Hydroxyl derivatives

We come now to the hydroxyl substitution products of the benzene hydrocarbons. These derivatives are of two classes A, phenols in which the hydroxyl group is substituted in the ring part of the compound. alcohols in which the hydroxyl group is substituted in the side chain of benzene homologues. Benzene having no side chain yields only the first class of derivatives. Toluene, however, and all the other homologues of benzene yield both classes as follows  

Phenols.—The ring hydroxyl compounds take the class name of phenols from the simplest member, hydroxy benzene or phenol. These are true aromatic compounds and in methods of formation, reactions and properties are distinctly different from aliphatic hydroxyl compounds or alcohols. Their outstanding distinction is their marked acid character, the alcohols being neutral (p. 103). This is attributed to the influence of the phenyl radical (CeHs—). The same influence is present in the amino derivatives, for the ring amines, CeHs— NH2, /CH3 

Alcohols.—The side chain hydroxyl compounds take the class name of alcohols for they are true aromatic alcohols in formation, reaction and properties. They are neutral not acid, and are formed by methods analogous to those by which the aliphatic alcohols are prepared. They may be looked upon as benzene derivatives of aliphatic alcohols, e.g. CeHs—CH2OH, benzyl alcohol or phenyl methyl alcohol. 

The acidic influence of the benzene ring or phenyl radical may be illustrated by a comparison of the two series of compounds given below. 

Di-phenyl amine, CeHj—NH—CeHg Cells—NH—CH3, Mono-methyl aniline 

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Naphthoic acids and their halogen, nitrogen and hydroxyl derivatives. (1953.)... 

An old name for benzene was phene and its hydroxyl derivative came to be called phe nol This like many other entrenched common names is an acceptable lUPAC name Likewise o m and p cresol are acceptable names for the various ring substituted hydroxyl derivatives of toluene More highly substituted compounds are named as deriv atives of phenol Numbering of the ring begins at the hydroxyl substituted carbon and proceeds m the direction that gives the lower number to the next substituted carbon Sub stituents are cited m alphabetical order... 

Conversion of the C-2 amide to a biologically inactive nitrile, which can be further taken via a Ritter reaction (29) to the corresponding alkylated amide, has been accomphshed. When the 6-hydroxyl derivatives are used, dehydration occurs at this step to give the anhydro amide. Substituting an A/-hydroxymethylimide for isobutylene in the Ritter reaction yields the acylaminomethyl derivative (30). Hydrolysis affords an aminomethyl compound. Numerous examples (31—35) have been reported of the conversion of a C-2 amide to active Mannich adducts which are extremely labile and easily undergo hydrolysis to the parent tetracycline. This reverse reaction probably accounts for the antibacterial activity of these tetracyclines. 

These 0-bonded substituents are easily cleaved with hydroxide ion to give the corresponding hydroxyl derivative, [B H (OH)] or [B H 2(OH)2] , n = 10,12. Halogenation of [B22H22] A by HCl and HF has been termed acid-catalyzed nucleophilic attack (95). 

As discussed in Section 4.01.5.2, hydroxyl derivatives of azoles (e.g. 463, 465, 467) are tautomeric with either or both of (i) aromatic carbonyl forms (e.g. 464,468) (as in pyridones), and (ii) alternative non-aromatic carbonyl forms (e.g. 466, 469). In the hydroxy enolic form (e.g. 463, 465, 467) the reactivity of these compounds toward electrophilic reagents is greater than that of the parent heterocycles these are analogs of phenol. 

Many mercaptoazoles exist predominantly as thiones. This behavior is analogous to that of the corresponding hydroxyazoles (c/. Section 4.02.3.7). Thus oxazoline-, thiazoline- and imidazoline-2-thiones (521) all exist as such, as do compounds of type (522). However, again analogously to the corresponding hydroxyl derivatives, other mercaptoazoles exist as such. 5-Mercaptothiazoles and 5-mercapto-l,2,3-triazoles (523), for example, are true SH compounds. 

This reduction is not as suitable for sterically hindered ketones, since in these cases the alcohol is the major product. The reduction of 11- and 12- " keto steroids, for example, is usually very slow. Furthermore, the 11-keto steroid (76) yields only about 10% of the 11,1 l-d2 labeled analog (77), the main product being the 1 IjS-dj-l la-hydroxyl derivative (78). ... 

The hydroxyl derivative of X-CN is cyanic acid HO-CN it cannot be prepared pure due to rapid decomposition but it is probably present to the extent of about 3% when its tautomer, isocyanic acid (HNCO) is prepared from sodium cyanate and HCI. HNCO rapidly trimerizes to cyanuric acid (Fig. 8.25) from which it can be regenerated by pyrolysis. It is a fairly strong acid (Ka 1.2 x 10 at 0°) freezing at —86.8° and boiling at 23.5°C. Thermolysis of urea is an alternative route to HNCO and (HNCO)3 the reverse reaction, involving the isomerization of ammonium cyanate, is the clas.sic synthesis of urea by F. Wohler (1828) ... 

Demethylation of trequinsin (3) with a 65 35 mixture of AcOH and 48% HBr at 115 °C for 3 h gave mainly 10-hydroxyl derivatives 148 (R = r = H), which was accompanied by traces of its 9-hydroxyl and 9,10-dihydroxy derivatives. In boiling 48% HBr for 2 h its 9,10-dihydroxy derivative formed in 63% yield (98IJC(B)1). 9-Methoxy group of 3 and that of its 2-[(2,6-dimethyl-4-carboxyphenyl)imino] derivative 178 (R = COOH) was selectively demethylated by the treatment with 60% NaOH and EtSH in HMPA. Treatment of 3 with pyridine HCl in boiling pyridine for 20 min afforded its 9,10-dihydroxy-3-desmethyl derivative in 65% yield. 4 -Hydroxymethyl... 

The reduction of hydroxy or acetoxy ketones by baker s yeast shows an interesting stereoselectivity. For the reduction of acetylbenzofuran derivatives with baker s yeast, the methyl ketones afforded (S)-alcohol in 20-68% ee. The hydroxyl derivatives afforded (S)-alcohol in 87-93% ee, and the acetoxy derivatives gave (R)-alcohols in 84-91% ee (Figure 8.33) [24bj. 

In phase 1 reactions, xenobiotics are generally converted to more polar, hydroxylated derivatives. In phase 2 reactions, these derivatives are conjugated with molecules such as glucuronic acid, sulfate, or glutathione. This renders them even more water-soluble, and they are eventually excreted in the urine or bile. 

Tyramine is produced by decarboxylation of tyrosine and is present in the CNS in higher (threefold) concentrations than m-tyramine, the hydroxylated derivative of phenylethylamine. In the periphery / -tyramine is easily hydroxylated to octopamine, which has some direct effects on ai adrenoceptors, unlike tyramine which functions by releasing NA. When tested on central neurons tyramine always produces the same effects as NA but they are slower and less marked, implying an indirect action. By contrast octopamine often produces the opposite effect to NA and it is probable that octopamine may have a functional role in the invertebrate CNS where it is found in higher concentrations (5pg/g) than in the mammalian brain (0.5ng/g). Neither tyramine nor octopamine have distinct behavioural effects, unlike phenylethylamine,... 

Mincing, cooking and maturing expose meat products to oxidative stress for a long time so that antioxidants added for lipid protection are slowly destroyed on storage. Onion juice is a powerful antioxidant in meat products, more efficient than garlic juice. Lipid hydroperoxides are reduced to inactive hydroxyl derivatives by reaction with sulphur compounds present in those juices. 

Grootveld, M. and Halliwell, B. (1986b). Aromatic hydroxyla-tion as a potential measure of hydroxyl radical formation in vivo. Identification of hydroxylated derivatives of salicylate in human body fluids. Biochem. J. 237, 499-504. 

Kupfer, R. Dwyer-Nield, L. D. Malkinson, A. M. Thompson, J. A. Lung toxicity and tumor promotion by hydroxylated derivatives of 2,6-di-rm-butyl-4-methylphenol (BHT) and 2-A/7-bu lyl-4-methy 1-6-iso-propyl phenol correlation with quinone methide reactivity. Chem. Res. Toxicol. 2002, 15, 1106-1112. 

Hydroxyl derivatives and condensation products (all intermediate hydrolysis products are toxic). 

This oxidation method was applied to determination of the absolute stereochemistry of berberastine (HO) and thalidastine (111). (+)-Tetra-hydrojatrorrhizine (112) was converted to 5a- and 5/J-hydroxyl derivatives 113 and 114 in a 2 1 ratio (Scheme 24). The major product 113 was dehydrogenated to give rise to the dextrorotatory quaternary protoberberine 115. Thus, 110 and 111, being dextrorotatory, should have the same absolute configuration as that of 115 (77). 

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