Reactions of Haloalkanes

(1) Nucleophilic Substitution: The General Picture

A nucleophile is an electron-rich species — it may be a negatively charged ion or a neutral molecule with a lone pair — and it seeks out the electron-deficient carbon of the C—X bond. When it attacks that carbon, it forms a new bond there while the halogen is pushed out as a halide ion. Because the whole event is triggered by the incoming nucleophile, the process is named a nucleophilic substitution reaction, and the haloalkane undergoing it is called the substrate:

This is one of the richest classes of reactions available to alkyl halides precisely because so many different nucleophiles can play the role of $\mathrm{Nu^-}$, and each one installs a different functional group in place of the halogen. Hydroxide ion gives an alcohol, an alkoxide gives an ether, cyanide gives a nitrile, ammonia gives a primary amine, a carboxylate gives an ester, and so on — a whole card of nucleophilic-substitution products is built up this way for a single substrate class, which is why this reaction is so central to converting a haloalkane into virtually any other functional group (the specific reagent–nucleophile–product correspondences are collected together as reference data, not repeated here).

Ambident Nucleophiles

A handful of nucleophiles are unusual in offering two distinct atoms through which they can bond, and these are called ambident nucleophiles. The cyanide ion is the standard example: it can be drawn as a resonance hybrid, $^-\mathrm{C}\!\equiv\!\mathrm{N} \leftrightarrow \mathrm{C}\!=\!\mathrm{N}^-$, so it is genuinely free to attack a substrate through either its carbon end or its nitrogen end. In practice which end is used depends on the character of the reagent supplying the cyanide. An ionic source such as $\mathrm{KCN}$ delivers a "naked," fully ionic cyanide ion in solution, and here the attack proceeds mainly through carbon (because the resulting C—C bond is more stable than a C—N bond), giving an alkyl cyanide as the chief product. A covalent source such as $\mathrm{AgCN}$, on the other hand, is not freely ionic; the silver holds the carbon end tightly, leaving the nitrogen free to act as the nucleophilic centre, so the same substrate now gives predominantly the isocyanide (isonitrile). The nitrite ion, $\mathrm{^-O\!-\!N\!=\!O}$, is the second common ambident nucleophile: linkage through its oxygen atom produces an alkyl nitrite, while linkage through its nitrogen atom produces a nitroalkane.

This reaction has been shown to occur through two distinct mechanistic pathways, and the pathway a given substrate follows has consequences for reaction rate, stereochemistry, and even the product distribution when several products are possible. These two mechanisms are examined next.

(a) The $S_N2$ Mechanism — Bimolecular Nucleophilic Substitution

When methyl chloride reacts with hydroxide ion to give methanol and chloride ion, careful kinetic measurement shows that the reaction rate depends on the concentration of both reactants at once — doubling either the haloalkane concentration or the hydroxide concentration doubles the rate. This is second-order kinetics, and a reaction obeying it is called bimolecular nucleophilic substitution, abbreviated $S_N2$.

Mechanism: A Single, Concerted Step

The defining feature of $S_N2$ is that there is only one step and no intermediate is ever formed. The incoming nucleophile does not wait for the halide to leave first — it approaches the carbon from the side directly opposite the leaving halogen (a "backside" approach) at the same moment that the carbon–halogen bond is weakening. As the nucleophile's bond to carbon strengthens and the carbon–halogen bond stretches and breaks, the three other substituents on that carbon (three C—H bonds, in the case of methyl chloride) are forced to sweep past the carbon and flip to the opposite side, exactly the way an open umbrella turns inside out when caught by a strong gust of wind.

At the mid-point of this process — the transition state — the reacting carbon is momentarily and simultaneously bonded to five groups: the three original substituents (now lying roughly in one plane), the partially-formed bond to the incoming nucleophile, and the partially-broken bond to the departing halogen. This five-coordinate arrangement is far too high in energy to be isolated as a real species; it exists only fleetingly, as a transition state, not an intermediate. Once past this point, the nucleophile's bond to carbon completes and the halide ion departs fully, leaving a product whose spatial arrangement at that carbon is the mirror image of what the substrate had.

Inversion of Configuration (Walden Inversion)

This flipping of the three retained substituents to the opposite face of the carbon is called inversion of configuration: the spatial arrangement of groups is inverted, exactly as an umbrella turned inside out has all its ribs pointing the opposite way.

Every genuine $S_N2$ step proceeds with complete inversion at the carbon under attack — the nucleophile always ends up bonded from the side opposite to where the leaving group departed, never from the same side.

Steric Effects and the $S_N2$ Reactivity Order

Because the nucleophile must be able to approach the back face of the carbon bearing the halogen, anything that physically crowds that face slows the reaction down. A methyl halide, with only three small hydrogen atoms around the reacting carbon, offers the least resistance and reacts fastest. Moving to a primary halide (one alkyl group in the way), then a secondary halide (two alkyl groups), then a tertiary halide (three bulky alkyl groups surrounding the carbon) progressively blocks the nucleophile's path of approach more and more, so the rate of $S_N2$ substitution falls steadily in that order. The overall reactivity sequence for $S_N2$ is therefore:

with tertiary halides essentially unreactive by this pathway because the bulky groups make backside attack geometrically impossible.

(b) The $S_N1$ Mechanism — Unimolecular Nucleophilic Substitution

A different kinetic pattern shows up for reactions such as tert-butyl bromide with hydroxide ion in a polar protic solvent (water, an alcohol, or acetic acid, for instance): the rate here depends only on the concentration of the alkyl halide and is completely unaffected by how much hydroxide is present. This is first-order kinetics, and the pathway is called unimolecular nucleophilic substitution, or $S_N1$.

Mechanism: Two Steps Through a Carbocation

$S_N1$ substitution happens in two distinct steps rather than one concerted motion.

Step 1 (slow, rate-determining, reversible). The polarised carbon–halogen bond breaks heterolytically on its own, without any help from the nucleophile, so the halide ion departs first and leaves behind a positively charged carbocation. Because breaking this bond costs energy, this ionisation step needs assistance — in a polar protic solvent, the departing halide ion is stabilised (solvated) by hydrogen-bonding to the solvent's protons, and this solvation is what supplies the energy needed for the bond to break. This step is the bottleneck of the whole reaction, which is exactly why the overall rate tracks only the alkyl halide's concentration: the hydroxide ion has no part to play until after the slow step is over.

Step 2 (fast). The nucleophile now attacks the carbocation that was generated in step 1, completing the substitution and giving the product.

Carbocation Stability Governs the Rate

Since the rate-determining step is the formation of the carbocation, anything that makes that carbocation more stable makes it form faster and so speeds up the whole reaction. Alkyl groups are electron-donating relative to hydrogen, so a carbocation surrounded by more alkyl groups is more stabilised. This gives tertiary carbocations markedly greater stability than secondary, and secondary greater than primary, so a tertiary halide undergoes $S_N1$ substitution the fastest of all, and the order runs:

Allylic and Benzylic Halides

For the same reason — carbocation stability controlling the rate — allylic and benzylic halides are also unusually reactive in $S_N1$ substitution, even though the carbon bearing the halogen may only be primary. The positive charge generated on ionisation is not confined to a single carbon; it is delocalised over the adjacent double bond (in an allylic system) or over the aromatic ring (in a benzylic system) through resonance, spreading the charge across several atoms and lowering the energy of the cation substantially. This resonance stabilisation is unavailable to an ordinary, unconjugated alkyl carbocation of the same degree, which is why allylic and benzylic substrates punch above their apparent (primary) weight in $S_N1$ reactions.

The Effect of the Halogen Itself

Independent of whether the mechanism is $S_N1$ or $S_N2$, the identity of the halogen atom also affects how readily it is displaced, and — for a given alkyl group — this order is the same in both mechanisms:

Iodide is the best leaving group because the C—I bond is the weakest and the large iodide ion is best able to disperse its negative charge, while fluoride is a very poor leaving group because the C—F bond is exceptionally strong.

Rearrangement (beyond NCERT)

Because $S_N1$ passes through a genuine, discrete carbocation intermediate, that intermediate is free to undergo the same kind of hydride or alkyl shifts any other carbocation can undergo before the nucleophile ever attacks it, so a rearranged product (built on a more stable, shifted skeleton) can sometimes appear alongside — or even instead of — the "straightforward" substitution product. This possibility of rearrangement is a direct consequence of a true intermediate existing, and it has no counterpart in the concerted, one-step $S_N2$ pathway.

(c) Stereochemistry of Nucleophilic Substitution Reactions

To describe how the shape of a molecule changes across a substitution reaction, a short set of stereochemical ideas is needed first.

(i) Optical Activity

Ordinary light vibrates in every direction perpendicular to its path; passing it through a Nicol prism selects out only the light vibrating in a single plane, called plane-polarised light. Certain compounds, when placed in the path of this plane-polarised light, rotate the plane through some angle — these are optically active compounds, and the angle of rotation is measured with a polarimeter. A compound that rotates the plane to the right (clockwise, as seen by the observer) is dextrorotatory, or the $d$-form, marked with a $(+)$ sign before the angle; one that rotates it to the left (anticlockwise) is laevorotatory, the $l$-form, marked with a $(-)$ sign. A pair of $(+)$ and $(-)$ forms of the same compound are called optical isomers, and the phenomenon itself is optical isomerism.

(ii) Chirality, Asymmetric Carbons, and Enantiomers

The tetrahedral arrangement of four groups (valencies) around a carbon atom means that if all four attached groups are different from one another, the mirror image of that arrangement cannot be superimposed on the original — no amount of rotation makes the two coincide. Such a carbon is called an asymmetric carbon or a stereocentre, and the molecule built around it is described as an asymmetric or chiral molecule. This tetrahedral picture of the asymmetric carbon was proposed in the same year, 1874, by the Dutch scientist J. van't Hoff and the French scientist C. Le Bel — building on Louis Pasteur's 1848 observation that certain tartaric-acid salt crystals exist as two non-identical, mirror-image forms. This non-superimposability of the mirror image on the original is exactly what produces optical activity.

The same idea of symmetry and asymmetry shows up in everyday objects. A sphere, a cube, or a cone is identical to its own mirror image and can be freely superimposed on it — such objects are achiral. A left hand and a right hand, by contrast, look alike but cannot be laid on top of one another once their mirror-image relationship is fixed — objects with this non-superimposable-mirror-image property are called chiral, and the property itself is chirality. Chiral molecules are optically active; achiral molecules are optically inactive.

The presence of a single asymmetric carbon is a convenient (though not the only) aid for spotting a chiral molecule. A molecule such as propan-2-ol, where the carbon bearing the $-\mathrm{OH}$ carries two identical methyl groups (along with H and OH), does not have an asymmetric carbon — all four attached groups are not distinct — and sure enough, its mirror image can be rotated back into exact coincidence with the original: propan-2-ol is achiral.

Butan-2-ol, on the other hand, has four genuinely different groups on the carbinol carbon ($-\mathrm{CH_3}$, $-\mathrm{OH}$, $-\mathrm{H}$, and $-\mathrm{C_2H_5}$); however its mirror image is rotated, it can never be brought back into coincidence with the original — butan-2-ol is chiral.

Other familiar chiral examples include 2-chlorobutane, 2,3-dihydroxypropanal, bromochloroiodomethane, and 2-bromopropanoic acid — in each, the reacting or stereogenic carbon carries four different substituents.

A pair of stereoisomers that are related to each other as non-superimposable mirror images of one another are called enantiomers. Enantiomers share every ordinary physical property — melting point, boiling point, refractive index, density, and so on — identically; the only property in which they differ is the direction in which they rotate plane-polarised light. If one enantiomer of a pair is dextrorotatory, the other is necessarily laevorotatory, and by exactly the same magnitude.

Racemic Mixtures and Racemisation

A mixture containing the two enantiomers of a compound in exactly equal proportions shows zero net optical rotation, because the rotation contributed by one enantiomer is exactly cancelled by the equal-and-opposite rotation of the other. Such a 50:50 mixture is called a racemic mixture (or racemic modification), and is denoted by prefixing $dl$- or $(\pm)$- to the compound's name. The process by which a single, optically active enantiomer is converted into this 50:50 mixture is called racemisation.

(iii) Retention

Retention of configuration means that the spatial arrangement of the bonds around a stereocentre is preserved through a chemical change. In general, if a reaction does not break any bond directly attached to the stereocentre, the product keeps the same general arrangement of groups that the reactant had, and the reaction is said to proceed with retention of configuration — even though, as noted above, the sign of rotation in the product need not match that of the reactant, since it is the spatial configuration, not the sign of rotation, that is preserved.

(iv) Inversion, Retention, and Racemisation

When a bond directly attached to an asymmetric carbon is broken during a reaction, three outcomes are possible for what happens at that carbon:

• If the product retains the same spatial arrangement as the reactant (with the new group taking the position vacated by the old one, on the same side), the process is inversion's opposite and is again called retention of configuration.
• If the new group ends up on the side directly opposite to where the old group was — the configuration has flipped — the process is called inversion of configuration.
• If the reaction gives a 50:50 mixture of both possible spatial outcomes, so that the net product is optically inactive, the process is racemisation.

$S_N2$ Proceeds with Inversion

When an optically active alkyl halide undergoes genuine $S_N2$ substitution, the product invariably shows inverted configuration relative to the starting material, because — as already described in the mechanism — the nucleophile can only attack from the face opposite to the leaving halogen. A reaction between an optically active secondary bromide and hydroxide ion illustrates this cleanly: the incoming $-\mathrm{OH}$ group ends up occupying the position on the carbon skeleton exactly opposite to the one the bromide had occupied. Since only a single, clean backside attack is geometrically possible, $S_N2$ substitution of an optically active substrate gives a single, fully inverted, optically active product — inversion is complete, not partial.

$S_N1$ Proceeds with Racemisation

When an optically active alkyl halide undergoes $S_N1$ substitution, the outcome is different: the product is (largely) racemised. The reason lies in the geometry of the intermediate. The carbocation generated in the slow, rate-determining step is $sp^2$-hybridised, so the three groups attached to the positively charged carbon — along with the carbon itself — lie flat, in one plane. A planar carbocation of this kind is itself achiral: it has no "front" or "back" face that is inherently different from the other. The incoming nucleophile in the fast second step is therefore free to attack this flat cation from either face with roughly equal likelihood, and each face of attack leads to a different spatial outcome at the carbon. Attack from the face the leaving halide vacated from regenerates the same configuration the substrate originally had; attack from the opposite face gives the inverted configuration. Because both faces are attacked with nearly equal probability, the two outcomes are formed in close to equal amounts, giving an essentially racemic — and hence largely optically inactive — product overall.

2. Elimination Reactions (Dehydrohalogenation)

Nucleophilic substitution is not the only fate available to a haloalkane that carries a hydrogen on the carbon adjacent to the one bearing the halogen (this adjacent carbon is called the $\beta$-carbon, and the carbon directly bonded to the halogen is the $\alpha$-carbon). When such a haloalkane is heated with an alcoholic solution of potassium hydroxide (rather than an aqueous one), a different reaction takes over: a base removes a hydrogen atom from the $\beta$-carbon at the same time that the halogen departs from the $\alpha$-carbon, and a new $\pi$ bond forms between the $\alpha$- and $\beta$-carbons in its place. The overall result is loss of one molecule of the hydrogen halide from the substrate and formation of an alkene:

Since it is specifically the hydrogen on the $\beta$-carbon that is removed, this class of elimination is commonly called $\beta$-elimination, and because the products lost are the elements of a hydrogen halide, the overall process is also known as dehydrohalogenation.

Saytzeff's Rule

Many haloalkanes have more than one type of $\beta$-hydrogen available — that is, hydrogens on more than one neighbouring carbon, or on carbons that would give differently substituted double bonds — so more than one alkene is, in principle, possible from a single elimination. In practice one of these alkenes usually dominates as the major product. The Russian chemist Alexander Zaitsev (Saytzeff) recognised this pattern in 1875 and stated it as a rule: in a dehydrohalogenation reaction, the preferred alkene is the one carrying the greater number of alkyl groups on its doubly bonded carbons — in other words, the more highly substituted, more stable alkene wins out as the major product, while the less-substituted alternative forms as the minor product. …