Ring closure Friedel-Crafts

A novel synthetic method for the preparation of two cytotoxic furonaphthoquinones 5a,b was reported. Regjospecific metallation of 3-furoic acid (3) at the 2-position using LDA at -78°C and subsequent treatment with the corresponding aldehydes ( R = H, OMe) affords the acids 4 (X = OH) which after reduction (to 4b with iodotrimethylsilane) and ring closure (Friedel-Crafts) were transformed to 5a,b <95JCS(P1)1085>. 

Chloroanthraquinone [131-09-9] (65) is prepared by Friedel-Crafts reaction of chlorobenzene and phthaUc anhydride ia the presence of aluminum chloride followed by ring closure ia concentrated sulfuric acid (91). 

Ainino-3-chloroanthraquiQone [84-46-8] (68) is prepared from 2,3-dichloroanthraquiQone by partial chlorine replacement by a NH2 group. 2,3-Dichloroanthraquiaone [84-45-7] (67) is prepared by Friedel-Crafts reaction of phthaUc anhydride and 1,2-dichlorobenzene followed by ring closure of the resultant benzoylbenzoic acidia sulfuric acid (94). 

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 ... 

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. 

An important use of the Friedel-Crafts alkylation reaction is to effect ring closure. The most common method is to heat with aluminum chloride an aromatic compound having a halogen, hydroxy, or alkene group in the proper position, as, for example, in the preparation of tetralin ... 

Another way of effecting ring closure through Friedel-Crafts alkylation is to use a reagent containing two groups, for example. 

These reactions are most successful for the preparation of six-membered rings, though five- and seven-membered rings have also been closed in this manner. For other Friedel-Crafts ring-closure reactions, see 11-13, 11-14, and 11-23. 

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. 

Furthermore, if the 2,4,6-triphenyl ester (187a) is dissolved in cone. H2S04 the brilliant colour of 1,3-diphenylfluorenone is at once observed—obtained via ring-closure (intramolecular Friedel-Crafts acylation) of the acyl cation (188a) ... 

The cyclic stage of the reaction with sodamide in liquid ammonia corresponds to a Friedel-Crafts ring closure reaction in the carbonium ion series, a reaction that is often an alternative to the carbonium ion rearrangement. 

It is well known (March, 1977) that an important synthetic application of Friedel Crafts alkylation and acylation is to effect ring closure. These reactions are most successful when 6-membered rings are formed, but 5- and 7-membered rings can be sythesised as well, although less readily. Quantitative data are not available, but the indication is strong that formation of... 

The Friedel-Crafts reaction, which proceeds via electrophilic aromatic substitution, as illustrated in the following scheme, is unique to the manufacture of anthanthrone pigments. Most other polycyclic anthraquinone pigments are synthesized via nucleophilic ring closure. 

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.38,39 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. 

Perimidine derivatives 1016 are best prepared from 1,8-naphthalenediamines 1015 by ring-closure methods <1981RCR816, 1995AQ151>, while benzo[g,4]perimidines 1017 are available in moderate yields from perimidines using Friedel-Crafts reaction conditions <2003CHE1417>. 

Related to these intramolecular Friedel-Crafts cyclizations are the aluminum chloride and PPA catalyzed ring closures of 3-phenylpropyl iso- and thioiso-cyanates to 2H-2-benzazepin-l-ones and their -1-thiones respectively (79H(12)131i, 77JCS(Pl)2357). The method has also been applied to the cyclization of o-isocyanatodiphenylmethanes to 5,6-dihydro[6,e]azepin-6-ones (65HCA336). 

Diaryl sulfides can be prepared by treating aromatic compounds with SC12 and a Friedel-Crafts catalyst. Other reagents that can bring about the same result are S2C12, thionyl chloride, and even sulfur itself. A catalyst is not always necessary. The reaction has been used for ring closure ... 

Scholl ring closure 1-14 Intramolecular Friedel-Crafts acylation... 

---