Arene-Aldehyde Condensations

1 Base-Catalyzed Condensation of -Substituted Phenols and Formaldehyde 

In the process of unravelling the intricacies of the condensation of p-tert-butyl-phenol and formaldehyde 23), it was discovered that if a stoichiometric amount of base is used in the condensation instead of the catalytic amount employed in the original Petrolite procedure the major product is the cyclic hexamer, p-tert-butyl-calix[6]arene (6, R = /err-Butyl), Yields as high as 70-75% of pure, crystalline 

Little is known about the overall mechanism of cyclic oligomer formation, although the mechanism of the initial stages of the sequence seems fairly clear. The first chemical event is the reaction of formaldehyde (formed in the Petrolite procedures by depolymerization of paraformaldehyde) with phenol to form 2-hydroxy-methyl- and 2,6-6w(hydroxymethyl)phenols in a base-catalyzed process, as shown in Fig. 3. Such compounds were characterized many years ago50), obtained from the action of aqueous formaldehyde on phenol in basic solution at room temperature. Subsequent condensation between the hydroxymethylphenols and the starting phenol occurs to form linear dimers, trimers, tetramers, etc. via a pathway that might involve o-quinonemethide intermediates which react with phenolate ions in a Michael-like reaction, as portrayed in Fig. 4. The condensation of hydroxymethyl- 

It is reported 23) that the yield of cyclic hexamer, which is the major product when a stoichiometric amount of base is used, is slightly better with RbOH than with CsOH, KOH, or NaOH LiOH is an ineffective catalyst. This has been interpreted as suggesting that a template effect may play a part in the cyclization 

Pseudocalix U1 arene Pseudocalix [61 arene Hemicalix 141 arene Hemicolix 161 arene 

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The condensation of an aldehyde with resorcinol gives rise to calix (3) arene (114). Isoprene reacts with resorcinol under acidic conditions to give ben2odipyran (24) and monochroman (25) (115). 

We have found several examples in which adjacent cationic charge centers are shown to activate carboxonium electrophiles. A convenient method for studying this activation is through the use of the hydroxyalkylation reaction, a commercially important, acid-catalyzed condensation of aldehydes and ketones with arenes.10 It is used for example in the synthesis of bis-phenol A from acetone and phenol (eq 6). While protonated acetone is able to react with activated arenes like phenol, it is not capable of reacting with less nucleophilic... 

Cavitands are originally host compounds based on the resorc[4]arene [35] platform obtained from the condensation of resorcinol with aldehyde [36,... 

The cavitands are essentially synthesized from their resorc[4]arene precursors which are readily obtained by resorcinol condensation with aldehydes. The main feature comes from the different configurations that are expected for this tetrameric species and the relative thermodynamical stability of each isomer, which has been widely investigated by several authors. In addition, the conformational mobility of the resorc[4]arene molecules will depend on substitution at the upper and lower rims [28, 36, 40, 41]. The first attempt to synthesize a phosphorus bridged cavitand was to treat resorc[4]arene la (1, R=CH3) with phenylphosphonic dichloride or phenylphosphonothioic dichloride. Only inseparable isomer mixtures were obtained and isolation of the desired cavitands was not possible [42]. The first isolated phosphorylated resorcinol-based cavitand was described in 1992 by Markovsky et al., who prepared compound D from la and four equivalents of o-phenylenechlorophos-phate in the presence of triethylamine [43, 44]. For this compound, a tautomeric temperature and solvent dependent equilibrium exists between the spirophosphorane structure and the cyclic phosphate form (Scheme 4). 

We will use the name resorc[4]arene to design the tetrameric product obtained from the condensation of resorcinol and aldehyde also named resorcinarene or resorcino-larene... 

It was previously noted that superelectrophilic carboxonium ions may be generated from suitable precursors, including amino-ketones, /V-heteroaromatic ketones and aldehydes, amino-acetals, and other substrates.45 In their superacid-promoted condensation reactions, these compounds often produce ammonium-carbenium superelectrophiles as intermediates in the reactions. As an example, the amino-acetal (229) reacts with arenes in the presence of superacid to give the arylated product (231, eq 72).43... 

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 synthesis of calixresorc[4]arenes from aldehydes and resorcinol is catalyzed by mineral acids and by Lewis acids. The presence of an alkyl or aryl substituent coining from the aldehyde results in formation of four conformers labeled rccc (all-c , the crown conformer), rcct (the diamond conformer), rctt, and rtct. SnCU, when used in the condensation of isovaleraldehyde with 1,3-dimethoxybenzene, catalyzes selective formation of the rccc conformer in high yield (Eq. 63) [95]. 

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. 

Given a Lewis structure, a condensed formula, or a line drawing for an organic compound, identify it as representing an alkane, alkene, alkyne, arene (aromatic), alcohol, carboxylic acid, ether, aldehyde, ketone, ester, amine, or amide. 

At a lower oxidation level, orffto-hydroxy-acyl-arenes undergo base-catalysed aldol condensations with aromatic aldehydes to give chalcones, °° which can be cyclised to 2,3-dihydro-chromones via an intramolecular Michael process the dihydro-chromones can in turn be dehydrogenated to produce chromones by a variety of methods, for example by bromination then dehydrobromination or by oxidation with the trityl cation, iodine, dimethyldioxirane or iodobenzene diacetate. ° ... 

Owing to its Lewis acidity, zinc complex 106 lends itself to schemes for alkylation of electron-rich arenes and heteroarenes such as pyrroles by way of conjugate addition. An even more valuable method is the 3-component condensation that unites indole with a nitroalkene and an aldehyde. Three contiguous stereocenters are established in a controlled manner and in an absolute sense by conducting the reaction in the presence of CuOTf, 126, and hexafluoroisopropanol. ... 

Usually, the condensation between arenes and aldehydes is carried out in the liquid phase, and large pore zeolites are necessary in order to make the reaction occur at an acceptable rate in the condensed phase. When formaldehyde is the reactant, one main problem is the presence of water, since the aqueous solution of formaldehyde (formalin) is the simplest, cheapest and most widely available reactant for use on an industrial scale. This implies the need for hydrophobic zeolites, in order to avoid preferential filling of the pores by more polar water molecules rather than by the aromatic substrate [8,9]. The objective of the work reported here was to compare the performance of different solid acids, and to study the effect of operating parameters on catalytic performance in the hydroxymethylation of guaiacol with formaldehyde catalyzed by a commercial dealuminated, and thus more hydrophobic, H-mordenite zeolite. 

Friedel-Crafts alkylations of arenes with mesylates, benzyl or allyl alcohols, aldehyde/diol combinations (reductive alkylation), 1,3-dienes, or alkenes in an ionic liquid are also effectively catalyzed by Sc(OTf)3. Sc(OTf)3 works as an efficient catalyst for the condensation reaction of trimethylhydroquinone with isophytol to afford a-tocopherol. 2-Aminoalkylation of phenols with a-iminoacetates (or glyoxylate/amine) is catalyzed by Sc(OTf)3 to produce amino acid derivatives. The Sc(OTf)3-catalyzed alkylations of indoles with a-hydroxy esters, aziri-dines, acetals, and aldehydes have been utilized as key steps of total syntheses as exemplified in eq 15. ... 

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