Calix furans

Other interesting new developments in pyrrole chemistry encompass the synthesis of calix[6]pyrrole and calix[ ]furan[m]pyrroles, where m + n = 6 <02CEJ3148>, and the formation of cyclo[8]pyrroles from 2,2 -bipyrrole fragments <02AGE1422>. 

Since a furan ring constitutes a unique synthon (74MI1), calix[ ]furans, for which many preparative-scale methodologies are available, have been advantageously utilized for procuring some unique and often otherwise inaccessible chemical entities, particularly some targeted receptors. 

F.H. Kohnke and co-workers prepared novel heterocyclophanes from cyclic poly-1,4-diketones, which were obtained by the oxidation of calix[6]furan and calix[4]furan. " One of the heterocyclophanes, calix[6]pyrrole, was prepared by the Paal-Knorr pyrrole synthesis from the corresponding dodecaketone. The substrate was heated with excess ammonium acetate in absolute ethanol. Interestingly, the analogous synthesis of calix[4]pyrrole under identical conditions failed, while calix[5]pyrrole is obtained only in 1% yield. 

Cafeo, G., Kohnke, F. H., La Torre, G. L., White, A. J. P., Williams, D. J. From large furan-based calixarenes to calixpyrroles and calix[n]furan[m]pyrroles syntheses and structures. Angew. Chem., Int. Ed. Engl. 2000, 39, 1496-1498. 

Although not formally classified as calixarenes, compounds closely related in architecture to the calix[4jarenes have been prepared by the condensation of furans, thiophenes, and pyrroles with aldehydes and ketones. Furan undergoes acid-catalyzed condensation with aldehydes and ketones to give 15 76-79), as shown in Fig. 9. 

In another version of the single-step approach, ZnCl2/HCl catalysed cyclocondensation of commercially available furfuryl alcohol uniquely provides the parent calix[4]furan (7) in 1% yield and the method on comparison with subsequently reported other methods has been advocated as a convenient preparative scale approach (89AGE1651). 

An indirect two-step synthetic methodology for calix[n]furans (C ) involves the formation of linear oligomers (L ) from furan and carbonyl compounds, followed by condensations of various L and carbonyl compounds or cyclization of an appropriate linear oligomer with a carbonyl compound. On the whole, this methodology constitutes a directed approach for a specified target but its utility depends largely on the availability of the precursor linear oligomers. 

Calix[7]furan derivatives are unknown. However, a recent practical synthesis of L7 9 (R = Me) (2001JCS(P1)3297) may pave the way for its synthesis. Earlier, in the BF3 Et20 catalysed condensation of furyl alcohol and furan (1 2), the formation of L7 25 was reported in 0.5% yield (94JCS(P1)2881). 

The parent calix[8]furan was formed in traces in a BF3 Et20 induced reaction of L3 25, difuryl methane and CH2(OMe)2 (94JCS(P1)2881). HCl induced cyclization of L4 9 (R = Me) with acetone gave Cg 31 in low yield along with major product C4 4 (85JCS(P1)973). The availability of Eg 9 (R = Me) (2001JCS(P1)3297) now could facilitate its formation. 

Acid-induced macrocyclization of L3 9 (R = Me) and acetone did not form the corresponding calix[9]furan either due to the insolubility of Lg or due to the unfavoured macrocyclization. However, Lg (R = Me) when solubilized on treatment with 6 mol of acetone in benzene saturated with HCl readily cyclized to Cg 32 in 45% yield. When L3 9 was subjected to macrocyclization under these conditions, the isolated yields of Cg 29 and Cg 32 were 18% and 6.5%, respectively (96TL4593). 

To provide additional coordination sites, silicon bridged calix[4]furan 33 ( = 1) and calix[6]furan 33 ( = 3) were formed by a condensation of lithiated furan with Me2SiCl2 in 16% and 10% yields, respectively. The X-ray crystal structure of 33 (n = 1) shows a 1,3-alternate conformation of the macrocycle (95JOC7406). 

In BF3 Et20-catalysed (3-I-1) condensations of 38 (Y = NH, R = H) and 38 (Y = O, R = H) with 2,5-Z)A(hydroxymethyl)pyrrole, unsubstituted calix[4]pyrrole (2) and calix[I]furan[3]pyrrole (37), respectively, were isolated for the first time (2001T2103). The appearance of only two singlets for four methylene bridges in the NMR spectrum of 37 suggests its conformational inversion in solution. However, its X-ray structure reveals 1,2-alternate conformation in the solid state. 

The bipyrrole based hybrid calix[2]bipyrrole[2]furan 48 (Z = O), obtained by BF3 Et20 catalysed reaction of 22 (R = Me) with 47 (Z = O) selectively recognizes benzoate ion. In its X-ray structure (Figure 4) two pyrrole rings in each bipyrrole unit are oriented in opposite directions (2003JA13646). 

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