Methylphenols synthesis

Amino-4-methylphenol, synthesis of spirobis[l,3,2-benzoxaza-phosphole], 163... 

The literature on basic- and acid-catalyzed alkylation of phenol and of its derivatives is wide [1,2], since this class of reactions finds industrial application for the synthesis of several intermediates 2-methylphenol as a monomer for the synthesis of epoxy cresol novolac resin 2,5-dimethylphenol as an intermediate for the synthesis of antiseptics, dyes and antioxidants 2,6-dimethylphenol used for the manufacture of polyphenylenoxide resins, and 2,3,6-trimethylphenol as a starting material for the synthesis of vitamin E. The nature of the products obtained in phenol methylation is affected by the surface characteristics of the catalyst, since catalysts having acid features address the electrophilic substitution in the ortho and para positions with respect to the hydroxy group (steric effects in confined environments may however affect the ortho/para-C-alkylation ratio), while with basic catalysts the ortho positions become the... 

Murakami et al. reported the total synthesis of 1-hydroxy-3-methylcarbazole (23) and murrayafoline A (7) by classical Fischer indolization of the O-methanesulfonyl phenylhydrazone derivative 614 (575). The compound 614 was prepared from the corresponding aminophenol 612 via 2-hydrazino-5-methylphenol p-toluenesulfonate... 

Chida et al. reported the first total synthesis of murrastifoline-A (186) starting from 2-amino-5-methylphenol (1062) (666,667). This synthesis involves a palladium(O)-catalyzed double N-arylation of the arylamine (1082) with 2,2 -dibromobiphenyl 1075 as a key step. 

Properties. Vanillin is a colorless crystalline solid mp 82-83 °C) with a typical vanilla odor. Because it possesses aldehyde and hydroxyl substituents, it undergoes many reactions. Additional reactions are possible due to the reactivity of the aromatic nucleus. Vanillyl alcohol and 2-methoxy-4-methylphenol are obtained by catalytic hydrogenation vanillic acid derivatives are formed after oxidation and protection of the phenolic hydroxyl group. Since vanillin is a phenol aldehyde, it is stable to autoxidation and does not undergo the Cannizzarro reaction. Numerous derivatives can be prepared by etherification or esterification of the hydroxyl group and by aldol condensation at the aldehyde group. Several of these derivatives are intermediates, for example, in the synthesis of pharmaceuticals. 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

SYNTHESIS To a solution of 9.5 g flaked KOH (10% excess) in 500 mL 95% EtOH there was added 20.4 g 4-methoxy-2-methylphenol (see under 2C-D for its preparation). This was followed with 23.5 gethyl iodide, and the mixture was held... 

Synthesis of Dinuclear and Tetranuclear Copper(ll) Complexes of 2,6-Diformyl-4-methylphenol-di(benzoylhydrazone) [256b]... 

In other cases substituents compete by directing to different positions. For example, in the synthesis of the food preservative BHT (p. 30) from 4-methylphenol (p-cresol) by a Friedel-Crafts alkylation, the methyl and OH groups each direct ortho to themselves. The -OH group is much more powerfully directing than the methyl group because it provides an extra pair of electrons, so it wins and directs the electrophile (a t-butyl cation) ortho to itself. The t-butyl cation can be made from the alkene or t-butanol with protic acid or from t-butyl chloride with AICI3. 

The cholesteric mesophase formed by cholesteryl p-nitrobenzoate at 200 °C has been used as the solvent to effect an asymmetric synthesis lrans-but-2-enyl p-tolyl ether gave the product of an ortho-Claisen rearrangement, 2-(but-1 -en-3 -yl)-4-methylphenol. This material exhibited circular dichroism, although neither the optical yield nor the configuration of the product is yet known.262 Decarboxylation of ethylphenylmalonic acid in cholesteryl benzoate at 160 °C (cholesteric liquid-crystalline phase) also proceeded with asymmetric induction to give (R)-(—)-2-phenylbutyric acid, with 18% optical yield.263 Electric dipole moments are reported for some esters of 5a-cholest-8(14)-en-3j8-ol there is some slight correlation with melting points.264... 

Costa Bizzarri, P., Della Casa, C., Ferruti, P., Ghedini, N., Pilati, F., and Scapini, G., Mannich bases in polymer synthesi.s, VI. Sulphur containing polymers by exchange reaction between 2,6-bis(dimethylamino-methyl)-4-methylphenol and dithiols. Polymer Commun., 25, 115, 1984. 

The reagent and sodium carbonate in 1,2-dichloroethane at 54° in the presence of 4,4 -thiobis(6-tert-bufyl-3-methylphenol) (4, 85-86) effect the Baeyer-Villiger oxidation of 1. This oxidation was unsuccessful with other peracids. The tricyclic compound (2) is an intermediate in Corey s total synthesis of gibberellic add. 

Dicyclopentadiene was used as another difunctional agent for the synthesis of an oligomeric AO from 4-methylphenol [120] (after tert-butylation, AO 99 was obtained) or diphenylamine [121]. Polymeric aromatic amines for application in rubber stabilization were obtained in the presence of acid catalysts from diphenylamine and l,4-bis(l-hydroxy-l-methylethyl)benzene or 1,4-diisopropylbenzene [122] or from iV,A -diphenyl-l,4-phenylenediamine and a,to-p-xylylenedi-chloride [123]. Polymerization of 2,2,4-trimethyl-1,2-dihydroquinoline in the presence of protic or Lewis adds [1] is very important commerdally. Oligomeric product 100 is an effective AO and AF agent for rubbers. 

Oxidative coupling was used for the synthesis of some stabilizers having properties of AO or FR. Products of oxidation of 4,4 -isopropylidenebis(2-methyl-6-tert-butylphenol with pota ium ferricyanide [151] or of 4,4 -thiobis(2-rcr/-butyl-5-methylphenol) with oxygen in the presence of copper salts [152] (118) were tested as AO. Thermostable fireproofing additives containing 1 to 4 bromine atoms on a phenolic moiety and designed for the stabilization of thermoplastics, e.g. 119, were prepared by oxidative coupling of brominated phenols [153]. 

An asymmetric reducing agent (49), prepared from LAH, (-)-)V-methylephedrine (14) and 3,5-di-methylphenol in a 1 1 2 ratio, reduces acetophenone with 83.8% A series of aromatic and alkynyl ketones are reduced by (49) to the corresponding (f )-alcohols (Scheme 1)P Some of the products are useful intermediates for the synthesis of 7-lactone insect pheromones. " ... 

Problem 23.15 Outline the synthesis from benzene or toluene of the following compounds w-nitrotoluene, m-iodotoluene, 3,5-dibromotoluene, 1,3,5-tribromo-benzene, the three toluic acids (CHJQH4COOH). the three methylphenols (cresols). 

Scheme 5.4.6 Linchpin strategy for the synthesis of -carotene and zeaxanthin (BHT 2,6-di-t.ert-butyl-4-methylphenol)...

IsoitaUcene, electrosynthesis of 1188, 1191 Isonitriles—see 4-Hydroxybenzoisonitrile o-lsophenol 298-300 2-lsopropyl-5-methylphenol, photorearrangement of 1048 Isoquinohnes—see Tetrahydroi soqui noU nes Isosilybin, synthesis of 1308, 1310 Isosteganadns, synthesis of 1300, 1302... 

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