{"id":5150,"date":"2020-06-29T11:56:14","date_gmt":"2020-06-29T11:56:14","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/?post_type=back-matter&#038;p=5150"},"modified":"2020-06-29T12:22:18","modified_gmt":"2020-06-29T12:22:18","slug":"appendix-1","status":"publish","type":"back-matter","link":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/back-matter\/appendix-1\/","title":{"raw":"Appendix 1: Summary of Part 1 reactions used for synthesis","rendered":"Appendix 1: Summary of Part 1 reactions used for synthesis"},"content":{"raw":"This appendix lists most, but not all, reactions covered in this textbook (part 1 only).\u00a0 The focus is on reactions that are most useful in synthesis.\r\n<h1>Appendix 1.1. Nucleophilic substitutions with alkyl halides<\/h1>\r\n<h2>Overview<\/h2>\r\nMost nucleophilic substitutions used in synthesis go via an S<sub>N<\/sub>2 mechanism.\r\n\r\n<img class=\"wp-image-4957 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01052516\/GenericSN2.png\" alt=\"A generic example of an SN2 reaction\" width=\"520\" height=\"48\" \/>\r\n<ul>\r\n \t<li>S<sub>N<\/sub>2 reactions work best with R\u2013X as an alkyl halide or sulfonate. Epoxides also work well for more complex targets.<\/li>\r\n \t<li>Best with 1<sup>o<\/sup> alkyl, OK with 2<sup>o<\/sup>, fails with 3<sup>o<\/sup> and aryl<\/li>\r\n \t<li>Works well with I, Br, OK with Cl, fails with F.<\/li>\r\n \t<li>It requires a strong nucleophile, which usually means one bearing a negative charge such as \u00afOH .<\/li>\r\n \t<li>Works well in polar aprotic solvents such as DMSO.<\/li>\r\n<\/ul>\r\n<h2>A. Formation of alkyl halides<\/h2>\r\nSee <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-3-preparation-of-alkyl-halides-related-rx\/\">section 9.3.<\/a>\u00a0 Most S<sub>N<\/sub>2 reactions utilize alkyl halides, so you need to know how to make them!\u00a0 The most common route is from the corresponding alcohol, using PX<sub>3<\/sub>.\u00a0 I recommend using alkyl bromides in synthesis, and these are made using PBr<sub>3<\/sub>.\r\n<ul>\r\n \t<li>Use PX<sub>3<\/sub> (X = Cl, Br, I) to convert primary and secondary ROH to RX<\/li>\r\n \t<li>SOCl<sub>2<\/sub> also good for ROH to RCl<\/li>\r\n \t<li>Mechanism involves activation of OH by PX<sub>3<\/sub> to make it a good leaving group, then S<sub>N<\/sub>2 attack by X\u00af.<\/li>\r\n<\/ul>\r\n<img class=\"wp-image-4960 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01055354\/GenericPX3reaction.png\" alt=\"Reaction of a generic alcohol with PX3 to produce an alkyl halide\" width=\"285\" height=\"66\" \/>\r\n\r\nFor example, (2<em>R<\/em>)-butan-2-ol reacts with PBr<sub>3<\/sub> produces (<em>2S<\/em>)-2-bromobutane with inversion; note that all three bromines can be delivered.\r\n\r\n<img class=\"wp-image-4965 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01062504\/PreparationOf2Bromobutane.png\" alt=\"\" width=\"591\" height=\"78\" \/>\r\n\r\nFor preparation of tertiary alkyl chlorides and bromides from the corresponding alcohols, HCl or HBr is the most effective reagent.\r\n<h2>B. Formation of alcohols<\/h2>\r\nThis is synthetically the reverse of the PBr<sub>3<\/sub> reaction.\u00a0 Here, the nucleophile is hydroxide ion (\u00afOH).\u00a0 As always with anions, it\u00a0 has to have a cation with it, usually sodium or potassium.\r\n\r\n<img class=\"wp-image-4972 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01145001\/GenericROHprep.png\" alt=\"RBr reacts with OH- to give ROH\" width=\"497\" height=\"47\" \/>\r\n\r\nFor example:\r\n\r\n<img class=\"size-full wp-image-4971 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01144950\/Butan1olPrep.png\" alt=\"BuBr reacts with KOH to give BuOH\" width=\"476\" height=\"65\" \/>\r\n<h2>C. Formation of amines<\/h2>\r\nSee <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-4-reaction-of-rx-with-nh3-and-amines\/\">section 9.4.<\/a>\r\n<ul>\r\n \t<li>NH<sub>3<\/sub>, R\u2019NH<sub>2<\/sub> and R\u2019<sub>2<\/sub>NH are strong enough to react with R\u2013X, to produce products containing a new R\u2013N bond.<\/li>\r\n \t<li>An excess of the NH<sub>3<\/sub> or amine reactant is needed to suppress the reaction of the product with a second mole of R\u2013X.<\/li>\r\n<\/ul>\r\n<img class=\"wp-image-4969 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01143126\/AminePrepViaExcessNH3.png\" alt=\"RBr reacts with large XS of NH3 to make RNH2\" width=\"437\" height=\"78\" \/>\r\n\r\nThere are also indirect methods for preparing amines, which avoid the need for a large excess of amine.\u00a0 One of the most popular uses azide (N<sub>3<\/sub><sup>\u2013<\/sup>) as nucleophile, followed by reduction to the amine.\r\n\r\n<img class=\"wp-image-4968 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01143121\/AminePrepViaAzide.png\" alt=\"RBr reacts with NaN3 to produce RN3, which is then reduced to RNH2 using LiAlH4\" width=\"660\" height=\"83\" \/>\r\n<h2>D. Williamson ether synthesis<\/h2>\r\n<div style=\"text-align: left\"><a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-5-williamson-ether-synthesis\/\">See section 9.5.<\/a> This is the most important way to make an ether group.\u00a0 The nucleophile is an alkoxide (the conjugate base of an alcohol).\u00a0 Often this has to be made from the alcohol using NaH.<\/div>\r\n<div><img class=\"alignnone wp-image-4974\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01154007\/GenericWilliamsonEther.png\" alt=\"Reaction of an alkoxide with an alkyl halide to form an ether\" width=\"802\" height=\"124\" \/><\/div>\r\n<div><\/div>\r\n<div>In the synthesis of ethers containing a tertiary alkyl group, the tertiary group should be in the alkoxide to ensure a good S<sub>N<\/sub>2 reaction - see example below.<\/div>\r\n<div><img class=\"alignnone size-full wp-image-4977\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/02033523\/WilliamsonEtherExample.png\" alt=\"Two alternatives for Williamson ether synthesis of a tert-butyl ether - good and bad.\" width=\"634\" height=\"240\" \/><\/div>\r\n<div><\/div>\r\n<h2>E. Enolate alkylation<\/h2>\r\n<a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-7-enolate-alkylation\/\">See section 9.7.<\/a>\r\n<div>\r\n<ul>\r\n \t<li>The enolate nucleophile is usually the conjugate base of a ketone or ester.<\/li>\r\n \t<li>As with the Williamson ether synthesis, the nucleophile has to be made from the ketone or ester with a strong base, usually LDA.\u00a0 (NaH sometimes works, but LDA is usually better.).\u00a0 At -78 <sup>o<\/sup>C, LDA forms the less substituted enolate.<\/li>\r\n \t<li>This reaction makes a new C\u2013C bond \u2013 often important in synthesis.\u00a0 The reaction works well with primary alkyl bromides or iodides, and moderately with secondary, and fails completely with tertiary alkyl bromides or iodides.<\/li>\r\n<\/ul>\r\n<\/div>\r\n<h2><img class=\" wp-image-4978 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/02034702\/GenericEnolateAlkylation.png\" alt=\"Generic formation of an enolate using LDA, followed by alkylation using RX\" width=\"716\" height=\"195\" \/><\/h2>\r\n<h2>F. Alkyne\/Acetylide alkylation<\/h2>\r\nSee <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-8-substitution-with-acetylides\/\">section 9.8<\/a>.\r\n<ul>\r\n \t<li>The nucleophile is the conjugate base of an alkyne, called an acetylide.<\/li>\r\n \t<li>Similar to D and E above, the nucleophile has to be made from the alkyne and a strong base, usually NaH or BuLi, though LDA also works.<\/li>\r\n \t<li>As with E above, this makes a new C\u2013C bond.<\/li>\r\n \t<li>Reaction only works well with 1<sup>o<\/sup> R\u2013X, since the acetylide is a strong base too.<\/li>\r\n<\/ul>\r\n<img class=\"wp-image-4982 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/03035705\/GenericAcetylideAlkylation.png\" alt=\"Formation of an acetylide using NaH, followed by SN2 reaction with an alkyl halide\" width=\"663\" height=\"143\" \/>\r\n<h2>G. Reduction of R\u2013X with LiAlH<sub>4<\/sub><\/h2>\r\n<ul>\r\n \t<li>LiAlH<sub>4<\/sub> is a strong reducing agent, which in effect delivers hydride ion, H\u00af.\u00a0 (Hydride ion itself is too small to react well in a direct S<sub>N<\/sub>2).<\/li>\r\n \t<li>Reaction only works well with 1<sup>o<\/sup> R\u2013X.<\/li>\r\n<\/ul>\r\n<img class=\"alignnone wp-image-4986\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/04032529\/GenericRXreductionwithLAH.png\" alt=\"RX reacts with LiAlH4 to produce RH\" width=\"262\" height=\"63\" \/>\r\n<h1>Appendix 1.2. Nucleophilic substitutions with Epoxides<\/h1>\r\n<h2>H. Reaction of epoxides with strong nucleophiles<\/h2>\r\n<ul>\r\n \t<li>Epoxides are strained 3-membered ring ethers that open very easily with strong nucleophiles, giving alcohols with the former nucleophile attached to the neighboring (less substituted) carbon.<\/li>\r\n \t<li>The mechanism is S<sub>N<\/sub>2, with the leaving being the O\u00af rather than a halide.<\/li>\r\n \t<li>Any of the above strong nucleophiles (NH<sub>3<\/sub>, R\u2019NH<sub>2<\/sub>, R\u2019<sub>2<\/sub>NH, \u00afOH, \u00afOR\u2019,\u00a0 enolates, acetylides, LiAlH<sub>4<\/sub>, will attack epoxides at the <strong>less substituted carbon<\/strong>.\u00a0 For example:<\/li>\r\n<\/ul>\r\n<div><img class=\" wp-image-4989 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/05033616\/EpoxideRingOpeningByMethoxide.png\" alt=\"Reaction of an epoxide with methoxide ion showing attack at the less substituted position\" width=\"487\" height=\"104\" \/><\/div>\r\n<div>\r\n<h2>I. Reaction of epoxides with weak nucleophiles<\/h2>\r\n<ul>\r\n \t<li>Epoxides do not open with weak nucleophiles, unless the epoxide is activated first with an acid such as H<sub>2<\/sub>SO<sub>4<\/sub>.<\/li>\r\n \t<li>The product is an alcohol on the less substituted carbon, with the former nucleophile attached to the neighboring (more substituted) carbon.<\/li>\r\n \t<li>Even at a tertiary center, the mechanism is S<sub>N<\/sub>2, with the leaving group being the OH rather than a halide.<\/li>\r\n \t<li>Any weak nucleophiles (H<sub>2<\/sub>O, ROH, Cl\u00af) will attack epoxides at the <strong>more substituted<\/strong> carbon, since this is the more electrophilic carbon.\u00a0 For example:<\/li>\r\n<\/ul>\r\n<\/div>\r\n<img class=\"wp-image-4992 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/05035737\/EpoxideRingOpeningByAcidicMethanol.png\" alt=\"\" width=\"504\" height=\"96\" \/>\r\n<h1>Appendix 1.3. Elimination reactions<\/h1>\r\n<h2>Overview<\/h2>\r\n<ul>\r\n \t<li>There are two main mechanisms \u2013 E2 and E1.<\/li>\r\n \t<li>E2 reactions make alkenes from alkyl halides and strong base<\/li>\r\n \t<li>E1 reactions are usually used to make alkenes from an alcohol and catalytic acid (H<sub>2<\/sub>SO<sub>4<\/sub> or H<sub>3<\/sub>PO<sub>4<\/sub>).<\/li>\r\n \t<li>E2 is usually better for synthesis, to avoid rearrangements, but alcohol dehydration often works OK.<\/li>\r\n \t<li>Both types of reaction usually obey Zaitsev\u2019s rule \u2013 the most substituted\/conjugated alkene is the major product.<\/li>\r\n \t<li>All elimination reactions are favored by heat.<\/li>\r\n<\/ul>\r\n<h2>J. Formation of alkenes from alkyl halides (E2)<\/h2>\r\n<a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-9-applications-of-eliminations\/\">See section 9.9.<\/a>\r\n<ul>\r\n \t<li>A strong base is needed, such as KOH, NaOCH<sub>3<\/sub>, or KO<sup>t<\/sup>Bu.<\/li>\r\n \t<li>Zaitsev\u2019s Rule is followed, unless a sterically hindered base such as KO<sup>t<\/sup>Bu is used.<\/li>\r\n \t<li>Works well with all types of alkyl halide<\/li>\r\n<\/ul>\r\n<img class=\"wp-image-5137 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/24043826\/E2EliminationExamples.png\" alt=\"Primary, secondary and tertiary alkyl halides react with strong bases to produce alkenes\" width=\"640\" height=\"246\" \/>\r\n<h2>K. Formation of alkenes from alcohols via dehydration (E1)<\/h2>\r\n<a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-9-applications-of-eliminations\/\">See section 9.9.<\/a>\r\n<ul>\r\n \t<li>Uses an acid (H<sub>2<\/sub>SO<sub>4<\/sub> or H<sub>3<\/sub>PO<sub>4<\/sub>) to protonate the OH and make it a good leaving group.<\/li>\r\n \t<li>Obeys Zaitsev\u2019s Rule.<\/li>\r\n \t<li>Works best with 3<sup>o<\/sup> and 2<sup>o<\/sup> but 1<sup>o<\/sup> will often work too.<\/li>\r\n<\/ul>\r\n<img class=\"wp-image-5136 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/24043356\/E1EliminationAlcoholDehydration.png\" alt=\"secondary and tertiary alcohols are heated with H2SO4 to produce Zaitsev alkenes\" width=\"612\" height=\"163\" \/>\r\n\r\n&nbsp;\r\n<h1>Appendix 1.4. Electrophilic additions to alkenes<\/h1>\r\n<h2>Overview<\/h2>\r\n<div>Four main types of additions of electrophiles to alkenes<\/div>\r\n<div>(a) Simple addition (seen with addition of H\u2013X and H3O+)<\/div>\r\n<div>(b) Additions that go via cyclic intermediates (addition of carbenes, halogens X2, oxymercuration, epoxidation (MCPBA)<\/div>\r\n<div>(c) Net anti\u2013Markovnikov additions<\/div>\r\n<div>(d) Radical\u2013type mechanisms (such as addition of H<sub>2<\/sub>, radical addition of HBr)<\/div>\r\n<h3>Markovnikov\u2019s Rule<\/h3>\r\n<div>When adding an electrophile to an alkene, it puts the electrophilic group (often an H) onto the less substituted carbon; the nucleophilic part (e.g., halogen or oxygen) goes onto the more substituted carbon.\u00a0 For example:<\/div>\r\n<h2>L. Addition of HCl or HBr to alkenes<\/h2>\r\n<a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-4-simple-addition-to-alkenes\/\">See section 10.4.<\/a>\r\n\r\nAddition obeys Markovnikov\u2019s Rule, and forms an alkyl halide with the halogen on the more substituted carbon.\r\n\r\n<img class=\"wp-image-5001 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/05130217\/AdditionOfHClToButene.png\" alt=\"HCl adds to but-1-ene to form 2-chlorobutane\" width=\"387\" height=\"83\" \/>\r\n<h2>M. Addition of H<sub>2<\/sub>O using H<sub>3<\/sub>O<sup>+<\/sup><\/h2>\r\n<a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-4-simple-addition-to-alkenes\/\">See section 10.4.<\/a>\r\n<ul>\r\n \t<li>H<sub>2<\/sub>O itself isn\u2019t electrophilic enough to add, but strong acids can add<\/li>\r\n \t<li>The reaction is usually done in two steps, with H<sub>2<\/sub>SO<sub>4<\/sub> followed by an H<sub>2<\/sub>O quench<\/li>\r\n<\/ul>\r\n<img class=\"wp-image-5003 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/05175539\/AcidHydrationOfMethylcyclohexene.png\" alt=\"1-Methylcyclohexene reacts with water and acid to form 1-methylcyclohexanol\" width=\"343\" height=\"92\" \/>\r\n<h2>N. Addition of carbenes: Making cyclopropanes<\/h2>\r\n<a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-7-additions-involving-cyclic-intermediates-2\/\">See section 10.7.<\/a>\r\n<ul>\r\n \t<li>Carbenes are made from diazo compounds such as diazomethane, by loss of N<sub>2<\/sub> using light.<\/li>\r\n \t<li>Reaction produces a new three-membered ring<\/li>\r\n<\/ul>\r\n<div><img class=\"wp-image-5004 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/06021407\/CarbeneFormation.png\" alt=\"CH2N2 decomposes in light to form the carbene :CH2\" width=\"391\" height=\"75\" \/><\/div>\r\n<div><img class=\"wp-image-5005 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/06022050\/CarbeneAddition.png\" alt=\"Reaction of :CH2 with cis-but-2-ene to form cis-1,2-dimethylcyclopropane\" width=\"519\" height=\"102\" \/><\/div>\r\n<div><\/div>\r\n<h2>O. Addition of Cl<sub>2<\/sub> or Br<sub>2<\/sub><\/h2>\r\n<a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-7-additions-involving-cyclic-intermediates-2\/\">See section 10.7.<\/a>\r\n<div>\r\n<ul>\r\n \t<li>Initial syn-addition forms a chloronium or bromonium ion with a three-membered ring.<\/li>\r\n \t<li>The halide ion present immediately does S<sub>N<\/sub>2 back-side attack to gives the product an anti-dihalide<\/li>\r\n<\/ul>\r\n<\/div>\r\n<div><img class=\"wp-image-5008 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/06024209\/Alkene-bromine-addition-2D-skeletal.png\" alt=\"Mechanism for addition of bromine to an alkene, showing the bromonium ion intermediate\" width=\"413\" height=\"134\" \/><\/div>\r\n<div><\/div>\r\n<h2>P. Epoxidation<\/h2>\r\n<a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-7-additions-involving-cyclic-intermediates-2\/\">See section 10.7.<\/a>\r\n<div>\r\n<ul>\r\n \t<li>Use MCPBA with the alkene<\/li>\r\n \t<li>Product is the <em>syn<\/em>-epoxide (oxirane) which contains a three-membered ring ether.<\/li>\r\n \t<li>Mechanism involves only a single step.<\/li>\r\n<\/ul>\r\n<\/div>\r\n<div><img class=\"wp-image-5139 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/24044822\/CyclohexeneEpoxidation.png\" alt=\"Cyclohexene reacts with MCPBA to produce epoxycyclohexane\" width=\"372\" height=\"89\" \/><\/div>\r\n<h2>Q. Oxymercuration-demercuration<\/h2>\r\n<div>See <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-7-additions-involving-cyclic-intermediates-2\/\">section 10.7.<\/a><\/div>\r\n<div>\r\n<ul>\r\n \t<li>This reaction gives the same alcohol product as with hydration, but the addition is exclusively <em>anti<\/em>.<\/li>\r\n \t<li>Obeys Markovnikov's Rule - OH goes on the more substituted carbon.<\/li>\r\n \t<li>Mechanism involves a three-membered ring mercurinium ion intermediate.<\/li>\r\n<\/ul>\r\n<\/div>\r\n<div><img class=\"wp-image-5013 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/06045142\/OxymercurationOf12Dimethylcyclohexene.png\" alt=\"Hydration of 1,2-dimethylcyclohexene using Hg(OAc)2 to give the anti alcohol\" width=\"412\" height=\"108\" \/><\/div>\r\n<h2>R. Anti-Markovnikov addition of water<\/h2>\r\n<div>See <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-8-anti-markovnikov-additions-to-alkenes-and-alkynes\/\">section 10.8.<\/a><\/div>\r\n<div><\/div>\r\n<div>\r\n<div>Use hydroboration-oxidation to form an alcohol on the<strong> less<\/strong> substituted carbon<\/div>\r\n<\/div>\r\n<div><\/div>\r\n<div><img class=\"wp-image-5015 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/06050045\/HydroborationOxidationOfIsobutylene.png\" alt=\"Hydroboration of isobutylene, followed by oxidation with alkaline hydrogen peroxide, to give an anti-Markovnikov alcohol\" width=\"544\" height=\"85\" \/><\/div>\r\n<div><\/div>\r\n<h2>S. Anti-Markovnikov addition of HBr<\/h2>\r\n<div>Compare with reaction L.\u00a0 <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-8-anti-markovnikov-additions-to-alkenes-and-alkynes\/\">See section 10.8.<\/a> In the presence of an organic peroxide (ROOR) and heat, a radical addition mechanism takes over and the Br ends up on the less substituted carbon.<\/div>\r\n<div><\/div>\r\n<div><img class=\"wp-image-5016 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/06051109\/AntiMvHBrAddition.png\" alt=\"HBr\/ROOR\/heat causes anti-Markovnikov addition of HBr to propene to give 1-bromopropane\" width=\"461\" height=\"75\" \/><\/div>\r\n<div>\r\n<h1>Appendix 1.5. Electrophilic additions to alkynes<\/h1>\r\nAlkynes do many of the same reactions as alkenes.\u00a0 However, we will just focus on three main ones.\r\n<h2>T. Addition of HCl, HBr or HI<\/h2>\r\nCompare with reaction L above.\u00a0 See <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-5-simple-addition-to-alkynes\/\">section 10.5.<\/a>\r\n<ul>\r\n \t<li>The reaction follows Markovnikov\u2019s Rule.<\/li>\r\n \t<li>\r\n<div>It can be done with either one or two moles of HX per mole of alkyne, to give different products.<\/div><\/li>\r\n \t<li>\r\n<div>When one mole HX is added to an internal alkyne, the product is mainly anti (with Z double bond).<\/div><\/li>\r\n \t<li>\r\n<div>If two HX are added, the X atoms both end up on the same (more substituted) carbon.<\/div><\/li>\r\n<\/ul>\r\n<\/div>\r\n<img class=\"wp-image-5019 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/06133141\/AlkyneHBrAddition.png\" alt=\"Addition of 1 HBr and 2 HBr to but-t-yne\" width=\"497\" height=\"123\" \/>\r\n<h2>U. Addition of water to alkynes<\/h2>\r\nCompare with reaction M above.\u00a0 See <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-5-simple-addition-to-alkynes\/\">section 10.5.<\/a>\r\n<ul>\r\n \t<li>Markovnikov's Rule applies.<\/li>\r\n \t<li>As with alkenes, an acid catalyst is needed.\u00a0 Internal alkynes can add water under similar conditions to alkenes \u2013 H<sub>2<\/sub>SO<sub>4<\/sub>\/H<sub>2<\/sub>O.<\/li>\r\n \t<li>Terminal alkynes require a mercury(II) catalyst, usually HgSO<sub>4<\/sub>.\u00a0 Unlike oxymercuration, NaBH<sub>4<\/sub> is not needed for forming the product.<\/li>\r\n \t<li>Although an enol is initially formed, this rearranges easily to give a ketone as the isolated product.<\/li>\r\n<\/ul>\r\n<div><\/div>\r\n<div><img class=\"wp-image-5023 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/07015802\/AlkyneMvHydration.png\" alt=\"But-2-yne adds H2O in presence of H2SO4; but-1-yne also does this but also needs HgSO4 catalyst\" width=\"326\" height=\"153\" \/><\/div>\r\n<h2>V. Anti-Markovnikov addition of H<sub>2<\/sub>O to alkynes<\/h2>\r\n<div>See <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-8-anti-markovnikov-additions-to-alkenes-and-alkynes\/\">section 10.8.<\/a>, and compare with reaction U above.<\/div>\r\n<div>\r\n<ul>\r\n \t<li>With alkenes, hydroboration-oxidation using BH<sub>3<\/sub>.THF produces net anti-Markovnikov hydration; with alkynes, a sterically hindered derivative of BH<sub>3<\/sub> is used, such as dicyclohexylborane (Cy<sub>2<\/sub>BH) or disiamylborane (Sia<sub>2<\/sub>BH).<\/li>\r\n \t<li>Internal alkynes produce ketones, similar to those formed using H<sub>2<\/sub>O\/H<sub>2<\/sub>SO<sub>4<\/sub>, but terminal alkynes produce aldehydes.<\/li>\r\n \t<li>As with H<sub>2<\/sub>O\/H<sub>2<\/sub>SO<sub>4<\/sub>\/HgSO<sub>4<\/sub>, the initial product is an enol, which then rearranges to the aldehyde or ketone.<\/li>\r\n<\/ul>\r\n<img class=\"wp-image-5032 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/07051712\/But1yneAntiMvHydration.png\" alt=\"Hydroboration-oxidation of but-1-yne to produce butanal\" width=\"291\" height=\"94\" \/>\r\n\r\n<\/div>","rendered":"<p>This appendix lists most, but not all, reactions covered in this textbook (part 1 only).\u00a0 The focus is on reactions that are most useful in synthesis.<\/p>\n<h1>Appendix 1.1. Nucleophilic substitutions with alkyl halides<\/h1>\n<h2>Overview<\/h2>\n<p>Most nucleophilic substitutions used in synthesis go via an S<sub>N<\/sub>2 mechanism.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4957 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01052516\/GenericSN2.png\" alt=\"A generic example of an SN2 reaction\" width=\"520\" height=\"48\" \/><\/p>\n<ul>\n<li>S<sub>N<\/sub>2 reactions work best with R\u2013X as an alkyl halide or sulfonate. Epoxides also work well for more complex targets.<\/li>\n<li>Best with 1<sup>o<\/sup> alkyl, OK with 2<sup>o<\/sup>, fails with 3<sup>o<\/sup> and aryl<\/li>\n<li>Works well with I, Br, OK with Cl, fails with F.<\/li>\n<li>It requires a strong nucleophile, which usually means one bearing a negative charge such as \u00afOH .<\/li>\n<li>Works well in polar aprotic solvents such as DMSO.<\/li>\n<\/ul>\n<h2>A. Formation of alkyl halides<\/h2>\n<p>See <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-3-preparation-of-alkyl-halides-related-rx\/\">section 9.3.<\/a>\u00a0 Most S<sub>N<\/sub>2 reactions utilize alkyl halides, so you need to know how to make them!\u00a0 The most common route is from the corresponding alcohol, using PX<sub>3<\/sub>.\u00a0 I recommend using alkyl bromides in synthesis, and these are made using PBr<sub>3<\/sub>.<\/p>\n<ul>\n<li>Use PX<sub>3<\/sub> (X = Cl, Br, I) to convert primary and secondary ROH to RX<\/li>\n<li>SOCl<sub>2<\/sub> also good for ROH to RCl<\/li>\n<li>Mechanism involves activation of OH by PX<sub>3<\/sub> to make it a good leaving group, then S<sub>N<\/sub>2 attack by X\u00af.<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4960 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01055354\/GenericPX3reaction.png\" alt=\"Reaction of a generic alcohol with PX3 to produce an alkyl halide\" width=\"285\" height=\"66\" \/><\/p>\n<p>For example, (2<em>R<\/em>)-butan-2-ol reacts with PBr<sub>3<\/sub> produces (<em>2S<\/em>)-2-bromobutane with inversion; note that all three bromines can be delivered.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4965 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01062504\/PreparationOf2Bromobutane.png\" alt=\"\" width=\"591\" height=\"78\" \/><\/p>\n<p>For preparation of tertiary alkyl chlorides and bromides from the corresponding alcohols, HCl or HBr is the most effective reagent.<\/p>\n<h2>B. Formation of alcohols<\/h2>\n<p>This is synthetically the reverse of the PBr<sub>3<\/sub> reaction.\u00a0 Here, the nucleophile is hydroxide ion (\u00afOH).\u00a0 As always with anions, it\u00a0 has to have a cation with it, usually sodium or potassium.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4972 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01145001\/GenericROHprep.png\" alt=\"RBr reacts with OH- to give ROH\" width=\"497\" height=\"47\" \/><\/p>\n<p>For example:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-4971 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01144950\/Butan1olPrep.png\" alt=\"BuBr reacts with KOH to give BuOH\" width=\"476\" height=\"65\" \/><\/p>\n<h2>C. Formation of amines<\/h2>\n<p>See <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-4-reaction-of-rx-with-nh3-and-amines\/\">section 9.4.<\/a><\/p>\n<ul>\n<li>NH<sub>3<\/sub>, R\u2019NH<sub>2<\/sub> and R\u2019<sub>2<\/sub>NH are strong enough to react with R\u2013X, to produce products containing a new R\u2013N bond.<\/li>\n<li>An excess of the NH<sub>3<\/sub> or amine reactant is needed to suppress the reaction of the product with a second mole of R\u2013X.<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4969 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01143126\/AminePrepViaExcessNH3.png\" alt=\"RBr reacts with large XS of NH3 to make RNH2\" width=\"437\" height=\"78\" \/><\/p>\n<p>There are also indirect methods for preparing amines, which avoid the need for a large excess of amine.\u00a0 One of the most popular uses azide (N<sub>3<\/sub><sup>\u2013<\/sup>) as nucleophile, followed by reduction to the amine.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4968 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01143121\/AminePrepViaAzide.png\" alt=\"RBr reacts with NaN3 to produce RN3, which is then reduced to RNH2 using LiAlH4\" width=\"660\" height=\"83\" \/><\/p>\n<h2>D. Williamson ether synthesis<\/h2>\n<div style=\"text-align: left\"><a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-5-williamson-ether-synthesis\/\">See section 9.5.<\/a> This is the most important way to make an ether group.\u00a0 The nucleophile is an alkoxide (the conjugate base of an alcohol).\u00a0 Often this has to be made from the alcohol using NaH.<\/div>\n<div><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-4974\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/01154007\/GenericWilliamsonEther.png\" alt=\"Reaction of an alkoxide with an alkyl halide to form an ether\" width=\"802\" height=\"124\" \/><\/div>\n<div><\/div>\n<div>In the synthesis of ethers containing a tertiary alkyl group, the tertiary group should be in the alkoxide to ensure a good S<sub>N<\/sub>2 reaction &#8211; see example below.<\/div>\n<div><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-4977\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/02033523\/WilliamsonEtherExample.png\" alt=\"Two alternatives for Williamson ether synthesis of a tert-butyl ether - good and bad.\" width=\"634\" height=\"240\" \/><\/div>\n<div><\/div>\n<h2>E. Enolate alkylation<\/h2>\n<p><a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-7-enolate-alkylation\/\">See section 9.7.<\/a><\/p>\n<div>\n<ul>\n<li>The enolate nucleophile is usually the conjugate base of a ketone or ester.<\/li>\n<li>As with the Williamson ether synthesis, the nucleophile has to be made from the ketone or ester with a strong base, usually LDA.\u00a0 (NaH sometimes works, but LDA is usually better.).\u00a0 At -78 <sup>o<\/sup>C, LDA forms the less substituted enolate.<\/li>\n<li>This reaction makes a new C\u2013C bond \u2013 often important in synthesis.\u00a0 The reaction works well with primary alkyl bromides or iodides, and moderately with secondary, and fails completely with tertiary alkyl bromides or iodides.<\/li>\n<\/ul>\n<\/div>\n<h2><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4978 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/02034702\/GenericEnolateAlkylation.png\" alt=\"Generic formation of an enolate using LDA, followed by alkylation using RX\" width=\"716\" height=\"195\" \/><\/h2>\n<h2>F. Alkyne\/Acetylide alkylation<\/h2>\n<p>See <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-8-substitution-with-acetylides\/\">section 9.8<\/a>.<\/p>\n<ul>\n<li>The nucleophile is the conjugate base of an alkyne, called an acetylide.<\/li>\n<li>Similar to D and E above, the nucleophile has to be made from the alkyne and a strong base, usually NaH or BuLi, though LDA also works.<\/li>\n<li>As with E above, this makes a new C\u2013C bond.<\/li>\n<li>Reaction only works well with 1<sup>o<\/sup> R\u2013X, since the acetylide is a strong base too.<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4982 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/03035705\/GenericAcetylideAlkylation.png\" alt=\"Formation of an acetylide using NaH, followed by SN2 reaction with an alkyl halide\" width=\"663\" height=\"143\" \/><\/p>\n<h2>G. Reduction of R\u2013X with LiAlH<sub>4<\/sub><\/h2>\n<ul>\n<li>LiAlH<sub>4<\/sub> is a strong reducing agent, which in effect delivers hydride ion, H\u00af.\u00a0 (Hydride ion itself is too small to react well in a direct S<sub>N<\/sub>2).<\/li>\n<li>Reaction only works well with 1<sup>o<\/sup> R\u2013X.<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-4986\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/04032529\/GenericRXreductionwithLAH.png\" alt=\"RX reacts with LiAlH4 to produce RH\" width=\"262\" height=\"63\" \/><\/p>\n<h1>Appendix 1.2. Nucleophilic substitutions with Epoxides<\/h1>\n<h2>H. Reaction of epoxides with strong nucleophiles<\/h2>\n<ul>\n<li>Epoxides are strained 3-membered ring ethers that open very easily with strong nucleophiles, giving alcohols with the former nucleophile attached to the neighboring (less substituted) carbon.<\/li>\n<li>The mechanism is S<sub>N<\/sub>2, with the leaving being the O\u00af rather than a halide.<\/li>\n<li>Any of the above strong nucleophiles (NH<sub>3<\/sub>, R\u2019NH<sub>2<\/sub>, R\u2019<sub>2<\/sub>NH, \u00afOH, \u00afOR\u2019,\u00a0 enolates, acetylides, LiAlH<sub>4<\/sub>, will attack epoxides at the <strong>less substituted carbon<\/strong>.\u00a0 For example:<\/li>\n<\/ul>\n<div><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4989 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/05033616\/EpoxideRingOpeningByMethoxide.png\" alt=\"Reaction of an epoxide with methoxide ion showing attack at the less substituted position\" width=\"487\" height=\"104\" \/><\/div>\n<div>\n<h2>I. Reaction of epoxides with weak nucleophiles<\/h2>\n<ul>\n<li>Epoxides do not open with weak nucleophiles, unless the epoxide is activated first with an acid such as H<sub>2<\/sub>SO<sub>4<\/sub>.<\/li>\n<li>The product is an alcohol on the less substituted carbon, with the former nucleophile attached to the neighboring (more substituted) carbon.<\/li>\n<li>Even at a tertiary center, the mechanism is S<sub>N<\/sub>2, with the leaving group being the OH rather than a halide.<\/li>\n<li>Any weak nucleophiles (H<sub>2<\/sub>O, ROH, Cl\u00af) will attack epoxides at the <strong>more substituted<\/strong> carbon, since this is the more electrophilic carbon.\u00a0 For example:<\/li>\n<\/ul>\n<\/div>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4992 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/05035737\/EpoxideRingOpeningByAcidicMethanol.png\" alt=\"\" width=\"504\" height=\"96\" \/><\/p>\n<h1>Appendix 1.3. Elimination reactions<\/h1>\n<h2>Overview<\/h2>\n<ul>\n<li>There are two main mechanisms \u2013 E2 and E1.<\/li>\n<li>E2 reactions make alkenes from alkyl halides and strong base<\/li>\n<li>E1 reactions are usually used to make alkenes from an alcohol and catalytic acid (H<sub>2<\/sub>SO<sub>4<\/sub> or H<sub>3<\/sub>PO<sub>4<\/sub>).<\/li>\n<li>E2 is usually better for synthesis, to avoid rearrangements, but alcohol dehydration often works OK.<\/li>\n<li>Both types of reaction usually obey Zaitsev\u2019s rule \u2013 the most substituted\/conjugated alkene is the major product.<\/li>\n<li>All elimination reactions are favored by heat.<\/li>\n<\/ul>\n<h2>J. Formation of alkenes from alkyl halides (E2)<\/h2>\n<p><a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-9-applications-of-eliminations\/\">See section 9.9.<\/a><\/p>\n<ul>\n<li>A strong base is needed, such as KOH, NaOCH<sub>3<\/sub>, or KO<sup>t<\/sup>Bu.<\/li>\n<li>Zaitsev\u2019s Rule is followed, unless a sterically hindered base such as KO<sup>t<\/sup>Bu is used.<\/li>\n<li>Works well with all types of alkyl halide<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-5137 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/24043826\/E2EliminationExamples.png\" alt=\"Primary, secondary and tertiary alkyl halides react with strong bases to produce alkenes\" width=\"640\" height=\"246\" \/><\/p>\n<h2>K. Formation of alkenes from alcohols via dehydration (E1)<\/h2>\n<p><a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-9-applications-of-eliminations\/\">See section 9.9.<\/a><\/p>\n<ul>\n<li>Uses an acid (H<sub>2<\/sub>SO<sub>4<\/sub> or H<sub>3<\/sub>PO<sub>4<\/sub>) to protonate the OH and make it a good leaving group.<\/li>\n<li>Obeys Zaitsev\u2019s Rule.<\/li>\n<li>Works best with 3<sup>o<\/sup> and 2<sup>o<\/sup> but 1<sup>o<\/sup> will often work too.<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-5136 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/24043356\/E1EliminationAlcoholDehydration.png\" alt=\"secondary and tertiary alcohols are heated with H2SO4 to produce Zaitsev alkenes\" width=\"612\" height=\"163\" \/><\/p>\n<p>&nbsp;<\/p>\n<h1>Appendix 1.4. Electrophilic additions to alkenes<\/h1>\n<h2>Overview<\/h2>\n<div>Four main types of additions of electrophiles to alkenes<\/div>\n<div>(a) Simple addition (seen with addition of H\u2013X and H3O+)<\/div>\n<div>(b) Additions that go via cyclic intermediates (addition of carbenes, halogens X2, oxymercuration, epoxidation (MCPBA)<\/div>\n<div>(c) Net anti\u2013Markovnikov additions<\/div>\n<div>(d) Radical\u2013type mechanisms (such as addition of H<sub>2<\/sub>, radical addition of HBr)<\/div>\n<h3>Markovnikov\u2019s Rule<\/h3>\n<div>When adding an electrophile to an alkene, it puts the electrophilic group (often an H) onto the less substituted carbon; the nucleophilic part (e.g., halogen or oxygen) goes onto the more substituted carbon.\u00a0 For example:<\/div>\n<h2>L. Addition of HCl or HBr to alkenes<\/h2>\n<p><a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-4-simple-addition-to-alkenes\/\">See section 10.4.<\/a><\/p>\n<p>Addition obeys Markovnikov\u2019s Rule, and forms an alkyl halide with the halogen on the more substituted carbon.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-5001 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/05130217\/AdditionOfHClToButene.png\" alt=\"HCl adds to but-1-ene to form 2-chlorobutane\" width=\"387\" height=\"83\" \/><\/p>\n<h2>M. Addition of H<sub>2<\/sub>O using H<sub>3<\/sub>O<sup>+<\/sup><\/h2>\n<p><a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-4-simple-addition-to-alkenes\/\">See section 10.4.<\/a><\/p>\n<ul>\n<li>H<sub>2<\/sub>O itself isn\u2019t electrophilic enough to add, but strong acids can add<\/li>\n<li>The reaction is usually done in two steps, with H<sub>2<\/sub>SO<sub>4<\/sub> followed by an H<sub>2<\/sub>O quench<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-5003 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/05175539\/AcidHydrationOfMethylcyclohexene.png\" alt=\"1-Methylcyclohexene reacts with water and acid to form 1-methylcyclohexanol\" width=\"343\" height=\"92\" \/><\/p>\n<h2>N. Addition of carbenes: Making cyclopropanes<\/h2>\n<p><a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-7-additions-involving-cyclic-intermediates-2\/\">See section 10.7.<\/a><\/p>\n<ul>\n<li>Carbenes are made from diazo compounds such as diazomethane, by loss of N<sub>2<\/sub> using light.<\/li>\n<li>Reaction produces a new three-membered ring<\/li>\n<\/ul>\n<div><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-5004 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/06021407\/CarbeneFormation.png\" alt=\"CH2N2 decomposes in light to form the carbene :CH2\" width=\"391\" height=\"75\" \/><\/div>\n<div><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-5005 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/06022050\/CarbeneAddition.png\" alt=\"Reaction of :CH2 with cis-but-2-ene to form cis-1,2-dimethylcyclopropane\" width=\"519\" height=\"102\" \/><\/div>\n<div><\/div>\n<h2>O. Addition of Cl<sub>2<\/sub> or Br<sub>2<\/sub><\/h2>\n<p><a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-7-additions-involving-cyclic-intermediates-2\/\">See section 10.7.<\/a><\/p>\n<div>\n<ul>\n<li>Initial syn-addition forms a chloronium or bromonium ion with a three-membered ring.<\/li>\n<li>The halide ion present immediately does S<sub>N<\/sub>2 back-side attack to gives the product an anti-dihalide<\/li>\n<\/ul>\n<\/div>\n<div><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-5008 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/06024209\/Alkene-bromine-addition-2D-skeletal.png\" alt=\"Mechanism for addition of bromine to an alkene, showing the bromonium ion intermediate\" width=\"413\" height=\"134\" \/><\/div>\n<div><\/div>\n<h2>P. Epoxidation<\/h2>\n<p><a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-7-additions-involving-cyclic-intermediates-2\/\">See section 10.7.<\/a><\/p>\n<div>\n<ul>\n<li>Use MCPBA with the alkene<\/li>\n<li>Product is the <em>syn<\/em>-epoxide (oxirane) which contains a three-membered ring ether.<\/li>\n<li>Mechanism involves only a single step.<\/li>\n<\/ul>\n<\/div>\n<div><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-5139 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/24044822\/CyclohexeneEpoxidation.png\" alt=\"Cyclohexene reacts with MCPBA to produce epoxycyclohexane\" width=\"372\" height=\"89\" \/><\/div>\n<h2>Q. Oxymercuration-demercuration<\/h2>\n<div>See <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-7-additions-involving-cyclic-intermediates-2\/\">section 10.7.<\/a><\/div>\n<div>\n<ul>\n<li>This reaction gives the same alcohol product as with hydration, but the addition is exclusively <em>anti<\/em>.<\/li>\n<li>Obeys Markovnikov&#8217;s Rule &#8211; OH goes on the more substituted carbon.<\/li>\n<li>Mechanism involves a three-membered ring mercurinium ion intermediate.<\/li>\n<\/ul>\n<\/div>\n<div><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-5013 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/06045142\/OxymercurationOf12Dimethylcyclohexene.png\" alt=\"Hydration of 1,2-dimethylcyclohexene using Hg(OAc)2 to give the anti alcohol\" width=\"412\" height=\"108\" \/><\/div>\n<h2>R. Anti-Markovnikov addition of water<\/h2>\n<div>See <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-8-anti-markovnikov-additions-to-alkenes-and-alkynes\/\">section 10.8.<\/a><\/div>\n<div><\/div>\n<div>\n<div>Use hydroboration-oxidation to form an alcohol on the<strong> less<\/strong> substituted carbon<\/div>\n<\/div>\n<div><\/div>\n<div><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-5015 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/06050045\/HydroborationOxidationOfIsobutylene.png\" alt=\"Hydroboration of isobutylene, followed by oxidation with alkaline hydrogen peroxide, to give an anti-Markovnikov alcohol\" width=\"544\" height=\"85\" \/><\/div>\n<div><\/div>\n<h2>S. Anti-Markovnikov addition of HBr<\/h2>\n<div>Compare with reaction L.\u00a0 <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-8-anti-markovnikov-additions-to-alkenes-and-alkynes\/\">See section 10.8.<\/a> In the presence of an organic peroxide (ROOR) and heat, a radical addition mechanism takes over and the Br ends up on the less substituted carbon.<\/div>\n<div><\/div>\n<div><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-5016 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/06051109\/AntiMvHBrAddition.png\" alt=\"HBr\/ROOR\/heat causes anti-Markovnikov addition of HBr to propene to give 1-bromopropane\" width=\"461\" height=\"75\" \/><\/div>\n<div>\n<h1>Appendix 1.5. Electrophilic additions to alkynes<\/h1>\n<p>Alkynes do many of the same reactions as alkenes.\u00a0 However, we will just focus on three main ones.<\/p>\n<h2>T. Addition of HCl, HBr or HI<\/h2>\n<p>Compare with reaction L above.\u00a0 See <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-5-simple-addition-to-alkynes\/\">section 10.5.<\/a><\/p>\n<ul>\n<li>The reaction follows Markovnikov\u2019s Rule.<\/li>\n<li>\n<div>It can be done with either one or two moles of HX per mole of alkyne, to give different products.<\/div>\n<\/li>\n<li>\n<div>When one mole HX is added to an internal alkyne, the product is mainly anti (with Z double bond).<\/div>\n<\/li>\n<li>\n<div>If two HX are added, the X atoms both end up on the same (more substituted) carbon.<\/div>\n<\/li>\n<\/ul>\n<\/div>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-5019 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/06133141\/AlkyneHBrAddition.png\" alt=\"Addition of 1 HBr and 2 HBr to but-t-yne\" width=\"497\" height=\"123\" \/><\/p>\n<h2>U. Addition of water to alkynes<\/h2>\n<p>Compare with reaction M above.\u00a0 See <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-5-simple-addition-to-alkynes\/\">section 10.5.<\/a><\/p>\n<ul>\n<li>Markovnikov&#8217;s Rule applies.<\/li>\n<li>As with alkenes, an acid catalyst is needed.\u00a0 Internal alkynes can add water under similar conditions to alkenes \u2013 H<sub>2<\/sub>SO<sub>4<\/sub>\/H<sub>2<\/sub>O.<\/li>\n<li>Terminal alkynes require a mercury(II) catalyst, usually HgSO<sub>4<\/sub>.\u00a0 Unlike oxymercuration, NaBH<sub>4<\/sub> is not needed for forming the product.<\/li>\n<li>Although an enol is initially formed, this rearranges easily to give a ketone as the isolated product.<\/li>\n<\/ul>\n<div><\/div>\n<div><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-5023 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/07015802\/AlkyneMvHydration.png\" alt=\"But-2-yne adds H2O in presence of H2SO4; but-1-yne also does this but also needs HgSO4 catalyst\" width=\"326\" height=\"153\" \/><\/div>\n<h2>V. Anti-Markovnikov addition of H<sub>2<\/sub>O to alkynes<\/h2>\n<div>See <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/10-8-anti-markovnikov-additions-to-alkenes-and-alkynes\/\">section 10.8.<\/a>, and compare with reaction U above.<\/div>\n<div>\n<ul>\n<li>With alkenes, hydroboration-oxidation using BH<sub>3<\/sub>.THF produces net anti-Markovnikov hydration; with alkynes, a sterically hindered derivative of BH<sub>3<\/sub> is used, such as dicyclohexylborane (Cy<sub>2<\/sub>BH) or disiamylborane (Sia<sub>2<\/sub>BH).<\/li>\n<li>Internal alkynes produce ketones, similar to those formed using H<sub>2<\/sub>O\/H<sub>2<\/sub>SO<sub>4<\/sub>, but terminal alkynes produce aldehydes.<\/li>\n<li>As with H<sub>2<\/sub>O\/H<sub>2<\/sub>SO<sub>4<\/sub>\/HgSO<sub>4<\/sub>, the initial product is an enol, which then rearranges to the aldehyde or ketone.<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-5032 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2020\/06\/07051712\/But1yneAntiMvHydration.png\" alt=\"Hydroboration-oxidation of but-1-yne to produce butanal\" width=\"291\" height=\"94\" \/><\/p>\n<\/div>\n\n\t\t\t <section class=\"citations-section\" role=\"contentinfo\">\n\t\t\t <h3>Candela Citations<\/h3>\n\t\t\t\t\t <div>\n\t\t\t\t\t\t <div id=\"citation-list-5150\">\n\t\t\t\t\t\t\t <div class=\"licensing\"><div class=\"license-attribution-dropdown-subheading\">CC licensed content, Original<\/div><ul class=\"citation-list\"><li><strong>Authored by<\/strong>: Martin A. Walker, Ph.D.. <strong>Provided by<\/strong>: SUNY Potsdam. <strong>Project<\/strong>: Organic Chemistry I. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by-sa\/4.0\/\">CC BY-SA: Attribution-ShareAlike<\/a><\/em><\/li><\/ul><\/div>\n\t\t\t\t\t\t <\/div>\n\t\t\t\t\t <\/div>\n\t\t\t <\/section>","protected":false},"author":89971,"menu_order":1,"template":"","meta":{"_candela_citation":"[{\"type\":\"original\",\"description\":\"\",\"author\":\"Martin A. Walker, Ph.D.\",\"organization\":\"SUNY Potsdam\",\"url\":\"\",\"project\":\"Organic Chemistry I\",\"license\":\"cc-by-sa\",\"license_terms\":\"\"}]","CANDELA_OUTCOMES_GUID":"","pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":[],"pb_section_license":""},"back-matter-type":[],"contributor":[],"license":[],"class_list":["post-5150","back-matter","type-back-matter","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/pressbooks\/v2\/back-matter\/5150","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/pressbooks\/v2\/back-matter"}],"about":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/wp\/v2\/types\/back-matter"}],"author":[{"embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/wp\/v2\/users\/89971"}],"version-history":[{"count":2,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/pressbooks\/v2\/back-matter\/5150\/revisions"}],"predecessor-version":[{"id":5152,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/pressbooks\/v2\/back-matter\/5150\/revisions\/5152"}],"metadata":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/pressbooks\/v2\/back-matter\/5150\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/wp\/v2\/media?parent=5150"}],"wp:term":[{"taxonomy":"back-matter-type","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/pressbooks\/v2\/back-matter-type?post=5150"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/wp\/v2\/contributor?post=5150"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/wp\/v2\/license?post=5150"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}