ORGANIC CHEMISTRY REACTION SCHEME - … · Web viewCH3COCl + H2N–CH2–COOH CH3–CO–NH–CH2COOH + HCl Esterification H2N–CH2–COOH + ROH +H3N–CH2–COOR + H2O Peptide Formation

ORGANIC CHEMISTRY REACTION SCHEMEAN OVERVIEW

ALKANESPreparation of Alkanes

1. Hydrogenation of AlkenesCnH2n CnH2n+2

2. Reduction of Alkyl Halidesa. Hydrolysis of Grignard Reagent

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 AcidRX RH + Zn2+ + X–

Reactions of Alkanes1. Halogenation [Free Radical Substitution]

CnH2n+1H + X2 CnH2n+1X + HX2. Combustion

CnH2n+2 + excess O2 nCO2 + (n+1)H2O3. Pyrolysis Cracking

alkane H2 + smaller alkanes + alkenes

ALKENESPreparation of Alkenes

1. Dehydrohalogenation of Alkyl Halides

2. Dehydration of Alcohols

3. Dehalogenation of Vicinal Dihalides

Reactions of Alkenes1. Addition of Hydrogen. Catalytic Hydrogenation

CnH2n CnH2n+2

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O R G A N I C C H E M I S T R Y R E A C T I O N S C H E M E – A N O V E R V I E W

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

3. Addition of Aqueous Halogen. Formation of Halohydrin

4. Addition of Hydrogen Halides

5. Addition of Water. Hydration a) Industrial Method

b) Laboratory Method

6. Oxidationa) Cold, alkaline KMnO4 Solution

b) Hot, acidic KMnO4 Solution

*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

ARENESReactions of Benzenes

1. Nitration [Electrophilic Substitution in mononitration of benzene]

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Dark, room temp

55oC


2. Sulphonation

3. Halogenation

4. Friedel-Crafts Alkylation

5. Friedel-Crafts Acylation

6. Hydrogenation

Preparation of Alkylbenzenes1. Attachment of Alkyl Group. Friedal-Crafts Alkylation

2. Conversion of side chain

*Note: This is known as the Clemmensen or Wolff-Kishner Reduction

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Note: acyl group

Or Fe

Or H2/Pd, ethanol

N2 + H2O


Reactions of Alkylbenzenes1. Hydrogenation

2. Oxidationa. Mild Oxidation

b. Strong Oxidation

3. Free Radical Aliphatic Halogenation

*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

5. Electrophillic Aromatic Nitration by Electrophillic Addition

6. Electrophillic Aromatic Friedal-Crafts Alkylation by Electrophillic Addition

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30oC


7. Electrophillic Aromatic Sulphonation by Electrophillic Addition

8. Electrophillic Aromatic Friedal-Crafts Acylation by Electrophillic Addition

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 DERIVATIVESPreparation of Halogenoalkanes

1. Substitution in Alcoholsa. Using HX (suitable for 3° alcohols)

R–OH R–X + H2Ob. Using PX3/PX5 (suitable for 1°, 2° alcohols)

R–OH R–X + POX3 + HXc. Using SOCl2 (sulphonyl chloride)

R–OH R–Cl + SO2 + HCl*Note: This is the best method because it is very clean. SO2 can be bubbled off and HCl, being an acid, will react with pyridine.

2. Electrophillic Addition to Alkenesa) Addition of Hydrogen Halides

b) Addition of Halogens

3. Free Radical Substitution of AlkanesCnH2n+1H + X2 CnH2n+1X + HX

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Reactions of Halogenoalkanes1. Alkaline Hydrolysis of Alcohols [Nucleophilic Substitution]

R–X + OH– R–OH + X–

*Note: Mechanism is SN2 for 1° halogenoalkane and SN1 for 3° halogenoalkane

2. Nitrile SynthesisR–X + NaCN R–C≡N + NaBr

*Note: Nitriles are useful because they can be used to synthesize 1o amines and carboxylic acids.Reduction to Amine:

R–C≡N RCH2NH2

Acidic Hydrolysis:

R–C≡N RCOOH + NH4+

Basic Hydrolysis:

R–C≡N RCOO–Na+ + NH3

3. Formation of Amines

R–X + excess conc NH3 [H3

δ +

N---R---δ –

X] RNH2 + NH4+X–

*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.

NH3 RNH2 R2NH R3N R4N+X–

4. Williamson Synthesis (Formation of Ether)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)

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

Reactions of Halogenoarenes1. Industrial Hydrolysis (Replacement of Halogen Atom, difficult due to strong C–X bond)

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

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Conc H2SO4, 140oC

Conc H2SO4, 140oC


HYDROXY COMPOUNDSPreparation of Alcohols

1. Alkene Hydration. Addition of Water.

2. Alkaline Hydrolysis of HalogenoalkanesR–X + OH– R–OH + X–

3. Reduction of Carboxylic Acids, Aldehydes and Ketonesa. Carboxylic Acids and Aldehydes are reduced to their primary alcohols.

b. Ketones are reduced to their secondary alcohols.

*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.

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

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

Reactions of Alcohols1. Substitution in Alcohols

a. Using HX (suitable for 3° alcohols)R–OH R–X + H2O

b. Using PX3/PX5 (suitable for 1°, 2° alcohols)R–OH R–X + POX3 + HX

c. Using SOCl2 (sulphonyl chloride)R–OH R–Cl + SO2 + HCl

*Note: This is the best method because it is very clean. SO2 can be bubbled off and HCl, being an acid, will react with pyridine.

2. Reaction with Sodium/Potassium

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

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–H

C O

R

H

CCH3

O-

HH

H 2OC

CH3OH

HH


3. Oxidation to Carbonyl Compounds and Carboxylic Acidsa. Primary Alcohols are oxidized to aldehydes first, then carboxylic acids.

*Note: MnO2 is also a milder oxidizing agent.

b. Secondary Alcohols are oxidized to ketones.

c. Tertiary alcohols are not readily oxidized.

4. Dehydration to Alkenesa. Excess conc H2SO4

b. Excess alcoholR–CH2OH + conc H2SO4 R–CH2–O– CH2–R

5. Esterification

6. Acylation a. Acid Chloride

b. Acid Anhydride

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.

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

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Note: acyl group


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

c. Overall Equation:

Preparations of Phenols1. Replacement of OH– group in diazonium salts

Reactions of Phenols1. Reaction with Reactive Metals (e.g. Na or Mg)

2. Reaction with NaOH

*Note: Phenols have no reactions with carbonates

3. Esterifications

*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.

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4. Halogenationa. With bromine(aq)

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

b. With bromine(CCl4)

5. Nitrationa. With conc nitric acid

b. With dilute nitric acid

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.

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CARBONYL COMPOUNDSPreparation of Aldehydes

1. Oxidation of Primary Alcohols

Preparations of Ketones1. Oxidation of Secondary Alcohols

2. Oxidative Cleavage of Alkenes

Reactions of Carbonyl Compounds1. Addition of Cyanide. Cyanohydrin formation.

[Nucleophilic Addition of Hydrogen Cyanide to Aldehyde and Ketone]

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

Basic Hydrolysis

*Note: Cyanohydrins can undergo reduction.

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

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

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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.

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

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

*Note: Aliphatic aldehydes reduce the copper(II) in Fehling’s solution to the reddish-brown copper(I) oxide.R–CHO + 2Cu2+ + 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)

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

*Note: Aldehydes redyce the Ag(I) in Tollen’s reagent to Ag, forming a silver mirror.RCHO + 2[NH3AgNH3]+ + 3OH– RCOO– + 2Ag (s) + 4NH3 + 2H2O

4. Reduction Reactions a. Reduction of Aldehydes to Primary Alcohols

R–CHO + 2[H] R–CH2OH

R–CHO + H2 R–CH2OHb. Reduction of Ketones to Secondary Alcohols

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

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 + POCl3CH3COCH3 + PCl5 CH3CCl2CH3 + POCl3

CARBOXYLIC ACIDS & DERIVATIVESPreparation of Carboxylic Acids

1. Oxidationa. Oxidation of Primary Alcohols and Aldehydes

b. Oxidative Cleavage of Alkenes

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c. Oxidation of an Alkylbenzene (Formation of Benzoic Acid)

2. Hydrolysisa. Hydrolysis of Nitriles (R–C≡N)

Acidic Hydrolysis

R–C≡N RCOOH + NH4+

Basic Hydrolysis

R–C≡N RCOO–Na+ + NH3

b. Hydrolysis of Esters (RCOOR’)Acidic Hydrolysis

RCOOR’ + H2O RCOOH + R’OHBasic Hydrolysis

RCOOR’ + H2O RCOO–Na+ + R’OH

RCOO–Na+ RCOOH

Reactions of Carboxylic Acids1. Salt Formation

a. Reaction with MetalRCOOH + Na RCOO–Na+ + ½H2

b. Reaction with BasesRCOOH + NaOH RCOO–Na+ + H2O

c. Reaction with Carbonates2RCOOH + Na2CO3 2RCOO–Na+ + H2O + CO2

2. Esterification

3. Conversion into Acyl Chlorides (RCOCl)RCOOH + PCl5 RCOCl + POCl3 + HCl

3RCOOH + PCl3 3RCOCl + H3PO3

RCOOH + SOCl2 RCOCl + HCl + SO2

4. Reduction to AlcoholsRCOOH + 4[H] RCH2OH + H2O

Preparation of Acyl Chlorides1. From Carboxylic Acid

RCOOH + PCl5 RCOCl + POCl3 + HCl3RCOOH + PCl3 3RCOCl + H3PO3

RCOOH + SOCl2 RCOCl + HCl + SO2

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Reactions of Acyl Chlorides1. Conversion into Acid. Hydrolysis

RCOCl + H2O RCOOH + HClArCOCl + 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.RCOCl + R’OH RCOOR’ + HCl

*Note: Reaction is slow when phenol is directly reacted with acyl chloride. 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’ + HClRCOCl + R’R’’NH RCONR’R’’ + HCl

4. Reduction to Aldehyde, then AlcoholRCOCl RCHO RCH2OH

Preparations of Esters1. Condensation Reaction of Acid and Alcohol

a. Ethyl Ethanoate

b. Phenyl BenzoateArOH + NaOH ArO–Na+ + H2O

ArCOCl + ArO–Na+ ArCOOAr + NaCl

Reaction of Esters1. Hydrolysis

a. Acidic Hydrolysis

RCOOR’ + H2O RCOOH + R’OH

b. Basic HydrolysisRCOOR’ + H2O RCOO–Na+ + R’OH

2. Reduction to Primary AlcoholsRCOOR’ RCH2OH

Preparation of Polyesters1. Condensation Reaction

nHOOCRCOOH + nHOR’OH ( OCRCOOR’O ) n + 2nH2O

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NITROGEN COMPOUNDSPreparation of Amines

1. Reaction of Halides with Ammonia or Amines. Ammonolysis

R–X + excess conc NH3 [H3

δ +

N---R---δ –

X] RNH2 + NH4+X–

NH3 RNH2 R2NH R3N R4N+X–

2. Reductiona. Reduction of Amide

RCONH2 RNH2

b. Reduction of NitrileR–C≡N RCH2NH2

c. Reductive Amination

Reactions of Amines1. Salt Formation

RNH2 + HCl RNH3+ Cl–

RNH2 + R’COOH RNH3+ –OOCR’

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

2. Formation of Amides. Acylation.

*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 Aminesa. Halogenation

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RCH2NH2

White ppt


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

*Note: NHCOCH3 is also 2,4-directing but moderately activating. Halogenation of ArNHCOCH3 will give N-(2-bromophenyl)acetamide or N-(4-bromophenyl)acetamide. Reacting this with aqueous NaOH and heating will give 2-bromophenylamine or 4-bromophenylamine.

b. Nitration

*Note: The same steps as above can be taken if we want monosubstituted nitrophenylamine.

Preparations of Amides1. Ammonolysis of Acid Derivatives

RCOCl + NH3 RCONH2 + HClRCOCl + R’NH2 RCONHR’ + HCl

RCOCl + R’R’’NH RCONR’R’’ + HCl

2. Reaction between Amine and Acid Chloride

Reactions of Amides1. Acidic Hydrolysis

RCONH2 R–COOH + NH4+

2. Basic HydrolysisRCONH2 R–COO– + NH3

Preparations of Amino Acids1. Hell-Volhard-Zelinsky Reaction

Reactions of Amino Acids1. 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

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3. EsterificationH2N–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.

5. Hydrolysis of Peptidesa. Acidic Hydrolysis

b. Basic Hydrolysis

*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.

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APPENDIXHalogenation 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).

CH4 + Cl2 CH3Cl + HCl

+ 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.

Markovnikov’s RuleIn 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 RuleFor 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.

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Cl● Atom: Attacks side chain

Cl+ Ion: Attacks ring

CH3

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ORGANIC CHEMISTRY REACTION SCHEME - … · Web viewCH3COCl + H2N–CH2–COOH CH3–CO–NH–CH2COOH + HCl Esterification H2N–CH2–COOH + ROH +H3N–CH2–COOR + H2O Peptide Formation