Organic Chemistry · Aldehydes and Ketones: Nucleophilic Addition Reactions
Nucleophilic Addition of Hydride and Grignard Reagents: Alcohol Formation
On this page 9 sections
In 30 seconds
Two families of reagents convert aldehydes and ketones into alcohols by nucleophilic addition of a carbanion-like species. Hydride reagents deliver the hydride ion (H⁻, a hydrogen with two electrons) to the carbonyl carbon; Grignard reagents (R–MgX) deliver a carbanion equivalent (R⁻, an alkyl or aryl group with its electron pair). In both cases the mechanism is the familiar two-step addition: the nucleophile attacks the carbonyl carbon, the π electrons move to oxygen giving an alkoxide, and aqueous Workup The aqueous treatment at the end of a reaction. Full entry → protonates the alkoxide to give the alcohol:
R2C=O H- or R-⟶\text{then H}_3\text{O}^+ R2C(H)(OH) or R2C(R')(OH)
The two most common hydride reagents are Sodium borohydride (NaBH₄) A mild hydride source stable in water/alcohol. Full entry → and Lithium aluminum hydride (LiAlH₄) A powerful, water-reactive hydride source. Full entry →. NaBH₄ is mild and selective — it reduces aldehydes and ketones but not esters, carboxylic acids, or nitriles — and can be used in water or alcohols. LiAlH₄ is far more powerful, reducing almost any carbonyl derivative, but it reacts violently with water and must be used in anhydrous ether solvents under inert atmosphere. Both deliver four hydrides per molecule, so the stoichiometry is one equivalent of reagent per four carbonyls.
Grignard reagents (R–MgX, made from an organic halide and magnesium metal in dry ether) are the most important carbon nucleophiles. Because they add a carbon group, they build new carbon–carbon bonds: formaldehyde gives primary alcohols, other aldehydes give secondary alcohols, and ketones give tertiary alcohols. Grignard reagents are extremely reactive toward water and protic solvents, so they are prepared and used under strictly Anhydrous conditions Reaction environment free of water. Full entry →, and the reaction is quenched with aqueous acid at the end. Hydride reduction adds no carbon (the carbonyl carbon count is unchanged); Grignard addition adds one carbon per reagent molecule. That single difference determines which method a synthesis uses.
Why this matters
Reduction of carbonyls to alcohols is one of the most common transformations in all of organic chemistry, from undergraduate labs to pharmaceutical and industrial synthesis. NaBH₄ is the workhorse: mild, safe in aqueous solution, and selective, making it the default choice for reducing aldehydes and ketones without touching other functional groups. LiAlH₄ is the heavy hammer used when stronger reducing power is needed. Grignard chemistry, meanwhile, is the classic route to carbon–carbon bonds: every time a drug molecule needs a new alkyl or aryl group attached to an alcohol carbon, a Grignard (or related organometallic) addition is the textbook strategy. In biology, the same hydride-addition concept runs the body's metabolism — NADH and NADPH deliver hydride equivalents to carbonyls in countless enzyme-catalyzed reductions, including the reduction of pyruvate to lactate. Understanding which reagent reduces what, and what kind of alcohol each aldehyde or ketone gives, is high-yield exam material and foundational lab knowledge.
The college version
Core Concepts
Hydride reagents: NaBH₄ vs. LiAlH₄
Sodium borohydride is a source of hydride that is stable in water and alcohols — it reacts slowly with protic solvents but rapidly reduces aldehydes and ketones. It does NOT reduce esters, carboxylic acids, amides, or nitriles under normal conditions, which makes it selective: a molecule with both a ketone and an ester is reduced only at the ketone. Lithium aluminum hydride reduces essentially every carbonyl derivative (aldehydes, ketones, esters, acids, amides, nitriles) and is correspondingly hazardous: it ignites or reacts explosively with water, so reactions run in anhydrous diethyl ether or THF under inert gas, and workup is done carefully with aqueous solutions. Both reagents transfer hydride to the carbonyl carbon, and both formally deliver four hydrides per molecule:
NaBH4 + 4R2C=O → Na+[B(OR2CH)4]- H3O+⟶ 4R2CHOH
The product from an aldehyde is a primary alcohol; from a ketone, a secondary alcohol.
Grignard reagents: carbon nucleophiles
A Grignard reagent has the general structure R–MgX (X = Cl, Br, I), prepared by placing the organic halide R–X and magnesium metal in dry ether:
R-X + Mg → R-MgX
The carbon–magnesium bond is highly polarized, so the carbon carries a strong partial negative charge and behaves like a carbanion R⁻ — a powerful nucleophile and base. It attacks the carbonyl carbon exactly as hydride does. The alcohol obtained depends on the carbonyl:
- Formaldehyde (H₂C=O) + RMgX gives a primary alcohol with one more carbon: R–CH₂OH.
- Any other aldehyde (R'CHO) + RMgX gives a secondary alcohol: R'–CH(OH)–R.
- A ketone (R'₂C=O) + RMgX gives a tertiary alcohol: R'₂C(OH)–R.
Grignard reagents also react with esters (two equivalents give a tertiary alcohol with two new R groups) and with nitriles (giving ketones after hydrolysis), but those additions are beyond the simple addition picture. Because R–MgX is a strong base and nucleophile, it reacts instantly with water, alcohols, and any O–H or N–H bond — so the reaction mixture must be absolutely dry, and the alcohol product appears only after the aqueous workup that protonates the alkoxide.
The mechanism in words
For both hydride and Grignard addition, the curved-arrow sequence is the same as every other addition in this chapter: (1) the nucleophile's lone pair forms a bond to the carbonyl carbon while the C=O π bond breaks, its electrons moving to oxygen (this is the rate-determining step); (2) the resulting alkoxide is protonated during workup. For NaBH₄, hydride transfer is followed by the alkoxide abstracting a proton from solvent or water. For Grignard addition, the alkoxide salt (R'₂C(O⁻)R with MgX⁺ counterion) is stable in dry ether and only becomes the neutral alcohol when aqueous acid is added at the end. No elimination occurs because there is no good leaving group.
Steric and electronic control of reactivity
As always in this chapter, aldehydes are reduced faster than ketones, and electron-poor carbonyls faster than electron-rich ones. Grignard additions are also sensitive to steric bulk: a ketone with two large groups (e.g., di-tert-butyl ketone) may react sluggishly or undergo enolization instead, because the bulky carbanion cannot reach the crowded carbonyl carbon. Hydride reagents are smaller and less sensitive to steric crowding.
Common Confusions
| Do Not Confuse | With | Difference |
|---|---|---|
| NaBH₄ | LiAlH₄ | NaBH₄ is mild, selective, water-tolerant; LiAlH₄ is powerful, unselective, and water-reactive (anhydrous required). |
| Hydride addition | Grignard addition | Hydride adds H⁻ (no new carbon); Grignard adds R⁻ (adds one carbon and builds a C–C bond). |
| Alcohol from aldehyde | Alcohol from ketone | Aldehydes give 1° alcohols (with hydride) or 2° alcohols (with Grignard); ketones give 2° (hydride) or 3° (Grignard) alcohols. |
| Grignard reagent (R–MgX) | Organolithium (R–Li) | Both are carbanion sources; R–Li is even more reactive/basic. Exam questions often ask which conditions each requires. |
| Reaction of R–MgX with carbonyl | Reaction of R–MgX with water | With carbonyl it builds a C–C bond; with water it forms R–H and Mg(OH)X — which is why anhydrous conditions are essential. |
| Reducing agent | Oxidizing agent | Hydride reagents donate electrons (reducing agents); oxidants like Cr(VI) remove electrons. |
| 1 equiv NaBH₄ per carbonyl | 1 equiv NaBH₄ per 4 carbonyls | NaBH₄ has four hydrides; one equivalent reduces four carbonyls (in theory). |
Eli explains
The same idea, in plain words
Explain it like I’m 10
Think of the carbonyl carbon as a hat rack with one empty hook. NaBH₄ and LiAlH₄ hang a tiny "hydrogen hat" (H⁻) on the hook, so you get an alcohol with the same number of carbons — nothing added, just a hat swapped. A Grignard reagent hangs a big "R hat" — a whole new carbon group — so the molecule grows: formaldehyde gives a one-carbon growth, other aldehydes give a two-branch result, and ketones end up with three branches (a tertiary alcohol). And Grignard hats are picky: they fall off in water, so the whole game is played in a dry room, and the hat is only "glued on" at the end with acid.
Worked example
Example 1: Stoichiometry of a NaBH₄ reduction
How many grams of NaBH₄ (molar mass 37.83 g/mol) are needed to reduce 0.200 mol of cyclohexanone to cyclohexanol, if each borohydride delivers all four hydrides?
Each hydride reduces one carbonyl, so four equivalents of ketone are reduced per mole of NaBH₄:
n(NaBH4) = n(ketone)4 = 0.200 mol4 = 0.0500 mol
Convert to mass:
m(NaBH4) = 0.0500 mol × 37.83 g/mol = 1.89 g
Unit check: mol ÷ 4 = mol; mol × (g/mol) = g. In practice, chemists use a modest excess (1.5–2×) because some hydride is lost to solvent or air, but the 4:1 accounting shows why so little reagent is needed — a common exam calculation.
Example 2: Choosing and planning a Grignard synthesis
Design the Grignard route to 2-phenyl-2-propanol, C₆H₅C(CH₃)₂OH, and compute the theoretical yield from 5.00 g of bromobenzene (molar mass 157.01 g/mol), assuming excess acetone and Mg.
2-Phenyl-2-propanol is a tertiary alcohol: the OH carbon carries two methyl groups and one phenyl group. Working backward, the two methyl groups come from the carbonyl (acetone, (CH₃)₂C=O) and the phenyl group from the Grignard reagent (C₆H₅MgBr). So the sequence is: (1) bromobenzene + Mg in dry ether → phenylmagnesium bromide; (2) add acetone; (3) aqueous workup → 2-phenyl-2-propanol.
Moles of bromobenzene:
n(C6H5Br) = 5.00 g157.01 g/mol = 0.03185 mol
The Grignard reagent forms 1:1 from bromobenzene, and the addition consumes 1:1 with acetone, so the product's theoretical moles equal the bromobenzene moles. Product molar mass: C₉H₁₂O = 9(12.01) + 12(1.008) + 16.00 = 136.19 g/mol.
m(product) = 0.03185 mol × 136.19 g/mol = 4.34 g
If the student isolated 3.7 g, the percent yield is:
% yield = 3.7 g4.34 g × 100% = 85%
Dimensional analysis: g ÷ (g/mol) = mol; mol × (g/mol) = g; the yield ratio is dimensionless. The key retrosynthetic insight — tertiary alcohol means ketone + Grignard — is what makes this a classic exam problem.
Key takeaways
- NaBH₄ reduces aldehydes → primary alcohols and ketones → secondary alcohols; mild, water-tolerant, selective (does not touch esters, acids, amides, nitriles).
- LiAlH₄ reduces almost all carbonyl derivatives but requires anhydrous conditions and inert atmosphere; dangerous with water.
- Both hydride reagents deliver 4 hydrides per molecule; plan stoichiometry accordingly (1 equiv reagent ≈ 4 equiv carbonyl).
- Grignard reagents R–MgX are carbon nucleophiles (carbanion equivalents) that add R to the carbonyl carbon, building C–C bonds.
- Product type from Grignard addition: formaldehyde → 1° alcohol; other aldehydes → 2° alcohol; ketones → 3° alcohol.
- Grignard reagents react with water/protic groups; reactions run dry and are quenched with aqueous acid.
- Aldehydes react faster than ketones with both hydride and Grignard reagents; bulky ketones may fail with Grignards.
- Hydride reduction adds no carbon; Grignard addition adds one carbon (the reagent's R group).
Check yourself
5 review questions from the chapter. Try each one, then open the answer.
What alcohol is obtained when NaBH₄ (then aqueous workup) is applied to (a) butanal and (b) cyclohexanone?
Show answer
(a) Butanal (CH₃CH₂CH₂CHO) gives 1-butanol, CH₃CH₂CH₂CH₂OH — a primary alcohol. (b) Cyclohexanone gives cyclohexanol — a secondary alcohol (the OH carbon bears two ring carbons).
Why can NaBH₄ be used in aqueous ethanol but LiAlH₄ cannot?
Show answer
NaBH₄ is kinetically stable in protic solvents — it reduces carbonyls much faster than it reacts with water/alcohol. LiAlH₄ reacts violently with water (it would be destroyed, and the reaction is dangerous), so it must be used in dry ether or THF.
What product results from adding phenylmagnesium bromide (C₆H₅MgBr) to formaldehyde; to benzaldehyde; to acetone?
Show answer
Formaldehyde + C₆H₅MgBr → primary alcohol, benzyl alcohol (C₆H₅CH₂OH). Benzaldehyde + C₆H₅MgBr → secondary alcohol, diphenylmethanol ((C₆H₅)₂CHOH). Acetone + C₆H₅MgBr → tertiary alcohol, 2-phenyl-2-propanol (C₆H₅C(CH₃)₂OH).
A molecule contains both a ketone and an ester. Which functional group is reduced by NaBH₄, and which by LiAlH₄?
Show answer
NaBH₄ reduces only the ketone (esters are untouched under normal conditions). LiAlH₄ reduces both the ketone and the ester (the ester gives a primary alcohol with its own carbon skeleton).
Why must Grignard reactions be run under strictly anhydrous conditions, and why is aqueous acid added at the end?
Show answer
Grignard reagents are destroyed by any O–H or N–H bond, including water, so moisture must be excluded during formation and reaction. Aqueous acid is added at the end (workup) to protonate the alkoxide intermediate, converting it into the neutral alcohol product that can be isolated.
Study tools & related lessonsKey vocabulary · Related
Key vocabulary
- Hydride ion (H⁻)
- A hydrogen atom carrying two electrons; a strong nucleophile.
- Sodium borohydride (NaBH₄)
- A mild hydride source stable in water/alcohol.
- Lithium aluminum hydride (LiAlH₄)
- A powerful, water-reactive hydride source.
- Grignard reagent (R–MgX)
- An organomagnesium compound acting as a carbanion equivalent R⁻.
- Primary/secondary/tertiary alcohol
- Alcohol whose OH carbon is bonded to 1, 2, or 3 carbon groups.
- Alkoxide (C–O⁻)
- The negatively charged intermediate after nucleophilic attack.
- Anhydrous conditions
- Reaction environment free of water.
- Workup
- The aqueous treatment at the end of a reaction.
Sources & references
This lesson was adapted from the open educational references above; their licenses and attributions are preserved. See Copyright & Licensing.
Educational content only. It is not medical, legal or professional advice. Found an error? Tell us.