Phenolic intermediates

The final phase of resole manufacture is known as the condensation stage (Scheme 3). This is the actual process by which molecular weight is developed and involves the combination of the hydroxymethyl phenol intermediates to form oligomers. It can be reasonably well separated from the resole methylolation reaction in practice by maintaining reaction temperatures below about 70°C. The activation energy for condensation is higher than that for methylolation. This is not to say that condensation does not occur at temperatures below 70°C. It simply means that the methylolation is much faster than condensation at this temperature. 

Figure 5.47 Synthesis of polybenzoxazole with isolation of polyamide phenol intermediate.

We also wanted to evaluate the disassembly of our dendritic system under physiological conditions. Thus, we synthesized a self-immolative AB6 dendron 32 with water-soluble tryptophan tail units and a phenylacetamide head as a trigger (Fig. 5.26) to evaluate disassembly in aqueous conditions. The phenylacetamide is selectively cleaved by the bacterial enzyme penicillin G amidase (PGA). The trigger was designed to disassemble through azaquinone methide rearrangement and cyclic dimethylurea elimination to release a phenol intermediate that will undergo six quinone methide elimination reactions to release the tryptophan tail units. 

The arylation of electron-rich arenes, such as azulene (55)206 and heteroarenes, has been sporadically described. Under similar conditions phenols undergo arylation, which is preferably directed at the ort/zo-positions, probably due to the involvement of palladium phenolate intermediates.188,207 Polysubstitution occurs readily.208 The para-position can be attacked only with the sterically hindered 2,6-di-t-butylphenol.209 Similar ortho-diarylation of arenes bearing carbonyl groups (acetophenone, anthrone, benzanilide, etc.) shows that the or//zo-di reeling effect of the substituent is more important than its other electronic effects.189... 

Sheradsky and LewinteH have reported a fascinating transformation involving the reaction of 0-arylhydroxylamine (58) and DMAD. The initially formed Michael adduct (59) undergoes valence tautomerism to 60, which gives rise to 3-amino-4-carbomethoxycoumarins (63), through the phenol intermediate 61 (Scheme 8). 

Scheme 13 Pathway for the oxidation of 3,5-di-tert-butylphenolate to the corresponding catechol and quinone products using dicopper species 28, via the spectroscopically observed bis(/x-oxo)phenolate intermediate 29 [190]...

An exemplary investigation of the biosynthesis of multicolic acid by fungi (from acetate via phenolic intermediates) made full use of H NMR spectra with LIS shifts and I3C spectra obtained for substrates enriched by [1-13C]-, [2-13C]- and [l,2-13C]-acetate (79MI31006). The 13C chemical shifts are shown with structure (150) the lJ values for the heavy bonds show intact acetate residues and are 48 Hz for the single bond and 90 Hz for... 

Sakamoto et al. (332) applied an HPLC method to analyze capsaicinoids and their phenolic intermediates in Capsicum annuum and to characterize their biosynthetic status. Descended fruit is extracted with 80% EtOH, the extract is evaporated to dryness, and the residue is dissolved in DMSO and analyzed on an Inertsil ODS-2 column with gradient elution (ACN-aq. TFA) and detection at 280 nm. The method was used to study changes in capsaicin content during ripening. 

Iodine-mediated removal of both prenyl protecting groups from aryl ether 506 leads to the unexpected formation of 3-(3-iodo-2,2-dimethylchroman-6-yl)propan-l-ol. The reaction proceeds via formation of the ortho-allylic phenol intermediate 507 by electrophilic removal of a prenyl species, followed by an iodine promoted electrophilic cycliza-tion (Scheme 111) <2001SL1989, 2002T5689>. 

Ishikawa, K., Janos, T., Sakamoto, S. and Nunomura, O. (1 998) The contents of capsaicinoids and their phenolic intermediates in the various tissues of the plants of Capsicum annuum L. Capsicum and Eggplant Newsletter 1 7, 22-25. 

Strongly basic catalysts such as MgO and Ca3 (P04)2 were found to be selective to C-alkylation, leading predominantly to the ortho-isomer of cresol (37). This high selectivity to ortho-cresol was proposed to be due to a more or less upright posture of phenolate intermediates on the catalyst surface (34). 

Additionally to phenolic intermediates, upon the aromatic ring opening, a series of carboxylic acids can be formed. Maleic acid, for instance, has been detected in the oxidation of byphenyls (Bouquet-Somrani et al., 1996), 1,2,4-THB (Li et al., 1991a), 1,2-dimethoxybenzene (Pichat, 1997), and acid orange 7 (Stylidi et al., 2003). Similarly, muconic acid has been reported as an intermediate of byphenyls oxidation (Bouquet-Sormani et al., 1996), while succinic and malonic acids were identified in polycarboxylic benzoic acid oxidation (Assabane et al., 2000). It is therefore expected that these or similar acids be formed during phenol oxidation. 

The HPLC retention behavior of a para bromo-monosubstituted phenol intermediate and its ortho isomer were investigated. The ortho isomer is a common impurity generated during the synthesis of the desired para isomer intermediate. It was critical to control this impurity because it would react at the hydroxyl functionality in the downstream chemistry to produce unwanted synthetic impurities in the API (active pharmaceutical ingredient). Implementing a recrystallization procedure to remove these downstream synthetic impuri-... 

In conclusion, toxic chlorinated phenol intermediates formed during the chemical, photochemical and/or enzymatic degradation of chlorophenoxyalkanoic compounds would temporarily be detoxified when they are incorporated into the humic acid, since their bioavailability and movement into terrestrial and aquatic ecosystems would be greatly reduced. However, the knowledge of the potential toxicity problems which these bound-residues could give rise to in the environment is still very limited. Xenobiotic chemicals incorporated into humic polymers are not really removed from the ecosystem and they may maintain their identity and toxic properties for unknown time spans, eventually causing time-delayed pollution problems, if and when they will be released from humic substances. 

Use Reagent for characterizing phenols intermediate in the manufacturing of bactericides, insecticides, surface-active agents, and the upgrading of drying oils. 

It was shown that benzo[fc]pyrylium salts 376 are capable also of recyclizations to produce the phenol derivatives 377 (equation 179). The 1,3-benzodioxanes 378 undergo an acid-induced fragmentation to xanthylium salts 380 via phenolic intermediate 379 (equation 180). 

Danishefsky has exploited his widely utilized silyloxydiene chemistry to complete a formal total synthesis of 90 (Scheme 1.20). By employing the appropriate oxidation levels for both the diene and dienophile, a resorcinyl ester possessing the required differentiation of the phenolic groups was obtained without further oxidative manipulation. To this end, the dianion of propiolic acid was alkylated with l-bromo-7-octene to give acid 98 in 68% yield. Further alkylation with methyl iodide then gave the ester 99. A Diels-Alder reaction with diene 100, a derivative of methyl acetoacetate, and alkyne 99 then furnished an initial phenolic intermediate which was protected as the benzyl ether to afford... 

The allenyl phenol intermediate (80) has been shown to be involved in the photochromic reaction of 2,2-di(4-fluorophenyl)-6-methoxy-2H-l-chromene. ° The chromene, 2,2-diphenyl-5,6-benzo(2H)chromene, undergoes colouration on irradiation. ... 

Alkylation. A synthetic approach to platensimycin entails a step of intramolecular alkylation, in which a phenolate intermediate is generated from a silyl ether. The process can be accomphshed with BU4NF. ... 

A range of selective procedures has been introduced for the formation of monochloro and dichlorophenols from phenolic intermediates in the great majority of which free chlorine has not been used. For the monochlorination of phenol and acylphenols these methods have been summarised in Table 8.1 (refs.7-13). 

In this sense it may well appeal more to postgraduates students in academic and industrial work. By no means all phenolic systems have been covered in detail, as for example phenolic propanoids, although most have been referred to at some stage amongst the fourteen chapters. The emphasis thoughout has been on synthesis, on what can be achieved by the use of phenolic intermediates and in the construction of phenolic end products. 

The extensive work of Dadak and co-workers(10-13), in the course of which many by-products of aromatic nitration were identified, did not include any well-established explanation of the mechanism by vdiich phenolic intermediates are produced and... 

Some examples of bioactivation to hepatotoxic or IDR electrophilic intermediates are shown in Fig. 10.33. Bioactivation may occur by both oxidation and conjugation reactions, such as those with diclofenac, which undergoes the formation of an acyl glucuronide and/or acyl CoA (acylator intermediates) or to produce iminoquinones via formation of a phenol intermediator (Fig. 10.33-1) (92). The anticonvulsant carbamazepine is 2-hydroxylated and the elimination of the amide group yields the reactive quinoneimine intermediate (Fig. 10.33-2), and the antidepressant paroxetine and other xenobiotics with the common methylenedioxyphenyl nucleus undergo methylene oxidation to a... 

The monoadduct of tetraene 11 and benzoquinone [107] can be reduced selectively into alcohol 37 (94%), the structure of which has been established by X-ray radiocrystaUography [163]. The corresponding mesylate 38 eliminates one equivalent of methanesulfonic acid in the presence of two equivalents of f-BuOH/THF giving a potassium phenolate 39 that is reacted with Mel to give the corresponding anisole 40 (99%). When an excess of base is used (4.3 equivalents of f-BuOK), the phenolate intermediate 39 is isomerized re-gioselectively (7 3) into the vinylphenolate 41. 

Sih, Wang, and their collaborators elucidated the pathway whereby 5 is transformed into 8 via 6 and 7. A key reaction is the 4-hydroxylation of the phenolic intermediate 5. Sih has recently shown that the same process is also implicated in the microbial degradation of estrone by a particular Nocardia sp. (Ap-13), which is illustrated here. Intermediate B corresponds to 6 and C to 7. The probable structure of... 

Fig. 13.15), through a commonly applicable methodology (635). The synthesis sequence (Scheme 13.8) involved manipulation of a silyl-protected 4-hydroxycyclohex-2-enone (902) through several steps to the 2-bromo-3-carboxymethyl ester 905, then reaction of this species with the aldehyde 906 to form the intermediate benzophenone 907. This product was first desilylated, then de-allylated, with a second deprotection followed by an in situ cyclization of the phenolic intermediate, to give blennolide C (897) and the diastereomer 908 in an approximately 2 1 diastereomeric ratio, after 11 steps from cyclohexenone 258 (635). 

In contrast with arylations of other heterocycles, the palladium-catalyzed arylation of benzoxazoles at C-2 proceeds readily at ambient temperature (Scheme 11.21) [67]. Although, as in other cases no kinetic isotope effect was found for 59a, a Hammett plot revealed a correlation with ct with a positive p, which indicates that a phenolate intermediate is formed in this reaction. Therefore, this reaction has been shown to proceed by a totally different mechanism. According to experimental results and DFT calculations, the reactions proceed by the deprotonation of benzoxazoles 59 to form 61, which is in equilibrium with o-phenoxyisocyanide 62. Coordination of the oxidative addition product PdI(Ph)L2 to the isocyanide then forms 63 which cyclizes to form palladate 64, from which the 2-phenylbenzoxazoles 60 are formed by reductive ehmination. 

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