Grignard Reagents and Carbon–Carbon Bond Formation
A concise revision guide to lengthening a carbon chain: Grignard reagents RMgX made from a halogenoalkane and magnesium in dry ether, their reactions with carbon dioxide to give carboxylic acids and with aldehydes and ketones to give primary, secondary and tertiary alcohols, and the nitrile route from a halogenoalkane with potassium cyanide.
Grignard Reagents: Adding a Carbon
Choose a step to watch ethylmagnesium bromide attack carbon dioxide and the dilute-acid work-up give propanoic acid, one carbon longer.
© Dr. Mohammed Al-Fatah – onlinelearningsystem.net
Before You Start
Every reaction on this page is one you have met before. This page puts them to a new use: making the carbon chain longer.
- A halogenoalkane has a δ+ carbon that nucleophiles attack: nucleophilic substitution. See Nucleophilic Substitution Reactions.
- A carbonyl carbon is δ+ too, so HCN adds across C=O: nucleophilic addition. See Reduction and Nucleophilic Addition.
- Nitriles are reduced to primary amines, R–C≡N + 4[H] → R–CH₂NH₂: see Preparing Amines.
- A benzene ring gains a carbon group by Friedel–Crafts alkylation or acylation: see Friedel–Crafts Alkylation and Acylation.
- The functional group tests and the spectra that identify the products: Identifying Functional Groups by Chemical Tests and Deducing Formulae from Analytical Data.
Why Chain Length Matters
Most reactions in organic chemistry change the functional group but keep the carbon skeleton. A target molecule often has more carbons than the starting material, so one step must make a new C–C bond.
- Converting a group (alcohol → aldehyde → acid, or halide → alcohol → aldehyde) never changes the number of carbons.
- Adding one carbon needs a carbon nucleophile: the cyanide ion, CN⁻, or the carbon of a Grignard reagent, RMgX.
- Adding a carbon chain to a benzene ring needs an electrophilic carbon: Friedel–Crafts alkylation or acylation with an AlCl₃ catalyst.
- Planning when to add the carbon is part of every route: see Planning a Synthetic Route.
The three ways to add a carbon atom, the conditions for each and what the new carbon can be turned into afterwards.
Exam focus: Count the carbons in the starting material and in the target before you plan anything. A difference of one carbon points to a nitrile or a Grignard step.
The Nitrile Route from a Halogenoalkane
The cyanide ion is a nucleophile with its lone pair on carbon. It substitutes the halogen of a halogenoalkane, and the new carbon arrives already bonded to the chain.
| Detail | |
|---|---|
| reagent | potassium cyanide, KCN |
| conditions | dissolved in ethanol, heated under reflux |
| equation | CH₃CH₂Br + CN⁻ → CH₃CH₂CN + Br⁻ (bromoethane → propanenitrile) |
| type of reaction | nucleophilic substitution |
| carbons | two in bromoethane, three in propanenitrile: one added |
- Ethanol is the solvent: in water the hydroxide ions present would compete and give the alcohol.
- Name the nitrile from the whole chain including the C≡N carbon: CH₃CH₂CN is propanenitrile, not ethyl cyanide.
- The C≡N group is then a branching point: it can become an amine or a carboxylic acid (below).
Remember: KCN in ethanol under reflux adds one carbon. The same halogenoalkane with ammonia or hydroxide keeps the chain length.
Nitriles from Aldehydes and Ketones
Hydrogen cyanide adds across the C=O bond of an aldehyde or ketone. The product is a hydroxynitrile (cyanohydrin), again with one carbon more.
| Detail | |
|---|---|
| reagent | HCN, generated from KCN with a little acid (the CN⁻ ion is the nucleophile) |
| conditions | room temperature, in solution; HCN is toxic, so work in a fume cupboard |
| equation | CH₃CHO + HCN → CH₃CH(OH)CN (ethanal → 2-hydroxypropanenitrile) |
| with a ketone | CH₃COCH₃ + HCN → (CH₃)₂C(OH)CN (propanone → 2-hydroxy-2-methylpropanenitrile) |
| type of reaction | nucleophilic addition |
- The OH and the C≡N finish on the same carbon, the old carbonyl carbon.
- Hydrolysing the nitrile group gives a 2-hydroxycarboxylic acid: CH₃CH(OH)CN → CH₃CH(OH)COOH, 2-hydroxypropanoic acid.
- The mechanism is on the carbonyl page, Reduction and Nucleophilic Addition.
Quick Check: Hydroxynitriles from New Carbonyl Compounds
Pick the one accurate statement in each set.
What the Nitrile Becomes
A nitrile is rarely the target. Its C≡N group is converted in one more step into an amine or a carboxylic acid, each keeping the extra carbon.
| Conversion | Reagents and conditions | Equation |
|---|---|---|
| reduction to a primary amine | LiAlH₄ in dry ether, or H₂ with a nickel catalyst | CH₃CH₂CN + 4[H] → CH₃CH₂CH₂NH₂ (propylamine) |
| acid hydrolysis to a carboxylic acid | dilute hydrochloric acid, heat under reflux | CH₃CH₂CN + 2H₂O + HCl → CH₃CH₂COOH + NH₄Cl (propanoic acid) |
| alkaline hydrolysis to the carboxylate | sodium hydroxide solution, heat under reflux, then add dilute acid | CH₃CH₂CN + H₂O + NaOH → CH₃CH₂COONa + NH₃; then CH₃CH₂COO⁻ + H⁺ → CH₃CH₂COOH |
- The nitrile carbon becomes the CH₂ next to nitrogen in the amine, or the COOH carbon in the acid.
- Acid hydrolysis gives the acid and an ammonium salt; alkaline hydrolysis gives the salt of the acid and ammonia gas.
- In a route, write the hydrolysis as a single step with its reagent and conditions.
Both nitrile routes as one scheme: bromoethane to propanenitrile and on to propylamine or propanoic acid; ethanal to 2-hydroxypropanenitrile and on to 2-hydroxypropanoic acid.
The nitrile as a branching point: reduce it to the amine, or hydrolyse it to the acid with acid or with alkali.
Exam focus: Two steps add one carbon and set the group: halogenoalkane → nitrile (KCN, ethanol, reflux) → acid (dilute HCl, reflux) or amine (LiAlH₄ or H₂/Ni). Give both reagents and both conditions.
Check: The Nitrile Routes
Give the reagents and conditions for turning a halogenoalkane or a carbonyl compound into a nitrile, count the carbons, and choose the step that converts the nitrile into an amine or an acid.
Quick Check: Choosing the First Step
Count the carbons at both ends of each route, then choose the first step.
Grignard Reagents: Preparation
A Grignard reagent, RMgX, is made by reacting a halogenoalkane with magnesium. Its carbon is bonded to a metal, so for once the carbon is δ− and acts as a nucleophile.
| Detail | |
|---|---|
| reagents | bromoethane and magnesium turnings; a crystal of iodine starts the reaction |
| solvent | dry ethoxyethane (dry ether); every piece of apparatus dried |
| conditions | heated under reflux, with no water present |
| equation | CH₃CH₂Br + Mg → CH₃CH₂MgBr (ethylmagnesium bromide) |
| polarity | C–Mg: carbon δ−, magnesium δ+ (magnesium is far less electronegative than carbon) |
- Water destroys the reagent: CH₃CH₂MgBr + H₂O → CH₃CH₃ + Mg(OH)Br. Hence dry ether and dry glassware.
- The δ− carbon attacks δ+ carbon atoms: the carbon of CO₂ and the carbonyl carbon of aldehydes and ketones.
- Every product has the two carbons of the ethyl group plus the carbons of the molecule added.
Making ethylmagnesium bromide, its attack on carbon dioxide and the dilute-acid work-up to propanoic acid, with the new C–C bond boxed.
Exam focus: Three conditions earn the marks: dry ether as solvent, anhydrous (no water) and heat under reflux. Then state that the carbon of the Grignard reagent is δ− and nucleophilic.
Grignard Reagents with Carbon Dioxide: an Acid One Carbon Longer
Bubbling or adding solid carbon dioxide into the Grignard reagent in dry ether forms a carboxylate salt. Dilute acid then releases the carboxylic acid.
- Write the reaction in two stages: dry ether and CO₂ first, dilute acid second. The acid is not present during the addition because it would destroy the reagent.
- Magnesium ends up as Mg²⁺ and Br⁻ in the aqueous layer; the acid is extracted into the ether layer.
Grignard Reagents with Aldehydes and Ketones: Alcohols
With a carbonyl compound the Grignard carbon bonds to the carbonyl carbon and the oxygen becomes O⁻. Dilute acid then gives an alcohol. The class of alcohol depends on the carbonyl compound used.
| Carbonyl compound | Product after dilute acid | Class of alcohol |
|---|---|---|
| methanal, HCHO | propan-1-ol, CH₃CH₂CH₂OH | primary |
| ethanal, CH₃CHO (any other aldehyde) | butan-2-ol, CH₃CH₂CH(OH)CH₃ | secondary |
| propanone, CH₃COCH₃ (any ketone) | 2-methylbutan-2-ol, CH₃CH₂C(OH)(CH₃)₂ | tertiary |
- Methanal has two hydrogens on its carbonyl carbon, so the new carbon keeps two hydrogens: a primary alcohol.
- Other aldehydes leave one hydrogen on that carbon: a secondary alcohol. Ketones leave none: a tertiary alcohol.
- The carbonyl carbon becomes the carbon that carries the OH group; the Grignard chain is attached to it.
- Equation for ethanal: CH₃CH₂MgBr + CH₃CHO → CH₃CH₂CH(OMgBr)CH₃, then + H⁺ (dilute acid) → CH₃CH₂CH(OH)CH₃ + Mg²⁺ + Br⁻.
Ethylmagnesium bromide with methanal, ethanal and propanone, then dilute acid: a primary, a secondary and a tertiary alcohol with the carbonyl carbon marked.
The conditions, the dry-ether warning and the four products of ethylmagnesium bromide in one poster.
Remember: Methanal → primary, other aldehydes → secondary, ketones → tertiary. The work-up with dilute acid is a separate step: always write it.
Quick Check: Working Back from a Target Alcohol
Split the target at the carbon that carries the OH group.
Worked Example: Propanoic Acid from Bromoethane in Two Ways
Both C–C bond-forming methods take bromoethane (two carbons) to propanoic acid (three carbons). Compare them.
Route 1. Nitrile: CH₃CH₂Br + KCN in ethanol under reflux → CH₃CH₂CN; then dilute HCl under reflux → CH₃CH₂COOH + NH₄Cl. Two reactions, aqueous conditions, KCN is highly toxic.
Route 2. Grignard: CH₃CH₂Br + Mg in dry ether under reflux → CH₃CH₂MgBr; then CO₂ in dry ether, then dilute acid → CH₃CH₂COOH. Two reactions, strictly anhydrous, flammable ether.
Exam focus: A question that says “in two steps” expects one of these routes. State the type of reaction for each step: nucleophilic substitution then hydrolysis, or formation of a Grignard reagent then its reaction with CO₂.
Adding Carbons to a Benzene Ring
A benzene ring is attacked by electrophiles, not nucleophiles, so a carbon chain is added to it with a δ+ carbon: Friedel–Crafts alkylation and acylation (Friedel–Crafts Alkylation and Acylation).
| Reaction | Reagents and conditions | Product |
|---|---|---|
| alkylation | a halogenoalkane such as chloroethane with an AlCl₃ catalyst, heat under reflux | ethylbenzene, C₆H₅CH₂CH₃ |
| acylation | an acyl chloride such as ethanoyl chloride with an AlCl₃ catalyst, heat under reflux | phenylethanone, C₆H₅COCH₃ |
- The catalyst AlCl₃ polarises the C–Cl bond so the carbon becomes a strong enough electrophile for the ring.
- Acylation adds one acyl group cleanly; the ketone made can be reduced to an alcohol or used in a nitrile step.
- The mechanism and the reasons for choosing acylation are on Friedel–Crafts Alkylation and Acylation; this page only places the step in a route.
Remember: Chain: cyanide or Grignard adds a carbon by nucleophilic attack. Ring: Friedel–Crafts adds a carbon by electrophilic substitution with an AlCl₃ catalyst.
Check: Grignard Reagents and Routes
Choose the reagent that adds a carbon to a chain or a ring, give its conditions, and work out the product and its class from the carbonyl compound used.
Common Exam Points
- Halogenoalkane + KCN in ethanol under reflux → nitrile, one carbon longer: CH₃CH₂Br + CN⁻ → CH₃CH₂CN + Br⁻ (nucleophilic substitution).
- Aldehyde or ketone + HCN (with KCN) → hydroxynitrile by nucleophilic addition: CH₃CHO + HCN → CH₃CH(OH)CN.
- Nitrile + 4[H] (LiAlH₄ in dry ether, or H₂ with a nickel catalyst) → primary amine; nitrile + dilute HCl under reflux → carboxylic acid + NH₄⁺.
- Grignard reagent: RBr + Mg in dry ether under reflux → RMgBr; the C–Mg bond has carbon δ−. Water destroys it.
- RMgBr + CO₂ in dry ether, then dilute acid → RCOOH (one carbon longer); + methanal → primary, + other aldehydes → secondary, + ketones → tertiary alcohol.
- Friedel–Crafts alkylation or acylation adds a carbon group to a benzene ring with an AlCl₃ catalyst: electrophilic substitution.
- Always count carbons: a target with one more carbon than the start needs a C–C bond-forming step somewhere in the route.
FAQs
Use these quick answers to check why a synthesis sometimes needs an extra carbon, how the nitrile route adds one from a halogenoalkane or a carbonyl compound, and how Grignard reagents do the same job.
Why does chain length matter when I plan a synthesis?
Most reactions keep the carbon skeleton and only change the functional group. If the target has more carbon atoms than the starting material, one step must form a new carbon–carbon bond, and the nitrile route is the simplest way to add exactly one carbon.
How does the nitrile route add one carbon to a halogenoalkane?
Heat the halogenoalkane under reflux with potassium cyanide in ethanol: bromoethane gives propanenitrile, CH₃CH₂CN, by nucleophilic substitution. Reduce the nitrile with hydrogen and a nickel catalyst (or LiAlH₄) to propylamine, or heat it with dilute hydrochloric acid to hydrolyse it to propanoic acid.
How does HCN add a carbon to an aldehyde or ketone?
The cyanide ion attacks the δ+ carbonyl carbon in a nucleophilic addition, using KCN with a little acid to supply HCN. Ethanal gives 2-hydroxypropanenitrile, CH₃CH(OH)CN, and hydrolysis of the nitrile with dilute acid then gives the 2-hydroxy acid, 2-hydroxypropanoic acid (lactic acid).
Why must everything be completely dry when I make a Grignard reagent?
The carbon bonded to magnesium is δ− and strongly basic, so water protonates it: CH₃CH₂MgBr + H₂O → CH₃CH₃ + Mg(OH)Br, destroying the reagent.
The magnesium turnings, bromoethane and the ethoxyethane solvent must all be dry, and the flask is fitted with a dry condenser.
Which alcohol do I get when a Grignard reagent reacts with a carbonyl compound?
Count the carbon groups on the carbonyl carbon.
Methanal gives a primary alcohol (ethylmagnesium bromide gives propan-1-ol), any other aldehyde gives a secondary alcohol (ethanal gives butan-2-ol) and a ketone gives a tertiary alcohol (propanone gives 2-methylbutan-2-ol). Dilute acid in the work-up protonates the alkoxide.
Copyright notice: This OLS revision content, including the explanations, layout, diagrams, tables and embedded learning structure, is authored for Online Learning System by Dr. Mohammed Al-Fatah. It may not be copied, reproduced, redistributed or adapted without written permission.
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