2-halophenol derivatives

A convenient preparation of dihydrobenzofurans has been achieved from the appropriately functionalized ort/ o-halophenol derivatives. Treatment of the aryl iodide (5)-33 with (TMS)3SiH and EtsB in the presence of air at room temperature, gave the aryl radical which cyclized in a 5-exo-trig mode and provided the bicyclic derivatives 34/35 as a 29 1 mixture of diastereoisomers in favour of 34 (Reaction 7.40) [51]. 

The molecular tags that were used are composed of a series of electrophone tags (halophenol derivatives) plus a photolabile linker [93],... 

Br > OTf Cl. Thus, sequential cross-coupling of halotriflates provides unsymmetrical terphenyls when two leaving groups with different reactivity are selected. An alternative method is a stepwise, double crosscoupling of halophenol derivatives (Eq. 40). However, care must be taken because the phosphine ligand changes the order of reactivity... 

Halophenol derivatives are promising substrates for the synthesis of oxygen-containing heterocyclic compounds. As early as 1989, the carbony-lation of 2-iodophenol with phenyl acetylene or norbornadiene was realized. Coumarin and aurone can be prepared under the same conditions from different substrates (Scheme 2.22). 

Recently, arylstannanes were prepared both from phenols via the corresponding aryl diethyl phosphate intermediates [138,139] and from the trimelhylammonium salts of arylamines [140]. Phosphate anion and trimethylamine were used in the place of haUde anions as the leaving groups in the reaction. Interestingly, when haloanilines or halophenol derivatives were used as the precursors, disubstitution products were obtained as illustrated in Scheme 4.25 starting from a phosphate or an anilinium salt [138-140]. 

The effect of the halogen substituent (fluoro, chloro, bromo and iodo) on the yield and mechanism of 4-halophenol photolysis was investigated by Durand et al. [24], Transient spectroscopy in aerated aqueous solutions indicated the formation of p-benzoquinone O-oxide from each derivative except 4-iodophenol for which no transients were detected p-benzoquinone and hydroquinone were found as photoproducts for all four compounds. It was concluded that the carbene mechanism was valid for the whole series. Under continuous irradiation, the 4-halophenol degradation quantum yields were determined to be

fluorescence lifetimes decreased in the same order, from 2.1 ns for 4-fluorophenol to 0.4 ns for 4-chlorophenol and < 0.1 ns for 4-bromophenol. 

Results derived from coupled-cluster calculations for halophenols are summarized in Table 31. It is remarkable that even the small variations due to substituents (as detected by experiments ) are correctly reproduced by the calculations. Accordingly, the meta-halophenols are consistently more acidic than the para-counterparts, in contrast to the pattern found for the cyano (CN) group, auother stroug electron-withdrawing one which tends to reduce the DPE to 14.56, 14.64 and 14.48 eV for ortho-, meta- and para-cyanophenols. The gas-phase acidity scale of cyanophenols is thus para > ortho > meta. 

Halophenols constitute the simplest structural model for the analysis of an intramolecular hydrogen bond since the syn-anti isomerization involves only the rotation of the OH proton around the single C—O bond. Furthermore, the two forms coexist in apolar solvents and give two characteristic absorptions in the OH stretching region of the IR spectrum with the notable exception of the fluoro derivative. In a series of papers Okuyama and Ikawa ° "° have re-examined by FTIR the relative stability of the syn-anti isomers by varying the temperature and the pressure. The enthalpies of isomerization are reported in Table 10. 

Carbene formation was mentioned in an earlier section. This elimination of HCl from 4-chlorophenol or elimination of other hydrogen halides from halophenols could have been inferred from earlier photochemical studies on this and other derivatives. Boule and his coworkers irradiated 4-chlorophenol under deoxygenated conditions and obtained the corresponding quinhydrone and the 2,4 -dihydroxy-5-chlorobiphenyl °. Other research demonstrated that its irradiation in neutral aqueous solutions gave the corresponding quinone " and also that de-aeration did not seem to affect the reaction. ... 

Chlorophenol is also reactive and irradiation in water leads to its conversion into resorcinoP" or in methanol to yield 3-methoxyphenol in 94% yield. Photoamidation with N-methylacetamide of 3-chlorophenol is also efficient and resnlts in the formation of the phenol 241 in a yield of 77%. Intramolecnlar amidation arises on irradiation of 242 in basic methanol. This resnlts in the formation of the indole derivative 243 as well as the methoxylated prodnct 244. More complex halophenols such as 245 are also photochemically reactive, but this yields a complex mixture of products including a benzofuran. The formation of this must be similar to the cychzations described earlier and involves the attack of a radical, produced by the C—I bond fission, on the other ring . 3-Nitrophenol is converted on irradiation in aqueous solution into a variety of products such as nitrocatechols, nitroresorcinol and resorcinol itself... 

In aqueous solutions, 2-halophenols, such as 2-bromophenol, are known to undergo photo-Wolff rearrangement (see also Scheme 6.171). In this reaction, the cyclopentadie-necarboxylic acid derivatives 487 are formed via the singlet a-ketocarbene (488) and ketene (489) intermediates, followed by nucleophilic addition of water (Scheme 6.238).1344-1346... 

Low-level chlorination of 0.5-1.5 mg/1, resulting in a chlorine residual of 0.1 -0.2 mg/1, is used to reduce the degree of biofouling. In sea-water, chlorine oxidizes bromide, present at about 65 mg/1, to bromine, which also contributes to the generation of halogenated by-products [176]. The by-products include hypobromous acid, hypobromite, chloramines, bromamines, trihalomethanes, haloacetonitriles,haloacetic acids, and small amounts of halophenols. However, some haloforms and bromophenols as well as other organobromine compounds are also produced naturally in coastal waters [ 181,182]. Empirical equations for the disappearance of chlorine/bromine derived oxidants from brackish water have been published [183]. 

The photochemical substitution reactions of 2-naphthoxide anion and o-halophenol (X = Br, I) in an aqueous sodium sulfite solution were also reported Photosubstitution of the sulfo group for hydrogen is observed under irradiation of sulfonated derivatives of hydroquinone. Benzo[a]phenanthridine-5-ones (156) (159) were synthesized by photo-induced substitution and cycloaddition of 3-chloroisoquinolin-l-ones... 

The s3mthesis of monohydroxy derivatives of benzophenone is accomplished by condensing the corresponding p-alkyl- or p-halophenol with a substituted or unsubstituted benzoic acid in an inert solvent medium during the passage of BF3 [5] ... 

Halophenols have broad applications in the synthesis of oxygen-containing heterocycles. Typically, 2-halophenol can be prepared by the halogenation of phenols. Then, 2-halophenol can be used for the preparation of the other derivatives. Notably, 2-halophenol also acts as the precursor for aiynes by activation of the C-O bond. 

In 2010, Bao and Shen reported a novel and efficient procedure for the synthesis of benzoxazole and benzimidazole derivatives. The one-pot cascade process is based on Cul under ligand-free conditions. A variety of carbodiimides coupled with o-halophenols or o-haloanilines to give the products in moderate to excellent yields under the mild conditions (Scheme 2.134). 

The considerable interest in the study of the degradation processes of halophenols is due to their presence as pollutants resulting from pulp and paper processes and from industrial production of herbicides and pesticides. Photochemical methods of breaking down these waste products have received considerable attention, and a detailed mechanistic review of the topic is available. The general mechanisms that govern the photochemical fates of simple (monohalogenated) derivatives are discussed here. 

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