{"id":3768,"date":"2018-07-16T20:46:00","date_gmt":"2018-07-16T20:46:00","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/?post_type=chapter&p=3768"},"modified":"2020-06-23T21:54:57","modified_gmt":"2020-06-23T21:54:57","slug":"9-2-common-nucleophilic-substitution-reactions","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-2-common-nucleophilic-substitution-reactions\/","title":{"raw":"9.2. Common nucleophilic substitution reactions","rendered":"9.2. Common nucleophilic substitution reactions"},"content":{"raw":"Most of this chapter focuses on specific reagents and conditions for performing nucleophilic substitutions in the lab or plant. Remember some of the main lessons from the previous chapter: Higher temperatures favor elimination (where this can happen) and colder conditions favor SN<\/sub>2 (as long as the reactants can still react at that temperature).\u00a0 For SN<\/sub>2, you will normally want to use a polar aprotic solvent (DMSO is my favorite).\r\n\r\nAll of these reactions fall into a common pattern of electrophile + nucleophile gives substitution product.\u00a0 You may see either reactant - electrophile or nucleophile - given above the arrow as a \"reagent.\"\u00a0 Consider the following:\r\n

The electrophile<\/h2>\r\nMost often this has an alkyl halide or sulfonate serving as \"RX\".\u00a0 An alkyl bromide is probably the most useful for you to know; it's stable, fairly cheap, easy to make using PBr3<\/sub> (see section 9.3.<\/a> which shows how to make all different RX).\u00a0 Remember that a primary or secondary alkyl halide will work best with SN<\/sub>2, and for a tertiary alkyl halide you will have to use SN<\/sub>1 methods.\u00a0 Most of the reactions that are effective in synthesis involve SN<\/sub>2, because these are usually the cleanest, especially with primary alkyl halides.\r\n\r\n\"\"\r\n\r\nIn section 9.6,<\/a> we'll learn about an alternative electrophile, the epoxide or oxirane.\u00a0 Epoxides are ethers that contain a strained three-membered ring that makes them quite reactive towards nucleophiles.\u00a0 The incoming group displaces the oxygen from one of the carbons (usually the less substituted one), leaving that oxygen attached to the other (neighboring) carbon.\r\n

The nucleophile<\/h2>\r\nA wide variety of nucleophiles is available to react with alkyl halides.\u00a0 Some of the most common are shown below, using bromobutane as a typical primary alkyl halide.\u00a0 The nucleophile is shown on the far left.\u00a0 Note that most nucleophiles (except amines\/NH3<\/sub>) are anions, but the actual reagents you use are usually sodium or potassium salts, which are always ionic.\u00a0 For example, when you see -<\/sup>OH in a scheme this will usually mean NaOH or KOH.\r\n

Preparation of alcohols<\/h4>\r\nHydroxide ion is very effective for primary and secondary alcohols.\u00a0 For tertiary alcohols, you have to use water to avoid elimination.\r\n\r\n\"\"\r\n

Preparation of ethers<\/h4>\r\nThe Williamson ether synthesis (see section 9.5<\/a>) uses alkoxide ion with primary and secondary alkyl halides.\u00a0 For making tertiary ethers, you have to use ROH to avoid elimination.\r\n\r\n\"\"\r\n

Preparation of amines<\/h4>\r\nSee section 9.4.<\/a>\u00a0 Amination of alkyl halides can be done using NH3<\/sub>, RNH2<\/sub> or R2<\/sub>NH, but a very large excess of the nitrogen compound must be used to avoid mixtures of products.\u00a0 A cleaner reaction can be done using azide ion (N3<\/sub>-<\/sup>) followed by reduction.\r\n\r\n\"\"\r\n

Preparation of alkyl iodides<\/h4>\r\n\"\"\r\n

Reactions using carbanions or carbanion equivalents<\/h4>\r\nThese are useful for making new C-C connections.\u00a0 See section 9.8.<\/a> for reactions of acetylides, which in two steps turn a terminal alkyne into a longer chain internal alkyne.\u00a0 A strong base (NaH or NaNH2<\/sub>) is used to make the carbanion nucleophile (the acetylide), which is then reacted with the alkyl halide.\u00a0 Only primary alkyl halides work.\r\n\r\nSee section 9.7<\/a> for reactions of enolates.\u00a0 Here a strong base (LDA) is used to make the carbanion nucleophiile (an enolate) from a ketone or similar compound.\u00a0 This reacts with the alkyl halide to produce a new ketone with a longer carbon chain.\u00a0 Again, only primary alkyl halides work.\r\n\r\n\"\"\r\n\r\nWe will now examine some of these reactions in more detail.\r\n

References<\/h3>\r\nJoel Karty, \"Organic Chemistry: Principles and Mechanisms,\" First Edition, Norton.","rendered":"

Most of this chapter focuses on specific reagents and conditions for performing nucleophilic substitutions in the lab or plant. Remember some of the main lessons from the previous chapter: Higher temperatures favor elimination (where this can happen) and colder conditions favor SN<\/sub>2 (as long as the reactants can still react at that temperature).\u00a0 For SN<\/sub>2, you will normally want to use a polar aprotic solvent (DMSO is my favorite).<\/p>\n

All of these reactions fall into a common pattern of electrophile + nucleophile gives substitution product.\u00a0 You may see either reactant – electrophile or nucleophile – given above the arrow as a “reagent.”\u00a0 Consider the following:<\/p>\n

The electrophile<\/h2>\n

Most often this has an alkyl halide or sulfonate serving as “RX”.\u00a0 An alkyl bromide is probably the most useful for you to know; it’s stable, fairly cheap, easy to make using PBr3<\/sub> (see section 9.3.<\/a> which shows how to make all different RX).\u00a0 Remember that a primary or secondary alkyl halide will work best with SN<\/sub>2, and for a tertiary alkyl halide you will have to use SN<\/sub>1 methods.\u00a0 Most of the reactions that are effective in synthesis involve SN<\/sub>2, because these are usually the cleanest, especially with primary alkyl halides.<\/p>\n

\"\"<\/p>\n

In section 9.6,<\/a> we’ll learn about an alternative electrophile, the epoxide or oxirane.\u00a0 Epoxides are ethers that contain a strained three-membered ring that makes them quite reactive towards nucleophiles.\u00a0 The incoming group displaces the oxygen from one of the carbons (usually the less substituted one), leaving that oxygen attached to the other (neighboring) carbon.<\/p>\n

The nucleophile<\/h2>\n

A wide variety of nucleophiles is available to react with alkyl halides.\u00a0 Some of the most common are shown below, using bromobutane as a typical primary alkyl halide.\u00a0 The nucleophile is shown on the far left.\u00a0 Note that most nucleophiles (except amines\/NH3<\/sub>) are anions, but the actual reagents you use are usually sodium or potassium salts, which are always ionic.\u00a0 For example, when you see –<\/sup>OH in a scheme this will usually mean NaOH or KOH.<\/p>\n

Preparation of alcohols<\/h4>\n

Hydroxide ion is very effective for primary and secondary alcohols.\u00a0 For tertiary alcohols, you have to use water to avoid elimination.<\/p>\n

\"\"<\/p>\n

Preparation of ethers<\/h4>\n

The Williamson ether synthesis (see section 9.5<\/a>) uses alkoxide ion with primary and secondary alkyl halides.\u00a0 For making tertiary ethers, you have to use ROH to avoid elimination.<\/p>\n

\"\"<\/p>\n

Preparation of amines<\/h4>\n

See section 9.4.<\/a>\u00a0 Amination of alkyl halides can be done using NH3<\/sub>, RNH2<\/sub> or R2<\/sub>NH, but a very large excess of the nitrogen compound must be used to avoid mixtures of products.\u00a0 A cleaner reaction can be done using azide ion (N3<\/sub>–<\/sup>) followed by reduction.<\/p>\n

\"\"<\/p>\n

Preparation of alkyl iodides<\/h4>\n

\"\"<\/p>\n

Reactions using carbanions or carbanion equivalents<\/h4>\n

These are useful for making new C-C connections.\u00a0 See section 9.8.<\/a> for reactions of acetylides, which in two steps turn a terminal alkyne into a longer chain internal alkyne.\u00a0 A strong base (NaH or NaNH2<\/sub>) is used to make the carbanion nucleophile (the acetylide), which is then reacted with the alkyl halide.\u00a0 Only primary alkyl halides work.<\/p>\n

See section 9.7<\/a> for reactions of enolates.\u00a0 Here a strong base (LDA) is used to make the carbanion nucleophiile (an enolate) from a ketone or similar compound.\u00a0 This reacts with the alkyl halide to produce a new ketone with a longer carbon chain.\u00a0 Again, only primary alkyl halides work.<\/p>\n

\"\"<\/p>\n

We will now examine some of these reactions in more detail.<\/p>\n

References<\/h3>\n

Joel Karty, “Organic Chemistry: Principles and Mechanisms,” First Edition, Norton.<\/p>\n\n\t\t\t

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Candela Citations<\/h3>\n\t\t\t\t\t
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