Chemca
Master 3-Step
Organic Conversions
Elevate your synthetic logic. This curated collection features 20 intricate three-step organic conversions. These sequences combine aliphatic and aromatic reactions from Class 11 and 12 chapters, teaching you how to step-up, step-down, and manipulate functional groups. Click to reveal detailed mechanistic pathways.
1 Convert Ethanol to Propan-2-ol
To add a carbon and branch it, we must synthesize a ketone or aldehyde. Ethanol (a primary alcohol) is subjected to mild oxidation using Pyridinium Chlorochromate ($\ce{PCC}$) in dichloromethane. This stops the oxidation at the aldehyde stage, yielding Ethanal.
Ethanal is reacted with Methylmagnesium bromide ($\ce{CH3MgBr}$, a Grignard reagent) in dry ether. The nucleophilic methyl carbanion attacks the electrophilic carbonyl carbon, breaking the pi bond to form a magnesium alkoxide complex.
The alkoxide intermediate is immediately hydrolyzed with dilute acid ($\ce{H3O+}$). The oxygen atom is protonated, yielding a secondary alcohol with one additional carbon atom: Propan-2-ol.
2 Convert Benzene to m-Nitroaniline
Benzene is treated with a standard nitrating mixture (concentrated $\ce{HNO3}$ and concentrated $\ce{H2SO4}$) at 330 K. The electrophilic attack of the nitronium ion ($\ce{NO2+}$) forms Nitrobenzene.
The $-\ce{NO2}$ group is strongly electron-withdrawing and meta-directing. A second, more vigorous nitration (fuming $\ce{HNO3}$, conc. $\ce{H2SO4}$, high heat) places a second nitro group at the meta position, yielding m-Dinitrobenzene.
To convert only one nitro group to an amine while leaving the other intact, we use a selective reducing agent such as Sodium sulfide ($\ce{Na2S}$) or Ammonium hydrogen sulfide ($\ce{NH4HS}$). This selective reduction yields m-Nitroaniline.
3 Convert Ethanoic acid to Propanenitrile
To add a carbon (step-up), we must convert the unreactive carboxylic acid to a reactive halide. First, Ethanoic acid is strongly reduced using Lithium Aluminum Hydride ($\ce{LiAlH4}$) followed by hydrolysis, yielding Ethanol.
Ethanol is converted into a good substrate for nucleophilic substitution by reacting it with Thionyl chloride ($\ce{SOCl2}$). This replaces the $-\ce{OH}$ group with chlorine, forming Chloroethane (along with gaseous $\ce{SO2}$ and $\ce{HCl}$).
Chloroethane (2 carbons) is heated with alcoholic Potassium Cyanide ($\ce{KCN(alc)}$). The cyanide ion displaces the chloride ion in an $S_N2$ reaction, extending the chain by one carbon to form Propanenitrile.
4 Convert Bromomethane to Ethanol
Bromomethane (1 carbon) must be stepped up to a 2-carbon chain. It is treated with alcoholic Potassium Cyanide ($\ce{KCN}$). The $S_N2$ substitution yields Ethanenitrile ($\ce{CH3CN}$).
The nitrile is then completely hydrolyzed by boiling with dilute mineral acid ($\ce{H3O+}$). The carbon-nitrogen triple bond is broken completely to form a carboxylic acid group, producing Ethanoic acid.
Finally, Ethanoic acid is reduced using the powerful reducing agent Lithium Aluminum Hydride ($\ce{LiAlH4}$), followed by aqueous workup, yielding the desired primary alcohol: Ethanol.
5 Convert Phenol to Aspirin
Phenol is reacted with aqueous Sodium Hydroxide ($\ce{NaOH}$) to form Sodium phenoxide. The phenoxide ion is highly activated for electrophilic aromatic substitution.
Sodium phenoxide undergoes Kolbe's reaction by heating with Carbon dioxide ($\ce{CO2}$) at 400 K under pressure, followed by acidification ($\ce{H+}$). The electrophile ($\ce{CO2}$) attacks the ortho position, forming 2-Hydroxybenzoic acid (Salicylic acid).
Salicylic acid is treated with Acetic anhydride ($\ce{(CH3CO)2O}$) in the presence of a few drops of concentrated sulfuric acid as a catalyst. This acetylates the phenolic $-\ce{OH}$ group, forming Acetylsalicylic acid (Aspirin).
6 Convert Ethene to Propanoic acid
Ethene (2 carbons) needs an extra carbon. First, it is reacted with Hydrogen Bromide ($\ce{HBr}$). The electrophilic addition across the double bond yields Bromoethane.
Bromoethane is heated with alcoholic Potassium Cyanide ($\ce{KCN(alc)}$). The $S_N2$ substitution extends the carbon skeleton from two to three atoms, producing Propanenitrile.
Propanenitrile is boiled with an aqueous mineral acid ($\ce{H3O+}$). The nitrile group undergoes complete hydrolysis, converting the triple bond directly to a carboxylic acid, yielding Propanoic acid.
7 Convert Nitrobenzene to Phenol
Nitrobenzene is reduced to an amine using active metal and acid, specifically Tin and Hydrochloric acid ($\ce{Sn/HCl}$). The $-\ce{NO2}$ group is fully reduced to an $-\ce{NH2}$ group, yielding Aniline.
Aniline is treated with a cold, aqueous solution of Sodium Nitrite and Hydrochloric acid ($\ce{NaNO2 + HCl}$) at strictly maintained ice-cold temperatures (0-5°C). This produces the versatile intermediate Benzene diazonium chloride.
The diazonium salt is highly unstable to heat. Simply warming the aqueous solution of benzene diazonium chloride allows water to act as a nucleophile, replacing the $\ce{-N2+}$ group to yield Phenol, with the evolution of nitrogen gas.
8 Convert Ethanol to Methanamine
To step down a carbon series, we need an amide. First, Ethanol (2 carbons) is subjected to complete oxidation using acidified Potassium Permanganate ($\ce{KMnO4/H+}$), yielding Ethanoic acid.
Ethanoic acid is treated with Ammonia ($\ce{NH3}$) and heated strongly. This eliminates a water molecule from the intermediate ammonium ethanoate to form Ethanamide (Acetamide).
Ethanamide is reacted with Bromine and a strong base ($\ce{Br2/KOH}$). This reaction excises the carbonyl carbon entirely, reducing the chain length from two to one, resulting in Methanamine.
9 Convert Toluene to 2-Phenylethanoic Acid
To extend the side chain, we must first activate it. Toluene is reacted with Chlorine gas in the presence of UV light ($\ce{Cl2/h\nu}$). This initiates a free-radical substitution exclusively on the methyl group, producing Benzyl chloride.
Benzyl chloride is heated with alcoholic Potassium Cyanide ($\ce{KCN}$). The nucleophilic cyanide ion displaces the chloride, extending the side chain by one carbon atom to yield Benzyl cyanide (Phenylethanenitrile).
The nitrile is completely hydrolyzed by boiling with aqueous mineral acid ($\ce{H3O+}$). The triple bond is converted into a carboxylic acid, producing 2-Phenylethanoic acid.
10 Convert 1-Bromopropane to Propanone
To move functionalization from the terminal carbon (C-1) to the middle carbon (C-2), we create a double bond. 1-Bromopropane is heated with alcoholic $\ce{KOH}$. The $\beta$-elimination of $\ce{HBr}$ yields Propene.
Propene is passed through water in the presence of dilute acid ($\ce{H2O/H+}$). Electrophilic addition follows Markovnikov's rule, placing the hydroxyl group on the secondary carbon, yielding Propan-2-ol.
The secondary alcohol is oxidized using acidified Potassium Dichromate ($\ce{K2Cr2O7/H+}$) or Chromium trioxide ($\ce{CrO3}$). Secondary alcohols oxidize cleanly into ketones, producing Propanone (Acetone).
11 Convert Benzene to Styrene
A 2-carbon chain is introduced to the ring. Benzene reacts with Acetyl chloride ($\ce{CH3COCl}$) and anhydrous Aluminum chloride ($\ce{AlCl3}$). The electrophilic acylium ion attack yields Acetophenone ($\ce{C6H5COCH3}$).
The ketone group is selectively reduced using Sodium Borohydride ($\ce{NaBH4}$) in ethanol. The hydride ion attacks the carbonyl carbon, producing the secondary alcohol 1-Phenylethanol.
The alcohol is heated with concentrated Sulfuric acid ($\ce{H2SO4}$ at $\Delta$). The elimination of water forms a double bond that is highly conjugated with the aromatic ring, yielding Phenylethene, commonly known as Styrene.
12 Convert Ethanal to Crotonic Acid
Ethanal ($\ce{CH3CHO}$) is treated with dilute $\ce{NaOH}$. Due to the presence of $\alpha$-hydrogens, two molecules condense. The enolate of one attacks the carbonyl of the other, forming 3-Hydroxybutanal (aldol).
Heating the aldol drives the elimination of a water molecule to form a stable, conjugated system. This yields the $\alpha,\beta$-unsaturated aldehyde, But-2-enal (Crotonaldehyde).
To convert the aldehyde to a carboxylic acid without cleaving the newly formed carbon-carbon double bond, a mild oxidizing agent is strictly required. Tollens' reagent ($\ce{[Ag(NH3)2]+}$) selectively oxidizes the $-\ce{CHO}$ group, yielding But-2-enoic acid (Crotonic acid).
13 Convert Aniline to p-Bromoaniline
Direct bromination of aniline yields 2,4,6-tribromoaniline because the $-\ce{NH2}$ group is highly activating. To get the mono-substituted product, we "protect" the amine. Aniline is reacted with Acetic anhydride ($\ce{Ac2O}$) in pyridine, forming Acetanilide. This reduces the activating power via resonance with the carbonyl oxygen.
Acetanilide is reacted with Bromine in acetic acid ($\ce{Br2/CH3COOH}$). Due to the bulkiness of the acetyl group, steric hindrance forces the incoming bromine electrophile exclusively to the para position, yielding p-Bromoacetanilide.
The acetyl protection is removed by boiling with aqueous acid or base ($\ce{H3O+}$ or $\ce{OH-}$). The amide bond is hydrolyzed, restoring the primary amine group, yielding pure p-Bromoaniline.
14 Convert Aniline to 1,3,5-Tribromobenzene
Aniline is highly activated. Reacting it directly with aqueous Bromine (Bromine water, $\ce{Br2(aq)}$) results in rapid electrophilic aromatic substitution at all available ortho and para positions simultaneously, precipitating 2,4,6-Tribromoaniline.
To remove the amino group, it must be converted to a diazonium salt. The tribromoaniline is treated with cold Sodium Nitrite and Hydrochloric acid ($\ce{NaNO2/HCl}$, 273K), yielding 2,4,6-Tribromobenzene diazonium chloride.
The diazonium group is completely removed and replaced by a hydrogen atom by reacting the salt with a mild reducing agent, Hypophosphorous acid ($\ce{H3PO2}$) in the presence of water, yielding 1,3,5-Tribromobenzene.
15 Convert Benzene to Benzyl Alcohol
First, a carbon side-chain must be added to the ring. Benzene reacts with Methyl chloride ($\ce{CH3Cl}$) catalyzed by anhydrous Aluminum chloride ($\ce{AlCl3}$). The electrophilic methyl cation attacks the ring to form Toluene (Methylbenzene).
Toluene is reacted with Chlorine gas in the presence of sunlight or UV light ($\ce{Cl2/h\nu}$). This directs the reaction via a free-radical mechanism exclusively to the benzylic position, substituting one hydrogen for a chlorine to yield Benzyl chloride.
The benzylic chloride is highly reactive towards $S_N2$ substitution. Boiling benzyl chloride with aqueous Potassium Hydroxide ($\ce{KOH(aq)}$) displaces the chloride ion with a hydroxyl group, yielding Benzyl alcohol.
16 Convert Propan-2-ol to 2-Methylpropan-2-ol
To create a tertiary alcohol, we must react a Grignard reagent with a ketone. Propan-2-ol (a secondary alcohol) is oxidized using Chromium trioxide in acid ($\ce{CrO3/H+}$) or Jones Reagent, forming Propanone (Acetone).
Propanone is reacted with Methylmagnesium bromide ($\ce{CH3MgBr}$) in dry ether. The methyl carbanion attacks the central electrophilic carbonyl carbon, forming a tertiary magnesium alkoxide intermediate.
The alkoxide intermediate is treated with dilute acid ($\ce{H3O+}$). Protonation of the oxygen yields the target tertiary alcohol, 2-Methylpropan-2-ol.
17 Convert Propan-1-ol to Ethanamine
A step-down reaction is required (3 carbons to 2 carbons). The first milestone is an acid. Propan-1-ol is oxidized using acidified Potassium Permanganate ($\ce{KMnO4/H+}$), driving it directly to Propanoic acid.
Propanoic acid is reacted with Ammonia ($\ce{NH3}$) to form an ammonium salt, which is then strongly heated to dehydrate it into Propanamide.
Propanamide is subjected to Hoffmann bromamide degradation using Bromine and aqueous $\ce{KOH}$. The carbonyl carbon is completely removed as carbonate, yielding the stepped-down primary amine, Ethanamine.
18 Convert Ethanol to Butane
To double the carbon chain symmetrically, we use the Wurtz reaction, which requires an alkyl halide. Ethanol is treated with Thionyl chloride ($\ce{SOCl2}$) in the presence of pyridine, cleanly converting it to Chloroethane.
Chloroethane (2 moles) is reacted with Sodium metal ($\ce{Na}$) in a strictly anhydrous medium (dry ether). The sodium extracts the halogens, allowing the two ethyl radicals to couple together symmetrically, forming Butane.
Note: Standard Wurtz is 2 steps. For 3 steps: 1. $\ce{SOCl2}$ -> Chloroethane, 2. Mg/ether -> Ethyl Mg Chloride, 3. Chloroethane -> Butane (Coupling). Wurtz conceptually combines 2 & 3. Both are highly acceptable in exams.
19 Convert Acetic Acid to Malonic Acid
Acetic acid ($\ce{CH3COOH}$) possesses $\alpha$-hydrogens. Treatment with Chlorine ($\ce{Cl2}$) in the presence of a small amount of Red Phosphorus ($\ce{P_{red}}$) substitutes one $\alpha$-hydrogen with chlorine, yielding Chloroacetic acid.
The $\alpha$-haloacid is then reacted with aqueous Potassium Cyanide ($\ce{KCN(aq)}$). The cyanide ion nucleophilically substitutes the chlorine atom via an $S_N2$ mechanism, resulting in Cyanoacetic acid.
The intermediate is boiled with dilute aqueous acid ($\ce{H3O+}$). The nitrile group ($\ce{-CN}$) is completely hydrolyzed into a second carboxylic acid group, producing Propanedioic acid, universally known as Malonic acid.
20 Convert Nitrobenzene to Iodobenzene
Direct iodination of benzene rings is reversible and difficult. Nitrobenzene is first reduced to a primary amine using Tin and Hydrochloric acid ($\ce{Sn/HCl}$), yielding Aniline.
Aniline is treated with a cold mixture of Sodium Nitrite and Hydrochloric acid ($\ce{NaNO2 + HCl}$) strictly between 0-5°C (273-278 K) to form Benzene diazonium chloride, which possesses the excellent nitrogen leaving group.
Unlike Sandmeyer reactions, introducing iodine does not require a copper catalyst. The diazonium salt is simply warmed with an aqueous solution of Potassium Iodide ($\ce{KI}$). The iodide ion nucleophilically replaces the diazonium group, liberating nitrogen gas and producing Iodobenzene.
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