Friedel Crafts cyclodehydration

Anthraquinone itself is traditionally available from the anthracene of coal tar by oxidation, often with chromic acid or nitric acid a more modern alternative method is that of air oxidation using vanadium(V) oxide as catalyst. Anthraquinone is also produced in the reaction of benzene with benzene-1,2-dicarboxylic anhydride (6.4 phthalic anhydride) using a Lewis acid catalyst, typically aluminium chloride. This Friedel-Crafts acylation gives o-benzoylbenzoic acid (6.5) which undergoes cyclodehydration when heated in concentrated sulphuric acid (Scheme 6.2). Phthalic anhydride is readily available from naphthalene or from 1,2-dimethylbenzene (o-xylene) by catalytic air oxidation. 

A -Acylamino aromatic ketones 790 can be prepared by arylation of saturated oxazolones in the presence of Lewis acids. Cyclodehydration of 790 leads to 2,5-diaryloxazoles 791. For example, saturated 5(4//)-oxazolones 789 from 7/-benzoyl-alanine or A-benzoylvaline undergo Friedel-Crafts arylation to afford substituted A-benzoylphenacylamines 790. In the presence of POCI3, 790 cyclizes to produce 5-aryl-2-phenyloxazoles 791 (Scheme 7.241). ... 

Cyclodehydration. Neat, anhydrous CH3S020H is at least as useful as polyphosphoric acid for cyclization of 3-arylpropanoic acids and 4-arylbutanoic acids to indanones and tetralones.1 However, it does not appear to be useful for intermolecular Friedel-Crafts condensation. Examples ... 

The commercial preparation of anthraquinone dyes begins with the synthesis of anthraquinone itself. In this regard, the three-step synthesis involves (1) the oxidation of naphthalene to phthalic anhydride, (2) Friedel-Crafts acylation of benzene to give a keto acid, and (3) cyclodehydration using H2S04. See Fig. 13.110. The preparation of 1,4-disubstituted anthraquinones utilizes the intermediates... 

The tanshinones are diterpenoid furanoquinones which occur in the roots of Salvia miltiorrhiza. The syntheses of tanshinone II and cryptotanshinone were accomplished from 1,2,4-trimethoxybenzene. This was converted by a Friedel-Crafts acylation to 2,4,5-trimethoxybenzoylpropionic acid and thence to the tetralone (125). The tetralone was condensed with ethyl y-bromocrotonate and the product converted directly to a naphthylbutyric ester. Curiously, an aromatic methoxy-group was displaced in this reaction. Reaction of the ethyl ester with methyl magnesium iodide and cyclodehydration afforded the tetra-hydrodimethoxyphenanthrene (126). The furan ring was added via the derivative (127) which underwent cyclization and decarboxylation to afford (128). Hydrolysis and oxidation gave the tanshinone (129). 

Oxazolones undergo Friedel-Crafts reactions with aromatic compounds to give keto intermediates which, under the reaction conditions, cyclodehydrate to give 5-aryl-oxazoles (Equation 7) <2005JOC4211>. 

Unmodified acid clays have been little utilized as catalysts for Friedel-Crafts acylation reaction. Among the scanty information from the literature, the production of AQ 22 through cyclodehydration of BBA 21 is of some interest (Scheme 4.22). The reaction is performed in the presence of different clays at 350°C for 30 min. AQ 22 is directly recovered by sublimation from the reaction mixture. Some interesting results are achieved with commercially available catalysts such as Tonsil BW3, a mixture of mica, quartz, feldspar, and amorphous silica with bentonite and mont-morillonite KIO, product 22 being obtained in 78%-89% yield. Reusability studies show that Tonsil BW3 still gives product 22 in 60% yield after five... 

A short synthesis of calamenene (208) has been achieved by cyclodehydration of the tertiary alcohol (207) with phosphorus pentoxide. The mechanism of this reaction probably involves a carbonium ion re-organization followed by an intramolecular Friedel-Crafts alkylation. In an independent study Wender and... 

In 2010, Kim and Kim [23] reported a noteworthy domino approach to the first total synthesis of diptoindonesin G (52) (Scheme 14.9). The oligostilbenoid, possessing strong cytotoxic and immunosuppressive activity [24], was recently isolated from the tree bark of Hopea mengarawan [25]. In a domino cyclodehydration/Friedel-Crafts acylation/demethylation sequence, Kim... 

Two mechanisms can be envisioned for the Pechmann condensation (1) acid-catalyzed transesterification of the P-keto ester followed by acid-catalyzed cyclodehydration of the resulting aryl acetoacetate (4), or (2) acid-catalyzed Friedel-Crafts-like phenol alkylation ortho to the phenolic hydroxyl group) followed by intramolecular transesterification/cyclization of the resulting o-hydroxycinnamic acid ester (5). 

As alluded (vide supra), some confusion may arise with respect to this named reaction as there is reference in the literature to an alternative reaction with the same name. The Bradsher reaction forms aromatic rings but via an acid-catalyzed Friedel-Crafts-like process. Thus diaryl-methanes having a carbonyl group in the ortho position can undergo a cyclodehydration reaction to generate the corresponding anthracene derivatives. In this respect, the Bradsher reaction is related to the Elbs reaction, which involves the pyrolytic cyclization of diaryl ketones 6 having an ortho methyl or methylene substituent for the formation of polycyclic aromatics 7. 

Later, they reported Friedel-Crafts type cyclodehydration of 1,3-diphenyl-1-propanone [35], Pictet-Spengler reaction [36], andphenylation ofbenzaldehyde [37], which was also reported by Olah et al. at the same time (Scheme 2.14) [38]. These reactions proceed through a dicationic intermediate. As dicationic intermediate of benzaldehyde, Shudo proposed 0,0-diprotonated compound, while Olah proposed 0,meta-C-diprotonated benzaldehyde. 

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