Nitration of Methyl Benzoate Demonstration of the effect of an electron withdrawing group on a monosubstituted benzene ring on subsequent substitution of other groups on the Benzene ring References: Pavia, et al. – pp 338 – 342 Slayden, et al. – pp 76 – 79 4/19/2017

Nitration of Methyl Benzoate Overview: Synthesis – Nitration of Methyl Benzoate through an Electrophilic Aromatic Substitution to form: Methyl m-Nitrobenzoate (MW – 181.15) Methyl 3-Nitrobenzoate (MP – 78oC) 3-Nitrobenzoic Acid Methyl Ester Determination of reactant Masses, Moles, Molar Ratio, Limiting Reagent, Theoretical Yield Reaction mixtures must be kept cool Separation and Purification of Product by Vacuum Filtration and Recrystallization from Methyl Alcohol Percent Yield Melting Point Summary of Results Analysis and Conclusions 4/19/2017

Nitration of Methyl Benzoate The Laboratory Report: Synthesis Experiment Mass, Moles, Molar Ratio, Limiting Reagent, Theoretical Yield Procedures Title – Concise: Mass reagent, Vacuum Filtration, Recrystallization, etc. Materials & Equipment (2 Columns in list (bullet) form) Note: include all reagents & principal equipment used Description: Descriptions must be detailed, but concise Use list (bullet) form Use your own words – Don’t copy book!! 4/19/2017

Nitration of Methyl Benzoate Synthesis Experiment (Con’t) Results – Neat, logically designed template to present results (in box to right of Procedure description) Summary Paragraph summarizing experimental observations and computed results Analysis & Conclusions Limiting reagent What is the nature of the product you expected and what evidence do you have to indicate you actually got what you expected? What was the yield of your product and what aspects of your experimental procedure could be improved? 4/19/2017

Nitration of Methyl Benzoate Background: Electrophilic Addition vs. Electrophilic Substitution Alkenes, which contain pi () (-C=C-) bonds, are electron-rich due to the excess of electrons in the () bonds These electrons are susceptible to electron-seeking (electrophilic) reagents called Electrophiles In an Electrophilic Addition of an Alkene, the Alkene acts as an Electron-Rich Nucleophile providing a source of electrons for the Electrophile, for example, a proton (H+) from an acid (acting as a Lewis acid) 4/19/2017

Nitration of Methyl Benzoate Example of Electrophilic Addition 4/19/2017

Nitration of Methyl Benzoate Background (Con’t) Electrophilic Aromatic Substitution Aromatic compounds also have the electron rich pi () bonds The resonance in the Benzene ring, however, makes the  electrons less susceptible to Electrophilic Additions An addition reaction would result in a loss of resonance stabilization Aromatic compounds do, however, react with strong electrophilic reagents at somewhat elevated temperatures in substitution reactions 4/19/2017

Nitration of Methyl Benzoate Background (Con’t) Electrophilic Aromatic Substitution In today’s experiment the Benzene ring of Methyl Benzoate is reacted with a mixture of concentrated Nitric and Sulfuric acids, i.e., source of Nitronium ion The positively charged Nitronium ion (NO2+) acts as the Electrophile, temporarily disrupting the ring resonance, and adds to the Nucleophilic Benzene Ring forming the intermediate resonance-stabilized Arenium ion, an electron deficient positively charged delocalized Carbocation The rate of formation of the Arenium ion, which is somewhat stabilized by ring resonance, determines the rate of reaction 4/19/2017

Nitration of Methyl Benzoate Background (Con’t) The Carbomethoxy group is electron withdrawing, thus; it deactivates the ring relative to Benzene. The resultant “resonance” structures favor “Meta” substitution over Ortho/Para 4/19/2017

Nitration of Methyl Benzoate 4/19/2017

Nitration of Methyl Benzoate Background (Con’t) Electrophilic Aromatic Substitution (Con’t) The Carbomethoxy group is electron withdrawing It has a moderately “Deactivating” effect on the ring relative to Benzene itself, thus the transition state to the Arenium ion is highly unstable, withdrawing electrons from the developing carbocation leading to increased positive charge on the ring The inductive effect of this electron withdrawal sets up a dipole with the ring at the positive end Any resonance form of the Arenium ion that would enhance this positive charge, e.g., either ortho or para resonance structures, would further destabilize the ring 4/19/2017

Nitration of Methyl Benzoate Background (Con’t) Electrophilic Aromatic Substitution (Con’t) The resonance forms of the Meta substituted Arenium ion, however, do not attempt to add additional positive charge at the carbon atom attached to the electron-withdrawing carbonyl group of the Carbomethoxy group (see previous slide) Electron withdrawing groups favor Meta substitution because the Meta resonance structures are more stable than O/P Full resonance is restored by eliminating the proton from the sp3-ring carbon (also containing the Nitronium ion) to the HSO4- ion By eliminating the proton, the Nitronium ion is therefore substituted on the ring 4/19/2017

Nitration of Methyl Benzoate Background (Con’t) Electrophilic Aromatic Substitution (Con’t) After the single substitution of the Nitro group to the first Meta position, the combination of the Carbomethoxy group and the Meta-Nitro group further “Deactivates” the ring against additional substitution Keeping the reaction mixture temperature low also inhibits the formation of “Dinitration” products Small amounts of the Ortho and Para isomers of Methyl m-Nitrobenzoate and the “Dinitration” products can be in the reaction mixture These are removed by recrystallizing the solution with Methanol 4/19/2017

Nitration of Methyl Benzoate Methyl & Alkyl groups are activating because of the stabilizing effect of sp2 hybridization (hyperconjugation) of an unbonded electron in methyl radical. Halogens are o,p directing because the electron donating resonance effect is more dominant than the withdrawal inductive effect of these electro-negative elements. Activators (Donate, Release Electrons) Available pair of unbonded electrons to donate to ring. More Shielding of Protons Less NMR Chemical Shift downfield Deactivators (Withdraw, Accept Electrons) No unbonded electron pairs Less Shielding of Protons More NMR Chemical Shift downfield 4/19/2017

Nitration of Methyl Benzoate Procedure Determine the mass of the Methyl Benzoate to the nearest 0.001g (MW – 136.15) Determine the mass of 2.000 mL of Conc HNO3 (MW – 63.01) from the volume, density and % Composition Den – 1.42 g/mL, % Acid - 70.0%) (Use a volumetric pipet to obtain the HNO3) Limiting Reagent & Theoretical Yield (in your report) Calculate the Moles of Methyl Benzoate and Nitric Acid Setup the Stoichiometric balanced equation Determine the Stoichiometric Molar Ratio Determine the limiting reagent from the Stoichiometric balanced equation and the actual moles of reagents used Compute the theoretical yield 4/19/2017

Nitration of Methyl Benzoate Procedure (Con’t) Note the following precautions Sulfuric Acid protonates Nitric Acid acting as a weak base to form the Electrophilic Nitronium Ion, which is added to the resonance disrupted Benzene ring replacing a Proton Use extreme care to avoid adding any additional water to the reaction mixtures Water must be kept to a minimum so as to enhance the reactivity of the nitrating mixture. Water is a stronger base than HNO3, which is basic relative to H2SO4; thus, it would interfere with the protonation of the Nitric Acid, hence the formation of the Nitronium ion The reaction temperature must be kept low to prevent the excessive formation of the Dinitration products 4/19/2017

Nitration of Methyl Benzoate Procedure (Con’t) Prepare an ice/water bath using a 150 ml beaker Place a 50 mL Erlenmeyer Flask containing approximately 6 mL of concentrated Sulfuric Acid (H2SO4) into the ice/water base; allow to cool Add the Methyl Benzoate to the Sulfuric Acid, swirl the mixture, and allow to cool Prepare another ice/water bath using a 100 mL beaker Pipet the 2.00 mL of concentrated Nitric Acid (HNO3) into a small, clean, dry vial and place the vial in the new ice/water bath (the sides of the vial should be immersed in the ice/water bath about half-way Measure another portion of about 2 ml (exact volume not critical) of concentrated sulfuric acid and carefully and slowly add it to the Nitric Acid in the vial 4/19/2017

Nitration of Methyl Benzoate Procedure (Con’t) Allow the mixture to cool for about 10 minutes Note: Avoid introducing any water into mixture! Using a medicine dropper or plastic disposable pipet, very slowly with continuous gentle swirling, add the cooled HNO3 / Sulfuric acid mixture to the cooled Methyl Benzoate / Sulfuric Acid mixture NOTE: The temperature of the reaction mixture must be kept below 15 oC After the two reaction mixtures have been combined, keep the combined mixture in the ice/water bath for at least 5 minutes in order to keep the solution temperature in a cooled state until the reaction is complete 4/19/2017

Nitration of Methyl Benzoate Procedure (Con’t) Allow the reaction mixture to warm to room temperature (10 min or so) Pour the reaction mixture over approximately 25 grams of ice in a 100 mL or 150 mL beaker The product precipitates; allow the ice to melt Note: If you get a small yield, you probably introduced some water from the ice/water bath Even a small drop of water is sufficient to shut down the reaction Pre-weigh the top of the Buckner Funnel Isolate the precipitated product by Vacuum Filtration through a Buckner Funnel 4/19/2017

Nitration of Methyl Benzoate Procedure (Con’t) Wash product with two 15 mL portions of cold distilled water Dispose of aqueous filtrate down the drain with lots of water Wash product again with two 5 mL portions of cold Methanol Dispose of the Methanol filtrate in the waste jar in the hood Weigh the Buckner funnel again to determine the weight of the crude product Transfer the crude product to another clean beaker 4/19/2017

Nitration of Methyl Benzoate Procedure (Con’t) Recrystallization Determine the starting volume of Methanol required from the mass of the crude product and the density of methanol. Density (g/mL) = mass (g) / Vol (mL) Density of Methanol = 0.79 g/mL  Volume Methanol = mass (sample) / density Add Methanol to Sample beaker Add enough additional Methanol to just cover the sample Place beaker containing sample and Methanol in a larger beaker ¼ full of water, i.e., a water-bath 4/19/2017

Nitration of Methyl Benzoate Procedure (Con’t) Recrystallization (Con ‘t) Heat water bath to about 80oC Swirl contents of sample beaker until product dissolves Note: Do not boil contents of sample beaker. It may be necessary to add small increments of Methanol to effect solution of product Cool solution slowly to room temperature Set up Buckner Funnel Pre-weigh the top of the cleaned/dried Buckner funnel or a weighing tray as directed Pre-moisten the filter with Methanol 4/19/2017

Nitration of Methyl Benzoate Procedure (Con’t) Transfer purified crystals to Buckner Funnel using small amounts of additional cold Methanol to complete transfer of all solid material to the Buckner Funnel Vacuum Filtration, washing with 2 5 mL increments of cold Methanol, to separate crystals from solution Dispose of Methanol filtrate in waste jar in hood Place the purified product (Methyl m-Nitro Benzoate) in a pre-weighed plastic weighing tray and put in your drawer or instructor’s drawer until next week Weigh the Buckner funnel containing the dry, purified product Compute the mass of the product Compute the percent yield Determine the Melting Point 4/19/2017