RCOCl + HCl + SO2

14

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

–

SCHEM E

AN

OVERVIEW

Reactions of Acyl Chlorides 1. Conversion into Acid. Hydrolysis RCOCl + H2O  RCOOH + HCl ArCOCl + H2O   ArCOOH + HCl *Note: Benzoyl chloride reacts much slower than acyl chlorides because of the reduce in the positive nature of the carbonyl carbon caused by resonance.

2. Ester Formation. Alcoholysis. room temperature RCOCl + R’OH   RCOOR’ + HCl *Note: Reaction is slow when phenol is directly reacted with acyl chloride. slow RCOCl + ArOH   RCOOAr + HCl *Note: Because phenol is a weaker nucleophile (lone pair of electron delocalizes into the ring), it is converted to phenoxide to increase nucleophilic strength. – + ArOH + NaOH   ArO Na + H2O –

–

RCOCl + ArO   RCOOAr + Cl

3. Amide Formation. Ammonolysis. RCOCl + NH3   RCONH2 + HCl RCOCl + R’NH2   RCONHR’ + HCl RCOCl + R’R’’NH   RCONR’R’’ + HCl 4. Reduction to Aldehyde, then Alcohol LiAlH4 in dry ether LiAlH4 in dry ether RCOCl  RCHO  RCH2OH H2SO4 ( aq ) Preparations of Esters 1. Condensation Reaction of Acid and Alcohol a. Ethyl Ethanoate

O R

O C

R1

+

OH

C

conc H2 SO4         heat 

O H

(can use acid or alkaline as catalyst)

R

R1

+

H2O

O

b. Phenyl Benzoate – + ArOH + NaOH   ArO Na + H2O ArCOCl + ArO–Na+  ArCOOAr + NaCl

Reaction of Esters 1. Hydrolysis a. Acidic Hydrolysis HCl ( aq ), reflux    RCOOH + R’OH RCOOR’ + H2O   conc   H2SO 4

b. Basic Hydrolysis – + NaOH (aq ) RCOOR’ + H2O    RCOO Na + R’OH reflux

2. Reduction to Primary Alcohols LiAlH4 in dry ether RCOOR’  RCH2OH H2SO4 ( aq ) Preparation of Polyesters 1. Condensation Reaction acid nHOOCRCOOH + nHOR’OH   ( OCRCOOR’O ) reflux

15

n

+ 2nH2O

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

SCHEM E

–

AN

OVERVIEW

NITROGEN COMPOUNDS Preparation of Amines 1. Reaction of Halides with Ammonia or Amines. Ammonolysis δ+

δ–

+ – NH3 ethanol, reflux R–X + excess conc NH3   RNH2 + NH4 X  [H3N---R---X]  sealed tube + – RX RX RX RX NH3    RNH2    R2NH    R3N    R4N X

2. Reduction a. Reduction of Amide LiAlH4 in dry ether RCONH2  RNH RCH22NH2 H2 / Ni or Pt

b. Reduction of Nitrile LiAlH , dry ether  RCH2NH2 R–C≡N  or 2H , Ni, heat 4

2

c.

Reductive Amination H

H

H C

O

+ NH 3 

H

H

C NH imine

H2 , Ni  H or NaBH3 CN

C

NH2

H

Reactions of Amines 1. Salt Formation + – RNH2 + HCl   RNH3 Cl +– RNH2 + R’COOH   RNH3 OOCR’

+

NH2

NH 3 Cl

+

HCl

-

 

*Note: Phenylamine is not soluble in water but dissolves in acid.

2. Formation of Amides. Acylation. R'COCl   R'CONHR + HCl ArSO2Cl   ArSO2NHR + HCl

RNH2 RR'NH

R''COCl   R''CONRR'  HCl ArSO2 Cl   ArSO2NRR'  HCl

RR'R''N

R'''COCl   no reaction ArSO2 Cl   no reaction

*Note: Since HCl is formed, some of the ammonia/amine will be protonated and cannot act as a nucleophile. Hence, at least double the amount of ammonia / amine must be used. *Note: Acylation of 1° and 2° amines leads to the formation of substituted amides. 3° do not undergo acylation because they do not have any replaceable H atoms. CH3CH2NH2 + CH2COCl   CH3CH2NHCOCH3 + HCl ArNH2 + Ar’COCl   ArNHCOAr’ + HCl ArNH2 +RCOCl   ArNHCOR + HCl

3. Ring Substitution Reactions of Aromatic Amines a. Halogenation NH2

NH2 Br

+

3Br2 (aq)

Br



(s)

+ 3HBr

White ppt

Br

16

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

–

SCHEM E

AN

OVERVIEW

*Note: To get monosubstituted compounds, react phenylamine with ethanoyl chloride to reduce the ‘strongly activating’ nature of the amino group to form phenylacetamide. NH2

NHCOCH 3

+

CH3COCl 

*Note: NHCOCH3 is also 2,4-directing but moderately activating. Halogenation of ArNHCOCH 3 will give N-(2bromophenyl)acetamide or N-(4-bromophenyl)acetamide. Reacting this with aqueous NaOH and heating will give 2-bromophenylamine or 4-bromophenylamine.

b. Nitration

NH2

NH2 O 2N

NO 2

conc HNO + conc H SO3  2 4

NO 2 *Note: The same steps as above can be taken if we want monosubstituted nitrophenylamine. Preparations of Amides 1. Ammonolysis of Acid Derivatives RCOCl + NH3   RCONH2 + HCl RCOCl + R’NH2   RCONHR’ + HCl RCOCl + R’R’’NH   RCONR’R’’ + HCl 2. Reaction between Amine and Acid Chloride R'COCl   R'CONHR + HCl RNH2 ArSO2Cl   ArSO2NHR + HCl RR'NH

R''COCl   R''CONRR'  HCl ArSO2 Cl   ArSO2NRR'  HCl

Reactions of Amides 1. Acidic Hydrolysis HCl, H2 O  R–COOH + NH4+ RCONH2  heat

2. Basic Hydrolysis NaOH, H2 O  R–COO– + NH3 RCONH2  heat

Preparations of Amino Acids 1. Hell-Volhard-Zelinsky Reaction H Br2 , PBr3   heat

C H

H

R

COOH

C Br

H excess conc NH3   COOH H2N R

C R

COOH

Reactions of Amino Acids 1. Salt Formation + a. Reaction with H . Cationic + + H3N–CH2–COO–(aq) + H+(aq)   H3N–CH2–COOH (aq) – b. Reaction with OH . Anionic + – – – H3N–CH2–COO (aq) + OH (aq)   H2N–CH2–COO (aq) + H2O(l) *Note: The above two equations explains the buffering capability of amino acids.

2. Acylation (Formation of Amides) CH3COCl + H2N–CH2–COOH   CH3–CO–NH–CH2COOH + HCl

17

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

SCHEM E

–

AN

OVERVIEW

3. Esterification HCl H2N–CH2–COOH + ROH    

+

H3N–CH2–COOR + H2O

4. Peptide Formation *Note: A peptide is any polymer of amino acids linked by amide bonds between the amino grup of each amino acid and the carboxyl group of the neighbouring amino acid. The –CO–NH– (amide) linkage between the amino acids is known as a peptide bond.

H2N

CH

C

R

O

OH

+ H2N

CH

C

R1

O

OH

H2N

5. Hydrolysis of Peptides a. Acidic Hydrolysis H O H

------

C

C

R

H ------

C R

N

C

H

R1

H2 SO4 ( aq )  -----------  heat

N

C

H

R1

C

N

CH

C

R

O

H

R1

O

H

O

C

C

OH

NaOH ( aq )  -----------  heat

+

OH

+

H3N

C

------

R1

H

O

C

C

R

+ H2 O

H

R

b. Basic Hydrolysis O H

C

CH

H O

-

+

H2N

C

------

R1

*Note: A peptide bond can be cleaved by hydrolysis in the presence of a suitable enzyme (trypsin, pepsin etc) or by heating in acidic or alkaline medium.

18

nh05

ORG ANIC

CHEM IST RY

RE ACT ION

SCHEM E

–

AN

OVERVIEW

APPENDIX Halogenation of Alkylbenzenes: Ring vs Side chain Alkylbenzenes clearly offer two main areas to attack by halogens: the ring and the side chain. We can control the position of attack simply by choosing the proper reaction conditions. Halogenation of alkanes requires conditions under which halogen atoms are formed, that is, high temperature or light. Halogenation of benzene, on the other hand, involves transfer of positive halogen, which is promoted by acid catalysts like ferric chloride (FeCl3). heat or light CH4 + Cl2   CH3Cl + HCl Cl

FeCl3 , cold + Cl2   

+ HCl

We might expect, then, that the position of attack in, for example, methylbenzene would be governed by which the attack particle is involved, and therefore by the conditions employed. This is so: if chlorine is bubbled into boiling methylbenzene that is exposed to ultraviolet light, substitution occurs almost exclusively in the side chain; in the absence of light and in the presence of ferric chloride, substitution occurs mostly in the ring.

CH3

Cl●

Atom: Attacks side chain

Cl+

Ion: Attacks ring

Markovnikov’s Rule In the ionic addition of an acid to the carbon-carbon double bond of an alkene, the hydrogen of the acid attaches itself to the carbon atom that already holds the greater number of hydrogens. Saytzeff’s Rule For elimination reactions, the preferred product is the alkene with the most alkyl groups attached to the doubly bonded carbon atoms i.e. the most substituted product.

19

nh05