Structure and Reactivity of Alkyl Halides: MDCAT Chemistry notes
Structure and Reactivity of Alkyl Halides for MDCAT: polar C-X bond, leaving group order RI > RBr > RCl > RF, nucleophiles, Grignard reagent, SN reactions.
The C–X bond
In an alkyl halide the carbon bonded to the halogen is sp$^3$ hybridized. The halogen is more electronegative than carbon, so the bond is polar: $\mathrm{C^{\delta+}-X^{\delta-}}$. The partially positive carbon is electrophilic and is attacked by nucleophiles, which displace the halogen as a halide ion. This is nucleophilic substitution (SN).
Reactivity order and bond strength
Polarity alone would suggest R–F is the most reactive, but the deciding factor is bond strength. Down the group the halogen atom grows, overlap with carbon becomes poorer and the C–X bond becomes longer and weaker.
| Bond | Bond length | Bond strength | Reactivity of R–X |
|---|---|---|---|
| C–F | shortest | strongest | least reactive |
| C–Cl | |||
| C–Br | |||
| C–I | longest | weakest | most reactive |
$$\mathrm{R{-}I > R{-}Br > R{-}Cl > R{-}F}$$
In ascending order this reads F, Cl, Br, I. The same bond-strength argument gives the reactivity of halogen acids: $\mathrm{HI > HBr > HCl > HF}$.
Leaving groups and nucleophiles
A good leaving group is a weak base that is stable on its own: $\mathrm{I^- > Br^- > Cl^- > F^-}$. Strong bases such as $\mathrm{OH^-}$, $\mathrm{NH_2^-}$ and $\mathrm{RO^-}$ are poor leaving groups; this is why alcohols need protonation before the $-\mathrm{OH}$ can leave.
A nucleophile is an electron-rich species with a lone pair or negative charge that attacks the positive carbon. Examples: $\mathrm{OH^-}$, $\mathrm{RO^-}$, $\mathrm{CN^-}$, $\mathrm{SH^-}$, $\mathrm{NH_3}$, $\mathrm{H_2O}$. A negatively charged small species such as $\mathrm{OH^-}$ is a stronger nucleophile than $\mathrm{Cl^-}$, $\mathrm{Br^-}$ or $\mathrm{HSO_4^-}$. Species such as $\mathrm{H^+}$ and $\mathrm{NO_2^+}$ are electrophiles, not nucleophiles.
Typical substitution products
| Reagent (nucleophile) | Product |
|---|---|
| Aqueous KOH ($\mathrm{OH^-}$) | Alcohol R–OH |
| Sodium alkoxide ($\mathrm{R'O^-}$) | Ether R–O–R' (Williamson synthesis) |
| KCN ($\mathrm{CN^-}$) | Nitrile R–CN |
| Alcoholic $\mathrm{NH_3}$ (lone pair on N) | Amine R–$\mathrm{NH_2}$ |
| Sodium thiolate/NaSH | Thiol R–SH |
In the Williamson synthesis the alcohol is first converted to its alkoxide, which then displaces the halide to give an ether.
Grignard reagent
An alkyl halide reacts with magnesium turnings in dry ether (a crystal of iodine helps start the reaction) to give an alkylmagnesium halide:
$$\mathrm{R{-}X + Mg \xrightarrow{\text{dry ether}} R{-}Mg{-}X}$$
The ease of formation follows the same order, RI > RBr > RCl; alkyl fluorides do not form Grignard reagents easily.
Effect of the alkyl group
- SN1 goes through a carbocation, so it is fastest for tertiary > secondary > primary.
- SN2 needs back-side attack, so it is fastest for primary > secondary > tertiary (least crowding).
Common MDCAT traps
- Reactivity follows bond strength, not polarity: R–F is least reactive even though it is most polar.
- $\mathrm{OH^-}$ is a strong nucleophile but a poor leaving group; do not confuse the two roles.
- In the reaction with ammonia, $\mathrm{NH_3}$ itself is the nucleophile.
- Grignard reagents are made with Mg, not Na, K or Ca.
Quick revision
- C–X carbon is $\delta+$ and electrophilic.
- R–I > R–Br > R–Cl > R–F.
- HI > HBr > HCl > HF in reactivity.
- Best leaving group: $\mathrm{I^-}$; poor leaving group: $\mathrm{OH^-}$.
- R–X + Mg (dry ether) → RMgX.