Electrophilic Aromatic Substitution

February 4, 2015 Experiment 1: Electrophilic Aromatic Substitution The purpose of the experiment is to demonstrate electrophilic aromatic substitution using Friedel-Crafts Alkylation and analyze the relative bromination rates of arene compounds. Introduction Since the 1800’s, the Friedel-Crafts alkylation is the most useful method for the introduction of alkyl group.1 From that point, alkylation of arenes was revolutionized. Different breakthroughs were discovered for the past two centuries to this day. Thomas discovered the use of FeCl3 instead of the original AlCl3 as the Lewis acid catalyst which is currently used in modern experiments. 1 A recent breakthrough in alkyl-arene synthesis is the use of solid support reagents, such as silica gel bound aluminum chloride (Si-AlClx) in conjunction with microwave chemistry in decreasing synthesis time with increased product yield and decreased waste.2 The solid support approach was discovered by Merrifield with the successful synthesis of tetrapeptide in 1963. 2 The biological synthesis of peptide chains in amino acids which is covalently bonded to solid resins, such as polystyrene was expanded into organic synthesis. 2 These breakthroughs in Friedel-Crafts method show the significance of the process in modern organic chemistry. The purpose of this study is to demonstrate the Friedel-Crafts alkylation, synthesize an alkyl substituted arene by reacting an arene and an alkyl halide in the presence of a Lewis acid catalyst. In this experiment, biphenyl will be reacted with two counts of tert-butyl chloride in the presence of catalytic iron (III) chloride to synthesize 4,4’-di-tert-butylbiphenyl and two counts of HCl. The Lewis acid, iron (III) chloride, helps generate the electrophile to attack the aromatic compound. The chloride from tert-butyl chloride is pulled away by the Lewis acid leaving the

carbocation t-butyl and a negatively charge aluminum bonded to four chlorine atoms. The positively charged carbocation attacks on the para or carbon 4 of the aromatic ring to minimize steric hindrance due to its bulky structure. The reaction generates 4,4’-di-tert-butylbiphenyl. The aluminum-chloride anion transfers electron to a chlorine atom which pulls on the hyrdrogen at carbon 4. The pull on the hydrogen results in an electron transfer to the ring to form pi bond. Calculations Limiting reagent = biphenyl Biphenyl + 2 tert-butyl chloride  4,4’-di-tert-butylbiphenyl + 2 HCl Biphenyl to 4,4’-di-tert-butylbiphenyl ratio = 1:1 Biphenyl used = 1.00g = 4,4’-di-tert-butylbiphenyl yield

Percent yield=

actual yield 0.79 g ×100 = × 100 =79 theoretical yield 1.00 g

TLC Rf Distance travelled by compound A = 3.8 cm; Distance travelled by compound B = 4.2 cm; Distance travelled by solvent = 4.8cm Rf =

distance travelled by compound distance travelled by solvent

RfA = 3.8 cm / 4.8 cm = 0.81 RfB = 4.2 cm / 4.8 cm = 0.89

TLC Compound A = Biphenyl A+B = Co-spot B = 4,4’-di-tert-butylbiphenyl

Rf

Conditions 0.81 Eluent: hexanes:ethyl acetate; 0.81, 0.89 Plate: silica; Visualization 0.89 method: UV

Melting point Compound

Experimental Melting Literature Melting Point Reference Point (°C) (°C) 4,4’-di-tert-butylbiphenyl ~25 126-129 1 1. ChemSpider.com. http://www.chemspider.com/Chemical-Structure.66804.html

Relative reaction rate Compound

Time (mins)

Anisole Acetanilide Diphenyl ether Toluene Benzhydrol

0.33 7.0 11 13 91

Experimental Rate Ranking (Fastest-Slowest) 1 2 3 5 4

Theoretical Rate Ranking (Fastest-Slowest) 1 2 3 4 5

The purity of the product is poor. The TLC co-spot shows two different spots under UV light. Spot B (product) is slightly higher than spot A (starting compound) but spot B shows two different compounds very similar to the co-spot. The product illuminates under UV light just above the starting material spot observed in spot B. The product obtained is waxy which means contaminants that are in liquid state at room temperature of 25°C are present. The product is to wet, or waxy, to perform a melting point analysis, therefore, the melting point is assumed to be around room temperature. The resulting order of arene reactivity from the experiment from fastest to slowest is anisole, acetanilide, diphenyl ether, toluene and benzhydrol. The experimental results did not

match with the theoretical order of anisole, acetanilide, diphenyl ether, benzhydrol and toluene. The toluene appears to have reacted too fast for the experiment compared to the other student’s data. This may be due to mishandling of compounds when the bromination of toluene is performed or the possibility of exposing the mixture to high temperature that increased the rate of reaction. The TLC shows three distinct spots under UV light. The co-spot and product spot is closely similar due to the high amount of starting material in the product. The short wavelength UV light illuminated the pure product, glowed in blue colour and is more defined in the product spot compared to the co-spot. The product spot is examined to have two halves, the top is the product and bottom half is the starting material. Under the conditions used in the experiment, there is adequate separation between product and starting material if observed in both short and long wavelength, but not enough separation to distinguish the product form starting material under long wavelength only. Tert-butyl chloride cannot be used as a co-spot because it is highly volatile if mixed with acetone.