Bimacrocycles

Lehn and Sauvage (1975) Lehn and Montavon (1978). No pAa values could be measured under comparable conditions (see discussion below). "One chain of the bimacrocycle is not a polyether chain but a (CH2)g chain. 

The expression bimacrocycle (OT macrocycle or po/ymacrocycle) is used instead of macrobicycle (macrotricycle, etc.) because polymacrocycles can contain further, non-macrocyclic ring systems (e.g. aromatic rings). 

In concave pyridines [13], the position of the pyridine nitrogen atom is even more defined. A large number of bimacrocyclic concave pyridines [13] were synthesized, and their relative basicities were determined in ethanol these are given in Table 7 (Liining, 1987 Liining et al., 1990, 1991a, 1993). 

Another class of bimacrocyclic 2,6-disubstituted pyridines is the bissul-fonamides [18]. They were synthesized in an analogous manner to the concave pyridines [13] and their basicities were also measured relative to thymol blue in ethanol (Liining et al., 1991a). The data are listed in Table 9. 

Table 13 Relative basicities (log )rei of bimacrocyclic (concave) and mono-macrocyclic 1,10-phenanthrolines [29].

So far, we have discussed monomacrocyclic intra-annular acids, but bimacrocyclic concave benzoic acids [74a]-[74c] and [75] have also been synthesized and their acidities determined at 25°C by photometric measurements in ethanol (Wangnick, 1991). Table 17 compares the (ethanol) values. No general trend could be found for the acidity of concave benzoic acids [74] and [75]. While [75] with 3,5-disubstituted outer phenyl rings was slightly more acidic than benzoic or acetic acid, [74] with 2,6-disubstituted outer phenyl rings was much less acidic than the non-macrocyclic analogues. 

Another class of phenol-binding pyridines has been synthesized by Vogtle (Ebmeyer and Vogtle, 1989 Seel and Vogtle, 1992). In the bimacrocycles [69], those phenols were especially well bound which form hydrogen bonds to all three bipyridine units, for example 1,3,5-trihydroxybenzene derivatives. 

In this review, acids and bases [8] (benzoic acids, pyridines and 1,10-phenanthrolines) will be discussed as functional groups (light bulbs). They have been incorporated into bimacrocyclic structures by bis-a- or bis-orrlio-substitu-tion of the acids or bases 2,6-disubstituted benzoic acids and pyridines, and 2,9-disubstituted 1,10-phenanthrolines were used. For the construction of the lamp shade , attention had to be paid to the components. They had to be unreactive in order not to interfere with the reactive light bulbs . Therefore, for instance amine nitrogen atoms cannot be used as bridgeheads because they may act as bases. 

Section 2 discusses the syntheses of different classes of concave acids and bases. Convergent synthetic strategies were chosen for an easy structural variation of the reagents (modular assembly). Section 3 characterizes the concave acids and concave bases and checks whether the acid/base properties of the parent compounds benzoic acid, pyridine and 1,10-phenanthroline are conserved in the bimacrocyclic structures. In Section 4, the influence of the concave shielding on the reactivity and selectivity of the concave reagents is measured in model reactions. In principle, the concave shielding should be able to influence inter- and intramolecular competitions as well as chemoselectivity and (dia)stereoselectivity. If the reagent is chiral, enantioselectivity should also be observable. 

The bridgeheads in a bimacrocycle must connect three bridges each. Therefore they must be trifunctional. This is given when trivalent atoms are used and also when trisubstituted groups are incorporated. 

If the functional group is a pyridine unit, 2,6-disubstituted, bimacrocyclic pyridine bislactams must be synthesized. In principle, three classes of such concave pyridines are conceivable (Structures 1). 

In the second macrocyclization, the reaction of the diamine 7 with a diacyl dichloride 8, the high dilution technique was used. Depending on the dia-mine/diacyl dichloride combination, the bimacrocycles 3 were obtained in yields... 

The synthetic strategy used for the construction of concave pyridine bislactams 3 (Scheme 1) can also be applied to other concave bases. When instead of a pyridine-2,6-dialdehyde 4, l,10-phenanthroline-2,9-dicarbaldehyde (9) was used in a metal ion template directed synthesis of macrocyclic diimines, after reduction, also macrocyclic 1,10-phenanthroline diamines 10 could be obtained in good yields. Here too, the crude diamines 10 were used in the next reaction step. Bridging of 10 with diacyl dichlorides 8 gave concave 1,10-phenanthroline bislactams 11. Scheme 2 summarizes the synthesis and lists the synthesized bimacrocycles 11 [18]. 

Whereas the identification of a [1 + 1] or a [2 + 2] cyclization product was unequivocal by MS, it was more difficult to distinguish between the concave bimacrocycles and the bis-cyclophanes. But a combination of NOE investigations with complexation studies followed by NMR, and finally X-ray analyses proved the bimacrocyclic concave structure of the concave acids and bases 21,29 and 38 [15, 20, 27a]. 

Besides the examination of the acid/base properties of the concave acids and bases, the geometry of the new bimacrocyclic acids and bases had to be investigated to show that the concave acids and bases were indeed concave. Therefore crystal structures were elucidated by X-ray analyses. For the pyridine bislactam 3e (s. Table 1) [12b], the pyridine bissulfonamide 13j (s. Scheme 3) [15], the 1,10-phenanthroline cyclophane 21a (Structures 3) [20] and the benzoic acid 3fe (s. Scheme 6) [27a], crystals could be obtained which were suitable for X-ray analyses. The structures are shown as stereoplots in Figs. 3(a)- (d). 

Besides concave pyridines, concave 1,10-phenanthrolines and concave benzoic acids, a large number of other concave adds and bases are conceivable containing other acidic or basic groups in the concave position. The central question for such new concave reagents is how can the new functionality be incorporated into the bimacrocyclic structure, and how can a concave orientation be assured ... 

The term bimacrocyck will be used instead of macrobicycle because bimacrocycles often also contain smaller rings (e.g. aryl rings). Then they are macropolycyclic although only two macrocycies exist. (In addition, no bicycle company has offered a sponsorship yet )... 

The overall kinetics of the mono- and double-protonation of cryptand [1.1.1] are even more complicated because the two ions [as for any other bimacrocyclic diamine (Alder, 1990)] may exist as different conformers. Scheme 2 shows the protonated forms in five different conformations... 

Table 5 Logarithms of the basicity constants log and log K2 for the bimacrocycles [8] in water at 25°C.

The acidity of a bimacrocyclic phenol [50] has also been measured and has been compared with analogues (Czech et al., 1988). Values of pA a are given in Table 23. In the bimacrocyclic phenol, no diversion from the expected pAa values could be found. The observed acidities were comparable to those of the analogues [1], [6] and [49], although a comparison is difficult due to the fact that, again, Coulomb forces probably play an important role. 

---