Elimination of Tosylates
Purpose: Propose a mechanism for elimination of a cyclic tosylate based on product distribution
Background: An elimination reaction can be defined as one in which two substituents are
removed from a molecule to form a pi bond. Although this definition is simple, the range of
mechanisms by which eliminations occur is broad. At one end of the spectrum, the reaction
might proceed by a complete breaking of the bond to the leaving group to form a carbocation
intermediate, followed by proton removal to give the pi bond. (This is called an E1 mechanism.)
At the other end of the spectrum, the reaction might proceed via a first step of base removal of a
proton to give a carbanion, followed in a second step by the leaving group leaving to form a pi
bond. (This is called an E1cb mechanism.)
Both of these mechanisms are regioselective, meaning that product distributions is based on the
relative energies of the transition states leading to different products. In the case of the E1
reaction, this step is the formation of the alkene from the carbocation intermediate, and therefore,
the alkene stability generally determines the relative product distribution. In the E1cb
mechanism, the deprotonation is the product determining step. The more stable carbanion is
therefore what determines the product distribution.
E1 and E1cb mechanisms are also stereoselective, meaning that the more stable stereoisomer
predominates. In many cases, both (E) and (Z) products are possible, and the more stable is the
major product. In the case of disubstituted compounds, the trans is generally preferred to the cis
compound.
In contrast to E1 and E1cb, the concerted mechanism, known as E2, is stereospecific. The
mechanism requires that the -hyrdrogen be oriented antiperiplanar to the leaving group.
Because the mechanism is concerted, this mechanistic requirement dictates the stereochemistry
of the product. Furthermore, because it is an absolute requirement, it can also dictate the
regiochemistry outcome in a conformationally locked system, such as a ring. If it is impossible
to achieve the conformationally required transition state leading to a particular product, that
product will not form, even if it is the more stable alkene.
In this experiment, the elimination of a cyclic tosylate will be conducted, and the product
outcome will be evidence used to support a proposed mechanism of elimination. In the first
week of the experiment, the tosylate will be synthesized from an alcohol. In the second week,
the elimination will be conducted under basic conditions.
Experimental:
Week 1: In an icebath, stir a solution of trans-2-methylcyclohexanol (0.98g, 8.5 mmol) in 6 mL
of pyridine. Add 3.67 g (19.2 mmol) of tosyl chloride in small portions with a spatula. Stir the
mixture in an icebath for 2 hours, then add 8 mL of 6M NaOH. Stir for 5 minutes, then extract
with ether (2 x 10 mL). Wash the organic layer with 6M HCl (2 x 10mL), 10% bicarb (2 x 10
mL), and then brine (10 mL.) Dry the organic layer with sodium sulfate, and remove the ether
via rotovap to give a pale yellow liquid. Characterize the product, and save it for next week.
Week 2: Place your whole sample of tosylate from week 1 in a 10 mL roundbottom flask, and
dissolve in DMSO (1.4 mL per gram of tosylate.) Add 1.1 equivalents of potassium t-butoxide.
Attach a Hickman still, then magnetically stir the reaction in an oilbath at 135 oC. Remove the
distillate continuously with a pipet until no more distillate collects. (Note: This distillate is your
product co-distilling with t-butanol.) Dissolve your distillate in about 5 mL of pentane, then wash
with water (3 x 5mL.) Dry the pentane with sodium soulfate, and remove the penate under
atmospheric pressue in a warm water bath at about 45 oC to yield a colorless liquid. Characterize
as you see fit. (Hint: GC is a great idea!)
Comment Questions:
Draw an E1 mechanism for this reaction. Draw all possible products, and predict major/minor
products based on a discussion of stereochemical and regiochemical considerations.
Draw an E1cb mechanism for this reaction. Draw all possible products, and predict major/minor
products based on a discussion of stereochemical and regiochemical considerations.
Draw an E2 mechanism for this reaction. Draw all possible products, and predict major/minor
products based on a discussion of stereochemical and regiochemical considerations.
Which mechanism would you propose to be most consistent with the data?
Draw a MOFJ energy diagram for this reaction. Based on your data, suggest the most likely
low-energy pathway, and place the transition state on the diagram.
Speculate on the outcomes you might see if you changed reaction paramenters. What if you used
a stronger base? What if you used a polar protic solvent?