SYNTHESIS halophenols

Halophenols without 2,6-disubstitution do not polymerize under oxidative displacement conditions. Oxidative side reactions at the ortho position may consume the initiator or intermpt the propagation step of the chain process. To prepare poly(phenylene oxide)s from unsubstituted 4-halophenols, it is necessary to employ the more drastic conditions of the Ullmaim ether synthesis. A cuprous chloride—pyridine complex in 1,4-dimethoxybenzene at 200°C converts the sodium salt of 4-bromophenol to poly(phenylene oxide) (1) ... 

Benzofurans. 2-Substituted benzofurans can be obtained in 65-83% yield by reaction of o-iodophenols and 1-alkynes in the presence of Cu20 suspended in pyridine. This synthesis has been conducted in the past by reaction of copper(I) acety-lides with o-halophenols, but yields are somewhat lower. In addition, copper(I) acetylides can be explosive. 

Zirconium-aryne complexes have also found application in the regiose-lective synthesis of halophenols.62 Reaction of 101 with methyl diethylbori-nate or triethylborate leads to insertion of a boron-oxygen bond into a Zr-benzyne bond with formation of 102 and 104, respectively (Scheme 12). Further reactions of 102 and 104 with bromine or iodine followed by excess NaOH and 30% hydrogen peroxide gives halomethyl(methoxy)phe-nols 103 and 105 in good yields. In most cases only one regioisomer of the halophenol was observed. 

Singular examples to form aromatic ethers are a base-catalyzed, multistep, one-pot reaction of aryl methyl ketones with the appropriate fluorinated arylidenemalonitriles, the mercury acetate assisted synthesis of pentahalophenylvinyl ethers from vinyl acetate and the corresponding phenol, and the radical displacements in aryloxycyclohexadienones (e.g., 27) by halophenols. 2,3-Dichloro-5,6-dicyanohydroquinone (28) and products such as 29 are readily formed when cyclohexadienone 27 is treated with different phenols. 

Construction/ secretion Synthesis of refractory or inhibitory structural products (tube linings, halophenols, body structural products) ... 

The reversible conversion of phenols to dienone intermediates is an important transformation in the synthesis of natural products. This rearrangement occurs efficiently in superacid solutions The corresponding version for the halophenols to give halodienones has been reviewed in an earlier volume of this series. 4-Bromo-2,4,6-trialkylcyclohexa-2,5-dienones have recently been synthesized by electrophilic bromination of the corresponding phenols. 

Recently, an efSdent method for the synthesis of 1,4-benzo- and pyrido-oxazepinones was also disdosed [46]. This reaction proceeds via a domino process through one-pot ring-opening/carboxamidation reaction sequences of N-tosylaziri-dines with 2-halophenols/pyridinol under phase-transfer conditions (benzyltriethy-lammonium chloride, TEBA). A variety of 1,4-benzo- and pyrido-oxazepinones... 

As mentioned earlier (Chapter 9.2.1.1), a formal [3 + 2] approach toward the synthesis of benzofurans 57 and related compounds involving a coupling-cydization reaction between ortho-halophenol 54 and copper(I) acetylides 55 was first established by Castro and coworkers (Scheme 9.21) [75-77, 111]. It was proposed that the formation of the benzofuran 57 is a stepwise reaction involving formation of the ortho-alkynylphenol intermediate 56 [77]. The authors demonstrated that a variety of substituted benzofurans could be synthesized in generally high yields via this stoichiometric approach. 

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. 

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). 

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 cyclisations and cycloadditions reported include the synthesis of benzofuranes from halophenols and alkynes,343 the generation of y-butyrolactams from chloroformamides,344 the intramolecular ring-closure to spirocyclic amides345 and the [3+2] cycloaddition of trimethylene methane precursors to a,p-unsaturated aldehydes,345 imines347 and activated alkenes (eq.33).348... 

In a reaction related to their indole synthesis (Scheme 19.55) [100], Larock et al. reported a convenient method for the preparation of benzofurans 252 using 2-halophenols 250 and internal alkynes 251 (Scheme 19.67) [121], The reaction tolerates various alkyne R /R substituents, such as butyl, ethoxycarbonyl, silyl, and hydroxymethyl groups. 

This domino Sonogashira-cyclization strategy can also be applied to the synthesis of benzofurans. The use of o-halophenols, as opposed to anilines, and terminal alkynes results in 2-substituted benzofurans. Many research groups have reported the use of such a strategy, which incorporates both palladium and/or copper catalysis [166], An illustrative example is shown in Scheme 24.55. Bates et al. demonstrated that the combination of o-iodophenols and arylacetylenes using copper catalyst 88 led to the desired benzofuran products such as 89 in excellent yields [169]. 

Scheme 69 Cul-catalyzed synthesis N-substituted dihydro-2//-l,4-benzoxazme-3-(4//)-ones from 2-halophenols and 2-chloroacetamides...

---