{"id":2776,"date":"2018-06-21T13:26:13","date_gmt":"2018-06-21T13:26:13","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/williamson-ether-synthesis\/"},"modified":"2018-08-06T15:17:09","modified_gmt":"2018-08-06T15:17:09","slug":"9-5-williamson-ether-synthesis","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-5-williamson-ether-synthesis\/","title":{"raw":"9.5. Williamson ether synthesis","rendered":"9.5. Williamson ether synthesis"},"content":{"raw":"
The Williamson ether synthesis is the easiest, and perhaps the fastest, way to create ethers<\/a>.\r\n
\r\n

Introduction<\/h3>\r\nThe Williamson ether synthesis involves an alkoxide reacting with a primary alkyl halide or a sulfonate ester. Alkoxides <\/a>consist of the conjugate base of an alcohol and are comprised of an R group bonded to an oxygen atom. They are often written as RO\u2013<\/sup>, where R is the organic substituent.\r\n\r\n\"Williamson\r\n\r\nSn<\/sub>2 reactions are characterized by the inversion <\/em>of stereochemistry at the site of the leaving group. Williamson ether synthesis is not an exception to this rule and the reaction is set in motion by the backside attack of the nucleophile.\r\n\r\n<\/div>\r\n
\r\n

Ethers are prepared by SN<\/sub>2 reactions<\/h3>\r\nEthers can be synthesized in standard SN<\/sub>2 conditions by coupling an alkoxide with a alkyl halide\/sulfonate ester. The alcohol that supplies the electron rich alkoxide can be used as the solvent, as well as dimethyl sulfoxide (DMSO) or hexamethylphosphoric triamide (HMPA).\r\n\r\n\"DMSO\r\n\r\nFor example\r\n

\"\"<\/p>\r\n\r\n

\r\n

Intramolecular Williamson ether reactions<\/h4>\r\nYou can also use the Williamson synthesis to produce cyclic ethers. You need a molecule that has a hydroxyl group on one carbon and a halogen atom attached to another carbon. This molecule will then undergo an SN<\/sub>2 reaction with itself, creating a cyclic ether and a halogen anion. Another way of deriving ethers is by converting halo alcohols into cyclic ethers. This reaction is prompted by the deprotonation of the hydrogen attached to the oxygen by an OH-<\/sup> anion. This leads to the departure of the halogen, forming a cyclic ether and halogen radical.\r\n\r\nAnother factor in determining whether a cyclic ether will be formed is ring size. Three-membered rings along with five membered rings form the fastest, followed by six, four, seven, and lastly eight membered rings. The relative speeds of ring formation are influenced by both enthalpic and entropic contributions.\r\n\r\n\"Picture\r\n\r\n<\/div>\r\n<\/div>\r\n
\r\n

References<\/h3>\r\n
    \r\n \t
  1. Ahluwalia,\u00a0V. K., and Renu Aggarwal. Organic Synthesis: Special Techniques. Delhi: CRC Press, 2001.<\/li>\r\n \t
  2. Vollhardt, K. Peter C., and Neil E. Schore.\u00a0Organic Chemistry: Structure and Function. New York: W.H. Freeman and Company, 2007.<\/li>\r\n<\/ol>\r\n<\/div>\r\n
    \r\n
    \r\n

    Problems<\/h3>\r\n\"Practice\r\n\r\n<\/div>\r\nKhan academy video:\r\n\r\n\"\"\r\n\r\n<\/div>\r\n[embed]https:\/\/www.youtube.com\/watch?v=X9ypryY7hrQ[\/embed]\r\n\r\n<\/section>","rendered":"
    The Williamson ether synthesis is the easiest, and perhaps the fastest, way to create ethers<\/a>.<\/p>\n
    \n

    Introduction<\/h3>\n

    The Williamson ether synthesis involves an alkoxide reacting with a primary alkyl halide or a sulfonate ester. Alkoxides <\/a>consist of the conjugate base of an alcohol and are comprised of an R group bonded to an oxygen atom. They are often written as RO\u2013<\/sup>, where R is the organic substituent.<\/p>\n

    \"Williamson<\/p>\n

    Sn<\/sub>2 reactions are characterized by the inversion <\/em>of stereochemistry at the site of the leaving group. Williamson ether synthesis is not an exception to this rule and the reaction is set in motion by the backside attack of the nucleophile.<\/p>\n<\/div>\n

    \n

    Ethers are prepared by SN<\/sub>2 reactions<\/h3>\n

    Ethers can be synthesized in standard SN<\/sub>2 conditions by coupling an alkoxide with a alkyl halide\/sulfonate ester. The alcohol that supplies the electron rich alkoxide can be used as the solvent, as well as dimethyl sulfoxide (DMSO) or hexamethylphosphoric triamide (HMPA).<\/p>\n

    \"DMSO<\/p>\n

    For example<\/p>\n

    \"\"<\/p>\n

    \n

    Intramolecular Williamson ether reactions<\/h4>\n

    You can also use the Williamson synthesis to produce cyclic ethers. You need a molecule that has a hydroxyl group on one carbon and a halogen atom attached to another carbon. This molecule will then undergo an SN<\/sub>2 reaction with itself, creating a cyclic ether and a halogen anion. Another way of deriving ethers is by converting halo alcohols into cyclic ethers. This reaction is prompted by the deprotonation of the hydrogen attached to the oxygen by an OH–<\/sup> anion. This leads to the departure of the halogen, forming a cyclic ether and halogen radical.<\/p>\n

    Another factor in determining whether a cyclic ether will be formed is ring size. Three-membered rings along with five membered rings form the fastest, followed by six, four, seven, and lastly eight membered rings. The relative speeds of ring formation are influenced by both enthalpic and entropic contributions.<\/p>\n

    \"Picture<\/p>\n<\/div>\n<\/div>\n

    \n

    References<\/h3>\n
      \n
    1. Ahluwalia,\u00a0V. K., and Renu Aggarwal. Organic Synthesis: Special Techniques. Delhi: CRC Press, 2001.<\/li>\n
    2. Vollhardt, K. Peter C., and Neil E. Schore.\u00a0Organic Chemistry: Structure and Function. New York: W.H. Freeman and Company, 2007.<\/li>\n<\/ol>\n<\/div>\n
      \n
      \n

      Problems<\/h3>\n

      \"Practice<\/p>\n<\/div>\n

      Khan academy video:<\/p>\n

      \"\"<\/p>\n<\/div>\n