{"id":2881,"date":"2019-01-07T21:40:02","date_gmt":"2019-01-07T21:40:02","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/?post_type=chapter&p=2881"},"modified":"2019-01-07T21:40:02","modified_gmt":"2019-01-07T21:40:02","slug":"11-3-some-common-sequences-in-synthesis","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/chapter\/11-3-some-common-sequences-in-synthesis\/","title":{"raw":"11.3. Some common sequences in synthesis","rendered":"11.3. Some common sequences in synthesis"},"content":{"raw":"Many reactions are used as part of a common sequence to achieve a specific synthetic goal.\u00a0 We saw that in the example synthesis in the previous section, where it was necessary to convert an alcohol into an ether using the Williamson ether synthesis.\u00a0 Below are given some of these common sequences:\r\n

The alkene shuffle<\/h3>\r\nWant to move a functional group from one carbon over to the neighboring carbon?\u00a0 Try this!\u00a0 Use Markovnikov's Rule to guide you.\u00a0 (Note: The HBr\/ROOR reaction is covered later, in section 18.4., but it's included here for completeness.)\r\n\r\n\"A\r\n

Extending a chain via an SN<\/sub>2 reaction<\/h3>\r\nThere are three common examples of this, and all three processes involve a key step.\u00a0 In each case, the starting material is converted into its conjugate base in the first step, and that conjugate base is used as an SN<\/sub>2 nucleophile for the second step.\u00a0 Usually you would use the same solvent for both steps.\u00a0 These reactions were all introduced in section 9.2<\/a>.\u00a0 In these reaction schemes, the added carbons are shown in orange.\u00a0 Since all three processes involve attachment of an alkyl group (to the conjugate base), they would all be classed as \"alkylation\" reactions.\r\n\r\n(a) Converting an alcohol to an ether via the Williamson ether synthesis\r\n\r\nSee section 9.5<\/a>. for more details.\u00a0 The conjugate base of an alcohol is called an alkoxide.\u00a0 Here you may have a choice of which alkyl group comes from the alcohol, and which one comes from the alkyl halide; you should always try to use the less substituted alkyl group (ideally methyl or 1o<\/sup> alkyl) in the alkyl halide, as that will lead to a cleaner SN<\/sub>2 reaction.\u00a0 This example is the one used in the previous section in the synthesis example:\r\n\r\n\"An\r\n\r\n(In practice, the first step of the reaction can be done on a small scale in DMSO, but on a larger scale NaH can catch fire when added to DMSO.)\u00a0 With liquid alcohols, sometimes Na metal is used instead of NaH for making the alkoxide.\r\n\r\n(b) Converting a terminal alkyne into an internal alkyne\r\n\r\nSee section 9.8<\/a> for more details.\u00a0 The conjugate base of a terminal alkyne is called an acetylide, and it is made using a strong base: Either NaH (possibly in DMSO on a small scale) or NaNH2<\/sub> (in liquid ammonia).\r\n\r\n\"Example\r\n\r\n(c) Extending the alkyl chain of a ketone.\r\n\r\nSee section 9.7<\/a> for more details.\u00a0 The conjugate base of a ketone is called an enolate.\u00a0 It is usually made using the strong lithium base LDA, which forms the conjugate base on the less substituted alpha carbon.\u00a0 The alpha carbons are the carbons either side of the carbonyl (C=O) group.\u00a0 The reaction is done as a two-step sequence in cold THF (often at -78 o<\/sup>C) as the polar aprotic solvent.\r\n\r\n\"Example","rendered":"

Many reactions are used as part of a common sequence to achieve a specific synthetic goal.\u00a0 We saw that in the example synthesis in the previous section, where it was necessary to convert an alcohol into an ether using the Williamson ether synthesis.\u00a0 Below are given some of these common sequences:<\/p>\n

The alkene shuffle<\/h3>\n

Want to move a functional group from one carbon over to the neighboring carbon?\u00a0 Try this!\u00a0 Use Markovnikov’s Rule to guide you.\u00a0 (Note: The HBr\/ROOR reaction is covered later, in section 18.4., but it’s included here for completeness.)<\/p>\n

\"A<\/p>\n

Extending a chain via an SN<\/sub>2 reaction<\/h3>\n

There are three common examples of this, and all three processes involve a key step.\u00a0 In each case, the starting material is converted into its conjugate base in the first step, and that conjugate base is used as an SN<\/sub>2 nucleophile for the second step.\u00a0 Usually you would use the same solvent for both steps.\u00a0 These reactions were all introduced in section 9.2<\/a>.\u00a0 In these reaction schemes, the added carbons are shown in orange.\u00a0 Since all three processes involve attachment of an alkyl group (to the conjugate base), they would all be classed as “alkylation” reactions.<\/p>\n

(a) Converting an alcohol to an ether via the Williamson ether synthesis<\/p>\n

See section 9.5<\/a>. for more details.\u00a0 The conjugate base of an alcohol is called an alkoxide.\u00a0 Here you may have a choice of which alkyl group comes from the alcohol, and which one comes from the alkyl halide; you should always try to use the less substituted alkyl group (ideally methyl or 1o<\/sup> alkyl) in the alkyl halide, as that will lead to a cleaner SN<\/sub>2 reaction.\u00a0 This example is the one used in the previous section in the synthesis example:<\/p>\n

\"An<\/p>\n

(In practice, the first step of the reaction can be done on a small scale in DMSO, but on a larger scale NaH can catch fire when added to DMSO.)\u00a0 With liquid alcohols, sometimes Na metal is used instead of NaH for making the alkoxide.<\/p>\n

(b) Converting a terminal alkyne into an internal alkyne<\/p>\n

See section 9.8<\/a> for more details.\u00a0 The conjugate base of a terminal alkyne is called an acetylide, and it is made using a strong base: Either NaH (possibly in DMSO on a small scale) or NaNH2<\/sub> (in liquid ammonia).<\/p>\n

\"Example<\/p>\n

(c) Extending the alkyl chain of a ketone.<\/p>\n

See section 9.7<\/a> for more details.\u00a0 The conjugate base of a ketone is called an enolate.\u00a0 It is usually made using the strong lithium base LDA, which forms the conjugate base on the less substituted alpha carbon.\u00a0 The alpha carbons are the carbons either side of the carbonyl (C=O) group.\u00a0 The reaction is done as a two-step sequence in cold THF (often at -78 o<\/sup>C) as the polar aprotic solvent.<\/p>\n

\"Example<\/p>\n","protected":false},"author":311,"menu_order":3,"template":"","meta":{"_candela_citation":"[]","CANDELA_OUTCOMES_GUID":"","pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":[],"pb_section_license":""},"chapter-type":[],"contributor":[],"license":[],"class_list":["post-2881","chapter","type-chapter","status-publish","hentry"],"part":300,"_links":{"self":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/wp-json\/pressbooks\/v2\/chapters\/2881","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/wp-json\/wp\/v2\/users\/311"}],"version-history":[{"count":1,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/wp-json\/pressbooks\/v2\/chapters\/2881\/revisions"}],"predecessor-version":[{"id":2882,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/wp-json\/pressbooks\/v2\/chapters\/2881\/revisions\/2882"}],"part":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/wp-json\/pressbooks\/v2\/parts\/300"}],"metadata":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/wp-json\/pressbooks\/v2\/chapters\/2881\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/wp-json\/wp\/v2\/media?parent=2881"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/wp-json\/pressbooks\/v2\/chapter-type?post=2881"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/wp-json\/wp\/v2\/contributor?post=2881"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/wp-json\/wp\/v2\/license?post=2881"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}