Friedel-Crafts alkylation condensation

Fluoroalkjiations are frequentiy performed indirectly using tandem reactions. Arenes react with sodium borohydride in trifluoroacetic acid to afford otherwise difficult to obtain l,l,l-trifluoro-2,2-diarylethanes. Presumably sodium borohydride reacts initially with the trifluoroacetic acid to produce the trifluoroacetaldehyde or its equivalent, which rapidly undergoes Friedel-Crafts-type condensation to give an intermediate carbinol. The carbinol further alkylates ben2ene under the reaction conditions giving the observed product. The reaction with stericaHy crowded arenes such as mesitylene and durene... 

Arylation of Aromatic Compounds. In contrast to Friedel-Crafts alkylations, arylations of aromatics are not as well known, and usually require drastic conditions. They iaclude (/) dehydrogenating condensation (SchoU reaction) (2) arylation with aryl haUdes and (J) arylation with dia2onium hahdes. 

The first step in the sequence may involve Friedel-Crafts-type condensation of resorcinol with the enolate of 10 to afford the unsaturated ester, 11. Alkylation of the free phenol on 12 by means of ethyl bromoacetate affords chromonar (13). ... 

A novel mesoporous intercalate belonging to the class of mesostructured solid acids known as porous clay heterostructures (PCH) has been synthesized through the surfactant - directed assembly of silica in the two - dimensional galleries of saponite. The new saponite PCH, denoted SAP-PCH, exhibits a basal spacing of 32.9 A, a BET surface area of 850 m2/g and pore volume of 0.46 cm3/g. SAP-PCH is an effective catalyst for the condensed phase Friedel-Crafts alkylation of bulky 2,4-di-tert-butylphenol (DBP) with cinnamyl alcohol to produce a large flavan, namely, 6,8-di-tert-butyl-2,3-dihydro[4H]benzopyran. 

Carbonyl compounds, particularly aromatic aldehydes, when activated with electrophilic catalysts, can also react with aromatics.241 The process is often called condensation or reductive alkylation, but it is actually a multistep Friedel-Crafts alkylation reaction. 

An interesting example of an application of this method pertains to the synthesis of pharmacologically active synthetic A1 -tetrahydrocannabinoids 134) of the type 267 which have a lipophilic tertiary alkyl side-chain. Equation 84 shows that organo-titanium chemistry provides a versatile means to prepare the precursors 264 (65-80 %)133). Demethylation of 264 using trimethylsilyl chloride and sodium iodide affords the resorcinol derivatives 265 ( 95%)133>. Compounds of this type have been previously condensed with 266 in the presence of acids to form the A1(6)-isomers of 267, which in turn can be converted into 267135). It should be mentioned that the meta-substitution pattern of 265 prohibits simple Friedel-Crafts alkylation of resorcinol, which is the reason why alternative multistep syntheses of 264 have had to be developed l34 136>. 

Pertinent examples of zeolite-catalyzed reactions in organic synthesis include Friedel-Crafts alkylations and acylations and other electrophilic aromatic substitutions, additions and eliminations, cyclizations, rearrangements and isomeriza-tions, and condensations. 

A new investigation of the Friedel-Crafts alkylation of 2-furoic esters with sec-butyl bromide (using AIC1S in CS2) yielded a mixture of 43% 5-other conditions, even furans which are not negatively substituted can be successfully alkylated. In this way 2-methyl- and 2-ethyIfuran condense with mesityl oxide in the presence of strong sulfuric acid129,130 (see also similar reactions mentioned in Sections III,B, III,C, and... 

Friedel-Crafts alkylations of arenes with higher cyclic ethers such as tetrahydrofiirans and pyrans are often accompanied by many side reactions such as intramolecular alkylation, condensation and further transformations of the initial alkylated product. However, it is possible to obtain one product selectively by choosing the proper reaction conditions. An example is shown in equation (62). ... 

In large measure syntheses of aglycones have relied on the employment of one (or more) of three general reaction classes Friedel Crafts alkylations or acylations, nucleophilic condensations, and Diels Alder reactions the various routes are conveniently discussed under these three headings. (Note unless otherwise Indicated, all compounds described in the section on aglycone synthesis are racemic.)... 

Bisphenol A is made by condensing two molecules of phenol with one molecule of acetone, with loss of a molecule of water. This is an electrophilic aromatic subsitution (more specifically, a Friedel-Crafts alkylation), and would require an acid catalyst to generate the carbocation. While a Lewis acid could be used, the mechanism below shows a protic acid. 

Friedel-Crafts alkylations of arenes with mesylates, benzyl or allyl alcohols, aldehyde/diol combinations (reductive alkylation), 1,3-dienes, or alkenes in an ionic liquid are also effectively catalyzed by Sc(OTf)3. Sc(OTf)3 works as an efficient catalyst for the condensation reaction of trimethylhydroquinone with isophytol to afford a-tocopherol. 2-Aminoalkylation of phenols with a-iminoacetates (or glyoxylate/amine) is catalyzed by Sc(OTf)3 to produce amino acid derivatives. The Sc(OTf)3-catalyzed alkylations of indoles with a-hydroxy esters, aziri-dines, acetals, and aldehydes have been utilized as key steps of total syntheses as exemplified in eq 15. ... 

A number of reactions relevant to fine chemicals manufacture can be catalyzed by superacids, for example, dehydration of carboxamides to nitriles, Friedel-Crafts alkylation and acylation, Fisher indole synthesis of coumarins, isomerization of limonene, condensation of hydroquinone with aniline, and esterification in general (Hino and Arata, 1980, 1985 Joshi and Rajadhyaksha, 1980 Rajadhyak-sha and Chaudhari, 1987 Kumbhar and Yadav, 1989 Rajadhyaksha and Joshi, 1991 Kumbhar et al., 1994). Two particularly important reactions are described here. 

Boron trifluoride is a highly moisture-sensitive gas (31). It is utilized in esterification, ether formation, Friedel-Crafts alkylation and acylation, and Lewis acid-catalyzed Diels-Alder reactions. A more widely used, easy-to-handle and convenient liquid source of BF3 is boron trifluoride etherate [BF3-0(C2H5)2] (32). Its main usage as catalyst is in the direct esterification of all types of acids, rearrangements, aldol condensation, and Lewis acid-catalyzed Diels-Alder reactions. It is the most frequently used acid in epoxide ring opening and rearrangement (33). 

Apart Ifom the aforementioned metal complexes there were entrapped in sol-gel matrices also several acids, bases and salts. Examples are the physically entrapped p-toluenesulfonic acid which has been used as an esterfication catalyst (Scheme 24-23) (Sarussi, 2000) the entrapped poly(vinylbenzyltrimetnyl)ammonium hydroxide which catalyzes aldol condensation (Scheme 24-24) (Gehnan, 2003a) and some entrapped sulfates and chlorides salts that promote dehydration of alcohols (Scheme 24-25) (Nishiguchi, 1989) and Friedel-Crafts alkylation (Scheme 24-26) (Miller, 1998), respectively. 

Because of their negligible vapor pressure, thermal stability and easy recyclability, neutral ILs have been referred to as environmentally benign solvents. These ILs have been employed as excellent and recyclable medium for a wide array of reactions e.g., Heck reaction [Park Alper, 2003], Bischler-Napierlaski cyclisation [fudeh et al, 2002], Beckmann rearrangement [Ren et al., 2001], addition of thiols to unsaturated ketones [Yadav et al., 2003], 1-proline catalysed aldol reaction [Loh et al., 2002], and Pechmann condensation of phenols and ethyl acetoacetate (EAA) catalyzed by POCI3 in [bmim]PF6 and [bmim]BF4 ILs [Potdar et al., 2005]. Other examples where ILs have been used as a reaction media include, but not limited to, Diels-Alder reactions [Reinhardt, 2009 Doherty, 2004 Song, 2001], Friedel-Crafts alkylation and acylation reactions [Xiao, 2006 Xiao Malhotra, 2005 ... 

Polverejan et al. (117) reported on another catalytic application of mesos-tructured clay catalysts. Saponite-daived PCH has been used for the condensed-phase Friedel-Crafts alkylation of bulky 2,4-di-rerr-butylphenol (DBP) with cin-namyl alcohol to produce a large flavan, namely, 6,8-di-rm-butyl-2,3-dihy-dro[4H]benzopyran. Because the molecular dimensions of DBP are very large (1.35 X 0.79 X 0.49 nm), conventional zeolites and pillared clays are not suitable to catalyze this reaction, while the mesopores of saponite PCH are large enough to allow access to the interlayer acid sites. The catalytic results obtained on saponite-PCH are compared to those on H -saponite, zeolite HY, and acid-treated montmorillonite K-10 (Table 9). The reaction is visualized in figure 24. 

---