Friedel cyclization

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). 

Unusual cyclocarbonylation of allylic acetates proceeds in the presence of acetic anhydride and an amine to afford acetates of phenol derivatives. The cinnamyl acetate derivative 408 undergoes carbonylation and Friedel-Crafts-type cyclization to form the a-naphthyl acetate 410 under severe condi-tions[263,264]. The reaction proceeds at 140-170 under 50-70 atm of CO in the presence of acetic anhydride and Et N. Addition of acetic anhydride is essential for the cyclization. The key step seems to be the Friedel-Crafts-type cyclization of an acylpalladium complex as shown by 409. When MeOH is added instead of acetic anhydride, /3,7-unsaturated esters such as 388 are... 

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. 

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... 

Acyclic C5. The C5 petroleum feed stream consists mainly of isoprene which is used to produce rubber. In a separate stream the linear C5 diolefin, piperylene (trans and cis), is isolated. Piperylene is the primary monomer in what are commonly termed simply C5 resins. Small amounts of other monomers such as isoprene and methyl-2-butene are also present. The latter serves as a chain terminator added to control molecular weight. Polymerization is cationic using Friedel-Crafts chemistry. Because most of the monomers are diolefins, residual backbone unsaturation is present, which can lead to some crosslinking and cyclization. Primarily, however, these are linear acyclic materials. Acyclic C5 resins are sometimes referred to as synthetic polyterpenes , because of their similar polarity. However, the cyclic structures within polyterpenes provide them with better solvency power and thus a broader range of compatibility than acyclic C5s. 

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,... 

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... 

Reaction of the potassium salt of salicylaldehyde with chlo-roacetone affords first the corresponding phenolic ether aldol cyclization of the aldehyde with the ketonic side chain affords the benzofuran (1). Reduction of the carbonyl group by means of the Wolf-Kischner reaction affords 2-ethyl-benzofuran. Friedel-Crafts acylation with anisoyl chloride proceeds on the remaining unsubstituted position on the furan ring (2). The methyl ether is then cleaved by means of pyridine hydrochloride (3). lodina-tion of the phenol is accomplished by means of an alkaline solution of iodine and potassium iodide. There is thus obtained benziodarone (4)... 

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). ... 

Starting material for the first of these agents can in principle be obtained by alkylation of phenol with benzyl chloride 89. Cyclization of the product (90) under Friedel-Crafts conditions leads directly to isoxepac (91). ... 

Raston has reported an acid-catalyzed Friedel-Crafts reaction [89] in which compounds such as 3,4-dimethoxyphenylmethanol were cyclized to cyclotriveratrylene (Scheme 5.1-57). The reactions were carried out in tributylhexylammonium bis(tri-fluoromethanesulfonyl)amide [NBu3(QHi3)][(CF3S02)2N] with phosphoric or p-toluenesulfonic acid catalysts. The product was isolated by dissolving the ionic liq-uid/catalyst in methanol and filtering off the cyclotriveratrylene product as white crystals. Evaporation of the methanol allowed the ionic liquid and catalyst to be regenerated. 

The Fries rearrangement can be viewed as a type of Friedel-Crafts acylation reaction. Two examples of this reaction are given in Scheme 5.1-61. The first is the rearrangement of 4,4 -diacetoxybiphenyl to 4,4 -dihydroxy-3,3 -diacetoxybiphenyl in a NaCl/AlCl3 (X(A1C13) = 0.69) molten salt [93]. The second example is the rearrangement of phenyl 3-chloropropionate to 2 -hydroxy-3-chloropropiophenone, followed by cyclization to an indanone [94]. 

Substituted 2-phenoxyphenylacetic acids readily cyclize under Friedel-Crafts conditions or acid catalysis to give dibenz[Z>,/]oxepin-10(l l//)-ones.71 85,104- 108 When this reaction is carried out in methanolic hydrochloric acid the 10-methoxy-substituted dibenz[6,/]oxepin system 9a can be isolated.109 5-(Nitro-2-phenoxyphenyl)-2-oxopropanoic acid undergoes cyclization in the presence of polyphosphoric acid yielding the carboxylated dibenzoxepin 9b.107... 

Dichloroalkyl)chlorosilanes undergo the Friedel-Crafts alkylation type reaction with biphenyl in the presence of aluniinurn chloride catalyst to afford 9-((chlorosilyl)alkyl)fluorenes through two step reactions (Eq. (16)). The results obtained from the alkylation of biphenyl and the cyclization reaction to 5-membered-ring product are summarized in Table XIIE... 

The acyclic oligoynes 23-26 can be cyclized under Friedel-Crafts conditions, i. e. by treatment with AICI3 in CS2, which presumably proceeds via the intermediate tertiary propargylic 27 and )3-silyl-substituted vinylic carbocations of type 28 (Scheme 5). 

The cyclization to structurally defined, soluble LPPP takes place in a two-step sequence, consisting of a reduction of the keto group followed by ring closure of the secondary alcohol groups of 28 in a Friedel-Crafts-type alkylation. 

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. 

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. 

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... 

Friedel-Crafts alkylation can occur intramolecularly to form a fused ring. Intramolecular Friedel-Crafts reactions provide an important method for constructing polycyclic hydrocarbon frameworks. It is somewhat easier to form six-membered than five-membered rings in such reactions. Thus, whereas 4-phenyl-1-butanol gives a 50% yield of a cyclized product in phosphoric acid, 3-phenyl-1-propanol is mainly dehydrated to alkenes.43... 

Cyclizations can also be carried out with an esterified oligomer of phosphoric acid called polyphosphate ester, which is chloroform soluble.55 Another reagent of this type is trimethylsilyl polyphosphate (Scheme 11.4, Entry 13).56 Neat methanesul-fonic acid is also an effective reagent for intramolecular Friedel-Crafts acylation (Scheme 11.4, Entry 14).57... 

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