{"id":1686,"date":"2018-11-29T21:38:49","date_gmt":"2018-11-29T21:38:49","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/?post_type=chapter&p=1686"},"modified":"2026-06-26T22:15:19","modified_gmt":"2026-06-26T22:15:19","slug":"21-2-general-mechanism","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/chapter\/21-2-general-mechanism\/","title":{"raw":"21.2 General mechanism","rendered":"21.2 General mechanism"},"content":{"raw":" \r\n\r\n
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General mechanism for addition of weak nucleophiles to carbonyls<\/strong><\/h2>\r\n
Recall (from chapter 20<\/a>) that strong nucleophiles are able to add directly to a C=O based on the type I resonance<\/a> of the C=O bond that makes the carbon moderately electrophilic.\u00a0 However, weak nucleophiles are not strong enough to add to C=O in this way.\u00a0 They require the carbon of the C=O to be made more electrophilic, and this is done using either a Lewis acid or simply H+<\/sup> (which in practice usually means a strong acid such as H2<\/sub>SO4<\/sub>).\u00a0 We will focus on activation using simple acid - a process called protonation.\u00a0 This activated, charged form of the C=O now is a stronger electrophile, with a bigger positive charge (via type III resonance) on the carbon so even weak nucleophiles will attack, allowing nucleophilic addition to occur.<\/header>
\"Overview<\/header>
Most often the weak nucleophiles are uncharged compounds such as alcohols (ROH) or amines (RNH2<\/sub> or similar).\u00a0 With these uncharged nucleophiles, the product of the nucleophilic addition step is a positively charged compound, and so there is usually a final acid-base step to remove the unwanted H+<\/sup> (\"deprotonation\") and form the final uncharged product.<\/header>
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Detailed mechanism<\/span><\/h2>\r\n<\/header>
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\r\n\r\nSTEP 1: Protonation on oxygen (an acid-base<\/strong> step) activates the carbonyl.\r\n\r\nSTEP 2: The weak nucleophile attacks this activated C=O via nucleophilic addition<\/strong>.\r\n\r\nSTEP 3: Finally, deprotonation (loss of H+<\/sup>) occurs by another acid-base<\/strong> step.\u00a0 We have used a second molecule of HNuc: as the base here, but you may also use the A- (produced in the first step) as your base for this step.\r\n\r\nNote that the overall starting molecule and product here are equivalent to what we saw in chapter 20 with strong nucleophiles, i.e., the outcome of the nucleophilic addition is the same.\u00a0 However, the mechanism (the route from reactant to product) is different.\r\n\r\n\"Graphic\r\n

Summary<\/h2>\r\nIn conclusion, there are two ways to add nucleophiles to C=O.\r\n\r\n(a) <\/strong>Strong nucleophiles<\/strong> (Nuc-, covered in chapter 20) do simple addition to C=O\r\n\r\n<\/div>\r\n\"Nucleophile\r\n\r\n \r\n\r\n \r\n\r\n \r\n\r\n(b) <\/strong>Weak nucleophiles<\/strong> (HNuc:) only add to activated C=O (covered in THIS chapter, chapter 21).\r\n\r\n\"Acid\r\n\r\n \r\n\r\n \r\n\r\n \r\n\r\nIn the rest of this chapter, we will explore in detail how this latter mechanism works in practice for different weak nucleophiles.\r\n
\r\n\r\nContributors<\/span>\r\n