Friedel Crafts reaction transformation

An example of a biological Friedel-Crafts reaction occurs during the biosynthesis of phylloquinone, or vitamin Kl( the human blood-clotting factor. Phylloquinone is formed by reaction of 1,4-dihydroxynaphthoic acid with phytyl diphosphate. Phytyl diphosphate first dissociates to a resonance-stabilized allylic carbocation, which then substitutes onto the aromatic ring in the typical way. Several further transformations lead to phylloquinone (Figure 16.10). 

Friedel-Crafts catalysts, 329, 331 Friedel-Crafts reaction, 297, 361 Front-end reactions, 235 FT Raman spectroscopy, 387 FTIR spectrometry. See Fourier transform infrared (FTIR) spectrometry Fuel cells, 272-273 Full prepolymers, 236, 237 Functionalized polyolefins, 459-460... 

In 2007, Womack et al. published the conversion of 2-aUcylcinnamyldehydes to 2-aLkylindanones via a catalytic intramolecular Friedel-Crafts reaction. In the presence of 5-10 mol% FeCls different in situ generated ( )-2-alkylcinnamaldehydes-derived dimethyl acetals cyclized to l-methoxy-2-aIkyl-7//-indenes in good to high yields (Scheme 6) [22]. The transformation corresponds to a formal intramolecular Friedel-Crafts acylation which is achieved with catalytic quantities of Lewis acid. This result is in strong contrast to traditional Friedel-Crafts acylations which require stoichiometric amounts of Lewis acid. 

Among the wide variety of organic reactions in which zeolites have been employed as catalysts, may be emphasized the transformations of aromatic hydrocarbons of importance in petrochemistry, and in the synthesis of intermediates for pharmaceutical or fragrance products.5 In particular, Friede 1-Crafts acylation and alkylation over zeolites have been widely used for the synthesis of fine chemicals.6 Insights into the mechanism of aromatic acylation over zeolites have been disclosed.7 The production of ethylbenzene from benzene and ethylene, catalyzed by HZSM-5 zeolite and developed by the Mobil-Badger Company, was the first commercialized industrial process for aromatic alkylation over zeolites.8 Other typical examples of zeolite-mediated Friedel-Crafts reactions are the regioselective formation of p-xylene by alkylation of toluene with methanol over HZSM-5,9 or the regioselective p-acylation of toluene with acetic anhydride over HBEA zeolites.10 In both transformations, the p-isomers are obtained in nearly quantitative yield. 

Thiourea catalyst 139 was also screened in the asymmetric Friedel-Crafts reaction between 2-naphthol trans-nitrostyrene (73% yield 0% ee 18 h in toluene at -20 °C and 10 mol%) [277], in the asymmetric aza-Michael reaction of O-benzyl-hydroxylamine to chalcone (72% conv. 19% ee 72 h in toluene at 20 °C and 20mol% catalyst loading) [293], and in the asymmetric Morita-BayUs-HiUman [176, 177] reaction between cyclohexenecarbaldehyde and 2-cyclohexene-l-one (20% yield 31% ee 46 h at rt and 20mol% DABCO and 139) [310]. In aU these transformations, thiourea 139 proved to be not competitive to the organocatalysts probed for these transformations under identical screening conditions and thus was not employed in the optimized protocols. 

In addition to large-scale industrial applications, solid acids, such as amorphous silica-alumina, zeolites, heteropoly acids, and sulfated zirconia, are also versatile catalysts in various hydrocarbon transformations. Zeolites are useful catalysts in fine-chemical production (Friedel-Crafts reactions, heterosubstitution).165-168 Heteropoly compounds have already found industrial application in Japan, for example, in the manufacture of butanols through the hydration of butenes.169 These are water tolerant, versatile solid-phase catalysts and may be used in both acidic and oxidation processes, and operate as bifunctional catalysts in combination with noble metals.158,170-174 Sulfated zirconia and its modified versions are promising candidates for industrial processes if the problem of deactivation/reactivation is solved.175-178... 

Methods were developed for the preparation of thienoindolizines 254 and thienoquinolizines 255 from derivatives of proline and pipecolinic acid (1993H2303, 1994JHC495, 1996JHC873, 1996PS169, 1999H445). Polyphosphoric acid (PPA) can be used as a cyclizing agent. The reaction can also be performed by the transformation of pipecolinic acids into acid chlorides followed by the intramolecular Friedel-Crafts reaction without isolation of the intermediate. 

Relatively little is known about the photochemistry of phosphorus containing organic substrates. Continuing our photochemical work on compounds of structure 1a and b which leads to thio- and selenoxanthones 3a,b via thiol ester-thiopyrone-, selenol ester-seleninone-transformations ( 1, 2, 3), or photo-Friedel-Crafts-reactions ( 3-6J, respectively, "(ScFeme 1) we have extended our interest to aroyl diphenyl phosphines 1c - k (Schemes 2-5) in which X in 1a and b stands for P-phenyl. 

Three common procedures are available for the transformation of aldehydes and ketones to hydrocarbons (1) reduction by zinc and hydrochloric acid (Clemmensen), (2) reduction by hydrazine in the presence of a base (Wolff-Kishner), and (3) catalytic hydrogenation. In view of the complicated mixtures obtained by the polyalkylation of benzene by the Friedel-Crafts reaction (method 1), reduction of alkyl aryl ketones is the most reliable method for the preparation of di- and poly-alkylbenzenes. 

At oxidation level 3, acid chlorides occupy a key position, since they may serve as a nearly universal substrate for an isohypsic transformation into any kind of carboxylic acid derivative. Acid halides are electrophiles that are synthetically equivalent to acyl cations (RCO ). In this capacity they are used for the synthesis of such important compounds as esters, amides (and hence, nitriles), thioesters, etc. (see Scheme 2.57), and for the formation of C-C bonds in the Friedel-Crafts reaction (see above). Acid chlorides may readily lose HCl upon treatment with triethylamine. This isohypsic conversion leads to ketenes, important reagents widely employed in [2 + 2] cycloadditions, as we will see later. 

It is a general rule that imidazoles and benzimidazoles are resistant to Friedel-Crafts reactions. This is not surprising since such basic compounds must be markedly deactivated in the presence of Lewis acids. Imidazolin-2-ones appear to be an exception and apparently possess sufficient activation to react. Reactions between imidazoles and Af-methylfor-manilide and phosphoryl chloride are also unproductive. With 4,5-diphenylimidazole, phenyl isocyanate at 80 °C gives products of both N- and C-substitution, but in boiling nitrobenzene only the latter (86) is formed. 2-Methyl-4-phenylimidazole gives (87) under the same conditions, and 1,3-diphenylimidazolium perchlorate is transformed by potassium t-butoxide into a ylide which reacts at C-2 with phenyl isothiocyanate. Sufficient activation is present in l-methyl-2-phenyl-4-phenylaminoimidazole for it to react by substitution at C-5 with acetic anhydride (71JOC3368). 

Chiral titanium complexes are also employed as effective asymmetric catalysts for other carbon-carbon bond-forming reactions, for example addition of diketene (Sch. 66) [154c,162], Friedel-Crafts reaction (Sch. 67) [163] (Sch. 68) [164], iodocar-bocyclization (Sch. 69) [165], Torgov cyclization (Sch. 70) [166], and [2 -i- 1] cycloaddition (Sch. 71) [167]. Asymmetric functional group transformations can also be catalyzed by chiral titanium complexes. These transformations, for example the Sharpless oxidation [168] or hydride reduction [169] are, however, beyond the scope of this review because of space limitations. Representative results are, therefore, covered by the reference list. 

Indium(III) chloride and indium(III) triflate have been introduced to organic syntheses as versahle Lewis acids. They are stable in water, and catalyze a variety of organic reachons, e.g. the Diels-Alder reaction, the aldol reaction, Michael addi-hon, the Friedel-Crafts reaction, and other organic transformations. 

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