Aromatic nucleophilic displacement cyclization

Sodium azide also adds to olefins of this t3rpe to give w-triazoles in fairly good yields. A mechanism involving nucleophilic displacement of the substituent X by azide, followed by cyclization of the vinyl azide in the presence of azide ions, has been suggested. An alternative mechanism involves conjugate addition of azide to the double bond, cyclization of the resulting anion, and aromatization. 

As is true for other classes of aromatic nucleophilic substitution, the halogen displacement can frequently be catalyzed by copper or copper(I) salts. Using sodium hydride as the base and copper(I) iodide as catalyst, a series of o-bromophenylethylamine derivatives, including both amides and carbamates, have been cyclized. Oxidation to the indole can be effected with manganese dioxide (81JCS(P1)290). 

We wondered if this reaction might be exploited to construct the angularly condensed benzo[a]anthracenes. A problem was the aromatization of the initially formed hydroaromatic ring A under the relatively drastic basic reaction conditions. The starting material 12 was synthesized in a stepwise manner from l-hydroxy-5-methoxy-9,10-anthraquinone [23]. The crucial cyclization can mechanistically be regarded as an intramolecular nucleophilic displacement of the methoxy group to afford a keto ester 13 with about 55% yield (Scheme 5). Only a few nucleophilic additions to electron-deficient anthraquinones are known [20,24,25] and intramolecular reactions of this type are more facile [21, 26-30]. The subsequent ethoxydecarbonylation under acidic conditions to yield ketone 14 presented no problem. 

The synthesis of non-peripherally substituted octa(alkoxymethyl)phthalocyanines is outlined in Seheme 57 [213, 214]. 2,5-fcij(Alkoxymethyl)furan can be prepared by lithiation of furan followed by quenching the anion with (bromomethyl)alkyl ether to give the mono-substituted furan, and repetition of the procedure to give the required product [213]. A more simple synthesis involves chlorination of 2,5-furan dimethanol with thionyl chloride, followed by nucleophilic displacement of chloride with sodium alkoxide [214]. The furan is equilibrated with fumaronitrile for about a week and the Diels-Alder adduct aromatized by treatment with lithium fcwftrimethylsilyl)-amide (a non-nucleophilic base), followed by an acidic work-up. The 3,6-/7i5(alkoxy-methyl)phthalonitrile is cyclized under standard conditions (lithium/pentanol). 

From -Chlorovinylmethine-immonium and Bunte Salts Types C and E). j8-Chloro-vinylmethine-immonium salts (9) react with alkali-metal thiocyanates in the presence of aromatic amines to give isothiazoles (10). The reaction is considered to proceed by a nucleophilic displacement to give eventually the jS-thiocyanovinyl aldehyde anils ArC(SCN)=CHCH=NR, which cyclize in situ. The reaction of (9) with sodium thiosulphate gives Bunte salts, which react with amines (R R NH) to give the stable j8-aminovinyl thioketones (11), and hence, by oxidative cycliza-tion, the isothiazolium salts (10 R = H) (Scheme 1). 

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