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 4/15/2017

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 4/15/2017

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  4/15/2017

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) 4/15/2017

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-butylbiphenyl Mol Wgt 266.43 g/mol M.P. 126 – 129oC CAS 1625-91-8 4/15/2017

Friedel-Crafts Alkylation The Reaction The Mechanism 4/15/2017

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 4/15/2017

Freidel-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 4/15/2017

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 difference 4/15/2017

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 4/15/2017

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 removed 4/15/2017

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 4/15/2017

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 4/15/2017

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 again 4/15/2017

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 4/15/2017