Friedel-Crafts Alkylation Purpose

Preparation of 4,4-di-tert-butylbiphenyl using the Friedel-Crafts alkylation of Biphenyl through Electrophilic substitution of a Lewis Base (t-Butyl Chloride (Haloalkane)) in the presence of Ferric Chloride acting as a Lewis Acid

References:

Slayden, et. al. pp. 93 – 95

Website: http://classweb.gmu.edu/jschorni

Solomon’s - pp. 669-671

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Friedel-Crafts Alkylation Background

Electrophile (Lewis Acid) – Electron Pair Acceptor

Electron deficient (positively charged) species seeking electron rich environment (electron pair donor)

e.g. – Protons, Aluminum, Zinc & Iron Halides

Nucleophile (Lewis Base) – Electron pair donor

e.g. – Ammonia, Alcohols, Alkyl Halides

Friedel–Crafts reactions are a set of reactions developed by Charles Friedel and James Crafts in 1877 to attach substituents to an aromatic ring through an electrophilic substitution process

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Friedel-Crafts Alkylation Background (con’t)

There are two main types of Friedel–Crafts reactions: Alkylation reactions Substitution of Alkanes (From Haloalkanes)

Acylation reactions Acyl Groups

Both proceeding by Electrophilic Aromatic Substitution 

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Friedel-Crafts Alkylation Background (con’t)

Friedel–Crafts Alkylation involves the alkylation of an aromatic ring (Biphenyl) with an alkyl halide (t-Butyl Chloride) using a strong Lewis acid catalyst (FeCl3)

The catalyst, anhydrous Ferric Chloride, acting as a Lewis Acid, attracts the Halide from the Alkyl Halide forming FeCl4

- and an Alkyl Carbocation

The Carbocation acts as an Electrophile seeking electrons and attacks the electrons in the Biphenyl ring forming an intermediate Arenium ion

The Arenium ion, a Pentadienyl Cation) is referred to as a non-aromatic Carbocation (also called sigma complex)

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Friedel-Crafts Alkylation Background (con’t)

The Arenium ion loses 2 protons to FeCl4- (Lewis Acid) regenerating

HCl and FeCl3 The ring electrons are regenerated, thus reestablishing stable ring

resonance and producing the product:

4,4-di-tert-butylbiphenylMol Wgt 266.43 g/mol

M.P. 126 – 129oC

CAS 1625-91-8

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Friedel-Crafts Alkylation The Reaction

The Mechanism

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Friedel-Crafts Alkylation Today's Reaction

Using Dichloromethane (Methylene Chloride – BP 40oC) as the solvent, Tertiary Butyl Chloride will be reacted with the catalyst, Ferric Chloride (FeCl3), acting as a Lewis acid to form the t-Butyl Carbocation, an Electrophile

The Carbocation then reacts with Biphenyl, acting as a Nucleophile, to form the product:

4,4-di-tert-butylbiphenyl The product is separated from the aqueous solution

by liquid/liquid extraction with 10% HCl The solvent is removed by evaporation The product is then recrystallized from hot 95%

Ethanol

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Freidel-Crafts AlkylationFreidel-Crafts Alkylation Reaction Issues

Biphenyl is substituted for Benzene, which is a known carcinogen

Anhydrous Ferric Chloride (FeCl3) is substituted for Anhydrous Aluminum Chloride

Note: Instructor will assist student with addition of Anhydrous Ferric Chloride in the hood

It is most important that the reaction vessel and the Ferric Chloride be as dry as possible

Moisture will cause the Ferric Chloride to undergo hydrolysis forming Fe(OH)3

which competes with and diminishes the effectiveness of Ferric Chloride as a Lewis acid

Methylene Chloride (Dichloroethane) is also a known carcinogen – use caution and work in the hood

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Friedel-Crafts Alkylation Procedure

Note: In the following procedure the beaker must be clean and very dry to avoid adding moisture to the Ferric Chloride, causing it to hydrolyze to Fe(OH)3; thus, reducing its effectiveness as a Lewis acid

Pre-weigh a 100 mL clean, dry beaker to nearest 0.001 g

Transfer the Biphenyl (~1.25 g) from the vial to the beaker

Determine the mass of the Biphenyl by difference

Add about 2.5 ml Tertiary Butyl Chloride (2-Chloro-2-Methyl Propane) to the beaker containing the Biphenyl

Determine the mass of t-butyl Chloride by difference04/22/23 9

Friedel-Crafts Alkylation Procedure (con’t)

Add about 10 ml (unweighed) of Dichloromethane (Methylene Chloride (BP – 40oC, Density 1.33 g/mL) to the beaker to act as a solvent for the reaction

In the hood, with instructors help, add about 0.1 g of anhydrous Ferric Chloride to the reaction mixture

Continuously swirl and heat the mixture gently on a hot plate for about 15 minutes while the HCl gas is being evolved

Be careful to not boil the Methylene Chloride solvent away

In the hood add about 10 mL cold 10% Hydrochloric acid to the reaction mixture with swirling

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Friedel-Crafts Alkylation Procedure (con’t)

Transfer the mixture to a 125 mL separatory funnel

Mix the two phases well and vent any gas

Repeat mixing & venting until no more gas is released

Allow the two phases to separate

Drain the product and Methylene Chloride mixture (lower layer) into a clean beaker

Drain upper aqueous HCl layer (waste) into separate beaker and put aside

Return product mixture to the separatory funnel and repeat liquid/liquid extraction with more 10% HCl

Repeat process until most of the color is removed04/22/23 11

Friedel-Crafts Alkylation Procedure (con’t)

Dry the product with anhydrous Sodium Sulfate and allow to settle

Carefully pour off (decant) liquid into a clean dry 50 mL beaker, leaving solid Na2SO4 particles behind

In the hood, remove the Methylene Chloride (BP – 40oC) solvent by gently evaporating the mixture until the bubbling action of the Methylene Chloride ceases – solution could go to dryness, but not likely

Note: If the liquid remains, cool to room temperature and then in an ice-water bath for a minute or two. This should precipitate the product

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Friedel-Crafts Alkylation Procedure (con’t)

Recrystallize the product Add 10 mL 95% Ethanol to the beaker Use a spatula to scrape the product from the

sides of the beaker into the Ethanol Place the beaker containing the product and

Ethanol in a 250 ml beaker containing just enough water to allow the sample beaker to sit on the bottom of the beaker

Heat the water bath until the solid particles dissolve completely

Note: water does not need to boil (85-90oC) If all of the solid does not dissolve, add more

EtOH in small increments until final dissolution

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Friedel-Crafts Alkylation Procedure (con’t)

After the product is fully dissolved, allow solution to cool slowly to room temperature Crystals of purified product should form as

solution cools Cool the mixture in a room temperature water

bath If the cooled product mixture looks like a non-

filterable mass, put the beaker back on the hot plate, add 3-4 ml EtOH, and repeat the recrystallization

Repeat as necessary until mixture can be swirled If the product does not recrystallize put the

beaker back in the water bath and evaporate some of the alcohol

Allow mixture to cool again04/22/23 14

Friedel-Crafts Alkylation Procedure (con’t)

Vacuum Filtration Set up vacuum filtration unit and moisten filter

paper in Buckner funnel with 95% Ethanol Filter the product by vacuum filtration, washing

the product with additional Ethanol Product will usually be yellow due to trace

amounts of hydrated Ferric Chloride Transfer the product to a pre-weighed weighing

tray and air-dry in the drawer until next lab session

Determine the mass of the dried product Compute the percentage yield Determine the Melting point

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