Para-cyclophane

SJ paracyclophane etc.] refers to the benzene rings in the structure, i.e. [8]-paracyclophane, [2,2,2]-para-cyclophane. Systems based upon heterocyclic molecules are also known. 

In the crystal of 1,4-dicinnamoylbenzene (1,4-DCB) (see Fig. 12), the distances between the intermolecular photoadductive carbons are 3.973 and 4.086 A for one cyclobutane ring, and 3.903 and 3.955 A for the other. The two topochemical pathways may occur competitively in a single crystal of 1,4-DCB at the initial stage of reaction. Then, both intramolecular photodimerization and intermolecular photopolymerization of the diolefinic mono-cyclobutane intermediate occur competitively to give tricyclic dimer 21,22,23,24-tetraphenyl-l,4,ll,14-tetraoxo-2(13),12(13-diethanol, [4.4] para-cyclophane or oligomers (Hasegawa et al., (1985). On photoirridation at room temperature the 1,4-DCB crystal gives >90% of the tricylic... 

Another type of face-to-face-arrangement is found in the multi-layered annulene systems [ 14] and [15], Here, unlike the para-cyclophanes, in which the phenyl units are connected by external alkanediyl groups, the stacking of annulene layers is achieved by internal linkages, with the bridge located inside the 7t-clouds. The advantage of the latter structure is that one can... 

Reductive coupling of l-chloro-6-[4-(chlorodimethylsilyl)phenyl]-1,1,2,2,3,3,4,4,5,5,6,6-dodecamethylhexasilane with sodium in refluxing toluene in the presence of [18 crown- afforded heptasila[7]para-cyclophane 47 in 1.2% yield. Compound 47, obtained as colorless crys-... 

A [2.2]paracydophane was prepared by dimerization of p-quinodimethane 232, which was obtained by a [4+ 2]-cycloaddition reaction of bisallene with DMAD [184], This sequence represents one of the most general approaches to functionalized para-cyclophanes. 

The properties of the cyclophanes are best illustrated by the para-cyclophanes. In contrast to the metacyclophanes and metapara-cyclophanes 2>, where aromatic nuclei come into close proximity, there are in paracyclophane molecules two aromatic nuclei pressed one on top... 

A) almost equals the van der Waals distance. As in [2.2]para-cyclophane, the hydrogen atoms of the aromatic moieties are directed towards the interior of the molecule because of the increased -electron density on the outside of the molecule caused by the intraannular interaction of the 7r-electron clouds. 

In the following section a few representatives from the series of [2.2]para-cyclophanes bearing bridge substituents will be described. This type of compound has so far not been studied to the same extent as the [2.2]para-cyclophanes having substituents in the nucleus (see Section 2.2.2.). 

During the synthesis of [2.2]paracyclophanediene, Dewhirst and Cram 83> prepared the bis-geminal dibromides 4a and 4b, which were subsequently converted into the diketones 5 a and 5 b. The UV spectra of the bromides 4a and 4 b show maxima at 236 nm. A comparison with the Amax values of other [2.2]paracyclophanes brominated at the bridges suggests that the absorption at 236 nm is the 235 nm band of [2.2]para-cyclophane, shifted bathochromically by the inductive effect of the... 

The absolute configuration of more than 20 optically active [2.2]para-cyclophane derivatives has been established in this way. 

Cram et a .15>46> have investigated the 1H—NMR spectra of [2.2]para-cyclophane and nuclear-substituted derivatives. 

The IR spectrum of the pseudo-geminal 46) 4-acetyl-13-bromo[2.2]para-cyclophane (18) shows a band for the carbonyl stretching vibration at 1663 cm-1. This frequency lies outside the range of frequencies (1666—1668 cm-1) found for the absorption of other isomers and has been attributed by Reich and Cram to transannular Br...C=0 interactions. 

In sharp contrast to 20a, 4,5,7,8,12,13,15,16-octamethyl[2.2]para-cyclophane 22 is extraordinarily unstable 61>. This substance polymerizes at room temperature, both in solution and in the solid state, even in an inert atmosphere. The reason is that the accumulation of pseudo-geminal methyl groups leads to steric overcrowding which cannot be circumvented because of the rigidity of the [2.2]paracyclophane system. Accordingly,... 

The following compounds which have a benzene moiety of [2.2]para-cyclophane replaced by a heteroring (e.g. furan) may be counted among the analogs of [2.2]paracyclophane, as their stereochemistry has many features in common with that of the carbophanes 64> 34—36. 

The shift of the aromatic protons of [2.2](4,4 )biphenylophane (47) 71> to higher field strength is smaller than in [2.2]paracyclophane (T(H)arom = 3.63 in CDCI3). Furthermore, the spectra of 47 and 4,4 -dimethyl-biphenyl differ less from each other than do the spectra of [2.2]para-cyclophane and p-xylene. 

In addition to chemical reactions which result in direct valency coupling, other reactions, for example, those that lead to the formation of charge-transfer complexes are rather generally characteristic of the [2.2]para-cyclophane system. 

Cram et al. have investigated whether and how the electronic effects of the substituents in one ring are transferred to the second ring of [2.2]para-cyclophane. 

The relative rates of acetylation in competition experiments in the [m.n]paracyclophane series 38> may be interpreted in terms of trans-annular electronic and steric effects. If the rate of acetylation of [6.6]para-cyclophane [(7), m =n =6] is is taken as one, the relative acetylation rates of the [4.4]-, [4.3]-, and [2.2]paracyclophanes are 1.6, 11, and >48, respectively. As the aromatic rings come closer together, the rate of entry of the first acetyl group into the nucleus increases, while that of the second acetyl group decreases. Both effects clearly indicate that the positive. partial charge can be distributed over both benzene rings in the monoacetylation transition state (64). 

Brewer, Heaney, and Marples 103> were able to isolate the mono adduct 142 from the reaction of tetrafluorodehydrobenzene (141) with [2.2]para-cyclophane. The 2 1 adducts 143 and 144 were obtained when an excess of pentafluorophenylmagnesium bromide was employed. 

Cram and Day 57> successfully synthesized a quinone of [2.2]para-cyclophane by coupling the phenol 148 with diazotized sulphanilic acid to give 149. Reduction of 149 gave the unstable aminophenol 150 on oxidation with ferric sulphate 150 afforded the quinone 30 in 68% overall yield. 

In the case of the tetrahydro derivative 154 108) it was demonstrated that there are two conceivable conformations that cannot be differentiated. Structures 154b and 154c can be ruled out on the basis of 1H—NMR spectral data. Disproportionation of 154 to 153 and [2.2]para-cyclophane occurs on heating to 150—160 °C in a closed system. 

Reich and Cram 111>112> have reported the results of a series of experiments, which all indicate thermal cleavage of [2.2]paracyclophane to the p,p-dimethylenebibenzyl diradical (157). After heating [2.2]para-cyclophane (2) at 250 °C in p-diisopropylbenzene, they isolated p,p-dimethylbibenzyl in 21% yield as the sole non-polymerizable product. 

Further papers relevant to the stereochemistry of the [2.2]Para-cyclophane system are mentioned ... 

Racemization and rearrangement mechanisms of chiral [2.2]para cyclophanes iso.isi). 

Stereochemical Elucidation of the Birch reduction product of [2.2]para-cyclophanes 132>. 

Among the three isomers of bis(phenylmethylenyl) [2.2]paracyclophanes [38], pseudo-ort/jo- and pseudo-para-isomers (o-[38j and p-[38], respectively) satisfy McConnell s condition to give quintet ground states. They were produced by photolysis of the corresponding bis(a-diazobenzyl)[2.2]para-cyclophanes [38a] in 2-MTHF at cryogenic temperatures, and their esr fine structures were studied. 

Fig. 19 Synthesis of para-cyclophanes through tandem Ugi-SNAr processes...

U-SNAr[15][CNlE] process was implemented. These para-cyclophanes 97 and 98 are interesting from the stereochemical point of view because they generate atropisomerism. Moreover, the stereogenic centres of the peptide backbone are configurationally unstable under the cyclization conditions, affording, under thermodynamic control, only two diastereoisomers (atropisomers) instead of the expected four. 

Cristau P, Vors JP, Zhu JP (2006) Rapid synthesis of cyclopeptide alkaloid-like para-cyclophanes by combined use of Ugi-4CR and intramolecular SNAr reaction. Qsar Comb Sci 25 519-526... 

In more recent works, Zhu and coworkers synthesized a variety of para-cyclophanes and biarylether containing macrocycles (14c and d) using a reaction sequence consisting of an Ugi reaction followed by an intramolecular Sj Ar cyclization (Scheme 14) [76-78]. Many linear precursors (14a and b) were achieved with the Ugi reaction by employing varied primary amines. This synthetic planning allowed the introduction of four points of diversity within the resulting scaffolds, thus producing a small library of cyclopeptoids. 

The photorearrangement of 7V-aryl lactams 34 to the ortho-position offers an interesting possibility for the preparation of cyclic benzo-aza-ketones of type 35, whereas the rearrangement to the para-position should lead to para-cyclophane 144 formation. 7-, 8-, and 13-Membered ring jV-aryl lactams (34, n = 5, 6, and 11) were successfully rearranged in ethanol to 35 in chemical yields of 60, 83, and 80%,13 and in quantum yields of 0.071, 0.11, and 0.082, respectively.14... 

The nomenclature of phanes is simple 32) It mainly defines the length(s) of the bridge(s) and their positions in the ring as illustrated by the following examples [6]para-cyclophane (2) 1,10-dioxa [10]paracyclophane (6), [2.2]paracyclophane (7), [2.2]meta-(8) and [2.2]metaparacyclophane (9) and [8](2,5)pyridinophane (70). The formulae show also the kind of projection used in this survey to illustrate stereochemical relations. 

For [2.2]paracyclophane-4-carboxylic acid (25) as (—)(R) This result has been mentioned in a footnote in Ref. 1011 but seems never to have been published (see also Ref. 61). The chirality of this acid was correlated via its ( )-aldehyde with a levo-rotatory hexahelicene derivative which, according to the paracyclophane moiety at the terminal, had to adopt (A/)-helicity. Its chiroptical properties are comparable to those of hexahelicene itself101. For the (—)-bromoderivative of the latter the (A/)-helicity was established by the Bijvoet-method 102). In a later study, (—)para-cyclophane-hexahelicene prepared from (—)-l,4-dimethylhexahelicene with known chirality (which in turn was obtained with approximately 12% enantiomeric purity by asymmetric chromatography) confirmed these results. It should be mentioned that [2.2]paracyclophane-4-carboxylic acid (25) was the first planar chiral cyclophane whose chirality was determined 1041 (see also Ref.54 ). The results justmentioned confirmed the assignment (+)( ). 

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