Aromatic compounds from benzylic alcohols

Figure 9.9 Plots of log Po vs. log k for a series of 21 aromatic compounds. AC18 column was used with (a) methanol-water 50 50 (v/v), and (b) 0.05 M SDS with 2% 1-propanol. Compounds (1) benzyl alcohol, (2) benzaldehyde, (3) 2,4-dinitrophenol, (4) benzo-nitrile, (5) acetophenone, (6) nitrobenzene, (7) p-nitroanisole, (8) methylbenzoate, (9) anisole, (10) benzene, (11) toluene, (12) chlorobenzene, (13) bromobenzene, (14) ethylbenzene, (15) resorcinol, (16) catechol, (17) phenol, (18) p-nitrophenol, (19) o-chlorophenol, (20) o-bromophenol and (21) 2,4-dichlorophenol. Reprinted from Ref 15 with permission ofElsevier.

Acid chloride 5 is readily available from the known benzylic alcohol 6,4e but intermediate 4 is still rather complex. It was recognized that compound 4 could conceivably be formed in one step from 2-methoxyfuran (9)10 and iodotriflate 10. The latter compound was designed with the expectation that it could be converted to benzyne 8," a highly reactive species that could be intercepted in an intermolecular Diels-Alder reaction with 2-methoxyfuran (9) to give 7. The intermediacy of 7 is expected to be brief, for it should undergo facile conversion to the aromatized isomer 4 either in situ or during workup. 

Recently, Behiman and coworkers discussed the mechanism of the Elbs oxidation reaction and explained why the para product predominates over the ortho product in this oxidation. According to the authors, semiempirical calculations show that the intermediate formed by the reaction between peroxydisulfate anion and the phenolate ion is the species resulting from reaction of the tautomeric carbanion of the latter rather than by the one resulting from the attack by the oxyanion. This is confirmed by the synthesis of the latter intermediate by the reaction between Caro s acid dianion and some nitro-substituted fluorobenzenes. An example of oxidative functionalization of an aromatic compound is the conversion of alkylated aromatic compound 17 to benzyl alcohols 20. The initial step in the mechanism of this reaction is the formation of a radical cation 18, which subsequently undergoes deprotonation. The fate of the resulting benzylic radical 19 depends on the conditions and additives. In aqueous solution, for example, further oxidation and trapping of the cationic intermediate by water lead to the formation of the benzyl alcohols 20 (equation 13) . ... 

Another powerful approach to prepare a-amino acids bearing an aromatic or unsaturated side chain in /I (but also many other compounds) is based on the reactivity of 5-fluoro-4-trifluoromethyloxazole, a starting material easily accessible from hexafluoroacetone. The fluorine atom in the 5 position is easily displaced by an allylic or benzylic alcohol. Then, the obtained ethers spontaneously undergo a Claisen rearrangement to afford, after acidic hydrolysis, an a-trifluoromethyl amino acid... 

The chemical properties of the chlorobenzenes and chloroethylenes differ strikingly from those of saturated aliphatic chlorine compounds and of aromatic compounds with chlorine substituted in a side chain. For example, methyl chloride and benzyl chloride are hydrolyzed by boiling alkali, giving the corresponding alcohols, whereas chlorobenzene is not affected by this treatment. In general there is a pronounced diminution in reactivity of a chlorine atom adjacent to an aromatic nucleus or double bond. 

Several reactions of aromatic compounds have been investigated for their energies of activation. These include p-bromophenol, phthalate, benzoate, henzensulphonate ions, benzyl alcohol, phenylalanine and phenyl acetate, the specific rates of which range from 3-7 x 107 to 1-2 x 1010 m—1 sec-1. The energies of activation of all these reactions were found to be the same, namely, 3-5 + 0-5 kcal mole-1 (Anbar et al., 1967). This corroborates the conclusion that the rate-determining step in e a-reactions with aromatic compounds involves one and the same process, namely, the accommodation of an electron into the aromatic substrate. The subsequent reactions discussed above may be fast or slow but are not involved in the rate-determining step of the reaction of the hydrated electron. 

Phenol AlcohoLs— Just as the aromatic alcohols are isomeric with certain phenols, e.g., benzyl alcohol and the cresols, so a di-hydroxyl compound derived from phenyl ethane, in which one hydroxyl group is in the side chain and the second one is in the ring, is isomeric with phenyl glycol. 

N03)j, a newcomer to the arena of oxidants, is useful for the acetoxylation of aromatic side chains in benzylic positions [415, 416] and for the oxidation of methylene or methyl groups that are adjacent to aromatic rings to carbonyl groups [238, 415, 417]. The reagent also oxidizes alcohols to aldehydes [418, 419, 420, 421] and phenols to quinones [422, 423], cleaves vicinal diols to ketones and a-hydroxy ketones to acids [424, 425], and converts diaryl sulfides into sulfoxides [426]. A specialty of ammonium cerium nitrate is the oxidative recovery of carbonyl compounds from their oximes and semicarbazones [422, 427] and of carboxylic acids from their hydrazides [428] under mild conditions. 

Barium manganate, BaMn04, is commercially available. The dark-blue crystals are obtained from aqueous solutions of barium chloride and potassium permanganate [552, 555]. It oxidizes alcohols, especially benzylic alcohols, to carbonyl compounds [552, 555] hydroquinone to quinone [555] benzylamines to benzaldehydes [555] aromatic amines to azo compounds [555] and phosphines to phosphine oxides [555],... 

Nickel peroxide, an undefined black oxide of nickel, is prepared from nickel sulfate hexahydrate by oxidation in alkaline medium with an ozone-oxygen mixture [929] or with sodium hypochlorite [930, 931, 932, 933]. Its main applications are the oxidation of aromatic side chains to carboxyls [933], of allylic and benzylic alcohols to aldehydes in organic solvents [929, 932] or to acids in aqueous alkaline solutions [929, 930, 932], and of aldehydes to acids [934, the conversion of aldehyde or ketone hydrazones into diazo compounds [935] the dehydrogenative coupling of ketones in the a positions with respect to carbonyl groups [931] and the dehydrogenation of primary amines to nitriles or azo compounds [936]. 

Compounds that have a hydroxyl group attached to a chain on a benzene ring are called aromatic alcohols. These alcohols differ from phenols and show similar properties to aliphatic alcohols. The most important aromatic alcohols are benzyl alcohol and (3-phenyl ethyl alcohol. 

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