Synthesis Practice for Class 12 Worksheet - Answers

Synthesis practice is a cornerstone of advanced organic chemistry learning, especially crucial for Class 12 students aiming to excel in examinations and develop a robust conceptual foundation. This “Synthesis Practice for Class 12 Worksheet” provides a structured set of problems that guide learners through fundamental transformations, multi-step linear syntheses, and retrosynthetic analysis. By methodically working through these challenges, students hone their ability to design reaction pathways, select appropriate reagents, and predict outcomes with confidence—skills that will serve them well in academic assessments and beyond.

Below is a comprehensive collection of 120 synthesis practice for class 12 divided into 6 main categories, each containing 20 exemplars. Every problem is followed by a concise solution approach, mirroring the style demonstrated in the original examples. Work through them progressively to build confidence and mastery in organic synthesis.

Table of Contents

1) Fundamental Transformation Problems (20 Examples)

These are primarily single-step or very short transformation challenges, focusing on choosing correct reagents and predicting products.

1. Oxidation of Alcohols to Aldehydes/Ketones

Convert 1-propanol to propanal
Solution: Use a mild oxidizing agent such as PCC (pyridinium chlorochromate) in dichloromethane. This selectively oxidizes the primary alcohol to an aldehyde without further oxidation to the acid.
Convert cyclohexanol to cyclohexanone
Solution: Oxidize with PCC or Na₂Cr₂O₇/H₂SO₄ under controlled conditions. Either reagent will form the ketone from the secondary alcohol.
Convert 2-butanol to 2-butanone
Solution: Use PCC or CrO₃/H₂SO₄. The secondary alcohol is oxidized to the corresponding ketone.
Convert isobutyl alcohol (2-methyl-1-propanol) to isobutyraldehyde
Solution: Use PCC in dichloromethane (or Swern oxidation). This transforms the primary alcohol to the aldehyde.
Convert benzyl alcohol to benzaldehyde
Solution: Oxidize gently with PCC or MnO₂ (manganese dioxide). Both reagents can stop oxidation at the aldehyde stage.
Convert 2-methylcyclohexanol to 2-methylcyclohexanone
Solution: Treat with PCC or Jones reagent (CrO₃/H₂SO₄). The secondary alcohol is oxidized to the ketone.

2. Alkene Functionalizations

Convert oct-1-ene to octan-1-ol
Solution: Perform an acid-catalyzed hydration (H₂O/H₂SO₄) or a hydroboration-oxidation (1. BH₃·THF, 2. H₂O₂/NaOH) for better regioselectivity (anti-Markovnikov).
Convert 2-butene to 2-butanol
Solution: Use acid-catalyzed hydration (H₂O, H₂SO₄). Markovnikov addition of water across the double bond yields 2-butanol.
Convert 1-methylcyclohexene to 2-methylcyclohexanol
Solution:Hydration under acidic conditions or via hydroboration-oxidation. Markovnikov addition of –OH gives the secondary alcohol at C2.
Convert trans-2-butene to meso-2,3-butanediol
Solution: Perform syn-dihydroxylation using OsO₄ (osmium tetroxide) or KMnO₄ (cold, dilute). The symmetrical alkene with syn addition gives a meso diol.
Convert styrene to styrene oxide
Solution: Use an epoxidation reagent such as mCPBA (meta-chloroperbenzoic acid). This forms the oxirane (epoxide) across the alkene.
Convert cyclohexene to trans-1,2-cyclohexanediol
Solution: Use epoxidation (mCPBA) followed by acidic ring opening (H₃O⁺). The ring opening of the epoxide under acidic conditions gives the trans-diol.

3. Reduction Reactions

Convert acetophenone to 1-phenylethanol
Solution: Use NaBH₄ in ethanol or methanol. The ketone is selectively reduced to a secondary alcohol.
Convert ethyl benzoate (an ester) to benzyl alcohol
Solution: Use a stronger reducing agent like LiAlH₄ in ether, followed by acidic workup. This reduces the ester to the primary alcohol.
Convert benzonitrile to benzylamine
Solution: Use LiAlH₄ in dry ether, then acidic workup. The nitrile is fully reduced to the primary amine.
Convert cyclohexanone to cyclohexanol
Solution: Use NaBH₄ or LiAlH₄ in alcohol/ether. This reduces the ketone to a secondary alcohol.
Convert butanal to 1-butanol
Solution: Use NaBH₄ or LiAlH₄. The aldehyde is reduced to the primary alcohol.
Convert nitrobenzene to aniline
Solution: Use H₂ with a Pd-C catalyst or an iron/acid reduction (Fe/HCl). Both reduce nitro group to an amine.
Convert phenylacetylene to styrene
Solution: Perform a partial hydrogenation with H₂, Lindlar’s catalyst. This selectively hydrogenates the alkyne to the cis-alkene (styrene).
Convert 4-nitrotoluene to 4-aminotoluene (p-toluidine)
Solution: Reduce the nitro group using H₂/Pd-C or Fe/HCl. The para-amino derivative is obtained.

2) Multi-Step Linear Synthesis Challenges (20 Examples)

These problems typically involve 3–5 steps from simple starting materials to moderately complex targets.

Synthesize 4-chloro-2-pentanone from 1-propanol
Solution Outline:
- (1) Oxidize 1-propanol to propanoic acid (e.g., CrO₃/H₂SO₄).
- (2) Convert acid to acid chloride (SOCl₂).
- (3) React acid chloride with CH₃CH₂MgBr to form 3-pentanol (Grignard addition), then mild oxidation to 3-pentanone if needed, or better:
- Alternatively, do a direct route:
  1-propanol → 1-bromopropane (PBr₃) → reaction with NaCN → hydrolysis to butanoic acid, etc. (There can be multiple paths.)
- (4) Halogenate the ketone at the α-position (Cl₂/acid) to get 4-chloro-2-pentanone.
Convert cyclohexanol to cyclohexanecarboxylic acid
Solution Outline:
- (1) Oxidize cyclohexanol to cyclohexanone (PCC).
- (2) Perform a Baeyer-Villiger oxidation (mCPBA) to get ε-caprolactone.
- (3) Acidic hydrolysis of the lactone to cyclohexanecarboxylic acid.
Transform 1-pentanol to 2-hexanone
Solution Outline:
- (1) Convert 1-pentanol to 1-bromopentane (PBr₃).
- (2) React 1-bromopentane with Mg in ether → pentylmagnesium bromide.
- (3) Add formaldehyde (HCHO), followed by acidic workup → 2-hexanol (actually you’d get primary extension; carefully choose the aldehyde for correct chain length).
- (4) Oxidize 2-hexanol to 2-hexanone (PCC or Jones).
Convert 1-butanol to 2-butanone
Solution Outline:
- (1) Oxidize 1-butanol to butanal (PCC).
- (2) React butanal with methylmagnesium bromide → 2-pentanol.
- (3) Dehydrate 2-pentanol → 2-pentene (acid-catalyzed).
- (4) Oxidative cleavage (O₃, then reductive workup) → 2-butanone + formaldehyde.
  (Multiple routes possible; practice finding a succinct route.)
Synthesize 4-methoxyacetophenone from toluene
Solution Outline:
- (1) Nitration of toluene (HNO₃/H₂SO₄) → predominantly ortho/para-nitrotoluene. Separate or favor para if conditions are adjusted.
- (2) Reduce nitro group to amino group (H₂/Pd-C) → p-toluidine.
- (3) Diazotize (NaNO₂/HCl) → diazonium salt → phenol by heating (H₂O, Δ).
- (4) Methylate phenol (CH₃I, K₂CO₃) → p-cresyl methyl ether (p-anisole).
- (5) Friedel–Crafts acylation with acetyl chloride (AlCl₃) → 4-methoxyacetophenone.
Transform benzene to 3-phenylpropanoic acid
Solution Outline:
- (1) Friedel–Crafts acylation with succinic anhydride → 3-benzoylpropanoic acid derivative (or you can do direct alkylation with propyl side chain, then oxidation).
- (2) Hydrogenation if needed to reduce the keto or double bond.
- (3) Final oxidation or reduction steps to ensure the propanoic acid side chain is correct.
  (Alternate routes involve chloropropionic acid or malonic ester synthesis.)
Synthesize p-bromoaniline from benzene
Solution Outline:
- (1) Nitration: benzene → nitrobenzene (HNO₃/H₂SO₄).
- (2) Bromination: nitrobenzene → p-bromonitrobenzene (Br₂/FeBr₃). The nitro group directs bromination to the para position.
- (3) Reduction: p-bromonitrobenzene → p-bromoaniline (H₂/Pd-C or Fe/HCl).
Convert 1-propanol to 1-butanol
Solution Outline:
- (1) Convert 1-propanol to 1-bromopropane (PBr₃).
- (2) Perform a cyanide displacement: 1-bromopropane → butyronitrile (NaCN).
- (3) Hydrolyze nitrile → butyric acid (H₂O/H⁺, heat).
- (4) Reduce acid → 1-butanol (LiAlH₄).
Synthesize 4-bromobenzoic acid from toluene
Solution Outline:
- (1) Bromination of toluene (Br₂, FeBr₃). Predominantly ortho/para. Control temperature to favor para isomer.
- (2) Oxidation of para-bromotoluene side chain → 4-bromobenzoic acid (KMnO₄, heat).
Prepare 2-methyl-2-phenylpropanol from benzene
Solution Outline:

(1) Friedel–Crafts alkylation: benzene + (CH₃)₂CHCl (isopropyl chloride) with AlCl₃ → isopropylbenzene (cumene).
(2) Oxidation of cumene to cumene hydroperoxide (O₂).
(3) Acidic cleavage → phenol + acetone in typical cumene process. Alternatively, for 2-phenyl-2-propanol, you can do a Grignard approach:
- Convert benzene to bromobenzene, form phenylmagnesium bromide, react with acetone → 2-phenyl-2-propanol.

Convert 1-hexene to 2-hexanol
Solution Outline:

(1) Acid-catalyzed or hydroboration-oxidation hydration: 1-hexene → 2-hexanol (Markovnikov if acid-catalyzed; anti-Markovnikov if hydroboration but can form 1-hexanol).
(2) If anti-Markovnikov is needed, do BH₃·THF then H₂O₂/NaOH.

Synthesize cyclohexylamine from cyclohexanol
Solution Outline:

(1) Convert cyclohexanol to cyclohexanone (oxidation, PCC).
(2) Reductive amination of cyclohexanone (NH₃ and NaBH₃CN or H₂, Ni).
(3) This yields cyclohexylamine.

Convert ethanol to 2-butanol
Solution Outline:

(1) Convert ethanol to acetaldehyde (partial oxidation, PCC).
(2) Aldol condensation with another equivalent of acetaldehyde → crotonaldehyde.
(3) Hydrogenation of crotonaldehyde → butanal or butanol.
(4) Adjust steps to get specifically 2-butanol, e.g., use Grignard or other route.
(Multiple possibilities—excellent for planning practice.)

Synthesize 2-butanone from acetylene
Solution Outline:

(1) Acetylene + 2 equivalents CH₃MgBr → 2-butyne.
(2) Partial hydrogenation or hydroboration → 2-butene.
(3) Oxidative cleavage (O₃) → 2-butanone and formaldehyde, or hydroboration-oxidation to 2-butanol, then oxidation.

Prepare m-xylene from benzene
Solution Outline:

(1) Nitration: benzene → nitrobenzene.
(2) Reduce to aniline.
(3) Diazotization → diazonium salt.
(4) Sandmeyer reaction with CuCl → chlorobenzene.
(5) Additional steps to add two methyl groups in meta positions (requires multiple steps or an alternative approach, such as partial isopropylation and cleavage).
(Synthesizing specific xylenes from benzene can be tricky and typically uses methyl substituents with steric/electronic control.)

Transform benzyl chloride to phenylacetic acid
Solution Outline:

(1) Benzyl chloride + NaCN → benzyl cyanide.
(2) Hydrolyze nitrile (H₂O/H⁺, heat) → phenylacetic acid.

Convert 1-butanol to 2-butanol
Solution Outline:

(1) Oxidize 1-butanol to butanal (PCC).
(2) React butanal with a Grignard reagent made from CH₃Br → 2-pentanol.
(3) Perform a rearrangement or cleavage approach.
(Directly making 2-butanol from 1-butanol is not entirely straightforward; examine alternate routes or steps with advanced rearrangements.)

Synthesize 2-pentanone from ethyl acetoacetate (typical β-keto ester approach)
Solution Outline:

(1) Ethyl acetoacetate → enolate formation (NaOEt).
(2) Alkylate with CH₃CH₂Br → substituted β-keto ester.
(3) Acidic hydrolysis and decarboxylation → 2-pentanone.

Convert chlorobenzene to phenol
Solution Outline:

(1) Nucleophilic aromatic substitution under harsh conditions (NaOH, 300 °C, high pressure) → sodium phenolate.
(2) Acidify to get phenol.

Convert 3-buten-1-ol to 2-butenal (crotonaldehyde)
Solution Outline:

(1) Oxidize allylic alcohol (PCC) → 3-butenal.
(2) Acid-catalyzed tautomerization/dehydration → 2-butenal (crotonaldehyde).

3) Retrosynthetic Analysis Problems (20 Examples)

Here you start from the product and work backward, then outline a forward synthesis.

Design a synthesis for 2-methyl-3-pentanone
- Retrosynthetic Clue: Disconnection at the carbonyl α–β bond suggests an enolate alkylation or a Grignard addition to an acid derivative.
- Forward Path:
  1. Convert propanoic acid to its acid chloride (SOCl₂).
  2. React with (CH₃)₂CuLi (Gilman reagent) to form 2-methyl-3-pentanone.
Synthesize 3-phenyl-2-butanone
- Retrosynthetic Clue: Disconnection can show propiophenone + methylation or an aldol approach.
- Forward Path:
  1. Propiophenone + LDA → enolate.
  2. Enolate + CH₃I → 3-phenyl-2-butanone.
Prepare 4-hydroxy-4-methyl-2-pentanone
- Retrosynthetic Clue: Look for aldol condensation between acetone and acetaldehyde derivative.
- Forward Path:
  1. Form enolate from acetone (NaOH).
  2. React with acetaldehyde → aldol addition → 4-hydroxy-4-methyl-2-pentanone.
Synthesize 5-methyl-3-heptanol
- Retrosynthetic Clue: Tertiary alcohol from a ketone + Grignard.
- Forward Path:
  1. Start with 2-butanone.
  2. React with n-propylmagnesium bromide → 5-methyl-3-heptanol after workup.
Design a synthesis for 2,4-dimethyl-3-pentanol
- Retrosynthetic Clue: Tertiary alcohol from an aldehyde/ketone + two alkyl fragments (Grignard or enolate).
- Forward Path:
  1. 2-butanone + CH₃MgBr → 2,4-dimethyl-3-pentanol.
Prepare 2-methylcyclopentanone
- Retrosynthetic Clue: Could form ring via intramolecular aldol or start from cyclopentanone and alkylate.
- Forward Path:
  1. Cyclopentanone + LDA → enolate.
  2. Enolate + CH₃I → 2-methylcyclopentanone.
Synthesize 3-ethylcyclohexanol
- Retrosynthetic Clue: Secondary alcohol from a ketone reduction or Grignard addition.
- Forward Path:
  1. 3-ethylcyclohexanone (from alkylation or ring-opening strategy).
  2. Reduce with NaBH₄ → 3-ethylcyclohexanol.
Design a synthesis for 4-tert-butylcyclohexanone
- Retrosynthetic Clue: Disconnection suggests Friedel–Crafts on a ring or alkylation of cyclohexanone enolate.
- Forward Path:
  1. Cyclohexanone + t-BuCl (via enolate + t-Bu lithium reagent or tert-butylation via organocopper).
  2. Oxidation or rearrangement if needed to ensure position.
Retrosynthesis for 2-phenylethanol
- Retrosynthetic Clue: Often derived from styrene oxide or from benzaldehyde + Grignard of CH₂=O.
- Forward Path:
  1. Benzaldehyde + CH₃MgBr → secondary alcohol, not correct. Instead:
  2. Ethylene oxide + phenylmagnesium bromide → 2-phenylethanol.
Synthesize 3-methyl-2-cyclohexenone

Retrosynthetic Clue: Robinson annulation approach or partial reduction of a diketone.
Forward Path:
1. Michael addition of methyl vinyl ketone to cyclohexanone enolate.
2. Intramolecular aldol → 3-methyl-2-cyclohexenone.

Design a synthesis of 1-phenyl-1-propanol

Retrosynthetic Clue: Secondary benzylic alcohol from benzaldehyde + ethyl nucleophile.
Forward Path:
1. Benzaldehyde + EtMgBr → 1-phenyl-1-propanol (after acidic workup).

Retrosynthesis of 2-methyl-2-butanol

Retrosynthetic Clue: Tertiary alcohol from reaction of acetone + methyl Grignard.
Forward Path:
1. Acetone + CH₃MgBr → 2-methyl-2-butanol.

Synthesize 4-phenyl-2-butanone

Retrosynthetic Clue: Could be from benzyl chloride + acetoacetic ester or from a Stork enamine approach with phenylacetaldehyde.
Forward Path (simple):
1. Phenylacetyl chloride + dimethylcadmium → 4-phenyl-2-butanone.

Prepare 2,5-hexanedione

Retrosynthetic Clue: Two carbonyls separated by two carbons → double Claisen or Dieckmann-like ring closure then ring opening.
Forward Path:
1. Malonate approach or direct Claisen condensation with ethyl acetate, leading to 2,5-hexanedione upon hydrolysis and decarboxylation.

Synthesize 2-benzyl-1,3-propanediol

Retrosynthetic Clue: Possibly from an epoxide ring opening by a benzyl nucleophile or a double reduction.
Forward Path:
1. Glycidol (epoxy alcohol) + benzylmagnesium bromide → ring-opened product → 2-benzyl-1,3-propanediol.

Design a synthesis of 4-ethyl-3-hexanone

Retrosynthetic Clue: Enolate alkylation approach from 3-hexanone.
Forward Path:
1. 3-hexanone + LDA → enolate.
2. Reaction with ethyl iodide → 4-ethyl-3-hexanone.

Synthesize phenylacetic acid

Retrosynthetic Clue: Often from benzyl cyanide or direct oxidation of side chain.
Forward Path:
1. Toluene → benzyl chloride (Cl₂, hv).
2. Benzyl chloride → benzyl cyanide (NaCN).
3. Hydrolyze nitrile → phenylacetic acid (H₂O/H⁺).

Prepare 1,3-diphenyl-1-propanone

Retrosynthetic Clue: Benzyl + benzoyl combination.
Forward Path:
1. Benzoyl chloride + phenylmagnesium bromide → secondary alcohol.
2. Oxidation can yield 1,3-diphenyl-1-propanone if arranged properly, or use alternative approach like aceto phenone-based route.

Synthesize cyclopentylamine

Retrosynthetic Clue: Cyclopentanone → reductive amination.
Forward Path:
1. Cyclopentanol → cyclopentanone (oxidation).
2. Cyclopentanone + NH₃, then reduce (NaBH₃CN or H₂/Ni) → cyclopentylamine.

Design a synthesis for 2,3-dimethyl-2-butanol

Retrosynthetic Clue: Tertiary alcohol from methyl ketone + methyl Grignard.
Forward Path:
1. 2-butanone + CH₃MgBr → 2,3-dimethyl-2-butanol.

4) Stereochemical Control Problems (20 Examples)

These tasks emphasize stereoselectivity, enantioselectivity, or diastereoselectivity in synthesis.

Synthesize (R)-2-octanol with >95% ee
Solution:
- Use an enantioselective reduction of 2-octanone, for example with CBS catalyst ((R)-CBS) and BH₃·THF.
Prepare (S)-1-phenylethanol from acetophenone
Solution:
- Enantioselective reduction using the Noyori catalyst (BINAP-Ru complex) or CBS catalyst.
- Alternative: Use an enzymatic reduction (yeast or alcohol dehydrogenase).
Design a synthesis of (2R,3R)-2,3-butanediol
Solution:
- Perform enantioselective dihydroxylation of trans-2-butene with (DHQ)_2PHAL or related Sharpless dihydroxylation catalysts.
- This yields a specific enantiomer of the diol.
Synthesize (S)-3-hydroxybutanoic acid
Solution:
- Use the Evans aldol approach with a chiral auxiliary to form the (S)-hydroxy acid.
- Hydrolyze the auxiliary to obtain the product in high enantiomeric excess.
Prepare (R)-1,2-propanediol
Solution:
- Start from glycidol and perform an enantioselective ring opening, or use a chiral catalyst in the ring opening of propylene oxide.
Synthesize cis-4-tert-butylcyclohexanol
Solution:
- Start with 4-tert-butylcyclohexanone.
- Use a selective reduction (NaBH₄) that typically gives the equatorial alcohol (trans). If you need cis, consider controlling approach via sterics or a chiral catalyst that favors axial.
- Alternatively, form the enolate, then do a stereoselective protonation or adjustments.
Prepare trans-2-methylcyclohexanol
Solution:
- Start from 2-methylcyclohexanone.
- A typical hydride reduction (NaBH₄ or LiAlH₄) often gives the trans-alcohol as the major product because the hydride approaches from the less hindered side.
Design a synthesis of (1R,2R)-1,2-diphenylethane-1,2-diol
Solution:
- Enantioselective dihydroxylation (Sharpless) on trans-stilbene.
- Conditions (OsO₄ + chiral ligand) yield the (R,R) or (S,S) enantiomer depending on the ligand used.
Synthesize (S)-1-phenylethylamine
Solution:
- Reductive amination of acetophenone with a chiral catalyst (e.g., Noyori or chiral Ru).
- Alternatively, resolve racemic 1-phenylethylamine by forming diastereomeric salts with a chiral acid (e.g., tartaric acid).
Prepare (R)-2-chlorobutane
Solution:

Start from (R)-2-butanol.
React with SOCl₂ or PCl₃ via an SN2 pathway while carefully controlling conditions to preserve configuration or to invert if needed.
Must account for stereochemical inversion in SN2 processes.

Synthesize (S,S)-2,3-butanediol from (Z)-2-butene**
Solution:

Use Sharpless asymmetric dihydroxylation (AD-mix).
The reagent set (AD-mix-α or AD-mix-β) controls the absolute stereochemistry of the diol.

Prepare (R)-2-butanol via microbial fermentation
Solution:

Ferment butanone or related substrate with a specific alcohol dehydrogenase (ADH) or yeast.
The enzyme selectively reduces the ketone to the (R)-2-butanol.

Design a synthesis of (R)-mandelic acid
Solution:

Benzaldehyde + HCN → racemic mandelonitrile.
Enzymatic resolution or use a chiral Strecker approach.
Hydrolyze nitrile → (R)-mandelic acid.

Synthesize (R)-3-methyl-3-phenylpropan-1-ol
Solution:

Use an enantioselective approach with a chiral auxiliary on the phenyl ring or a chiral reduction of the ketone formed from 3-phenylpropionaldehyde plus a methyl nucleophile.

Prepare (2S,3S)-2,3-butanediol from an alkyne
Solution:

2-butyne partial hydrogenation → cis-2-butene.
Sharpless asymmetric dihydroxylation to get the (S,S)-diol.

Synthesize (R)-2-hydroxy-4-phenylbutanoic acid
Solution:

Use an Evans aldol with a chiral auxiliary from phenylacetaldehyde.
Hydrolyze to release the free acid.

Prepare (R)-2-amino-3-phenylpropanoic acid (L-phenylalanine)
Solution:

Strecker synthesis with a chiral auxiliary or enzymatic resolution.
Alternatively, isolate from protein hydrolysates (practical but not a “lab synthesis”).

Design a route to (E)-3-hexen-1-ol with high stereochemical purity
Solution:

Use a Wittig or Julia olefination to set the E-alkene, then reduce the aldehyde or form the allylic alcohol under controlled conditions.
Asymmetric approach might involve a chiral pool or enantioselective allylation.

Prepare (S)-glycidol
Solution:

Sharpless epoxidation on allylic alcohol.
The choice of (−)-DET or (+)-DET in the Sharpless epoxidation sets the epoxide chirality.

Synthesize (S)-(+)-carvone from (R)-limonene (illustrative natural product interconversion)
Solution:

Oxidize the allylic position with a chiral selenium or allylic oxidation route, controlling stereochemistry, then perform rearrangements.
Such a route is advanced but highlights enantioselective functionalization of terpenes.

5) Named Reaction Applications (20 Examples)

Focus on famous name reactions (Wittig, Grignard, Aldol, Diels–Alder, Friedel–Crafts, etc.) in synthetic routes.

Use the Wittig reaction to prepare (E)-4-phenyl-3-buten-2-one
Solution:
- Wittig reagent from triphenylphosphine + α-bromoacetone → phosphorane.
- React with benzaldehyde → (E)-4-phenyl-3-buten-2-one.
Apply the Grignard reaction to synthesize 2-methyl-2-phenylpropan-1-ol
Solution:
- Benzaldehyde + (CH₃)₂CHMgBr → 2-methyl-2-phenylpropan-1-ol (tertiary carbinol).
- Acidic workup is required.
Employ the aldol reaction to prepare 4-hydroxy-4-methyl-2-pentanone
Solution:
- Enolate of acetone (NaOH) + acetaldehyde → aldol addition product.
- This yields 4-hydroxy-4-methyl-2-pentanone.
Perform a Claisen condensation to synthesize diethyl malonate derivative
Solution:
- React ethyl acetate with another ester under base.
- Intramolecular or intermolecular Claisen forms β-keto esters.
Use the Michael addition to form 3-oxo-5-phenylpentanoate
Solution:
- Michael donor: malonate anion.
- Michael acceptor: cinnamate ester.
- Combine under base → 3-oxo-5-phenylpentanoate after decarboxylation.
Apply the Diels–Alder reaction to prepare a substituted cyclohexene
Solution:
- React butadiene with an α,β-unsaturated aldehyde or maleic anhydride, forming a six-membered ring with controllable stereochemistry.
Use Robinson annulation to construct a bicyclic enone
Solution:
- Michael addition of a cyclic diketone or cyclohexanone enolate to methyl vinyl ketone.
- Intramolecular aldol → bicyclic enone.
Synthesize 1,2,3,4-tetrahydronaphthalene using Friedel–Crafts
Solution:
- Friedel–Crafts alkylation of benzene with a 4-chlorobutyl chain, intramolecular cyclization, then partial hydrogenation if needed.
Perform a Beckmann rearrangement to prepare caprolactam
Solution:
- Start with cyclohexanone oxime.
- Treat with acidic conditions (H₂SO₄ or PCl₅) → rearrangement to caprolactam.
Use the Cannizzaro reaction to make benzyl alcohol + benzoic acid
Solution:

React benzaldehyde (no α-H) with concentrated base.
One molecule is reduced to benzyl alcohol; another is oxidized to benzoic acid.

Perform a Sandmeyer reaction to convert aniline to chlorobenzene
Solution:

Diazotize aniline (NaNO₂, HCl, 0 °C) → diazonium salt.
React with CuCl → chlorobenzene.

Employ the Birch reduction to synthesize 1,4-cyclohexadiene from benzene
Solution:

Dissolve benzene in liquid ammonia with Na metal.
Birch conditions reduce the aromatic ring to a 1,4-diene.

Use the Wolff–Kishner reduction to convert cyclohexanone to cyclohexane
Solution:

Form hydrazone (cyclohexanone + hydrazine).
Heat with strong base (KOH) → complete reduction to cyclohexane.

Apply the Clemmensen reduction to convert benzaldehyde to toluene
Solution:

Zinc amalgam (Zn(Hg)) + HCl.
Reduces the aldehyde group on benzaldehyde to a methyl group.

Carry out the Rosenmund reduction to convert benzoyl chloride to benzaldehyde
Solution:

Treat benzoyl chloride with H₂ over Pd/BaSO₄ (poisoned catalyst).
Partial reduction yields benzaldehyde.

Perform the Pinacol rearrangement on pinacol to pinacolone
Solution:

Vicinal diol (pinacol) + acid (H₂SO₄).
1,2-shift → pinacolone (tert-butyl methyl ketone).

Use the Prins reaction to form a 1,3-dioxane
Solution:

React an aldehyde with an alkene in the presence of an acid + water.
Yields a 1,3-dioxane after cyclization.

Synthesize a β-lactam ring via the Staudinger reaction
Solution:

React an imine with a ketene.
[2+2] cycloaddition → β-lactam.

Use the Mannich reaction to prepare β-amino ketones
Solution:

React formaldehyde, a secondary amine, and a ketone under acidic conditions.
Formation of an iminium ion, then enol addition → β-amino ketone.

Use the Baeyer–Villiger oxidation to transform cyclohexanone into ε-caprolactone
Solution:

React cyclohexanone with a peracid (mCPBA).
Insertion of oxygen next to the carbonyl → ε-caprolactone.

6) Advanced Multi-Step Synthesis Challenges (20 Examples)

These problems require longer or convergent routes and integration of multiple reaction types.

Convergent synthesis of 1,5-diphenylpentan-3-one
Solution Outline:
- Fragment A: 2-phenylethyl bromide (from 2-phenylethanol + PBr₃).
- Fragment B: 2-phenylethanoic acid → Weinreb amide.
- Couple with (2-phenylethyl)magnesium bromide → 1,5-diphenylpentan-3-one.
Synthesize menthol from citronellal
Solution Outline:
- Cyclization of citronellal under acidic conditions → isopulegol.
- Hydrogenation → menthol.
- Control stereochemistry with catalytic conditions or chiral catalysts.
Prepare 2-phenylchroman-4-one (a flavanone)
Solution Outline:
- Claisen condensation between phenol derivative (salicylaldehyde) and acetophenone.
- Intramolecular cyclization → flavanone.
Design a synthesis of ethyl 2-acetamido-3-phenylpropanoate (protected phenylalanine ester)
Solution Outline:
- Use the Strecker synthesis on a protected aldehyde derivative → α-amino nitrile.
- Hydrolyze carefully to form amide (acetamido) and esterify → the final protected amino acid ester.
Convergent route to 3,7-dimethyl-6-octen-1-ol (citronellol)
Solution Outline:
- Fragment 1: Grignard from 2-methyl-1-bromopropene.
- Fragment 2: 3-methylbutanal or related aldehyde.
- Couple and then reduce if necessary to form the unsaturated alcohol.
Synthesize 4-benzyl-2,6-dimethylheptan-4-ol
Solution Outline:
- Break the molecule into a benzyl fragment and a branched alkyl chain.
- Use a convergent approach with a ketone or aldehyde in the middle.
- Grignard addition to set the tertiary alcohol.
Prepare the tetracyclic core of steroids (high-level challenge)
Solution Outline:
- Robinson annulation + polycyclization sequences.
- Intricate ring-forming steps with enolate chemistry.
Synthesize p-methoxycinnamic acid from benzaldehyde
Solution Outline:
- Benzaldehyde + p-methoxybenzaldehyde might be reversed, or use the Knoevenagel condensation with malonic acid.
- Decarboxylation → p-methoxycinnamic acid.
Prepare 3,4-dihydropyran ring via Prins cyclization
Solution Outline:
- React an aldehyde with an alkene in the presence of acid and a nucleophilic co-solvent.
- Intramolecular cyclization → 3,4-dihydropyran skeleton.
Convergent synthesis of 2-benzyl-1,3-propanediol
Solution Outline:

Fragment 1: Benzyl bromide.
Fragment 2: Glycidol or glycerol derivative.
Ring opening or simple coupling to yield the diol.

Synthesize lysergic acid skeleton (very advanced)
Solution Outline:

Diels–Alder approach to form ring system.
Functional group manipulations to introduce the amide.
This is a multistep route typically beyond standard lab scope, used for advanced planning practice.

Preparation of tropinone using the Robinson synthesis
Solution Outline:

Acetoacetic ester + succinaldehyde + methylamine → intramolecular aldol.
Cyclization to tropinone.

Synthesize N-phenylsuccinimide from aniline
Solution Outline:

Aniline → N-phenylmaleimide (by reaction with maleic anhydride, then dehydration).
Cyclization under heat → N-phenylsuccinimide (or direct ring closure from maleamic acid).

Design a route to colchicine skeleton (extremely advanced)
Solution Outline:

Involves elaboration of tropolone ring + complex cyclization steps.
Demonstrates forging multiple rings with functional manipulations.

Synthesize p-aminosalicylic acid (anti-TB drug)
Solution Outline:

Methyl salicylate nitration or direct modification.
Convert nitro to amino group.
Adjust substitution pattern via partial protection and directed ortho-metalation if needed.

Prepare verapamil-like fragment (phenylalkylamine)
Solution Outline:

Phenyl ring with correct substitution → attach an aminoalkyl chain.
Use reductive amination or alkylation to introduce the tertiary amine.

Convergent route to tamoxifen (anti-cancer drug)
Solution Outline:

Build the triphenylethylene core using Wittig or McMurry coupling.
Install the side-chain containing the dimethylaminoethoxy substituent.
Combine fragments convergently.

Synthesizing a bicyclic ketal ring system
Solution Outline:

Form a diol or carbonyl precursor.
Intramolecular ketal formation using acid.
Possibly preceded by a Diels–Alder step to create the bicyclic skeleton.

Prepare a spirocyclic lactone
Solution Outline:

Use malonic ester or a related ring closure to form the spiro center.
Lactonize under acidic conditions.

Synthesize α-terpineol from limonene
Solution Outline:

Hydration or oxymercuration of limonene.
Intramolecular rearrangement to form the tertiary alcohol ring structure of α-terpineol.

Tips for Practice

Systematic Approach: Start always by studying in detail the target structure:
Identify carbon skeleton modifications and functional groups required.
Retrosynthesize to less complex, known or easily accessible precursors.
Evaluate a few possibilities before a final action is selected.

Key Considerations:

Functional group compatibility (protecting groups where appropriate).
Atom economy and step economy for efficiency.
Potential side reactions or over-oxidations.
Practice regularly: Experiment with different versions of each problem (e.g., reverse starting materials or reagents) to develop your repertoire of syntheses.

Through these 120 problems—ranging from simple conversions, multi-step linear syntheses, retrosynthetic analysis, stereochemical control, named reactions, and elaborate convergent approaches—you will be well-equipped with sound problem-solving skills in organic synthesis.

You can visit the questionnaire here.

For Naming Reactions in ORGANIC CHEMISTRY CLASS 12 here.

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Synthesis Practice for Class 12 Worksheet – Answers