Methoxyphenyl cyclisation

Hydrolysis of the ester functions of dimethyl 2,2-bis(4-methoxyphenyl)-277-naphtho[l,2-6]pyran-5,6-dicarboxylate and cyclisation of the resulting dicarboxylic acid yields the cyclic anhydride 51. Reduction affords a mixture of two isomeric furano-fused naphthopyrans. Treatment of the anhydride with primary amines provides a route to the corresponding pyrrole derivatives. Both types of hetero-fused naphthopyrans show a red shift relative to the starting naphthopyran diester and reduced half-lives <01 WOP32661>. 

The treatment of saturated enolisable aldehydes and ketones with acids is known to result in aldol condensation [1]. In the case of arylethanoid derivatives, this treatment results concomitantly in aldol condensation followed by cyclisation and aromatisation. Furthermore, when the acid used is known to promote the demethylation of methoxyphenyl derivatives into phenols, this reaction appears to lead to a great structural diversity of biologically active natural and synthetic polyphenols. In this review, I will focus on the reaction of arylpropanoid and arylethanoid derivatives with acids, mainly boron tribromide but also simple protic acids. The former allows, in a one-pot procedure, aldol condensation, cyclisation, aromatisation and demethylation. The latter may be used... 

In connection with our studies on the dimerisation of aylethanals and arylacetones with boron tribromide, we first turn to the reaction of methoxylated arylpyruvic acids [38], Arylpyruvic acids that were obtained mainly in their Z-enol form, did not dimerise. When the ortho aromatic position is unsubstituted, only an isomerisation occurs that allowed us to isolate some 2-hydroxyarylpropenoic acids in their E-form. In the cases of (2-methoxyphenyl)arylpropenoic acids, cyclisations were also observed leading of mixtures of benzofuran-2-carboxylic acids and 3-hydroxycoumarins that are easily separated, Fig. (12). We observed a competition between cyclisation and isomerisation that have apparently similar kinetic parameters. 

The fourth part of this review concerns the development of the previously described intramolecular cyclisation of 2-methoxyphenyl acetones and 2-hydroxy-3-(2-methoxyphenyl)propenoic acids leading to 2-substituted benzofurans [17, 38]. 

In a similar general way trifluoroacetyl derivatives have been cyclised. N-Hydroxy 1-(3-methoxyphenyl)-2-aminopropane in trifluoroacetic acid and trifluoroacetic anhydride upon refluxing for 15 hours afforded... 

Methoxy-1,2,3,4-tetrahydroisoquinoline has been obtained through lithiation with butyllithium between the methoxyl group and the side-chain in N-pivaloyl 2-(3-methoxyphenyl)ethylamine (X = H), formylation with dimethylformamide to give the formyl compound (X = CHO), followed by cyclisation with 10% hydrochloric acid and finally reduction with sodium borohydride (ref. 150). 

With the related 6-methoxy compound shown the cyclisation to a morphinan with hydrochloric acid proceeded to the unwanted product C in 37% yield and the desired one in only a 3% yield (ref. 179). The same precursor, synthesised from 2-(3-methoxyphenyl)ethylamine and 3,4-dimethoxyphenylacetic acid by amide formation and ring closure by the Bischler-Napieralski cyclisation, followed by reduction, methylation and Birch reduction, was used by others with similar results (ref. 180). The route constitutes a synthesis of morphine by the use of the final steps of earlier work (refe. 169,171), albeit in low yield, although in considerably fewer steps than the earlier syntheses. 

Cyclisation of some unsymmetrically substituted 2,6-dihydroxyphenyl ketones with ethyl oxalyl chloride gives isomeric chromones, as, for example, compounds (19) and (20) from the ketone (18). The product whidi was originally believed [91] to be the 6-methyl isomer (20) was later shown [92, 93] to be a mixture of chromones (19) and (20). Some unsymmetrical ketones behave similarly [74,94] but others react to give one isomer only for example, 2,4,6-trihydroxy-3-methoxyphenyl 4-hydroxybenzyl ketone (21) cyclises with ethyl oxalyl chloride to give the 8-methoxychromone (22) [65] whose structure has bwn confirmed [95] by an independent synthesis. 

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