Calixarenes formaldehyde

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). 

A further category of cavitands are the calixarenes (Gutsche, Dhawan, No Muthukrishnan, 1981 Gutsche Levine, 1982). Structure (255) illustrates an example of this type which is readily prepared by treatment of 4-f-butylphenol with formaldehyde and base. The compound may exist in other conformations besides the saucer-shaped one illustrated by (255). Similarly, f-butyl-calix[4]arene (256 R = CH2COOH) has an enforced hydrophilic cavity in the shape of a cone the alkali and ammonium salts of this host are soluble in water (Arduini, Pochini, Reverberi Ungaro, 1984). 

Calix[n]arenes (n=4,6,8) are cyclic condensation products of ap-substituted phenol and formaldehyde [58]. Gutsche and co-workers [59,60] have developed procedures for the synthesis of calixarenes and caHxarene derivatives. 

Macrocyclic phenol-formaldehyde condensation products have been termed calixarenes509 and are capable of providing a cavity for complexation (132). Rb+ was shown to be a good templating device during synthesis and this hinted at complex formation. Transport experiments have shown calixarenes-[4], -[6] and -[8] to be selective for Cs+ using MN03 no transport was detected but with MOH it occurred. 18-Crown-6 behaved in a contrary fashion ... 

Calixarenes (12), from the Greek meaning chalice and arene (incorporation of aromatic rings), are macrocyclic phenol-formaldehyde condensation products. 

While the selective interactions of functionalised calixarenes with cations have been studied broadly for almost three decades, the application of cal-ixarene-based receptors for anion recognition is a relatively new research topic [2]. This review is focused on recent developments in the design and synthesis of calixarene-based anion receptors. Although the name calixarene was originally designated only for phenol-formaldehyde derivatives 1, recently many structural variations and mutations have been formed. Some of them, such as calixpyrroles [3], are widely used for anion recognition nevertheless, this review is restricted only to classical calixarenes 1 and newly discovered thiacalix-arenes 2 [4]. 

Calix[ ]arenes are a family of macrocycles prepared by condensation reactions between n /v/ra-substituted phenols and n formaldehyde molecules under either base or acid catalysis. Different sizes of the macrocycles can be obtained (n = 4-20) (Stewart and Gutsche, 1999) depending on the exact experimental conditions, which were mastered in the 1960 s (Gutsche, 1998), but the most common receptors are those with n =4,6,8 (macrocycles with an odd number of phenol units are more difficult to synthesize). We use here the simplified nomenclature in which the number of phenolic units is indicated between square brackets and para substituents are listed first.4 Calixarenes, which can be easily derivatized both on the para positions of the phenolic units and on the hydroxyl groups, have been primarily developed for catalytic processes and as biomimics, but it was soon realized that they can also easily encapsulate metal ions and the first complexes with d-transition metal ions were isolated in the mid-1980 s (Olmstead et al., 1985). Jack Harrowfield characterized the first lanthanide complex with a calixarene in 1987, a bimetallic europium complex with p-terf-butylcalix[8]arene (Furphy etal., 1987). 

Much interest has centred on the branch of cyclophanes known as calixarenes. They are polyphenol systems that can act as hosts in the formation of inclusion compounds, where a small guest molecule resides completely in a cavity within a single host they are cone-shaped cavitands . Several accounts have appeared of their history. The discovery by Baeyer of a formaldehyde/phenol resin led to Bakelite and to the work of A. Zincke and E. Ziegler, who gave to the first oligomer a tetrameric structure of a calix[4]arene. Later syntheses by Gutsche (1978) led to calixarenes with 4, 6 or 8 phenol residues.107-109... 

Calixarenes are formed by condensation of a p-substituted phenol with formaldehyde [8]. These macrocycles are conformationally quite flexible but, by introducing suitable substituents in the aromatic subunits, the so-called cone conformation, in which all aromatic subunits point into the same direction, can be stabilized. This conformation is usually best suited to complex guest molecules because it has a well defined hydrophobic cavity. An inclusion of cations such as ammonium ions or quaternary ammonium ions into this cavity can be demonstrated, for example, by the characteristic upfield shifts of guest signals in the NMR, an effect that is a consequence of the close proximity of the corresponding protons to the surfaces of the aromatic receptor subunits in the complex. 

Scheme 5. Base-induced condensation of certain phenols with formaldehyde leads to the production of the calixarene class of molecular receptors [58-60], e.g. 21. The cone conformation shown in the box is only one of several possible conformations.

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). 

The acid-catalysed reaction of resorcinol with aldehydes leads to cyclic tetra-mers which are grouped in the class of resorc[4]arenes (exo-calixarenes).3 This reaction is quite general with respect to the aldehyde and to the starting resorcinol, which can bear several substituents in the 2-position.15 Niederl and Hogberg showed in a typical example, the synthetic procedure by which an ethanol solution of resorcinol, acetaldehyde and 37% hydrochloric acid maintained at 80 °C for 16 h, afforded 75% of the all cis C-methylresorc[4]arene. A shorter reaction time leads to the kinetic stereoisomer (trans,cis,trans,cis).16 This procedure is general for many aldehydes (Scheme 7.4), but the use of formaldehyde is limited to some special cases.17... 

Again at the beginning of the 1970 s, other classes of synthetic macrocycles were being investigated, not necessarily in connection with biological problems. For instance, the rich chemistry of Schiff base derivatives (Fig. 4.8) was being developed and yielded the first macrocyclic complexes in 1979 (Fig. 4.9). Another type of interesting macrocyclic molecules are the calixarenes (Fig. 4.8) the history of which can be traced back to the first experiments, in Berlin in 1872, of Adolf von Baeyer (Nobel prize in chemistry in 1905) who treated p-substituted phenols with formaldehyde in the presence of acid or base. 

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... 

Calixarenes (23) are the macrocyclic result of condensations between phenols and formaldehyde and have been referred to as the most easily accessible molecular basket. ... 

Calixarenes (23) are obtained from base-catalyzed condensations of / -snbstituted phenols with formaldehyde. ... 

Bunte salts Salts of S-alkyl thiosulfates with structure RSS(0)20 M+. calixarenes Cyclic oligomers formed from para-substituted phenols and formaldehyde. 

Calixarenes, the cyclic oligomers formed from condensation reactions between para-substituted phenols and formaldehyde, are inexpensive compounds that are stable to both basic and acidic media. ... 

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. 

Calixarenes are cyclic oligomers obtained by condensation reactions between para-t-butyl phenol and formaldehyde. By judicious choice of base, reaction temperature, and reaction time, calixarenes having different ring sizes can be prepared in good yield. Calixarenes are like crowns in that they are preorganized complexants, yet, unlike crowns, they can be readily synthesized in large quantities. Unlike porphyrins, calixarenes are not fully conjugated, and the three-dimensional structure leads to cavities. 

Calixarenes are synthesized by heating a mixture of pura-t-butylphenol and formaldehyde. Since all of the common ring isomers are obtained by the same procedure, both the reaction time and... 

Calix[4]arenes 14 a and 14 b have been prepared from mesitylene and from 1,2,3,5-tetramethylbenzene by condensation with formaldehyde in the presence of acetic acid 74>. Calixarene 14a has also been prepared by a Friedel-Crafts reaction with chloromethylmesitylene 75). 

The rapid development of calixarene chemistry in the 1980s followed by an explosionlike development in the 1990s is due to the ease by which larger amounts of f-butyl calixarenes are available on a laboratory scale by alkali-catalysed condensation of p-t-butylphenol 1 with formaldehyde (Scheme 1). 

Calixarene-like macrocycles such as 10,11 and 12 have been also prepared by condensation of the respective bisphenols with formaldehyde under alkaline conditions (Scheme 6). 

SCHEME 6. One-pot synthesis of calixarene analogues by condensation of bisphenols with formaldehyde... 

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