Friedel-Crafts reaction intramolecular

This reflects a rather general tendency for the formation of six-membered rings in preference to five- and seven-membered rings in ring closure by intramolecular Friedel-Crafts reactions. Intramolecular Friedel-Crafts reactions provide an important method for constructing polycyclic hydrocarbon frameworks. Entries 5-7 in Scheme 11.3 are examples of this type of reaction. 

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. 

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... 

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... 

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

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. 

A bottle of the dichloride exploded violently while on a bench. No cause was established, but diffusive ingress of moisture, or an intramolecular Friedel-Crafts reaction, both of which would form free hydrogen chloride, seem possible contributory factors. 

Typically in ring-opening reactions of aziridines, the amine functional group is retained in the product molecule. An example of such a reaction where the amine group has been lost has recently been reported <06TL977>. An intramolecular Friedel-Craft reaction of aziridine 91 leads to the expected product as an intermediate. Under the rather drastic reaction conditions, the sulfonamide is lost leading to formation of the naphthalene ring. 

Intramolecular Friedel-Crafts reactions can sometimes compete with organosil-icon hydride reductions of benzylic-type alcohols to cause formation of undesired products. An example is the attempted reduction of alcohol 26 to the corresponding hydrocarbon. When 26 is treated with triethylsilane in trifluoroacetic acid at room temperature for 15 hours, a mixture of the two fluorene isomers 27 and 28 is obtained in a combined yield of 45%. None of the hydrocarbon structurally related to the substrate alcohol 26 is obtained.171 Whether this problem could be circumvented by running the reduction at a lower temperature or with a different acid remains subject to experimentation. 

Intramolecular Friedel-Crafts reactions have also been used to synthesize benzannelated dibenzofurans. 126... 

In a similar manner, an intramolecular Friedel-Crafts reaction of 2-aryl-4-(2-thienylidine)-5(477)-oxazolones 600 has been reported and, in this case, cycliza-tion and decarboxylation generates thienopyridines 601 (Scheme 7.192). ... 

Several of the well known cyclization reactions of aromatics that are used for the preparation of benzoheterocycles also work for pyridines (66AHC(6)229). 3-Aminopyridine undergoes the Skraup reaction (equation 59), and the substituted 3-amino derivative (97) undergoes intramolecular Friedel-Crafts reaction (equation 60). Further examples of these reactions can be found in the appropriate part of Chapter 2.06. 

Dihydroarsanthridines (106) have been prepared by an intramolecular Friedel-Crafts reaction. By this route were prepared the 5-methyl and 5-phenyl derivatives which were characterized as the crystalline methiodides (49JCS2888). The second system is the 2,3-dihydro-LF/-naphth[l,8-a/]arsenin ring system (107). This is an oil which could not be obtained crystalline but was characterized as the methiodide (50JCS1917). 

SE-Substitution has been found when a-bromoallylsilane 7 is treated with tert-alkyl chloride in the presence of TiCLt at —78°C to give 9440. The reaction with a-bromoethylbenzene under the same conditions yields the corresponding indane 96. Apparently, the intermediate 95 may further undergo an intramolecular Friedel-Crafts reaction under these conditions (equation 74)... 

The intramolecular cyclization of 2-(3,4-dimethoxybenzyl)-3-(N-ben-zyl-4-piperidinyl)propionic acid 1 followed by treatment with HC1 [18] as shown in Scheme 3.6. Cyclization of compound 1 was carried out under Friedel-Crafts reaction conditions, optionally with previous derivatization of the carboxylic group to a halocarbonyl group. Preferably, the cyclization process was carried out in the presence of protic acids or Lewis acids or a mixture of protic and Lewis acids gives donepezil 2 which is converted to the hydrochloride salt 3. 

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