Benzene monohydroxylation

Besides a variety of other methods, phenols can be prepared by metal-catalyzed oxidation of aromatic compounds with hydrogen peroxide. Often, however, the selectivity of this reaction is rather poor since phenol is more reactive toward oxidation than benzene itself, and substantial overoxidation occurs. In 1990/91 Kumar and coworkers reported on the hydroxylation of some aromatic compounds using titanium silicate TS-2 as catalyst and hydrogen peroxide as oxygen donor (equation 72) . Conversions ranged from 54% to 81% with substituted aromatic compounds being mainly transformed into the ortho-and para-products. With benzene as substrate, phenol as the monohydroxylated product... 

It is well-recognized that phenols are completely protonated in superacidic solutions.420 This raised the possibility that protonated phenols, once formed in these media, might resist further electrophilic attack. Electrophilic hydroxylations of aromatics with hydrogen peroxide (98%) in superacidic media has been achieved by Olah and Ohnishi617 in Magic Acid, which allows clean, high-yield preparation of monohydroxylated products. Benzene, alkylbenzenes, and halobenzenes are efficiently hydroxylated at low temperatures. The obtained yields and isomer distributions are shown in Table 5.36. Subsequently, Olah et al.618 found that benzene and... 

Hydroxylation of Benzenic Rings. Intermediate products corresponding to the monohydroxylation of the aromatic ring have been identified in many cases (43,76,77,83,84,88-90). Electron-donating substituents exert the expected orientation effects to para and ortho positions. No orientation dominates for nitrobenzene (90). Dihydroxylated intermediates have also been identified, as well as the corresponding quinones. 

The natural product was synthesized together with its 8-hydroxy isomer (160) via the cyclization of 4-methyl-2-(3-hydroxyphenyl) nicotinic acid (90). A11 four ring C monohydroxylated onychines have been prepared by a different, unambiguous route and their mass, UV, and H-NMR spectra discussed in detail, showing that the base- and aluminum chloride-induced bathochromic shifts are useful criteria for the location of phenol functions on the benzene ring of aza-fluorenones (97). 

The fact that Weiss and Downs have been aide to isolate phenol in the products of their reactions with solid catalysts indicates a hydroxylation mechanism similar to that postulated in the case of vapor phase catalysis, in whidi the formation of the monohydroxylated derivative is the first step. The presence of the hydroxyl group as a substituent in the benzene molecule activates the para and ortho positions so that the introduction of a second oxygen molecule would be expected to result in the formation of quinol (C6H4(OH)2l 4) and catechol (C0H4(OH)21 2) with a preponderance of the former. Quinone which would result from the further oxidation of quinol has been found in the oxidation products from benzene for the case of the homogeneous catalytic reaction. 

The introduction of an alcoholic or a phenolic hydroxy group into an active molecule changes the partition coefficient towards more hydrophilicity and renders the molecule more water-soluble. Thus in changing benzene to phenol, or benzamide to p-hydroxybenzamide, the partition coefficient drops from log P = 2.13 to logP= 1.46 and from log P = 0.64 to log P = 0.33, respectively. The value of the Hansch ir constant for a hydroxy group is — 0.67. This means that to compensate the loss in lipophilicity due to the monohydroxylation of an active compound, it is necessary to attach at an appropriate site on the molecule a chlorine atom (tt = 0.71), for example. 

In contrast to benzene, toluene has a much lower melting point (-93 °C) which allows the use of much lower reaction temperatures which should aid in the prevention of any unwanted side-reactions. In addition, the oxidation of toluene is expected to result in more favorable yields, due to the presence of the activating effect of the methyl group which should facilitate aromatic substitution. As shown in Fig. 2.2, toluene can be converted to the monohydroxylated product in decent yields with the ortho-isomer as the predominant product. 

Zhou N-Y, Jenkins A, Chion CKNCK, Leak DJ. 1999. The alkene monooxygenase from Xanthobacter strain Py2 is closely related to aromatic monooxygenases and catalyzes aromatic monohydroxylation of benzene, toluene, and phenol. Appl Environ A/i-craWo/65 1589-1595. 

A mixture of ester is obtained, and the ratio of monoester to diester is controlled by ratios of the compounds charged to the reactor. Excess polyoxyethylene is used to maximize monoester production (5), and excess fatty acid is used to maximize diester formation (6). Because of the existing equilibrium, it is important that water be removed with an azeotroping agent such as toluene, xylene, etc., and/or by use of an inert-gas sparge to carry off water as it is formed to force the equilibrium toward the desired product. Catalysts such as sulfuric acid (7), benzene sulfonic acid, and other aromatic sulfonic acids (5, 8, 9), as well as cationic ion-exchange resins such as polystyrene-sulfonic acids (5, 9), are used. The latter compounds have the advantage of easy removal from batch reactions and of use in a fixed bed for continuous processes. Metals such as tin, iron, and zinc, as well as their salts in powdered form, have been used as catalysts (10,11). Catalysts can improve the yield of monoester. Of course, use of a monohydroxyl-functional polyoxyethylene, such as that from methanol-started ethylene oxide polymers (methoxy-polyoxyethylene), can be esterified with fatty acids to yield effectively all monoester. 

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