Nucleophilic Substitution - PowerPoint Presentation

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Nucleophilic Substitution

Synthesis of 1-Iodobutane

Nucleophilic Substitution of Alkyl Halides:

Synthesis of 1-Iodobutane

1-Bromobutane is a primary alkyl halide (not sterically hindered).

Acetone is a polar aprotic solvent. It poorly solvates the iodide nucleophile, promoting the SN2 mechanism.Despite having an unfavourable equilibrium (the products are less stable than the starting materials), the reaction still proceeds essentially to completion. Why is this?

sodium bromide is

insoluble in acetone

Reaction Work-Up

Filter the reaction

mixture to remove the precipitated sodium bromide.Wash with water to remove remaining traces of sodium iodide. The primary purpose, however, is to remove the bulk of the acetone solvent from the reaction mixture. The lower layer is the organic layer (containing our product).Wash with aqueous sodium bisulfite (NaHSO3) to remove any colouration due to a small amount of iodine that is often formed as a by-product in reactions of this type:

Dry the organic product by standing over sodium sulfate (Na2

SO4).I

2 + HSO3– + 3 H

2O



2I

–

+

HSO

4

–

+

2 H

3

O

+

Product Purification

The 1-iodobutane product is purified by distillation.

Before performing the distillation, you should pre-calculate the expected

boiling point of the 1-iodobutane product:B.P.760mmHg = B.P.observed – 0.05×(A.P.mmHg

– 760)

You know the literatureboiling point (for 760 mmHg)

You know the currentatmospheric pressure

You can thus predict the boiling point in today’s lab (at the current atmospheric pressure)

Qualitative Tests

Perform these test-tube tests once reflux is underway!

NaI

in Acetone – test for SN2 reactivity Iodide ion (I–) is a good nucleophile and a poor base. Acetone is a polar aprotic solvent. A positive result is indicated by formation of a white precipitate, since NaBr and NaCl are insoluble in acetone.

AgNO3

in Ethanol – test for SN1 reactivity Nitrate ion (NO3

–) is a poor nucleophile and a poor base. Ethanol is a polar protic solvent.

Silver ion (Ag+

) promotes

cation

formation (and thus S

N

1 reactivity):

A positive result is indicated by formation of

AgX

precipitate

Qualitative Tests

Substrate structure is very important in determining the mechanism of reactivity. You’ll test a range of substrate structural types.

Note that the only difference between 1-bromobutane and 1-chlorobutane is the identity of the leaving group. We can compare these two substrates to determine whether bromide or chloride is a better leaving group.

Qualitative Tests

Note that the only difference between 1-bromobutane and 1-chlorobutane is the identity of the leaving group. We can compare these two substrates to determine whether bromide or chloride is a better leaving group.

The observed reactivity (S

N1 and SN

2) sequence for halides is:

C-X bond strength as well as the stability of the X– ion control

this order.

Qualitative Tests

Owing to

steric

effects, the order of reactivity in SN2 chemistry is:In SN1 chemistry, the order of reactivity reflects the ease of cation formation:

aryl and vinyl substrates do

not readily undergo substitution

aryl and vinyl substrates do

not readily undergo substitution

Tips and Reminders

Today’s experiment will be conducted in pairs

Note that most alkyl halides, particularly iodides, are very toxic and are cancer suspect agents

During the work-up procedure, the precipitate may be washed with an additional (small) quantity of fresh acetone in order to maximize the percent yield During liquid-liquid extraction, the lower layer is the organic layer (halogenated compounds are almost always more dense than water)

Before performing the distillation, pre-calculate the expected boiling point

Atmospheric pressure today: Don’t forget that a lab report is required for this experiment!