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ACID CHLORIDES / ACYL CHLORIDES
▢ Definition: RCOCl = carboxylic acid derivative formed by replacement of −OH of −COOH by −Cl
▢ Functional Group: −COCl / acyl chloride group
▢ Nomenclature:
❖ Rule:
◉ Common: −ic acid → −yl chloride
◉ IUPAC: alkanoic acid → alkanoyl chloride
❖ Examples:
◈ Formula: HCOCl
◈ Common: Formyl chloride
◈ IUPAC: Methanoyl chloride
◈ Formula: CH3COCl
◈ Common: Acetyl chloride
◈ IUPAC: Ethanoyl chloride
◈ Formula: CH3CH2COCl
◈ Common: Propionyl chloride
◈ IUPAC: Propanoyl chloride
▢ Preparation:
❖ From Carboxylic Acid:
- RCOOH + PCl5 → RCOCl + POCl3 + HCl
- 3RCOOH + PCl3 → 3RCOCl + H3PO3
- RCOOH + SOCl2 → RCOCl + SO2↑ + HCl↑
❖ Preferred Reagent: SOCl2 → gaseous by-products SO2 + HCl escape → pure acyl chloride
❖ From Salt of Acid:
- CH3COONa + PCl3 → CH3COCl + Na3PO3
- CH3COONa + PCl5 → CH3COCl + POCl3 + NaCl
- CH3COONa + POCl3 → CH3COCl + NaPO3 + NaCl
- CH3COONa + SOCl2 → CH3COCl + SO2 + NaCl
❖ Industrial Point: Carboxylate salts cheaper than acids
❖ From Ketene:
- CH2=C=O + HCl → CH3COCl
- CH3CH=C=O + HCl → CH3CH2COCl
▢ Physical Properties:
❖ State: Lower members → colourless low-boiling liquids; higher members → colourless low-melting solids
❖ Smell: Pungent, irritating
❖ Fuming: RCOCl + H2O → RCOOH + HCl fumes
❖ Solubility: Insoluble in water; soluble in ether, chloroform, acetone, benzene
❖ Boiling Point:
◉ Order: Acid chloride < corresponding carboxylic acid
◉ Reason: No intermolecular H-bonding in acyl chlorides
◉ Examples:
- CH3COOH: 391 K > CH3COCl: 324 K
- C6H5COOH: 523 K > C6H5COCl: 470 K
▢ Chemical Properties:
❖ Reactivity:
◉ Reason: −Cl has strong −I effect; weak +R effect; acyl carbon strongly electrophilic
◉ Acid Derivative Reactivity Order: RCOCl > (RCO)2O > RCOOR′ > RCONH2
❖ Nucleophilic Acyl Substitution:
◉ Hydrolysis: RCOCl + H2O → RCOOH + HCl
◉ Alcoholysis: RCOCl + R′OH → RCOOR′ + HCl
◉ With Sodium Alkoxide: RCOCl + R′ONa → RCOOR′ + NaCl
◉ Ammonolysis: RCOCl + 2NH3 → RCONH2 + NH4Cl
◉ With 1° Amine: RCOCl + 2R′NH2 → RCONHR′ + R′NH3Cl
◉ With 2° Amine: RCOCl + 2R′2NH → RCONR′2 + R′2NH2Cl
◉ With Carboxylate Salt: RCOCl + R′COONa → RCO−O−COR′ + NaCl
❖ Reduction:
◉ Rosenmund Reduction: RCOCl + H2 / Pd-BaSO4 → RCHO + HCl
◉ LiAlH4: RCOCl → RCH2OH
◉ Organocadmium: RCOCl + R′2Cd → RCOR′
❖ Grignard Reagent: RCOCl + 2R′MgX → tertiary alcohol after hydrolysis
❖ Friedel-Crafts Acylation: Ar−H + RCOCl / anhyd. AlCl3 → ArCOR + HCl
❖ Special Example: C6H6 + CH3COCl / AlCl3 → C6H5COCH3
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ACID ANHYDRIDES
▢ Definition: Acid derivative formed by removal of H2O from two carboxylic acid molecules
▢ General Formula: CnH2n−2O3
▢ Functional Group: RCO−O−COR′
▢ Types:
❖ Simple Anhydride: R = R′
❖ Mixed Anhydride: R ≠ R′
❖ Simplest Theoretical: HCO−O−COH; unstable
▢ Nomenclature:
◉ Formula: CH3CO−O−COCH3
◉ Common: Acetic anhydride
◉ IUPAC: Ethanoic anhydride
◉ Formula: C2H5CO−O−COC2H5
◉ Common: Propionic anhydride
◉ IUPAC: Propanoic anhydride
◉ Formula: CH3CO−O−COC2H5
◉ Common: Acetic propionic anhydride
◉ IUPAC: Ethanoic propanoic anhydride
◉ Formula: C6H5CO−O−COC6H5
◉ Common: Benzoic anhydride
◉ IUPAC: Benzoic anhydride
▢ Preparation:
❖ From Carboxylic Acid: 2RCOOH / P2O5 or heat → RCO−O−COR + H2O
❖ From Dicarboxylic Acids:
◉ Rule: Ortho dicarboxylic acids or suitable dicarboxylic acids lose H2O intramolecularly
◉ Example: Phthalic acid → phthalic anhydride + H2O
❖ Lab Method: RCOCl + RCOONa / anhydrous → RCO−O−COR + NaCl
❖ Example: CH3COCl + CH3COONa → (CH3CO)2O + NaCl
▢ Physical Properties:
❖ State: Lower aliphatic anhydrides → colourless liquids; higher/aromatic anhydrides → solids
❖ Smell: Pungent
❖ Solubility: Insoluble in water; soluble in alcohol, ether, acetone
❖ Boiling Point:
◉ Order: Acid anhydride > corresponding carboxylic acid
◉ Reason: Greater molecular mass → stronger Van der Waals forces
◉ Example: Acetic acid: 391 K < acetic anhydride: 413 K
▢ Chemical Properties:
❖ Acylating Nature: Less vigorous than acid chloride; easily controlled
❖ Hydrolysis:
◉ Reaction: RCO−O−COR + H2O → 2RCOOH
◉ Rate Order: Alkaline > acidic > neutral
❖ Alcoholysis: RCO−O−COR + R′OH → RCOOR′ + RCOOH
❖ Example Alcoholysis: (CH3CO)2O + C2H5OH → CH3COOC2H5 + CH3COOH
❖ Ammonolysis: RCO−O−COR + NH3 → RCONH2 + RCOOH
❖ Example Ammonolysis: (CH3CO)2O + NH3 → CH3CONH2 + CH3COOH
❖ With Amines: RCO−O−COR + R′NH2 → RCONHR′ + RCOOH
❖ Reduction: (RCO)2O + LiAlH4 → 2RCH2OH
❖ With PCl5: (RCO)2O + PCl5 → 2RCOCl + POCl3
❖ With SOCl2: (RCO)2O + SOCl2 → 2RCOCl + SO2
❖ With HX: RCO−O−COR + HX → RCOX + RCOOH
❖ With Acetaldehyde: (CH3CO)2O + CH3CHO → CH3CH(OCOCH3)2
❖ Friedel-Crafts Acylation:
◉ General: Ar−H + (RCO)2O / anhyd. AlCl3 → ArCOR + RCOOH
◉ Example: C6H6 + (CH3CO)2O / AlCl3 → C6H5COCH3 + CH3COOH
◉ Dicarboxylic Anhydrides: Readily give keto acids in Friedel-Crafts acylation
▢ Uses:
- Acylating agent for alcohols, phenols, amines
- Detection/estimation of −OH and −NH2 groups
- Manufacture of aspirin
- Manufacture of acetophenone
- Manufacture of acetamide
- Manufacture of cellulose acetate
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ACID AMIDES
▢ Definition: Carboxylic acid derivatives formed by replacement of −OH of −COOH by −NH2, −NHR or −NR2
▢ General Formula: CnH2n+1NO
▢ Types:
◉ Type: Primary amide
◉ Formula: RCONH2
◉ Type: Secondary amide
◉ Formula: RCONHR′
◉ Type: Tertiary amide
◉ Formula: RCONR′2
▢ Preparation:
❖ From Carboxylic Acid:
- RCOOH + NH3 → RCOO−NH4+
- RCOO−NH4+ / Δ → RCONH2 + H2O
❖ Example: CH3COOH + NH3 → CH3COONH4 → CH3CONH2 + H2O
❖ Ammonolysis of Acid Chloride: RCOCl + 2NH3 → RCONH2 + NH4Cl
❖ Ammonolysis of Acid Anhydride: (RCO)2O + NH3 → RCONH2 + RCOOH
❖ Ammonolysis of Ester: RCOOR′ + NH3 → RCONH2 + R′OH
❖ Partial Hydrolysis of Nitrile: RCN + H2O / acid or alkaline H2O2 → RCONH2
❖ From Urea: RCOOH + NH2CONH2 / Δ → RCONH2 + CO2 + NH3
▢ Physical Properties:
❖ State: Formamide → liquid; other amides → colourless crystalline solids
❖ Solubility: Lower aliphatic amides up to C6 soluble in water; higher/aromatic amides insoluble
❖ Reason for Solubility: Intermolecular H-bonding with water
❖ Melting/Boiling Point:
◉ High: Strong intermolecular H-bonding
◉ Order: Amide > corresponding carboxylic acid
◉ Examples:
- Acetamide: 494 K > acetic acid: 391 K
- Benzamide: 563 K > benzoic acid: 523 K
▢ Chemical Properties:
❖ Reactivity:
◉ Order: Least reactive acid derivative
◉ Reason: Strong +R effect of −NH2 decreases electrophilicity of carbonyl carbon
❖ Amphoteric Nature:
◉ Nature: Very weak acid + very weak base
◉ Litmus: No effect
◉ Acidic Character: 2RCONH2 + 2Na → 2RCONHNa + H2↑
◉ Basic Character: RCONH2 + HCl → RCONH2·HCl
❖ Hydrolysis:
◉ Acidic: RCONH2 + H2O + HCl → RCOOH + NH4Cl
◉ Alkaline: RCONH2 + NaOH → RCOONa + NH3
❖ Dehydration:
◉ Reagents: P2O5, SOCl2, POCl3
◉ Reaction: RCONH2 → RCN + H2O
❖ Reduction:
◉ LiAlH4: RCONH2 → RCH2NH2
◉ Meaning: Amide → 1° amine
❖ Hofmann Bromamide Degradation:
◉ Reaction: RCONH2 + Br2 + 4KOH → RNH2 + K2CO3 + 2KBr + 2H2O
◉ Product: 1° amine with one carbon less
◉ Key: Carbonyl carbon removed as carbonate
❖ With Nitrous Acid: RCONH2 + HNO2 → RCOOH + N2 + H2O
❖ With Grignard Reagent:
◉ Primary/Secondary Amide: Acidic N−H reacts with RMgX → hydrocarbon + magnesium salt
◉ Tertiary Amide: RCONR′2 + RMgX → ketone after hydrolysis
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ACID DERIVATIVES: HIGH-YIELD COMPARISON
▢ General Derivative Pattern: RCO−Z
▢ Leaving Group Strength: Cl− > RCOO− > RO− > NH2−
▢ Reactivity Order: Acid chloride > Acid anhydride > Ester > Amide
▢ Common Reaction Type: Nucleophilic acyl substitution
▢ Boiling Point Trend:
❖ Acid Chloride: Lower than acid; no H-bonding
❖ Ester: Lower than acid; no self H-bonding
❖ Acid Anhydride: Higher than acid; larger molecular size
❖ Amide: Highest; strong H-bonding
▢ Hydrolysis Products:
◉ Derivative: RCOCl
◉ Product: RCOOH + HCl
◉ Derivative: (RCO)2O
◉ Product: 2RCOOH
◉ Derivative: RCOOR′
◉ Product: RCOOH + R′OH / acid; RCOO− + R′OH / base
◉ Derivative: RCONH2
◉ Product: RCOOH + NH4+ / acid; RCOO− + NH3 / base
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READ AND DIGEST
- Sodium benzoate → food preservative
- Formamide → liquid; other amides → crystalline solids
- Alkaline K2Cr2O7 not used for oxidation of 1° alcohols/aldehydes because K2CrO4 forms
- Formic acid lab preparation: glycerol + hydrated oxalic acid at 110°C
- Esterification reactivity decreases with steric hindrance
- Alcohol reactivity: CH3OH > CH3CH2OH > (CH3)2CHOH
- Acid reactivity: HCOOH > CH3COOH > (CH3)2CHCOOH
- β-keto acids and β-dicarboxylic acids decarboxylate readily on heating
- 100% acetic acid = glacial acetic acid; m.p. 289.6 K
- Sucrose + conc. HNO3 → oxalic acid
- Carboxylic acids do not show usual carbonyl reactions due to resonance with −OH
- CuO·CuCr2O4 = copper chromite = Adkins catalyst
- Formic acid reduces Tollens reagent, Fehling solution, HgCl2 and KMnO4
- Sodium formate + soda lime → H2
- Sodium formate on heating → sodium oxalate
- Cream of tartar = potassium hydrogen tartrate; used in baking powder
- Glacial acetic acid appears ice-like below 16.6°C
Q1.
In the following chain of reactions, what is the product C? (start: CH₃COOH → … → C) [IOM 2006]
📅IOM 2006
Q2.
An organic compound 'A' on treatment with silver nitrate followed by acid hydrolysis gives acetic acid. The compound 'A' is.
📅IOM 2004
Q3.
The product of acylation is
📅IOM 2002
Q4.
Acetyl salicylic acid (Aspirin) acts as
📅KU 2008•MOE 2008
Q5.
Aspirin is
Q6.
Which of the following compound is Aspirin?
📅MOE 2062
Q7.
Formic acid is formed by
📅MOE 2056
Q8.
Which of the following acids do not contain a carboxyl group?
Q9.
The catalyst used in the hydrogenation of oil is
📅MOE
Q10.
The reaction of formic acid with conc. H₂SO₄ gives
📅MOE
Q11.
The reaction CH₃COOH + C₂H₅OH → CH₃COOC₂H₅ + H₂O is an example of
📅MOE
Q12.
Acetamide will form methyl amine when treated with:
📅MOE
Q13.
Formic acid is prepared in the lab by
📅MOE
Q14.
The acid which reduces Fehling's solution is
📅BPKIHS
Q15.
The general formula (RCO)₂O represents
📅LE/K.U.
Q16.
Acetamide is