Comprehensive Study Notes: Aldehydes, Ketones, and Carboxylic Acids

Introduction to Carbonyl Compounds

Organic compounds containing a carbon-oxygen double bond, represented as $C=O$ as the functional group, are classified as aldehydes, ketones, and carboxylic acids. These substances are collectively known as carbonyl compounds. The carbonyl group consists of a carbon atom double-bonded to an oxygen atom, which may be attached to various alkyl chains or other functional groups.

Aldehydes follow the general structure $R-CHO$, where the carbonyl carbon is bonded to at least one hydrogen atom. Ketones follow the general structure $R-C(=O)-R'$, where the carbonyl carbon is bonded to two carbon-containing groups. Carboxylic acids have the structure $R-COOH$, where the carbonyl carbon is bonded to a hydroxyl group ($-OH$).

Carbonyl Derivatives and Related Functional Groups

Beyond basic aldehydes and ketones, various acid derivatives share the carbonyl structural motif. These include:

• Acid Chlorides (Acyl chlorides): $R-C(=O)Cl$ where a halogen (specifically chlorine) is attached to the acyl group.
• Acid Anhydrides: Formed by the dehydration of carboxylic acids, represented as $R-C(=O)OC(=O)R$.
• Esters: Represented as $R-C(=O)OR'$, where an alkoxy group replaces the hydroxyl group of an acid.
• Amides: Represented as $R-C(=O)NH_2$, where an amino group is attached to the carbonyl carbon.
• Acyl Halides: General formula $R-C(=O)X$, where $X$ represents a halogen.

Nomenclature of Aldehydes and Ketones

Common names for aldehydes are historically derived from the corresponding carboxylic acids into which they can be oxidized. For example, formic acid ($HCOOH$) corresponds to formaldehyde ($HCHO$), and acetic acid ($CH_3COOH$) corresponds to acetaldehyde ($CH_3CHO$). Substituents in common naming use Greek letters (̑, ̒, ̓) to indicate position relative to the carbonyl group, such as ̑-chloro acetaldehyde.

In the IUPAC system, aldehydes are named as alkanals. The longest carbon chain containing the $-CHO$ group is identified, and the suffix "-al" replaces "-e" from the parent alkane. Examples include:

• $HCHO$: Methanal
• $CH_3CHO$: Ethanal
• $CH_3-CH_2-CH(CH_3)-CHO$: 2-Methylbutanal
• $CH_2=CH-CHO$: Prop-2-enal
• $CH_3-CH=CH-CHO$: But-2-enal
• $CH_3-CH_2-CH(Br)-CH(C_2H_5)-CHO$: 3-Bromo-2-ethylpentanal

Aromatic aldehydes are often named as derivatives of benzaldehyde. Substituents are indicated by prefixes: 2-Hydroxybenzaldehyde (Salicylaldehyde), 4-Methylbenzaldehyde, and 3-Methoxybenzaldehyde. When multiple aldehyde groups are present on a chain, terms like Propan-1,2,3-tricarbaldehyde are used.

Ketones are named by identifying the alkyl groups attached to the carbonyl group (common system) or as alkanones (IUPAC). Simple or symmetrical ketones use the prefix "di-", such as dimethyl ketone ($CH_3COCH_3$, also known as propanone or acetone). Mixed or unsymmetrical ketones list alkyl groups in alphabetical order, such as ethyl methyl ketone. IUPAC examples include:

• $CH_3COCH_2CH_3$: Butanone
• $CH_3-CH(CH_3)-CO-CH_3$: 3-Methylbutan-2-one
• $CH_3-C(OH)(CH_3)-CH_2-CO-CH_3$: 4-Hydroxy-4-methylpentan-2-one
• $CH_3-CO-COOH$: 2-Oxopropanoic acid

Aromatic ketones include 1-Phenylethanone (Acetophenone), 1-Phenylpropanone, and Diphenylmethanone (Benzophenone).

Methods of Preparation: Aldehydes and Ketones

Aldehydes and ketones can be synthesized through several chemical routes:

From Alcohols: Primary alcohols can be oxidized to aldehydes using controlled oxidizing agents like PCC (Pyridinium chlorochromate) or PDC (Pyridinium dichromate). Secondary alcohols are oxidized to ketones using reagents like acidic $K_2Cr_2O_7$ or $KMnO_4$ with heat.

From Alkenes: Reductive ozonolysis involves dissolving alkenes in an inert solvent (ether or $CCl_4$) at low temperatures ($196\,K$ to $200\,K$) and passing a stream of ozonized oxygen. The resulting unstable ozonide is decomposed by reductive cleavage using zinc dust and water ($Zn/H_2O$) to yield aldehydes or ketones.

From Alkynes: Hydration of alkynes involves adding water in the presence of mercuric sulphate ($HgSO_4$) and dilute sulphuric acid ($H_2SO_4$) at $333\,K$. This forms an unstable enol intermediate that rearranges (tautomerism) to a carbonyl compound. Ethyne produces acetaldehyde, while higher alkynes produce ketones.

Specialized Preparations for Aldehydes

Rosenmund's Reduction: Acid chlorides are reduced to aldehydes using hydrogen gas with a palladium ($Pd$) or platinum ($Pt$) catalyst supported on barium sulphate ($BaSO_4$) in boiling xylene. The $BaSO_4$ acts as a catalyst poison to prevent further reduction of the aldehyde to a primary alcohol.

Reduction of Esters and Nitriles: Diisobutylaluminium hydride (DIBAL-H) is a selective reducing agent used to convert esters and nitriles into aldehydes. DIBAL-H is notable for not reducing unsaturated bonds (double bonds) within the molecule.

Stephen Reaction: Alkyl cyanides (nitriles) dissolved in ether are reduced with stannous chloride ($SnCl_2$) and concentrated hydrochloric acid ($HCl$) to form an imine intermediate, which is then hydrolyzed with water to yield the aldehyde.

Preparations for Aromatic Aldehydes

Oxidation of Methylbenzene Derivatives:

• Etard's Reaction: Toluene is treated with chromyl chloride ($CrO_2Cl_2$) in $CS_2$ to form a brown chromium complex, which gives benzaldehyde upon hydrolysis.
• Chromic Oxide/Acetic Anhydride: Toluene reacts with $CrO_3$ in acetic anhydride at $273\,K$ to $283\,K$ to form benzylidene diacetate, which yields benzaldehyde when hydrolyzed.
• Side Chain Chlorination: Toluene is chlorinated via free radical substitution to form benzal chloride, which is kemudian hydrolyzed to benzaldehyde.

Gattermann-Koch Reaction: Benzene or its derivatives react with carbon monoxide ($CO$) and hydrogen chloride ($HCl$) in the presence of anhydrous aluminium chloride ($AlCl_3$) or cuprous chloride to produce benzaldehyde.

Preparations for Ketones

From Acyl Chlorides: Treating acyl chlorides with dialkylcadmium (prepared from the reaction of cadmium chloride with a Grignard reagent) produces ketones.

From Nitriles: Alkyl cyanides react with Grignard reagents in dry ether to form an intermediate that produces ketones upon hydrolysis.

Friedel-Crafts Acylation: Benzene or substituted benzenes react with acid chlorides in the presence of anhydrous $AlCl_3$ to afford aromatic ketones, such as acetophenone or benzophenone.

Physical Properties

Physical State: Formaldehyde ($HCHO$) is a pungent-smelling gas at room temperature. Lower aldehydes are colorless liquids with unpleasant odors, while lower ketones have pleasant smells. Higher members are colorless solids.

Boiling Points: The boiling points of aldehydes and ketones are higher than those of non-polar hydrocarbons of similar molecular mass due to dipole-dipole interactions. However, they are lower than those of corresponding alcohols because alcohols exhibit stronger intermolecular hydrogen bonding ($C=O$ compounds cannot form hydrogen bonds with themselves).

Solubility: Lower aldehydes and ketones are soluble in water due to their ability to form hydrogen bonds with water molecules. Solubility decreases as the length of the non-polar alkyl chain increases.

Relative Reactivity

In aliphatic compounds, reactivity is determined by the magnitude of the positive charge on the carbonyl carbon and steric hindrance.

Electronic Factors (+I effect): Alkyl groups are electron-donating. In ketones, two alkyl groups release electrons toward the carbonyl carbon, reducing its partial positive charge (̔+) and making it less susceptible to nucleophilic attack compared to aldehydes (which have only one such group or none in the case of formaldehyde).

Steric Factors: Larger alkyl groups create crowding around the carbonyl carbon, hindering the approach of nucleophiles. Increased steric hindrance leads to decreased reactivity.

Aromatic aldehydes and ketones are generally less reactive than their aliphatic counterparts due to the resonance effect, where the lone pair of the aromatic ring or the pi-system stabilizes the carbonyl group through electron delocalization.

Chemical Reactions: Reductions and Additions

Clemmensen's Reduction: Carbonyl groups are converted into methylene groups ($-CH_2-$), forming alkanes, when treated with zinc amalgam ($Zn-Hg$) and concentrated $HCl$.

Wolff-Kishner Reduction: Carbonyl compounds react with hydrazine ($NH_2NH_2$) to form hydrazones, which are then heated with a strong base like $KOH$ in a high-boiling solvent like ethylene glycol to form hydrocarbons. This reaction is base-catalyzed and also facilitates dehydrohalogenation if halogens are present.

Nucleophilic Addition of HCN: Aldehydes and ketones react with $HCN$ (catalyzed by base at $pH\,9-10$) to form cyanohydrins (gem-hydroxynitriles). These compounds contain both hydroxyl and cyano groups on the same carbon.

Addition of Sodium Bisulphite ($NaHSO_3$): Most aldehydes and methyl ketones react with saturated sodium bisulphite to form crystalline bisulphite addition products. These can be hydrolyzed back to the original carbonyl compound, making this reaction useful for purification and separation.

Addition of Grignard Reagents: Grignard reagents ($RMgX$) add to carbonyl groups. Hydrolysis of the resulting adduct produces alcohols: formaldehyde yields primary alcohols, other aldehydes yield secondary alcohols, and ketones yield tertiary alcohols.

Addition of Alcohols: Aldehydes react with alcohols in the presence of dry $HCl$ gas to form hemiacetals (unstable), which then react further to form stable acetals (gem-dialkoxy compounds). Ketones react with dihydric alcohols like ethylene glycol to form cyclic ketals.

Reduction to Alcohols: Carbonyls are reduced to alcohols using hydrogen and a catalyst ($Ni, Pt, Pd$) or complex metal hydrides like $LiAlH_4$ and $NaBH_4$. Note that while $LiAlH_4$ can reduce carboxylic acids and esters, $NaBH_4$ is generally too weak for those functional groups.

Distinctive Chemical Tests

Haloform Reaction: Compounds containing the methyl ketone group ($CH_3CO-$), or alcohols that can be oxidized to this group, react with halogens ($X_2$) and alkali ($NaOH$) to form a haloform ($CHX_3$). The iodoform test ($X=I$) produces a characteristic yellow precipitate of $CHI_3$.

Tollen's Test (Silver Mirror Test): Aldehydes (both aliphatic and aromatic) and formic acid reduce Tollen's reagent (ammoniacal silver nitrate) to metallic silver, forming a silver mirror on the reaction vessel. Ketones do not respond to this test.

Fehling's Test: Aliphatic aldehydes and formic acid reduce Fehling's solution (a mixture of copper sulphate and sodium potassium tartrate). The deep blue cupric ion ($Cu^{2+}$) is reduced to a red precipitate of cuprous oxide ($Cu_2O$). Benzene-based aromatic aldehydes do not reduce Fehling's solution.

Reaction with Ammonia Derivatives

Aldehydes and ketones react with derivatives of ammonia ($NH_2-Z$) in a weakly acidic medium ($pH\,3-4$) to form imines ($C=N-Z$) with the elimination of water. Specific products include:

• Hydroxylamine ($NH_2-OH$) → Oximes
• Hydrazine ($NH_2-NH_2$) → Hydrazones
• Semicarbazide ($NH_2NHCONH_2$) → Semicarbazones
• Primary Amines ($R-NH_2$) → Schiff's Bases (Azomethines)
• 2,4-Dinitrophenylhydrazine (2,4-DNP or Brady's Reagent) → 2,4-DNP Hydrazones (Yellow/Orange precipitate used as a diagnostic test for carbonyls).

Aldol Condensation

Aldol condensation occurs in carbonyl compounds containing at least one ̑-hydrogen. In the presence of dilute base (e.g., $10\%\,NaOH$), two molecules condense to form a ̒-hydroxy aldehyde (aldol) or ̒-hydroxy ketone (ketol). Dehydration of these products easily occurs to yield ̑, ̒-unsaturated carbonyl compounds.

Self-condensation involves two identical molecules. Cross-aldol condensation occurs between two different aldehydes or ketones, often resulting in a mixture of four different products if both reactants have ̑-hydrogens.

Cannizzaro's Reaction

Aldehydes that lack ̑-hydrogen atoms (e.g., formaldehyde, benzaldehyde) undergo self-oxidation and reduction (disproportionation) when treated with concentrated alkali ($50\%\,NaOH$). One molecule is reduced to an alcohol, while the other is oxidized to the salt of a carboxylic acid.

Substitution Reactions (Aromatic Carbonyls)

The aldehyde and ketone groups are meta-directing and deactivating for electrophilic substitution reactions such as nitration, sulphonation, and chlorination.

Carboxylic Acids: Preparation and Properties

Methods of Preparation:

1. Oxidation of Primary Alcohols and Aldehydes: Using reagents like acidic $KMnO_4, K_2Cr_2O_7$, or $CrO_3$.
2. Hydrolysis of Nitriles: Nitriles ($R-CN$) are hydrolyzed in acidic or basic media. They first form amides, which further hydrolyze to carboxylic acids.
3. From Grignard Reagents: Reaction of $RMgX$ with solid carbon dioxide (dry ice) in dry ether forms a salt that yields carboxylic acid upon acidic hydrolysis.
4. Hydrolysis of Esters: Esters are hydrolyzed by aqueous acid or alkali to produce carboxylic acids and alcohols.
5. From Acid Derivatives: Hydrolysis of acid amides, acid halides, and anhydrides with water or dilute mineral acids.
6. Oxidation of Alkyl Benzenes: Alkyl-substituted benzenes (regardless of chain length) are oxidized by alkaline $KMnO_4$ and heat to benzoic acid, provided they have at least one benzylic hydrogen.

Physical Properties: Aliphatic acids ($C_1-C_4$) are soluble in water due to hydrogen bonding. Solubility decreases with increasing molecular mass. Carboxylic acids have higher boiling points than alcohols of similar mass because they form stable intermolecular dimers through hydrogen bonding.

Acidity: The acidity is quantified by the dissociation constant ($K_a$) or $pK_a$ ($pK_a = -\log(K_a)$). Smaller $pK_a$ values indicate stronger acids. Carboxylic acids are more acidic than alcohols and phenols because the carboxylate ion is stabilized by resonance (two equivalent structures).

Effect of Substituents on Acidity:

• Electron Withdrawing Groups (EWG) like $-Cl$, $-NO_2$: Stabilize the carboxylate anion by dispersing negative charge through the inductive effect ($-I$), thus increasing acidity.
• Electron Donating Groups (EDG) like $-CH_3$: Destabilize the anion, decreasing acidity.

Chemical Reactions of Carboxylic Acids

1. Reaction with Metals/Alkali: React with electropositive metals ($Na, Zn$) and alkalis ($NaOH, NH_4OH$) to form salts and release hydrogen or water.
2. Test for Carboxyl Group: Carboxylic acids react with sodium bicarbonate ($NaHCO_3$) and sodium carbonate ($Na_2CO_3$) to produce brisk effervescence of $CO_2$ gas, which turns lime water milky.
3. Formation of Anhydrides: Heating two molecules of acid with a dehydrating agent like concentrated $H_2SO_4$ or $P_2O_5$ results in the loss of a water molecule to form an acid anhydride.
4. Formation of Amides and Nitriles: Acids react with ammonia to form ammonium salts, which on heating lose water to form amides. Amides heated with $P_2O_5$ yield cyanides (nitriles).
5. Decarboxylation: Salts of carboxylic acids heated with soda lime ($NaOH$ and $CaO$ in a $3:1$ ratio) lose carbon dioxide to form alkanes.
6. Hell-Volhard-Zelinsky (HVZ) Reaction: Carboxylic acids with at least one ̑-hydrogen react with halogens ($Cl_2$ or $Br_2$) in the presence of red phosphorus to form ̑-halo carboxylic acids.
7. Substitution in Aromatic Acids: The $-COOH$ group is meta-directing and deactivating. Examples include nitration to m-nitrobenzoic acid.
8. Hunsdiecker Reaction: The silver salt of a carboxylic acid reacts with bromine in $CCl_4$ to produce an alkyl/aryl bromide and $CO_2$.

Practice Problems and Transformations

• Reaction of Benzaldehyde with $C_2H_5Cl/AlCl_3$: Results in Friedel-Crafts products.
• Reaction of $(CH_3CH_2)_2Cd$ with $2\,CH_3COCl$: Yields $2\,CH_3COCH_2CH_3$ and $CdCl_2$.
• Reaction of $CH_3-C\equiv C-H$ with $Hg^{2+}, H_2SO_4$: Produces Propanone ($CH_3COCH_3$) via hydration and tautomerism.
• Etard reaction on 1-methylnitronaphthalene: Yields corresponding aldehyde derivatives.
• Reaction of cyclohexanone with semi-carbazide: Yields cyclohexanone semi-carbazone.
• Reduction of $R-CH=CH-CHO$ using $LiAlH_4$: Yields $R-CH=CH-CH_2OH$ (only the carbonyl group is reduced).
• Reaction of 1-phenylethanone with primary amine: Produces a Schiff's base.

Questions & Discussion

Question: Write the structures of products of the following reactions: (i) Benzene + $C_2H_5Cl \xrightarrow{Anhyd. AlCl_3}$ Ethyl Benzene. (ii) $(CH_3CH_2)_2Cd + 2\,CH_3COCl \rightarrow 2\,CH_3COCH_2CH_3 + CdCl_2$. (iii) $H_3C-C\equiv C-H \xrightarrow{Hg^{2+}, H_2SO_4, 333\,K}$ Propanone. (iv) Toluene + $CrO_2Cl_2 \xrightarrow{H_2O^+}$ Benzaldehyde.

Predicting products from ammonia derivatives: (i) Cyclopentanone + $NH_2OH \xrightarrow{H^+}$ Cyclopentanone oxime. (ii) Cyclohexanone + 2,4-DNP → Cyclohexanone 2,4-dinitrophenylhydrazone. (iii) $R-CH=CH-CHO$ + Semicarbazide → $R-CH=CH-CH=NNHCONH_2$. (iv) Aromatic ketone + primary amine → Imine (Schiff's base).