Why Some Reactions Flip a Molecule Inside Out Like an Umbrella

The polar C–X bond makes haloalkanes excellent starting points for building other molecules. Depending on structure and conditions, a haloalkane can swap its halogen for another group, lose HX to form an alkene, or react with a metal.

This part covers SN1 and SN2 substitution, chirality and stereochemistry, elimination and reactions with metals, and haloarenes with the uses and hazards of polyhalogen compounds.

SN2 is a one-step reaction in which the nucleophile attacks from the back as the halide leaves, so its rate depends on both reactants; SN1 happens in two steps through a carbocation, so its rate depends only on the haloalkane.

SN2:

- Rate $=k[\text{RX}][{\text{Nu}}^{-}]$ — second order
- One step, through a transition state with five groups around carbon
- Favoured by primary haloalkanes, strong nucleophiles and polar aprotic solvents such as acetone
- Reactivity: CH${}_3$X > primary > secondary > tertiary, since bulky groups block back-side attack

SN1:

- Rate $=k[\text{RX}]$ — first order
- Slow step: RX ionises to a carbocation and X${}^{-}$; fast step: the nucleophile attacks
- Favoured by tertiary, allylic and benzylic halides, which form stable carbocations, and polar protic solvents such as water and alcohols
- Reactivity: tertiary > secondary > primary > CH${}_3$X

Worked example. An SN2 reaction runs at $2.0\times 10^{-4}$ mol L${}^{-1}$ s${}^{-1}$ with $[\text{RX}]=0.10$ M and $[{\text{OH}}^{-}]=0.10$ M:

$$k=\frac{2.0\times 10^{-4}}{0.10\times 0.10}=2.0\times 10^{-2}{\text{ L mol}}^{-1}{\text{ s}}^{-1}$$

Doubling [OH${}^{-}$] would double this rate; an SN1 rate would not change.

An everyday example. Benzyl chloride hydrolyses readily in water because the benzyl carbocation is stabilised by the benzene ring.

The substance. Tertiary halides rarely react by SN2 — three bulky groups leave no room for the nucleophile to approach from behind.

A chiral molecule cannot be superimposed on its mirror image, usually because one carbon carries four different groups; its two mirror-image forms are enantiomers, an equal mixture of them is racemic and optically inactive, SN2 inverts the configuration, and SN1 mostly gives racemisation.

Key terms:

- Chiral centre — a carbon bonded to four different groups, as in 2-chlorobutane
- Enantiomers — non-superimposable mirror images that rotate plane-polarised light by equal amounts in opposite directions
- Racemic mixture — equal amounts of both enantiomers, with zero net rotation
- Retention keeps the spatial arrangement; inversion flips it

Optical outcome:

- SN2 — back-side attack gives complete inversion, like an umbrella turning inside out in the wind
- SN1 — the flat carbocation can be attacked from either face, giving racemisation

Worked example. A sample containing $0.75$ of one enantiomer and $0.25$ of the other has an enantiomeric excess of

$$0.75-0.25=0.50$$

so it rotates light half as much as the pure enantiomer, while a racemic $0.50$ and $0.50$ mixture rotates it by zero.

An everyday example. Your left and right hands are mirror images that cannot be superimposed — a left glove never fits a right hand, just as enantiomers cannot be laid over each other.

The substance. Inversion of configuration does not automatically reverse the sign of rotation — the direction of rotation is measured, not predicted from the geometry.

Heating a haloalkane with alcoholic KOH removes HX to form an alkene, with Saytzeff's rule predicting the more substituted alkene as the major product; with sodium in dry ether haloalkanes couple in the Wurtz reaction, and with magnesium in dry ether they form Grignard reagents.

Elimination:

- Reagent: alcoholic KOH, heated
- Saytzeff's rule — the alkene with more alkyl groups on its double-bond carbons is preferred

$${\text{CH}}_3{\text{CH}}_2{\text{CHBrCH}}_3\stackrel{\text{alc. KOH}}{\to }{\text{CH}}_3{\text{CH=CHCH}}_3\text{ (major)}+{\text{CH}}_2{\text{=CHCH}}_2{\text{CH}}_3\text{ (minor)}$$

Wurtz reaction:

$$2\text{RX}+2\text{Na}\stackrel{\text{dry ether}}{\to }\text{R-R}+2\text{NaX}$$

Grignard reagent:

$$\text{RX}+\text{Mg}\stackrel{\text{dry ether}}{\to }\text{RMgX}$$

Grignard reagents react with any source of protons, as in $\text{RMgX}+{\text{H}}_2\text{O}\to \text{RH}+\text{Mg(OH)X}$, so everything must be kept dry.

Worked example. Bromoethane with sodium gives butane:

$$2{\text{C}}_2{\text{H}}_5\text{Br}+2\text{Na}\to {\text{C}}_4{\text{H}}_{10}+2\text{NaBr}$$

From $21.8$ g of bromoethane, $\frac{21.8}{109}=0.20$ mol, at most $0.10$ mol of butane, or $5.8$ g, can form.

An everyday example. Pharmaceutical chemists use Grignard reagents to join carbon chains when building the molecules of medicines.

The substance. Wurtz coupling of two different haloalkanes gives a mixture of three alkanes, so it is useful mainly for symmetrical ones.

In haloarenes, resonance gives the C–X bond partial double-bond character, so nucleophilic substitution is very difficult, although halogens still direct electrophiles to the ortho and para positions.

Low reactivity:

- Resonance gives the C–Cl bond partial double-bond character
- The phenyl cation is unstable, ruling out SN1, and the ring blocks back-side attack, ruling out SN2
- Chlorobenzene gives phenol only with NaOH at about $623$ K and high pressure; **–NO${}_2$ groups at ortho and para positions make substitution much easier

Directive influence. Halogens are deactivating but ortho–para directing: they withdraw electrons inductively but release them by resonance to the ortho and para positions.

Polyhalogen compounds:

- Dichloromethane — solvent and paint remover; harms the nervous system
- Trichloromethane — solvent; oxidised by air in light to poisonous phosgene, so it is stored in full, dark bottles
- Iodoform — an antiseptic that works by releasing iodine
- Tetrachloromethane — solvent; damages the liver and depletes ozone
- Freons (chlorofluorocarbons) — refrigerants; they break down in the upper atmosphere and destroy ozone
- DDT — insecticide against malaria-carrying mosquitoes; it persists and builds up in food chains, harming birds and fish

An everyday example. Old refrigerators and air conditioners used freons, whose release is linked to thinning of the ozone layer.

The substance. Halogens are the exception to the usual rule** — they slow electrophilic substitution yet still direct it to ortho and para positions.