{"id":411,"date":"2018-11-29T22:17:39","date_gmt":"2018-11-29T22:17:39","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/?post_type=chapter&p=411"},"modified":"2019-01-08T14:50:44","modified_gmt":"2019-01-08T14:50:44","slug":"16-2-preparation-of-alkylbenzenes","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/chapter\/16-2-preparation-of-alkylbenzenes\/","title":{"raw":"16.2 Preparation of alkylbenzenes","rendered":"16.2 Preparation of alkylbenzenes"},"content":{"raw":"
\r\n

Friedel-Crafts reactions<\/span><\/h2>\r\n<\/header>
\r\n
\r\n
\r\n\r\nCompounds containing aromatic groups are widespread in nature, and for this reason chemists who aim to synthesize naturally occurring compounds in the laboratory often need to introduce substituents to aromatic rings.\u00a0\u00a0 In the organic synthesis laboratory, electrophilic aromatic substitutions which result in the formation of new carbon-carbon bonds are called \u2018Friedel-Crafts\u2019\u00a0 alkylations and acylations, named for Charles Friedel of France and James Crafts of the United States, who together developed the procedures in 1877.\u00a0\u00a0 The Friedel-Crafts reactions are an important part of a synthetic chemist's toolbox to this day.\r\n\r\nFriedel Crafts reactions, like their biochemical counterparts, require reactive electrophiles with significant carbocation character.\u00a0 One of the most common ways to alkylate an aromatic ring is to use an alkyl chloride electrophile that is activated by the addition of aluminum or iron trichloride.\u00a0 The metal chloride serves as a Lewis acid, accepting electron density from the alkyl chloride.\u00a0 This has the effect of magnifying the carbon-chlorine dipole, making the carbon end more electropositive - and thus more electrophilic \u2013 even to the point where the bond breaks and an ion-pair is formed.\r\n\r\n\"FC\r\n\r\n \r\n\r\nAn alternative method for carrying out a Friedel-Crafts alkylation is to start with an alkene, which is protonated by a strong acid such as H2<\/sub>SO4<\/sub> to generate a carbocation.\r\n\r\n\"image126.png\"\r\n

Limitations of Friedel-Crafts Alkylation<\/h3>\r\n
    \r\n \t
  1. Carbocation Rearrangement<\/a><\/strong> - Only certain alkylbenzenes can be made due to the tendency of cations to rearrange.<\/li>\r\n \t
  2. Compound Limitations<\/strong> - Friedel-Crafts fails when used with compounds such as nitrobenzene and other strongly deactivated aromatics.<\/li>\r\n \t
  3. Polyalkylation<\/strong> - Products of Friedel-Crafts alkylations are even more reactive than starting material. Alkyl groups produced in Friedel-Crafts Alkylation are electron-donating substituents meaning that the products are more susceptible to electrophilic attack than what we began with. For synthetic purposes, this is a big disappointment, because the reaction is hard to stop with just a single alkylation.<\/li>\r\n<\/ol>\r\nTo remedy some of these limitations (1 and 3), Friedel-Crafts acylation is often used instead, followed by reduction of the ketone product.\r\n\r\nThe Friedel-Crafts acylation reaction is essentially an acyl substitution (chapter 22<\/a>) reaction with an aromatic \u03c0 bond serving as the nucleophile.\u00a0 As in many other laboratory acyl transfer reactions, acyl chlorides are used as activated carboxylic acids.\u00a0 Because of the low reactivity of the aromatic \u03c0 bond nucleophile, however, the acyl chloride electrophile in a Friedel-Crafts acylation must be further activated with a Lewis acid reagent such as aluminum chloride, which again serves to polarize the carbon-chlorine bond and increase the electrophilicity of the acyl carbon.\u00a0 The activated electrophile in Friedel-Crafts acylations is often depicted as an ionic species.\r\n\r\n\"image128.png\"\r\n\r\nThe resultant aryl ketone can be reduced to CH3<\/sub>CH2<\/sub>Ph (ethylbenzene) using H2<\/sub>\/Pd on C, or Zn(Hg) and HCl, as described in the latter part of section 14.2<\/a>.\r\n\r\n<\/div>\r\n<\/div>\r\n
    \r\n
    \r\n

    Substituent effects in Friedel-Crafts reactions<\/h2>\r\nThe reactivity of aromatic pi bonds in SE<\/sub>Ar reactions is very sensitive to the presence of electron-donating groups (EDG) and electron-withdrawing groups (EWG) on the aromatic ring.\u00a0 This is due to the carbocation nature of the intermediate, which is stabilized by electron-donating groups and destabilized by electron-withdrawing groups.\u00a0 As a rule, both the acylation and alkylation Friedel-Crafts reactions fail when meta-directing deactivators are present. Thus nitrobenzene (a deactivated ring) fails to react in the Friedel-Crafts reaction. However the reaction is successful with halogen substituents are present, as in chlorobenzene.\r\n\r\n\"image134.png\"\r\n\r\nThe Friedel-Crafts alkylation of methoxy benzene would be expected to produce a mixture of the ortho<\/em> and para<\/em> substituted products, but no meta<\/em>-substituted product.\r\n\r\n\"image144.png\"\r\n\r\nIn addition, the para<\/em> product would be expected to be preferred over the ortho<\/em> product, due to steric and inductive considerations.\r\n\r\n<\/div>\r\n<\/div>\r\n
    \r\n
    \r\n

    Contributors<\/span><\/h3>\r\n