Macro Rings . XXXVII . Multiple Electrophilic Substitution

Dibromination of [2.2]paracyclophane (I) led to predominantly pseudo-ortho2 (11) and pseudo-para2 (111) disubstituted compounds, and to lesser amounts of pseudo-meta (IV) and para (V) isomers. Oxidation of these dibromides gave terephthalic acids whose esters were identified by vpc, and whose structures allowed homoannular and transannular bromination to be differentiated. Tetrabromination of I gave compound VI with two p-bromines in each ring with a set of pseudo-ortho and a set of pseudo-para relationships between transannular bromines. This compound by lithiation and methylation of the organometallic gave the known tetramethyl[2.2]paracyclophane, VIII. Dibromination of dibromide I1 also gave VI. Compound VI1 was also isolated from the tetrabromination of I and the dibromination of 111; it contains two o-bromines in each ring with a set of pseudo-meta and a set of pseudo-para relationships between transannular bromines. Dehalogenation of VI1 with n-butyllithium in the presence of furan gave the bis(furan)benzyne adduct IX, which was converted to the known [2.2]paracyclonaphthane. Dibromide I11 was converted to dilithium derivative X. Methylation of X gave pseudo-p-dimethyl[2.2]paracyclophane2 (XI). Oxidation of X produced the pseudo-p-dihydroxy derivative, XII, and iodination, the pseudo-p-diiodo derivative, XIII. Dibromide I1 was also lithiated, and the dilithio derivative converted to pseudon-dihydroxy[2.2]paracyclophane2 (XVI). Attempts to oxidize diphenols XI1 and XVI to the corresponding bis quinones failed. Cuprous cyanide cyanation of pseudo-oor pseudo-p-dibromo compounds (I1 or 111) at 225 O gave, besides a mixture of I1 and 111, four compounds : pseudo-o-bromocyano[2.2]paracyclophane (XVIII), pseudop-bromocyano[2.2lparacyclophane (XIX), pseudo-o-dicyano[2.2]paracyclophane (XX), and pseudo-p-dicyano[2.21paracyclophane (XXI). Thermal isomerization by ring rotation accompanied substitution. The yield pattern showed no difference in activation or deactivation effects between the bromo and cyano groups toward the cyanation reaction. Chlorination of I was less discrete than bromination, and only pseudo-p-dichloro[2.2]paracyclophane (XXII) was isolated from a multitude of products. Dinitration of I gave four dinitro derivatives whose yield pattern revealed little evidence of a dominant transannular directive effect of a nitro group in one ring on the position of entry of a second into the transannular ring. The presence of the pseudo-gem isomer (XXIII), along with the pseudo-m(XXIV), pseudo-o(XXV), and pseudo-p(XXVI) dinitro[2.2]paracyclophanes, indicates the availability of the special mechanism for proton transfer in the pseudo-gem u complex for introduction of the second nitro group into the system. n paper XXXV of this series the patterns of transI annular directive influences of substituents in 4substituted [2.2]paracyclophanes on the positions of entry of electrophiles into the system were discussed. Bromination and acetylation reactions were found to substitute predominantly at those positions in the unsubstituted ring pseudo-gem2 to the most basic carbon or substituent in the originally substituted ring.3a Proton transfer from a u complex intermediate appeared to be the rate-limiting and product-determining step. In paper XXXVI, pseudo-gemand pseudo-metadisubstituted [2.2]paracyclophanes were found to equilibrate thermally at 200", as were pseudo-ortho and pseudo-para isomers.3b Paper XXXVIII reports the determination of structure by nmr and mass spectral techniques3' of the large number of disubstituted [2.2]paracyclophanes reported in the three previous (1) The authors wish to thank the National Science Foundation for a grant used in support of this research. H. J. R. also wishes to acknowledge a Woodrow Wilson Fellowship (19641965) and a U. S. Rubber Co. tuition grant for 1967. (2) The colloquial nomenclature is self-evident : pseudo-gem denotes two transannularly adjacent positions on the benzene rings ; pseudoortho, pseudo-meta, and pseudo-para specify orrho, meta, and para relationships displaced from the usual homoannular into a transannular context. (3) (a) H. 3. Reich and D. J. Cram, J . Am. Chem. SOC., 91, 3505 (1969); (b) H. J. Reich and D. J. Cram, ibid., 91, 3517 (1969); (c) H. J. Reich and D. J. Cram, ibid., 91, 3534 (1969). papers. Correlations of physical properties with positions of substituents are also r ep~r t ed .~ ' This paper reports results of multiple halogenation and nitration reactions of [2.2]paracyclophane, and of conversions of halo-substituted [2.2]paracyclophanes into other substituted compounds. This ring system is highly rigid,4 and can act as a scaffold for placing functional groups in set geometric relationships to one another for systematic studies of transannular and multiple functional group effects on physical and chemical properties. This study is concerned with development of synthetic methods whose ultimate objective is to bring to hand any desired multiply substituted [2.2]paracyclophane. Direct introduction of two or more bromine5 or chlorine and of two nitro groups6 has been reported, but without fully distinguishing isomeric structures. Metalation and cyanation of mono and dihalo derivatives of [2.2]paracyclophane have been previously r e p ~ r t e d . ~ ' ~ (4) P. K. Gantzel and K. N. Trueblood, Acta Cryst., 18, 958 (1965). (5) (a) W. F. Gorham, Candian Patent 638,335 (1962); (b) Y. L. Yeh, U. S. Patent 3,155,172 (1962); (c) Y. L. Yeh, U. S. Patent 3,349,124 (1967); (d) Y. L. Yeh, Canadian Patent 705,457 (1965); (e) Y. L. Yeh, Canadian Patent 772,189 (1967); (f) Y. L. Yeh, U. S Patent 3,155,712 (1964); (g) W. F. Gorham, U. S. Patent 3,117,168 (1964); (h) Y. L. Yeh and W. F. Gorham, J . Org. Chem., in press; (i) D. J. Cram and A. C. Day, ibid., 31,1227 (1966). (6) D. J. Cram, R. H. Bauer, N. L. Allinger, R. A. Reeves, w. J. Wechter, and E. Heilbronner, J . Am. Chem. SOC., 81,5977 (1959). Reich, Cram Electrophilic Substitutions in [2.2lParacyclophane~