Difficulty: Intermediate | Prerequisites: CHEM 211, Lewis structures, electronegativity, resonance structures, functional group identification.
Acidity, electronic effects, and alkene/alkyne transformations are threaded through every topic in Organic Chemistry II. Understanding why one proton is more acidic than another (and what stabilises the conjugate base) is the key to predicting reactivity in carbonyl chemistry, enolate chemistry, and aromatic substitution. Electron-withdrawing and electron-donating groups control the reactivity and selectivity of aromatic rings, carbonyls, and acidic protons. Alkene and alkyne reactions round out the toolkit, giving you ways to cleave, functionalise, and stereoselectively reduce double and triple bonds.
Acidity is governed by how well the conjugate base is stabilised, primarily through resonance (more powerful) and induction. EWGs increase acidity by stabilising the anion; EDGs decrease it. On a benzene ring, EWGs like -NO2 deactivate the ring toward electrophilic aromatic substitution. Epoxidation with mCPBA is a stereospecific syn-addition; ozonolysis cleaves double bonds into carbonyls. Lindlar reduction gives cis-alkenes from alkynes; dissolving metal reduction (Na/NH3) gives trans-alkenes.
pKa
A measure of acid strength. Lower pKa = stronger acid (more readily donates a proton). The pKa reflects how stable the conjugate base is after the proton is lost.
Electron-withdrawing group (EWG)
A substituent that pulls electron density away from the molecule, either by induction (electronegativity through sigma bonds) or by resonance (delocalisation through pi bonds). Examples: -NO2, -CN, -C=O, -CF3.
Electron-donating group (EDG)
A substituent that pushes electron density toward the molecule, typically by resonance donation of a lone pair into the pi system. Examples: -OCH3, -NH2, -OH.
Inductive effect
Stabilisation or destabilisation of charge through sigma bonds, based on electronegativity differences. Falls off with distance.
Resonance effect
Stabilisation or destabilisation of charge through delocalisation across pi bonds. Generally more powerful than induction because charge is spread over multiple atoms.
Enolate
The conjugate base formed when an alpha-proton (adjacent to a carbonyl) is removed. Stabilised by resonance between the carbanion and the carbonyl oxygen.
Alpha-proton
A hydrogen on the carbon directly adjacent to a carbonyl group. Its acidity depends on how well the resulting enolate is stabilised.
Epoxidation
Conversion of an alkene to an epoxide (a three-membered ring containing oxygen) using a peracid such as mCPBA. A concerted, stereospecific syn-addition.
mCPBA (meta-chloroperoxybenzoic acid)
The standard peracid used for alkene epoxidation in the lab.
Ozonolysis
Cleavage of a C=C double bond using ozone (O3), followed by a workup step. Reductive workup (DMS or Zn) gives aldehydes and ketones; oxidative workup (H2O2) gives carboxylic acids.
Lindlar catalyst
A poisoned palladium catalyst (Pd/CaCO3 with lead acetate and quinoline) that partially reduces an alkyne to a cis-alkene via syn-addition of H2. The poisoning prevents further reduction to the alkane.
Dissolving metal reduction
Reduction of an internal alkyne using sodium metal in liquid ammonia (Na/NH3). Proceeds through a radical anion mechanism and produces the trans-alkene (anti-addition).
Resonance vs induction
Resonance effects are generally more significant than inductive effects in determining acidity, because resonance delocalises charge over multiple atoms, while induction operates only through sigma bonds and diminishes with distance.
Carboxylic acid vs alcohol acidity
A carboxylic acid (pKa around 5) is far more acidic than an alcohol (pKa around 16). When a carboxylic acid loses its O-H proton, the resulting carboxylate anion is stabilised by resonance: the negative charge is delocalised equally over two identical oxygen atoms. An alkoxide (from an alcohol) has the charge localised on a single oxygen, so it is much less stable.
Aldehyde C-H acidity
The hydrogen directly bonded to the carbonyl carbon of an aldehyde is not acidic (pKa over 40). That proton sits on a carbon, which is less electronegative than oxygen, and losing it would produce a carbanion with no resonance stabilisation. This is very different from the alpha-protons adjacent to the carbonyl, which are moderately acidic.
Amide N-H acidity
An amide's N-H proton has a pKa of roughly 15, compared with roughly 38 for a typical amine. When the amide is deprotonated, the resulting negative charge on nitrogen can be delocalised onto the electronegative oxygen of the adjacent carbonyl via resonance. A simple amine has no such stabilisation.
Substituted phenol acidity ranking
For phenol, p-nitrophenol, and p-methoxyphenol:
p-Nitrophenol has the lowest pKa (most acidic, around 7.15). The -NO2 group is a strong EWG by both induction and resonance, stabilising the phenoxide conjugate base.
Phenol is intermediate (pKa around 9.98).
p-Methoxyphenol has the highest pKa (least acidic, around 10.20). The -OCH3 group is an EDG by resonance, destabilising the phenoxide anion.
Alpha-proton acidity ranking
For acetone, ethyl acetate, and acetyl chloride, in order of increasing alpha-proton acidity:
Ethyl acetate < Acetone < Acetyl chloride
Ethyl acetate is least acidic: the ester oxygen donates electron density by resonance, which destabilises the enolate.
Acetone is intermediate.
Acetyl chloride is most acidic: chlorine is a strong EWG by induction, which stabilises the enolate conjugate base.
Electron-withdrawing groups (EWGs): -NO2, -CN, -C=O, -COOH, -CF3
These groups pull electron density away from the ring. The nitro group (-NO2) is the classic example: it withdraws through both induction (the electronegative nitrogen and oxygens pull electron density through the sigma bonds) and resonance (the pi system of the ring can delocalise a positive charge into the nitro group). This reduces the electron density on the ring, making it a poorer nucleophile in electrophilic aromatic substitution. The ring is "deactivated."
Electron-donating groups (EDGs): -OCH3, -NH2, -OH, alkyl groups
These groups push electron density into the ring, typically by resonance donation of a lone pair. The -OCH3 group, for instance, donates through the oxygen lone pair into the ring's pi system, making the ring more electron-rich and a better nucleophile. The ring is "activated."
Identifying EWGs vs EDGs
-NO2 and -CN are EWGs (withdraw by both resonance and induction).
-OCH3 and -NH2 are EDGs (donate by resonance, even though oxygen and nitrogen are inductively withdrawing; the resonance effect dominates).
Epoxidation with mCPBA
A concerted, stereospecific syn-addition of an oxygen atom across the double bond.
The geometry of the alkene is conserved: a cis-alkene yields a cis-epoxide, and a trans-alkene yields a trans-epoxide.
No radical intermediates are involved.
Acid-catalysed epoxide ring opening (H3O+)
Water attacks the protonated epoxide in an SN2-like fashion from the opposite face (anti-addition). The net result of epoxidation followed by acid-catalysed ring opening is a trans-1,2-diol (vicinal diol). The overall stereochemistry is anti: epoxidation is syn, but the ring opening is anti.
Ozonolysis
Ozone (O3) cleaves the C=C bond. The workup determines the products:
Reductive workup (DMS or Zn/H2O): gives aldehydes and/or ketones, depending on the substitution of the original alkene.
Oxidative workup (H2O2): pushes further, oxidising any aldehyde products to carboxylic acids.
Catalytic hydrogenation (H2/Pt or H2/Pd)
Syn-addition of two hydrogen atoms across the double bond, converting the alkene to an alkane. Both hydrogens are delivered from the same face of the metal surface.
Lindlar reduction (H2, Lindlar catalyst)
Partial reduction of an internal alkyne to a cis-alkene (Z-alkene).
The Lindlar catalyst is a poisoned palladium catalyst that stops reduction at the alkene stage.
Both hydrogens add from the same face (syn-addition), so the product has cis geometry.
Dissolving metal reduction (Na/NH3)
Reduction of an internal alkyne to a trans-alkene (E-alkene).
Proceeds via a radical anion mechanism: sodium donates an electron to the triple bond, forming a radical anion that is protonated by ammonia. A second electron transfer and protonation completes the reduction.
The trans product is thermodynamically favoured because the bulky groups end up on opposite sides.
Summary
Need a cis-alkene from an alkyne? Use Lindlar. Need a trans-alkene? Use Na/NH3.
Lower pKa = stronger acid = more stable conjugate base
Resonance effect > inductive effect (in most comparisons)
Substituted phenol acidity: p-nitrophenol (7.15) > phenol (9.98) > p-methoxyphenol (10.20)
Alpha-proton acidity: ethyl acetate < acetone < acetyl chloride
Ozonolysis + DMS: alkene --> aldehydes + ketones
Ozonolysis + H2O2: alkene --> carboxylic acids + ketones
Lindlar: internal alkyne --> cis-alkene
Na/NH3: internal alkyne --> trans-alkene
mCPBA: alkene --> epoxide (syn-addition, geometry conserved)
Epoxide + H3O+: --> trans-1,2-diol (anti ring opening)
Students often think induction is more important than resonance for acidity. In most cases, resonance is the dominant effect because it delocalises charge over multiple atoms.
Confusing the aldehyde C-H proton with an alpha-proton. The aldehyde proton sits directly on the carbonyl carbon and is not acidic (pKa > 40). The alpha-protons sit on the carbon next door and are moderately acidic (pKa 20 to 25 for a simple ketone).
Assuming -OCH3 is an EWG because oxygen is electronegative. Oxygen is inductively withdrawing, but its resonance donation into the ring dominates, making -OCH3 an EDG overall.
Thinking epoxidation with mCPBA involves radicals. It does not; it is a concerted mechanism.
Mixing up Lindlar (cis) and Na/NH3 (trans). Lindlar is syn-addition (both H from the same face, cis product). Na/NH3 proceeds through a radical anion (anti, trans product).
Ranking substituted phenols by acidity (matching pKa values to compounds) is a classic exam question. Know whether each substituent is an EWG or EDG.
Alpha-proton acidity ranking questions require you to evaluate the substituent's effect on enolate stability.
Predicting ozonolysis products (reductive vs oxidative workup) is a common test of whether you understand the workup distinction.
Lindlar vs Na/NH3 alkyne reduction is a guaranteed exam topic. Know which gives cis and which gives trans.
The overall stereochemical outcome of epoxidation followed by acid-catalysed ring opening (trans-diol) versus catalytic hydrogenation (syn-addition to alkane) is a favourite comparison question.
True or False: Resonance effects are generally less significant than inductive effects in influencing acidity. (False)
Fill in the blank: p-Nitrophenol has the ______ pKa of the three substituted phenols. (lowest)
True or False: Ozonolysis with a reductive workup (DMS) produces carboxylic acids. (False, it produces aldehydes and ketones)
Fill in the blank: Lindlar reduction of an internal alkyne gives a ______-alkene. (cis)
True or False: Epoxidation with mCPBA involves radical intermediates. (False)
Q: Which compound corresponds to the pKa of 7.15: phenol, p-nitrophenol, or p-methoxyphenol?
A: p-Nitrophenol. The -NO2 group is a strong EWG that stabilises the phenoxide conjugate base by both resonance and induction, making it the most acidic.
Q: Rank acetone, ethyl acetate, and acetyl chloride in order of increasing alpha-proton acidity.
A: Ethyl acetate < Acetone < Acetyl chloride. Ethyl acetate's ester oxygen donates by resonance (destabilises enolate). Chlorine in acetyl chloride withdraws by induction (stabilises enolate).
Q: What is the primary product when 2-butyne is treated with Na/NH3?
A: trans-2-Butene. The dissolving metal reduction proceeds through a radical anion mechanism, giving the trans-alkene.
Q: What products does ozonolysis of an alkene with reductive workup (DMS) give?
A: Aldehydes and/or ketones, depending on the substitution pattern of the original alkene. Reductive workup prevents further oxidation.
Q: Using pKa data, explain why a carboxylic acid (pKa ~5) is so much more acidic than an alcohol (pKa ~16).
A: The carboxylate anion (conjugate base of the acid) is stabilised by resonance between two equivalent oxygen atoms, spreading the charge. The alkoxide (conjugate base of the alcohol) has the charge localised on a single oxygen, with no resonance stabilisation. Better stabilisation of the conjugate base means a lower pKa.
Acidity and electronic effects connect to carbonyl reactivity (Doc 1) because the electrophilicity of a carbonyl depends on the same EWG/EDG principles. They connect to organometallic chemistry (Doc 2) because Grignard incompatibility with protic groups is an acid-base problem. Alkene and alkyne reactions link to stereochemistry (syn vs anti addition) and to retrosynthetic analysis, where choosing the right reduction method (Lindlar vs Na/NH3) is a key planning step.
pKa, acidity, conjugate base stability, resonance stabilisation, inductive effect, electron-withdrawing group, EWG, electron-donating group, EDG, nitro group, cyano group, methoxy group, amino group, substituted phenols, p-nitrophenol, p-methoxyphenol, alpha-proton, enolate, alpha-proton acidity, acetone, ethyl acetate, acetyl chloride, carboxylic acid acidity, alcohol pKa, amide N-H acidity, epoxidation, mCPBA, syn-addition, stereospecific, epoxide ring opening, trans-diol, vicinal diol, ozonolysis, reductive workup, DMS, oxidative workup, H2O2, Lindlar catalyst, cis-alkene, Z-alkene, dissolving metal reduction, Na/NH3, trans-alkene, E-alkene, catalytic hydrogenation, H2/Pt, H2/Pd, CHEM 212, organic chemistry II