Friedel—Crafts methodology

The other type of compound considered here is where two benzene rings are bonded via a methylene bridge. The simplest such compound is diphenylmethane (12), which can be synthesized in a number of ways using Friedel-Crafts methodology. The reaction of an excess of benzene with dichloromethane in the presence of aluminium chloride results in the displacement of both halogen atoms. It can also be prepared from benzene and (chloromethyl)benzene, and from benzoyl chloride and benzene followed by reduction of the carbonyl group of the resulting ben-zophenone (Scheme 3.10). 

Although it is possible to synthesize anthracene in a number of ways using Friedel-Crafts methodology, the usual routes involve either an adaptation of the Haworth synthesis of naphthalene or a Dicls-Alder reaction using naphtho-l,4-quinone as the dienophile. 

In comparison with the reactions described in the previous section, arylation reactions, related to allylation reactions and illustrated in Figure 7.9, can be more convenient and versatile. For example, in most cases, Friedel-Crafts methodology applies. Additionally, not only is the conversion from O- to C-glycosides feasible, but both a and p anomers are accessible. 

We developed two highly efficient approaches toward the 5HT2b receptor antagonist LY414197. The first route utilized a Pictet-Spengler reaction to construct the racemic TH(3C derivative. Access to the most active (5)-enantiomer was then achieved in up to 70% yield through a one-pot resolu-tion-racemization process. The second approach is based on the chiral A-arenesulfonylated-1,2-diamine/ruthenium(II)-catalyzed asymmetric reduction of a 3,4-dihydro- 3-carboline precursor, obtained from a Bischler-Napieralski or related Friedel-Crafts methodology. 

Applications to Doxepin Synthesis. The next synthetic objective to be discussed is doxepin (75). The structure of doxepin is shown below. Doxepin (also marketed as Adapin or Sinequan) is a tricyclic heterocyclic compound that is widely prescribed. Doxepin is prepared in very large quantities using a traditional Friedel-Crafts methodology. Of importance from the point of view of synthetic planning is that doxepin is sold as a mixture of E- and Z- double bond isomers. This leads to a simplification of the synthesis of doxepin. 

The regioselective synthesis of complex aromatic compounds has been an important and active research area for chemists over decades. Various strategies and documented synthetic methods have found favor for the synthesis of aromatic compounds. These would include the use of Diels-Alder reactions, Friedel-Crafts methodology, and a range of annulation methods such as those developed by Hauser, Kraus, Staunton, and Weinreb, as well as a range of transition... 

Metallation reaction chemistry of ferrocene has been used as the most prevalent route to the preparation of substituted ferrocenes, even more so than Friedel-Crafts methodology. The lithiation of ferrocene with... 

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