Organic Halides Notes

and Haloarenes

Classification

  • Based on the type of carbon to which the halogen is attached:

    • Alkyl halides (R-X)

    • Phenyl halides (Ph-X)

Types of Carbon

  • Alkyl halides: Halogen is attached to an sp3sp^3 hybridized carbon.

  • Phenyl halides: Halogen is directly attached to a benzene ring.

Examples of Carbon Types

  • Allylic: −CH=CH−CH2−X-CH=CH-CH_2-X

    • The carbon adjacent to a double bond.

  • Vinylic: CH2=CH−XCH_2=CH-X

    • The carbon directly involved in a double bond (sp2sp^2 hybridized).

  • Benzylic: A phenyl group attached to a carbon that contains a halogen. (Ph−CH2−XPh-CH_2-X)

Examples

  • Vinylic chloride: C=CH−CH3C=CH-CH_3

  • Allylic halide: CH=CH−CH<em>2−CH</em>2−XCH=CH-CH<em>2-CH</em>2-X

Reactions and Preparations of Haloalkanes

From Alcohols

  • Alcohols react with PCl5,,PCl3,or, orSOCl_2toformalkylchlorides.</p><ul><li><p>to form alkyl chlorides.</p><ul><li><p>R-OH + PCl5 \rightarrow R-Cl + HCl + POCl3</p><ul><li><p>Notall</p><ul><li><p>Not allPCl_5moleculesreactduetosterichindrance.</p></li><li><p>Reactivityorderofaxialvs.equatorialchlorine.</p></li></ul></li><li><p>molecules react due to steric hindrance.</p></li><li><p>Reactivity order of axial vs. equatorial chlorine.</p></li></ul></li><li><p>R-OH + PCl3 \rightarrow R-Cl + H3PO_3</p></li><li><p></p></li><li><p>3 R-OH + PBr3 \rightarrow 3 R-Br + H3PO_3</p></li><li><p></p></li><li><p>R-OH + SOCl2 \rightarrow R-Cl + SO2 + HCl(Darzenprocess)</p><ul><li><p>Thisisafavorablereactionbecausethebyproductsaregasesandescapethesystem.</p></li></ul></li></ul></li><li><p>UsingRedP+(Darzen process)</p><ul><li><p>This is a favorable reaction because the byproducts are gases and escape the system.</p></li></ul></li></ul></li><li><p>Using Red P +Br2orRedP+or Red P +I2:</p><ul><li><p>:</p><ul><li><p>R-OH + Red P + Br2 \rightarrow R-Br + H3PO_3</p></li><li><p></p></li><li><p>R-OH + Red P + I2 \rightarrow R-I + H3PO_3</p><ul><li><p>Areducingagentisneededtopreventiodinefromleavingthegroup.</p></li><li><p></p><ul><li><p>A reducing agent is needed to prevent iodine from leaving the group.</p></li><li><p>R-I + HI \rightarrow R-H + I_2</p></li></ul></li></ul></li></ul><h5id="4187ed49−4ae3−4a2f−8956−b0f33c020033"data−toc−id="4187ed49−4ae3−4a2f−8956−b0f33c020033"collapsed="false"seolevelmigrated="true">WithHydrohaloacids(HX)</h5><ul><li><p>Alcoholsreactwithhydrohaloacidstoformalkylhalides.</p><ul><li><p></p></li></ul></li></ul></li></ul><h5 id="4187ed49-4ae3-4a2f-8956-b0f33c020033" data-toc-id="4187ed49-4ae3-4a2f-8956-b0f33c020033" collapsed="false" seolevelmigrated="true">With Hydrohaloacids (HX)</h5><ul><li><p>Alcohols react with hydrohaloacids to form alkyl halides.</p><ul><li><p>R-OH + HCl \xrightarrow{\Delta, anhyd. ZnCl2} R-Cl + H2O</p></li><li><p></p></li><li><p>R-OH + HBr \xrightarrow{anhyd. ZnCl2} R-Br + H2O</p></li><li><p></p></li><li><p>R-OH + HI \rightarrow R-I + H_2O</p></li><li><p></p></li><li><p>R-I + HI \rightarrow R-H + I_2</p></li></ul></li></ul><h5id="7834361e−db9d−49f9−a0cb−2647f4665650"data−toc−id="7834361e−db9d−49f9−a0cb−2647f4665650"collapsed="false"seolevelmigrated="true">MechanismwithHCl</h5><ul><li><p></p></li></ul></li></ul><h5 id="7834361e-db9d-49f9-a0cb-2647f4665650" data-toc-id="7834361e-db9d-49f9-a0cb-2647f4665650" collapsed="false" seolevelmigrated="true">Mechanism with HCl</h5><ul><li><p>R-OH + HCl \xrightarrow{anhyd. ZnCl2} R-Cl + H2O</p><ul><li><p></p><ul><li><p>HCl \rightleftharpoons H^+ + Cl^-(electrophileandnucleophile)</p></li><li><p>(electrophile and nucleophile)</p></li><li><p>R-OH + H^+ \rightarrow R-OH_2^+(LA=LewisAcid)</p></li><li><p>(LA = Lewis Acid)</p></li><li><p>R^+ + H2O \rightarrow R-OH2^+</p></li><li><p>Functionof</p></li><li><p>Function ofanhyd. ZnCl2toabsorbto absorbH2O</p></li></ul></li></ul><h5id="6beb6bdf−b105−4ae6−a7ed−5e076590db6a"data−toc−id="6beb6bdf−b105−4ae6−a7ed−5e076590db6a"collapsed="false"seolevelmigrated="true">ReactionsThatDon′tOccur</h5><ul><li><p></p></li></ul></li></ul><h5 id="6beb6bdf-b105-4ae6-a7ed-5e076590db6a" data-toc-id="6beb6bdf-b105-4ae6-a7ed-5e076590db6a" collapsed="false" seolevelmigrated="true">Reactions That Don't Occur</h5><ul><li><p>R-OH + NaCl \nrightarrow R-Cl + NaOH(Noreaction)</p><ul><li><p>(No reaction)</p><ul><li><p>NaCl \rightleftharpoons Na^+ + Cl^-</p></li></ul></li></ul><h4id="c8b19e8d−f3f5−472c−bfc9−b4dae3434af6"data−toc−id="c8b19e8d−f3f5−472c−bfc9−b4dae3434af6"collapsed="false"seolevelmigrated="true">Borodine−HunsdieckerReaction</h4><ul><li><p>Silversaltsofmonocarboxylicacidsreactwith</p></li></ul></li></ul><h4 id="c8b19e8d-f3f5-472c-bfc9-b4dae3434af6" data-toc-id="c8b19e8d-f3f5-472c-bfc9-b4dae3434af6" collapsed="false" seolevelmigrated="true">Borodine-Hunsdiecker Reaction</h4><ul><li><p>Silver salts of monocarboxylic acids react withBr2inthepresenceofin the presence ofCCl4toformalkylbromideswithonecarbonless.</p><ul><li><p>to form alkyl bromides with one carbon less.</p><ul><li><p>R-COOAg + Br2 \xrightarrow{CCl4} R-Br + CO_2 + AgBr</p></li></ul></li></ul><h5id="ad8a6c8b−5d44−4494−8142−79ea5d693d1f"data−toc−id="ad8a6c8b−5d44−4494−8142−79ea5d693d1f"collapsed="false"seolevelmigrated="true">Mechanism</h5><ul><li><p></p></li></ul></li></ul><h5 id="ad8a6c8b-5d44-4494-8142-79ea5d693d1f" data-toc-id="ad8a6c8b-5d44-4494-8142-79ea5d693d1f" collapsed="false" seolevelmigrated="true">Mechanism</h5><ul><li><p>Br_2 \rightarrow 2Br(homolyticfission)</p></li><li><p>(homolytic fission)</p></li><li><p>R-COOAg + Br \rightarrow R-COO + AgBr</p></li><li><p></p></li><li><p>R-COO \rightarrow R + CO_2</p><ul><li><p>Minorproducts:ester(R−CO−O−R)andalkane(R−R)</p></li><li><p>Radical+Bromine=AlkylBromide(Mainproduct)</p></li></ul></li><li><p></p><ul><li><p>Minor products: ester (R-CO-O-R) and alkane (R-R)</p></li><li><p>Radical + Bromine = Alkyl Bromide (Main product)</p></li></ul></li><li><p>R + Br \rightarrow R-Br</p></li></ul><h4id="47373810−43d9−4dda−9b37−514df0612586"data−toc−id="47373810−43d9−4dda−9b37−514df0612586"collapsed="false"seolevelmigrated="true">HalideExchangeReactions</h4><h5id="c1c6f7f7−cf12−4322−b70d−f2ebbb36f854"data−toc−id="c1c6f7f7−cf12−4322−b70d−f2ebbb36f854"collapsed="false"seolevelmigrated="true">FinkelsteinReaction</h5><ul><li><p>AlkylchloridesreactwithNaIindryacetonetoformalkyliodides.</p><ul><li><p></p></li></ul><h4 id="47373810-43d9-4dda-9b37-514df0612586" data-toc-id="47373810-43d9-4dda-9b37-514df0612586" collapsed="false" seolevelmigrated="true">Halide Exchange Reactions</h4><h5 id="c1c6f7f7-cf12-4322-b70d-f2ebbb36f854" data-toc-id="c1c6f7f7-cf12-4322-b70d-f2ebbb36f854" collapsed="false" seolevelmigrated="true">Finkelstein Reaction</h5><ul><li><p>Alkyl chlorides react with NaI in dry acetone to form alkyl iodides.</p><ul><li><p>R-Cl + NaI \xrightarrow{dry acetone} R-I + NaCl</p></li><li><p>Thefunctionofdryacetoneistoenhancethepolarityandnucleophilicityof</p></li><li><p>The function of dry acetone is to enhance the polarity and nucleophilicity ofI^-byion−dipoleinteraction.</p></li></ul></li></ul><h5id="3e556042−4651−4cd7−9322−2f9b9b592582"data−toc−id="3e556042−4651−4cd7−9322−2f9b9b592582"collapsed="false"seolevelmigrated="true">SwartzReaction</h5><ul><li><p>Alkylhalidesareheatedwithby ion-dipole interaction.</p></li></ul></li></ul><h5 id="3e556042-4651-4cd7-9322-2f9b9b592582" data-toc-id="3e556042-4651-4cd7-9322-2f9b9b592582" collapsed="false" seolevelmigrated="true">Swartz Reaction</h5><ul><li><p>Alkyl halides are heated withAgF,,Hg2F2,or, orSbF_3toformalkylfluorides.</p><ul><li><p>to form alkyl fluorides.</p><ul><li><p>2R-Cl + Hg2F2 \rightarrow 2R-F + Hg2Cl2</p></li><li><p></p></li><li><p>3R-Cl + SbF3 \rightarrow 3R-F + SbCl3</p></li></ul></li></ul><h4id="55cbb7c9−c8d8−489f−82d4−3eaf2779361c"data−toc−id="55cbb7c9−c8d8−489f−82d4−3eaf2779361c"collapsed="false"seolevelmigrated="true">FromAlkenes</h4><ul><li><p>AdditionofHBr:</p><ul><li><p>AccordingtoMarkovnikov′srule:</p><ul><li><p></p></li></ul></li></ul><h4 id="55cbb7c9-c8d8-489f-82d4-3eaf2779361c" data-toc-id="55cbb7c9-c8d8-489f-82d4-3eaf2779361c" collapsed="false" seolevelmigrated="true">From Alkenes</h4><ul><li><p>Addition of HBr:</p><ul><li><p>According to Markovnikov's rule:</p><ul><li><p>CH3-CH=CH2 + HBr \rightarrow CH3-CHBr-CH3(Electrophilicaddition)</p></li></ul></li><li><p>Inthepresenceof(Electrophilic addition)</p></li></ul></li><li><p>In the presence ofR2O2:</p><ul><li><p>:</p><ul><li><p>CH3-CH=CH2 + HBr \xrightarrow{R2O2} CH3-CH2-CH_2-Br(Freeradical,Anti−Markovnikov′srule)</p></li></ul></li></ul></li><li><p>BrominationofalkanesusingNBS(N−bromosuccinimide):Thisreplacesallylichydrogenswithbromine.</p><ul><li><p>(Free radical, Anti-Markovnikov's rule)</p></li></ul></li></ul></li><li><p>Bromination of alkanes using NBS (N-bromosuccinimide): This replaces allylic hydrogens with bromine.</p><ul><li><p>NBS + CH3-CH=CH2 \rightarrow Br-CH2-CH=CH2</p><ul><li><p>NBSfacilitatesfreeradicalsubstitutionintheallylicposition.</p></li></ul></li></ul></li></ul><h4id="814bc7f8−a5f6−452b−a509−6b69b412fca8"data−toc−id="814bc7f8−a5f6−452b−a509−6b69b412fca8"collapsed="false"seolevelmigrated="true">HalogenationofAlkanes</h4><ul><li><p>Freeradicalsubstitutionreaction:</p><ul><li><p></p><ul><li><p>NBS facilitates free radical substitution in the allylic position.</p></li></ul></li></ul></li></ul><h4 id="814bc7f8-a5f6-452b-a509-6b69b412fca8" data-toc-id="814bc7f8-a5f6-452b-a509-6b69b412fca8" collapsed="false" seolevelmigrated="true">Halogenation of Alkanes</h4><ul><li><p>Free radical substitution reaction:</p><ul><li><p>CH4 + Cl2 \xrightarrow{h\nu} CH_3-Cl + HCl(E−R=ElectrophilicReagent)</p></li><li><p>(E-R = Electrophilic Reagent)</p></li><li><p>CH3-CH2-CH3 + Cl2 \xrightarrow{h\nu} CH3-CHCl-CH3</p></li></ul></li></ul><h4id="6d98f8ba−d946−49ed−87a9−48ead85782db"data−toc−id="6d98f8ba−d946−49ed−87a9−48ead85782db"collapsed="false"seolevelmigrated="true">PreparationofHaloarenes</h4><h5id="eec39058−66f7−4ed1−bb71−ac28ea3be200"data−toc−id="eec39058−66f7−4ed1−bb71−ac28ea3be200"collapsed="false"seolevelmigrated="true">HalogenationofBenzene</h5><ul><li><p>Electrophilicsubstitutionreaction:</p><ul><li><p></p></li></ul></li></ul><h4 id="6d98f8ba-d946-49ed-87a9-48ead85782db" data-toc-id="6d98f8ba-d946-49ed-87a9-48ead85782db" collapsed="false" seolevelmigrated="true">Preparation of Haloarenes</h4><h5 id="eec39058-66f7-4ed1-bb71-ac28ea3be200" data-toc-id="eec39058-66f7-4ed1-bb71-ac28ea3be200" collapsed="false" seolevelmigrated="true">Halogenation of Benzene</h5><ul><li><p>Electrophilic substitution reaction:</p><ul><li><p>Benzene + Cl2 \xrightarrow{FeCl3} Chlorobenzene + HCl</p></li><li><p></p></li><li><p>Benzene + Br_2 \xrightarrow{Fe} Bromobenzene + HBr</p></li></ul></li></ul><h5id="ddd0f8a4−b6e9−4b22−afad−96028a638fb9"data−toc−id="ddd0f8a4−b6e9−4b22−afad−96028a638fb9"collapsed="false"seolevelmigrated="true">Sandmeyer′sReaction</h5><ul><li><p>Conversionofbenzenediazoniumchloridetohalobenzeneusingsuitablereagents.</p></li><li><p></p></li></ul></li></ul><h5 id="ddd0f8a4-b6e9-4b22-afad-96028a638fb9" data-toc-id="ddd0f8a4-b6e9-4b22-afad-96028a638fb9" collapsed="false" seolevelmigrated="true">Sandmeyer's Reaction</h5><ul><li><p>Conversion of benzenediazonium chloride to halobenzene using suitable reagents.</p></li><li><p>Aniline \xrightarrow{NaNO2 + HX, 0-5^\circ C} Benzenediazonium Chloride \xrightarrow{CuX} Halobenzene + N2</p><ul><li><p>FromHCl:</p><ul><li><p>From HCl:Benzenediazonium Chloride \xrightarrow{Cu2Cl2} Chlorobenzene + N_2</p></li></ul></li></ul><h5id="24ac9c8f−1455−4b18−ab01−e8c83886cd21"data−toc−id="24ac9c8f−1455−4b18−ab01−e8c83886cd21"collapsed="false"seolevelmigrated="true">GattermannReaction</h5><ul><li><p>SimilartoSandmeyer′s,butusesCu+HXinsteadof</p></li></ul></li></ul><h5 id="24ac9c8f-1455-4b18-ab01-e8c83886cd21" data-toc-id="24ac9c8f-1455-4b18-ab01-e8c83886cd21" collapsed="false" seolevelmigrated="true">Gattermann Reaction</h5><ul><li><p>Similar to Sandmeyer's, but uses Cu + HX instead ofCu2X2.</p><ul><li><p>.</p><ul><li><p>Benzenediazonium Chloride \xrightarrow{Cu + HCl} Chlorobenzene + N_2</p></li></ul></li></ul><h5id="fb9a768e−ed52−416c−98b2−e4d684393755"data−toc−id="fb9a768e−ed52−416c−98b2−e4d684393755"collapsed="false"seolevelmigrated="true">Balz−SchiemannReaction</h5><ul><li><p>Preparationofarylfluorides:</p></li><li><p></p></li></ul></li></ul><h5 id="fb9a768e-ed52-416c-98b2-e4d684393755" data-toc-id="fb9a768e-ed52-416c-98b2-e4d684393755" collapsed="false" seolevelmigrated="true">Balz-Schiemann Reaction</h5><ul><li><p>Preparation of aryl fluorides:</p></li><li><p>Benzenediazonium Chloride \xrightarrow{HBF4} Aryl-N2^+BF4^- \xrightarrow{\Delta} Aryl-F + N2 +BF_3</p></li></ul><h4id="0ade6007−c5b3−46b8−93c0−43c8e4e18e0d"data−toc−id="0ade6007−c5b3−46b8−93c0−43c8e4e18e0d"collapsed="false"seolevelmigrated="true">PropertiesofHaloalkanesandHaloarenes</h4><h5id="f9e7cc0b−09be−4b74−96e3−a78ff0385ae7"data−toc−id="f9e7cc0b−09be−4b74−96e3−a78ff0385ae7"collapsed="false"seolevelmigrated="true">Reactivity</h5><ul><li><p>Factorsaffectingreactivity:</p><ul><li><p>Hybridization:</p><ul><li><p>Bondenergyishigherfor</p></li></ul><h4 id="0ade6007-c5b3-46b8-93c0-43c8e4e18e0d" data-toc-id="0ade6007-c5b3-46b8-93c0-43c8e4e18e0d" collapsed="false" seolevelmigrated="true">Properties of Haloalkanes and Haloarenes</h4><h5 id="f9e7cc0b-09be-4b74-96e3-a78ff0385ae7" data-toc-id="f9e7cc0b-09be-4b74-96e3-a78ff0385ae7" collapsed="false" seolevelmigrated="true">Reactivity</h5><ul><li><p>Factors affecting reactivity:</p><ul><li><p>Hybridization:</p><ul><li><p>Bond energy is higher forsp^2hybridizedcarbon(asinarylhalides)comparedtohybridized carbon (as in aryl halides) compared tosp^3hybridizedcarbon(asinalkylhalides).</p></li></ul></li><li><p>Resonance:</p><ul><li><p>Duetoresonanceinarylhalides,apartialdoublebondcharacterisformedbetweenthecarbonandhalogen,increasingthebondenergyanddecreasingreactivity.</p></li></ul></li><li><p>DipoleMoment:</p><ul><li><p>Polarityandreactivityincreasewithdipolemoment(hybridized carbon (as in alkyl halides).</p></li></ul></li><li><p>Resonance:</p><ul><li><p>Due to resonance in aryl halides, a partial double bond character is formed between the carbon and halogen, increasing the bond energy and decreasing reactivity.</p></li></ul></li><li><p>Dipole Moment:</p><ul><li><p>Polarity and reactivity increase with dipole moment (\mu = e \times l).</p></li><li><p>SincetheC−Xbondlengthisgreaterinalkylhalides,theyaremorepolarandreactivethanarylhalides.</p></li></ul></li></ul></li></ul><h5id="03598957−ee9f−4724−9756−41e451253ee8"data−toc−id="03598957−ee9f−4724−9756−41e451253ee8"collapsed="false"seolevelmigrated="true">ComparingHydrolysisRates</h5><ul><li><p>Cyclohexylchloridehydrolyzesfasterthanchlorobenzene.</p></li><li><p>ResonanceformsofchlorobenzenestabilizetheC−Clbond.</p></li></ul><h4id="23383b23−2780−4aea−b7cc−22eb2d5e1b7c"data−toc−id="23383b23−2780−4aea−b7cc−22eb2d5e1b7c"collapsed="false"seolevelmigrated="true">PhysicalProperties</h4><ul><li><p>Assurfaceareaincreases,themagnitudeofvanderWaalsforcesincreases,andsodoboilingpointandosmoticpressure;volatilitydecreases.</p></li></ul><h4id="03062475−32e8−4747−ae67−70e73b150d8e"data−toc−id="03062475−32e8−4747−ae67−70e73b150d8e"collapsed="false"seolevelmigrated="true">ReactionswithKCNandAgCN</h4><ul><li><p>AmbidentNucleophiles:CNcanformbothcyanideandisocyanide.</p><ul><li><p>KCN(ionic)vs.AgCN(covalent):</p><ul><li><p>).</p></li><li><p>Since the C-X bond length is greater in alkyl halides, they are more polar and reactive than aryl halides.</p></li></ul></li></ul></li></ul><h5 id="03598957-ee9f-4724-9756-41e451253ee8" data-toc-id="03598957-ee9f-4724-9756-41e451253ee8" collapsed="false" seolevelmigrated="true">Comparing Hydrolysis Rates</h5><ul><li><p>Cyclohexyl chloride hydrolyzes faster than chlorobenzene.</p></li><li><p>Resonance forms of chlorobenzene stabilize the C-Cl bond.</p></li></ul><h4 id="23383b23-2780-4aea-b7cc-22eb2d5e1b7c" data-toc-id="23383b23-2780-4aea-b7cc-22eb2d5e1b7c" collapsed="false" seolevelmigrated="true">Physical Properties</h4><ul><li><p>As surface area increases, the magnitude of van der Waals forces increases, and so do boiling point and osmotic pressure; volatility decreases.</p></li></ul><h4 id="03062475-32e8-4747-ae67-70e73b150d8e" data-toc-id="03062475-32e8-4747-ae67-70e73b150d8e" collapsed="false" seolevelmigrated="true">Reactions with KCN and AgCN</h4><ul><li><p>Ambident Nucleophiles: CN can form both cyanide and isocyanide.</p><ul><li><p>KCN (ionic) vs. AgCN (covalent):</p><ul><li><p>R-X + KCN \rightarrow R-CN + KX(Alkylcyanide)</p></li><li><p>(Alkyl cyanide)</p></li><li><p>R-X + AgCN \rightarrow R-NC + AgX(Alkylisocyanide)</p></li></ul></li></ul></li><li><p>Explanation:</p><ul><li><p>KCNdissociatesinto(Alkyl isocyanide)</p></li></ul></li></ul></li><li><p>Explanation:</p><ul><li><p>KCN dissociates intoK^+andandCN^-.</p><ul><li><p>Thealkylgroupcombineswiththecarbonend.</p></li></ul></li><li><p>AgCNiscovalentandthealkylgroupcombineswiththenitrogenendtoproduceisocyanide.</p></li></ul></li></ul><h4id="da7dd1c7−40a1−45b5−b1d7−b531c4228162"data−toc−id="da7dd1c7−40a1−45b5−b1d7−b531c4228162"collapsed="false"seolevelmigrated="true">Reactionswith.</p><ul><li><p>The alkyl group combines with the carbon end.</p></li></ul></li><li><p>AgCN is covalent and the alkyl group combines with the nitrogen end to produce isocyanide.</p></li></ul></li></ul><h4 id="da7dd1c7-40a1-45b5-b1d7-b531c4228162" data-toc-id="da7dd1c7-40a1-45b5-b1d7-b531c4228162" collapsed="false" seolevelmigrated="true">Reactions withKNO2andandAgNO2</h4><ul><li><p></h4><ul><li><p>R-X + KNO_2 \rightarrow R-O-N=O(Alkylnitrite)</p></li><li><p>(Alkyl nitrite)</p></li><li><p>R-X + AgNO2 \rightarrow R-NO2(Nitroalkane)</p></li></ul><h4id="8a78966d−383d−4f70−9905−295d595cf6b3"data−toc−id="8a78966d−383d−4f70−9905−295d595cf6b3"collapsed="false"seolevelmigrated="true">ReactionswithAqueousandAlcoholicKOH</h4><ul><li><p>AqueousKOH(KOH+(Nitroalkane)</p></li></ul><h4 id="8a78966d-383d-4f70-9905-295d595cf6b3" data-toc-id="8a78966d-383d-4f70-9905-295d595cf6b3" collapsed="false" seolevelmigrated="true">Reactions with Aqueous and Alcoholic KOH</h4><ul><li><p>Aqueous KOH (KOH +H2O):Nucleophilicsubstitution(): Nucleophilic substitution (SN).</p></li><li><p>AlcoholicKOH(KOH+EtOH):Eliminationreaction.</p></li><li><p>AqueousKOHismorenucleophilicandlessbasicthanalcoholicKOH.</p></li></ul><h5id="53cea22f−e1b7−4009−bf26−d0b55b48a95e"data−toc−id="53cea22f−e1b7−4009−bf26−d0b55b48a95e"collapsed="false"seolevelmigrated="true">ConditionA(SN)</h5><ul><li><p>Nuattackoccursmore.</p></li></ul><h4id="542380a3−8671−4a72−a35a−b5d9db595dff"data−toc−id="542380a3−8671−4a72−a35a−b5d9db595dff"collapsed="false"seolevelmigrated="true">NucleophilicSubstitution().</p></li><li><p>Alcoholic KOH (KOH + EtOH): Elimination reaction.</p></li><li><p>Aqueous KOH is more nucleophilic and less basic than alcoholic KOH.</p></li></ul><h5 id="53cea22f-e1b7-4009-bf26-d0b55b48a95e" data-toc-id="53cea22f-e1b7-4009-bf26-d0b55b48a95e" collapsed="false" seolevelmigrated="true">Condition A (SN)</h5><ul><li><p>Nu attack occurs more.</p></li></ul><h4 id="542380a3-8671-4a72-a35a-b5d9db595dff" data-toc-id="542380a3-8671-4a72-a35a-b5d9db595dff" collapsed="false" seolevelmigrated="true">Nucleophilic Substitution (S_N)Reactions</h4><h5id="505a3f7e−868f−458f−a677−8e7ce238709f"data−toc−id="505a3f7e−868f−458f−a677−8e7ce238709f"collapsed="false"seolevelmigrated="true">Conditions</h5><ul><li><p>Thenucleophilicityoftheattackinggroupshouldbegreaterthantheleavinggroup.</p></li></ul><h5id="be6a9d91−372b−4b44−b886−82123ca6e639"data−toc−id="be6a9d91−372b−4b44−b886−82123ca6e639"collapsed="false"seolevelmigrated="true">Mechanisms</h5><ul><li><p>) Reactions</h4><h5 id="505a3f7e-868f-458f-a677-8e7ce238709f" data-toc-id="505a3f7e-868f-458f-a677-8e7ce238709f" collapsed="false" seolevelmigrated="true">Conditions</h5><ul><li><p>The nucleophilicity of the attacking group should be greater than the leaving group.</p></li></ul><h5 id="be6a9d91-372b-4b44-b886-82123ca6e639" data-toc-id="be6a9d91-372b-4b44-b886-82123ca6e639" collapsed="false" seolevelmigrated="true">Mechanisms</h5><ul><li><p>S_N2(Bimolecular):</p><ul><li><p>Rate=(Bimolecular):</p><ul><li><p>Rate =k[CH_3-X][OH^-]</p></li><li><p>Molecularity=2</p></li><li><p>Inversionofconfiguration(Waldeninversion).</p></li></ul></li><li><p></p></li><li><p>Molecularity = 2</p></li><li><p>Inversion of configuration (Walden inversion).</p></li></ul></li><li><p>S_N1(Unimolecular):</p><ul><li><p>Rate=(Unimolecular):</p><ul><li><p>Rate =k[alkyl halide]</p></li></ul></li></ul><h4id="ba7d3c93−92db−4a53−8a10−2948ef6cb330"data−toc−id="ba7d3c93−92db−4a53−8a10−2948ef6cb330"collapsed="false"seolevelmigrated="true">Typesof</p></li></ul></li></ul><h4 id="ba7d3c93-92db-4a53-8a10-2948ef6cb330" data-toc-id="ba7d3c93-92db-4a53-8a10-2948ef6cb330" collapsed="false" seolevelmigrated="true">Types ofS_NReactions</h4><ul><li><p>Reactions</h4><ul><li><p>S_N1:Formsacarbocationintermediate.</p><ul><li><p>Favoredinpolarproticsolvents.</p></li></ul></li><li><p>: Forms a carbocation intermediate.</p><ul><li><p>Favored in polar protic solvents.</p></li></ul></li><li><p>S_N2:Occursviaatransitionstate.</p><ul><li><p>Favoredinpolaraproticsolvents.</p></li><li><p>Backsideattack.</p></li></ul></li><li><p>: Occurs via a transition state.</p><ul><li><p>Favored in polar aprotic solvents.</p></li><li><p>Backside attack.</p></li></ul></li><li><p>S_Ni:Intramolecularnucleophilicsubstitution(e.g.,Darzenprocess).</p></li></ul><h4id="e38cee45−54b9−4744−ad45−876df2005371"data−toc−id="e38cee45−54b9−4744−ad45−876df2005371"collapsed="false"seolevelmigrated="true">FactorsAffecting: Intramolecular nucleophilic substitution (e.g., Darzen process).</p></li></ul><h4 id="e38cee45-54b9-4744-ad45-876df2005371" data-toc-id="e38cee45-54b9-4744-ad45-876df2005371" collapsed="false" seolevelmigrated="true">Factors AffectingS_N1Reactions</h4><ul><li><p>Stabilityofcarbocation(3°>2°>1°).</p></li><li><p>Leavinggroupability.</p></li></ul><h4id="32729dd7−7822−430d−8db1−0104fa4f4295"data−toc−id="32729dd7−7822−430d−8db1−0104fa4f4295"collapsed="false"seolevelmigrated="true">Examples</h4><ul><li><p>Alkalinehydrolysisoftert−butylbromideoccursviaReactions</h4><ul><li><p>Stability of carbocation (3° > 2° > 1°).</p></li><li><p>Leaving group ability.</p></li></ul><h4 id="32729dd7-7822-430d-8db1-0104fa4f4295" data-toc-id="32729dd7-7822-430d-8db1-0104fa4f4295" collapsed="false" seolevelmigrated="true">Examples</h4><ul><li><p>Alkaline hydrolysis of tert-butyl bromide occurs viaS_N1.</p></li><li><p>Alkalinehydrolysisofethylbromideoccursvia.</p></li><li><p>Alkaline hydrolysis of ethyl bromide occurs viaS_N2.</p></li></ul><h4id="99b99f24−f2fc−4ff5−8a5d−e5dd25973cc5"data−toc−id="99b99f24−f2fc−4ff5−8a5d−e5dd25973cc5"collapsed="false"seolevelmigrated="true">Stereochemistryof.</p></li></ul><h4 id="99b99f24-f2fc-4ff5-8a5d-e5dd25973cc5" data-toc-id="99b99f24-f2fc-4ff5-8a5d-e5dd25973cc5" collapsed="false" seolevelmigrated="true">Stereochemistry ofS_NReactions</h4><ul><li><p>Opticalisomers:Rotateplanepolarizedlight.</p><ul><li><p>Dextrorotatory(d−form):(+)</p></li><li><p>Levorotatory(l−form):(−)</p></li><li><p>Racemicmixture:50:50mixtureofenantiomers(opticallyinactive).</p></li></ul></li><li><p>Reactions</h4><ul><li><p>Optical isomers: Rotate plane polarized light.</p><ul><li><p>Dextrorotatory (d-form): (+)</p></li><li><p>Levorotatory (l-form): (-)</p></li><li><p>Racemic mixture: 50:50 mixture of enantiomers (optically inactive).</p></li></ul></li><li><p>S_N2:Inversionofconfiguration.</p><ul><li><p>: Inversion of configuration.</p><ul><li><p>S_N1:Racemization.</p></li></ul></li></ul><h4id="e3e405ea−216b−40f4−85fe−1708f573065b"data−toc−id="e3e405ea−216b−40f4−85fe−1708f573065b"collapsed="false"seolevelmigrated="true">MesoCompounds</h4><ul><li><p>Havechiralcentersbutareopticallyinactiveduetoaninternalplaneofsymmetry.</p><ul><li><p>Totalnumberofopticalisomers=: Racemization.</p></li></ul></li></ul><h4 id="e3e405ea-216b-40f4-85fe-1708f573065b" data-toc-id="e3e405ea-216b-40f4-85fe-1708f573065b" collapsed="false" seolevelmigrated="true">Meso Compounds</h4><ul><li><p>Have chiral centers but are optically inactive due to an internal plane of symmetry.</p><ul><li><p>Total number of optical isomers =2^n(wherenisthenumberofchiralcarbons).</p></li></ul></li></ul><h4id="fa2256d9−23a3−4721−b2ee−baa7100908e6"data−toc−id="fa2256d9−23a3−4721−b2ee−baa7100908e6"collapsed="false"seolevelmigrated="true">FischerProjections</h4><ul><li><p>Two−dimensionalrepresentationofa3Dmolecule.</p></li><li><p>Horizontallines:Substituentsabovetheplane.</p></li><li><p>Verticallines:Substituentsbelowtheplane.</p></li></ul><h4id="bdb6c140−e5e5−4bf2−8e52−73646e4f8bbc"data−toc−id="bdb6c140−e5e5−4bf2−8e52−73646e4f8bbc"collapsed="false"seolevelmigrated="true">R/SNomenclature</h4><ul><li><p>Cahn−Ingold−Prelog(CIP)rules:</p><ul><li><p>Assignprioritybasedonatomicmass.</p></li><li><p>Ifthe4thprioritygroup(lowestpriority)isontheverticalline,theconfigurationisasdetermined.</p></li><li><p>Ifthe4thprioritygroupisonthehorizontalline,thedeterminedconfigurationmustbereversed.</p></li></ul></li></ul><h4id="e879849f−405f−4b58−9968−72303be9713e"data−toc−id="e879849f−405f−4b58−9968−72303be9713e"collapsed="false"seolevelmigrated="true">EliminationReactions</h4><h5id="13567066−bc51−41b8−973d−4a8b4a4eab20"data−toc−id="13567066−bc51−41b8−973d−4a8b4a4eab20"collapsed="false"seolevelmigrated="true">ReactionwithAlc.KOH</h5><ul><li><p>(where n is the number of chiral carbons).</p></li></ul></li></ul><h4 id="fa2256d9-23a3-4721-b2ee-baa7100908e6" data-toc-id="fa2256d9-23a3-4721-b2ee-baa7100908e6" collapsed="false" seolevelmigrated="true">Fischer Projections</h4><ul><li><p>Two-dimensional representation of a 3D molecule.</p></li><li><p>Horizontal lines: Substituents above the plane.</p></li><li><p>Vertical lines: Substituents below the plane.</p></li></ul><h4 id="bdb6c140-e5e5-4bf2-8e52-73646e4f8bbc" data-toc-id="bdb6c140-e5e5-4bf2-8e52-73646e4f8bbc" collapsed="false" seolevelmigrated="true">R/S Nomenclature</h4><ul><li><p>Cahn-Ingold-Prelog (CIP) rules:</p><ul><li><p>Assign priority based on atomic mass.</p></li><li><p>If the 4th priority group (lowest priority) is on the vertical line, the configuration is as determined.</p></li><li><p>If the 4th priority group is on the horizontal line, the determined configuration must be reversed.</p></li></ul></li></ul><h4 id="e879849f-405f-4b58-9968-72303be9713e" data-toc-id="e879849f-405f-4b58-9968-72303be9713e" collapsed="false" seolevelmigrated="true">Elimination Reactions</h4><h5 id="13567066-bc51-41b8-973d-4a8b4a4eab20" data-toc-id="13567066-bc51-41b8-973d-4a8b4a4eab20" collapsed="false" seolevelmigrated="true">Reaction with Alc. KOH</h5><ul><li><p>CH3-CH2-Cl + alc. KOH \rightarrow CH2=CH2</p><ul><li><p>Morebasicbutlessnucleophilic.</p></li><li><p>Formsalkene.</p></li></ul></li></ul><h4id="6e208b0b−ed3d−4dc7−8e12−c1bedb3824b9"data−toc−id="6e208b0b−ed3d−4dc7−8e12−c1bedb3824b9"collapsed="false"seolevelmigrated="true">TypesofEliminationReactions</h4><ul><li><p>E1(Unimolecularelimination).</p></li><li><p>E2(Bimolecularelimination):</p></li><li><p>E1cB(Unimoleculareliminationviaconjugatebase).</p></li></ul><h4id="6a3088a5−7704−4c46−bbc6−6e5d7a0337fd"data−toc−id="6a3088a5−7704−4c46−bbc6−6e5d7a0337fd"collapsed="false"seolevelmigrated="true">ReactionwithDry</p><ul><li><p>More basic but less nucleophilic.</p></li><li><p>Forms alkene.</p></li></ul></li></ul><h4 id="6e208b0b-ed3d-4dc7-8e12-c1bedb3824b9" data-toc-id="6e208b0b-ed3d-4dc7-8e12-c1bedb3824b9" collapsed="false" seolevelmigrated="true">Types of Elimination Reactions</h4><ul><li><p>E1 (Unimolecular elimination).</p></li><li><p>E2 (Bimolecular elimination):</p></li><li><p>E1cB (Unimolecular elimination via conjugate base).</p></li></ul><h4 id="6a3088a5-7704-4c46-bbc6-6e5d7a0337fd" data-toc-id="6a3088a5-7704-4c46-bbc6-6e5d7a0337fd" collapsed="false" seolevelmigrated="true">Reaction with DryAg_2O</h4><ul><li><p>Formsether.</p></li></ul><h4id="b3f6fbeb−0b07−42e1−9d86−7547863abaa3"data−toc−id="b3f6fbeb−0b07−42e1−9d86−7547863abaa3"collapsed="false"seolevelmigrated="true">ReactionswithOtherReagents</h4><ul><li><p></h4><ul><li><p>Forms ether.</p></li></ul><h4 id="b3f6fbeb-0b07-42e1-9d86-7547863abaa3" data-toc-id="b3f6fbeb-0b07-42e1-9d86-7547863abaa3" collapsed="false" seolevelmigrated="true">Reactions with Other Reagents</h4><ul><li><p>R-X + NaSH \rightarrow R-SH(Thioalcohol).</p></li><li><p>(Thioalcohol).</p></li><li><p>R-X + Na_2S \rightarrow R-S-R(Thioether).</p></li><li><p>(Thioether).</p></li><li><p>R-X + NaN3 \rightarrow R-N3(Alkylazide).</p></li><li><p>(Alkyl azide).</p></li><li><p>R-X + R'ONa \rightarrow R-O-R'(Williamsonsynthesis,ether).</p></li><li><p>ReactionwithAmmonia(Hoffmannammonolysis):<br>(Williamson synthesis, ether).</p></li><li><p>Reaction with Ammonia (Hoffmann ammonolysis):<br>R-X + NH3 -> R-NH2</p></li><li><p>ReactionwithSodiumAcetylide:<br></p></li><li><p>Reaction with Sodium Acetylide:<br>H-C≡CNa + R-X -> H-C≡C-R</p></li></ul><h5id="a132c681−82ee−456f−ac56−16a229f441f8"data−toc−id="a132c681−82ee−456f−ac56−16a229f441f8"collapsed="false"seolevelmigrated="true">WurtzReaction</h5><ul><li><p></p></li></ul><h5 id="a132c681-82ee-456f-ac56-16a229f441f8" data-toc-id="a132c681-82ee-456f-ac56-16a229f441f8" collapsed="false" seolevelmigrated="true">Wurtz Reaction</h5><ul><li><p>R-X + Na \xrightarrow{dry ether} R-R</p></li></ul><h5id="477e09fd−b5fe−4557−9b1f−5887ddea38e8"data−toc−id="477e09fd−b5fe−4557−9b1f−5887ddea38e8"collapsed="false"seolevelmigrated="true">GrignardReagent</h5><ul><li><p></p></li></ul><h5 id="477e09fd-b5fe-4557-9b1f-5887ddea38e8" data-toc-id="477e09fd-b5fe-4557-9b1f-5887ddea38e8" collapsed="false" seolevelmigrated="true">Grignard Reagent</h5><ul><li><p>R-X + Mg \xrightarrow{dry ether} R-Mg-X</p></li></ul><h5id="46221acd−d459−4761−84b4−e0d20b73b2d7"data−toc−id="46221acd−d459−4761−84b4−e0d20b73b2d7"collapsed="false"seolevelmigrated="true">FittigReaction</h5><ul><li><p></p></li></ul><h5 id="46221acd-d459-4761-84b4-e0d20b73b2d7" data-toc-id="46221acd-d459-4761-84b4-e0d20b73b2d7" collapsed="false" seolevelmigrated="true">Fittig Reaction</h5><ul><li><p>Ar-X + Na \xrightarrow{dry ether} Ar-Ar</p></li></ul><h5id="d6fbe41b−079b−40c2−9657−20f77ae42988"data−toc−id="d6fbe41b−079b−40c2−9657−20f77ae42988"collapsed="false"seolevelmigrated="true">Wurtz−Fittig</h5><ul><li><p></p></li></ul><h5 id="d6fbe41b-079b-40c2-9657-20f77ae42988" data-toc-id="d6fbe41b-079b-40c2-9657-20f77ae42988" collapsed="false" seolevelmigrated="true">Wurtz-Fittig</h5><ul><li><p>\text{Wurtz reaction} > \text{Wurtz-Fittig} > \text{Fittig}</p></li></ul><h5id="12b2dce5−7589−4611−b57c−2427958e2810"data−toc−id="12b2dce5−7589−4611−b57c−2427958e2810"collapsed="false"seolevelmigrated="true">UllmannReaction</h5><ul><li><p></p></li></ul><h5 id="12b2dce5-7589-4611-b57c-2427958e2810" data-toc-id="12b2dce5-7589-4611-b57c-2427958e2810" collapsed="false" seolevelmigrated="true">Ullmann Reaction</h5><ul><li><p>Ar-X + Cu \rightarrow Ar-Ar</p></li></ul><h5id="a5eb5255−43b8−48f3−b68c−64cdaae88961"data−toc−id="a5eb5255−43b8−48f3−b68c−64cdaae88961"collapsed="false"seolevelmigrated="true">Di−haloalkanes</h5><ul><li><p>Geminal:2halogensonthesamecarbon.</p></li></ul><h5id="b2b745d3−fd4b−4fee−8630−f09c31f4589f"data−toc−id="b2b745d3−fd4b−4fee−8630−f09c31f4589f"collapsed="false"seolevelmigrated="true">PreparationofChloroform(</p></li></ul><h5 id="a5eb5255-43b8-48f3-b68c-64cdaae88961" data-toc-id="a5eb5255-43b8-48f3-b68c-64cdaae88961" collapsed="false" seolevelmigrated="true">Di-haloalkanes</h5><ul><li><p>Geminal: 2 halogens on the same carbon.</p></li></ul><h5 id="b2b745d3-fd4b-4fee-8630-f09c31f4589f" data-toc-id="b2b745d3-fd4b-4fee-8630-f09c31f4589f" collapsed="false" seolevelmigrated="true">Preparation of Chloroform ((CHCl_3))</h5><ul><li><p>FromEthylAlcoholandAcetoneusingBleachingPowder:</p></li><li><p>Chloroformisacolourless,volatileliquid.</p></li></ul><h4id="c838c59d−3172−4e48−a00c−43a652b4f933"data−toc−id="c838c59d−3172−4e48−a00c−43a652b4f933"collapsed="false"seolevelmigrated="true">HaloformReaction</h4><ul><li><p>FromKetomethylGroups()</h5><ul><li><p>From Ethyl Alcohol and Acetone using Bleaching Powder:</p></li><li><p>Chloroform is a colourless, volatile liquid.</p></li></ul><h4 id="c838c59d-3172-4e48-a00c-43a652b4f933" data-toc-id="c838c59d-3172-4e48-a00c-43a652b4f933" collapsed="false" seolevelmigrated="true">Haloform Reaction</h4><ul><li><p>From Ketomethyl Groups (CH3-C=O)orPotentialKetomethylGroupsinthePresenceofBaseReactswithHalogentoform) or Potential Ketomethyl Groups in the Presence of Base Reacts with Halogen to formCHX3.

Mechanism

  • Base-Catalyzed Alpha-Halogenation: Enolates are intermediates in the halogenation, deuterium exchange, and racemization of ketones and are formed more readily when base is used rather than acid. Once a monohalogenated product forms, it forms a similar enolate to get to the dihalogenated product through essentially the same mechanism and so on and so forth until a trihalogenated product is formed.

Properties of chloroform
Acidity

  • Chloroform is acidic due to the -I effect of three chlorine atoms.

Oxidation & how to store chloroform in laboratory

  • Oxidation in the presence of air and sunlight converts chloroform into phosgene (carbonyl dichloride). Is placed into a brown bottle while adding 1%-2% ethanol.

  • CHCl3 + \frac{1}{2} O2 \rightarrow COCl_2 + HCl</p><ul><li><p>Todetectphosgeneaddsilvernitrate(</p><ul><li><p>To detect phosgene add silver nitrate (AgNO3).Awhiteprecipitate,insolublein). A white precipitate, insoluble inHNO3butsolubleinbut soluble inNH_4OH,indicatesphosgene.</p></li></ul></li></ul><h5id="d4ce8f10−246a−4376−95f6−f856852243a5"data−toc−id="d4ce8f10−246a−4376−95f6−f856852243a5"collapsed="false"seolevelmigrated="true">ReactionwithAg/Cumetalwithnitricacid</h5><ul><li><p>ReactionwithSilverMetal:Reduceshalotoalkynechain.<br>[1marks]</p></li><li><p>ReactionwithNitricAcid:Produceschloropicrin,apotentinsecticide.</p></li></ul><h4id="6509e386−cf77−4fa5−946b−2db162f01f87"data−toc−id="6509e386−cf77−4fa5−946b−2db162f01f87"collapsed="false"seolevelmigrated="true">ReductionofChloroform</h4><ul><li><p>Reductionformsdichloromethaneandmethylchloride<br>CHCl+232+dilHel→CHC</p></li><li><p><em>H</em>2<em>+HClZn+dilHill→CHCl+4</em><br>+2HClZn+H2OPCH4+3Ha</p></li></ul><h4id="39c5f9cd−8c96−45e0−a77e−85981860d4fa"data−toc−id="39c5f9cd−8c96−45e0−a77e−85981860d4fa"collapsed="false"seolevelmigrated="true">PropertiesofHaloarenes</h4><h5id="c25ae9be−a15a−43f7−861b−09f289c6cc8f"data−toc−id="c25ae9be−a15a−43f7−861b−09f289c6cc8f"collapsed="false"seolevelmigrated="true">ReactionwithChloral</h5><ul><li><p>, indicates phosgene.</p></li></ul></li></ul><h5 id="d4ce8f10-246a-4376-95f6-f856852243a5" data-toc-id="d4ce8f10-246a-4376-95f6-f856852243a5" collapsed="false" seolevelmigrated="true">Reaction with Ag/Cu metal with nitric acid</h5><ul><li><p>Reaction with Silver Metal: Reduces halo to alkyne chain.<br>[1 marks]</p></li><li><p>Reaction with Nitric Acid: Produces chloropicrin, a potent insecticide.</p></li></ul><h4 id="6509e386-cf77-4fa5-946b-2db162f01f87" data-toc-id="6509e386-cf77-4fa5-946b-2db162f01f87" collapsed="false" seolevelmigrated="true">Reduction of Chloroform</h4><ul><li><p>Reduction forms dichloromethane and methyl chloride<br>CHCl+232 + dilHel\rightarrow CH C</p></li><li><p><em>H</em> { 2 }<em>+HClZn + dil Hill\rightarrow CHCl+ 4</em> <br>+2HClZn+H2OPCH4+ 3H _ a</p></li></ul><h4 id="39c5f9cd-8c96-45e0-a77e-85981860d4fa" data-toc-id="39c5f9cd-8c96-45e0-a77e-85981860d4fa" collapsed="false" seolevelmigrated="true">Properties of Haloarenes</h4><h5 id="c25ae9be-a15a-43f7-861b-09f289c6cc8f" data-toc-id="c25ae9be-a15a-43f7-861b-09f289c6cc8f" collapsed="false" seolevelmigrated="true">Reaction with Chloral</h5><ul><li><p>2 Ph-Cl + Cl3C-CHO \rightarrow (ClC6H4)2CHCCl_3$$ (DDT)

Electrophilic Substitution

  • Halobenzenes are ortho-para directing due to resonance but are deactivating.
    Reactions and directing effects are related with the location for the upcoming addition.

Chlorination