Phenols metacyclophanes, phenolic

Calixarenes (from the Latin ca/ x) may be understood as artificial receptor analogues of the natural cyclodextrins (96,97). In its prototypical form they feature a macrocycHc metacyclophane framework bearing protonizable hydroxy groups made from condensation of -substituted phenols with formaldehyde (Fig. 15b). Dependent on the ring size, benzene derivatives are the substrates most commonly included into the calix cavity (98), but other interesting substrates such as C q have also been accommodated (Fig. 8c) (45). 

In light of the present evidence the biogenesis of metacyclophane Ly-thraceae alkaloids required revision, since the only published proposal (9) was based on pelletierine. A new biogenetic scheme was proposed which invoked intermediacy of A piperideine and two C6-C4 units [derived from /i-kctoester (193)]. An intermediate disubstituted piperidine (194) would give rise to two types of metacyclophane alkaloids as a result of reduction and phenol coupling as well as Michael addition in the case of the quinoli-zidine bases (10). 

The term calix[n]arenes indicates a class of phenolic metacyclophanes derived from the condensation of phenols and aldehydes. The name was coined by Gutsche and derives from the Latin calix because of the vase-like structure that these macrocycles assume when all the aromatic rings are oriented in the same direction.1 The bracketed number indicates the number of aromatic rings and hence defines the size of the macrocycle. To identify the phenol from which the calixarene is derived, the para substituent is designated by name. Thus the cyclic tetramer derived from p-f-butylphenol and formaldehyde is named p-f-butylcalix[4]arene, or with a more systematic but still simplified nomenclature proposed by Gutsche and used in this chapter 5,11,17,23-Te trakis( 1,1 -dimethylethyl)-25,26,27,28-tetrahydroxy calix [4] arene, 1 (Scheme 7.1). The systematic name reported by Chemical Abstracts is pentacyclo[19.3.1.13,7.19 13.115 19]octacosa-l (25),3,5,7(28),9,11,13(27),15,17, 19(26), 21,23-dodecaene-25,26,27,28-tetrol-5,l l,17,23-tetrakis(l, 1 -dimethylethyl). 

Although nowadays the term calixarene tends to be used for all [l ]-meta-cyclophanes, this chapter will deal with [l ]-metacyclophanes bearing phenolic OH groups in the intraannular (endo, e.g. calix[ ]arenes) or extraannular (exo, e.g. resorc[4]arenes) position. 

Calixarenes [77] are defined as [l.n]metacyclophanes with its basic structural unit consisting of phenolic groups linked by ortho-methylene groups. Two examples are shown in Fig. 25. Several reviews are available on this subject [77-79]. These compounds can be synthesized by the acid- or base-catalyzed condensation reaction of a substituted phenol with formaldehyde or an aldehyde (Fig. 26). Calixarenes have also been synthesized by a stepwise reaction that sequentially add phenolic groups followed by a cyclization step. More efficient convergent synthesis have also been developed [80-82], The bowl-like structural conformation generally... 

The calix[ ]arene ( indicates the number of aromatic units in the metacyclophane) building block provides a three-dimensional skeleton that is needed to fix different donor ligands in the optimal spatial positions for binding one ion selectively [94,95]. Calix[n]arenes are easily accessible from the base-eatalyzed condensation of p-tert-butylphenol and formaldehyde [96]. Gutsche proposed to define the two faces of a calix[4]arene molecule as the lower (phenolic groups) and the upper rim. The calix[4]arene with free hydroxyl groups is conformationally flexible and the... 

Thallium trifluoroacetate has not enjoyed widespread use as a reagent for quinone synthesis, possibly because it is still a relatively new reagent but more probably because of its toxicity. One example of its use lies in the synthesis of metacyclophanes and related compounds as reported by Tashiro et al Thus the r-butylphenol (59) gave the bisquinone (61), while the phenol (60) afforded the monoquinone (62). An alternative and more practical synthesis of the bisquinone (61) for large scale work involved dealkylation to afford the bisphenol (63) which was then treated with sodium nitrite to give the bisoxime (64). Hydrolysis of the bisoxime did not give the quinone (61), but it could be obtained by zinc/acetic acid reduction of the bisoxime followed by oxidation with nitric acid (Scheme 13). 

Calixarenes are macrocyclic molecules synthesized with high yield by condensation of appropriate arenes and aldehyde derivatives. Calix means bowF in Latin and Greek, and this phrase reflects the shape of the tetramer, which usually adopts a bowl or beaker-like conformation. Gutsche first introduced the name calixarene for this class of compounds [38]. Several authors have exhaustively reviewed the chemistry and synthetic procedures, which lead to different structural modifications of calixarenes [39-42]. In general, three types of calixarenes derivatives are known first, metacyclophanes (type 1) second, those obtained by condensation of formaldehyde with phenol (type 11), and third, those obtained by reaction with resorcinol (type III) (Scheme 6). The latter modifications are also called resorcarenes to distinguish calixarenes of type III from those of type II. 

The basic skeleton of these compounds, calixarenes in the original (narrow) sense, is that of a [l ]metacyclophane and it is appropriate to include into the family of calixarenes also those cyclic oligomers, in which the phenolic hydroxy groups are situated in exo-position at the wide rim . Here especially cyclic compounds II (nearly exclusively tetramers) built up by resorcinol units (eventually substituted in the 2-position) are important and will be called resorcarenes within this article. Alternatively calixresorcinols is used for n, in distinction to calixphenols for I. 

It has been suggested to distinguish the single phenolic units by letters A, B,C,. .. instead of 1,2,3,... since numbers are also used for the single carbon atoms of the metacyclophane skeleton. 

Hogbeig AG (1980) Cyclooligomeric phenol-aldehyde condensation products. Stereoselective synthesis and DNMR study of two l,8,15,22-tetraphenyl[14]metacyclophan-3,5,10,12,17,19,24,26-octols. J Am Chem Soc 102 6046-6050... 

The synthetic route to dihydroxy[2.n]metacyclophanes 7 is shown in Scheme 1. Anisole derivatives 5 and 6 were treated with excess of boron tribromide in dry CH2CI2 at r.t. for 12 h [19]. Phenol derivatives 7b and c were obtained in 95 and 93% yields, respectively. On the other hand, 5c did not give any desired products under the same conditions. Since the reaction gave a complex product mixture, we chose milder conditions. Thus, 5c was carefully treated with an equimolar amount of BBr3 at 0°C for 2 h and then gave 7a in 78% yield. Unfortunately, 5a, 5b, and... 

Closely related to the spherands are the calixarenes , [ln]metacyclophanes, prepared by base-catalyzed condensation of / -substituted phenols with formaldehyde [6]. These are attractive building blocks, their phenolic hydroxyl groups being ordered in well-shaped cyclic arrays [6-8] which can be functionalized [7-14] to give novel guest inclusion blocks. The combination of structural elements of both... 

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