{  (set: $showFooter to true) (set:$mechanismSN2 to false) (set:$mechanismSN1 to false) (set:$mechanism = "") (set:$SN2complete to false) (set:$SN1complete to false) (set: $SubstSummaryLink to "<a href=\"_twine_sub/documents/Substitution-Summary.pdf\" target=\"_blank\">Substitution Reaction Summary (PDF)</a>") (set: $ExpDesWorkLink to "<a href=\"_twine_sub/documents/Exp-Design-Worksheet.pdf\" target=\"_blank\">Experiment Design Worksheet (PDF)</a>")  (set:$SN2stereo to "enantiospecific") (set:$SN2stereoCap to "Enantiospecific") (set:$SN1stereo to "racemic") (set:$SN1stereoCap to "Racemic") (set:$SN2mech to "S<sub>N</sub>2") (set:$SN1mech to "S<sub>N</sub>1")  (set: $reag1Cap to "Sulfuric Acid (H<sub>2</sub>SO<sub>4</sub>)") (set: $reag1 to "sulfuric acid (H<sub>2</sub>SO<sub>4</sub>)") (set: $reag2Cap to "Sodium Hydroxide (NaOH)") (set: $reag2 to "sodium hydroxide (NaOH)") (set: $reag3Cap to "The Electrophile has a Good Leaving Group Already!") (set: $reag3 to "the electrophile has a good leaving group already!") (set: $reag4Cap to "Toluenesulfonyl chloride (TsCl)") (set: $reag4 to "toluene sulfonyl chloride (TsCl)") (set: $nuc1Cap to "Hydrogen Sulfide (H<sub>2</sub>S)") (set: $nuc1 to "hydrogen sulfide (H<sub>2</sub>S)") (set: $nuc2Cap to "Methanethiol (MeSH)") (set: $nuc2 to "methanethiol (MeSH)") (set: $nuc3Cap to "Dimethyl Sulfide (Me<sub>2</sub>S)") (set: $nuc3 to "dimethyl sulfide (Me<sub>2</sub>S)") (set: $nuc4Cap to "Sodium Thiomethoxide (NaSMe)") (set: $nuc4 to "sodium thiomethoxide (NaSMe)") (set: $nuc5Cap to "Sodium Hydrosulfide (NaSH)") (set: $nuc5 to "sodium hydrosulfide (NaSH)") (set: $solvtype1Cap to "Polar Protic") (set: $solvtype1 to "polar protic") (set: $solvtype2Cap to "Polar Aprotic") (set: $solvtype2 to "polar aprotic") (set: $solvtype3Cap to "Non-Polar") (set: $solvtype3 to "non-polar") (set: $solvtype4Cap to "Aqueous") (set: $solvtype4 to "aqueous") (set: $solvtype5Cap to "Organic") (set: $solvtype5 to "organic") (set: $solv1Cap to "Acetonitrile") (set: $solv1 to "acetonitrile") (set: $solv2Cap to "Toluene") (set: $solv2 to "toluene") (set: $solv3Cap to "Methanol") (set: $solv3 to "methanol") (set: $solv4Cap to "Hexane") (set: $solv4 to "hexane") (set: $solv5Cap to "Water") (set: $solv5 to "water") (set: $solv6Cap to "Ethyl Acetate") (set: $solv6 to "ethyl acetate") (set: $solv7Cap to "Sulfuric Acid") (set: $solv7 to "sulfuric acid") (set: $SN2chiralyes to "Yes") (set: $SN2chiralno to "No") (set: $SN1chiralyes to "Yes") (set: $SN1chiralno to "No") (set: $SN2stereoR to "(<i>R</i>)") (set: $SN2stereoS to "(<i>S</i>)") (set: $SN2optionA to "A") (set: $SN2optionB to "B") (set: $SN2optionC to "C") (set: $SN2optionD to "D") (set: $SN1stereo1 to "Top is (<i>R</i>); Bottom is (<i>S</i>)") (set: $SN1stereo2 to "Top is (<i>S</i>); Bottom is (<i>R</i>)") (set: $SN1stereo3 to "Top is (<i>R</i>); Bottom is (<i>R</i>)") (set: $SN1stereo4 to "Top is (<i>S</i>); Bottom is (<i>S</i>)")  (set: $overallstereo to "<img src=\"_twine_sub/images/schemes/overall-stereo.png\"; alt=\"Reaction scheme of the two substitution reactions converting (S)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide enantiospecifically or as a racemic mixture\"><figcaption>Enantiospecific or racemic conversion of (<i>S</i>)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide.</figcaption>") (set: $overallrac to "<img src=\"_twine_sub/images/schemes/overall-racemic.png\"; alt=\"Reaction scheme of the racemic conversion of (S)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide\"><figcaption>Racemic conversion of (<i>S</i>)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide.</figcaption>") (set: $overallSN1 to "<img src=\"_twine_sub/images/schemes/overall-SN1.png\"; alt=\"Reaction scheme of the unimolecular substitution of (S)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide\"><figcaption>Conversion of (<i>S</i>)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide under S<sub>N</sub>1 mechanism.</figcaption>") (set: $overallenant to "<img src=\"_twine_sub/images/schemes/overall-enant.png\"; alt=\"Reaction scheme of the enantiospecific conversion of (S)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide\"><figcaption>Enantiospecific conversion of (<i>S</i>)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide.</figcaption>") (set: $overallSN2 to "<img src=\"_twine_sub/images/schemes/overall-SN2.png\"; alt=\"Reaction scheme of the bimolecular substitution of (S)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide\"><figcaption>Conversion of (<i>S</i>)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide under S<sub>N</sub>2 mechanism.</figcaption>") (set: $SN1LG to "<img src=\"_twine_sub/images/schemes/SN1-ionization.png\"; alt=\"Scheme showing the departure of the leaving group to form the carbocation in SN1 reactions\"><figcaption>Formation of the carbocation via leaving group (LG = leaving group) departure in S<sub>N</sub>1 reactions.</figcaption>") (set: $H2SO4rxn to "<img src=\"_twine_sub/images/schemes/H2SO4-scheme.png\"; alt=\"Scheme of the reaction between (S)-1-phenylethan-1-ol and sulfuric acid to give the protonated alcohol\"><figcaption>Reaction of (<i>S</i>)-1-phenylethan-1-ol with sulfuric acid to form the protonated alcohol.</figcaption>") (set: $SN2LG to "<img src=\"_twine_sub/images/schemes/SN2-LG.png\"; alt=\"Scheme showing the conversion of a molecule with a leaving group to a molecule incorporating a nucleophile\"><figcaption>Formation of the S<sub>N</sub>2 product by attack of the nucleophile on the electrophile containing a leaving group (LG = leaving group).</figcaption>") (set: $TsClrxn to "<img src=\"_twine_sub/images/schemes/TsCl-scheme.png\"; alt=\"Scheme of the reaction between (S)-1-phenylethan-1-ol and toluenesulfonyl chloride to give the sulfonate group\"><figcaption>Reaction of (<i>S</i>)-1-phenylethan-1-ol with toluenesulfonyl chloride to form a sulfonate group.</figcaption>") (set: $electrophilereagents to "<img src=\"_twine_sub/images/molecules/electrophile-reagents.png\"; alt=\"Chemical structures of sulfuric acid, sodium hydroxide and toluenesulfonyl chloride\"><figcaption>Chemical structures of the reagent options to activate the electrophile.</figcaption>") (set: $nucleophilereagents to "<img src=\"_twine_sub/images/molecules/nucleophile-reagents.png\"; alt=\"Chemical structures of hydrogen sulfide, methanethiol, dimethyl sulfide, sodium thiomethoxide and sodium hydrosulfide\"><figcaption>Chemical structures of the nucleophile options</figcaption>") (set: $H2Snuc to "<img src=\"_twine_sub/images/molecules/H2S-nuc.png\"; alt=\"Comparison of the chemical structures of hydrogen sulfide and methyl 1-phenylethyl sulfide showing there is a methyl group missing to obtain the correct product\"><figcaption>Chemical structures of hydrogen sulfide and methyl 1-phenylethyl sulfide. There is a methyl group missing!</figcaption>") (set: $NaSHnuc to "<img src=\"_twine_sub/images/molecules/NaSH-nuc.png\"; alt=\"Comparison of the chemical structures of sodium hydrosulfide and methyl 1-phenylethyl sulfide showing there is a methyl group missing to obtain the correct product\"><figcaption>Chemical structures of sodium hydrosulfide and methyl 1-phenylethyl sulfide. There is a methyl group missing!</figcaption>") (set: $Me2Snuc to "<img src=\"_twine_sub/images/molecules/Me2S-nuc.png\"; alt=\"Comparison of the chemical structures of dimethylsulfide and methyl 1-phenylethyl sulfide showing there is a methyl group too many to obtain the correct product\"><figcaption>Chemical structures of dimethylsulfide and methyl 1-phenylethyl sulfide. There is an extra methyl group!</figcaption>") (set: $NaSMenuc to "<img src=\"_twine_sub/images/molecules/NaSMe-nuc.png\"; alt=\"Comparison of the chemical structures of sodium thiomethoxide and methyl 1-phenylethyl sulfide showing they both include a single methyl group on the sulfur atom\"><figcaption>Chemical structures of sodium thiomethoxide and methyl 1-phenylethyl sulfide. The carbon count is correct!</figcaption>") (set: $MeSHnuc to "<img src=\"_twine_sub/images/molecules/MeSH-nuc.png\"; alt=\"Comparison of the chemical structures of methanethiol and methyl 1-phenylethyl sulfide showing they both include a single methyl group on the sulfur atom\"><figcaption>Chemical structures of methanethiol and methyl 1-phenylethyl sulfide. The carbon count is correct!</figcaption>") (set: $nucPAsolv to "<img src=\"_twine_sub/images/molecules/nuc-PAsolv.png\"; alt=\"Negatively charged nucleophile and its counterion solvated by a polar aprotic solvent, using dimethyl sulfoxide as example. There are dipole-ion interactions between the positive counterion and the solvent. There is no hydrogen bonding interaction between the solvent and the nucleophilic ion\"><figcaption>Polar aprotic solvents (such as DMSO in this example) can only interact with the positive counterion via dipole-ion interaction, this leaves the negatively charged nucleophile less solvated and therefore more nucleophilic.</figcaption>") (set: $nucPPsolv to "<img src=\"_twine_sub/images/molecules/nuc-PPsolv.png\"; alt=\"Negatively charged nucleophile and its counterion solvated by a polar protic solvent, using water as example. There are hydrogen bonding between the solvent and the nucleophilic ion and dipole-ion interactions between the positive counterion and the solvent\"><figcaption>Polar protic solvents (such as water in this example) interact with the negatively charged nucleophile via hydrogen-bonding, which reduces its nucleophilicity since the electrons are less available for the reaction with the electrophile.</figcaption>") (set: $carbPAsolv to "<img src=\"_twine_sub/images/molecules/carb-PAsolv.png\"; alt=\"Carbocation and leaving group dissociated and solvated by a polar aprotic solvent, using dimethyl sulfoxide as example. There are dipole-ion interactions between the positive carbocation and the solvent. There is no hydrogen bonding interaction between the solvent and the negative leaving group\"><figcaption>Polar aprotic solvents (such as DMSO in this example) can only interact with the positive carbocation via dipole-ion interaction, making the dissociation of the leaving group more difficult as the leaving group could re-associate with the carbocation without effective solvation.</figcaption>") (set: $carbPPsolv to "<img src=\"_twine_sub/images/molecules/carb-PPsolv.png\"; alt=\"Carbocation and leaving group dissociated and solvated by a polar aprotic solvent, using water as example. There are dipole-ion interactions between the positive carbocation and the solvent and hydrogen bonding interaction between the solvent and the negative leaving group\"><figcaption>Polar protic solvents (such as water in this example) effectively solvate both the carbocation and the negatively charged leaving group, making the dissociation less energetic due to the stabilization of both charged intermediates. The solvation also avoids the reversible process where the leaving group adds to the carbocation.</figcaption>") (set: $solventsSN2 to "<img src=\"_twine_sub/images/molecules/solv-SN2.png\"; alt=\"Chemical structures of acetonitrile, toluene, methanol, water and hexane\"><figcaption>Chemical structures of the solvent options for the S<sub>N</sub>2 reaction.</figcaption>") (set: $solventsSN1 to "<img src=\"_twine_sub/images/molecules/solv-SN1.png\"; alt=\"Chemical structures of acetonitrile, toluene, methanol, hexane and ethyl acetate\"><figcaption>Chemical structures of the solvent options for the S<sub>N</sub>1 reaction.</figcaption>") (set: $MeCNsolv to "<img src=\"_twine_sub/images/molecules/MeCN-solv.png\"; alt=\"Chemical structure of acetonitrile highlighting the lone pair on the nitrogen, allowing the molecule to accept hydrogen bonding\"><figcaption>Acetonitrile is a polar aprotic solvent because its dipole moment is non-zero (making it polar) and it is only able to accept hydrogen bonds due to the presence of a nitrogen atom but the absence of a N–H, O–H or F–H bond.</figcaption>") (set: $Tolsolv to "<img src=\"_twine_sub/images/molecules/Tol-solv.png\"; alt=\"Chemical structure of toluene\"><figcaption>Toluene is considered a non-polar solvent since its structure contains only carbon and hydrogen atoms. This makes for a negligible dipole moment in the molecule.</figcaption>") (set: $Hexsolv to "<img src=\"_twine_sub/images/molecules/Hex-solv.png\"; alt=\"Chemical structure of hexane\"><figcaption>Hexane is considered a non-polar solvent since its structure contains only carbon and hydrogen atoms. This makes for a negligible dipole moment in the molecule.</figcaption>") (set: $MeOHsolv to "<img src=\"_twine_sub/images/molecules/MeOH-solv.png\"; alt=\"Chemical structure of methanol highlighting its ability to form hydrogen bonds with itself\"><figcaption>Methanol is a polar protic solvent since it contains an O–H bond. Whenever a solvent can hydrogen bond with itself as shown here, it is considered polar protic.</figcaption>") (set: $H2Osolv to "<img src=\"_twine_sub/images/molecules/H2O-solv.png\"; alt=\"Chemical structure of methanol highlighting its ability to form hydrogen bonds with itself\"><figcaption>Water is a polar protic solvent since it contains an O–H bond. Whenever a solvent can hydrogen bond with itself as shown here, it is considered polar protic.</figcaption>") (set: $H2SO4solv to "<img src=\"_twine_sub/images/molecules/H2SO4-solv.png\"; alt=\"Figure showing the ability of sulfuric acid to hydrogen bond with itself\"><figcaption>Since sulfuric acid can hydrogen bond with itself, it is a polar protic solvent.</figcaption>") (set: $SN2TS to "<img src=\"_twine_sub/images/schemes/SN2-TS.png\"; alt=\"Reaction scheme of the bimolecular substitution of (S)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide including the transition state\"><figcaption>Reaction scheme of the bimolecular substitution of (<i>S</i>)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide including the transition state.</figcaption>") (set: $SN1steps to "<img src=\"_twine_sub/images/schemes/SN1-step.png\"; alt=\"Reaction scheme of the unimolecular substitution of the protonated (S)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide including the formation of the carbocation\"><figcaption>Reaction scheme of the unimolecular substitution of (<i>S</i>)-1-phenylethan-1-ol (in protonated state) to methyl 1-phenylethyl sulfide (in protonated state) including the formation of the carbocation.</figcaption>") (set: $SN1carb to "<img src=\"_twine_sub/images/schemes/SN1-carb.png\"; alt=\"Reaction scheme of the formation of the carbocation from protonated (S)-1-phenylethan-1-ol\"><figcaption>Reaction scheme of the formation of the carbocation from (<i>S</i>)-1-phenylethan-1-ol. The empty p orbital of the carbocation is parallel to the aromatic ring to allow for the resonance stabilization of the benzylic carbocation.</figcaption>") (set: $SN1nuc to "<img src=\"_twine_sub/images/schemes/SN1-nuc.png\"; alt=\"Reaction scheme of the nucleophilic addition of methane thiol to the carbocation to form 1-phenylethyl sulfide\"><figcaption>Reaction scheme of the addition of methane thiol to the carbocation. The nucleophile attacks either from the top or the bottom of the carbocation since both approaches allow to populate the empty p orbital. This explains the formation of both enantiomers of methyl 1-phenylethyl sulfide (in protonated state).</figcaption>") (set: $SN1acidbase to "<img src=\"_twine_sub/images/schemes/SN1-acidbase.png\"; alt=\"Reaction scheme showing the abstraction of a proton from the activated electrophile by sodium thiomethoxide\"><figcaption>Reaction scheme of the acid-base side reaction between sodium thiomethoxide and the protonated alcohol. Negatively charged nucleophiles are also basic and are therefore not compatible with protonated alcohols as electrophiles.</figcaption>") (set: $SN1water to "<img src=\"_twine_sub/images/schemes/SN1-water.png\"; alt=\"Reaction scheme showing the reaction of the electrophile with water. The product is racemic 1-phenylethan-1-ol\"><figcaption>Reaction scheme of the S<sub>N</sub>1 reaction between water and the activated 1-phenylethan-1-ol. Since the reaction goes through a carbocation intermediate the product is racemic.</figcaption>") (set: $SN1methanol to "<img src=\"_twine_sub/images/schemes/SN1-methanol.png\"; alt=\"Reaction scheme showing the reaction of the electrophile with methanol. The product is racemic (1-methoxyethyl)benzene\"><figcaption>Reaction scheme of the S<sub>N</sub>1 reaction between methanol and the activated 1-phenylethan-1-ol. Since the reaction goes through a carbocation intermediate the product is racemic.</figcaption>") (set: $SN1deprot to "<img src=\"_twine_sub/images/schemes/SN1-deprot.png\"; alt=\"Reaction scheme showing the deprotonation of the nucleophilic addition adduct to form methyl 1-phenylethyl sulfide\"><figcaption>Reaction scheme of the deprotonation of the nucleophilic addition product during the post-reaction extration using a weakly basic aqueous layer.</figcaption>") (set: $SN2options to "<img src=\"_twine_sub/images/molecules/pdt-options.png\"; alt=\"Four different options for representing the product of the SN2 pathway, labelled A through D\"><figcaption>Different ways of drawing methyl 1-phenylethyl sulfide with its stereochemistry defined. Identify which has the correct configuration based on the S<sub>N</sub>2 reaction performed.</figcaption>") (set: $Roptions to "<img src=\"_twine_sub/images/molecules/pdt-r-enant.png\"; alt=\"Four different ways of representing the R enantiomer of methyl 1-phenylethyl sulfide\"><figcaption>All of the above molecules are correct ways to draw (<i>R</i>)-methyl 1-phenylethyl sulfide using wedge and dash representations. You can convince yourself by assigning the stereochemistry of each one!</figcaption>") (set: $Soptions to "<img src=\"_twine_sub/images/molecules/pdt-r-enant.png\"; alt=\"Four different ways of representing the R enantiomer of methyl 1-phenylethyl sulfide\"><figcaption>All of the above molecules are correct ways to draw (<i>R</i>)-methyl 1-phenylethyl sulfide using wedge and dash representations. You can convince yourself by assigning the stereochemistry of each one!</figcaption>") }

<div class="step">Introduction</div> <h1>Virtual Lab: Substitution Reactions</h1> <h2> Synthesis of Methyl 1-Phenylethyl Sulfide: Stereoselective and Racemic</h2> <p>In this virtual laboratory, you will use both substitution mechanisms (S<sub>N</sub>2 and S<sub>N</sub>1) to convert <b>(<i>S</i>)-1-phenylethan-1-ol</b> to <b>methyl 1-phenylethyl sulfide</b>. The virtual lab will include 3D animations of the reactions involved to help you better visualize why each reaction mechanism leads to a different reaction pathway.</b> <p>Through this activity, you will be called to make choices to direct the reaction. Although this virtual laboratory does not include laboratory footage of the experiment being performed, thinking about the choice of <b>solvent</b> and <b>reagents</b> will help you better understand how to answer exam questions and help you with the related laboratory experiments (Experiments 4 and 5 of CHEM 266L). <br><ul class="flex-container"><li class="flex-image">$overallstereo</li></ul></br> <p>During this virtual lab, you will: <ul><li><b>Design</b> both a S<sub>N</sub>2 and a S<sub>N</sub>1 reaction to synthesize methyl 1-phenylethyl sulfide.</li><li>View <b>3D animations</b> and <b>energy diagrams</b> of the reaction processes, powered by Density Functional Theory, a computational chemistry model that can calculate the energy of molecules.</li><li>Review the <b>stereochemical outcome</b> of S<sub>N</sub>2 and S<sub>N</sub>1 reactions.</li></ul></p> <p><h2>Before You Begin</h2></p> <p><b>Review the Substitution Reaction Summary linked below</b>. You should have an idea of which conditions favours S<sub>N</sub>2 vs S<sub>N</sub>1 to complete this virtual with ease, but the feedback at each decision point is meant to help correct any misconceptions you may have.</p> <p><div class="dwnld-doc"><span class="instruction-text">Download File</span><br>Download the $SubstSummaryLink here.</br></div></p> <p>Set aside <b>60 minutes</b> to complete the virtual laboratory.</p> <div class="flex-proceed"> <button class="button proceed"><span>[[Continue->instructions]]</span></button></div>

<div class="step">Introduction</div> <h1>Instructions for the Virtual Lab</h1> <p>This virtual lab incorporates figures and 3D animations graphics to help you visualize the different substitution reaction mechanisms. The images will <b><i>will adapt</i></b> to the reaction you are designing based on your individual choices. This will equip you with a strong understanding of the substitution reactions which are central to the first semester of organic chemistry.</p> <p><h2>Experimental Design Choices</h2></p> <p>Throughout this lab, you will reach <b>Decision Points</b>, where you need to make experimental design choice. The options presented will help you design either a S<sub>N</sub>2 or S<sub>N</sub>1 reaction, and most will have a clear correct or incorrect answer. If you select incorrectly, you can return and try again after viewing the feedback. This feedback describes why each choice is correct or incorrect. This is a learning process! Use wrong answers as a learning opportunity, and you will not be penalized for making errors along the way in the virtual lab.</p> <p><div class="selection"><span class="instruction-text">Decision Point</span><br>Select your nucleophile:</br><ul> <li>Option 1</li><li>Option 2</li><li>Option 3</li><li>Option 4</li></ul></div></p> <p><h2>The Experimental Design Worksheet</h2></p> <p>You will see the <b>Experimental Design Worksheet </b> highlight box reminding you to record your choices and results. This organizes your answers to the virtual lab and demonstrates that you’ve completed this activity. This experimental design worksheet is not required for the completion of the course, but is a good exercise to practice designing your experimental conditions.</p> <p><div class="exp-outline"><span class="instruction-text">Experimental Outline</span><br>Note down your data in your experimental outline!</br></div></p> <p>Download the Experimental Design Worksheet file below. It is a fillable PDF form you can complete electronically or print it to fill it by hand.</p> <p><div class="dwnld-doc"><span class="instruction-text">Download File</span><br>Download the $ExpDesWorkLink here.</br></div></p> <p><h2>Why 60 minutes?</h2></p <p>One hour should give you time to go through all stages of the experiment, interact with the animation, read the feedback, and complete the experimental design worksheet. This time limit is not enforced (the virtual lab will not quit!). You can take longer than one hour, but we encourage you to review the laboratory and be prepared for the virtual experiment just as you would before an in-person lab.</p> <p><b>Important! <i>If you need to exit this lab mid-completion, you cannot return to where you left off.</i></b> You will need to return and start from the beginning. This is why we recommend allowing yourself at least one hour of time.</p> <p>The more prepared you are, the faster you will complete the experiment – just like in a physical lab! While in this virtual lab, you can return and repeat the full experiment, this is often not possible in a physical laboratory.</p> <p><h2>Tips</h2></p <p>You are welcome to take screenshots for your personal notes. You must have written consent of your instructor to post any course content online.</p> <div class="flex-proceed"> <button class="button proceed"><span>[[Continue->learning objectives]]</span></button></div>

<div class="step">Introduction</div> <h1>Learning Objectives</h1> <p>By the end of this virtual lab, you should be able to:<ul><li>Distinguish the two substitution mechanisms: Bimolecular (S<sub>N</sub>2) and Unimolecular (S<sub>N</sub>1).</li><li>Choose the appropriate reagents and solvents to direct either type of substitution reactions.</li><li>Gain a greater understanding of the substitution reactions by visualizing them in three dimensions.</li><li>Understand the mechanistic rationale behind the stereochemical outcome of S<sub>N</sub>1 and S<sub>N</sub>2 reactions.</li></ul></p> <div class="flex-proceed"> <button class="button proceed"><span>[[Begin->stereo]]</span></button></div><div style="clear: both;"></div>

<div class="step">Stereoselectivity and Substitution Reactions</div><h1>Choosing the Appropriate Mechanism</h1> <p>To begin the experiment design process, we will choose what stereoselectivity control we want to exert on the reaction. What would you like to begin with?</p><ul class="flex-container"><li class="flex-image">$overallstereo</li></ul><br></br> <div class="selection"><span class="instruction-text">Decision Point</span><br>Select your desired stereoselectivity:</br><ul> <li>(link: $SN2stereoCap)[(set: $SN2mechanism to true)(goto: "stereoSN2")]</li><li>(link: $SN1stereoCap)[(set: $SN1mechanism to true)(goto: "stereoSN1")]</li></ul></div>

(set: $SN2complete to true)[<div class="step">Stereoselectivity and Substitution Reactions</div> <h1>Choosing the Appropriate Mechanism</h1> <p>Great! Let’s go for a $SN2stereo reaction. Which reaction mechanism should we use?</p><ul class="flex-container"><li class="flex-image">$overallenant</li></ul><br></br> <div class="selection"><span class="instruction-text">Decision Point</span><br>Select your desired mechanism:</br><ul> <li>(link: $SN2mech)[(set: $mechanismSN2 to $SN2mech)(goto: "stereofeedbackSN2")]</li> <li>(link: $SN1mech)[(set: $mechanismSN2 to $SN1mech)(goto: "stereofeedbackSN2")]</li></ul></div>]

(set: $SN1complete to true)[<div class="step">Stereoselectivity and Substitution Reactions</div> <h1>Choosing the Appropriate Mechanism</h1> <p>Great! Let’s go for a $SN1stereo reaction. Which reaction mechanism should we use?</p><ul class="flex-container"><li class="flex-image">$overallrac</li></ul><br></br> <div class="selection"><span class="instruction-text">Decision Point</span><br> Select your desired mechanism:</br><ul> <li>(link: $SN2mech)[(set: $mechanismSN1 to $SN2mech)(goto: "stereofeedbackSN1")]</li><li>(link: $SN1mech)[(set: $mechanismSN1 to $SN1mech)(goto: "stereofeedbackSN1")]</li></ul></div>]

<div class="step">Stereoselectivity and Substitution Reactions</div> (if: $mechanismSN2 is $SN2mech)[<div class="correct"><br>Correct answer for the mechanism type!</br></div><p><b>Correct</b>, since we want a $SN2stereo reaction, and since S<sub>N</sub>2 reactions are <b>concerted</b>, if we use a enantiopure electrophile, the product will also be enantiopure.</p><ul class="flex-container"><li class="flex-image">$overallSN2</li></ul><p>Once you complete the selection of the reagents we will discuss the origin of the stereochemical outcome in greater detail assisted by 3D animations.</p><div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Note down the stereoselectivity in the S<sub>N</sub>2 column of the worksheet.</br></div><div class="flex-proceed"><button class="button proceed"><span>[[Next->leaving groupSN2]]</span></button></div>](else-if: $mechanismSN2 is $SN1mech)[<div class="incorrect"><br>Incorrect answer for the mechanism type!</br></div><p>This is <b>not correct</b>. S<sub>N</sub>1 reactions go through a sp<sup>2</sup>-hybridized carbocation intermediate, we lose the enantiopurity of the starting electrophile. </p><div class="flex-return"><button class="button return"><span>[[Choose another option->stereoSN2]]</span></button></div>]

<div class="step">Stereoselectivity and Substitution Reactions</div> (if: $mechanismSN1 is $SN1mech)[<div class="correct"><br>Correct answer for the mechanism type!</br></div><p><b>Correct</b>, since we want a $SN1stereo reaction, and since S<sub>N</sub>1 reactions go through a <b>sp<sup>2</sup>-hybridized carbocation intermediate</b>, we lose the enantiopurity of the starting electrophile.</p><ul class="flex-container"><li class="flex-image">$overallSN1</li></ul><br></br><p>Once you complete the selection of the reagents we will discuss the origin of the stereochemical outcome in greater detail assisted by 3D animations. </p><div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Note down the stereoselectivity in the S<sub>N</sub>1 column of the worksheet.</br></div><div class="flex-proceed"><button class="button proceed"><span>[[Next->leaving groupSN1]]</span></button></div>] (else-if: $mechanismSN1 is $SN2mech)[<div class="incorrect"><br>Incorrect answer for the mechanism type!</br></div><p>This is <b>not correct</b>. S<sub>N</sub>2 reactions are concerted, and if we use a enantiopure electrophile, the product will also be enantiopure. </p><div class="flex-return"><button class="button return"><span>[[Choose another option->stereoSN1]]</span></button></div>]

<div class="step">Leaving Group Ability</div> <h1>Choosing the Reagent to Activate the Leaving Group in S<sub>N</sub>1</h1> <p>In S<sub>N</sub>1, the formation of the carbocation following the leaving group departure is the <b>rate-determining step</b> of the reaction. Therefore a neutral or well-stabilized negative leaving group will be best to ensure a straightforward ionization, although the stability of the carbocation is a bigger factor. <ul class="flex-container"><li class="flex-image">$SN1LG</li></ul> <p>The starting material is <b>(<i>S</i>)-1-phenylethan-1-ol</b>, how good is the current starting leaving group? Regardless of the leaving group, a secondary carbocation is generally not the most stable carbocation, but in this system the carbocation is <b>benzylic</b>. The empty p orbital of the carbocation is in parallel with the ones of the aromatic ring and therefore part of the resonance system. <b><u>Remember</u>: resonance stabilization is usually stronger than hyperconjugation!</b></p> <p>Some thoughts to consider regarding leaving groups:</p><ul><li>Weak bases make for better leaving groups.</li><li>The leaving group should be a weaker base than the nucleophile to ensure the forward reaction is favored.</li><li>A non-nucleophilic weak base (such as sulfonates) is preferred so the reverse reaction pathway is suppressed.</li></ul> <p>What reagent could we use to improve the leaving group ability of <b>(<i>S</i>)-1-phenylethan-1-ol</b> while still ensuring a <b>S<sub>N</sub>1 process</b> will occur once we add a nucleophile? <div class="selection"><span class="instruction-text">Decision Point</span><br>Select your reagent:</br><ul> <li>(link: $reag1Cap)[(set: $leavinggroupSN1 to $reag1)(goto: "lgfeedbackSN1")]</li> <li>(link: $reag2Cap)[(set: $leavinggroupSN1 to $reag2)(goto: "lgfeedbackSN1")]</li> <li>(link: $reag3Cap)[(set: $leavinggroupSN1 to $reag3)(goto: "lgfeedbackSN1")]</li> <li>(link: $reag4Cap)[(set: $leavinggroupSN1 to $reag4)(goto: "lgfeedbackSN1")]</li></ul></div>

<div class="step">Leaving Group Ability</div> <h1>Choosing the Reagent to Activate the Leaving Group in S<sub>N</sub>2</h1> <p>The first consideration in our design of the S<sub>N</sub>2 reaction will be the leaving group ability. Since S<sub>N</sub>2 is a concerted reaction, the nucleophile attacks the electrophile as the leaving group departs, a leaving group that can stabilize a negative charge will be preferred.</p> <ul class="flex-container"><li class="flex-image">$SN2LG</li></ul><p>The starting material is <b>(<i>S</i>)-1-phenylethan-1-ol</b>, how good is the current starting leaving group? Some thoughts to consider regarding leaving groups:</p><ul><li>Weak bases make for better leaving groups.</li><li>The leaving group should be a weaker base than the nucleophile to ensure the forward reaction is favored.</li><li>A non-nucleophilic weak base (such as sulfonates) is preferred so the reverse reaction pathway is suppressed.</li></ul> <p>What reagent could we use to improve the leaving group ability of <b>(<i>S</i>)-1-phenylethan-1-ol</b> while still ensuring a <b>S<sub>N</sub>2 process</b> will occur once we add a nucleophile? <div class="selection"><span class="instruction-text">Decision Point</span><br>Select your reagent:</br><ul> <li>(link: $reag1Cap)[(set: $leavinggroupSN2 to $reag1)(goto: "lgfeedbackSN2")]</li> <li>(link: $reag2Cap)[(set: $leavinggroupSN2 to $reag2)(goto: "lgfeedbackSN2")]</li> <li>(link: $reag3Cap)[(set: $leavinggroupSN2 to $reag3)(goto: "lgfeedbackSN2")]</li> <li>(link: $reag4Cap)[(set: $leavinggroupSN2 to $reag4)(goto: "lgfeedbackSN2")]</li></ul></div>

<div class="step">Leaving Group Ability</div> (if:$leavinggroupSN2 is $reag4)[<div class="correct"><br>Correct answer for the reagent used to increase the leaving group ability in (<i>S</i>)-1-phenylethan-1-ol!</br></div> <p>You chose $leavinggroupSN2. This is the <b>correct</b> choice! Reacting (<i>S</i>)-1-phenylethan-1-ol with $leavinggroupSN2 will form a sulfonate which is a very good leaving group for S<sub>N</sub>2 since they would be both weak bases and poor nucleophiles due to the resonance stabilization of the negative charge by resonance.</p> <ul class="flex-container"><li class="flex-image">$TsClrxn</li></ul><br></br> <p><div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Note down the reagent used to increase the leaving group ability of the electrophile in the S<sub>N</sub>2 column of the worksheet.</p></div> <p>In the next section, you will choose a nucleophile appropriate for the S<sub>N</sub>2 reaction pathway.</p><div class="flex-proceed"><button class="button proceed"><span>[[Next->nucleophileSN2]]</span></button></div>] (else-if:$leavinggroupSN2 is $reag1)[<div class="incorrect"><br>Incorrect answer for the reagent used to increase the leaving group ability in (<i>S</i>)-1-phenylethan-1-ol.</br></div><p>While $leavinggroupSN2 can protonate the alcohol functional group, making the leaving group water it is not the best strategy for S<sub>N</sub>2. Normally, for <b>S<sub>N</sub>2 you will need a strong nucleophile, which will usually be a strong base or negatively charged. With the protonated alcohol as electrophile, you risk having an acid-base reaction instead of a substitution.</p> INSERT IMAGE <p>Consider the other reagent options to find one that will increase the leaving group ability in (<i>S</i>)-1-phenylethan-1-ol without including an acidic proton.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->leaving groupSN2]]</span></button></div>] (else-if:$leavinggroupSN2 is $reag2)[<div class="incorrect"><br>Incorrect answer for the reagent used to increase the leaving group ability in (<i>S</i>)-1-phenylethan-1-ol.</br></div><p>With $leavinggroupSN2, you would have a deprotonated alcohol undergoing <b>S<sub>N</sub>2, making the leaving group O<sup>2–</sup>. This would be a very unfavourable leaving group, no matter how electronegative oxygen is!</p> <p>Consider that a good leaving group in <b>S<sub>N</sub>2 will be a weak base, which reagent will be able to create a good leaving group in (<i>S</i>)-1-phenylethan-1-ol?</p><div class="flex-return"><button class="button return"><span>[[Choose another option->leaving groupSN2]]</span></button></div>] (else-if:$leavinggroupSN2 is $reag3)[<div class="incorrect"><br>Incorrect answer for the reagent used to increase the leaving group ability in (<i>S</i>)-1-phenylethan-1-ol.</br></div><p>Without modifying (<i>S</i>)-1-phenylethan-1-ol, you would have hydroxide as leaving group. This would be a very unfavourable leaving group since hydroxide is a strong base.</p><p>Consider that a good leaving group in <b>S<sub>N</sub>2 will be a weak base, which reagent will be able to create a good leaving group in (<i>S</i>)-1-phenylethan-1-ol?</p><div class="flex-return"><button class="button return"><span>[[Choose another option->leaving groupSN2]]</span></button></div>]

<div class="step">Nucleophile Choice</div> (if:$nucSN2 is $nuc4)[<div class="correct"><br>Correct answer for the nucleophile in S<sub>N</sub>2!</br></div> <p>You chose $nucSN2. This is the <b>correct</b> choice! $nuc4Cap is a weak base but strong nucleophile. The negatively charged sulfur atom donates its electrons readily since its electronegativity is lower and its larger atomic radius means a higher degree of polarizability.</p><ul class="flex-container"><li class="flex-image">$NaSMenuc</li></ul><br></br> </p><div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Note down the nucleophile used in the S<sub>N</sub>2 column of the worksheet.</br></div><p>In the next section, you will choose an appropriate solvent for the S<sub>N</sub>2 reaction pathway.</p><div class="flex-proceed"><button class="button proceed"><span>[[Next->solvtypeSN2]]</span></button></div>] (else-if:$nucSN2 is $nuc1)[<div class="incorrect"><br>Incorrect answer for the nucleophile in S<sub>N</sub>2!</br></div> <p>First, $nuc1 does not have the correct number of carbon atoms to yield methyl 1-phenylethyl sulfide after reacting with the electrophile. In addition, for S<sub>N</sub>2, strong nucleophiles bearing a negative charge are usually preferred.</p><ul class="flex-container"><li class="flex-image">$H2Snuc</li></ul><br></br> <p>Consider the other nucleophile options to find one that will convert (<i>S</i>)-1-phenylethan-1-ol to <b>methyl 1-phenylethyl sulfide</b> via S<sub>N</sub>2.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->nucleophileSN2]]</span></button></div>] (else-if:$nucSN2 is $nuc2)[<div class="incorrect"><br>Incorrect answer for the nucleophile in S<sub>N</sub>2!</br></div> <p>While $nuc2 has the correct number of carbon atoms to yield methyl 1-phenylethyl sulfide after reacting with the electrophile, for S<sub>N</sub>2, strong nucleophiles bearing a negative charge are preferred.</p> <p>Consider the other nucleophile options to find one that will convert (<i>S</i>)-1-phenylethan-1-ol to <b>methyl 1-phenylethyl sulfide</b> via S<sub>N</sub>2.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->nucleophileSN2]]</span></button></div>] (else-if:$nucSN2 is $nuc3)[<div class="incorrect"><br>Incorrect answer for the nucleophile in S<sub>N</sub>2!</br></div> <p>First, $nuc3 does not have the correct number of carbon atoms to yield methyl 1-phenylethyl sulfide after reacting with the electrophile. In addition, for S<sub>N</sub>2, strong nucleophiles bearing a negative charge are usually preferred.</p><ul class="flex-container"><li class="flex-image">$Me2Snuc</li></ul><br></br> <p>Consider the other nucleophile options to find one that will convert (<i>S</i>)-1-phenylethan-1-ol to <b>methyl 1-phenylethyl sulfide</b> via S<sub>N</sub>2.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->nucleophileSN2]]</span></button></div>] (else-if:$nucSN2 is $nuc5)[<div class="incorrect"><br>Incorrect answer for the nucleophile in S<sub>N</sub>2!</br></div><p>$nuc5Cap does not have the correct number of carbon atoms to yield methyl 1-phenylethyl sulfide after reacting with the electrophile.</p><ul class="flex-container"><li class="flex-image">$NaSHnuc</li></ul><br></br> <p>Consider the other nucleophile options to find one that will convert (<i>S</i>)-1-phenylethan-1-ol to <b>methyl 1-phenylethyl sulfide</b> via S<sub>N</sub>2.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->nucleophileSN2]]</span></button></div>]

<div class="step">Solvent Choice</div> <h1>Choosing the Solvent for S<sub>N</sub>2</h1> <p>Now that we established we need a $solvtypeSN2 solvent for the S<sub>N</sub>2 reaction, choose the best solvent out of the options available in the laboratory. </p><ul class="flex-container"><li class="flex-image">$solventsSN2</li></ul><br></br> <div class="selection"><span class="instruction-text">Decision Point</span><br>Select your solvent for S<sub>N</sub>2:</br><ul> <li>(link: $solv1Cap)[(set: $solventSN2 to $solv1)(goto: "solventfeedbackSN2")]</li> <li>(link: $solv2Cap)[(set: $solventSN2 to $solv2)(goto: "solventfeedbackSN2")]</li> <li>(link: $solv3Cap)[(set: $solventSN2 to $solv3)(goto: "solventfeedbackSN2")]</li> <li>(link: $solv4Cap)[(set: $solventSN2 to $solv4)(goto: "solventfeedbackSN2")]</li> <li>(link: $solv5Cap)[(set: $solventSN2 to $solv5)(goto: "solventfeedbackSN2")]</li></ul></div>

<div class="step">Nucleophile Choice</div> <h1>Choosing the Nucleophile for S<sub>N</sub>2</h1> <p>Next, you will select an appropriate nucleophile to convert (<i>S</i>)-1-phenylethan-1-ol to <b>methyl 1-phenylethyl sulfide</b> via S<sub>N</sub>2. Remember that in these types of reactions, the nucleophile should be strong. This usually means using a negatively charged nucleophile.</p> <ul class="flex-container"><li class="flex-image">$nucleophilereagents</li></ul><br></br> <div class="selection"><span class="instruction-text">Decision Point</span><br>Select your nucleophile:</br><ul> <li>(link: $nuc1Cap)[(set: $nucSN2 to $nuc1)(goto: "nucfeedbackSN2")]</li><li>(link: $nuc2Cap)[(set: $nucSN2 to $nuc2)(goto: "nucfeedbackSN2")]</li><li>(link: $nuc3Cap)[(set: $nucSN2 to $nuc3)(goto: "nucfeedbackSN2")]</li><li>(link: $nuc4Cap)[(set: $nucSN2 to $nuc4)(goto: "nucfeedbackSN2")]</li><li>(link: $nuc5Cap)[(set: $nucSN2 to $nuc5)(goto: "nucfeedbackSN2")]</li></ul></div>

<div class="step">Leaving Group Ability</div> (if:$leavinggroupSN1 is $reag1)[<div class="correct"><br>Correct answer for the reagent used to increase the leaving group ability in (<i>S</i>)-1-phenylethan-1-ol!</br></div> <p>You chose $leavinggroupSN1. This is the <b>correct</b> choice! Reacting (<i>S</i>)-1-phenylethan-1-ol with $leavinggroupSN1 will lead to water being the leaving group in the S<sub>N</sub>1 reaction. As this is a neutral leaving group, it is very favored and non-basic. In addition, sulfuric acid is very cheap (less than $4 per mole) making it a reagent that is practical even at large scale.</p> <ul class="flex-container"><li class="flex-image">$H2SO4rxn</li></ul><br></br><div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Note down the reagent used to increase the leaving group ability of the electrophile in the S<sub>N</sub>1 column of the worksheet.</br></div> <p>In the next section, you will choose a nucleophile appropriate for the S<sub>N</sub>1 reaction pathway.</p><div class="flex-proceed"><button class="button proceed"><span>[[Next->nucleophileSN1]]</span></button></div>] (else-if:$leavinggroupSN1 is $reag2)[<div class="incorrect"><br>Incorrect answer for the reagent used to increase the leaving group ability in (<i>S</i>)-1-phenylethan-1-ol.</br></div><p>With $leavinggroupSN1, you would have a deprotonated alcohol undergoing S<sub>N</sub>1, making the leaving group O<sup>2–</sup>. This would be a very unfavourable leaving group, no matter how electronegative oxygen is!</p> <p>Consider that a good leaving group in <b>S<sub>N</sub>1 will be a weak base, which reagent will be able to create a good leaving group in (<i>S</i>)-1-phenylethan-1-ol?</p><div class="flex-return"><button class="button return"><span>[[Choose another option->leaving groupSN1]]</span></button></div>] (else-if:$leavinggroupSN1 is $reag3)[<div class="incorrect"><br>Incorrect answer for the reagent used to increase the leaving group ability in (<i>S</i>)-1-phenylethan-1-ol.</br></div><p>Without modifying (<i>S</i>)-1-phenylethan-1-ol, you would have hydroxide (HO<sup>–</sup>) as leaving group. This would be a very unfavourable leaving group since hydroxide is a strong base.</p> <p>Consider that a good leaving group in <b>S<sub>N</sub>1 will be a weak base, which reagent will be able to create a good leaving group in (<i>S</i>)-1-phenylethan-1-ol?</p><div class="flex-return"><button class="button return"><span>[[Choose another option->leaving groupSN1]]</span></button></div>] (else-if:$leavinggroupSN1 is $reag4)[<div class="incorrect"><br>Incorrect answer for the reagent used to increase the leaving group ability in (<i>S</i>)-1-phenylethan-1-ol.</br></div><p>While sulfonates are very good leaving groups and can be excellent choices as electrophiles for S<sub>N</sub>1, there is a better option here! Considering the fact that toluenesulfonyl chloride is a bit expensive (about $27 per mole), there is a more cost effective option that would allow for the S<sub>N</sub>1 reaction to occur.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->leaving groupSN1]]</span></button></div>]

<div class="step">Nucleophile Choice</div> <h1>Choosing the Nucleophile for S<sub>N</sub>1</h1> <p>Next, you will select an appropriate nucleophile to convert (<i>S</i>)-1-phenylethan-1-ol to <b>methyl 1-phenylethyl sulfide</b> via S<sub>N</sub>1. Remember that in these types of reactions, the nucleophile can be weak as the rate-determining step is the formation of the carbocation, not the nucleophilic addition. This usually means using a neutral nucleophile.</p> <ul class="flex-container"><li class="flex-image">$nucleophilereagents</li></ul><br></br> <div class="selection"><span class="instruction-text">Decision Point</span><br>Select your nucleophile:</br><ul> <li>(link: $nuc1Cap)[(set: $nucSN1 to $nuc1)(goto: "nucfeedbackSN1")]</li><li>(link: $nuc2Cap)[(set: $nucSN1 to $nuc2)(goto: "nucfeedbackSN1")]</li><li>(link: $nuc3Cap)[(set: $nucSN1 to $nuc3)(goto: "nucfeedbackSN1")]</li><li>(link: $nuc4Cap)[(set: $nucSN1 to $nuc4)(goto: "nucfeedbackSN1")]</li><li>(link: $nuc5Cap)[(set: $nucSN1 to $nuc5)(goto: "nucfeedbackSN1")]</li></ul></div>

(if: $showFooter is true)[<center><div class="footer">All material licensed under the Ontario Commons License (Version 1.0) See (link: "Credits and Copyright")[(goto: "credits and copyright")]</div></center>]

(set: $showFooter to false)<div class="step">Credits and Copyrights</div> <center><img src="_twine_sub/images/ecampus-logo.png";alt="eCampus Ontario logo"></center><p>This project is made possible with funding by the Government of Ontario and through eCampusOntario’s support of the Virtual Learning Strategy. To learn more about the Virtual Learning Strategy visit: <a href="https://vls.ecampusontario.ca" target="_blank">https://vls.ecampusontario.ca</a>.</p><br> <b><u>Lead Subject Matter Experts</u></b> <ul><li><a href="mailto:lracicot@uwaterloo.ca">Dr. Leanne Racicot</a>, Laboratory Instructor, Chemistry Department, University of Waterloo</li><li>Dr. Pier Alexandre Champagne, Assistant Professor, Department of Chemistry and Environmental Science, New Jersey Institute of Technology</li></ul><b><u>Instructional Designers</u></b> <ul><li>Julia Burke, Online Learning Consultant, Centre for Extended Learning, University of Waterloo</li> <li>Marie Lippens, Lead Learning Consultant, WatSPEED, University of Waterloo</li></ul> <b><u>Developers</u></b> <ul><li>Nick Szyngiel, Instructional Digital Media Developer, Centre for Extended Learning, University of Waterloo</li> <li>Renzo Gutierrez, Lab Simulation Development Assistant (co-op student), Chemistry Department, University of Waterloo</li> <li>Benjamin MacKenzie, Lab Simulation Development Assistant (co-op student), Chemistry Department, University of Waterloo</li></ul> <b><u>Consulting Subject Matter Experts</u></b> <ul><li>Dr. Steven P. Forsey, Lecturer, Chemistry Department, University of Waterloo</li><li>Julie Goll, Laboratory Instructor, Chemistry Department, University of Waterloo</li></ul> <b><u>Icons</u></b> <ul><li><a href="https://thenounproject.com/icon/download-1939626/" target="_blank">Download</a> by icon 54 from NounProject.com</li> <li><a href="https://thenounproject.com/icon/compose-1939615/" target="_blank">Compose</a> by icon 54 from NounProject.com</li> <li><a href="https://thenounproject.com/icon/checkmark-circle-1939611/" target="_blank">Checkmark circle</a> by icon 54 from NounProject.com</li><li><a href="https://thenounproject.com/icon/remove-speech-bubble-1939784/" target="_blank">Remove speech bubble</a> by icon 54 from NounProject.com</li><li><a href="https://thenounproject.com/icon/honour-badge-1939674/" target="_blank">Honour badge</a> by icon 54 from NounProject.com</li> <li><a href="https://thenounproject.com/icon/done-postit-396616/" target="_blank">Done Post-it</a> by icon 54 from NounProject.com</li>

<div class="step">Nucleophile Choice</div> (if:$nucSN1 is $nuc2)[<div class="correct"><br>Correct answer for the nucleophile in S<sub>N</sub>1!</br></div> <p>You chose $nucSN1. This is the <b>correct</b> choice! $nuc2Cap is a weak base and weak nucleophile. It is a good choice for S<sub>N</sub>1 since a stronger base or nucleophile would undergo acid-base reaction with the protonated alcohol instead of nucleophilic substitution. This is not a problem with $nuc2 since it is a very weak base.</p><ul class="flex-container"><li class="flex-image">$MeSHnuc</li></ul></p><div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Note down the nucleophile used in the S<sub>N</sub>1 column of the worksheet.</br></div><p>In the next section, you will choose an appropriate solvent for the S<sub>N</sub>1 reaction pathway.</p><div class="flex-proceed"><button class="button proceed"><span>[[Next->solvtypeSN1]]</span></button></div>] (else-if:$nucSN1 is $nuc1)[<div class="incorrect"><br>Incorrect answer for the nucleophile in S<sub>N</sub>1!</br></div><p>$nuc1Cap does not have the correct number of carbon atoms to yield methyl 1-phenylethyl sulfide after reacting with the electrophile.</p><ul class="flex-container"><li class="flex-image">$H2Snuc</li></ul><p>Consider the other nucleophile options to find one that will convert (<i>S</i>)-1-phenylethan-1-ol to <b>methyl 1-phenylethyl sulfide</b> via S<sub>N</sub>1.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->nucleophileSN1]]</span></button></div>] (else-if:$nucSN1 is $nuc3)[<div class="incorrect"><br>Incorrect answer for the nucleophile in S<sub>N</sub>1!</br></div><p>$nuc3Cap does not have the correct number of carbon atoms to yield methyl 1-phenylethyl sulfide after reacting with the electrophile.</p><ul class="flex-container"><li class="flex-image">$Me2Snuc</li></ul><p>Consider the other nucleophile options to find one that will convert (<i>S</i>)-1-phenylethan-1-ol to <b>methyl 1-phenylethyl sulfide</b> via S<sub>N</sub>1.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->nucleophileSN1]]</span></button></div>] (else-if:$nucSN1 is $nuc4)[<div class="incorrect"><br>Incorrect answer for the nucleophile in S<sub>N</sub>1!</br></div><p>While $nuc4 would have the correct number of carbon atoms to yield methyl 1-phenylethyl sulfide after reacting with the electrophile, since it is negatively charged it will also be more basic. Since we are using the protonated alcohol as electrophile, there would be an acid-base reaction instead of the nucleophilic substitution.</p><ul class="flex-container"><li class="flex-image">$SN1acidbase</li></ul><p>Consider the other nucleophile options to find one that will convert (<i>S</i>)-1-phenylethan-1-ol to <b>methyl 1-phenylethyl sulfide</b> via S<sub>N</sub>1.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->nucleophileSN1]]</span></button></div>] (else-if:$nucSN1 is $nuc5)[<div class="incorrect"><br>Incorrect answer for the nucleophile in S<sub>N</sub>1!</br></div><p>$nuc5Cap does not have the correct number of carbon atoms to yield methyl 1-phenylethyl sulfide after reacting with the electrophile. Additionally, the fact it is a negatively charged reagent would make it more basic, and we would likely see an acid-base reaction instead of substitution.</p><ul class="flex-container"><li class="flex-image">$NaSHnuc</li></ul><p>Consider the other nucleophile options to find one that will convert (<i>S</i>)-1-phenylethan-1-ol to <b>methyl 1-phenylethyl sulfide</b> via S<sub>N</sub>1.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->nucleophileSN1]]</span></button></div>]

<div class="step">Solvent Choice</div> <h1>Choosing the Solvent for S<sub>N</sub>1</h1> <p>Now that we established we need a $solvtypeSN1 solvent for the S<sub>N</sub>1 reaction, choose the best solvent out of the options available in the laboratory.</p><ul class="flex-container"><li class="flex-image">$solventsSN1</li></ul><br></br> <div class="selection"><span class="instruction-text">Decision Point</span><br>Select your solvent for S<sub>N</sub>1:</br><ul> <li>(link: $solv1Cap)[(set: $solventSN1 to $solv1)(goto: "solventfeedbackSN1")]</li> <li>(link: $solv2Cap)[(set: $solventSN1 to $solv2)(goto: "solventfeedbackSN1")]</li> <li>(link: $solv3Cap)[(set: $solventSN1 to $solv3)(goto: "solventfeedbackSN1")]</li> <li>(link: $solv4Cap)[(set: $solventSN1 to $solv4)(goto: "solventfeedbackSN1")]</li> <li>(link: $solv7Cap)[(set: $solventSN1 to $solv7)(goto: "solventfeedbackSN1")]</li></ul></div>

<div class="step">Solvent Choice</div> <h1>Choosing the Solvent Type for S<sub>N</sub>2</h1> <p>When considering an acceptable solvent choice for S<sub>N</sub>2 reaction, we will first look at which <i>type</i> of solvent would be appropriate. Note that the role of the solvent in S<sub>N</sub>2 would be to help dissolve the polar nucleophile (often a salt since negatively charged species would be more nucleophilic) without too much stabilizing solvation of the anion which would hinder the nucleophilic attack.</p><p>If needed, you will find definitions of each solvent type in Module 5 (Physical Properties) and Module 9 (Substitution Reactions) outlines their role in substitution reactions.</p> <div class="selection"><span class="instruction-text">Decision Point</span><br>Select your type of solvent for S<sub>N</sub>2:</br><ul> <li>(link: $solvtype1Cap)[(set: $solvtypeSN2 to $solvtype1)(goto: "solvtypefeedbackSN2")]</li> <li>(link: $solvtype2Cap)[(set: $solvtypeSN2 to $solvtype2)(goto: "solvtypefeedbackSN2")]</li> <li>(link: $solvtype3Cap)[(set: $solvtypeSN2 to $solvtype3)(goto: "solvtypefeedbackSN2")]</li> <li>(link: $solvtype4Cap)[(set: $solvtypeSN2 to $solvtype4)(goto: "solvtypefeedbackSN2")]</li> <li>(link: $solvtype5Cap)[(set: $solvtypeSN2 to $solvtype5)(goto: "solvtypefeedbackSN2")]</li></ul></div>

<div class="step">Solvent Choice</div> <h1>Choosing the Solvent Type for S<sub>N</sub>1</h1> <p>When considering an acceptable solvent choice for S<sub>N</sub>1 reaction, we will first look at which <i>type</i> of solvent would be appropriate. Solvent choice is critical in S<sub>N</sub>1 since it must help the formation of the carbocation by solvating both the leaving group (anion) and the carbocation (cation). Without this stabilization, the carbocation would not be able to form due to its high energy.</p><p>If needed, you will find definitions of each solvent type in Module 5 (Physical Properties) and Module 9 (Substitution Reactions) outlines their role in substitution reactions.</p> <div class="selection"><span class="instruction-text">Decision Point</span><br>Select your type of solvent for S<sub>N</sub>1:</br><ul> <li>(link: $solvtype1Cap)[(set: $solvtypeSN1 to $solvtype1)(goto: "solvtypefeedbackSN1")]</li> <li>(link: $solvtype2Cap)[(set: $solvtypeSN1 to $solvtype2)(goto: "solvtypefeedbackSN1")]</li> <li>(link: $solvtype3Cap)[(set: $solvtypeSN1 to $solvtype3)(goto: "solvtypefeedbackSN1")]</li> <li>(link: $solvtype4Cap)[(set: $solvtypeSN1 to $solvtype4)(goto: "solvtypefeedbackSN1")]</li> <li>(link: $solvtype5Cap)[(set: $solvtypeSN1 to $solvtype5)(goto: "solvtypefeedbackSN1")]</li></ul></div>

<div class="step">Solvent Choice</div> (if:$solvtypeSN2 is $solvtype2)[<div class="correct"><br>Correct answer for the best type of solvent for S<sub>N</sub>2!</br></div> <p>You chose $solvtype2. This is the <b>correct</b> choice! $solvtype2Cap solvents favor S<sub>N</sub>2 reactions because they interact less with anions in solutions since they are not hydrogen bond donors.</p><ul class="flex-container"><li class="flex-image">$nucPAsolv</li></ul><br><div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Note down the type of solvent used in the S<sub>N</sub>2 column of the worksheet.</br></div><p>In the next section, you will choose which exact solvent would be best for the S<sub>N</sub>2 reaction pathway.</p><div class="flex-proceed"><button class="button proceed"><span>[[Next->solventSN2]]</span></button></div>] (else-if:$solvtypeSN2 is $solvtype1)[<div class="incorrect"><br>Incorrect answer for the type of solvent used in S<sub>N</sub>2!</br></div> <p>$solvtype1Cap solvents are not the best choice for S<sub>N</sub>2 since they will interact strongly with anions via the formation of hydrogen bonds. This makes the nucleophile less likely to encounter the electrophile in solution and cause the substitution reaction.</p><ul class="flex-container"><li class="flex-image">$nucPPsolv</li></ul><br><p>Consider the other types of solvents to find one that will favor S<sub>N</sub>2 reactions.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solvtypeSN2]]</span></button></div>](else-if:$solvtypeSN2 is $solvtype3)[<div class="incorrect"><br>Incorrect answer for the type of solvent used in S<sub>N</sub>2!</br></div><p>$solvtype3Cap solvents are not the best choice for S<sub>N</sub>2 since they cannot dissolve polar molecules like the nucleophiles we are using in these reactions.</p><p>Consider the other types of solvent to find one that will favor S<sub>N</sub>2 reactions.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solvtypeSN2]]</span></button></div>] (else-if:$solvtypeSN2 is $solvtype4)[<div class="incorrect"><br>Incorrect answer for the type of solvent used in S<sub>N</sub>2!</br></div><p>$solvtype4Cap solutions would imply water is the solvent. This is not the best choice for S<sub>N</sub>2 since water (a polar protic solvent) will interact strongly with anions via the formation of hydrogen bonds. This makes the nucleophile less likely to encounter the electrophile in solution and cause the substitution reaction.</p><ul class="flex-container"><li class="flex-image">$nucPPsolv</li></ul><br><p>Consider the other types of solvent to find one that will favor S<sub>N</sub>2 reactions.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solvtypeSN2]]</span></button></div>](else-if:$solvtypeSN2 is $solvtype5)[<div class="incorrect"><br>Incorrect answer for the type of solvent used in S<sub>N</sub>2!</br></div><p>$solvtype5Cap solvents implies a wide variety of solvents with varying properties. This is too general of an answer, review the types of solvents seen in Module 5!</p><p>Consider the other types of solvent to find one that will favor S<sub>N</sub>2 reactions.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solvtypeSN2]]</span></button></div>]

<div class="step">Solvent Choice</div> (if:$solvtypeSN1 is $solvtype1)[<div class="correct"><br>Correct answer for the best type of solvent for S<sub>N</sub>1!</br></div> <p>You chose $solvtype1. This is the <b>correct</b> choice! $solvtype1Cap solvents favor S<sub>N</sub>1 reactions because they can stabilize both anions and cations due to their ability to be both hydrogen bond donors and acceptors. This allows them to facilitate the formation of the carbocation by solvating both the leaving group and the carbocation itself.</p><ul class="flex-container"><li class="flex-image">$carbPPsolv</li></ul><br></br><div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Note down the type of solvent used in the S<sub>N</sub>1 column of the worksheet.</br></div><p>In the next section, you will choose which exact solvent would be best for the S<sub>N</sub>1 reaction pathway.</p><div class="flex-proceed"><button class="button proceed"><span>[[Next->solventSN1]]</span></button></div>] (else-if:$solvtypeSN1 is $solvtype2)[<div class="incorrect"><br>Incorrect answer for the type of solvent used in S<sub>N</sub>1!</br></div> <p>$solvtype2Cap solvents are not the best choice for S<sub>N</sub>1 since they do not solvate anions very well (only hydrogen bond donors) and therefore the leaving group could attack the carbocation instead of the nucleophile.</p><ul class="flex-container"><li class="flex-image">$carbPAsolv</li></ul><br><p>Consider the other types of solvent to find one that will favor S<sub>N</sub>1 reactions.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solvtypeSN1]]</span></button></div>] (else-if:$solvtypeSN1 is $solvtype3)[<div class="incorrect"><br>Incorrect answer for the type of solvent used in S<sub>N</sub>1!</br></div><p>$solvtype3Cap solvents are not the best choice for S<sub>N</sub>1 since they cannot dissolve polar molecules like the carbocation being formed in the reaction.</p><p>Consider the other types of solvent to find one that will favor S<sub>N</sub>1 reactions.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solvtypeSN1]]</span></button></div>] (else-if:$solvtypeSN1 is $solvtype4)[<div class="incorrect"><br>Incorrect answer for the type of solvent used in S<sub>N</sub>1!</br></div> <p>$solvtype4Cap solutions would imply water is the solvent. While this could be a useful solvent for S<sub>N</sub>1, water could act as nucleophile or abstract a proton from the electrophile instead of the desired formation of methyl 1-phenylethyl sulfide.</p><ul class="flex-container"><li class="flex-image">$SN1water</li></ul><p>Consider the other types of solvent to find one that will favor S<sub>N</sub>1 reactions.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solvtypeSN1]]</span></button></div>](else-if:$solvtypeSN1 is $solvtype5)[<div class="incorrect"><br>Incorrect answer for the type of solvent used in S<sub>N</sub>1!</br></div> <p>$solvtype5Cap solvents implies a wide variety of solvents with varying properties. This is too general of an answer, review the types of solvents seen in Module 5!<p> <p>Consider the other types of solvent to find one that will favor S<sub>N</sub>1 reactions.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solvtypeSN1]]</span></button></div>]

<div class="step">Solvent Choice</div> <p>(if:$solventSN2 is $solv1)[<div class="correct"><br>Correct answer for the best solvent for S<sub>N</sub>2!</br></div> <p>You chose $solv1. This is the <b>correct</b> choice! $solv1Cap is an appropriate choice as S<sub>N</sub>2 reaction solvent since it is <b>$solvtype2</b>. As seen from its structure below, it can accept hydrogen bonding (via the nitrogen lone pair) but not donate (no N–H, O–H or F–H bond).</p><ul class="flex-container"><li class="flex-image">$MeCNsolv</li></ul><br> <div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Note down the solvent used in the S<sub>N</sub>2 column of the worksheet.</br></div><p>In the next section, you will investigating the stereochemical outcome of the S<sub>N</sub>2 reaction pathway.</p><div class="flex-proceed"><button class="button proceed"><span>[[Next->animationSN2]]</span></button></div>] (else-if: $solventSN2 is $solv2)[<div class="incorrect"><br>Incorrect answer for the solvent used in S<sub>N</sub>2!</br></div> <p>$solv2Cap is not the best choice for S<sub>N</sub>2 since it is <b>non-polar</b>.</p><ul class="flex-container"><li class="flex-image">$Tolsolv</li></ul><br> <p>Consider the other solvents to find one that will favor S<sub>N</sub>2 reactions. Reflect back on the type of solvent that you deemed appropriate in the last step!</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solventSN2]]</span></button></div>](else-if: $solventSN2 is $solv3)[<div class="incorrect"><br>Incorrect answer for the solvent used in S<sub>N</sub>2!</br></div> <p>$solv3Cap is not the best choice for S<sub>N</sub>2 since it is <b>polar protic.</b></p></p><ul class="flex-container"><li class="flex-image">$MeOHsolv</li></ul><br><p>Recall that polar protic solvents are disfavorable for S<sub>N</sub>2 because they would donate hydrogen bonds to the nucleophile, thus reducing</p><p>Consider the other solvent to find one that will favor S<sub>N</sub>2 reactions. Reflect back on the type of solvent that you deemed appropriate in the last step!</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solventSN2]]</span></button></div>] (else-if: $solventSN2 is $solv4)[<div class="incorrect"><br>Incorrect answer for the solvent used in S<sub>N</sub>2!</br></div> <p>$solv4Cap is not the best choice for S<sub>N</sub>2 since it is <b>non-polar.</b></p><ul class="flex-container"><li class="flex-image">$Hexsolv</li></ul><br><p>Consider the other solvent to find one that will favor S<sub>N</sub>2 reactions. Reflect back on the type of solvent that you deemed appropriate in the last step!</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solventSN2]]</span></button></div>] (else-if: $solventSN2 is $solv5)[<div class="incorrect"><br>Incorrect answer for the solvent used in S<sub>N</sub>2!</br></div> <p>$solv5Cap is not the best choice for S<sub>N</sub>2 since it is <b>polar protic.</b></p></p><ul class="flex-container"><li class="flex-image">$H2Osolv</li></ul><br><p>Recall that polar protic solvents are disfavorable for S<sub>N</sub>2 because they would donate hydrogen bonds to the nucleophile, thus reducing</p><p>Consider the other solvent to find one that will favor S<sub>N</sub>2 reactions. Reflect back on the type of solvent that you deemed appropriate in the last step!</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solventSN2]]</span></button></div>]

<div class="step">S<sub>N</sub>2 Mechanism Animation</div> <h1>Optical Activity of S<sub>N</sub>2 Product</h1> <p>The S<sub>N</sub>2 mechanism is concerted, meaning that the nucleophile attacks the electrophile and the leaving group departs at the exact same time. Since the reaction must occur by backside attack of the nucleophile on the electrophile, we say that S<sub>N</sub>2 reactions are <b>enantiospecific</b>: a single enantiomer is formed as the product and its configuration depends on the stereochemistry of the reactant. This fact is explained by looking at the <b>transition state</b> of the reaction, as the nucleophile approaches the C–(leaving group) bond with an 180° angle, causing the inversion of the carbon undergoing the nucleophilic attack.</p> <ul class="flex-container"><li class="flex-image">$SN2TS</li></ul><br></br><p>In the animation below, the thiomethoxide ion (CH<sub>3</sub>S<sup>–</sup>) attacks the electrophile, causing the departure of the TsO<sup>–</sup> leaving group.</p> <p>Notes regarding the visualization of the 3D animation:<ul> <li>Use your mouse to zoom and rotate the reaction, the speed slider at the bottom of the animation window controls how fast the reaction evolves.</li><li>The sodium cation was ommitted for clarity.</li> <li>The animation shows a pause around the transition state. This is meant to help you identify at which point we are reaching the transition state. In real life, the reaction would not pause at this point. Transition states are structures that occur for a very short time, and cannot be isolated.</li></ul><br></br><ul class="flex-container"><li class="flex-anim"><div class="viewer_container"><div id="irc_4" class="mol_container" style="width: 100%;"></div></div><div id="irc_4_speed"><div class="slidecontainer"><input type="range" min="1" max="10" value="6" class="slider" oninput="change_speed(this, 'irc_4');" style="width: 100%;"></div><div class="btn_title"><p style="text-align:center; font-size: 20px; color:black;">Speed</p></div></div> <script> $(document).ready(function(){ $.get("_twine_sub/anim/SN2 ANIM.xyz", function(data) { wid = $3Dmol.createViewer("irc_4"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_4"] = wid; settings["irc_4"] = set; }); }); </script></li></ul> <div class="selection"><span class="instruction-text">Decision Point</span><br>Based on the mechanism, is the solution of the S<sub>N</sub>2 reaction product(s) optically active?</br><ul> <li>(link: $SN2chiralyes)[(set: $SN2chiral to $SN2chiralyes)(goto: "optactSN2")]</li> <li>(link: $SN2chiralno)[(set: $SN2chiral to $SN2chiralno)(goto: "optactSN2")]</li></ul></div>

<div class="step">Solvent Choice</div> <p>(if:$solventSN1 is $solv7)[<div class="correct"><br>Correct answer for the best solvent for S<sub>N</sub>1!</br></div> <p>You chose $solv7. This is the <b>correct</b> choice! Sulfuric acid is the best choice for solvent as it is polar protic while being completely non-nucleophilic.</p><ul class="flex-container"><li class="flex-image">$H2SO4solv</li></ul><p>When using $solv7, there will be no competition with methane thiol (MeSH) for the nucleophilic attack. Sulfuric acid is already needed in the reaction to protonate the alcohol, therefore using a larger excess for it to act as solvent is a good option, especially considering its low cost.</p><div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Note down the type of solvent used in the S<sub>N</sub>1 column of the worksheet.</br></div><p>In the next section, you will investigating the stereochemical outcome of the S<sub>N</sub>1 reaction pathway.</p><div class="flex-proceed"><button class="button proceed"><span>[[Next->animationSN1]]</span></button></div>] (else-if: $solventSN1 is $solv1)[<div class="incorrect"><br>Incorrect answer for the solvent used in S<sub>N</sub>1!</br></div> <p>$solv1Cap is not the best choice for S<sub>N</sub>1 since it is polar <b>aprotic</b>.</p><ul class="flex-container"><li class="flex-image">$MeCNsolv</li></ul><br></br><p>Consider the other solvents to find one that will favor S<sub>N</sub>1 reactions. Reflect back on the type of solvent that you deemed appropriate in the last step!</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solventSN1]]</span></button></div>] (else-if: $solventSN1 is $solv2)[<div class="incorrect"><br>Incorrect answer for the solvent used in S<sub>N</sub>1!</br></div> <p>$solv2Cap is not the best choice for S<sub>N</sub>1 since is is <b>non-polar</b></p><ul class="flex-container"><li class="flex-image">$Tolsolv</li></ul><br></br><p>Consider the other solvents to find one that will favor S<sub>N</sub>1 reactions. Reflect back on the type of solvent that you deemed appropriate in the last step!</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solventSN1]]</span></button></div>] (else-if: $solventSN1 is $solv3)[<div class="incorrect"><br>Incorrect answer for the solvent used in S<sub>N</sub>1!</br></div> <p>$solv3Cap is not the best choice for this S<sub>N</sub>1 reaction. While it is a polar protic solvent and would help form the carbocation, it could also interfere with the desired substitution. </p><ul class="flex-container"><li class="flex-image">$MeOHsolv</li></ul><br></br>Although the nucleophile used in the S<sub>N</sub>1 reaction could be overall stronger than $solv3, there are usually much more molecules of solvent than of the nucleophile, and we would see competing reactions, with the result of $solv3 acting as nucleophile.</p><ul class="flex-container"><li class="flex-image">$SN1methanol</li></ul><p>This fact explains why a lot of the S<sub>N</sub>1 reactions seen are <b>solvolysis reactions</b>, where the solvent is also the nucleophile.</p><p>Consider the other solvents to find one that will favor S<sub>N</sub>1 reactions. Reflect back on the type of solvent that you deemed appropriate in the last step!</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solventSN1]]</span></button></div>](else-if: $solventSN1 is $solv4)[<div class="incorrect"><br>Incorrect answer for the solvent used in S<sub>N</sub>1!</br></div> <p>$solv4Cap is not the best choice for S<sub>N</sub>1 since it is <b>non-polar</b></p><ul class="flex-container"><li class="flex-image">$Hexsolv</li></ul><br></br><p>Consider the other solvents to find one that will favor S<sub>N</sub>1 reactions. Reflect back on the type of solvent that you deemed appropriate in the last step!</p><div class="flex-return"><button class="button return"><span>[[Choose another option->solventSN1]]</span></button></div>]

<div class="step">S<sub>N</sub>1 Mechanism Animation</div> <h1>Optical Activity of S<sub>N</sub>1 Products</h1> <p>The S<sub>N</sub>1 mechanism occurs in two major stages:<ol><li>Departure of the leaving group to form the carbocation</li><li>Attack of the nucleophile</li></ol></p><p>In the first step, the leaving group (H<sub>2</sub>O in this case) departs to form the carbocation intermediate.</p><ul class="flex-container"><li class="flex-image">$SN1LG</li></ul><p>The positively charged carbocation is sp<sup>2</sup>-hybridized and trigonal planar. The empty p orbital is in the same plane as the aromatic ring. This provides resonance stabilization to the carbocation, called a benzylic carbocation.</p> <p>In the animation below, the water molecule (H<sub>2</sub>O) dissociates from the rest of the molecule.</p><p>Notes regarding the visualization of the 3D animation:<ul><li>Use your mouse to zoom and rotate the reaction, the speed slider at the bottom of the animation window controls how fast the reaction evolves.</li><li>As the leaving group departs, observe how the carbon becoming a carbocation "flattens" as its hybridization goes from sp<sup>3</sup> to sp<sup>2</sup>.</li><li>The charge of the carbocation ot its empty p orbital is not depicted, but don't forget that it is there!</li></ul><br></br><ul class="flex-container"><li class="flex-anim"><div class="viewer_container"><div id="irc_12" class="mol_container" style="width: 100%;"></div></div><div id="irc_12_speed"><div class="slidecontainer"><input type="range" min="1" max="10" value="6" class="slider" oninput="change_speed(this, 'irc_12');" style="width: 100%;"></div><div class="btn_title"><p style="text-align:center; font-size: 20px; color:black;">Speed</p></div></div> <script> $(document).ready(function(){ $.get("_twine_sub/anim/SN1 CARB FORM.xyz", function(data) { wid = $3Dmol.createViewer("irc_12"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_12"] = wid; settings["irc_12"] = set; }); }); </script></li></ul> <p>The carbocation then undergoes nucleophilic attack with methanethiol. Since the carbocation is flat and there are two lobes to the empty p-orbital, the nucleophile can attack from either face of the carbocation to form the product.</p><ul class="flex-container"><li class="flex-image">$SN1nuc</li></ul><p>The initial product of nucleophilic attack must then be deprotonated to obtain the neutral methyl 1-phenylethyl sulfide. <p>The two animations below show both possibilities of the nucleophilic addition on the carbocation in S<sub>N</sub>1. Note that the compound after the nucleophilic attack would have a positive on the sulfur atom (yellow) but is not shown in the animation. =|= [<p>Attack of the carbocation from its "top" face:</p><ul class="flex-container"><li class="flex-anim-col"><div class="viewer_container"><div id="irc_3" class="mol_container" style="width: 100%;"></div></div><div id="irc_3_speed"><div class="slidecontainer"><input type="range" min="1" max="10" value="6" class="slider" oninput="change_speed(this, 'irc_3');" style="width: 100%;"></div><div class="btn_title"><p style="text-align:center; font-size: 20px; color:black;">Speed</p></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN1 ADD TOP.xyz", function(data) { wid = $3Dmol.createViewer("irc_3"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.rotate(90,'z'); wid.rotate(90,'y'); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_3"] = wid; settings["irc_3"] = set; }); }); </script></li></ul>] =|= [<p>Attack of the carbocation from its "bottom" face:</p><ul class="flex-container"><li class="flex-anim-col"><div class="viewer_container"><div id="irc_2" class="mol_container" style="width: 100%;"></div></div><div id="irc_2_speed"><div class="slidecontainer"><input type="range" min="1" max="10" value="6" class="slider" oninput="change_speed(this, 'irc_2');" style="width: 100%;"></div><div class="btn_title"><p style="text-align:center; font-size: 20px; color:black;">Speed</p></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN1 ADD BOTTOM.xyz", function(data) { wid = $3Dmol.createViewer("irc_2"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.rotate(270,'x'); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_2"] = wid; settings["irc_2"] = set; }); }); </script></li></ul>] |==| Because the reaction is performed in strongly acidic condition (H<sub>2</sub>SO<sub>4</sub> acts as solvent), this deprotonation likely occurs during the extraction (often called "work-up") after the reaction. Water and weak base (likely Na<sub>2</sub>CO<sub>3</sub> or NaHCO<sub>3</sub>) would be added to neutralize the reaction mixture and isolate methyl 1-phenylethyl sulfide.</p><ul class="flex-container"><li class="flex-image">$SN1deprot</li></ul> <div class="selection"><span class="instruction-text">Decision Point</span><br>Based on the mechanism, is the solution of the S<sub>N</sub>1 reaction product(s) optically active?</br><ul> <li>(link: $SN1chiralyes)[(set: $SN1chiral to $SN1chiralyes)(goto: "optactSN1")]</li> <li>(link: $SN1chiralno)[(set: $SN1chiral to $SN1chiralno)(goto: "optactSN1")]</li></ul></div>

(if: $SN2complete and $SN1complete)[<div class="step">End of the Virtual Laboratory</div> <p>You now have completed both branches of the substitution reaction design: <b>Racemic</b> and <b>Enantioselective</b>!<p><div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Check that all fields of your experimental design worksheet have been filed out and follow the submission instructions given.</br></div><div class="flex-proceed"><button class="button proceed"><span>[[Next->Exit]]</span></button></div>] (else-if: $SN2complete)[<div class="step">Next Reaction Mechanism</div><p>You will now need to repeat the reaction design process, but for the <b>racemic reaction pathway.</b><br><ul class="flex-container"><li class="flex-image">$overallrac</li></ul></br><div class="flex-proceed"><button class="button proceed"><span>[[Next->stereoSN1]]</span></button></div>](else-if: $SN1complete)[<div class="step">Next Reaction Mechanism</div><p>You will now need to repeat the reaction design process, but for the <b>enantioselective reaction pathway.</b><br><ul class="flex-container"><li class="flex-image">$overallenant</li></ul></br><div class="flex-proceed"><button class="button proceed"><span>[[Next->stereoSN2]]</span></button></div>]

<div class="step">End of the Virtual Laboratory</div> <p>With both reaction mechanisms completed, you have now finished the <b>Separation and Identification of a Binary Mixture: Ionizable Base and Non-ionizable Compound Virtual Laboratory</b>.</p> <p><div class="done-doc"><br>Follow the submission guidelines for Your Experimental Design Outline</br></div></p> <h2>Want to try this again?</h2><p>If you wish, you can repeat this virtual lab! Simply reload the lab by exiting this browser window and re-opening the link.</p>

<div class="step">Stereochemistry of the S<sub>N</sub>2 Reaction</div> (if:$SN2chiral is $SN2chiralyes)[<div class="correct"><br>Correct answer for the optical activity of the solution of the S<sub>N</sub>2 reaction product(s)!</br></div><p>Since the S<sub>N</sub>2 reaction is <b>enantiospecific</b>, only one stereoisomer is formed and the solution is optically active.</p><div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Check the appropriate box for the optical activity of the product solution in the S<sub>N</sub>2 column of the worksheet.</br></div><p>The stereoisomer formed is shown as a 3D model below, you can use your mouse to zoom in and rotate the molecule.</p><ul class="flex-container"><li class="flex-anim"><div class="viewer_container"><div id="irc_5" class="mol_container" style="width: 100%;"></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN2 PRODUCT.xyz", function(data) { wid = $3Dmol.createViewer("irc_5"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_5"] = wid; settings["irc_5"] = set; }); }); </script></li></ul><div class="flex-proceed"><button class="button proceed"><span>[[Next->configSN2]]</span></button></div>] (else-if:$SN2chiral is $SN2chiralno)[<div class="incorrect"><br>Incorrect answer for the optical activity of the solution of the S<sub>N</sub>2 reaction product(s)!</br></div><p>Consider the fact that the S<sub>N</sub>2 reaction is <b>enantiospecific</b>, what does this mean? What are the requirements for a non-optically active solution? Review the stereochemistry concepts and look at the animation for the S<sub>N</sub>2 reaction once more.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->animationSN2]]</span></button></div>]

<div class="step">Stereochemistry of the S<sub>N</sub>2 Reaction</div> (if:$SN2stereo is $SN2stereoR)[<div class="correct"><br>Correct answer for the stereochemical configuration of the S<sub>N</sub>2 product!</div></br><p>Since the S<sub>N</sub>2 reaction goes through an inversion of the carbon undergoing the nucleophilic attack, we obtain (<i>R</i>)-methyl 1-phenylethyl sulfide. Note that the configuration does not always flip from (<i>S</i>) to (<i>R</i>) and vice-versa in S<sub>N</sub>2, you must always check the priority of the groups in the product to assign the stereochemistry correctly!</p><div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Check the appropriate box for the stereochemical configuration in the S<sub>N</sub>2 column of the worksheet.</br></div><div class="flex-proceed"><button class="button proceed"><span>[[Next->SN2wedgedash]]</span></button></div>](else-if:$SN2stereo is $SN2stereoS)[<div class="incorrect"><br>Incorrect answer stereochemical configuration of the S<sub>N</sub>2 product!</br></div><p>Be sure to review the priority order of the substituents on the molecule and look closely at the stereoisomer shown in 3D. You can rotate the molecule to have on orientation that may make the stereochemical assignment easier!</p><div class="flex-return"><button class="button return"><span>[[Choose another option->configSN2]]</span></button></div>]

<div class="step">Stereochemistry of the S<sub>N</sub>2 Reaction</div> <h1>Stereochemical Configuration of S<sub>N</sub>2 Product</h1> <p>After the S<sub>N</sub>2 reaction, you obtain methyl 1-phenylethyl sulfide. As stated, the reaction is <b>enantiospecific</b>, meaning that you form a single enantiomer. The animation below shows this stereoisomer, use your mouse to zoom and rotate the 3D figure. <ul class="flex-container"><li class="flex-anim"><div class="viewer_container"><div id="irc_5" class="mol_container" style="width: 100%;"></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN2 PRODUCT.xyz", function(data) { wid = $3Dmol.createViewer("irc_5"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_5"] = wid; settings["irc_5"] = set; }); }); </script></li></ul> <div class="selection"><span class="instruction-text">Decision Point</span><br>What is the stereochemical configuration of the S<sub>N</sub>2 product?</br><ul><li>(link: $SN2stereoR)[(set: $SN2stereo to $SN2stereoR)(goto: "configSN2feedback")]</li> <li>(link: $SN2stereoS)[(set: $SN2stereo to $SN2stereoS)(goto: "configSN2feedback")]</li></ul></div>

<div class="step">Stereochemistry of the S<sub>N</sub>1 Reaction</div>(if:$SN1chiral is $SN1chiralno)[<div class="correct"><br>Correct answer for the optical activity of the solution of the S<sub>N</sub>1 reaction product(s)!</br></div><p>Since the S<sub>N</sub>1 reaction goes through an achiral intermediate (the carbocation is planar due to its sp<sup>2</sup> hybridization!), the reaction leads to a racemic mixture. Racemic mixtures are a 50:50 ratio of a pair of enantiomers and enantiomers have equal but opposite values of specific rotation. The overall result is no optical activity for a solution of a racemic mixture.</p><div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Check the appropriate box for the optical activity of the product solution in the S<sub>N</sub>1 column of the worksheet.</br></div><p>The two stereoisomers formed are shown as a 3D models below, you can use your mouse to zoom in and rotate the molecules.</p> =|= [<p>S<sub>N</sub>1 "top" attack product:</p><ul class="flex-container"><li class="flex-anim-col"><div class="viewer_container"><div id="irc_10" class="mol_container" style="width: 100%;"></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN1 TOP STATIC.xyz", function(data) { wid = $3Dmol.createViewer("irc_10"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.rotate(90,'z'); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_10"] = wid; settings["irc_10"] = set; }); }); </script></li></ul>] =|= [<p>S<sub>N</sub>1 "bottom" attack product:</p><ul class="flex-container"><li class="flex-anim-col"><div class="viewer_container"><div id="irc_9" class="mol_container" style="width: 100%;"></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN1 BOTTOM STATIC.xyz", function(data) { wid = $3Dmol.createViewer("irc_9"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_9"] = wid; settings["irc_9"] = set; }); }); </script></li></ul>] |==| <div class="flex-proceed"><button class="button proceed"><span>[[Next->configSN1]]</span></button></div>] (else-if:$SN1chiral is $SN1chiralyes)[<div class="incorrect"><br>Incorrect answer for the optical activity of the solution of the S<sub>N</sub>1 reaction product(s)!</br></div><p>Consider the fact that the S<sub>N</sub>1 reaction is <b>racemic</b>, what does this mean? What are the requirements for an optically active solution? Review the stereochemistry concepts and look at the animation for the S<sub>N</sub>1 reaction once more.</p><div class="flex-return"><button class="button return"><span>[[Choose another option->animationSN1]]</span></button></div>]

<div class="step">Stereochemistry of the S<sub>N</sub>1 Reaction</div> <h1>Stereochemical Configuration of S<sub>N</sub>1 Products</h1> <p>The two stereoisomers formed in the S<sub>N</sub>1 reaction are shown as a 3D models below, you can use your mouse to zoom in and rotate the molecules.</p> =|= [<p>S<sub>N</sub>1 "top" attack product:</p><ul class="flex-container"><li class="flex-anim-col"><div class="viewer_container"><div id="irc_10" class="mol_container" style="width: 100%;"></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN1 TOP STATIC.xyz", function(data) { wid = $3Dmol.createViewer("irc_10"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.rotate(90,'z'); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_10"] = wid; settings["irc_10"] = set; }); }); </script></li></ul>] =|= [<p>S<sub>N</sub>1 "bottom" attack product:</p><ul class="flex-container"><li class="flex-anim-col"><div class="viewer_container"><div id="irc_9" class="mol_container" style="width: 100%;"></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN1 BOTTOM STATIC.xyz", function(data) { wid = $3Dmol.createViewer("irc_9"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_9"] = wid; settings["irc_9"] = set; }); }); </script></li></ul>] |==| <div class="selection"><span class="instruction-text">Decision Point</span><br>What is the stereochemical configuration of each of the S<sub>N</sub>1 products?</br><ul> <li>(link: $SN1stereo1)[(set: $SN1stereo to $SN1stereo1)(goto: "configSN1feedback")]</li> <li>(link: $SN1stereo2)[(set: $SN1stereo to $SN1stereo2)(goto: "configSN1feedback")]</li> <li>(link: $SN1stereo3)[(set: $SN1stereo to $SN1stereo3)(goto: "configSN1feedback")]</li> <li>(link: $SN1stereo4)[(set: $SN1stereo to $SN1stereo4)(goto: "configSN1feedback")]</li></ul></div>

<div class="step">Testing animations style</div> <p>SN2 Mechanism</p><ul class="flex-container"><li class="flex-anim"><div class="viewer_container"><div id="irc_4" class="mol_container" style="width: 100%;"></div></div><div id="irc_4_speed"><div class="slidecontainer"><input type="range" min="1" max="10" value="6" class="slider" oninput="change_speed(this, 'irc_4');" style="width: 100%;"></div><div class="btn_title"><p style="text-align:center; font-size: 20px; color:black;">Speed</p></div></div> <script> $(document).ready(function(){ $.get("_twine_sub/anim/SN2 ANIM.xyz", function(data) { wid = $3Dmol.createViewer("irc_4"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_4"] = wid; settings["irc_4"] = set; }); }); </script></li></ul> =|= <p>SN2 Tosylate (static, no speed slider)</p> <ul class="flex-container"><li class="flex-anim-col"><div class="viewer_container"><div id="irc_6" class="mol_container" style="width: 100%;"></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN2 OTs.xyz", function(data) { wid = $3Dmol.createViewer("irc_6"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_6"] = wid; settings["irc_6"] = set; }); }); </script></li></ul> =|= <p>SN2 Product (static, no speed slider)</p> <ul class="flex-container"><li class="flex-anim-col"><div class="viewer_container"><div id="irc_5" class="mol_container" style="width: 100%;"></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN2 PRODUCT.xyz", function(data) { wid = $3Dmol.createViewer("irc_5"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_5"] = wid; settings["irc_5"] = set; }); }); </script></li></ul> |==| <p>SN1 Formation carbocation (new)</p><ul class="flex-container"><li class="flex-anim"><div class="viewer_container"><div id="irc_12" class="mol_container" style="width: 100%;"></div></div><div id="irc_12_speed"><div class="slidecontainer"><input type="range" min="1" max="10" value="6" class="slider" oninput="change_speed(this, 'irc_12');" style="width: 100%;"></div><div class="btn_title"><p style="text-align:center; font-size: 20px; color:black;">Speed</p></div></div> <script> $(document).ready(function(){ $.get("_twine_sub/anim/SN1 CARB FORM.xyz", function(data) { wid = $3Dmol.createViewer("irc_12"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_12"] = wid; settings["irc_12"] = set; }); }); </script></li></ul> =|= <p>SN1 Alcohol (static, no speed slider)</p><ul class="flex-container"><li class="flex-anim-col"><div class="viewer_container"><div id="irc_7" class="mol_container" style="width: 100%;"></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN1 ALCOHOL (OH).xyz", function(data) { wid = $3Dmol.createViewer("irc_7"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_7"] = wid; settings["irc_7"] = set; }); }); </script></li></ul> =|= <p>SN1 Protonated Alcohol (static, no speed slider)</p><ul class="flex-container"><li class="flex-anim-col"><div class="viewer_container"><div id="irc_8" class="mol_container" style="width: 100%;"></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN1 PROTONATED (OH2+).xyz", function(data) { wid = $3Dmol.createViewer("irc_8"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_8"] = wid; settings["irc_8"] = set; }); }); </script></li></ul> |==| =|= <p>SN1 Attack Bottom Face</p><ul class="flex-container"><li class="flex-anim-col"><div class="viewer_container"><div id="irc_2" class="mol_container" style="width: 100%;"></div></div><div id="irc_2_speed"><div class="slidecontainer"><input type="range" min="1" max="10" value="6" class="slider" oninput="change_speed(this, 'irc_2');" style="width: 100%;"></div><div class="btn_title"><p style="text-align:center; font-size: 20px; color:black;">Speed</p></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN1 ADD BOTTOM.xyz", function(data) { wid = $3Dmol.createViewer("irc_2"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.rotate(270,'x'); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_2"] = wid; settings["irc_2"] = set; }); }); </script></li></ul> =|= <p>SN1 Attack Top Face</p><ul class="flex-container"><li class="flex-anim-col"><div class="viewer_container"><div id="irc_3" class="mol_container" style="width: 100%;"></div></div><div id="irc_3_speed"><div class="slidecontainer"><input type="range" min="1" max="10" value="6" class="slider" oninput="change_speed(this, 'irc_3');" style="width: 100%;"></div><div class="btn_title"><p style="text-align:center; font-size: 20px; color:black;">Speed</p></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN1 ADD TOP.xyz", function(data) { wid = $3Dmol.createViewer("irc_3"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.rotate(90,'z'); wid.rotate(90,'y'); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_3"] = wid; settings["irc_3"] = set; }); }); </script></li></ul> |==| =|= <p>SN1 Bottom Attack Product (static, no speed slider)</p><ul class="flex-container"><li class="flex-anim-col"><div class="viewer_container"><div id="irc_9" class="mol_container" style="width: 100%;"></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN1 BOTTOM STATIC.xyz", function(data) { wid = $3Dmol.createViewer("irc_9"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_9"] = wid; settings["irc_9"] = set; }); }); </script></li></ul> =|= <p>SN1 Top Attack Product (static, no speed slider)</p><ul class="flex-container"><li class="flex-anim-col"><div class="viewer_container"><div id="irc_10" class="mol_container" style="width: 100%;"></div></div><script> $(document).ready(function(){ $.get("_twine_sub/anim/SN1 TOP STATIC.xyz", function(data) { wid = $3Dmol.createViewer("irc_10"); set = { interval: 30, animation: 'forward', } wid.addModelsAsFrames(data, "xyz"); wid.setBackgroundColor(0xF8F8F8); wid.setStyle({}, {stick:{radius: 0.15}, sphere: {scale: 0.2}}); wid.zoomTo(); wid.rotate(90,'z'); wid.render(); wid.animate({'loop': set['animation'], 'interval': set['interval']}); widgets["irc_10"] = wid; settings["irc_10"] = set; }); }); </script></li></ul> |==| <div class="flex-return"><button class="button return"><span>[[Return to virtual lab->intro]]</span></button></div>

<div class="step">Stereochemistry of the S<sub>N</sub>1 Reaction</div> (if:$SN1stereo is $SN1stereo2)[<div class="correct"><br>Correct answer for the stereochemical configurations of the S<sub>N</sub>1 products!</br></div><p>Since the S<sub>N</sub>1 reaction yields a racemic mixture, you obtain both enantiomers of methyl 1-phenylethyl sulfide, one being <i>R</i> and the other is <i>S</i>.</p><p>We will rarely ask you which "face" of attack leads to which product, since this can be defined in multiple ways, but we wanted to utilize our 3D graphics and help you practice your stereochemical assignments!</p><div class="exp-outline"><span class="instruction-text">Experimental Design Worksheet</span><br>Check both boxes for the stereochemical configuration of the product in the S<sub>N</sub>1 column of the worksheet.</br></div><div class="flex-proceed"><button class="button proceed"><span>[[Next->mechanismcheckpoint]]</span></button></div>] (else-if:$SN1stereo is $SN1stereo1)[<div class="incorrect"><br>Incorrect answer stereochemical configuration of the S<sub>N</sub>1 products!</br></div><p>Be sure to review the priority order of the substituents on the molecule and look closely at the stereoisomer shown in 3D. You can rotate the molecule to have on orientation that may make the stereochemical assignment easier!</p><div class="flex-return"><button class="button return"><span>[[Choose another option->configSN1]]</span></button></div>](else-if:$SN1stereo is $SN1stereo3)[<div class="incorrect"><br>Incorrect answer stereochemical configuration of the S<sub>N</sub>1 products!</br></div><p>Be sure to review the priority order of the substituents on the molecule and look closely at the stereoisomer shown in 3D. You can rotate the molecule to have on orientation that may make the stereochemical assignment easier!</p><p>Recall also that overall the S<sub>N</sub>1 leads to a racemic mixture, what would this mean in terms of stereochemical configuration of the two stereoisomers formed?<div class="flex-return"><button class="button return"><span>[[Choose another option->configSN1]]</span></button></div>] (else-if:$SN1stereo is $SN1stereo4)[<div class="incorrect"><br>Incorrect answer stereochemical configuration of the S<sub>N</sub>1 products!</br></div><p>Be sure to review the priority order of the substituents on the molecule and look closely at the stereoisomer shown in 3D. You can rotate the molecule to have on orientation that may make the stereochemical assignment easier!</p><p>Recall also that overall the S<sub>N</sub>1 leads to a racemic mixture, what would this mean in terms of stereochemical configuration of the two stereoisomers formed?<div class="flex-return"><button class="button return"><span>[[Choose another option->configSN1]]</span></button></div>]

<div class="step">Stereochemistry of the S<sub>N</sub>2 Reaction</div> <h1>Stereochemical Configuration of S<sub>N</sub>2 Product</h1> <p>When drawing molecules on paper, we often use the wedge dash representation to show chiral molecules in 2D. There are always multiple orientations one can use when representing molecules, and it is important to be able to recognize which show the correct stereochemistry even if they are given in a different orientation from the one you would prefer.</p><p>To complete our S<sub>N</sub>2 reaction scheme, look at the four molecules represented in the diagram below. Which one show the correct stereochemistry of methyl 1-phenylethyl sulfide formed in the S<sub>N</sub>2 pathway?<p><ul class="flex-container"><li class="flex-image">$SN2options</li></ul><br> <div class="selection"><span class="instruction-text">Decision Point</span><br>Select which molecule has the correct stereochemical configuration:</br><ul> <li>(link: $SN2optionA)[(set: $SN2option to $SN2optionA)(goto: "SN2wedgedashfeedback")]</li> <li>(link: $SN2optionB)[(set: $SN2option to $SN2optionB)(goto: "SN2wedgedashfeedback")]</li> <li>(link: $SN2optionC)[(set: $SN2option to $SN2optionC)(goto: "SN2wedgedashfeedback")]</li> <li>(link: $SN2optionD)[(set: $SN2option to $SN2optionD)(goto: "SN2wedgedashfeedback")]</li></ul></div>

<div class="step">Stereochemistry of the S<sub>N</sub>2 Reaction</div> (if:$SN2option is $SN2optionC)[<div class="correct"><br>Correct answer for the wedge dash representation of (<i>R</i>)-methyl 1-phenylethyl sulfide!</div></br><p>It is important to be able to recognize the stereochemistry of a molecule given multiple orientations, below are just some of the ways we could correctly draw the product from the S<sub>N</sub>2 pathway:<ul class="flex-container"><li class="flex-image">$Roptions</li></ul><br><div class="flex-proceed"><button class="button proceed"><span>[[Next->mechanismcheckpoint]]</span></button></div>] (if:$SN2option is $SN2optionA)[<div class="incorrect"><br>Incorrect answer, the molecule you chose is (<i>S</i>)-methyl 1-phenylethyl sulfide, the enantiomer of the S<sub>N</sub>2 product!</br></div><p>Carefully assign the stereochemistry of the options you are choosing from. Learning to distinguish which molecules are the same or different in different orientation will be important for the rest of the organic chemistry course!</p><div class="flex-return"><button class="button return"><span>[[Choose another option->SN2wedgedash]]</span></button></div>] (if:$SN2option is $SN2optionB)[<div class="incorrect"><br>Incorrect answer, the molecule you chose is (<i>S</i>)-methyl 1-phenylethyl sulfide, the enantiomer of the S<sub>N</sub>2 product!</br></div><p>Carefully assign the stereochemistry of the options you are choosing from. Learning to distinguish which molecules are the same or different in different orientation will be important for the rest of the organic chemistry course!</p><div class="flex-return"><button class="button return"><span>[[Choose another option->SN2wedgedash]]</span></button></div>] (if:$SN2option is $SN2optionD)[<div class="incorrect"><br>Incorrect answer, the molecule you chose is (<i>S</i>)-methyl 1-phenylethyl sulfide, the enantiomer of the S<sub>N</sub>2 product!</br></div><p>Carefully assign the stereochemistry of the options you are choosing from. Learning to distinguish which molecules are the same or different in different orientation will be important for the rest of the organic chemistry course!</p><div class="flex-return"><button class="button return"><span>[[Choose another option->SN2wedgedash]]</span></button></div>]

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Introduction

Virtual Lab: Substitution Reactions

Synthesis of Methyl 1-Phenylethyl Sulfide: Stereoselective and Racemic

In this virtual laboratory, you will use both substitution mechanisms (S_N2 and S_N1) to convert (S)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide. The virtual lab will include 3D animations of the reactions involved to help you better visualize why each reaction mechanism leads to a different reaction pathway.

Through this activity, you will be called to make choices to direct the reaction. Although this virtual laboratory does not include laboratory footage of the experiment being performed, thinking about the choice of solvent and reagents will help you better understand how to answer exam questions and help you with the related laboratory experiments (Experiments 4 and 5 of CHEM 266L).

Enantiospecific or racemic conversion of (S)-1-phenylethan-1-ol to methyl 1-phenylethyl sulfide.

During this virtual lab, you will:

Design both a S_N2 and a S_N1 reaction to synthesize methyl 1-phenylethyl sulfide.
View 3D animations and energy diagrams of the reaction processes, powered by Density Functional Theory, a computational chemistry model that can calculate the energy of molecules.
Review the stereochemical outcome of S_N2 and S_N1 reactions.

Before You Begin

Review the Substitution Reaction Summary linked below. You should have an idea of which conditions favours S_N2 vs S_N1 to complete this virtual with ease, but the feedback at each decision point is meant to help correct any misconceptions you may have.

Download File
Download the Substitution Reaction Summary (PDF) here.

Set aside 60 minutes to complete the virtual laboratory.