Electrophilic Aromatic Substitution (Bromination of Toluene)

1. Electrophilic Aromatic Substitution(Bromination of Toluene) Demonstration of the Effect of an Electron Donar Group (ring activator) on a monosubstituted Benzene on subsequent substitution of other groups References • Slayden Lab Manual – p. 75-76 • Website: http://classweb.gmu.edu/jschorni/chem318 (Bromination of Toluene)

2. Electrophilic Aromatic Substitution(Bromination of Toluene) • Overview • Determine the effect of a monosubstituted Methyl group on a Benzene ring on the number of Bromine substitutions on the ring and the orientation of the substituted Bromine atoms (Ortho, Para, Meta) relative to the Methyl group • Approach • Electrophilic Aromatic Substitution reaction involving the halogenation of a mono-substituted Benzene ring (Toluene) with Bromine (Br2)

3. Electrophilic Aromatic Substitution(Bromination of Toluene) • Bromine (Br2) in the presence of FeBr3 forms Br+ ions which act as the electrophile in attacking the exposed electrons of the Benzene ring acting as the Nucleophile • Determine the Limiting Reagent and Theoretical Yield of the Bromotoluene reaction • Obtain IR Spectra of Bromotoluene isomers using IR Spectrophotometer in “Absorbance” mode • Use two methods (Triangulation Method and IR Spectrophotometer software) to compute the Mole Percents of the Bromotoluene isomers using the relationship between peak area and mole content of the reaction.

4. Electrophilic Aromatic Substitution(Bromination of Toluene) • Background • Nucleophile - A Lewis Base with a pair of unshared electrons that seeks a positive part of an atom. • Electrophile - A Lewis Acid seeking an electron pair

5. Electrophilic Aromatic Substitution(Bromination of Toluene) • Background • Electrophilic Aromatic Substitution • Electrophiles (Electron deficient species, such as Br+ ions), attack the electron rich Nucleophile (Benzene Pi bond) replacing one of the Hydrogen atoms • Benzene and substituted Benzenes - as Aromatic Nucleophiles - can undergo Electrophilic Substitution • There are five (5) common Electrophilic Aromatic Substitutions used in organic chemistry synthesis • Halogenation – X2 • Nitration – HONO2/H2SO4 • Sulfonation – SO3/H2SO4 • Friedel-Crafts Alkylation – RCl/AlCl3 • Friedel-Crafts Acylation – RC=OCl (acetyl chloride), AlCl3.

6. Electrophilic Aromatic Substitution(Bromination of Toluene) • Background (Con’t) • Today’s experiment involves Halogenation of a substituted Benzene ring (Toluene) with Br2 in the presence of FeBr3, which produces the Br+ ions (Electrophilic reagent) that are substituted on the ring • Aromatic Hydrocarbons, e.g., Benzene and substituted benzenes, are referred to as Arenes - The symbol for an Arene is ArH • An Aryl group is derived from an Arene by removing one of the Hydrogen atoms - The symbol for an Aryl group is Ar- • Common Reactions of Arenes include Electrophilic Substitutions involving the Arene and an Electrophilic reagent, i.e., an electron seeking species with a positive charge (E+) • Arenes are susceptible to Electrophilic attack because of the exposed  electrons

7. Electrophilic Aromatic Substitution(Bromination of Toluene) • Background (Con’t) • When substituted benzenes undergo Electrophilic attack, groups already on the ring affect both the rate of the reaction (reactivity) and the site of the attack (orientation) • If the initial substitution group (see 1st reaction) is an electron-releasing (donating) group relative to Hydrogen – an activator, such as a Methyl (CH3) group - the 2nd substitution occurs faster than substitution on an unsubstituted aromatic ring. The 2nd substitution tends to favor the Ortho/Para (o/p) positions • If the 1st substitution is an electron-withdrawing (accepting) group – a deactivator, such as the Nitronium Ion - the reaction occurs slower than substitution on an unsubstituted aromatic ring and favors meta substitution, i.e. (m) directing

8. Electrophilic Aromatic Substitution(Bromination of Toluene) • Background (Con’t) • In today’s experiment you will be performing an Electrophilic Substitution on the Benzene ring of Toluene, i.e., Methyl Benzene • The Methyl group is an electron donor (activator) of the Benzene ring • Electron density from one of the carbon-hydrogen sigma bonds of the Methyl group flows to the vacant p orbital of the Carbocation (positively charged Carbon atom of the Benzene ring) because the orbitals can overlap – this is called Hyperconjugation • The electron density of the sp2-hybridized carbocation carbon on the Benzene ring becomes less dense; the Hydrogens of the Methyl group assuming some of this dispersed positive charge

9. Electrophilic Aromatic Substitution(Bromination of Toluene) • Background (Con’t) • This dispersal (delocalization) of the charge stabilizes the ring • The resonance structures that maximize the positive charge on the carbocation carbon attached to the Methyl group are the Ortho/Para positions (see slide 14) • Thus, substituted Methyl/Alkyl groups favor additional substitution at the Ortho and Para positions relative to the Methyl group • The relative reactivity of an activating group is a strong influence on the number of times a substitution will occur on the ring • One of the objectives of today’s experiment is to determine the effect of the Methyl group on the number of Bromine substitutions and the orientation of the substituted Bromine atoms

10. Electrophilic Aromatic Substitution(Bromination of Toluene) • Background (Con’t) • When Toluene (Methyl Benzene), an Aromatic Hydrocarbon, is mixed with Bromine in the presence of Lewis Acid Catalyst, it undergoes an Electrophilic Aromatic Substitution • In this experiment the Catalyst is Ferric Bromide (FeBr3) produced by reaction of Bromine (Br2) with a “staple” as the source of Iron • Actually, the Ferric Bromide and some additional Bromine (Br2) form a complex that dissociates to produce the positive Br+ ions that act as the electrophilic agent seeking the exposed  electrons of the Benzene ring activated by the electron donor Methyl group

11. Electrophilic Aromatic Substitution(Bromination of Toluene) • Background (Con’t) • The products of the reaction are the Ortho, Para, and Meta forms of Bromotoluene and HBr • Substitution Positions on Benzene Ring: • If all sites on the Benzene ring are assumed to be equally reactive – they are not – the product mixture would produce a statistical 2:2:1 (40%, 40%, 20%) ratio of ortho, meta, and para isomers (there are two Ortho positions, 2 Meta positions, and 1 Para position) • Since the sites are not equally reactive, one of your tasks today is to determine the actual mole ratios in the product mixture

12. Electrophilic Aromatic Substitution(Bromination of Toluene) • Background (Con’t) • You will do this by using the IR Spectrophotometer in a new way • Each of the 3 isomers of Bromotoluene in the product mixture produces a unique absorption; and the relative peak areas for these absorptions are proportional to the mole ratios in the mixture • You will measure the areas by Triangulation as you did in the Gas Chromatography experiments last semester • You can also have the FT-IR instrument measure the areas

13. Electrophilic Substitution Directing Effectson Aromatic Ring Activators (Donate, Release Electrons to ring) • Available pair of unbonded electrons to donate to ring. • Protons on ring are more shielded • Tendency for decreased Chemical Shift • Deactivators (Withdraw, Accept Electrons) • No unbonded electron pairs • Less Shielding of Protons on the ring • Tendency for increase Chemical Shift Methyl & Alkyl groups are activating because of the stabilizing effect of sp2 hybridization (hyperconjugation) of an unbonded electron in the Methyl radical. Halogens are o,p directing because the electron donating resonance effect is more dominant than the withdrawal inductive (Dipole) effect of these electro-negative elements.

14. Electrophilic Aromatic Substitution(Bromination of Toluene) • The Reactions • The Electrophiles attack the  system to form a “Nonaromatic Carbocation” known as an Arenium ion • An electron releasing Electrophile, an Activator such as the Methyl group, stabilizes the ring resulting in a faster predominate Ortho/Para substitution reaction • An electron withdrawing Electrophile, a Deactivator, such as the Nitronium ion, destabilizes the ring, promoting a slower less predominate Meta substitution reaction

15. Electrophilic Aromatic Substitution(Bromination of Toluene) • The Reactions (Con’t) • Bromine Cations • In today’s experiment, Bromine (Br2) in the presence of Fe (from an ordinary “staple”) will produce positive Bromine ions (Br+). The Bromine reacts with the Iron to form the Lewis Acid Ferric Bromide (FeBr3), which in turn reacts with excess Br2 to form a polarized complex that dissociates to form positive Bromine ion, Br+ and FeBr4- • The Positive Br+ ion acts as the positively charged Electrophilic reagent (seeking electrons) which attacks the exposed electrons of the bond of the benzene ring

16. Electrophilic Aromatic Substitution(Bromination of Toluene) • The Reactions (Con’t) • Substitution of Bromine

17. Electrophilic Aromatic Substitution(Bromination of Toluene) • Electrophilic attack on a Benzene ring containing an Electron donating group (Methyl group) • Substitution of Electrophile at the Ortho/Para positions is favored

18. Electrophilic Aromatic Substitution(Bromination of Toluene) • Procedure • Obtain a sample vial with cap containing a pre-treated “staple” (source of iron) from the instructor’s desk. Note: The staple must be lying flat on the bottom of the vial • Put a small tape label on the outside with your name(s) and section number • In the hood, the instructor will use a pre-calibrated “autopipet” to deliver the following volumes of Toluene and Bromine to your vial: • 115 l (0.115 mL) of Toluene (Mol Wgt – 92.139; Den – 0.867 g/mL) • 65 l (0.065 mL) of Bromine (Br2) (Mol Wgt – 159.81; Den – 3.119 g/mL)

19. Electrophilic Aromatic Substitution(Bromination of Toluene) • Procedure (Con’t) • When preparing your report: 1. Use the Volume and Density of Bromine to compute the Mass of Toluene and Bromine used 2. From the Mass and Molecular Weight calculate the Moles of Toluene and Bromine • Set up the stoichiometric equation • Determine the molar ratios involved. Do you use mol wgt of Br2 (159.81) or Br (79.90) to compute moles of bromine used in the reaction? • Show the reaction mechanism • Determine the Limiting Reagent • Compute the Theoretical Yield as mass (g)

20. Electrophilic Aromatic Substitution(Bromination of Toluene) • Procedure (Con’t) • Cap the vial loosely to allow the vapors to escape and set the vial in the hood to continue the reaction. Record any observations • Observe reaction for 10 minutes; then insert a “dry” piece ofLitmus paper into the reaction vapor in the upper portion of the vial – Do Not put litmus into the solution • Record observation – Does the Litmus paper change color; why? • Allow vial to sit in the hood for a total 45 minutes or until the deep reddish-brown Bromine color has faded to yellow • Record color change observations

21. Electrophilic Aromatic Substitution(Bromination of Toluene) • FT-IR Absorbance Mode (Setup will be done by Instructor) • Press “T/A” to change the ordinate of the spectrum to “Absorbance” mode. • Change “Scan Range” • Press “Setup” • Select “Scan” using 1st Soft Key from left • Select “Range” using 3rd Soft Key from left • Enter “high frequency” value using the numeric keypad (Suggest 850 cm-1 to start) • Press “Enter” • Enter “Low frequency” value using the numeric keypad (Suggest 650 cm-1 to start) • Press ”Enter” • Press “Execute” Soft Key – Last Soft Key on right

22. Electrophilic Aromatic Substitution(Bromination of Toluene) • FT-IR Absorbance Mode • Change “Absorbance Range” • Press “Setup” • Select “View” using 3rd Soft Key from left • Select “Rescale” using 4th Soft Key from left • Enter “Low Absorbance” value using the numeric keypad. Suggest 0.0 to start • Press “Enter” • Enter “High Absorbance” value using the numeric keypad Suggest 2.0 to start • Press”Enter” • Press “Execute” Soft Key – Last Soft Key on right. • Range values may have to be changed depending on actual peak ranges in spectrum

23. Electrophilic Aromatic Substitution(Bromination of Toluene) • IR Spectroscopy • Place a drop of the reaction mixture between two IR salt plate • Obtain an IR spectrum in “Absorbance Mode” in the region between 900 – 600 cm-1. The instrument will be preset for this spectrum determination. • Press Scan; “X”; 4; Execute • As the instrument processes the sample, the status window on right side of screen counts down from 4 to “ready.” • Press “Plot” and label the principle peaks Bromotoluene Reference Peaks p-Bromotoluene m-Bromotoulene o-Bromotoluene Toluene 801 cm-1770 cm-1 747 cm-1726 cm-1 Note: The Toluene peak should be very small (missing!!) The m-Bromotoluene peak should also be small

24. Electrophilic Aromatic Substitution(Bromination of Toluene) • Compute Peak Areas by Triangulation. • The areas under the IR spectra reference peaks are proportional to the mole ratio of the Bromotoluene isomer products in the reaction mixture. • The molar percentage composition of a mixture can be approximated by comparing the relative areas of the peaks in the spectra. • Define the “Baseline” by drawing a best-fit (eye-balled) straight line along the bottom of the spectra plot, similar to the way you did it in gas chromatography. • The area of the peak is determined by multiplying the height of the peak (in mm) above the baseline by the width of the peak (in mm) at half the height. • Add areas to get the total area. • Divide each area by total area to get mole fraction. • Multiply the mole fraction by 100 to get the mole percent.

25. Electrophilic Aromatic Substitution(Bromination of Toluene) • Peak Area by theTriangulation Method Peak Area = h * w½ * 1.064 Where h = Peak Height w½ = width of peak at ½ the Peak Height Note: The curve is assumed gaussian and the h * w1/2 value is about 6.4% less than the true value, thus the correction factor. Total Peak Area(TA) = A + B Mole Fraction(MF) = A/TA, B/TA Mole Percent = MF x 100

26. Electrophilic Aromatic Substitution(Bromination of Toluene) • Measure Peak Area using FT-IR software (To be done only if directed by Instructor) • Press “T/A” to change the ordinate of the spectrum to “Absorbance” mode • Press “Area” (Shift 7) • Press “X” region key, i.e. select the buffer region for your spectrum • Press “vcursor (Shift ←). The “vertical cursor” appears • Move the vertical cursor to a point representing the upper limit (left side) of the frequency range of the peak you want to calculate • Type the wave number of the vertical cursor in the “From” field, then press “Enter”

27. Electrophilic Aromatic Substitution(Bromination of Toluene) • Move the vertical cursor to the lower frequency limit (right side) of the range of a peak you want to calculate • Type the wave number of the vertical cursor in the “To” field, then press “Enter” Note: The Baseline range determined below is inclusive of the three peaks you are calculating; use the same baselinerange for all three determinations • Move the vertical cursor to a point corresponding to a frequency slightly higher than the upper frequency limit of the peak with the highest frequency range. This first “Baseline Point” is the upper frequency (left side) of the Baseline range • Type the wave number of the vertical cursor in the “Basefrom” field, then press “Enter”

28. Electrophilic Aromatic Substitution(Bromination of Toluene) • Peak Area by FTR Software • Move the vertical cursor to the second “Baseline Point” at a frequency slightly lower than the lower frequency limit of the peak with the lowest frequency range • This second “Baseline Point” is the lower frequency (right side) of the Baseline range • Type the wave number of the vertical cursor in the “Baseto” field • Press “Execute” to calculate the area. The calculated result appears on the command line • Record the result in your notebook • Repeat steps 4 to 9 for the other peaks

29. Electrophilic Aromatic Substitution(Bromination of Toluene) • Laboratory Report • Synthesis Experiment • Mass, Moles, Molar Ratio, Limiting Reagent, Theoretical Yield • Procedures • Title – Concise: Simple Distillation, Dry Sample, IR Spectrum, etc. • Materials & Equipment (2 Columns in list (bullet) form) Note: include all reagents & principal equipment used • Procedure Description: • Use complete sentences in list (bullet) form • Concise, but complete description • Use your own words – Don’t copy book!!

30. Electrophilic Aromatic Substitution(Bromination of Toluene) • Summary • Paragraph summarizing the experimental results, computed results, and the principal absorptions from IR spectra • Analysis / Conclusions • Discuss the isomeric makeup of the product relative to what you expected from theory • No. of Isomers • Orientation of the Substituted groups • Molar Composition of the isomers • Compare Triangulation vs. IR Software area calculation