Chemca
Master 5-Step
Organic Conversions
The pinnacle of synthetic logic and competitive exam preparation. This collection features 20 intricate five-step organic conversions. Learn to sequence step-ups, rigorous protections, meta-directing flips, and functional group migrations. Click to unveil the complete architectural pathways.
1 Convert Methanol to Lactic Acid (2-Hydroxypropanoic acid)
Methanol is converted to a reactive alkyl halide using Thionyl chloride ($\ce{SOCl2}$), yielding Chloromethane.
Chloromethane is heated with alcoholic $\ce{KCN}$. The nucleophilic attack extends the chain to 2 carbons, forming Acetonitrile (Ethanenitrile).
The nitrile is partially reduced to an aldehyde. Using Diisobutylaluminum hydride ($\ce{DIBAL-H}$) followed by hydrolysis yields Ethanal.
Ethanal undergoes nucleophilic addition with Hydrogen Cyanide ($\ce{HCN}$), extending the chain to 3 carbons and forming Ethanal cyanohydrin.
The nitrile group is completely hydrolyzed by boiling with dilute mineral acid ($\ce{H3O+}$), yielding 2-Hydroxypropanoic acid (Lactic Acid).
2 Convert Ethene to 1-Bromobutane
Ethene (2 carbons) undergoes acid-catalyzed hydration ($\ce{H2O / H+}$) to form Ethanol.
Ethanol is oxidized with Pyridinium Chlorochromate ($\ce{PCC}$) to halt at the aldehyde stage, yielding Ethanal.
Ethanal is treated with dilute $\ce{NaOH}$ (Aldol addition) then heated ($\Delta$). The dimerization and dehydration form the 4-carbon unsaturated aldehyde, But-2-enal.
But-2-enal is completely reduced using Hydrogen gas over a Nickel catalyst ($\ce{H2 / Ni}$). Both the double bond and the aldehyde are reduced, yielding Butan-1-ol.
The primary alcohol is reacted with Phosphorus Tribromide ($\ce{PBr3}$) or $\ce{HBr}$ to substitute the hydroxyl group, yielding 1-Bromobutane.
3 Convert Benzene to m-Fluoronitrobenzene
Benzene is nitrated using a mixture of concentrated $\ce{HNO3}$ and $\ce{H2SO4}$ at 330 K to yield Nitrobenzene, installing a meta-directing group.
Nitrobenzene requires vigorous conditions (fuming $\ce{HNO3}$, conc. $\ce{H2SO4}$, high heat) to nitrate again. The electrophile attacks the meta position, yielding m-Dinitrobenzene.
To differentiate the groups, one nitro group is selectively reduced using Ammonium hydrogen sulfide ($\ce{NH4HS}$) or $\ce{Na2S}$. This yields m-Nitroaniline.
m-Nitroaniline is diazotized with cold $\ce{NaNO2 / HCl}$ (273 K) to convert the amino group into the excellent diazonium leaving group, forming m-Nitrobenzene diazonium chloride.
The diazonium salt is treated with Fluoroboric acid ($\ce{HBF4}$) to precipitate the fluoroborate salt. Heating this dry salt decomposes it, yielding m-Fluoronitrobenzene.
4 Convert 1-Bromopropane to 2-Methylpropan-1-ol
To shift functionalization to the middle carbon, 1-Bromopropane is heated with alcoholic $\ce{KOH}$. The $\beta$-elimination forms Propene.
Propene is reacted with $\ce{HBr}$. The electrophilic addition places the bromine on the secondary carbon, yielding 2-Bromopropane.
2-Bromopropane is heated with alcoholic $\ce{KCN}$. The nucleophilic substitution creates a branch and extends the chain, yielding 2-Methylpropanenitrile (Isopropyl cyanide).
The nitrile is completely hydrolyzed by boiling with dilute mineral acid ($\ce{H3O+}$), converting the $-\ce{CN}$ to a $-\ce{COOH}$, yielding 2-Methylpropanoic acid (Isobutyric acid).
The carboxylic acid is strongly reduced using Lithium Aluminum Hydride ($\ce{LiAlH4}$), converting the carboxyl group to a primary alcohol, yielding 2-Methylpropan-1-ol.
5 Convert Benzene to p-Iodotoluene
Benzene is reacted with Methyl chloride and $\ce{AlCl3}$. This places a methyl group on the ring, yielding Toluene, an ortho/para-directing activator.
Toluene is nitrated ($\ce{HNO3 / H2SO4}$). Due to steric hindrance at the ortho position, the para-isomer predominates. We isolate p-Nitrotoluene.
The nitro group is reduced to a primary amine using Tin and Hydrochloric acid ($\ce{Sn / HCl}$). This yields p-Toluidine (p-Methylaniline).
p-Toluidine is diazotized with cold $\ce{NaNO2 / HCl}$ (273K). This converts the amino group into a diazonium group, forming p-Toluenediazonium chloride.
The diazonium salt is simply warmed with an aqueous solution of Potassium Iodide ($\ce{KI}$). The iodide ion nucleophilically replaces the diazonium group, yielding p-Iodotoluene.
6 Convert Propan-1-ol to 2-Methylbutan-2-ol
Propan-1-ol is heated with concentrated $\ce{H2SO4}$ at 443 K. The elimination of water forms Propene.
Propene is passed through water in the presence of dilute acid ($\ce{H2O / H+}$). Electrophilic addition yields the secondary alcohol, Propan-2-ol.
Propan-2-ol is oxidized using acidified $\ce{K2Cr2O7}$ or $\ce{PCC}$. The secondary alcohol cleanly oxidizes to a ketone, yielding Propanone (Acetone).
Propanone is reacted with Ethylmagnesium bromide ($\ce{CH3CH2MgBr}$) in dry ether. The nucleophilic ethyl group attacks the carbonyl carbon, forming a tertiary magnesium alkoxide intermediate.
The alkoxide intermediate is treated with dilute acid ($\ce{H3O+}$). Protonation of the oxygen yields the branched tertiary alcohol, 2-Methylbutan-2-ol.
7 Convert Ethene to But-2-yne
Ethene reacts with Bromine in a non-polar solvent ($\ce{Br2/CCl4}$). The anti-addition across the double bond yields the vicinal dihalide, 1,2-Dibromoethane.
The vicinal dihalide is heated with strong base Sodium amide ($\ce{NaNH2}$) in liquid ammonia. Two successive elimination reactions remove two moles of $\ce{HBr}$, yielding Ethyne (Acetylene).
Ethyne is treated with another mole of Sodium amide ($\ce{NaNH2}$). The strongly basic amide ion extracts one weakly acidic terminal proton, forming Sodium acetylide ($\ce{HC\equiv CNa}$).
Sodium acetylide is reacted with Methyl iodide ($\ce{CH3I}$). The $S_N2$ substitution extends the chain by one carbon, yielding Propyne.
Propyne still has one acidic terminal proton. It is reacted with $\ce{NaNH2}$ to form sodium propynide, which is immediately reacted with another mole of Methyl iodide ($\ce{CH3I}$), yielding the internal alkyne, But-2-yne.
8 Convert Phenol to p-Hydroxyazobenzene (Orange Dye)
Phenol is heated with Zinc dust. The zinc acts as a reducing agent, extracting the oxygen to form Zinc oxide, leaving pure Benzene.
Benzene is nitrated using a mixture of concentrated $\ce{HNO3}$ and $\ce{H2SO4}$ at 330 K. The electrophilic attack forms Nitrobenzene.
Nitrobenzene is reduced to a primary amine using active metal and acid, specifically Tin and Hydrochloric acid ($\ce{Sn / HCl}$). This yields Aniline.
Aniline is treated with a cold, aqueous solution of Sodium Nitrite and Hydrochloric acid ($\ce{NaNO2 + HCl}$) at 0-5°C. This produces the highly reactive electrophile, Benzene diazonium chloride.
The diazonium salt is reacted with another molecule of Phenol in a mildly alkaline medium (pH 9-10). The diazonium ion attacks the para-position of the activated phenoxide ring, forming the extended conjugated azo system, p-Hydroxyazobenzene.
9 Convert Toluene to 1-Phenylethanol
Toluene is reacted with Chlorine gas under UV light ($\ce{Cl2/h\nu}$). This directs the free-radical substitution exclusively to the methyl group, producing Benzyl chloride.
Benzyl chloride is boiled with aqueous Potassium Hydroxide ($\ce{KOH(aq)}$). The chloride is displaced by a hydroxyl group via $S_N2$ mechanism, yielding Benzyl alcohol.
Benzyl alcohol is oxidized using Pyridinium Chlorochromate ($\ce{PCC}$) in dichloromethane. This stops the oxidation exactly at the aldehyde stage, yielding Benzaldehyde.
Benzaldehyde is reacted with Methylmagnesium bromide ($\ce{CH3MgBr}$) in dry ether. The nucleophilic methyl carbanion attacks the carbonyl carbon, forming a magnesium alkoxide complex.
The alkoxide intermediate is immediately hydrolyzed with dilute acid ($\ce{H3O+}$). Protonation of the oxygen yields the secondary alcohol, 1-Phenylethanol.
10 Convert Calcium Carbide to Butan-1-ol
Calcium carbide ($\ce{CaC2}$) reacts with water at room temperature, releasing Ethyne (Acetylene) gas.
Ethyne is hydrated in the presence of Mercuric sulfate and dilute Sulfuric acid ($\ce{HgSO4 / H2SO4}$). The addition of water forms vinyl alcohol, which tautomerizes instantly into Ethanal.
Ethanal is treated with dilute $\ce{NaOH}$. Two molecules condense (Aldol addition) to form the $\beta$-hydroxyaldehyde, 3-Hydroxybutanal.
Heating 3-Hydroxybutanal causes E1cB elimination of water. This creates a highly stable, conjugated $\alpha,\beta$-unsaturated aldehyde, But-2-enal.
But-2-enal is completely reduced using Hydrogen gas over a Nickel or Platinum catalyst ($\ce{H2 / Ni}$). Both the double bond and the carbonyl group are hydrogenated, yielding the primary alcohol, Butan-1-ol.
11 Convert Benzene to m-Bromobenzyl Alcohol
Benzene is reacted with Methyl chloride and anhydrous $\ce{AlCl3}$. This places a methyl group on the ring, yielding Toluene.
Toluene is oxidized with acidified Potassium Permanganate ($\ce{KMnO4 / H+}$, heat). The methyl group is fully oxidized to a carboxyl group, yielding Benzoic acid. The carboxyl group is strongly meta-directing.
Benzoic acid is reacted with Bromine and Iron(III) bromide catalyst ($\ce{Br2 / FeBr3}$). The electrophile is directed to the meta position, yielding m-Bromobenzoic acid.
Direct reduction of a carboxylic acid is difficult and often incompatible with other halogens. The acid is first converted to a highly reactive acid chloride using Thionyl chloride ($\ce{SOCl2}$), yielding m-Bromobenzoyl chloride.
The acid chloride is smoothly reduced using Sodium Borohydride ($\ce{NaBH4}$) or mild Lithium Aluminum Hydride ($\ce{LiAlH4}$). This reduces the carbonyl group down to a primary alcohol, yielding m-Bromobenzyl alcohol.
12 Convert Benzene to p-Nitroaniline
Benzene is treated with a nitrating mixture ($\ce{HNO3 / H2SO4}$) at 330K to yield Nitrobenzene.
Nitrobenzene is fully reduced using Tin and Hydrochloric acid ($\ce{Sn / HCl}$) to form Aniline, which acts as a strong ortho/para director for the second substituent.
Aniline is highly susceptible to oxidation during subsequent nitration. It is protected by reacting it with Acetic anhydride ($\ce{Ac2O}$) in pyridine, forming Acetanilide. This also mitigates its activating power.
Acetanilide is nitrated using a cold mixture of $\ce{HNO3 / H2SO4}$. Due to the steric bulk of the acetyl group, the electrophile attacks the para position exclusively, yielding p-Nitroacetanilide.
The acetyl protecting group is removed by boiling with dilute aqueous acid or base ($\ce{H3O+}$ or $\ce{OH-}$, $\Delta$). This restores the primary amine group, yielding pure p-Nitroaniline.
13 Convert Benzene to 1,3,5-Tribromobenzene
Benzene is treated with a nitrating mixture ($\ce{HNO3 / H2SO4}$) at 330 K, yielding Nitrobenzene.
Nitrobenzene is reduced to an amine using active metal and acid ($\ce{Sn / HCl}$). The product is Aniline, which highly activates the aromatic ring.
Aniline is treated with aqueous Bromine (Bromine water). The highly activated ring undergoes rapid electrophilic substitution at all free ortho and para positions, precipitating 2,4,6-Tribromoaniline.
The amino group must now be removed to leave only the bromines in a meta relationship. The tribromoaniline is diazotized using cold $\ce{NaNO2 / HCl}$ at 273 K, yielding 2,4,6-Tribromobenzene diazonium chloride.
The diazonium salt is reacted with a mild reducing agent, Hypophosphorous acid ($\ce{H3PO2}$) and water. This completely removes the diazonium group, replacing it with a hydrogen atom, yielding 1,3,5-Tribromobenzene.
14 Convert Methanol to Butan-2-ol
Methanol is converted to Chloromethane by reacting with Phosphorus Pentachloride ($\ce{PCl5}$) or Thionyl chloride ($\ce{SOCl2}$).
Chloromethane is heated with alcoholic $\ce{KCN}$. The $S_N2$ substitution extends the chain to 2 carbons, forming Acetonitrile (Ethanenitrile).
Acetonitrile is reacted with Ethylmagnesium bromide ($\ce{CH3CH2MgBr}$). The nucleophilic ethyl group attacks the nitrile carbon, breaking the triple bond to form an unstable Imine magnesium salt.
The imine salt is boiled with dilute mineral acid ($\ce{H3O+}$). The nitrogen is expelled as ammonia, yielding the 4-carbon ketone, Butan-2-one.
Butan-2-one is reduced using Sodium Borohydride ($\ce{NaBH4}$). The hydride attacks the carbonyl, forming a secondary alcohol: Butan-2-ol.
15 Convert Phenol to p-Methoxybenzyl Alcohol
Phenol is reacted with aqueous Sodium Hydroxide ($\ce{NaOH}$) to form Sodium phenoxide, setting up the molecule for Williamson ether synthesis.
Sodium phenoxide is reacted with Methyl iodide ($\ce{CH3I}$). The phenoxide nucleophile displaces the iodide, yielding Methoxybenzene (Anisole). This protects the oxygen and makes the ring highly ortho/para directing.
Anisole is reacted with Methyl chloride ($\ce{CH3Cl}$) and anhydrous $\ce{AlCl3}$. The methyl electrophile attacks the less sterically hindered para position, yielding p-Methoxytoluene.
p-Methoxytoluene is treated with Chlorine gas under UV light ($\ce{Cl2 / h\nu}$). Substitution occurs selectively at the benzylic position (free radical mechanism), yielding p-Methoxybenzyl chloride.
The benzylic chloride is boiled with aqueous Potassium Hydroxide ($\ce{KOH(aq)}$). $S_N2$ substitution replaces the chloride with a hydroxyl group, yielding p-Methoxybenzyl alcohol.
16 Convert Toluene to m-Aminobenzyl Alcohol
To direct an incoming group to the meta position, the methyl group must be oxidized. Toluene is vigorously oxidized with acidified Potassium Permanganate ($\ce{KMnO4 / H+}$, heat) to yield Benzoic acid.
Benzoic acid is nitrated ($\ce{HNO3 / H2SO4}$). The carboxyl group strongly directs the electrophile to the meta position, yielding m-Nitrobenzoic acid.
The carboxylic acid is converted to an acid chloride using Thionyl chloride ($\ce{SOCl2}$). This activates the carbonyl group for easy reduction, yielding m-Nitrobenzoyl chloride.
The acid chloride is reduced with Sodium Borohydride ($\ce{NaBH4}$). This mild reducing agent converts the acid chloride to a primary alcohol while leaving the nitro group completely unaffected, yielding m-Nitrobenzyl alcohol.
The nitro group is finally reduced to an amine using Tin and Hydrochloric acid ($\ce{Sn / HCl}$). This yields the target product, m-Aminobenzyl alcohol.
17 Convert Propene to Propan-2-amine
Propene is reacted with $\ce{HBr}$. The electrophilic addition places the bromine on the secondary carbon, yielding 2-Bromopropane.
2-Bromopropane is heated with alcoholic $\ce{KCN}$. The $S_N2$ substitution replaces the bromine, yielding 2-Methylpropanenitrile (Isopropyl cyanide).
The nitrile is completely hydrolyzed by boiling with dilute mineral acid ($\ce{H3O+}$). The $-\ce{CN}$ converts to $-\ce{COOH}$, yielding 2-Methylpropanoic acid.
The acid is treated with Ammonia ($\ce{NH3}$) and heated strongly. Dehydration of the ammonium salt yields 2-Methylpropanamide.
The amide undergoes Hoffmann bromamide degradation with Bromine and $\ce{KOH}$. The carbonyl carbon is completely removed, yielding the secondary branched primary amine, Propan-2-amine (Isopropylamine).
18 Convert Methane to Ethanol
Methane is reacted with Chlorine gas under UV light ($\ce{Cl2 / h\nu}$). Free-radical substitution yields Chloromethane.
Chloromethane is reacted with Sodium metal in dry ether. The symmetrical coupling of two methyl radicals yields the 2-carbon alkane, Ethane.
Ethane is reactivated using Chlorine gas under UV light ($\ce{Cl2 / h\nu}$). Substitution yields Chloroethane.
Chloroethane is heated with an excess of alcoholic Ammonia ($\ce{NH3}$). Nucleophilic substitution displaces the chloride, yielding the primary amine, Ethanamine.
Ethanamine is reacted with Nitrous acid ($\ce{HNO2}$ from $\ce{NaNO2 + HCl}$). The highly unstable aliphatic diazonium intermediate immediately decomposes with water, yielding Ethanol and nitrogen gas.
19 Convert Benzene to p-Fluorobenzoic Acid
Benzene is reacted with $\ce{CH3Cl / AlCl3}$ to place an ortho/para directing methyl group on the ring, yielding Toluene.
Toluene is nitrated ($\ce{HNO3 / H2SO4}$). Due to steric effects, the para isomer is isolated as the major product, yielding p-Nitrotoluene.
The nitro group is reduced to an amine using $\ce{Sn / HCl}$. This yields p-Toluidine (p-Methylaniline).
p-Toluidine is diazotized ($\ce{NaNO2 / HCl}$, 273K) and subsequently reacted with Fluoroboric acid ($\ce{HBF4}$). Heating the resulting diazonium fluoroborate salt yields p-Fluorotoluene.
The methyl side-chain is oxidized using acidified Potassium Permanganate ($\ce{KMnO4 / H+}$, heat). The $-\ce{CH3}$ group converts directly into a $-\ce{COOH}$ group, yielding p-Fluorobenzoic acid.
20 Convert Benzene to Aspirin (Acetylsalicylic Acid)
Benzene is reacted with Oleum (fuming sulfuric acid, $\ce{H2S2O7}$). The electrophilic $\ce{SO3}$ attacks the ring to form Benzene sulfonic acid.
Benzene sulfonic acid is fused with solid $\ce{NaOH}$ at high temperatures (600 K), followed immediately by acidification ($\ce{H+}$). This replaces the sulfonic acid group with a hydroxyl group, yielding Phenol.
Phenol is reacted with aqueous Sodium Hydroxide ($\ce{NaOH}$) to form Sodium phenoxide. This drastically activates the ring for the upcoming weak electrophile.
Sodium phenoxide is heated with Carbon dioxide ($\ce{CO2}$) at 400 K and 4-7 atm pressure. The electrophile attacks the ortho position. Subsequent acidification ($\ce{H+}$) yields 2-Hydroxybenzoic acid (Salicylic acid).
Salicylic acid is treated with Acetic anhydride ($\ce{(CH3CO)2O}$) in the presence of an acid catalyst ($\ce{H+}$). This acetylates the phenolic $-\ce{OH}$ group, yielding Acetylsalicylic acid (Aspirin).
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