Cyclophanes

3. Cyclophanes. These consist of benzene rings held face-to-face (in some cases) by short bridges. Shown here are the various [2,2] cyclophanes; note that the ortho and meta forms have the possibility of existing in two different conformations. What are the relative energies of the five forms shown? How bent are the benzene rings?

[Tsuzuki, S.; Tanabe, K. J. Chem. Soc., Perkin Trans. 2 1990, 1687.]

27. Calculate the strain energy and geometry of the various [n]- paracyclophanes (related to the cyclophanes in Problem 3, but with only one benzene ring).





[Tobe, Y.; Takahashi, T.; Ishikawa, T.; Yoshimura, M.; Suwa, M.; Kobiro, K.; Kakiuchi, K.; Gleiter, R. J. Am. Chem. Soc. 1990, 112, 8889;
Tobe, T.; Takahashi, T.; Kobiro, K.; Kakiuchi, K. Chem. Lett. 1990, 1587;
see also the reference from Problem 3.]

34. Use molecular mechanics to analyze the conformations of the (CH2)n bridge in the (n)-metacyclophanes with n = 4 to n = 8. Discuss the strain, geometry, etc. as a function of n.




[Jenneskens, L. W.; de Boer, H. J. R.; de Wolf, W. H..; Bickelhaupt, F. J. Am. Chem. Soc. 1990, 112, 8941 and references cited therein.]

44. Although most of the interest in cyclophanes has been devoted to the para,para and meta,meta types (see Problem 3), ortho,ortho-cyclophanes are also intriguing molecules when they are constructed on rigid frameworks which force the aromatic rings to be parallel (or nearly so) to one another. Consider the molecules shown to the right in which two quinolines are held in close proximity. Do calculations of geometry and energy for the cases n = 1, 2, and 3. Compare your answers for the internuclear distances with those found in Table II and in the discussion on p. 1495 in the cited article.




[Lim, J.-L.; Chirayil, S.; Thummel, R. P. J. Org. Chem. 1991, 56, 1492;
Taffarel, E.; Chirayil, S.; Thummel, R. P. J. Org. Chem. 1994, 59, 823.]

45. Another pair of molecules which have approximately parallel benzene rings in close proximity is shown to the right. Use MM calculations to determine the separation between carbon atoms of the rings; determine the degree of planarity of each ring. Compare your answers with the experimental values from the X-ray crystal structures in the cited article.

[Grimme, W.; Kämmerling, H. T.; Lex, J.; Gleiter, R.; Heinze, J.; Dietrich, M. Angew. Chem., Int. Ed. Engl. 1991, 30, 205.]

51. meta,meta-Cyclophane conformations A and B equilibrate at room temperature, presumably via unstable conformation C. Use molecular mechanics (a) to calculate the energies of these three conformations for comparison with the experimental equilibrium values and (b) to determine the various bond lengths and dihedral angles for comparison with the calculated and experimental values in Table III of the cited article.

[Nishimura, J.; Horikoshi, Y.; Wada, Y.; Takahashi, H.; Sato, M. J. Am. Chem. Soc. 1991, 113, 3485.]

52. Shown to the right are [2.2.2](1,3,5)-cyclophane and [2.2.2.2](1,2,3,5)-cyclophane. Do MM calculations of each of these as well as on all of the other two-carbon bridged structures: (1,2,3)-, (1,2,4)-, (1,2,3,4)-, (1,2,4,5)-, (1,2,3,4,5)-, and (1,2,3,4,5,6)-cyclophane; the latter is known as "superphane." Compare the computed angles and distances with those measured by X-ray crystallography (see the cited article).

[Sekine, Y.; Boekelheide, V. J. Am. Chem. Soc. 1991, 103, 1777 and references cited therein;
also Gleiter, R.; Kratz, D. Acc. Chem. Res. 1993, 26, 311.]

53. Shown to the right is [3.3](1,3)-cyclophane. There are at least five reasonable conformations for this compound (see the cited article). Use molecular mechanics to calculate the energy and geometry of each of these five conformations; assess which factors are responsible for the energy differences among the conformations.



[Biali, S. E. J. Chem. Educ. 1990, 67, 1039.]

56. Tetramethyl para,para-cyclophane 1 is a chiral compound, capable of showing optical activity. Use molecular mechanics to calculate the energies of the two lowest energy conformations of chiral 1 and of the two lowest energy conformations of its meso diastereomer 2; compare your energies and geometries with those in the reference.

[Finocchiaro, P.; Mamo, A.; Pappalardo, S.; Weissensteiner, W.; Widhalm, M. J. Chem. Soc., Perkin Trans. 2 1991, 449.]

57. Compute the geometry and degree of bending of the benzene rings in [2.2]-paracyclophane (1) and its cyclobutano-fused derivatives 2 and 3. Compare your results with the experimental X-ray crystal structures for 1 and for a substituted version of 2 which are given in Table I of the reference.

[Maekawa, Y.; Kato, S.; Hasegawa, M. J. Am. Chem. Soc. 1991, 113, 3867.]

58. Various meta- and para-cyclophanes with adamantane spacers have been prepared. Do MM calculations of the geometries and degree of benzene ring bending for dithia compounds 1 and 2 and for hydrocarbon 3. Compare your values with the experimental X- ray crystal structure values given in the various figures and tables of the reference.


[Dohm, J.; Nieger, M.; Rissanen, K.; Vögtle, F. Chem. Ber. 1991, 124, 915.]

63. A series of orthoparacyclophanes has recently been prepared. Do MM calculations on hydrocarbons 1 and 2a, and on dithia analog 2b. Compare your calculated geometries with those suggested by the NMR data of 1 and 2a, and the X-ray crystal structure for 2b.




[Asami, M.; Krieger, C.; Staab, H. A. Tetrahedron Lett. 1991, 33, 2117.]

119. Several 1,4-bridged cyclophanes, including [6]-(1,4)-naphthalenophane (shown to the right), have been the subject of experimental and theoretical inquiry. Calculate the heat of formation, strain energy, bond distances, and deformation angles of this structure, relative to those in the unstrained analog, 1,4-dimethylnaphthalene; compare your results with those in Tables I and II of the cited reference. Then do calculations on the carbocations formed by: (a) protonation at C1; (b) rearrangement of that ion to the meta-bridged material; and (c) alternative initial protonation at C2. Compare your results (for the first two ions) with those in Table IV. Explain why protonation does not occur at C2 and why the initial ion by protonation at C1 does not rearrange.

[Tobe, Y.; Takemura, A.; Jimbro, M.; Takahashi, T.; Kobiro, K.; Kakiuchi, K. J. Am. Chem. Soc. 1992, 114, 3479.]

181. Shown to the right is [2.2]-paracyclophane-1,9-diene in which not only are the benzene rings distorted from planarity but there should be very poor pi-overlap between the rings and the double bonds. Do calculations on this compound and on its mono- and bisbenzoderivatives (at the 1 and 9 positions). Discuss the structures, the strain, the extent of overlap, etc.

[Reiser, O.; König, B.; Meerholz, K.; Heinze, J.; Wellauer, T.; Gerson, F.; Frim, R.; Rabinovitz, M.; de Meijere, A. J. Am. Chem. Soc. 1993, 115, 3511.]

187. The MMX treatment of the [2,2]-meta- cyclophanes was addressed in Problems 3, 51, and 52. The present problem probes yet another aspect of their structure, namely how substitution at C5 and C13 perturbs the position of the syn/anti equilibrium. Do calculations on the sets where R = H, CH3, and t-Bu; comment on any change in the relative energies of the conformations. Compare your structural and energy results with the experimental and computational values reported in the reference. Do your results support the contention that the difference between the conformations is principally the difference between eclipsed and staggered conformations in the saturated bridges?

[Ito, D.; Nakasato, Y.; Fujise, Y.; Hioki, H.; Nagaku, M.; Fukazawa, Y. Tetrahedron Lett. 1993, 34, 3787.]

189. The structure to the right, [3,3]-orthocyclophane, is not as strained as the various meta and paracyclophanes. It has recently been synthesized, and its x-ray crystal structure has been determined. This MMX problem consists of calculating the energies of the various conformations (three anti and two syn) and comparing them with those in the cited reference. Discuss why these conformations differ in energy.

[Wang, Z.-H.; Usui, S.; Fukuzawa, Y. Bull. Chem. Soc. Jpn. 1993, 66, 1239.]

193. Structure 1 is a paracyclophane in which an adamantyl unit is connected to the bridges. Compounds 2 and 3, similarly, have seven carbons bridging the C1 and C4 positions of the benzene ring. Do calculations on the energy and structure of these compounds; compare your results with the energy estimates in the cited reference.

[Lemmerz, R.; Nieger, M.; Vögtle, F. J. Chem. Soc., Chem. Commun. 1993, 1168.]

197. Shown to the right are [34](1,2,3,5)cyclophane and [34](1,2,4,5)cyclophane in their preferred conformations (as determined in the cited reference). Do MMX calculations on these known compounds and on [34](1,2,3,4)cyclophane [not known and not shown] in whatever conformations you think are of reasonable energy for it. Compare the relative energies of the isomeric (1,2,3,5), (1,2,4,5), and (1,2,3,4) isomers and comment on what factors are responsible for the differences.

[Shinmyozu, T.; Kusumoto, S.; Nomura, S.; Kawase, H.; Imazu, T. Chem. Ber. 1993, 126, 1815.]

220. Shown to the right is a stylized picture of [2,2](meta,para)cyclophane. As in most cyclophanes, the rings are bent out of planarity and are in more-or-less parallel planes. For the parent compound (all R's = H), there are two conformations of equal energy. Do MMX calculations on the parent; on the two different conformations for the monomethyl derivative (R1 = Me); on the two different conformations for the dimethyl derivative with R1 = R2 = Me; and on the two different conformations for the trimethyl derivative (R1 = R2 = R3 = Me). Discuss the factors that are responsible for the differences in conformational energy.

[Lai, Y.-H.; Yap, A. H.-T.; Novak, I. J. Org. Chem. 1994, 59, 3381.]

234. [2.2]-Paracyclophane (R = H) has a skewed conformation, shown here, along the sp3-sp3 bonds (e.g., C2-C1). For the parent compound, the two conformations are of equal energy. Do MMX computations on the dihedral angles (C3-C2-C1-C14) and the energies for the parent compound and for the two conformations of the 4- methyl and of the 4-t-butyl derivatives. Compare your results with those in the cited reference. Discuss those factors that lead to the unequal energy of the conformations.

[Ernst, L. Liebigs Ann. Chem. 1995, 13.]

244. The three compounds to the right, all based on a 1,2,4-double cyclophane framework and including the beginnings of ladderane extensions, have been synthesized (as diester derivatives). Do MMX calculations on these. Discuss their strain energy and structural parameters; compare your results with the x-ray crystal data reported in the article.


[Hopf, H.; Greiving, H.; Jones, P. G.; Bubenitschek, P. Angew. Chem., Int. Ed. Engl. 1995, 34, 685.]

257. In Problem No. 197, calculations were done on various tetra-bridged cyclophanes. The penta- and hexabridged compounds, A and B, have now been made. The latter has been dubbed a "Molecular Pinwheel." Do MMX calculations on the conformation of A shown here (the same as in the article) and on other reasonable conformations; identify the factors that lead to instability. Then do calculations on B and compare your results with those obtained for A.

[Sakamoto, Y.; Miyoshi, N.; Shinmyozu, T. Angew. Chem., Int. Ed. Engl. 1996, 35, 549.]


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