Hydroxybenzene *Phenol

Oxy-aldehyd, n, hydroxy aldehyde, -ammo-niak, n, oxyammonia (hydroxylamine), -azoverbindung, /. hydroxyazo compound, -benzol, n, hydroxybenzene (phenol), -bem-steinsaure. /, hydroxysuccinic acid (malic acid). -biazol, n. oxadiazole, oxdiazole. -bitumen, n, oxidized bitumen, -carbon-s ure, /, hydroxycarboxylic acid, -chlnoltn, n. hydroxyquinoline, -clunon, n. hydroxy-quinone. -chlorid, n. oxychloride, -chlor-kupfer, n. copper oxychloride, -cyan, n. oxycyanogen. 

The very significant effect of the presence of a bipolar group on Tb and p L can be nicely seen when comparing hydroxybenzene (phenol) and toluene (Table 4.2). In this case, the difference in Tb ( 70°C) and in p,). (factor of 40 at 25°C) can be attributed primarily to the polar interactions among the phenol molecules because both compounds have similar sizes and a similar specific ability to be engaged in vdW interactions. 

By definition, phenol is hydroxybenzene. Phenol is a common name for the compound. Its IUPAC name would be benzenol, derived in the same manner as the IUPAC names for aliphatic alcohols. 

Hydroxybenzenes (phenols, quinols, catechols) (18) C-18 RP Aq. NaLS HPLC 105... 

Another commonly encountered acidic functional group found in drug molecules is phenol, or hydroxybenzene. Phenols are weak acids that liberate protons to give the phenoxide anion. This anion is resonance-stabilised and four canonical forms may be drawn (see Figure 3.5). 

Hydroxybenzene (C HsOH,phenol),and substituted hydroxybenzenes (phenols), much like the arenes to which they are related, enjoy the same enhanced stability (and other properties) of arenes. As a consequence, although both alcohols and phenols possess the hydroxyl (or -OH) functional group, phenols are frequently considered as a separate class of compounds. 

Now, the hydroxyl radical, in what is thought to be a process similar to electrophilic and nucleophilic aromatic substitution vide supra) adds to the aromatic ring, generating a resonance stabilized radical species that, in a subsequent step, loses a hydrogen atom ( H) to, for example, another hydroxyl radical ( 0H), forming hydroxybenzene (phenol, CeHsOH) and water (H2O). 

Interestingly, the results of oxidation (and other reactions) provide some evidence that carbonyl compounds are in equilibrium with the hydroxybenzenes (phenols). Indeed, in extreme cases such as 13,5-trihydroxybenzene (phloroglu-cinol) (Rgure 8.9), some reactions occur as if the tricarbonyl compound were present as the major tautomer. However, it is generally the case that for phenols, as with enols, oxidation occurs either at the adjacent a (or ortho) position or at the more remotely conjugated y (or para) position. 

Figure 8.9. Proton tautomers of hydroxybenzene (phenol), 1,3-dihydroxybenzene (resorcinol), and 1,3,5-trihydroxybenzene (phloroglucinol).

Scheme 8.36. The conversion of hydroxybenzene (phenol, CsHsOH) to aminobenzene (aniline, C6H5NH2) via a substitution reaction involving a phosphate intermediate.

The observation that an aldehyde group can be substituted for a hydrogen ortho-or para- to a phenolic hydroxyl (an HO- on an aromatic ring) by treatment of the hydroxybenzene (phenol) with trichloromethane (chloroform, CHCI3) in the presence of concentrated aqueous sodium hydroxide (NaOH(aq)) was reported by Reimer and Tiemann in 1876 vide supra and Chem. Ber., 1876, 9, 824). Thus, as shown in Equation 9.67, hydroxybenzene (phenol) undergoes conversion to... 

Scheme 9.91. One possible pathway (involving a-elimination of hydrogen chloride [HCl] from chloroform [HCCI3] to generate singlet dichlorocarbene, which is then attacked by the phenoxide anion ortho- or para- to the original hydroxyl [-OH] group) for the Reimer-Tiemann conversion of a phenol to a mixture of phenolic aldehydes. The hydroxybenzene (phenol) is treated with trichloromethane (chloroform, CHCI3) and aqueous sodium hydroxide (NaOH(aq)).

Interestingly, nitroxyl radicals can also be produced by reduction of nitroso compounds. So, for example, nitrosation of hydroxybenzene (phenol) (Chapter 8, Section IV, b) with, for example, nitrosyl chloride (NOCl) produces the corresponding p-hydroxynitrosobenzene and reduction of the latter with, for example, a thiol such as thiophenol, yields the corresponding nitroxyl radical (and dithiophe-nol) (Scheme 10.11). 

H V Br J "" benzene CH3 bromobenzene CH=CH2 chlorobenzene OH nitrobenzene NH2 CN methylbenzene (toluene) ethenylbenzene (styrene) hydroxybenzene (phenol) aminobenzene (aniline) cyanobenzene (benzonitrile)... 

Benzophenol Carbolic Acid Hydroxybenzene Phenol Butyl Butyrate Dibutyl Sebacate Sebacic Acid Dibutyl Ester Propyl Acetate n-Pentane Butyl Chloride 1-Chlorobutane 1-Amlnobutane... 

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