Hydroxy amines from phenols

NaH-dispersion added carefully to a soln. of 2-(benzo[b]thien-4-yloxy)-2-methyl-propanamide in dry hexamethylphosphoramide, and heated 1 hr. on a steam bath N-benzo[b]thien-4-yl-2-hydroxy-2-methylpropanamide. Y 72%. - This is a stage of a 4-step sequence for the prepn. of ar. amines from phenols. F. e. s. R. Bayles et al., Synthesis 1977, 33, 31. 

Phenols.—The ring hydroxyl compounds take the class name of phenols from the simplest member, hydroxy benzene or phenol. These are true aromatic compounds and in methods of formation, reactions and properties are distinctly different from aliphatic hydroxyl compounds or alcohols. Their outstanding distinction is their marked acid character, the alcohols being neutral (p. 103). This is attributed to the influence of the phenyl radical (CeHs—). The same influence is present in the amino derivatives, for the ring amines, CeHs— NH2, /CH3... 

Via intermediates Phenols from hydrocarbons via amines s. 1,192 a-Hydroxy ketones from ketones via a-isonitrosoketones s. 2,145 a-Hydroxycarboxylic acids from carboxylic acids via a-halogenocarboxylic acids s. 1,451 v.l. H —OH... 

Robinson (115) took a different view in proposing a derivation of the corresponding phenolic aldehyde and amine from a-hydroxy- 8-ketobutyral-dehyde and acetone. 

Dinitrofluorobenzene (DNFB) or Sangers Reagent has also been used for similar applications such as the analysis of amino acids and amines (32). Tt reacts with both primary and secondary amines and phenols but not with aliphatic alcohols consequently it is useful for determining phenols in the presence of aliphatic hydroxy compounds. The sensitivity realized from this reagent is similar to that obtained from the dinitrobenzoyl derivatives. 

Examination of the history of antioxidants such as hindered phenols and amines shows a move from low-MW products to higher-MW products. Specifically, polymer industries have abandoned the use of, e.g., butylated hydroxy toluene (BHT) in favor of tetrakismethylene (3,5-di-f-butyl-4-hydroxydrocinnamate)methane (see Figure 15.9). Likewise, polymeric HALS, like poly-methylpropyl-3-oxy-(4(2,2,6,6-tetramethyl)piperidinyl) siloxane, replaced the low-MW hindered amine Lowilite 77 (see Figure 15.10). The next obvious step was to produce a new class of stabilizers. 

The first asymmetric synthesis of (-l-)-abresoline was achieved from the chiral piperidine derivative 153, which upon treatment of its hydroxy side-chain substituent with carbon tetrabromide, triphenylphosphine, and triethyl-amine cyclized to the frarcr-quinazolidine 154. Deketalization and silyl protection of the phenolic group, followed by stereoselective reduction with lithium tri-t -butylborohydride (L-Selectride ), gave an alcohol, which after acylation and deprotection furnished (-l-)-abresoline 155 (Scheme 25) <2005TL2669>. 

Tyramine (4-hydroxy-phenethylamine, para-tyramine, / -tyramine) A phenolic amine CgHnNO, a monoamine compound derived from the amino acid tyrosine. 

Other alkylation reactions are observed in the condensation of cyclo-propanium ions (generated in situ) with ketones 89.92)> enamines6, nitroalkanes 93>, dimethylmalonate 92>, and phenol. 92> Thus, 7-hydroxy-7-pyrrolidinobicyclo[4.1.0]heptane (56) as well as the 7,7-dipyrrolidino derivative (54) react with acetone to give the amino ketone 113. 89> This reaction may be pictured as an addition of the enol form of the ketone to the reactive iminium salt formed from the carbinol amine. In like manner, phenol undergoes ortho substitution with the carbinol amine 114 formed from cyclopropanone and dimethyl amine. 

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