Friedel intramolecular

The Y-phenylbutyric acid is cyclised to a-tetralone by converting it into the acid chloride with thionyl chloride or phosphorus pentachloride and then an intramolecular Friedel and Crafts reaction is carried out ... 

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

Rctrosynthetic path a corresponds to Pd-catalysed exo-trig cyclization of o-halo-JV-allylanilines. Path b involves the endo-trig cyclization of o-halo-JV-vinyl anilines. Path c is a structurally similar cyclization which can be effected photochemically in the absence of an o-substituent. Retrosynthetic path d involves intramolecular Friedel-Crafts oxyalkylation followed by aromatiz-ation. 

Laurino examined a similar method in which methanesulfonanilides were alkylated with bromoacetaldehyde diethyl acetal and then cyclized with TiCU[4J. 1 hese methods presumably involve generation of an electrophilic intermediate from the acetal functionality, followed by an intramolecular Friedel-Crafts reaction. As a consequence, the cyclization is favoured by ER substituents and retarded by EW groups on the benzene ring. 

Intramolecular Friedel-Crafts substitution has also figured prominently in the synthesis of oxindoles from cx-haloacelanilides. Typical reaction conditions for cyclizalion involve heating with A1CI,[13-17]. 

Preformed Carbocationic Intermediates. Propargyl cations stabilized by hexacarbonyl dicobalt have been used to effect Friedel-Crafts alkylation of electron-rich aromatics, such as anisole, /V, /V- dim ethyl a n il in e and 1,2,4,-trimethoxybenzene (24). Intramolecular reactions have been found to be regio and stereo-selective, and have been used ia the preparatioa of derivatives of 9JT- uoreaes and dibenzofurans (25). 

Intramolecular Friedel-Crafts acylations of olefins also give cycHc a,P-unsaturated cycHc ketones. Cyclopropane fused bicyclo[5.3.0]octenones, thus obtained, were used in the preparation of the marine sesquiterpenes, africanol [53823-07-7] and dactjlol [58542-75-9] (174). 

Quinolin-2-one, 3-cyano-4-hydroxy-synthesis, 2, 428 Quinolin-2-one, 3,4-dialkyl-Knorr synthesis, 2, 425 Quinolin-2-one, dihydro-Camps synthesis, 2, 418 synthesis, 2, 402 from benzazepinones, 2, 506 from indanone oxime, 2, 487 from indanones, 2, 488 by intramolecular Friedel-Crafts reactions, 2, 421... 

Each of the compounds indicated undergoes an intramolecular Friedel-Crafts acylation reaction to yield a cyclic ketone. Write the structure of the expected product in each case. 

An ingenious synthesis of 1-arylisoindolcs has been developed by Vebor and Lwowski, based upon the reaction of an o-phthalimido-methylbenzophenone (41, R = aryl) with hydrazine (Table IV). The benzophenone is prepared by a Friedel-Crafts reaction with o-phthalimidomethylbenzoyl chloride (40). The mechanism of isoindole formation can be represented sehematically by a sequence involving attack by hydrazine at the imide to give the ring-opened hj drazide (42), followed by cyclization to phthalazine-l,4-dione (44) with displacement of the o-aminomethylbenzophenone (43). Intramolecular condensation of the latter can lead, via the isoindolenine... 

An important application of the Friedel-Crafts acylation is the intramolecular reaction, leading to ring closure. This variant is especially useful for the closure of six-membered rings, but five-membered ring products and larger rings, as well as heterocycles, are also accessible ... 

The. synthesis starts with the Stobbe condensation of diethylsuccinate and 3,4-dichloroben-zophenone (13). The product (14) is hydrolyzed and decarboxylated to a cis-trans mixture of olefins (15). This last is reduced using a Pd/C catalyst and then undergoes unidirectional Friedel-Crafts intramolecular acylation into the more reactive ring to produce substituted tetralone 16. 

Dibenzo[7>,/]thiepins, e.g. 2, are obtained from 2-(arylsulfanyl)benzenepyruvic or -acetic acids by intramolecular Friedel-Crafts acylation, followed by elimination of water or hydrochloric acid.3 60... 

Polyphosphoric acid is a commonly used catalyst for this reaction however, in some cases a mixture of hydrogen bromide/acetic acid gives better results. Acylation of the S-phenyl-, V-(4-tolyl)- or S-(l-naphthyl)-substituted thiobenzenepyruvic acids 3a-c affords the corresponding dibenzo[A,/]thiepins in satisfactory yields, while reaction of the S-(4-methoxyphenyl) or S-(2-naphthyl) derivatives fails to provide any thiepin.60 The intramolecular Friedel-Crafts acylation of 2-(arylsulfanyl)benzeneacetic acids also yields the corrresponding dibenzothiepins in this case the use of hydrogen fluoride sometimes results in purer products.38 The applicability of this method is restricted to the synthesis of stable bisannulated thiepins. 

Of Acid Chlorides by Intramolecular Friedel-Crafts Reaction... 

Intramolecular Friedel-Crafts acylation has been observed with bonellin dimethyl ester (20).53 The reaction proceeds in contrast to corresponding porphyrins, very smoothly with concentrated sulfuric acid because the propanoic acid side chain at the sp3 center is located above the macrocyclic ring system and therefore can better fulfill the stereoelectronic requirements for the ring-closure reaction. The ring closure is accompanied by racemization in the product 21. 

Other methods for the regioselective SN2-opening of vinyloxiranes include intramolecular enolate addition for formation of cyclohexane systems [135, 136] and Friedel-Crafts alkylations [49, 137, 138]. 

For example /-butyl phenyl ether with aluminium chloride forms para-t-butyl phenol155. Often the de-alkylated phenol is also formed in considerable quantity. The reaction formally resembles the Fries and Claisen rearrangements. Like the Fries rearrangement the question of inter- or intramolecularity has not been settled, although may experiments based on cross-over studies156, the use of optically active ethers157 and comparison with product distribution from Friedel-Crafts alkylation of phenols158 have been carried out with this purpose in view. 

By Arenes Intramolecular Friedel-Crafts Arene Acylation.189... 

Chromium carbene complexes having electron-rich arenes tethered to the car-bene oxygen or carbon underwent photodriven intramolecular Friedel-Crafts acylation in the presence of zinc chloride (Eqs. 32 and 33) [118]. The process was highly regioselective, undergoing acylation exclusively para to the activating group. 

Aryl halides can be dehalogenated by Friedel-Crafts catalysts. Iodine is the most easily cleaved. Dechlorination is seldom performed and defluorination apparently never. The reaction is most successful when a reducing agent, say, Br or 1 is present to combine with the I" or Br coming off." Except for deiodination, the reaction is seldom used for preparative purposes. Migration of halogen is also found," both intramolecular and intermolecular." The mechanism is probably the reverse of that of 11-11." ... 

Intramolecular Friedel-Crafts acylation of diaryl ketones Oxidation of phenols or aromatic amines Oxidation of aromatic hydrocarbons... 

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. 

Scheme 6 Iron(III)-catalyzed conversion of 2-alkylcinnamaldehydes to 2-alkylindanones via a catalytic intramolecular Friedel-Craft reaction...

As described above, propargylic alcohols can serve as electrophilic aUcyl equivalents in intermolecular Friedel-Crafts reactions. However, the related intramolecular... 

Friedel-Crafts reaction remains unexplored, possibly due to the difficulty of the cycloalkyne formation. A mild, versatile, and efficient method for the one-step synthesis of substituted dihydro- and tetrahydroisoquinolines has been developed by the FeCl3-6H20-catalyzed intramolecular allenylation/cyclization reaction of benzylamino-substituted propargylic alcohols, representing the first example of the intramolecular Friedel-Crafts reaction of propargylic alcohols (Scheme 8) [24, 25]. FeCls, InCls, and Yb(OTf)3 also exhibit good catalytic activity for the reaction. 

Scheme 8 One-step synthesis of substituted dihydro- and tetrahydroisoquinolines by FeCl3-6H20-catalyzed intramolecular Friedel-Crafts...

An interesting intramolecular Friedel-Crafts-type cyclization was developed by Pericas et al. Thus, aryl glycidyl ethers reacted to 3-chromanols as the only reaction product when treated with a catalytic amount of FeBr3 in the presence of AgOTf in CH2CI2 at room temperature (Scheme 9) [26]. The addition of a silver salt proved to... 

Ferrocene Bisimidazoline Platinacycle-Catalyzed Intramolecular Friedel-Crafts Alkylations... 

Highly reactive mixed anhydrides can also promote acylation. Phenylacetic acid reacts with alkenes to give 2-tetralones in TFAA-H3P04.55 This reaction involves an intramolecular Friedel-Crafts alkylation subsequent to the acylation. 

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