Friedel-Crafts cyclizations

Friedel-Crafts cyclization benzo[i]thiophenes from, 4, 873 Ethanol, 2-(4-imidazolyl)-synthesis, 5, 484 Ethanol, (S)-l-phenyl-synthesis, 1, 434 Ethanol, 2-phenyl-isochroman synthesis from, 3, 788 Ether, allyl pyridyl... 

Styryl sulfonyl chloride Friedel-Crafts cyclization benzo[h]thiophenes from, 4, 873 Succinic anhydrides polymers, I, 277 mass spectrometry, 4, 585 structure, 4, 552... 

The Friedel-Crafts cyclization of w-(2-thienyl) substituted longer fatty acids (130, n = 5,8,9) under high dilution conditions has been investigated by Goldfarb et They used boiling ethereal AlClg,... 

A great many organic quaternary bases can inhibit the action of acetyl choline in organ systems activated by that neurotransmitter and thus possess anticholinergic-antispasmodic activity. One such agent is methantheline bromide (4), used in the treatment of peptic ulcer and as an antispasmodic agent in intestinal disorders. Its synthesis Involves Friedel-Crafts cyclization of o-... 

Friedel-Crafts cyclization of phenoxy ether 70 leads to the corresponding xanthone TJ Exhaustive oxidation of the methyl group leads to the carboxyl lie acid, xanoxate (72). ... 

Friedel-Crafts cyclization of the dibasic acid gives thiaxanthone 4. Note that the symmetry of this intermediate assures formation of a single product. Desulfurization by means of Raney nickel leads, finally, to the antiinflammatory agent, ketopirofen... 

Base-catalyzed condensation between phenylacetic acid and phthalic acid produces enol lactone 78, which is reduced to benzoate 79 with HI and phosphorous. Friedel-Crafts cyclization by polyphosphoric acid followed by reduction produces alcohol 80. This alcohol forms ethers exceedingly easily, probably via the carbonium ion. Treatment with N-methyl-4— piperidinol in the presence 6f acid leads to the antidepressant hepzidine (81). 

Friedel-Crafts cyclization of that sulfide by means of sulfuric acid gives the desired thioxanthone... 

Finally, the reactions were examined in order to determine their compatibility with the initiation of Friedel-Crafts cyclizations (Scheme 19, Eq. 2). Both the use of an a-stannyl ether and an a-stannyl amide substrates led to cyclized product. 

The Friedel-Crafts cyclization of biphenyl-2-sulfonyl chloride to give dibenzothiophene sulfone has been described (55%) ° however, thermal cyclization in octachloronaphthalene at 250°, under nitrogen, is reported to yield dibenzothiophene itself rather than the sulfone (47%). Reaction of biphenyl compounds with oleum (H2SO4 + SO3) to yield derivatives of dibenzothiophene 5,5-dioxide is widely used for the preparation of dyestuff intermediates (Section VI, E, 2). A typical example is shown in Eq. (3), starting from o-tolidine. ... 

An alternative route to dibenzothiophenebut3o ic acids has been developed involving reaction of 4-lithiodibenzothiophene with menthyl levulate, yielding, after ester hydrolysis, y-hydroxy-y-methyl-4-dibenzothiophenebutyric acid (139). The bulky menthyl group was employed to direct reaction to the ketone moiety of the levulate. Dehydration followed by catalytic hydrogenation yields y-methyl-4-dibenzothiophenebutyric acid, Friedel-Crafts cyclization of which yielded the ketone (140). ... 

Two years later, Craig and Robinson attempted an alternative synthesis of 8 with a more symmetrical pathway starting from derivatives of fluoranthene. Cycliza-tion of fluoranthene-7,10-diacetic acid 14 was attempted to produce diketone 15, expected to enolize to the dihydroxycorannulene 16. Unfortunately, several attempts at cyclization failed, including anhydrous hydrofluoric acid, concentrated sulfuric acid, and polyphosphoric acid. Friedel-Crafts cyclization of the corresponding acid chloride of 14 with aluminum or stannic chloride was similarly unsuccessful. However, although Craig and Robinson were not successful, they developed a convenient synthesis of 7,10-disubstituted fluoranthenes which turned out later to be of premium importance in a new, successful synthesis of corannulene. 

Benzopyrrolo[l,2]oxazepines 68 (X = O) can be obtained from the corresponding acids 67 by an intramolecular Friedel-Crafts acylation (Scheme 14, Section 2.1.1.5 (1996JMC3435, 2002JMC4276)). Similarly, pyrrolo-benzoxazepines 261 are accessible by intramolecular Friedel-Crafts cyclization of acids 260... 

As noted earlier, most classical antidepressant agents consist of propylamine derivatives of tricyclic aromatic compounds. The antidepressant molecule tametraline is thus notable in that it is built on a bicyclic nucleus that directly carries the amine substituent. Reaction of 4-phenyl-l-tetralone (18) (obtainable by Friedel-Crafts cyclization of 4,4-diphenyl butyric acid) with methyl amine in the presence of titanium chloride gives the corresponding Schiff base. Reduction by means of sodium borohydride affords the secondary amine as a mixture of cis (21) and trans (20) isomers. The latter is separated to afford the more active antidepressant of the pair, tametraline (20). 

As mentioned in the introduction, recent synthetic developments now allow access to the 1,2-thiazine structure via disconnection type C (Figure 23). This process can be accomplished by a Friedel-Crafts-type cyclization of sulfamoyl chlorides. The initial report of this reaction utilized a stoichometric amount of aluminium chloride promoter <19920PP463>. Recently, however, A -ethyl phenethylsulfamoyl chloride 214 was shown to undergo Friedel-Crafts cyclization to form sultam 215 with just a catalytic amount of In(OTf)3 (Equation 33) <2002SL1928>. 

An anionic equivalent of the Friedel-Crafts cyclization reaction has been developed for the formation of the C /C-5 bond of the 1,2-benzothiazine structure (Equation 35 Table 5) <1997SL1079>. In this reaction, directed metalation of sulfonamide-substituted aromatic systems 233 with an excess of LDA affords aryl lithium species 234 in a regiocontrolled fashion. This intermediate then reacts in situ with a proximal amide to form l,2-benzothiazine-4-one 1,1-dioxides 235. The yields of this transformation appear to be highly dependent upon the substitution pattern in 233. The authors attribute the low yield when = methyl and = H to a-deprotonation of the amide moiety. 

Among the simplest syntheses of this type are those of tetrahydro-quinolines or -iso-quinolines based on Friedel-Crafts cyclizations. The use of side-chain halides is shown by the synthesis of 1,2,3,4-tetrahydroisoquinolines (158) (71CC799), and of 3,4-dihydroquinol-2-ones (159) (27CB858). Electrophilic carbon atoms can be developed from secondary or tertiary alcohols, or from alkenes or alkynes. In the synthesis of the tetrahydroisoquinoline... 

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