Exhaustive Notes on Aldehydes, Ketones, Carboxylic Acids, and Acid Derivatives

Introduction to Carbonyl Compounds

• Definition: Carbonyl compounds are organic compounds containing the carbonyl group (>C=O).

• General Formula: These compounds have the general formula $C_nH_{2n}O$.

• Classification:

  • Aldehyde: If a hydrogen atom is attached to the carbonyl group, it is an aldehyde ($R-CHO$).

  • Ketone: If alkyl groups ($R$) are present on both sides of the carbonyl group, it is a ketone ($R-CO-R$).

  • Simple Ketone: Both alkyl groups attached to the carbonyl group are the same.

  • Mixed Ketone: The alkyl groups attached to the carbonyl group are different.

• Physical Features:

  • Hybridization: The carbon atom in the carbonyl group is in an $sp^2$ hybridization state.

  • Bond Length: The $C=O$ bond length is $1.23 \text{ Å}$.

  • Formaldehyde: The ratio of $C$, $H$, and $O$ in formaldehyde ($CH_2O$) is $1:2:1$. It is referred to as the "simplest sugar."

• Isomerism:

  • Aldehydes: Exhibit chain, position, and functional isomerism.

  • Ketones: Exhibit chain, position, functional isomerism, and metamerism.

  • Aldehydes and ketones are functional isomers of each other.

IUPAC Nomenclature of Aldehydes and Ketones

Specific examples from the transcript include:

• Ketones:

  • Propanone: $CH_3-C(=O)-CH_3$

  • Butanone: $CH_3-C(=O)-CH_2-CH_3$

  • Pentan-2-one: $CH_3-C(=O)-CH_2-CH_2-CH_3$

  • Butanedione: $CH_3-C(=O)-C(=O)-CH_3$

  • 2,4-Dimethylpentan-3-one: $(CH_3)_2CH-C(=O)-CH(CH_3)_2$

  • 1-Phenylpropan-1-one: $C_6H_5-C(=O)-CH_2-CH_3$

  • 3-Methylcyclopentanone: A cyclopentane ring with a ketone at position 1 and a methyl at position 3.

  • Cyclohex-2-en-1-one: A cyclohexene ring with a ketone at position 1 and a double bond starting at position 2.

  • 4-Hydroxy-4-methylpentan-2-one: $CH_3-C(=O)-CH_2-C(OH)(CH_3)_2$

• Aldehydes:

  • Ethanal: $CH_3CHO$

  • Propanal: $CH_3CH_2CHO$

  • Butanal: $CH_3CH_2CH_2CHO$

  • 3-Hydroxybutanal: $CH_3-CH(OH)-CH_2-CHO$

  • Pent-2-en-1-al (Pent-2-enal): $CH_3-CH_2-CH=CH-CHO$

  • 4-Bromo-3-methylheptanal: $CH_3-CH_2-CH_2-CH(Br)-CH(CH_3)-CH_2-CHO$

  • Cyclohexanecarbaldehyde: A cyclohexane ring attached to a $-CHO$ group.

  • 2-Hydroxycyclopentane-1-carbaldehyde: A cyclopentane ring with $-CHO$ at position 1 and $-OH$ at position 2.

  • 3-Oxopentanal: $CH_3-CH_2-C(=O)-CH_2-CHO$

  • 3-Oxobutanoic acid: $CH_3-C(=O)-CH_2-COOH$

  • 2-Formylbenzoic acid: A benzene ring with a $-COOH$ at position 1 and a $-CHO$ at position 2.

  • 2-Ethylhex-2-en-1-al: $CH_3CH_2CH_2CH=C(CH_2CH_3)CHO$

  • 3-Chloro-2-methylbutanal: $CH_3-CH(Cl)-CH(CH_3)-CHO$

General Methods of Preparation

I. Hydration of Alkyne

• Reagents: Addition of water in the presence of heavy metal ions ($Hg^{2+}/H_2SO_4$).

• Acetylene: Always gives an aldehyde.

  • $H-C≡C-H → CH_3-CH=O$

• Higher Alkynes: Always give ketones.

  • $R-C≡C-H → R-C(=O)-CH_3$

II. Hydroboration of Alkyne

• Used to obtain aldehydes from terminal alkynes (alkyne-1).

• Reagents: (i) Diborane ($B_2H_6$), (ii) $H_2O_2(OH^-)$.

• Mechanism: Borane ($BH_3$) acts as an electrophile. The intermediate is an enol which tautomerizes to the carbonyl compound.

  • $3R-C≡C-H + BH_3 → (R-CH=CH)_3B$

  • $(R-CH=CH)_3B + H_2O_2/OH^- → R-CH=CH-OH → R-CH_2-CH=O$

• Non-terminal alkynes yield ketones through this process.

III. Ozonolysis of Alkenes

• Used to produce carbonyl compounds from alkenes.

• Reagent: $O_3$ followed by a reductive workup ($Zn-H_2O$ or $(CH_3)_2S$).

• Note: Zinc is used to prevent the further oxidation of produced aldehydes into carboxylic acids.

• This method allows for the location of double bonds in olefins by identifying the carbonyl products.

IV. Dehydrogenation of Alcohol

• Reagent: Heated copper ($Cu$) at $300 ^┦C$.

• 1º Alcohol: Yields Aldehyde ($RCH_2OH → R-CH=O$).

• 2º Alcohol: Yields Ketone ($R_2CHOH → R_2C=O$).

• 3º Alcohol: Undergoes dehydration to yield an Alkene.

V. Dry Distillation of Calcium Salts

• Heating the calcium salt of a fatty acid: $(RCOO)_2Ca → R-C(=O)-R + CaCO_3$.

VI. Catalytic Preparation from Fatty Acids

• Passing vapors of fatty acids over Manganous oxide ($MnO$) at $300 ^┦C$.

  • $2RCOOH → R-C(=O)-R + CO_2 + H_2O$

• A mixture of fatty acid and formic acid yields a mixture of aldehyde, ketone, and formaldehyde.

VII. Hydrolysis of Gem-dihalides

• Terminal gem-dihalides: Yield aldehydes upon aqueous $KOH$ hydrolysis.

  • $R-CHCl_2 + \text{aq. } KOH → R-CH(OH)_2 → R-CHO + H_2O$

• Non-terminal gem-dihalides: Yield ketones.

VIII. Wacker Process

• Alkenes are oxidized to aldehydes or ketones using a solution of $PdCl_2$ and a catalytic amount of $CuCl_2$ in the presence of air or $O_2$.

• Ethene: Yields Acetaldehyde.

• Higher Alkenes: Yield Ketones.

• $PdCl_2$ is reduced to $Pd$, and $CuCl_2$ is reduced to $Cu(I)$.

IX. Using Grignard's Reagent

• From Hydrogen Cyanide: Treat $HCN$ with Grignard reagent followed by hydrolysis to get aldehyde via imine.

• From Alkyl Cyanide: Treat $R'CN$ with Grignard reagent to get ketone via ketimine.

• From Esters: Alkyl formate with Grignard reagent yields a secondary alcohol via an aldehyde; alkyl alkanoates yield tertiary alcohols via ketones.

Specific Preparation Methods for Aldehydes or Ketones Only

(A) Preparation of Aldehydes Only

1. Rosenmund's Reaction: Acid chlorides are reduced with $H_2$ in boiling xylene using a Palladium catalyst supported on Barium Sulphate ($Pd-BaSO_4$).

   • $R-COCl + H_2 → R-CHO + HCl$

2. Stephen's Reduction: Reduction of alkyl cyanides ($R-C≡N$) with $SnCl_2/HCl$ to aldimine hydrochloride, followed by hydrolysis to aldehyde.

3. Oxo-process (Carbonylation): Alkenes react with water gas ($CO + H_2$) at high temperature and pressure with a cobalt carbonyl catalyst ($[Co(CO)_4]_2$) to give aldehydes.

4. Reimer-Tiemann Reaction: Preparation of salicylaldehyde (phenolic aldehyde) by reacting phenol with $CHCl_3$ and $KOH$.

(B) Preparation of Ketones Only

1. Using Alkanoyl Chloride and Organometallics: Alkanoyl chloride reacts with dialkyl cadmium ($R'_2Cd$) to produce ketones and $CdCl_2$.

   • $2R-COCl + R'_2Cd → 2R-CO-R' + CdCl_2$

2. Friedel-Crafts Reaction: Acylation or benzoylation of aromatic hydrocarbons using anhydrous $AlCl_3$.

3. From Alkyl Cyanide: Hydrolysis after reaction of alkyl magnesium halide with ethyl cyanide or its homologues.

4. Oppenauer Oxidation: Secondary alcohols are refluxed with aluminum tert-butoxide in excess acetone. Acetone is reduced to isopropyl alcohol while the secondary alcohol is oxidized to a ketone.

5. Acid Hydrolysis of ̧-Ketoesters: Beta-ketoesters undergo hydrolysis to beta-ketoacids, which then readily decarboxylate upon heating to yield ketones.

Physical Properties

• State and Odor: Aldehydes are typically colorless liquids with pungent smells (Formaldehyde is a gas). Ketones are pleasant-smelling liquids.

• Solubility: Lower carbonyl compounds are water-soluble due to the polarity of the carbonyl group. Higher compounds are insoluble as covalent/carbon-chain character increases.

• Boiling Points:

  • Maintained by dipole-dipole attractions.

  • Boiling Point ∝ Molecular Mass.

  • Boiling Point ∝ $1 / \text{number of branches}$.

  • Specific B.P. values: Formaldehyde ($-21 ^┦C$), Acetaldehyde ($+21 ^┦C$), Acetone ($+56 ^┦C$).

• Formalin: A 40 \text{ %} solution of formaldehyde (40 \text{ % } HCHO, 54\text{--}56 \text{ % } H_2O, 4\text{--}6 \text{ % methanol}).

• Formamint: A mixture of formaldehyde and lactose sugar used for throat infections.

Chemical Reactions: Nucleophilic Addition

Carbonyl compounds undergo nucleophilic addition because of the partial positive charge on the carbonyl carbon.

• Reactivity Order: H-CHO > CH_3-CHO > CH_3-CO-CH_3. Reactivity decreases as the size/number of alkyl groups increases (steric and inductive effects).

I. Addition of Alcohols

• Aldehydes react with alcohols in the presence of dry $HCl$ gas to form acetals via unstable hemiacetals.

• Ketones react to form ketals via hemiketals.

• Acetals act as protecting groups for aldehydes; they are stable in base but decompose in dilute acid.

• Reaction with ethylene glycol results in cyclic acetals or ketals (1,3-dioxolanes).

II. Addition of Alkane Thiol

• Form thioacetals (from aldehydes) and thioketals/mercaptols (from ketones).

• Oxidation of these yields sulfonyl compounds (e.g., sulphonal, mercaptol) used as hypnotic drugs.

III. Addition of HCN

• Base-catalyzed addition to form cyanohydrins.

• The nucleophile is $CN^-$.

IV. Addition of Sodium Bisulpite ($NaHSO_3$)

• Forms a crystalline salt (bisulphite adduct).

• This addition is used for the purification and isolation of carbonyl compounds (only methyl ketones and aldehydes react).

• The attacking nucleophile is $SO_3^{2-}$ (prepared from $OH^- + HSO_3^- → H_2O + SO_3^{2-}$).

Addition-Elimination Reactions (Ammonia Derivatives)

Reaction involves nucleophilic attack at the carbonyl carbon followed by elimination of a water molecule ($-H_2O$). Product contains a $C=N$ bond.

• Media: Reaction requires slightly acidic media to activate the carbonyl group. Strongly acidic media protonates the ammonia derivative, destroying its nucleophilicity.

• Specific Derivatives ($NH_2-Z$):

  • Hydroxylamine ($NH_2OH$): Forms Oximes ($C=NOH$).

  • Hydrazine ($NH_2NH_2$): Forms Hydrazones ($C=NNH_2$).

  • Phenylhydrazine ($NH_2NHC_6H_5$): Forms Phenylhydrazones.

  • 2,4-Dinitrophenylhydrazine (Brady's Reagent): Forms yellow-orange precipitates of 2,4-DNP hydrazones.

  • Semicarbazide ($NH_2NHCONH_2$): Forms Semicarbazones.

Name Reactions and Rearrangements

I. Claisen Ester Condensation

• Reaction between two moles of ester in the presence of sodium ethoxide ($C_2H_5ONa$) to form a ̧-ketoester.

• Anion of one ester replaces the ethoxy part of the other.

• Dieckmann Condensation: Intramolecular Claisen condensation yielding a cyclic beta-ketoester.

II. Pinacol-Pinacolone Rearrangement

• Pinacol: Obtained by heating 2 moles of acetone with Magnesium ($Mg$) followed by water.

• In acidic media ($H^+$), pinacol ($2,3\text{-dimethylbutane-2,3-diol}$) rearranges to pinacolone ($3,3\text{-dimethylbutan-2-one}$).

III. Beckmann Rearrangement

• Oximes undergo rearrangement in acidic media (e.g., $H_2SO_4$, $PCl_5$) to produce isomeric amides.

• The group that is anti to the $-OH$ group on the nitrogen always migrates.

IV. Aldol Condensation

• Requires at least one ̡-hydrogen.

• Occurs in dilute basic media between two moles of carbonyl compounds.

• Forms ̧-hydroxy aldehyde/ketone (aldol), which eliminates water upon heating to form an ̡,̧-unsaturated carbonyl compound.

V. Cannizzaro Reaction

• Occurs in carbonyl compounds with no ̡-hydrogen.

• A disproportionation (redox) reaction in concentrated (50 \text{ %}) basic media.

• Produces one mole of alcohol (reduced) and one mole of carboxylic acid salt (oxidized).

• Crossed Cannizzaro: Between two different aldehydes (e.g., formaldehyde and benzaldehyde). Formaldehyde is preferentially oxidized to formate.

VI. Perkin Reaction

• Aromatic aldehyde (e.g., Benzaldehyde) + Anhydride + Sodium salt of the corresponding acid → ̡,̧-unsaturated acid (e.g., Cinnamic acid).

VII. Reformatsky Reaction

• Carbonyl compound + ̡-halogenated ester + Zinc ($Zn$) → ̧-hydroxyester.

VIII. Wittig Reaction

• Carbonyl compound + Phosphorus ylide ($Ph_3P=CR_2$) → Alkene and Triphenylphosphine oxide ($Ph_3P=O$).

• Proceeds via a four-membered cyclic intermediate called betaine.

IX. Baeyer-Villiger Oxidation

• Ketone + Peracid ($RCO_3H$) → Ester.

• An oxygen atom is inserted between the carbonyl carbon and one of the alkyl groups.

X. Haloform Reaction

• Acetaldehyde or methyl alkyl ketones containing a $-CH_3$ group react with halogen ($Cl_2, Br_2, I_2$) and alkali ($NaOH$).

• Produces a Haloform ($CHX_3$, e.g., yellow iodoform) and an acid salt.

XI. Reduction Reactions

• Clemmensen Reduction: Carbonyl compound + $Zn-Hg/HCl → \text{Alkane}$.

• Wolff-Kishner Reduction: Carbonyl compound + $NH_2NH_2/KOH$ in a high-boiling solvent (ethylene glycol) → Alkane.

• Reduction to Alcohols: Using $NaBH_4$, $LiAlH_4$, or $H_2/Ni$.

• Reduction to Pinacols: Using $Mg-Hg/H_2O$.

Identification Tests

• Tollen's Reagent: Ammoniacal silver nitrate ($[Ag(NH_3)_2]OH$). Weak oxidizing agent. Aldehydes reduce it to metallic silver (Silver Mirror).

• Fehling's Solution:

  • Fehling A: $CuSO_4$ solution.

  • Fehling B: Alkaline sodium potassium tartrate (Rochelle salt).

  • Aldehydes produce a red-brown precipitate of $Cu_2O$.

• Benedict Solution: $CuSO_4$, sodium citrate, and $Na_2CO_3$. Aldehydes give a red precipitate.

• Schiff's Reagent: Rosaniline hydrochloride solution decolorized by $SO_2$. Aldehydes restore the magenta/red color.

Polymerization

• Formaldehyde:

  • Paraformaldehyde: White crystalline solid formed by evaporation of aqueous solution ($n$ up to 100).

  • Metaformaldehyde (Trioxane): Cyclic trimer formed with conc. $H_2SO_4$.

  • Formose: Carbohydrate-like sweetener formed with lime water.

  • Bakelite: Cross-linked polymer from formaldehyde and phenol via Lederer-Manasse Reaction.

  • Hexamethylene tetramine (Urotropine): Formed with ammonia ($NH_3$); used for urinary infections.

• Acetaldehyde:

  • Paraldehyde: Cyclic trimer formed with conc. $H_2SO_4$ at room temp. Used as a sedative/hypnotic.

  • Metaldehyde: Cyclic tetramer formed with dry $HCl$ at low temp. Used as solid fuel or slug bait.

• Acetone:

  • Mesitylene: Cyclic trimer formed with conc. $H_2SO_4$ and heating ($1,3,5\text{-trimethylbenzene}$).

  • Phorone: Product of triple condensation using $ZnCl_2/HCl$.

Questions & Discussion

• Reactivity towards Nucleophilic Attack: Correct order is Acid chloride > Aldehyde > Ketone > Ester.

• Brady's Reagent Function: Specifically indicates the presence of a carbonyl group (>C=O) by forming colored precipitates.

• Cannizzaro Reaction and Hydride Transfer: Hydride ion transfer from the intermediate to the carbonyl group is the rate-determining step.

• Stability of Hydrates: Depends on steric hindrance, presence of electron-withdrawing groups ($-I$ groups like halogens), and bond angle strain.

• Distinction between 2-pentanone and 3-pentanone: Use Iodoform test ($I_2/NaOH$); 2-pentanone gives a positive test as it is a methyl ketone.