Protection Of phenol

See also E. Haslam, Protection of Phenols and Catechols, in Protective Groups in Organic Chemistry, J. F. W. McOmie, Ed., Plenum Press, New York and London, 1973. pp. 145-182. 

Protection of phenols. Zinc, previously activated by treatment with HC1, is an effective catalyst for deacylation of aryl acetates in methanol in high yield. Aliphatic acetates are not affected. 

The important methods for the protection of phenols are very similar to those used for the alcoholic hydroxyl group (Section 5.4.6, p. 550), namely (a) ether formation, and (b) ester formation. 

Protection of phenols.1 This highly O-selective reagent is preferred to benzyl chloride for preparation of benzyl ethers of phenols containing substituents prone to C-alkylation. Thus 2 is converted into the dibenzyl ether 3 in high yield using 1, whereas the yield of the ether is only 18% when benzyl chloride is used. 

Reversible sorption of phenolic acids by soils may provide some protection to phenolic acids from microbial degradation. In the absence of microbes, reversible sorption 35 days after addition of 0.5-3 mu mol/g of ferulic acid or p-coumaric acid was 8-14% in Cecil A(p) horizon and 31-38% in Cecil B-t horizon soil materials. The reversibly sorbed/solution ratios (r/s) for ferulic acid or p-coumaric acid ranged from 0.12 to 0.25 in A(p) and 0.65 to 0.85 in B-t horizon soil materials. When microbes were introduced, the r/s ratio for both the A(p) and B-t horizon soil materials increased over time up to 5 and 2, respectively, thereby indicating a more rapid utilization of solution phenolic acids over reversibly sorbed phenolic acids. The increase in r/s ratio and the overall microbial utilization of ferulic acid and/or p-coumaric acid were much more rapid in A(p) than in B-t horizon soil materials. Reversible sorption, however, provided protection of phenolic acids from microbial utilization for only very short periods of time. Differential soil fixation, microbial production of benzoic acids (e.g., vanillic acid and p-hydroxybenzoic acid) from cinnamic acids (e.g., ferulic acid and p-coumaric acid, respectively), and the subsequent differential utilization of cinnamic and benzoic acids by soil microbes indicated that these processes can substantially influence the magnitude and duration of the phytoxicity of individual phenolic acids (Blum, 1998). 

Protection of phenols by the foregoing methods is complicated by the rapid Friedel-Crafts rearrangement of the nascent rm-butyl ether. By using trifluoro-methanesulfonic add at -78 PC, the rate of /erf-butyl ether formation is fast and the Friedel-Crafts alkylation does not compete [Scheme 4.126].226 Similarly, attempts to deprotect phenol ferf-butyl ethers with trifluoroacetic acid or titanium tetrachloride may give complex mixtures, again as a result of Friedel-Crafts alkylation of the phenol but this side reaction can be suppressed by using a catalytic amount of trifluoromethanesulfonic acid in 2.2,2-trifluoroethanol as solvent at -5 DC. 

Miura and co-workers reported the protection of phenols by allyl alcohols in the presence of catalytic amounts of palladium(II) acetate and titanium(IV) isopropoxide. The reaction is remarkably general however, it fails in the case of 3,5-dimethoxyphenol because of the exclusive formation of a C-allylated product. 

Protection of phenols. Aryl isopropyl ethers are also obtained by reaction of phenols with 2-bromopropane in DMF. The protective group is cleaved by BCl, in C HjCIj at 0°, but it is stable to SnCl, or TiCl, under these conditions. It is recommended for protection of phenolic groups during formylation with ilichloromethyl methyl ether in the presence of SnCl,. 

Heipieper, H. J., Diefenbach, R., Keweloh, H. (1992). Conversion of cis unsaturated fatty acids to trans, a possible mechanism for the protection of phenol-degrading Pseudomonas putida P8 from substrate toxicity. Applied and Environmental Microbiology 58 1847-1852. 

Soluble resin 51, based on an acrylamide backbone, was also prepared by Berg-breiter, using an approach similar to that considered for 50. In this case the polymer is soluble in polar solvents. The presence of the azo dye (DFdye = 0.0002) is used to check that less than 0.1% of the resin remains in the solution after precipitation with hexanes. This catalyst was able to both catalyze efficiently the acetylation of 1-methylcyclohexanol to give 45 and afford BOC protection of phenols to prepare structures similar to 53 in DCM at room temperature (Scheme 10.11). These reactions required very low catalyst loadings (0.2-5 mol.%). No problems were found for the recycling of 51 [190]. 

Protection of phenols. Aryl methyllhiomethyl ethers can be obtained in 90 95% yield by reaction of sodium phenoxides with chloromethyl methyl sulfide in HMPT (20 , 16 hours). Deprotection is accomplished (90-95% yield) with HgCta in refluxing CHJCN-H2O (10 hours). 

Protection of phenolic OH. This reagent has been used in the synthesis of... 

Protection of phenolic hydroxyl groups. Rail et al. encountered difficulties In methoxymethylation of the phenol (1) by standard procedures (reaction with lodium ethoxide, ethanol, and chloromethyl methyl ether). They then found... 

POCI3 added during 15 min. to a stirred refluxing soln.of N-(4-hydroxy-3-methoxy-phenethyl) - 3 - (3,5 - dimethoxy - 4 - hydroxyphenyl)propionamide in acetonitrile, refluxing continued 1 hr., and the product isolated as the hydrodiloride -> 7-hydroxy-6-methoxy -l-(3,5- dimethoxy-4-hydroxyphenethyl)-3,4- dihydroisoquinoline hydro-diloride. Y 85%. - This ring closure can be efficiently performed without protection of phenolic hydroxyl groups. F. e. s. S. Teitel and A. Brossi, and F. Sdienker, J. Heterocyclic Chem. 5, 825 (1968) Helv. 51, 1965 (1968). 

A report has appeared on the protection of phenols as their methylthiomethyl (MTM) ethers, which can be formed from sodium phenoxides and chloromethyl... 

Miscellaneous. Protection of phenols as methylthiomethyl ethers and of amines as dithiasuccinoyl or -nitrophenylsulphenyl derivatives has been recom-... 

Hydrogen chloride Protection of phenol groups as tetrahydro-2-pyranyl ethers... 

Protection of phenol groups as methoxymethyl ethers Removal of the protective group... 

Protection of phenol groups as carbonic acid esters s. 18, 259... 

Without additional reagents Preferential protection of phenol groups as aryloxysilanes... 

As shown in Fig. 2.19, starting from o-cresol 2.2.16, with NBS ortho-bro-mination and then MOM protection of phenolic hydroxyl group, compound 2.2.17 was obtained in two steps with 55 % overall yield. Reacted in butyl lithium and then quenched with trimethyl borate, arylboronic acid ester was obtained. The boric acid ester was in situ hydrolyzed to boric acid compound 2.2.18 with diluted HCl to give 45 % yield. Compound 2.2.18 was reacted with lead (IV) acetate/ mercury (II) acetate to convert the boric acid into lead reagent 2.2.19. Without... 

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