Phenol haloarene

The complete elimination of functional groups is often an undesirable side reaction in organic synthesis, but on the other hand it is a possibility for the recycling of environmentally harmful compounds, for example phenols and haloarenes such as polychlorinated dibenzodioxins (PCDDs or dioxins ). For example, aryl chlorides can be effectively dechlorinated with Pd(0) NPs in tetra-butylammonium salts with almost quantitative conversions also after 19 runs (entry H, Table 1.4) [96]. On the other hand, a C-0 bond cleavage reaction also seems suitable for the fragmentation of sugar-based biomass such as cellulose or cello-biose in that way, sugar monomers and bioalcohol can be derived from renewable resources (entry F, Table 1.4) [164]. 

Haloarene Alcohol/phenol Reaction conditions % yield... 

There are relatively few reports of phase-transfer catalysed syntheses of phenols from activated haloarenes using quaternary ammonium salts, presumably because of the instability of the ammonium salts under the reaction conditions. A patented procedure for the conversion of, for example, 2,6-dichloropyridine into 6-chloropyrid-2-one (98%) using aqueous sodium hydroxide in the presence of benzyl-triethylammonium chloride at 120-150°C has been filed [32], A possible route to the phenols, however, comes from the observed reaction of phenols with potassium carbonateipotassium hydrogen carbonate to yield the aryl carbonates (80-85%) using the procedure described for the preparation of dialkyl carbonates (3.3.13) [50]. 

It is interesting to note that boiling points of alcohols and phenols are higher in comparison to other classes of compounds, namely hydrocarbons, ethers, haloalkanes and haloarenes of comparable molecular masses. For example, ethanol and propane have comparable molecular masses but their boiling points differ widely. The boiling point of methojqmiethane is intermediate of the two boiling points. 

Alcohols may be prepared (1) by hydration of alkenes (1) in presence of an acid and (11) by hydroboratlon-oxidatlon reaction (2) from carbonyl compounds by (1) catalytic reduction and (11) the action of Grignard reagents. Phenols may be prepared by (1) substitution of (1) halogen atom In haloarenes and (11) sulphonic acid group In aiyl sulphonic acids, by -OH group (2) by hydrolysis of diazonium salts and (3) industrially from cumene. 

Acceptor-substituted haloarenes have been successfully used to O-arylate phenols by aromatic nucleophilic substitution (Table 7.14). The most common arylating agents are 2-fluoro-l-nitroarenes, 2-halopyridines, 2-halopyrimidines, and 2-halotriazines. When sufficiently reactive haloarenes are used, the reaction proceeds smoothly with either the arylating agent or the phenol linked to the support. The thallium(III) nitrate catalyzed arylation of phenols with aryl iodides has been used for macrocycli-zations on solid phase [184], Burgess and co-workers have developed a solid-phase synthesis of 3-turri mimetics based on ring-closure by aromatic nucleophilic substitution (Entry 4, Table 7.14 see also Table 10.5). Phenols, alkylamines, and thiols have been successfully used as nucleophiles for this type of macrocyclization [185],... 

The synthetic route is based on the preparation of the M(4-6) and the M(2-4) subunit by intramolecular Sf.jAr cyclizations of suitable precursor peptides with ort/ o-nitro-substituted haloarene residues and a central phenolic unit (Schemes 2 and 4). This concept was originally developed by Zhu and co-workers and applied successfully to the synthesis of cyclic peptides of the vancomycin family, e. g. to the synthesis of K-13 [13]. 

Intramolecular coupling of phenols with haloarenes. Using Cs COj as a base in... 

During oxidation of haloarenes 1,2 migration of the halogen, leaving a phenolic hydroxy group at the original position of the halogen, the so-called NIH shift, often occurs [7, 52] (Scheme 4.20). 

Scheme 4.20 Oxidation of aromatic substructures leads, via an electrophilic epoxide, to the formation of phenols. The so-called NIH shift in haloarenes involves 1,2 migration of the halogen substituent [52].

The electrophile substrates for C—O bond formation have been divided into the following categories electron-deficient haloarenes, unactivated haloarenes, and vinyl halides. l-Butanol, alcohols with /3-hydrogens, silanols, and phenols are the classes of nucleophile substrate. Table 1 shows the various ligands for palladium that have been shown to accomplish these different types of transformations as of May 15, 1999, when this section was prepared. 

These reports on copper-mediated coupling reactions set the stage for pioneering reports by UUmarm and Irma Goldberg (his later wife) on the use of catalytic amounts of copper for coupling reactions of haloarenes. Thus, the arylation of phenol (16) and its derivatives with low catalyst loadings of copper enabled the selective syntheses of diarylethers (Scheme 1.5) [29]. 

Due to their availability, haloarenes are frequently used for synthetic reactions, and when nucleophilic attack is rate limiting, as is usually the case, the reactivity order is F C1, Br>I. Although reaction can occur in unactivated systems, this requires the use of high temperatures and/or pressures and may be aided by metal catalysts. Thus, reaction of chlorobenzene with aqueous sodium hydroxide or ammonia can yield phenol and aniline, respectively. In systems containing one or more EWGs, reaction with alkoxides or phenoxides can be used to form alkyl aryl ethers and... 

Haloarenes devoid of electron-withdrawing substituents do not undergo simple ipso substitution. Nevertheless, when haloarenes are treated with nucleophiles that are also strong bases, if necessary at highly elevated temperatures, they convert to products in which the halide has been replaced by the nucleophile. For example, if exposed to hot sodium hydroxide followed by neutralizing work-up, chlorobenzene furnishes phenol. 

Mechanism of the Pd-Catalyzed Phenol Synthesis from Haloarenes... 

As mentioned in Section 22-4, V-nitrosation of primary benzenamines (anilines) furnishes arenediazonium salts, which can be used in the synthesis of phenols. Arenediazonium salts are stabilized by resonance of the tt electrons in the diazo function with those of the aromatic ring. They are converted into haloarenes, arenecarbonitriles, and other aromatic derivatives through replacement of nitrogen by the appropriate nucleophile. 

In Summary Arenediazonium salts, which are more stable than alkanediazonium salts because of resonance, are starting materials not only for phenols, but also for haloarenes, arenecarbonitriles, and reduced aromatics by displacement of nitrogen gas. The intermediates in some of these reactions may be aryl cations, highly reactive because of the absence of any electronically stabilizing features, but other, more complicated mechanisms may be followed. The ability to transform arenediazonium salts in this way gives considerable scope to the regioselective construction of substituted benzenes. 

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