{"id":7871,"date":"2014-01-10T14:35:13","date_gmt":"2014-01-10T19:35:13","guid":{"rendered":"https:\/\/www.masterorganicchemistry.com\/?p=7871"},"modified":"2025-07-03T05:51:48","modified_gmt":"2025-07-03T10:51:48","slug":"reactions-of-alkyl-halides","status":"publish","type":"post","link":"https:\/\/www.masterorganicchemistry.com\/2014\/01\/10\/reactions-of-alkyl-halides\/","title":{"rendered":"Alkyl Halide Reaction Map And Summary"},"content":{"rendered":"

Alkyl Halide Reaction Map<\/strong><\/p>\n

In the last post, we began our discussion of synthesis by starting with the reactions of alkanes<\/strong><\/a>. Since we’ve learned only one important class of alkane reactions so far (free-radical halogenation), our “reaction map” was very small.<\/strong><\/p>\n

Table of Contents<\/strong><\/p>\n

    \n
  1. Key Transformations of Alkyl Halides<\/a><\/li>\n
  2. Substitution Reactions of Alkyl Halides: Why The SN<\/sub>2 Is Powerful<\/a><\/li>\n
  3. What About The SN<\/sub>1?<\/a><\/li>\n
  4. Alkyl Halides To Alkenes: Elimination Reactions<\/a><\/li>\n
  5. The Alkyl Halide Reaction Map<\/a><\/li>\n
  6. Notes<\/a><\/li>\n
  7. Quiz Yourself!\u00a0<\/a><\/li>\n<\/ol>\n
    \n

    <\/a>1. Key Transformations Of Alkyl Halides<\/h2>\n

    Today we will visit the reactions of a much more synthetically versatile functional group: alkyl halides. Using our analogy to airports, if alkanes can be compared to Bozeman, Montana (not exactly a hub), alkyl halides are more like Denver or ORD<\/strong>. There are many connecting flights!<\/p>\n

    Here are some of the reactions of alkyl halides we have covered so far, divided by the type of alkyl halide [primary, secondary, and tertiary]. Note that we are excluding alkyl fluorides here, as fluoride is not a good enough leaving group for our purposes.<\/p>\n

    \"four<\/p>\n

    <\/a>2. Substitution Reactions Are Extremely Useful For Transforming Alkyl Halides Into A Wide Variety Of Functional Groups<\/b><\/h2>\n

    The SN<\/sub>2 is an extremely versatile reaction<\/a> from a synthetic standpoint.<\/p>\n

    Primary alkyl halides can be converted into a wide variety of functional groups – alcohols, ethers, thiols, azides – the list goes on.<\/p>\n

    Secondary alkyl halides can be used as well, although one has to be careful about competition with elimination reactions if<\/strong> the nucleophile is too basic [a good rule of thumb: species with a pKa<\/sub> higher than 12<\/strong><\/a> will have a strong enough conjugate base to possibly produce E2 products along with SN<\/sub>2 products – that means you will need to pay close attention to the conditions you choose. Low temperature and polar aprotic solvents will tend to favor SN<\/sub>2 over E2. ].<\/em><\/span><\/p>\n

    In particular, on the diagram shown below, “strong” bases include hydroxide “HO-“, alkoxide “RO-” and “acetylide” (deprotonated alkyne), although other strong bases [such as NH2<\/sub>\u2013<\/sup>] fall into the same category. One prominent exception in many courses is the “bulky” base tert-butoxide [(CH3<\/sub>)3<\/sub>CO-] which generally favors elimination over substitution<\/a>, even on primary alkyl halides.<\/p>\n

    \"sn2<\/p>\n

    <\/a>3. What about the SN<\/sub>1?\u00a0<\/strong><\/h2>\n

    The most useful application of SN<\/sub>1 reactions in synthesis is in “solvolysis” reactions<\/strong>, where the alkyl halide is dissolved in a nucleophilic solvent such as water or an alcohol. This works best for tertiary alkyl halides.<\/strong>\u00a0 The resulting products are either alcohols<\/strong> (in the case of water as solvent) or ethers<\/strong> (when an alcohol is used as a solvent). If you care about preserving stereochemistry [at this stage, you probably don’t] don’t forget that since the SN<\/sub>1 proceeds through a [flat] carbocation<\/a>, chiral alkyl halides will form mixtures of stereoisomers.<\/p>\n

    For secondary alkyl halides, keep in mind that carbocations can be prone to rearrangements<\/a><\/strong> if a more stable carbocation can form through an alkyl or hydride shift. For this reason (as well as for preserving stereochemistry) it is generally best to avoid incorporating SN<\/sub>1 reactions of secondary alkyl halides into a synthesis unless you are really sure that no other competing products will form<\/strong>. Use SN<\/sub>2 conditions [strong nucleophile, polar aprotic solvent] instead.<\/p>\n

    \"sn1<\/p>\n

    <\/a>4. Alkyl Halides To Alkenes: Elimination Reactions<\/b><\/h2>\n

    Elimination reactions are very useful for producing alkenes from alkyl halides<\/strong>. Of the two pathways by which elimination can occur (E1 and E2) the E2 is greatly preferred from a synthetic standpoint<\/strong> since the products of the reaction are much more predictable, it works well with both secondary and tertiary alkyl halides, and is not accompanied by rearrangements.<\/p>\n

    There are always several things to keep in mind with the E2 reaction.<\/p>\n