MACRO RINGS .35. TRANSANNULAR DIRECTIVE INFLUENCES IN ELECTROPHILIC SUBSTITUTION OF MONOSUBSTITUTED [2.2]PARACYCLOPHANES

The patterns of electrophilic substitution of the monosubstituted [2.2]paracyclophanes have been examined. The isolated yields (minimal) of products were as follows.3 Acetylation (methylene dichloride-alu-minum chloride) of 4-bromo[2.2]paracyclophane (I) gave 6% pseudo-o- (II), 41% pseudo-p- (III), and 17% p- (IV) (indirect detection) bromoacetyl derivatives. Nitration of I in acetic acid gave 5% pseudo-o- (IX), 4% pseudo-p-(X), 3% pseudo-m- (XI), and 2% p- (XII) bromonitro derivatives. Small amounts of pseudo-p-bromoacetoxy derivative XIV and of a substance derived by adding the elements of nitronium acetate to I (possibly compound XVIa) were also isolated. When treated with base, the latter substance gave pseudo-gem-bromonitro derivative (XIII). Iron-catalyzed bromination in methylene dichloride of 4-carbomethoxy[2.2]paracyclophane (XVII), of 4-carboxy-[2.2]paracyclophane (XVIII), or of 4-acetyl[2.2]paracyclophane (XXII) gave substituted pseudo-gem materials as sole products. Bromo ester XIX was obtained in 89% yield, bromo acid XX in 63%, and bromoacetyl compound VI in 59% yield. Iron-catalyzed bromination of 4-nitro[2.2]paracyclophane in methylene dichloride gave bromonitro derivatives in the following yields: pseudo-gem (XIII), 70%; pseudo-ortho (IX), 3%; pseudo-para (X), 6%; pseudo-mera (XI), 8%. Iron-catalyzed bromination in methylene dichloride of 4-cyano[2.2]paracyclophane (XXIII) gave 16% pseudo-ortho (XXIV), 28% pseudo-para (XXV), and 26% pseudo-meta (XXVI) bromocyano derivatives. Compatibility of structural assignments based on nmr spectra of these compounds was demonstrated through many interconversions. Iron-catalyzed bromination in methylene dichloride or noncatalyzed bromination in acetic or trifluoroacetic acid of 4-methyl[2.2]paracyclophane (XXX) gave predominantly o- and p-bromomethyl derivatives XXXI and XXXII, respectively. The ratios of yields of these isomers varied depending on medium, and on whether XXX contained deuterium in the position para to the methyl group. From the change in ratio, with the isotope being substituted, primary isotope effects were estimated for para substitutions: kHkD ≥ 3.7 (methylene dichloride-iron); kh/kD ≥3.9 (trifluoroacetic acid); and kh/kd≥1.5 (acetic acid). The para product (XXXII) from deuterated starting material contained no deuterium when bromination was carried out in acetic acid, but did contain 45% of one atom of deuterium in the unsubstituted ring from bromination in trifluoroacetic acid or in methylene dichloride with an iron catalyst. These patterns of substitution reactions, when not random, are correlated in terms of a rate-limiting and product-determining step in which the proton being substituted is transferred from a ücomplex to the strongest base in the proximity. In very nonbasic solvents the most basic position of the transannular ring accepts the proton in substitution of 4-methyl- and 4-bromo[2.2]paracyclophanes. Substituents that carry basic oxygen su h as carbomethoxy, carboxy, acetyl, or nitro direct entering substituents pseudo-gem by accepting the leaving group. © 1969, American Chemical Society. All rights reserved.