Joseph K. Myers

3-16-04

S_N2 and S_N1 Reactions: Experiments 6 and 7

(Preparation of 1-bromobutane from 1-butanol, 2-chloro-2-methylbutane from 2-methyl-2-butanol)

Introduction

In the name S_N1 or S_N2, the S stands for substitution. One part of the starting molecule is replaced by something else.

The N stands for nucleophilic, which refers to a reaction where a nucleophile (also referred to as Nu) is attracted to the electrophile (usually a carbon atom). The nucleophile attacks the electrophile to form a bond.

When the nucleophile attacks, it either forces the leaving group to break off (in an S_N2 reaction), or it simply forms a bond to a carbocation which has already lost its leaving group (in an S_N1) reaction.

Now it is clear to explain the meaning of the 1 or 2. The 2 stands for bimolecular, because two components are involved simultaneously in a "concerted" reaction. Therefore, the leaving group is breaking off while the nucleophile is attaching, and so the result is that the nucleophile will be attached to the opposite side. This is called an "inversion of configuration."

Then, in the other kind of reaction, called 1 or "unimolecular," the nucleophile can attack from either side. The carbocation is very reactive, and the transition state involving the carbocation shows a trigonal planar stereochemistry.

If in fact there is an equal energy of activation for the approach from either side, then S_N1 will produce a racemic mixture after starting from a chiral compound. Often, however, there are reasons why activation energy for approach from one side is greater, and so the product retains some unequal proportion of stereoisomers.

All the four parts involved in these reactions are important: the substrate, the nucleophile, the leaving group, and the solvent.

To be a nucleophile, a molecule must have an unbonded pair of electrons. To be a good nucleophile, generally, a molecule should be a strong base.

A good leaving group will be a weak base, or form a strong conjugate acid.

For an S_N2 reaction, a good substrate will be preferably 1-degree and not beta-branched. This is because, due to the mechanism of the reaction, it is affected by steric hindrances. It is also an acceptable mechanism under good conditions for 2-degree substrates. (That is, the alpha carbon is bonded to two other carbons in the substrate.) For 3-degree substrates, this reaction is virtually not possible.

The opposite is the case for S_N1 reactions, because the carbocations which are formed are more stabilized in the order 3-deg > 2-deg >> 3-deg.

To be a good solvent for S_N2 reactions, the solvent should be polar aprotic. The best of all is HMPA, and others such as DMSO also strongly encourage the S_N2 mechanism. If the solvent, such as a protic solvent, solvates the nucleophile too greatly, it cages it in to interfere with its ability to attack the substrate.

The best solvent for S_N1 reactions should be polar protic, to maximally stabilize the carbocation transition state and thereby lower the energy of activation.

Table of reagents and reactants

(Table 01)

Table of Reactant

(Table 02)

Note: 1-butanol and sodium bromide are used together as reactants for the first experiment, and 2-methyl-2-butanol and hydrochloric acid are used together as reactants for the second experiment.

Reactions and mechanisms

(These reactions and mechanisms are illustrated on separate paper.)

Formation of 1-bromobutane from 1-butanol:

This is a very simple reaction. In biology it is referred to as a dehydration synthesis reaction. The main point of learning is in knowing how to displace the equilibrium to the right, such as using a large excess of acid.

In general, the H-X + R-OH is a reversible reaction to R-X + H₂O.

Specifically,

CH₃CH₂CH₂CH₂-OH + HBr

is a reversible reaction to

CH₃CH₂CH₂CH₂-Br + H₂O.

The mechanism has electron movement from the OH to an H⁺ ion.

Then in the presence of Br:^- ions, electron movement is from the Br:^- ion to the CH₂ portion of -CH₂-OH. Final electron movement from the CH₂-O bond breaks off H₂O, and the electrons moved from Br:^- now form a bond, with Br in the place of OH.

Formation of 2-chloro-2-methylbutane from 2-methyl-2-butanol:

This reaction is extremely similar. However, a greater variety of mechanisms have a reasonable chance of participating.

The loss of a proton from the tertiary carbocation gives two products, 2-methyl-1-butene and 2-methyl-2-butene.

Addition of the HCl to these gives the desired 2-chloro-2-methyl butane.

Flowchart

For preparation of 1-bromobutane:

Mix 11.1 g NaBr + 10 mL H₂O + 10 mL 1-butanol + 10 mL HCl in 100 mL RB flask; mix well while cooling in ice (must be in ice when 10 mL HCl is added), set up apparatus for reflux.

Warm gently 30 min.

Simple distillation--collect water and 1-bromobutane in ice-cooled receiver. (115-deg-C head temperature).

Transfer to separatory funnel, then add 10 mL water. Separate layers.

Wash organic layer: a) twice with 5 mL of 2 M NaOH, b) 10 mL water, c) 10 mL sat. aq. NaCl.

Dry over anhydrous Na₂SO₄ (4 spatula tips) for 10 min.

Transfer 1-bromobutane to 50 mL RB flask. Set up short path distillation. Collect product at bp > 90-deg-C.

For preparation of 2-chloro-2-methylbutane:

Mix 10 mL 2-methyl-2-butanol + 25 mL conc. 12 M HCl in separatory funnel.

Wash organic layer with a) 10 mL sat. aq. NaCl, b) cold sat. aq. NaHCO₃, c) 10 mL water, d) sat. aq. NaCl.

Dry over anhydrous NaSO₄ (4 spatula tips).

Distill with short-path distillation.

Collect fraction at bp > 75-deg-C.

For both procedures:

Weigh product. Calculate %-yield. Save the sample.

Observations

The reaction of NaBr and 1-butanol plus HCl is very exothermic. It melted a great deal of ice.

The organic layer in the 1-bromobutane washing is always the lower of the two layers.

To avoid losing some of the product, do not rinse out the washing container between returning the product mixture to the separatory funnel, unless it is necessary.

For instance, when ready to wash with aqueous NaCl, and after just washing with 10 mL of water, don't rinse the residue of water and product out of the container before washing with NaCl in the same container.

The smoke from HCl can cause one to cough.

Results

Discussion and conclusion

There are several significant things about the results of these two experiments.

Most importantly, we were successful in understanding the two types of reactions, and the differences between them.

We also have to think about how to be more efficient in making product, and what produces low yields versus what produces high yields, as well as what saves time in laboratory.

With small quantities of reaction material it is hard to generate good yield.

A lot of the product is lost through repeated transfers between containers.

Funnels also cause product loss.

Higher product yields also are caused by careful planning of which containers are used. Containers with excess volume increase the amount of wasted product.

Probably the large difference in percent yield (19.96 to 40.65) is due to not enough care being taken in separating the layers and washing at each step of production of 1-bromobutane. The container should be capped and mixed thoroughly, and the separation to be complete before separating. Also, minimal product should be discarded along with the inorganic layer of the separation.

References

1. Gilbert JC, Martin SF. Experimental Organic Chemistry. 2002. 3rd Edition. p425-443.