{"id":12004,"date":"2018-11-26T06:00:42","date_gmt":"2018-11-26T11:00:42","guid":{"rendered":"https:\/\/www.masterorganicchemistry.com\/?p=12004"},"modified":"2026-05-07T10:55:29","modified_gmt":"2026-05-07T15:55:29","slug":"sulfonyl-blocking-groups-aromatic-synthesis","status":"publish","type":"post","link":"https:\/\/www.masterorganicchemistry.com\/2018\/11\/26\/sulfonyl-blocking-groups-aromatic-synthesis\/","title":{"rendered":"Aromatic Synthesis (3) – Sulfonyl Blocking Groups"},"content":{"rendered":"

The Sulfonyl Blocking-Group Strategy For Synthesis of Aromatic Molecules<\/strong><\/p>\n

Or, how to just get the “ortho<\/em>” product without any para-<\/em> .<\/p>\n

\"sulfonyl<\/a><\/p>\n

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

    \n
  1. Why do para<\/em> products tend to be favored over\u00a0ortho-\u00a0<\/em>products?\u00a0<\/a><\/li>\n
  2. How Do You Get Just The\u00a0ortho-\u00a0<\/em>Product?<\/a><\/li>\n
  3. The Sulfonyl “Blocking Group” Strategy<\/a><\/li>\n
  4. The Sulfonyl Blocking Group Strategy In Action<\/a><\/li>\n
  5. Combining Sulfonyl Blocking Groups With Polarity Reversal<\/a><\/li>\n
  6. Two Practice Problems<\/a><\/li>\n
  7. Summary: Sulfonyl Blocking Groups<\/a><\/li>\n
  8. Notes<\/a><\/li>\n
  9. Quiz Yourself!<\/a><\/li>\n<\/ol>\n
    \n

    <\/a>1. I Just Want The ORTHO-<\/em>\u00a0Product, Thank You<\/strong><\/h2>\n

    Question: Just how selective are\u00a0ortho-<\/em>\u00a0para<\/em>, directors for the ortho-<\/em> and\u00a0para-\u00a0<\/em>products, respectively?<\/p>\n

    There are two\u00a0ortho<\/em> positions and one\u00a0para<\/em>. All else being equal, we’d expect a ratio of about 2:1 favoring the\u00a0ortho<\/em>.<\/p>\n

    Is that what we get? No.<\/p>\n

    In reality, most electrophilic aromatic substitutions give a ratio of products slightly favoring\u00a0para<\/em>\u00a0over\u00a0ortho<\/em>. A 60:40 ratio is typical.<\/p>\n

    \"in<\/p>\n

    Why the preference for para<\/em>?<\/p>\n

    Steric effects<\/strong>, mostly. The\u00a0ortho-\u00a0<\/em>positions are adjacent to the substituent, which can block the path of the electrophile. The\u00a0para-\u00a0<\/em>position is therefore more accessible for the electrophile to attack.<\/p>\n

    This 60:40 ratio is just a rough number, and depends on the particular substituent. To really drive products to the\u00a0para<\/em>-, use a\u00a0\u00a0really bulky group like\u00a0t<\/em>-butyl. This gives\u00a0para<\/em> products almost exclusively.<\/p>\n

    <\/a>2. How Do You Get Just The ortho-<\/em>\u00a0Product?<\/strong><\/h2>\n

    This preference for the\u00a0para<\/em>– product can be annoying. What if we just want the\u00a0ortho<\/em>– product?<\/p>\n

    \"in<\/p>\n

    Sorry, not an option.\u00a0 At least: not yet.\u00a0 There aren’t any reactions we’ve learned that are selective for the\u00a0ortho<\/em>– product. So getting to the\u00a0ortho-\u00a0<\/em>in one step, without ever having to separate it from the\u00a0para-<\/em>, just isn’t possible with the knowledge we have.<\/p>\n

    But, as often happens in organic chemistry, there IS a\u00a0work-around<\/strong>. Here it is.<\/p>\n

    What if we take advantage of the natural preference for\u00a0para-\u00a0<\/em>substitution, and install\u00a0a group that can be reversibly<\/em> added to an aromatic ring? This\u00a0blocks<\/strong> the para<\/em> position, which means that any subsequent reaction must go onto the\u00a0ortho <\/em>position.<\/p>\n

    Then we remove the blocking group, and\u00a0voila!<\/em> we have our\u00a0ortho-\u00a0<\/em>substituted product exclusively.<\/p>\n

    <\/a>3. The Sulfonyl “Blocking Group” Strategy<\/strong><\/h2>\n

    Have we seen any substituents that can be installed reversibly on benzene?<\/p>\n

    Yes. There are two: sulfonyl (SO3<\/sub>H) and\u00a0t<\/em>-butyl.<\/p>\n

    Here, we’ll mostly cover\u00a0sulfonyl. (If you just can’t get enough of this topic – completely understandable! –\u00a0 I’ll cover\u00a0t-butyl in the endnotes.)<\/em><\/span><\/p>\n

    Let’s review sulfonation:<\/p>\n