Phenol ring

Product identification does not distinguish OH versus hole oxidation, because the products are identical. For example, the products identified in the photo oxidation of phenol (qv) (Fig. 7) may originate either by OH radical attack of the phenol ring, or by direct hole oxidation to give the cation radical which subsequendy undergoes hydration in solvent water. 

Thioglycohc acid is recommended as a cocatalyst with strong mineral acid in the manufacture of bisphenol A by the condensation of phenol and acetone. The effect of the mercapto group (mercaptocarboxyhc acid) is attributed to the formation of a more stable carbanion intermediate of the ketone that can alkylate the phenol ring faster. The total amount of the by-products is considerably reduced (52). 

The effect substitution on the phenolic ring has on activity has been the subject of several studies (11—13). Hindering the phenolic hydroxyl group with at least one bulky alkyl group ia the ortho position appears necessary for high antioxidant activity. Neatly all commercial antioxidants are hindered ia this manner. Steric hindrance decreases the ability of a phenoxyl radical to abstract a hydrogen atom from the substrate and thus produces an alkyl radical (14) capable of initiating oxidation (eq. 18). 

Scheme 4a shows the condensation of a benzyl alcohol group with a phenolic ring position occupied by hydrogen to produce a methylene linkage between two phenolic rings and producing one mole of water as a by-product. This type of condensation occurs at both high and low pH. It is the type most commonly seen in both resoles and novolacs. 

Scheme 4b depicts condensation between a hydroxymethyl group and a phenolic ring where the hydroxybenzyl attacks at a ring position that is already hydroxymethylated. In this case, a methylene linkage is produced between the rings with concurrent loss of one mole each of formaldehyde and water. Both Jones and Grenier-Loustalot et al. demonstrated the occurrence of this reaction pathway beyond doubt under basic conditions. 

Scheme 10. Mechanislic possibililies for PF condensalion. Mechanism a involves an SN2-like attack of a phenolic ring on a methylol. This attack would be face-on. Such a mechanism is necessarily second-order. Mechanism b involves formation of a quinone methide intermediate and should be Hrst-order. The quinone methide should react with any nucleophile and should show ethers through both the phenolic and hydroxymethyl oxygens. Reaction c would not be likely in an alkaline solution and is probably illustrative of the mechanism for novolac condensation. The slow step should be formation of the benzyl carbocation. Therefore, this should be a first-order reaction also. Though carbocation formation responds to proton concentration, the effects of acidity will not usually be seen in the reaction kinetics in a given experiment because proton concentration will not vary.

The influence of an ort/io-imidazole substituent on the bond dissociation energy of the O—H bond in phenol was studied by DFT calculations [00IJQ714]. The imidazole ring is twisted with respect to the phenol ring by 59° and causes a decrease of the bond dissociation energy by about -1 kcal/mol with respect to the unsubstituted molecule only. 

Mor alpha-) Dinitrophenol- Yel orthorhombic crysts from w, leaflets from ale mp 112—14° bp (decomp) d 1.683g/cc at 24°, 1.4829 at 72.5/4°. Sublimes when carefully heated volatile with steam. Can be prepd by the nitration of phenol, but this method is not considered commercially practicable because of partial decompn of the phenolic ring. A better method is by hydrolysis under pressure of 2,4-dinitrochloro-benzene, which in turn can be obtained by nitrating chlorobenzene. Other methods are given in Ref 1... 

Another interesting observation was made by Bagal et al. a year later (1992). In the reaction of 4-nitrobenzenediazonium ions with various 4-phenylazophenols, with or without substituents in the 2- and 3-positions of the phenolic ring and in the 4 -position of the phenylazo ring, in addition to azo coupling in the 6-position they obtained a product that had the same atomic composition as 2,4-bis(4 -nitrophenyl-azo)-phenol (Ci8Hi4N605), but whose 13C NMR spectrum clearly showed a tetrahedral and a carbonyl carbon in the 4- and 1-positions. This product must therefore be the compound 12.153. 

An additional activating hydroxyl group on the phenolic ring allows resorcinol to react rapidly widi formaldehyde even in die absence of catalysts.8 Hiis provides a method for room temperature cure of resorcinol-formaldehyde resins or mixed phenol-formaldehyde/resorcinol-formaldehyde resins. Trihydric phenols have not achieved commercial importance, probably due to tiieir higher costs. 

Novolacs are prepared with an excess of phenol over formaldehyde under acidic conditions (Fig. 7.6). A methylene glycol is protonated by an acid from the reaction medium, which then releases water to form a hydroxymethylene cation (step 1 in Fig. 7.6). This ion hydroxyalkylates a phenol via electrophilic aromatic substitution. The rate-determining step of the sequence occurs in step 2 where a pair of electrons from the phenol ring attacks the electrophile forming a car-bocation intermediate. The methylol group of the hydroxymethylated phenol is unstable in the presence of acid and loses water readily to form a benzylic carbo-nium ion (step 3). This ion then reacts with another phenol to form a methylene bridge in another electrophilic aromatic substitution. This major process repeats until the formaldehyde is exhausted. 

C—H bonds. Phenol, mono-ortho, and di- and tri-substituted phenolic rings can be monitored between 814-831, 753-794, 820-855, and 912-917 cm-1, respectively. Para-substituted phenolic rings also absorb in the 820-855-cm 1 region. 

Resole syntheses entail substitution of formaldehyde (or formaldehyde derivatives) on phenolic ortho and para positions followed by methylol condensation reactions which form dimers and oligomers. Under basic conditions, pheno-late rings are the reactive species for electrophilic aromatic substitution reactions. A simplified mechanism is generally used to depict the formaldehyde substitution on the phenol rings (Fig. 7.21). It should be noted that this mechanism does not account for pH effects, the type of catalyst, or the formation of hemiformals. Mixtures of mono-, di-, and trihydroxymethyl-substituted phenols are produced. 

Thermal degradation below 300°C in inert atmospheres produces only small amounts of gaseous products. These are mostly unreacted monomers or water, which are by-products eliminated from condensation reactions between hydroxymethyl groups and reactive ortho or para positions on phenolic rings. A small... 

A huge group of macrocycles which contain 2,6-disubstituted phenols are the calixarenes [51]-[53]. Their conformation has been investigated intensively (Gutsche, 1989, 1991). In most conformations, however, the phenolic rings are oriented almost vertically in relation to the plane of the macrocydic ring. Therefore the OH functions are not oriented in an intra-annular fashion. Nevertheless the pK values of calixarenes [51] differ from those of other comparable phenols. The reason for this is the... 

Transformation of the widely used over-the-counter analgesic acetaminophen (paracetamol) during chlorination produced the toxic 1,4-benzoquinone via the A-acetylquinone-imine and minor amounts of products from chlorination of the phenolic ring (Bedner and Maccrehan 2006). 

Compounds with cis double bonds in the side chain were in general found to be more potent and efficacious than their triple-bond congeners, both in in vivo and in in vitro functional assays [98, 106, 107]. QSAR models have been generated for the compounds with unsaturated [108] and l, l -dimethyl [96] side chains to determine more precisely the pharmacophoric requirements of the receptor. It is postulated that for optimum potency, the side chain must be of a suitable length and flexibility to have the ability to loop back so that its terminus is in proximity to the phenolic ring. The widely used, potency enhancing 1 - and 2 -methyl substituents would be expected to increase the tendency of the side chain to adopt a looped back, rather than an extended conformation. 

Oxidation of the phenol ring of cannabidiol (73) or cannabinol to a qui-none ring has been shown to afford compounds with anti-tumour activity. However, these compounds do not bind to the CBi receptor and their mechanism of action is unclear [128],... 

Substituents on the 2- and 6-positions of phenol rings greatly influence QM reactivity. Reaction rates for QMs derived from several of the phenols, shown in Fig. 10.1, were determined in methanolic or aqueous solutions and are listed in Table 10.1. Replacing a tert-butyl substituent of BHT by a methyl group (i.e., BDMP-QM) increased the rate of hydration by 60-70-fold at pH 7.4 and this... 

Figure 22 Positioning of the Tyr8 phenol ring (colored stick structures) relative to the Ni11 (purple sphere) and its chelate ring (ball-and-stick structure). The lowest-energy representatives of conformational families 1-3 are shown in blue, green, and yellow, respectively. The phenol oxygen is a red sphere.1747...

The synthesized CPMV-alkyne 42 was subjected to the CuAAC reaction with 38. Due to the strong fluorescence of the cycloaddition product 43 as low as 0.5 nM, it could be detected without the interference of starting materials. TMV was initially subjected to an electrophilic substitution reaction at the ortho-position of the phenol ring of tyrosine-139 residues with diazonium salts to insert the alkyne functionality, giving derivative 44 [100]. The sequential CuAAC reaction was achieved with greatest efficiency yielding compound 45, and it was found that the TMV remained intact and stable throughout the reaction. 

Figure 1.82 The hydroxyl group of serine residues and the phenolate ring of tyrosine groups may be modified with succinic anhydride to produce relatively unstable ester bonds. In aqueous conditions these reactions are minor due to competing hydrolysis by water.

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