In hydroxylation

The conversion of indoles to oxindoles can be achieved in several ways. Reaction of indoles with a halogenaling agent such as NCS, NBS or pyridin-ium bromide perbromide in hydroxylic solvents leads to oxindoles[l]. The reaction proceeds by nucleophilic addition to a 3-haloindolenium intermediate. 

Protic solvent (Section 8 12) A solvent that has easily ex changeable protons especially protons bonded to oxygen as in hydroxyl groups... 

Acid-cataly2ed hydroxylation of naphthalene with 90% hydrogen peroxide gives either 1-naphthol or 2-naphthiol at a 98% yield, depending on the acidity of the system and the solvent used. In anhydrous hydrogen fluoride or 70% HF—30% pyridine solution at — 10 to + 20°C, 1-naphthol is the product formed in > 98% selectivity. In contrast, 2-naphthol is obtained in hydroxylation in super acid (HF—BF, HF—SbF, HF—TaF, FSO H—SbF ) solution at — 60 to — 78°C in > 98% selectivity (57). Of the three commercial methods of manufacture, the pressure hydrolysis of 1-naphthaleneamine with aqueous sulfuric acid at 180°C has been abandoned, at least in the United States. The caustic fusion of sodium 1-naphthalenesulfonate with 50 wt % aqueous sodium hydroxide at ca 290°C followed by the neutralization gives 1-naphthalenol in a ca 90% yield. 

The oxidation of vitreous siUca appears to proceed by one of two mechanisms, depending on the material s hydroxyl content (109,111). In hydroxyl-containing material, the rapid oxidation probably occurs by the diffusion and removal of hydrogen, according to the following reaction ... 

Conversely, in hydroxyl-free vitreous siUca, the oxidation is much slower and is controlled by the diffusion of oxygen through the soHd according to the following reaction ... 

In another process, diosgenin is degraded to 16-dehydropregnenolone by chemical methods. Conversion of 16-dehydropregnenolone to 11-deoxycortisol (125) can be accompHshed in 11 chemical steps. These steps result in hydroxylations at C21 and C17, oxidation at C3, and to double-bond isomeri2ation (175). Microbial oxidation of (125) also produces cortisol (29). 

It has already been mentioned that some radical reactions can occur as side reactions by irradiation of pyridazine derivatives, especially in hydroxylic solvents. 

The UV spectra of quinoxalines have been examined in several solvents. In cyclohexane, three principal absorptions are observed (Table 2). In hydroxylic solvents the vibrational fine structure disappears and in methanol or water the weak n- ir transitions are obscured by the intense ir->ir transition (79HC(35)l). 

Chlorination of thiiranes in hydroxylic solvents gives /3-chloroethylsulfonyl chlorides due to further oxidation of the intermediate sulfenyl chloride by chlorine or hypochlorous acid (Scheme 40). Polymer is usually obtained also unless the reaction is done in concentrated hydrochloric acid, which causes rapid ring cleavage to 2-chloroethylthiols which are subsequently oxidized to the sulfonyl chlorides. An 85% yield of (37) is obtained in concentrated hydrochloric acid-HCl(g) whereas only a 15% yield is obtained in CCI4-H2O. 

On treatment with alkaline reagents, -toluenesulfonylhydra-zones of aldehydes and ketones yield diazo compounds which decompose in hydroxylic solvents to yield olefinic (or bicylic) compounds and in aprotic solvents to yield olefins and cyclo-propanes. ... 

The reaction course taken by photoexcited cycloalkenes in hydroxylic solvents depends on ring size. 1-Methylcyclohexene, 1-methylcycloheptene, and 1-methylcyclooc-tene all add methanol, but neither 1-methylcyclopentene nor norbomene does so. The key intermediate in the addition reactions is believed to be the highly reactive -isomer of the cycloalkene. 

As tannins contain many phenolic -type subunits (Fig. 3), one may be tempted to think that they will exhibit a similar reactive potential to that of phenol, and that therefore procedures used in standard PF production can be transferred to those containing tannin. This, however, is not the case. The real situation is that tannin is far more reactive than unsubstituted phenol due to the resorcinol and catchecol rings present in the tannin. This increase in hydroxyl substitution on the two aromatic rings affords an increase in reactivity to formaldehyde by 10 to 50... 

Localized positive charge in hydroxyl-protonated benzoic acid... 

We consider first the Sn2 type of process. (In some important Sn2 reactions the solvent may function as the nucleophile. We will treat solvent nucleophilicity as a separate topic in Chapter 8.) Basicity toward the proton, that is, the pKa of the conjugate acid of the nucleophile, has been found to be less successful as a model property for reactions at saturated carbon than for nucleophilic acyl transfers, although basicity must have some relationship to nucleophilicity. Bordwell et al. have demonstrated very satisfactory Brjinsted-type plots for nucleophilic displacements at saturated carbon when the basicities and reactivities are measured in polar aprotic solvents like dimethylsulfoxide. The problem of establishing such simple correlations in hydroxylic solvents lies in the varying solvation stabilization within a reaction series in H-bond donor solvents. 

Sn2 reactions with anionic nucleophiles fall into this class, and observations are generally in accord with the qualitative prediction. Unusual effects may be seen in solvents of low dielectric constant where ion pairing is extensive, and we have already commented on the enhanced nucleophilic reactivity of anionic nucleophiles in dipolar aprotic solvents owing to their relative desolvation in these solvents. Another important class of ion-molecule reaction is the hydroxide-catalyzed hydrolysis of neutral esters and amides. Because these reactions are carried out in hydroxy lie solvents, the general medium effect is confounded with the acid-base equilibria of the mixed solvent lyate species. (This same problem occurs with Sn2 reactions in hydroxylic solvents.) This equilibrium is established in alcohol-water mixtures ... 

Thus the reactions of cyclic or acyclic enamines with acrylic esters or acrylonitrile can be directed to the exclusive formation of monoalkylated ketones (3,294-301). The corresponding enolate anion alkylations lead preferentially to di- or higher-alkylation products. However, by proper choice of reaction conditions, enamines can also be used for the preferential formation of higher alkylation products, if these are desired. Such reactions are valuable in the a substitution of aldehydes, which undergo self-condensation in base-catalyzed reactions (117,118). Monoalkylation products are favored in nonhydroxylic solvents such as benzene or dioxane, whereas dialkylation products can be obtained in hydroxylic solvents such as methanol. The difference in products can be ascribed to the differing fates of an initially formed zwitterionic intermediate. Collapse to a cyclobutane takes place in a nonprotonic solvent, whereas protonation on the newly introduced substitutent and deprotonation of the imonium salt, in alcohol, leads to a new enamine available for further substitution. 

Compound 7 is reduced to 2-benzamidocinnamyl alcohol by calcium borohydride in hydroxylic solvents at low temperatures. This reduction had been accomplished previously using lithium aluminum hydride in tetrahydrofuran. 

The distributions of phenolic isomers in hydroxylations in the animal body arc often similar to those obtained by Fenton s reagent. For example, the hydroxylation of coumarin by the rabbit gives the six hydroxycoumarins in amounts decreasing in the order 3- >7->6- >8- >4- /—5-, whereas Fenton s reagent gives mainly the 3-, 5-, and 7-derivatives with traces of the 6- and 8-derivatives. It may, however, be misleading to draw conclusions about the nature of... 

Generation of radicals by redox reactions has also been applied for synthesizing block copolymers. As was mentioned in Section II. D. (see Scheme 23), Ce(IV) is able to form radical sites in hydroxyl-terminated compounds. Thus, Erim et al. [116] produced a hydroxyl-terminated poly(acrylamid) by thermal polymerization using 4,4-azobis(4-cyano pentanol). The polymer formed was in a second step treated with ceric (IV) ammonium nitrate, hence generating oxygen centered radicals capable of starting a second free radical polymeriza-... 

Nitroso-5//-dibenz[/j,/ azepine (see Section 3.2.1.5.4.1.) in methanolic hydrochloric acid undergoes rearrangement and ring contraction to a mixture of acridine (59%), acridine-9-carbaldehyde (trace), and 2-nitro-5//-dibenz[/ ,/ azepine (3% mp 176-178 C).184 However, in acetone and hydrochloric acid, the aldehyde (57 %) becomes the major product. On thermolysis, (or photolysis in the presence of oxygen), in hydroxylic solvents, the nitroso compound yields mainly acridine (36-76%) together with minor amounts of either 2-nitrodibenzazepine (4-6% by thermolysis) or acridine-9-carbaldehyde (18% by photolysis). However, in non-hydroxylic solvents, e.g. cumene, acridine-9-carbaldehyde (64%) is the major product. 

Studies of halogenation of the partially reduced systems (e.g., 148) have shown that the 6- (148) or 8-nitro-2,3-dihydrothiazolo[3,2-a]pyridinium bromides were brominated in hydroxylic solvents with a regiochemistry and ease of reaction consistent with the intermediacy of a pseudo base... 

In hydroxylation, quinones are usually obtained since the initial hydroxyl product is further oxidised. Kinetic studies on the hydroxylation of 1,3,5-tri-methoxybenzene with perbenzoic acid gave second-order rate coefficients (Table 29) which remained fairly constant for a wide variation in concentration of aromatic and acid thus indicating that the rate-determining step is bimolecular133. The variation was considered to be within the rather large experimental error for the reaction which was very fast and, therefore, studied at low temperature (—12.4 °C). Since more than one mole of acid per mole of aromatic was eventually consumed, the mechanism was formulated as... 

The generally accepted mechanism for electrophilic bromination of olefins in hydroxylic solutions of medium to high polarity, and at low [Br2], is given in equation 1 (ref. 1). 

---