SN1 Reaction – Nucleophilic Substitution reaction

S_N1 Reaction: First-Order Nucleophilic Substitution

– When tert-butyl bromide is placed in boiling methanol, methyl tert butyl ether can be isolated from the reaction mixture.

– Because this reaction takes place with the solvent acting as the nucleophile, it is called a solvolysis (solvo for “solvent,” plus lysis, meaning “cleavage”)

– This solvolysis is a substitution because methoxide has replaced bromide on the tertbutyl group.

– It does not go through the S_N2 mechanism, however. The S_N2 requires a strong nucleophile and a substrate that is not too hindered.

– Methanol is a weak nucleophile, and tert-butyl bromide is a hindered tertiary halide—a poor S_N2 substrate.

– If this substitution cannot go by the S_N2 mechanism, what kind of mechanism might be involved? An important clue is kinetic: Its rate does not depend on the concentration of methanol, the nucleophile.

– The rate depends only on the concentration of the substrate, tert butyl bromide.

– This rate equation is first order overall: first order in the concentration of the alkyl halide and zeroth order in the concentration of the nucleophile.

– Because the rate does not depend on the concentration of the nucleophile, we infer that the nucleophile is not present in the transition state of the rate-limiting step.

– The nucleophile must react after the slow step.

– This type of substitution is called S_N1 an reaction, for Substitution, Nucleophilic, unimolecular.

– The term unimolecular means there is only one molecule involved in the transition state of the rate-limiting step.

– The mechanism of the S_N1 reaction of tertbutyl bromide with methanol is shown here.

– Ionization of the alkyl halide (first step) is the rate-limiting step.

Mechanism of The S_N1 Reaction

– The S_N1 mechanism is a multistep process.

– The first step is a slow ionization to form a carbocation.

– The second step is a fast attack on the carbocation by a nucleophile.

– The carbocation is a strong electrophile; it reacts very fast with nucleophiles, including weak nucleophiles.

– The nucleophile in S_N1 reactions is usually weak, because a strong nucleophile would be more likely to attack the substrate and force some kind of second-order reaction.

– If the nucleophile is an uncharged molecule like water or an alcohol, the positively charged product must lose a proton to give the final uncharged product.

– The general mechanism for the S_N1 reaction is summarized in the following Mechanism.

– The S_N1 reaction involves a two-step mechanism.

– A slow ionization gives a carbocation that reacts quickly with a (usually weak) nucleophile.

Reactivity: 3° > 2° > 1°.

Step 1. Formation of the carbocation (rate-limiting).

Step 2. Nucleophilic attack on the carbocation (fast).

If the nucleophile is water or an alcohol, a third step is needed to deprotonate the product.

EXAMPLE: Solvolysis of 1-iodo-1-methylcyclohexane in methanol.

Step 1: Formation of a carbocation (rate-limiting).

Step. 2: Nucleophilic attack by the solvent (methanol).

Step 3: Deprotonation to form the product.

Reaction-energy diagram of The S_N1 Reaction

– The reaction-energy diagram of the S_N1 reaction (see Figure) shows why the rate does not depend on the strength or concentration of the nucleophile.

– The ionization (first step) is highly endothermic, and its large activation energy determines the overall reaction rate.

– The nucleophilic attack (second step) is strongly exothermic, with a lower-energy transition state.

– In effect, a nucleophile reacts with the carbocation almost as soon as it forms.

– The reaction-energy diagrams of the S_N1 mechanism and the S_N2 mechanism are compared in the preivous Figure.

– The S_N1 has a true intermediate, the carbocation.

– The intermediate appears as a relative minimum (a low point) in the reaction-energy diagram.

– Reagents and conditions that favor formation of the carbocation (the slow step) accelerate the S_N1 reaction; reagents and conditions that hinder its formation retard the reaction.

Substituent Effects on S_N1 Reaction

– The rate-limiting step of the S_N1 reaction is ionization to form a carbocation, a strongly endothermic process.

– The first transition state resembles the carbocation (Hammond postulate); consequently, rates of S_N1 reactions depend strongly on carbocation stability.

– we saw that alkyl groups stabilize carbocations by donating electrons through sigma bonds (the inductive effect) and through overlap of filled orbitals with the empty p orbital of the carbocation (hyperconjugation).

– Highly substituted carbocations are therefore more stable.

Reactivity toward S_N1 substitution mechanisms follows the stability of carbocations:

• This order is opposite that of the S_N2 reaction.

– Alkyl groups hinder the S_N2 by blocking attack of the strong nucleophile, but alkyl groups enhance the S_N1 by stabilizing the carbocation intermediate.

– Resonance stabilization of the carbocation can also promote the S_N1 reaction.

– For example, allyl bromide is a primary halide, but it undergoes the S_N1 reaction about as fast as a secondary halide.

– The carbocation formed by ionization is resonance stabilized, with the positive charge spread equally over two carbon atoms.

– Vinyl and aryl halides generally do not undergo S_N1 or S_N2  reactions.

-An S_N1 reaction would require ionization to form a vinyl or aryl cation, either of which is less stable than most alkyl carbocations.

– An S_N2 reaction would require back-side attack by the nucleophile, which is made impossible by the repulsion of the electrons in the double bond or aromatic ring.

Leaving-Group Effects on S_N1 Reaction

– The leaving group is breaking its bond to carbon in the rate-limiting ionization step of the S_N1 mechanism.

– A highly polarizable leaving group helps stabilize the rate-limiting transition state through partial bonding as it leaves.

– The leaving group should be a weak base, very stable after it leaves with the pair of electrons that bonded it to carbon.

– The following figure shows the transition state of the ionization step of the S_N1 reaction.

– Notice how the leaving group is taking on a negative charge while it stabilizes the new carbocation through partial bonding.

– The leaving group should be stable as it takes on this negative charge, and it should be polarizable to engage in effective partial bonding as it leaves.

– A good leaving group is just as necessary in the S_N1 reaction as it is in the S_N2 , and similar leaving groups are effective for either reaction.

– The following Table lists some common leaving groups for either reaction.

Solvent Effects

– The S_N1 reaction goes much more readily in polar solvents that stabilize ions.

– The ratelimiting step forms two ions, and ionization is taking place in the transition state.

– Polar solvents solvate these ions by an interaction of the solvent’s dipole moment with the charge of the ion.

– Protic solvents such as alcohols and water are even more effective solvents because anions form hydrogen bonds with the -OH hydrogen atom, and cations complex with the nonbonding electrons of the -OH oxygen atom.

– Ionization of an alkyl halide requires formation and separation of positive and negative charges, similar to what happens when sodium chloride dissolves in water.

– Therefore, S_N1 reactions require highly polar solvents that strongly solvate ions.

– One measure of a solvent’s ability to solvate ions is its dielectric constant a measure of the solvent’s polarity.

– The following table lists the dielectric constants of some common solvents and the relative ionization rates for tert-butyl chloride in these solvents.

– Note that ionization occurs much faster in highly polar solvents such as water and alcohols.

– Although most alkyl halides are not soluble in water, they often dissolve in highly polar mixtures of acetone and alcohols with water.