Organic reaction mechanisms

A nucleophile ("nucleus-loving") is a species with a lone pair of electrons that it can donate to form a new covalent bond. Nucleophiles seek out electron-poor sites. Common examples are $OH^-$, $CN^-$, $NH_3$ and $H_2O$.

In a halogenoalkane the carbon is bonded to a halogen (Cl, Br, I), which is more electronegative than carbon. This pulls electron density away, so that carbon carries a partial positive charge, $C^{\delta+}$. This $\delta+$ carbon is the target for nucleophilic attack.

In nucleophilic substitution, the nucleophile donates its lone pair to the $\delta+$ carbon and the halogen leaves as a halide ion. For example:

$$\text{CH}_3\text{CH}_2\text{Br} + \text{OH}^- \rightarrow \text{CH}_3\text{CH}_2\text{OH} + \text{Br}^-$$

• The incoming group substitutes (replaces) the leaving halogen.
• The product depends on the nucleophile: $OH^-$ gives an alcohol, $CN^-$ gives a nitrile, $NH_3$ gives an amine.
• A curly arrow runs from the nucleophile's lone pair to the carbon, and a second from the C-halogen bond to the halogen.

When a covalent bond breaks there are two possibilities. Homolytic fission splits the bond evenly, giving each atom one electron and producing radicals (species with an unpaired electron). This happens in the free-radical substitution of alkanes.

Heterolytic fission is the type that drives the mechanisms in this topic. The bond breaks unevenly: both shared electrons go to ONE atom. This produces two oppositely charged ions, a positive cation and a negative anion.

For example, when a halogenoalkane reacts the C-Br bond breaks heterolytically so that bromine takes both electrons:

$$\text{C}{-}\text{Br} \rightarrow \text{C}^+ + \text{Br}^-$$

Key points:

• Heterolytic fission is shown by a full (double-headed) curly arrow representing a PAIR of electrons.
• The more electronegative atom usually keeps both electrons.
• It generates ions (carbocations, halide ions), which are the reactive intermediates in nucleophilic and electrophilic mechanisms.
• Contrast with homolytic fission, shown by half-arrows (single-headed "fish-hook" arrows) for single electrons.

An electrophile ("electron-loving") is an electron-pair acceptor: a species attracted to regions of high electron density. Electrophiles are usually positively charged or carry a partial positive charge.

Examples include:

• $H^{\delta+}$ in a polar molecule such as $HBr$.
• $Br_2$, which has no permanent dipole but becomes polarised (an induced dipole) as it approaches an electron-rich double bond.

(At HL you also meet $NO_2^+$, the nitronium ion, as the electrophile in the nitration of benzene.)

The natural target for an electrophile is the C=C double bond of an alkene. The pi bond sits above and below the line of the carbon atoms and is exposed and electron-rich, making it an easy site to attack. When an electrophile approaches an alkene, the electron-rich pi bond is donated towards it and an addition reaction occurs (the detailed stepwise mechanism, with the carbocation intermediate and curly arrows, is covered as HL material).

Alkenes are unsaturated: their C=C double bond is electron-rich and reactive. The typical reaction is electrophilic addition, in which a small molecule adds across the double bond. No atoms are lost, so it is an addition (not substitution).

Classic examples (overall equations):

• Bromine: $\text{CH}_2{=}\text{CH}_2 + \text{Br}_2 \rightarrow \text{CH}_2\text{Br}\text{CH}_2\text{Br}$. Orange bromine water is decolourised - this is the test for a C=C double bond.
• Hydrogen halides: $\text{CH}_2{=}\text{CH}_2 + \text{HBr} \rightarrow \text{CH}_3\text{CH}_2\text{Br}$.
• Water (steam, with $H_3PO_4$ catalyst): gives an alcohol.

Key observations to know at SL:

• The reaction is addition across the C=C double bond, so the product is a saturated compound (a dihalogenoalkane, halogenoalkane or alcohol).
• The decolourisation of orange bromine water is the standard test that distinguishes an unsaturated alkene from a saturated alkane.

(The full stepwise mechanism - electrophile attack, carbocation intermediate, addition of the anion, shown with curly arrows - is treated as HL material; see "Electrophilic addition mechanisms".)

The Lewis definition broadens acid-base chemistry beyond proton transfer:

• A Lewis acid is an electron-pair acceptor.
• A Lewis base is an electron-pair donor.

Every Bronsted-Lowry base is also a Lewis base (it donates a lone pair to $H^+$), but the Lewis idea also covers species that have no proton to transfer. For example $BF_3$ has an electron-deficient boron with an empty orbital, so it acts as a Lewis acid:

$$\text{BF}_3 + \text{NH}_3 \rightarrow \text{F}_3\text{B}{\leftarrow}\text{NH}_3$$

Here $NH_3$ donates its lone pair (Lewis base) into boron's empty orbital, forming a coordinate bond.

Links to mechanisms:

• A nucleophile is a Lewis base (donates an electron pair).
• An electrophile is a Lewis acid (accepts an electron pair).
• Transition-metal ions act as Lewis acids; ligands act as Lewis bases.

So nucleophilic and electrophilic attack are really just Lewis acid-base reactions, with a curly arrow showing the lone pair moving from the base to the acid.

A coordination (dative covalent) bond is a covalent bond in which both of the shared electrons come from the same atom. The donor is a Lewis base (called a ligand) and the acceptor is a Lewis acid with an empty orbital, usually a transition-metal ion.

When several ligands bond to one central metal ion, the result is a complex ion. For example, $Cu^{2+}$ in water is surrounded by six water molecules:

$$[\text{Cu}(\text{H}_2\text{O})_6]^{2+}$$

Features to remember:

• Each ligand donates one lone pair to form one coordination bond.
• The number of coordination bonds to the central ion is the coordination number (commonly 6 or 4).
• Common ligands: $H_2O$, $NH_3$, $Cl^-$, $CN^-$, $OH^-$.
• The overall charge of the complex = metal-ion charge + sum of ligand charges. For six neutral water ligands on $Cu^{2+}$, the charge stays $2+$.

Once formed, a coordination bond is identical to any other covalent bond - the "dative" label only records where the electrons came from.

There are two mechanisms for nucleophilic substitution.

SN2 (substitution, nucleophilic, bimolecular)

• One concerted step: the nucleophile attacks as the leaving group departs.
• Passes through a transition state with the carbon partially bonded to both groups.
• The nucleophile attacks from the opposite side to the leaving group, causing inversion of configuration (like an umbrella turning inside-out).
• Rate $= k[\text{halogenoalkane}][\text{nucleophile}]$ - second order overall.
• Favoured by primary halogenoalkanes (little steric hindrance).

SN1 (substitution, nucleophilic, unimolecular)

• Two steps: first the C-halogen bond breaks heterolytically to form a carbocation (slow, rate-determining); then the nucleophile attacks.
• Rate $= k[\text{halogenoalkane}]$ - first order (the nucleophile is not in the rate-determining step).
• Favoured by tertiary halogenoalkanes, because the resulting carbocation is stabilised by three electron-donating alkyl groups.

Secondary halogenoalkanes can react by either mechanism. The kinetics (order of reaction) is the key experimental clue to which pathway operates.

The leaving group is the atom or group that departs with the bonding electron pair (the halide ion in a halogenoalkane). How easily it leaves strongly affects the rate of nucleophilic substitution.

A good leaving group is one that forms a stable ion. For the halogens, the controlling factor is the C-halogen bond strength:

• C-I is the weakest bond, so iodoalkanes react fastest.
• C-Br is intermediate.
• C-Cl is stronger, so chloroalkanes are slower.
• C-F is the strongest bond, so fluoroalkanes react slowest (essentially unreactive in these conditions).

So the rate order is:

$$\text{R-I} > \text{R-Br} > \text{R-Cl} > \text{R-F}$$

Key ideas:

• Although fluorine gives the most $\delta+$ carbon, bond strength wins: the very strong C-F bond is hard to break.
• The weaker the C-X bond, the more easily heterolytic fission occurs and the better the halide leaves.
• This trend holds for both SN1 and SN2, because bond breaking is part of the rate-determining step in each.

The full mechanism of electrophilic addition uses curly arrows to track electron pairs.

Alkene + HBr (e.g. ethene):

• Step 1: the electron-rich C=C bond attacks the $H^{\delta+}$ of HBr. A curly arrow goes from the double bond to the H; a second curly arrow goes from the H-Br bond to the Br. This forms a C-H bond and releases $Br^-$, leaving a carbocation.
• Step 2: the $Br^-$ ion's lone pair attacks the positive carbon, forming the C-Br bond and the final halogenoalkane.

Alkene + Br2 is similar: as $Br_2$ approaches the double bond it is polarised (an induced dipole), the pi bond attacks the nearer $\delta+$ bromine, and $Br^-$ leaves and then adds to the carbocation.

Markovnikov's rule (asymmetric alkenes): when HBr adds to an asymmetric alkene such as propene, H adds to the carbon already bearing more hydrogens. This is because the more stable carbocation forms preferentially:

• Stability order: tertiary > secondary > primary carbocation, due to the electron-donating effect of alkyl groups.
• So the major product comes from the more stable intermediate.

Benzene's six pi electrons are delocalised in a ring, making it unusually stable. Because of this, benzene reacts by electrophilic substitution (an H is replaced) rather than addition, so the stable delocalised system is kept in the product.

The classic example is nitration:

$$\text{C}_6\text{H}_6 + \text{HNO}_3 \rightarrow \text{C}_6\text{H}_5\text{NO}_2 + \text{H}_2\text{O}$$

• Generating the electrophile: concentrated $HNO_3$ and concentrated $H_2SO_4$ react so that sulfuric acid protonates nitric acid, producing the nitronium ion $NO_2^+$ (sulfuric acid is the catalyst).
• Attack: the delocalised ring donates a pair of electrons to $NO_2^+$, forming a positively charged, partly broken intermediate.
• Restoration: an $H^+$ is lost from that carbon, the delocalised ring re-forms, and $H_2SO_4$ is regenerated.

Key contrasts to remember:

• Alkenes undergo addition; benzene undergoes substitution, because preserving the delocalised ring is energetically favourable.
• The overall pattern is still electron-pair sharing: an electrophile accepts a pair of electrons from an electron-rich pi system.