Aldehydes, Ketones and Carboxylic Acids · Lesson 2 of 15
Preparing Aldehydes Selectively
“Choose oxidation, reduction and aromatic formylation routes while controlling overreaction.”
• Select conditions that stop primary alcohol oxidation at an aldehyde. • Explain Rosenmund, Stephen and controlled DIBAL-H routes. • Predict carbonyl products of ozonolysis and alkyne hydration. • Compare routes from alkylbenzenes to aromatic aldehydes.
An aldehyde sits between an alcohol and an acid
Oxidation of a primary alcohol removes two hydrogen equivalents to form RCHO; further oxidation produces RCOOH. This makes selectivity the main problem in aldehyde preparation. A strongly oxidising aqueous mixture may not stop where desired. Controlled oxidation, for example pyridinium chlorochromate (PCC) in a suitable dry medium, allows many primary alcohols to give aldehydes. In contrast, hot acidified dichromate under reflux commonly carries the product onward to acid. A reagent must be chosen for the substrate, including any other functional groups.
Alcohol vapours passed over heated copper, commonly around 573 K in this model, can undergo dehydrogenation: RCH₂OH → RCHO + H₂. Secondary alcohols analogously form ketones. This removes hydrogen without introducing oxygen. The method is useful for volatile substrates and should not be confused with acid-catalysed dehydration, which removes water to form an alkene.
Create carbonyl groups by breaking or hydrating unsaturation
In reductive ozonolysis, cleave the alkene C=C and make each former alkene carbon a carbonyl carbon. Treatment with O₃ followed by Zn/H₂O preserves aldehydes that form. An alkene carbon that carried H can give an aldehyde; one bearing two carbon groups gives a ketone. But-2-ene gives two ethanal molecules. A terminal CH₂ end gives methanal. Oxidative work-up may oxidise aldehydes further, so the work-up belongs to the reaction specification.
Acidic hydration of ethyne with HgSO₄/H₂SO₄ initially gives an enol, CH₂=CHOH, which rearranges by keto–enol tautomerism to ethanal. Other ordinary alkynes give ketones under this hydration method; propyne gives propanone. Unsymmetrical internal alkynes can give a mixture. The enol and carbonyl structures differ in both proton position and π-bond position; hydration does not leave an ordinary stable vinyl alcohol as the final product.
Problem
Convert hexan-1-ol to hexanal, allyl alcohol to prop-2-enal, and but-2-ene to ethanal.
- 1.For hexan-1-ol use controlled PCC oxidation to CH₃(CH₂)₄CHO. The chain retains six carbons. Avoid an aqueous excess oxidant that would give hexanoic acid.
- 2.For CH₂=CHCH₂OH use a suitable controlled oxidant such as PCC to give CH₂=CHCHO while retaining C=C.
- 3.For but-2-ene use O₃ followed by Zn/H₂O. Cleaving its central C=C gives 2CH₃CHO; using only an alcohol oxidant would not perform that bond cleavage.
Reduce an acid derivative without continuing to an alcohol
The Rosenmund reaction hydrogenates an acyl chloride over moderated palladium on barium sulphate, Pd/BaSO₄: RCOCl + H₂ → RCHO + HCl. The moderated catalyst suppresses further hydrogenation. Benzoyl chloride gives benzaldehyde. Ordinary vigorous catalytic hydrogenation is not an interchangeable substitute. The route is not a general practical route to methanal from formyl chloride, which is unstable.
A nitrile already contains the required future carbonyl carbon. In Stephen reduction, SnCl₂/HCl reduces R–C≡N to an iminium salt; subsequent hydrolysis gives RCHO. Hydrolysis is essential because the reduction intermediate is nitrogen-containing. In a formal neutral representation, RCH=NH + H₂O → RCHO + NH₃; in acid, nitrogen leaves as ammonium. Do not confuse this partial reduction with complete nitrile reduction to RCH₂NH₂.
Diisobutylaluminium hydride, DIBAL-H, can partially reduce nitriles and esters under carefully controlled low-temperature, stoichiometric conditions, followed by hydrolysis. The intermediates are aluminium-bound, not simply bottles of free imine or aldehyde. For a nitrile, RCN gives RCHO; for an ester, RCOOR′ gives RCHO and the R′O fragment becomes R′OH on work-up. Excess reagent or unsuitable conditions can cause overreduction. LiAlH₄ generally carries an ester to primary alcohols and is not a selective replacement for this route.
Problem
Convert ethanenitrile and ethyl propanoate to their aldehydes.
- 1.CH₃CN has two carbons. Controlled DIBAL-H reduction and hydrolysis gives CH₃CHO, ethanal; the CN carbon is retained as CHO. Stephen reduction is another suitable route for the nitrile.
- 2.CH₃CH₂COOCH₂CH₃ contains a three-carbon acyl portion and a two-carbon alcohol portion. Controlled DIBAL-H followed by hydrolysis gives propanal from the acyl portion, with ethanol from the ethoxy portion. Counting all five carbons into one aldehyde would break the starting connectivity.
Stop benzylic oxidation at the aldehyde
Strong side-chain oxidation of toluene normally gives benzoic acid. In the Etard reaction, chromyl chloride, CrO₂Cl₂, in a nonaqueous medium forms a benzylic chromium complex; hydrolysis yields benzaldehyde. Another controlled route uses CrO₃ in acetic anhydride at 273–283 K to form benzylidene diacetate, C₆H₅CH(OCOCH₃)₂, which releases benzaldehyde on acidic hydrolysis. The protected intermediate prevents the intended product from being exposed directly to the original oxidation mixture.
Side-chain chlorination of toluene under light can form benzal chloride, C₆H₅CHCl₂. Hydrolysis with water on heating, around 373 K in the illustrative scheme, gives C₆H₅CHO + 2HCl. Benzyl chloride, C₆H₅CH₂Cl, would instead hydrolyse to benzyl alcohol; benzotrichloride, C₆H₅CCl₃, leads to acid on hydrolysis. The number of side-chain chlorines matters. Directing chlorination to the ring rather than the side chain would not accomplish this preparation.
Gattermann–Koch formylation introduces –CHO into a suitable arene using CO and HCl with the conventional anhydrous AlCl₃/CuCl catalyst system. Benzene gives benzaldehyde. It is an electrophilic aromatic substitution that replaces a ring H by CHO; it is not side-chain oxidation. Do not assume the method works unchanged on every strongly deactivated or catalyst-binding substituted arene.
Problem
Prepare 4-fluorobenzaldehyde from 4-fluorotoluene.
- 1.Target p-FC₆H₄CHO: only the side-chain CH₃ should change. Use controlled benzylic oxidation, such as the CrO₃/acetic anhydride route followed by acidic hydrolysis, or the Etard sequence.
- 2.The ring fluorine remains a substituent. Hot excess permanganate instead targets the acid stage, p-fluorobenzoic acid, so “oxidation” alone is an incomplete reagent answer.
Quick Quiz
Quiz
Which reagent commonly stops suitable primary alcohols at aldehydes?
Explanation: Controlled oxidation avoids routine overoxidation to acid.
What does CH₃CN give after selective partial reduction and hydrolysis?
Explanation: The nitrile carbon is retained; two carbons remain.
What is the carbonyl product of ethyne hydration with HgSO₄/H₂SO₄?
Explanation: The initially formed enol tautomerises to ethanal.
Which toluene chlorination product hydrolyses to benzaldehyde?
Explanation: The geminal dichloride forms C=O with retention of one benzylic H.
What is essential after DIBAL-H reduction of a nitrile?
Explanation: Work-up converts the bound nitrogen-containing intermediate to an aldehyde.
Practice Problems
- Give the balanced organic transformation for Rosenmund reduction of propanoyl chloride.
- Predict reductive ozonolysis products of CH₃CH=C(CH₃)₂.
- Why are benzyl chloride and benzal chloride not interchangeable in aldehyde synthesis?
- Contrast Stephen reduction, nitrile hydrolysis and complete nitrile reduction.
- Why would LiAlH₄ be a poor direct substitute for controlled DIBAL-H in converting an ester to an aldehyde?
CH₃CH₂COCl + H₂ → CH₃CH₂CHO + HCl over moderated Pd/BaSO₄. The carbon count stays at three and chlorine is replaced by hydrogen at the acyl carbon. Controlling the catalyst helps avoid reducing propanal further.
Key Takeaways
• Primary alcohol oxidation requires control to stop at an aldehyde. • Dehydrogenation removes H₂; dehydration removes H₂O. • Reductive ozonolysis maps each alkene carbon to a carbonyl carbon. • Ethyne hydration yields ethanal through an enol. • Rosenmund reduction uses a moderated catalyst. • Stephen and DIBAL-H routes require hydrolysis after partial reduction. • Aromatic aldehyde routes must prevent overoxidation of the side chain.