Difficulty: Intermediate | Prerequisites: Functional groups, nucleophilic addition basics, oxidation states of carbon.
Aldehydes and ketones are the two core carbonyl families in Organic Chemistry II. You need to know how each one is made (oxidation, reduction, Grignard routes) and what happens when a nucleophile attacks the carbonyl carbon. The same handful of reagents (NaBH4, LAH, Grignard, HCN, Wittig) come up repeatedly, so learning the pattern once covers most of the reactions on an exam.
Aldehyde (RCHO)
A carbonyl group bonded to at least one hydrogen. The carbonyl carbon is less sterically hindered than in a ketone, making it more reactive toward nucleophilic addition.
In simple terms: the carbonyl with a hydrogen on it, so nucleophiles reach it more easily.
Ketone (RCOR')
A carbonyl group flanked by two carbon-containing groups. More sterically hindered than an aldehyde, and the extra alkyl groups donate electron density, making the carbonyl slightly less electrophilic.
Think of it as: the "busier" carbonyl, harder to attack but still central to Org Chem II.
PCC (pyridinium chlorochromate)
A mild oxidising agent that converts a primary alcohol to an aldehyde without over-oxidising to the carboxylic acid. Works in anhydrous conditions (typically CH2Cl2).
In simple terms: the gentle oxidant that stops at the aldehyde stage.
Jones reagent (CrO3 / H2SO4 / acetone)
A strong oxidising agent. Oxidises primary alcohols all the way to carboxylic acids and secondary alcohols to ketones.
Think of it as: the heavy-duty oxidant that does not stop early.
DIBAL-H (diisobutylaluminium hydride)
A selective reducing agent. At low temperature it reduces an ester to an aldehyde (a two-electron reduction) rather than going further to the alcohol.
In simple terms: the cold, controlled reducer that lets you stop at the aldehyde.
LAH (lithium aluminium hydride, LiAlH4)
A powerful reducing agent that reduces carboxylic acids, esters, and amides all the way down to alcohols (or aldehydes when used with specific modifications such as LiAlH(OtBu)3).
Think of it as: the sledgehammer reducer, takes almost everything to an alcohol.
NaBH4 (sodium borohydride)
A milder reducing agent than LAH. Reduces aldehydes to primary alcohols and ketones to secondary alcohols, but does not reduce esters or carboxylic acids.
In simple terms: the selective reducer for plain carbonyls only.
Grignard reagent (RMgBr / RMgX)
An organomagnesium compound that acts as both a strong nucleophile and a strong base. Adds an alkyl or aryl group to the carbonyl carbon, extending the carbon chain.
Think of it as: the carbon nucleophile that builds new C-C bonds at a carbonyl.
Weinreb amide (N-methoxy-N-methylamide)
A modified amide that reacts with one equivalent of a Grignard or LAH to give a ketone or aldehyde, respectively, without over-addition. The chelation of the metal by the methoxy group stabilises the tetrahedral intermediate.
In simple terms: the "controlled" amide that lets you stop after one addition.
Acetal / Ketal
An acetal forms when an aldehyde reacts with two equivalents of alcohol under acid catalysis, replacing the C=O with two C-OR bonds plus loss of water. A ketal is the same product from a ketone. Both are stable under basic conditions and are widely used as carbonyl protecting groups.
Think of it as: a disguise for the carbonyl, removable later with aqueous acid.
Cyanohydrin
The product of HCN (or NaCN as a catalytic source) adding across a carbonyl. The result is an alcohol with a nitrile group on the same carbon.
In simple terms: adding -CN and -OH to what used to be the C=O.
Wolff-Kishner reduction
Converts a carbonyl (C=O) all the way to a methylene group (CH2) using hydrazine (NH2NH2) and strong base at high temperature. The oxygen is lost entirely.
Think of it as: erasing the carbonyl completely, leaving just C-H bonds.
Wittig reaction
Replaces a C=O with a C=C by reacting the carbonyl with a phosphorus ylide (PPh3=CHR). Produces an alkene and triphenylphosphine oxide as a by-product.
In simple terms: swapping a double bond to oxygen for a double bond to carbon.
Imine
Formed when a primary amine (RNH2) reacts with an aldehyde or ketone, losing water. Contains a C=N bond.
Think of it as: a nitrogen version of the carbonyl.
Enamine
Formed when a secondary amine (R2NH) reacts with a ketone, losing water. Contains a C=C bond adjacent to nitrogen. Enamines are useful nucleophiles for alpha-functionalisation.
In simple terms: the nitrogen-substituted alkene that lets you do chemistry at the alpha carbon.
There are three main routes to aldehydes. Each controls the oxidation state carefully so you do not overshoot to a carboxylic acid.
Oxidation of a 1° alcohol (2-electron oxidation)
Reagent: PCC (pyridinium chlorochromate) in CH2Cl2.
1° alcohol --> aldehyde. PCC is mild enough to stop here.
If you used Jones reagent instead, the primary alcohol would oxidise all the way to the carboxylic acid.
Reduction of an ester (2-electron reduction)
Reagent: DIBAL-H at low temperature (-78 °C).
Ester --> aldehyde. The low temperature is critical; at room temperature DIBAL would reduce all the way to the primary alcohol.
Reduction of a carboxylic acid (2-electron reduction, modified LAH)
Reagent: LiAlH(OtBu)3 (a bulky, hindered version of LAH).
Carboxylic acid --> aldehyde. The bulky tert-butoxy groups slow the reagent down enough to stop at the aldehyde.
From a Weinreb amide
Reagent: LAH (LiAlH4).
Weinreb amide --> aldehyde. The methoxy group on the amide nitrogen chelates the aluminium, which prevents over-reduction.
Tags: aldehyde synthesis, PCC oxidation, DIBAL ester reduction, Weinreb amide, LiAlH(OtBu)3
Grignard addition
Aldehyde + RMgBr --> 2° alcohol (after aqueous workup).
The Grignard adds its alkyl group to the carbonyl carbon. You gain a new C-C bond and extend the chain.
Reduction with NaBH4
Aldehyde + NaBH4 --> 1° alcohol.
A hydride is delivered to the carbonyl carbon. Simple, selective, and does not reduce esters.
Cyanation (cyanohydrin formation)
Aldehyde + HCN (or NaCN, catalytic) --> cyanohydrin (alpha-hydroxy nitrile).
CN- attacks the carbonyl carbon. The nitrile can later be hydrolysed to a carboxylic acid, which makes this a chain-extension strategy.
Wolff-Kishner reduction
Aldehyde + NH2NH2, strong base, heat --> alkane (CH2 in place of C=O).
Completely removes the oxygen, converting the carbonyl carbon to a methylene. This is the complement of Clemmensen reduction (which uses Zn/Hg, HCl).
Wittig reaction
Aldehyde + PPh3=CHR (ylide) --> alkene + Ph3P=O.
Replaces C=O with C=C. The geometry of the resulting alkene (E or Z) depends on whether the ylide is stabilised or non-stabilised.
Acetal formation
Aldehyde + 2 eq. ROH, cat. H3O+ --> acetal + H2O.
Reversible under acidic aqueous conditions (back to the aldehyde + alcohol).
With a diol (e.g. ethylene glycol), a cyclic acetal forms, which is the more common protecting-group strategy.
Oxidation (Jones reagent)
Aldehyde + Jones reagent (CrO3/H2SO4) --> carboxylic acid.
Aldehydes oxidise easily because the H on the carbonyl is abstractable.
Imine formation
Aldehyde + RNH2 (primary amine) --> imine (C=N) + H2O.
Acid-catalysed, reversible. Imines are intermediates in many biological processes (e.g. transamination).
Tags: Grignard aldehyde, NaBH4 reduction, cyanohydrin, Wolff-Kishner, Wittig, acetal protecting group, Jones oxidation aldehyde, imine
Nitrile + Grignard reagent
Nitrile + RMgBr, then H2O workup --> ketone.
The Grignard adds to the C-N triple bond. Aqueous workup hydrolyses the resulting imine salt to give the ketone.
Oxidation of a 2° alcohol
2° alcohol + PCC or Jones reagent --> ketone.
Either oxidant works here because there is no risk of over-oxidation (ketones cannot be oxidised further to a carboxylic acid under these conditions).
Acid chloride + lithium dialkylcuprate (Gilman reagent)
Acid chloride (RCOCl) + R'2CuLi --> ketone.
The cuprate is a "soft" nucleophile that adds once to the acid chloride without over-adding. This selectivity is the reason you use the cuprate rather than a Grignard here.
Weinreb amide + Grignard
Weinreb amide + 1 eq. RMgBr --> ketone.
The same chelation logic as in the aldehyde case: the metal coordinates to the OMe, preventing a second addition.
Tags: ketone synthesis, nitrile Grignard, 2° alcohol oxidation, Gilman reagent, cuprate, Weinreb amide ketone
Grignard addition
Ketone + RMgBr --> 3° alcohol (after aqueous workup).
Same mechanism as with aldehydes, but because the ketone already has two carbon groups, the product is a tertiary alcohol.
Reduction (LAH or NaBH4)
Ketone + LAH or NaBH4 --> 2° alcohol.
Both reagents deliver hydride to the carbonyl carbon. NaBH4 is milder and more selective; LAH is more powerful but less discriminating.
Wolff-Kishner reduction
Ketone + NH2NH2, base, heat --> alkane.
Same as with aldehydes: total removal of the oxygen, replacing C=O with CH2.
Wittig reaction
Ketone + PPh3=CHR (ylide) --> alkene + Ph3P=O.
Works on ketones as well as aldehydes, though ketones are somewhat less reactive.
Ketal formation
Ketone + 2 eq. ROH, cat. H3O+ --> ketal + H2O.
Reversible with aqueous acid. Ketals serve as protecting groups for ketones, stable under basic and nucleophilic conditions.
With a diol, a cyclic ketal forms (more common in synthesis).
Enamine formation
Ketone + R2NH (secondary amine), cat. acid --> enamine + H2O.
Enamines are nucleophilic at the alpha carbon. They are used in the Stork enamine reaction for alpha-functionalisation (alkylation or acylation at the alpha position).
Alpha-functionalisation (overview)
Ketones can be halogenated at the alpha carbon using Br2 under acidic or basic conditions.
The alpha-bromo ketone is an important electrophile for further substitution reactions.
Tags: ketone Grignard, NaBH4 ketone, Wolff-Kishner ketone, Wittig ketone, ketal, cyclic ketal, enamine, Stork enamine, alpha-halogenation
Students often assume PCC and Jones reagent are interchangeable. They are not. PCC stops at the aldehyde; Jones pushes a primary alcohol all the way to the carboxylic acid. Choosing the wrong one on an exam costs the entire problem.
Students frequently forget that NaBH4 cannot reduce esters or carboxylic acids. If the substrate is an ester, you need LAH or DIBAL, not NaBH4.
A common error is drawing a Grignard addition to a ketone and labelling the product as a secondary alcohol. The product is a tertiary alcohol (two R groups from the ketone plus one from the Grignard).
Students often confuse acetals/ketals with hemiacetals. An acetal has two -OR groups and no -OH on the former carbonyl carbon. A hemiacetal still has one -OH. The distinction matters because acetals are stable protecting groups; hemiacetals are not.
Reagent selection (PCC vs Jones, NaBH4 vs LAH, DIBAL vs LAH) is one of the most frequently tested skills in Org Chem II exams. Know what each reagent can and cannot do.
Grignard reactions appear on nearly every exam. Be prepared to identify the product's degree of alcohol (1°, 2°, or 3°) based on whether the substrate is formaldehyde, an aldehyde, or a ketone.
Protecting-group chemistry (acetals and ketals) often appears in multi-step synthesis problems. You will be expected to install a protecting group, carry out a reaction elsewhere in the molecule, and then remove it.
The Wittig reaction is a favourite for synthesis questions because it offers a way to make alkenes with control over where the double bond goes.
Wolff-Kishner vs Clemmensen: both achieve the same transformation (C=O to CH2), but under opposite conditions. Wolff-Kishner uses basic conditions; Clemmensen uses acidic. You pick the one compatible with the rest of the molecule.
True or false: PCC can oxidise a primary alcohol directly to a carboxylic acid.
Answer: False. PCC stops at the aldehyde.
Fill in the blank: A Grignard reagent added to a ketone produces a ____° alcohol.
Answer: 3° (tertiary).
True or false: NaBH4 can reduce an ester to a primary alcohol.
Answer: False. NaBH4 is too mild; you need LAH for esters.
Fill in the blank: The Wittig reaction replaces a C=O with a ______.
Answer: C=C (an alkene).
True or false: An acetal is stable under basic conditions but cleaved by aqueous acid.
Answer: True.
Q: What reagent would you use to convert a primary alcohol to an aldehyde without further oxidation?
A: PCC (pyridinium chlorochromate) in CH2Cl2.
Q: You need to convert an ester to an aldehyde. Which reagent do you choose, and what condition is critical?
A: DIBAL-H at -78 °C. The low temperature prevents full reduction to the primary alcohol.
Q: Draw the product of reacting acetaldehyde (CH3CHO) with methylmagnesium bromide (CH3MgBr), followed by aqueous workup.
A: 2-propanol (a secondary alcohol). The methyl group from the Grignard adds to the carbonyl carbon of the aldehyde.
Q: A synthesis problem requires you to protect a ketone while performing a Grignard reaction on an ester elsewhere in the molecule. How do you protect the ketone?
A: Convert the ketone to a cyclic ketal using ethylene glycol and catalytic acid (H3O+). After the Grignard step, remove the ketal with aqueous acid to regenerate the ketone.
Q: You want to convert a ketone to an alkane under basic conditions. Name the reaction and the key reagent.
A: Wolff-Kishner reduction, using hydrazine (NH2NH2) and strong base (e.g. KOH) at high temperature.
Q: What is the difference between an imine and an enamine in terms of the amine used to form them?
A: An imine forms from a primary amine (RNH2) and contains a C=N bond. An enamine forms from a secondary amine (R2NH) and contains a C=C bond adjacent to nitrogen.
This material connects directly to alpha-substitution and enolate chemistry, because the alpha protons of aldehydes and ketones are the starting point for halogenation, alkylation, and condensation reactions. It also connects to carbonyl condensation (aldol and Claisen), where the nucleophilic enolate of one carbonyl attacks the electrophilic carbonyl of another. Protecting-group strategies (acetals and ketals) show up again in multi-step synthesis problems throughout the rest of the course.
aldehyde reactions, ketone reactions, CHEM 212 carbonyl chemistry, Grignard reaction aldehyde, Grignard reaction ketone, NaBH4 reduction, LAH reduction, DIBAL ester to aldehyde, PCC oxidation, Jones oxidation, Wolff-Kishner reduction, Wittig reaction, acetal formation, ketal formation, cyclic acetal, cyclic ketal, protecting group carbonyl, cyanohydrin formation, imine formation, enamine formation, Stork enamine, Weinreb amide, acid chloride cuprate, Gilman reagent ketone, nucleophilic addition to carbonyl, organic chemistry II study notes, Penn State CHEM 212