{"id":5153,"date":"2020-06-29T12:34:49","date_gmt":"2020-06-29T12:34:49","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/?post_type=back-matter&p=5153"},"modified":"2020-06-29T12:35:24","modified_gmt":"2020-06-29T12:35:24","slug":"appendix-2","status":"publish","type":"back-matter","link":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/back-matter\/appendix-2\/","title":{"raw":"Appendix 2: Main Mechanisms","rendered":"Appendix 2: Main Mechanisms"},"content":{"raw":"

A. Nucleophilic substitution<\/h1>\r\nGeneral reaction:\r\n\r\n\"A\r\n\r\nwhere R is alkyl and X is usually a halogen or sulfonate; may sometimes be \u2013OH2<\/sub>+<\/sup> with alcohols.\r\n

SN<\/sub>2: With primary and secondary RX + strong nucleophile<\/h2>\r\nUsually a negatively charged<\/em> nucleophile such as I\u00af, \u00afOH, \u00afSH, \u00afOR, but uncharged nitrogen nucleophiles NH3<\/sub>\/RNH2<\/sub>\/R2<\/sub>NH also work.\r\n\r\nOne step only:\r\n\r\n\"Nuc\r\n\r\nFavored by:\r\n
    \r\n \t
  • Polar aprotic<\/em> solvents (e.g., DMSO, DMF, CH3CN, acetone)<\/li>\r\n \t
  • Cold temperatures reduce chances of E2 elimination<\/li>\r\n \t
  • Primary and secondary R only; simple tertiary R\u2013X never does SN<\/sub>2<\/li>\r\n \t
  • Resonance stabilization of the transition state can also speed up SN<\/sub>2.<\/li>\r\n<\/ul>\r\n \r\n

    SN<\/sub>1: With tertiary and secondary RX + weak nucleophile<\/h2>\r\nUsually an uncharged<\/em> nucleophile such as H2<\/sub>O, ROH, H2<\/sub>S, RSH, but nonbasic negative nucleophiles such as Cl\u00af, Br\u00af, I\u00af also work.\u00a0 With uncharged nucleophiles, there will be an acid\u2013base step at the end to lose H+ and give an uncharged final product.\r\n\r\nNote: If \u00afOH or \u00afOR are used instead, E2 elimination will dominate over SN<\/sub>1.\r\n\r\nTwo steps for substitution (heterolysis followed immediately by coordination), then an acid-base step.\r\n\r\n\"Shows\r\n\r\nFavored by:\r\n
      \r\n \t
    • Polar protic<\/em> solvents \u2013 often use the nucleophile as the solvent.<\/li>\r\n \t
    • Cold temperatures reduces chances of E1 elimination<\/li>\r\n \t
    • Tertiary & secondary R. Never primary unless resonance stabilizing R+<\/sup><\/li>\r\n<\/ul>\r\nExamples of nucleophilic substitution<\/strong>\r\n\r\nIn the SN<\/sub>2 example, note the primary alkyl group, the strong nucleophile (\u00afSCH3<\/sub>) and the polar aprotic solvent (DMF) \u2013 all point to SN<\/sub>2 as the mechanism.\r\n\r\n\"pentyl\r\n\r\nIn the SN<\/sub>1 example, note the resonance-stabilized secondary carbocation, and the weak nucleophile (water), which also serves as the polar protic solvent.\u00a0 R, Nuc and solvent all point to SN<\/sub>1 as the mechanism.\r\n\r\n\"1-chloro-1-phenylethane\r\n

      B. Elimination reactions<\/h1>\r\nGeneral reaction type:\r\n\r\n\"Generic\r\n
        \r\n \t
      • R can be H, alkyl or aryl \u2013 easiest with aryl, hardest with H, but all will do the reaction.<\/li>\r\n \t
      • For E2, X is a halogen or sulfonate<\/li>\r\n \t
      • For E1, X is a halogen, sulfonate or \u2013OH2<\/sub>+<\/sup> (protonated alcohol).<\/li>\r\n \t
      • Zaitsev\u2019s Rule applies in most cases, i.e., the most substituted\/conjugated alkene is formed the most.<\/li>\r\n \t
      • If R3<\/sup> and\/or R4<\/sup> contain hydrogens, then elimination may lead to other isomers with the double bond going into R3<\/sup> and\/or R4<\/sup>.<\/li>\r\n<\/ul>\r\n

        E2 elimination: RX + strong base<\/h2>\r\n\"Mechanism\r\n
          \r\n \t
        • Shown above with \u00afOH as base, but \u00afOR works similarly.<\/li>\r\n \t
        • Works with most alkyl halides, tertiary is easiest but others work fine.<\/li>\r\n \t
        • However, there must be an H anti<\/em> to the X on the neighboring carbon (Anti Rule).<\/li>\r\n \t
        • This anti constraint means that only one stereoisomer of the product is formed, alkene 1<\/strong>.<\/li>\r\n \t
        • Favored by heat.<\/li>\r\n \t
        • Zaitsev\u2019s Rule applies with most bases, unless they are sterically hindered (e.g., KOt<\/sup>Bu). Common bases include KOH (for \u00afOH), NaOCH3<\/sub>, NaOEt, KOt<\/sup>Bu and some amine bases.<\/li>\r\n<\/ul>\r\n

          E1 elimination: Tertiary RX + weak base, or ROH + acid<\/h2>\r\nE1 elimination of tertiary alkyl halides (X = Cl, Br, I) or sulfonates (e.g., X = OTs) involves just two steps:\r\n\r\n\"Mechanism\r\n
            \r\n \t
          • Only works well with tertiary or resonance-stabilized carbocation intermediates.<\/li>\r\n \t
          • Other products are possible, due to competing carbocation rearrangements.<\/li>\r\n \t
          • This reaction is less used in synthesis than E2, because E2 gives good yields, is more selective, and has fewer side reactions (such as rearrangements).<\/li>\r\n \t
          • Favored by heat.<\/li>\r\n \t
          • Zaitsev\u2019s Rule applies.<\/li>\r\n<\/ul>\r\nHowever, with E1 elimination of alcohols, an initial acid-base step is needed to turn the \u2013OH into \u2013OH2<\/sub>+<\/sup> so it can be a leaving group, as shown.\r\n\r\n\"Mechanism\r\n\r\nAll the above bullet points (from the alkyl halide E1) apply, but also:\r\n