Unit 4: Carboxylic Acids and Their Derivatives

1. Monocarboxylic Acids: Preparation, Properties, and Reactions

1.1 Introduction

Monocarboxylic acids are organic compounds containing a single carboxyl functional group (-COOH). This group consists of a carbonyl group (C=O) directly bonded to a hydroxyl group (-OH). The unique electronic environment of this functional group governs both its physical properties and chemical reactivity.

1.2 Methods of Preparation

Monocarboxylic acids can be synthesized through several classical routes, which are critical for academic exams:

• Oxidation of Primary Alcohols and Aldehydes: Primary alcohols are readily oxidized to carboxylic acids using strong oxidizing agents such as potassium permanganate (KMnO4) in acidic or alkaline media, or acidic potassium dichromate (K2Cr2O7). The reaction proceeds through an aldehyde intermediate.

  R-CH2OH + [O] (via KMnO4) -> R-CHO + [O] -> R-COOH

• Hydrolysis of Nitriles (Cyanides): Alkyl nitriles can be hydrolyzed under either acidic or basic conditions to yield carboxylic acids. Complete hydrolysis yields the acid and an ammonium salt (under acidic conditions) or a carboxylate salt and ammonia (under basic conditions).

  R-CN + 2H2O + HCl -> R-COOH + NH4Cl

• Carbonation of Grignard Reagents: Grignard reagents (R-MgX) react nucleophilically with solid carbon dioxide (dry ice) to form a magnesium carboxylate salt adduct. Subsequent acidic hydrolysis yields the corresponding carboxylic acid. This reaction is highly useful as it increases the carbon chain length by one carbon atom.

  R-MgX + CO2 -> R-COOMgX + HCl/H2O -> R-COOH + Mg(Cl)X

• Hydrolysis of Esters: Acidic or basic hydrolysis of esters provides a direct route back to carboxylic acids. This is discussed in deep mechanical detail in Section 5.

1.3 Physical Properties

The physical properties of carboxylic acids are highly characteristic and frequently tested in conceptual exams:

• Boiling Point: Carboxylic acids have exceptionally high boiling points compared to alcohols, aldehydes, and alkanes of similar molecular weight. This is due to their ability to form highly stable, cyclic hydrogen-bonded dimers in both the liquid phase and gas phase. Each dimer is held together by two strong hydrogen bonds.
• Solubility: Lower members of the aliphatic carboxylic acid series (up to 4 carbon atoms) are completely miscible with water because they form strong hydrogen bonds with water molecules. Solubility decreases sharply as the hydrophobic carbon chain length increases.
• Acidity: Carboxylic acids are weak acids compared to mineral acids (such as HCl), but they are significantly more acidic than alcohols and phenols. This enhanced acidity is due to two factors: the polar nature of the O-H bond caused by the adjacent electron-withdrawing carbonyl group, and the resonance stabilization of the resulting carboxylate anion (R-COO-), which distributes the negative charge equally over two electronegative oxygen atoms.

1.4 Inductive Effects on Acidity

The acidity of a carboxylic acid is strongly influenced by substituents on the alkyl group:

1.5 Chemical Reactions

The chemical reactions of monocarboxylic acids can be classified into reactions involving the acidic hydrogen, reactions involving the hydroxyl group, and reactions involving the entire carboxyl group or alkyl chain:

• Salt Formation: Carboxylic acids react with active metals, hydroxides, and carbonates/bicarbonates to form carboxylate salts. The reaction with sodium bicarbonate (NaHCO3) releases carbon dioxide gas, which serves as a classical laboratory test for identifying the carboxyl group.

  R-COOH + NaHCO3 -> R-COONa + H2O + CO2 (gas effervescence)

• Reduction: Carboxylic acids are highly resistant to mild reducing agents but are reduced directly to primary alcohols using lithium aluminum hydride (LiAlH4) or diborane (B2H6). Note that sodium borohydride (NaBH4) does *not* reduce carboxylic acids.

  R-COOH + LiAlH4 / Ether followed by H3O+ -> R-CH2OH

• Decarboxylation: The elimination of carbon dioxide from the carboxyl group.
  • Soda-lime Decarboxylation: Heating sodium salts of carboxylic acids with soda-lime (a mixture of NaOH and CaO in a 3:1 ratio) yields alkanes with one less carbon atom than the parent acid.

    R-COONa + NaOH (heated with CaO) -> R-H + Na2CO3

  • Kolbe's Electrolytic Decarboxylation: Electrolysis of aqueous solutions of sodium or potassium salts of carboxylic acids yields symmetrical alkanes at the anode.

    2R-COONa + 2H2O (Electrolysis) -> R-R + 2CO2 + H2 + 2NaOH

• Halogenation at Alpha-Carbon (Hell-Volhard-Zelinsky or HVZ Reaction): Aliphatic carboxylic acids containing alpha-hydrogens react with chlorine or bromine in the presence of a catalytic amount of red phosphorus to form alpha-halo carboxylic acids.

  R-CH2-COOH + X2 (where X = Cl, Br) in the presence of red Phosphorus -> R-CH(X)-COOH + HX

2. Dicarboxylic, Hydroxy, and Unsaturated Acids

This section explores the chemistry and thermal behavior of specific dicarboxylic, hydroxy, and unsaturated acids. The effect of heat on these compounds is a major exam focus.

2.1 Succinic Acid and Phthalic Acid (Dicarboxylic Acids)

• Succinic Acid (Butanedioic Acid, HOOC-CH2-CH2-COOH): Heating succinic acid to approximately 300 degrees Celsius causes intramolecular dehydration, yielding a stable five-membered cyclic anhydride.

  HOOC-CH2-CH2-COOH + Heat -> Succinic Anhydride + H2O

• Phthalic Acid (Benzene-1,2-dicarboxylic Acid, C6H4(COOH)2): Because the two carboxyl groups are in close spatial proximity on the benzene ring (ortho position), phthalic acid readily dehydrates upon heating to form phthalic anhydride.

  C6H4(COOH)2 + Heat -> Phthalic Anhydride + H2O

  Reaction of phthalic acid with ammonia (NH3) under heat initially forms phthalic anhydride, which then reacts with ammonia to form phthalimide.

  Phthalic Anhydride + NH3 + Heat -> Phthalimide + H2O

2.2 Lactic Acid, Malic Acid, Tartaric Acid, and Citric Acid (Hydroxy Acids)

• Lactic Acid (2-Hydroxypropanoic Acid, CH3-CH(OH)-COOH): Upon heating, two molecules of lactic acid undergo intermolecular esterification to form a stable cyclic six-membered diester called a lactide.

  2 CH3-CH(OH)-COOH + Heat -> Lactide (cyclic diester) + 2H2O

  Oxidation of lactic acid with mild oxidizing agents like dilute nitric acid or Fenton's reagent yields pyruvic acid (CH3-CO-COOH).
• Malic Acid (2-Hydroxybutanedioic Acid, HOOC-CH2-CH(OH)-COOH): Controlled heating of malic acid at 140-150 degrees Celsius results in dehydration to form fumaric acid (the trans-isomer) along with some maleic acid (the cis-isomer). Stronger heating leads to maleic anhydride.

  HOOC-CH2-CH(OH)-COOH + Heat -> Fumaric Acid / Maleic Acid + H2O

• Tartaric Acid (2,3-Dihydroxybutanedioic Acid, HOOC-CH(OH)-CH(OH)-COOH): Heating tartaric acid causes dehydration, decarboxylation, and pyrolysis, ultimately yielding pyruvic acid (CH3-CO-COOH) and carbon dioxide. Mild oxidation of tartaric acid yields dihydroxytartaric acid.
• Citric Acid (2-Hydroxypropane-1,2,3-tricarboxylic Acid): Heating citric acid at 150 degrees Celsius causes dehydration to yield aconitic acid. Further heating results in decarboxylation to give itaconic acid and citraconic anhydride.

2.3 Maleic Acid and Fumaric Acid (Unsaturated Acids)

Maleic and fumaric acids are classical geometric isomers. Maleic acid is the cis-isomer, and fumaric acid is the trans-isomer. Their reactions, particularly under heat, differ significantly due to spatial arrangements:

• Maleic Acid (cis-isomer): Because the two carboxyl groups are on the same side of the double bond, they are in close spatial proximity. Maleic acid dehydrates easily at a relatively low temperature (140 degrees Celsius) to form maleic anhydride.

  Maleic Acid + Heat (140 C) -> Maleic Anhydride + H2O

• Fumaric Acid (trans-isomer): Because the carboxyl groups are on opposite sides of the double bond, they cannot interact directly to dehydrate. Fumaric acid does not form an anhydride at 140 degrees Celsius. When heated to high temperatures (about 270 degrees Celsius), it undergoes isomerization to maleic acid first, which then dehydrates to form maleic anhydride.

  Fumaric Acid + High Heat (270 C) -> Maleic Anhydride + H2O

2.4 Summary of Heat Effects

3. Acid Derivatives: Preparation and Reactions

Carboxylic acid derivatives are compounds in which the -OH group of the carboxyl unit is replaced by another electronegative heteroatom. The four major families are acid chlorides, acid anhydrides, esters, and amides.

3.1 Acid Chlorides (R-COCl)

• Preparation: Synthesized by treating carboxylic acids with phosphorus trichloride (PCl3), phosphorus pentachloride (PCl5), or thionyl chloride (SOCl2). Thionyl chloride is the preferred reagent because the byproducts (SO2 and HCl) are gases, leaving a pure product.

  R-COOH + SOCl2 -> R-COCl + SO2 (gas) + HCl (gas)

  3 R-COOH + PCl3 -> 3 R-COCl + H3PO3

• Reactions: Acid chlorides are highly reactive electrophiles.
  • Hydrolysis: React rapidly with water to form the parent carboxylic acid and HCl.

    R-COCl + H2O -> R-COOH + HCl

  • Alcoholysis (Ester Formation): React with alcohols to yield esters.

    R-COCl + R'OH -> R-COOR' + HCl

  • Aminolysis (Amide Formation): React with ammonia or primary/secondary amines to yield amides.

    R-COCl + 2 NH3 -> R-CONH2 + NH4Cl

  • Rosenmund Reduction: Hydrogenation of acid chlorides over palladium catalyst poisoned with barium sulfate (Pd-BaSO4) yields aldehydes. The poison prevents further reduction to alcohols.

    R-COCl + H2 (over Pd-BaSO4) -> R-CHO + HCl

3.2 Acid Anhydrides ((RCO)2O)

• Preparation: Prepared by heating carboxylic acids in the presence of strong dehydrating agents like phosphorus pentoxide (P2O5), or by reacting an acid chloride with a carboxylate salt.

  R-COCl + R'-COONa -> R-CO-O-CO-R' + NaCl

• Reactions: Anhydrides are less reactive than acid chlorides but undergo similar substitution reactions:
  • Hydrolysis: Yields two molecules of carboxylic acid.

    (RCO)2O + H2O -> 2 R-COOH

  • Alcoholysis: Yields one molecule of ester and one molecule of carboxylic acid.

    (RCO)2O + R'OH -> R-COOR' + R-COOH

  • Aminolysis: Reacts with ammonia to yield an amide and an ammonium carboxylate salt.

    (RCO)2O + 2 NH3 -> R-CONH2 + R-COONH4

3.3 Esters (R-COOR')

• Preparation: Primarily prepared via Fischer Esterification, where a carboxylic acid and an alcohol are heated in the presence of an acid catalyst (usually concentrated H2SO4 or gaseous HCl). The reaction is highly reversible.

  R-COOH + R'OH + Acid Catalyst <=> R-COOR' + H2O

• Reactions:
  • Hydrolysis: Described in deep mechanistic detail in Section 5 (Acidic vs. Alkaline).
  • Transesterification: Reaction of an ester with an alcohol in the presence of an acid or base catalyst to yield a new ester. This involves exchanging the alkoxy group.

    R-COOR' + R"-OH + Acid/Base <=> R-COOR" + R'-OH

  • Reduction: Reduced by LiAlH4 to yield two alcohols.

    R-COOR' + LiAlH4 -> R-CH2OH + R'-OH

  • Grignard Reaction: React with excess Grignard reagent (2 equivalents) to form tertiary alcohols containing two identical R-groups derived from the Grignard.

    R-COOR' + 2 R"MgX followed by H3O+ -> R-C(OH)(R")2 + R'OH

3.4 Amides (R-CONH2)

• Preparation: Synthesized by heating ammonium carboxylate salts, which are formed by reacting carboxylic acids with ammonia.

  R-COOH + NH3 -> R-COONH4 + Heat -> R-CONH2 + H2O

  They are also formed by the reaction of acid chlorides or anhydrides with ammonia or amines.
• Reactions: Amides are the least reactive of all acid derivatives.
  • Hydrolysis: Requires heating in strong aqueous acid or alkali to yield the parent acid/salt and ammonia/amine.

    R-CONH2 + H2O + HCl + Heat -> R-COOH + NH4Cl

  • Dehydration: Heating primary amides with phosphorus pentoxide (P2O5) dehydrates them to nitriles.

    R-CONH2 + P2O5 + Heat -> R-CN + H2O

  • Reduction: Unlike other derivatives that reduce to alcohols, amides reduce to primary amines when treated with LiAlH4.

    R-CONH2 + LiAlH4 / Ether followed by H2O -> R-CH2NH2

4. Comparative Study of Nucleophilic Acyl Substitution

4.1 General Mechanism

Unlike aldehydes and ketones, which undergo nucleophilic addition, carboxylic acid derivatives undergo Nucleophilic Acyl Substitution. This reaction proceeds via a two-step addition-elimination mechanism through a tetrahedral intermediate:

1. Addition Step (Rate-Determining Step in most cases): The nucleophile (Nu:-) attacks the electrophilic carbonyl carbon of the acyl derivative (R-CO-L), breaking the carbon-oxygen pi bond and pushing electron density to oxygen to form a tetrahedral intermediate.
2. Elimination Step: The negative charge on the oxygen reformats the carbonyl double bond, expelling the leaving group (L:-) from the tetrahedral carbon.

R-CO-L + Nu:- <=> [R-C(O-)(Nu)(L)] (Tetrahedral Intermediate) -> R-CO-Nu + L:-

4.2 Relative Reactivity Order

The reactivity of acid derivatives toward nucleophilic acyl substitution follows this strict order:

Acid Chloride > Acid Anhydride > Ester > Amide

4.3 Theoretical Explanation of Reactivity

This reactivity trend is dictated by two main electronic factors:

• Leaving Group Ability (Basicity): The weaker the base, the better it acts as a leaving group. Chloride (Cl-) is the conjugate base of a very strong acid (HCl) and is a very weak, highly stable base, making it an excellent leaving group. Conversely, the amide ion (NH2-) is the conjugate base of a weak acid (NH3) and is an extremely strong base, making it a very poor leaving group.
• Resonance Stabilization: In amides, the nitrogen lone pair is highly effective at donating electron density into the carbonyl group via resonance. This is because nitrogen is less electronegative than oxygen and its 2p orbital overlaps extremely well with the 2p orbital of carbon. This strong resonance stabilizes the starting material, lowering its potential energy and raising the activation energy barrier for nucleophilic attack. In contrast, the chlorine atom in acid chlorides is highly electronegative and has a 3p orbital, which overlaps poorly with the 2p orbital of carbon, providing almost no resonance stabilization and leaving the carbonyl highly electrophilic.

5. Mechanisms of Acidic and Alkaline Ester Hydrolysis

Ester hydrolysis can occur via two primary pathways, differing fundamentally in thermodynamics, kinetics, and mechanism.

5.1 Acidic Hydrolysis of Esters (AAC2 Mechanism)

Acidic hydrolysis of esters is catalyzed by mineral acids. It is completely reversible and is formally known as the AAC2 mechanism (Acid-catalyzed, Acyl-oxygen cleavage, Bimolecular).

Step-by-Step Mechanism:

1. Protonation of the Carbonyl Oxygen: The acid catalyst protonates the carbonyl oxygen, increasing the electrophilic character of the carbonyl carbon.

   R-CO-OR' + H+ <=> R-C(+OH)-OR'

2. Nucleophilic Attack by Water: A water molecule (acting as a weak nucleophile) attacks the activated carbonyl carbon to form a tetrahedral intermediate.

   R-C(+OH)-OR' + H2O <=> R-C(OH)(OH2+)-OR'

3. Proton Transfer: A proton is transferred from the incoming water oxygen to the alkoxy oxygen (R'-O-), converting the alkoxy group into a good leaving group (R'-OH+).

   R-C(OH)(OH2+)-OR' <=> R-C(OH)(OH)-O+HR'

4. Elimination of Alcohol (Leaving Group): The carbonyl oxygen reforms the pi bond, expelling the neutral alcohol molecule.

   R-C(OH)(OH)-O+HR' <=> R-C(+OH)-OH + R'-OH

5. Deprotonation: Loss of a proton from the carbonyl oxygen regenerates the acid catalyst, yielding the free carboxylic acid.

   R-C(+OH)-OH <=> R-COOH + H+

Exam Note: Because every step in this mechanism is in dynamic equilibrium, the reaction does not go to completion unless a large excess of water is used to shift the equilibrium toward the products (Le Chatelier's Principle).

5.2 Alkaline Hydrolysis of Esters (BAC2 Mechanism / Saponification)

Alkaline hydrolysis is promoted by a strong base (such as NaOH or KOH). It is formally known as the BAC2 mechanism (Base-promoted, Acyl-oxygen cleavage, Bimolecular). Unlike acidic hydrolysis, this reaction is irreversible because the base is consumed stoichiometrically.

Step-by-Step Mechanism:

1. Nucleophilic Attack by Hydroxide: The strong hydroxide nucleophile (OH-) directly attacks the carbonyl carbon, forming a tetrahedral intermediate. This does not require protonation.

   R-CO-OR' + OH- <=> R-C(O-)(OH)-OR'

2. Elimination of Alkoxide: The tetrahedral intermediate collapses, reforming the C=O double bond and expelling the alkoxide ion (R'O-) as the leaving group.

   R-C(O-)(OH)-OR' <=> R-COOH + R'O-

3. Proton Transfer (Irreversible Step): The newly formed carboxylic acid is a strong acid, and the expelled alkoxide ion is a very strong base. An instantaneous, highly exothermic proton transfer occurs, yielding a carboxylate anion and an alcohol.

   R-COOH + R'O- -> R-COO- + R'OH

Common Mistake to Avoid: Do not refer to alkaline hydrolysis as "base-catalyzed." The base is a reactant, not a catalyst, because it is converted into water and consumed in the final deprotonation step. Acidic workup is required if the free carboxylic acid is desired instead of the carboxylate salt.

6. Named Reactions and Rearrangements

This section details the critical named reactions and molecular rearrangements specified in the syllabus.

6.1 Claisen Condensation

The Claisen condensation is a base-catalyzed self-condensation of esters containing at least two alpha-hydrogens to yield beta-keto esters. The reaction is typically promoted by a sodium alkoxide base whose alkyl group matches the alkoxy group of the ester to prevent transesterification side reactions.

Step-by-Step Mechanism:

1. Enolate Formation: The alkoxide base (such as NaOEt) deprotonates the alpha-carbon of one ester molecule, generating a resonance-stabilized enolate anion.

   CH3-COOR + RO- <=> [CH2-COOR]- + ROH

2. Nucleophilic Attack: The nucleophilic enolate carbon attacks the electrophilic carbonyl carbon of a second (unreacted) ester molecule, forming a tetrahedral intermediate.

   R-CO-OR + [CH2-COOR]- <=> R-C(O-)(OR)-CH2-COOR

3. Elimination of Alkoxide: The intermediate collapses, expelling the alkoxide leaving group to yield a beta-keto ester.

   R-C(O-)(OR)-CH2-COOR -> R-CO-CH2-COOR + RO-

4. Deprotonation (Driving Force): Because the beta-keto ester contains highly acidic protons flanked by two carbonyl groups, the alkoxide base rapidly deprotonates it to form a highly stable, resonance-delocalized mono-anion. This irreversible step thermodynamically drives the entire reaction forward.

   R-CO-CH2-COOR + RO- -> [R-CO-CH-COOR]- + ROH

5. Acidic Workup: Dilute acid is added at the end of the reaction to protonate the anion, yielding the neutral beta-keto ester product.

   [R-CO-CH-COOR]- + H3O+ -> R-CO-CH2-COOR + H2O

6.2 Dieckmann Condensation

The Dieckmann condensation is simply an intramolecular Claisen condensation. It occurs when a dicarboxylic ester (diester) containing alpha-hydrogens is treated with a strong base, undergoing cyclization to yield a cyclic beta-keto ester.

Key Observation: This reaction is highly favored for the formation of stable five-membered and six-membered rings (typically using diethyl adipate or diethyl pimelate) because of the lack of ring strain in these transitions. The mechanism is identical to the intermolecular Claisen condensation, except the enolate attacks the ester carbonyl located on the opposite end of the same molecule.

6.3 Reformatsky Reaction

The Reformatsky reaction involves the condensation of an aldehyde or ketone with an alpha-halo ester (typically an alpha-bromo ester) in the presence of metallic zinc, followed by acidic hydrolysis to yield a beta-hydroxy ester.

Why Zinc is Used instead of Magnesium:

Organomagnesium compounds (Grignard reagents) are highly reactive and would immediately attack the ester group of the alpha-halo ester itself. Metallic zinc forms a much less reactive organozinc intermediate (a "Reformatsky enolate"), which is nucleophilic enough to attack highly electrophilic aldehydes or ketones but does not react with its own ester group.

Step-by-Step Mechanism:

1. Insertion of Zinc: Metallic zinc inserts into the carbon-bromine bond of the alpha-bromo ester to form an organozinc reagent. This intermediate is stabilized via coordination to form a zinc enolate.

   Br-CH2-COOR + Zn -> ClZn-CH2-COOR

2. Nucleophilic Attack: The nucleophilic carbon of the organozinc enolate attacks the carbonyl carbon of the aldehyde or ketone, forming a zinc-coordinated tetrahedral complex.

   R2C=O + ClZn-CH2-COOR -> R2C(OZnCl)-CH2-COOR

3. Acidic Hydrolysis: Addition of dilute acid hydrolyzes the zinc salt to yield the final beta-hydroxy ester.

   R2C(OZnCl)-CH2-COOR + H3O+ -> R2C(OH)-CH2-COOR + Zn(II) salts

6.4 Hofmann Bromamide Degradation

The Hofmann bromamide degradation converts a primary amide (R-CONH2) into a primary amine (R-NH2) containing one less carbon atom. This reaction is carried out by treating the primary amide with bromine (Br2) in an aqueous or alcoholic solution of sodium hydroxide (NaOH).

Step-by-Step Mechanism:

1. N-Deprotonation: The hydroxide base deprotonates the amide nitrogen, making it nucleophilic.

   R-CONH2 + OH- <=> [R-CONH]- + H2O

2. Halogenation: The amide anion attacks bromine to form an N-bromoamide.

   [R-CONH]- + Br-Br -> R-CONH-Br + Br-

3. Second Deprotonation: The remaining proton on the nitrogen is highly acidic due to both the carbonyl group and the bromine atom. Hydroxide deprotonates it to form a highly reactive anion.

   R-CONH-Br + OH- -> [R-CON-Br]- + H2O

4. Rearrangement (The Concerted Step): The alkyl or aryl group (R) migrates with its bonding electron pair from the carbonyl carbon directly to the adjacent nitrogen. Simultaneously, the bromide ion (Br-) departs as a leaving group. This concerted rearrangement yields an isocyanate intermediate.

   [R-CON-Br]- -> R-N=C=O (Isocyanate) + Br-

5. Hydrolysis and Decarboxylation: Hydroxide attacks the carbon of the isocyanate, yielding an unstable carbamate salt (R-NH-COO-). Decarboxylation occurs rapidly, releasing carbonate and the primary amine.

   R-N=C=O + 2 OH- -> R-NH2 + CO3(2-)

6.5 Curtius Rearrangement

The Curtius rearrangement involves the thermal decomposition of an acyl azide (R-CON3) to form an alkyl or aryl isocyanate (R-N=C=O). Subsequent hydrolysis yields a primary amine with one less carbon atom, similar to the Hofmann degradation.

Preparation of Acyl Azides:

Acyl azides are prepared either by reacting an acid chloride with sodium azide (NaN3) or by reacting an acyl hydrazide with nitrous acid (HNO2).

R-COCl + NaN3 -> R-CON3 + NaCl

Step-by-Step Mechanism:

1. Thermal Decomposition and Migration: Upon heating, the acyl azide undergoes a concerted rearrangement. The R-group migrates from the carbonyl carbon to the nitrogen atom, with the simultaneous expulsion of a highly stable nitrogen gas (N2) molecule as an excellent leaving group.

   R-CON3 + Heat -> R-N=C=O (Isocyanate) + N2 (gas)

2. Hydrolysis to Amine: If water is present, the isocyanate is attacked by water to form an unstable carbamic acid (R-NH-COOH), which spontaneously decarboxylates to yield the primary amine.

   R-N=C=O + H2O -> [R-NH-COOH] -> R-NH2 + CO2

Exam Tip: If the rearrangement is carried out in the presence of an alcohol (R'-OH) instead of water, the isocyanate intermediate reacts to form a stable carbamate (urethane). If carried out in the presence of an amine, it forms a urea derivative.