Para-methyl phenol

We have seen that electron-withdrawing substituents increase the acidity of a compound (Sections 1.18 and 7.10). Therefore, when a substituent either withdraws electrons from or donates electrons into a benzene ring, the values of substituted phenols, benzoic acids, and protonated anilines will reflect this withdrawal or donation. For example, the of phenol in H2O at 25 °C is 9.95. The pK of para-m xo-phenol is lower (7.14) because the nitro substituent withdraws electrons from the ring, whereas the pK of para-methyl phenol is higher (10.19) because the methyl substituent donates electrons into the ring. 

The o-MBpl4 antioxidant is synthesized from para-methyl phenol and isobutylene as shown below. 

Also, para-methyl phenol is produced from aikyiation of phenoi see Figure 11.16. 

Tables XXVIII and XXIX, respectively. Excellent correlations were obtained for all three sets. The stereochemistry of the sy -methyl ketoximes is discussed by Charton and Charton (73). The values of pj obtained for the trans-heterovinylene sets are not in good agreement with each other. Two sets gave values of 54 and 55, respectively, and the third set gave a value of 35. The difference in pj values cannot be accounted for. A value of 54 to 55 for pj suggests the possibility of some exaltation between substituent and reaction site such as that which occurs in para-substituted phenols and anilines. To demonstrate this with certainty requires that the value of pj be determined for a set of imines bearing a reaction site on the nitrogen which will not interact strongly with substituents. No such set of data is extant in the literature at the present time.

Oxidation of hindered phenols bearing additionally a para methyl group leads to substituted stilbenequinones. These may be reduced in the presence of zinc and acid to the corresponding dihydroxystilbenes. 

In benzene derivatives, electron-donating substituents direct into the ortho-and para-positions, while in the case of the electron-withdrawing substituents considerable meta-addition is observed (Table 3.1) otherwise a more equal distribution is established [reactions (6)-(9) and Table 3.1]. In agreement with the pronounced regioselectivity, ipso-addition at a bulky substituent such as the chlorine substituent in chlorobenzene is disfavored. Evidence for this is the low HC1 yield in the case of chlorobenzene, the low yield of para adduct in 4-methyl-phenol (Table 3.1), or the decarboxylation in the case of benzoic acid [reactions (6) and (10)]. 

In their early studies, Pinhey et al. showed that, when the reaction of a phenol with an aryllead triacetate is performed in the presence of pyridine, only the C-arylated dienones 35 and 36 are formed in a nearly quantitative yield (90% ortho para ratio of 4 1) (Equation (38)). Under their classical conditions (phenol organolead triacetate base in a ratio 1 1 3), the reaction of methylated phenols only proceeded in high yield when both ortho-positions are substituted. There is a preference for attack ipso to a methoxyl group compared to a methyl group.45 453... 

The subtlety of the factors deciding the reaction path of a particular dienone is emphasized by some further observations. Cholesta-i,4-dien-3"One (i), which gave only the " para phenol (5) with sulphuric acid in acetic anhydride, afforded a mixture in which the i-methyl-phenol (2) was the major component when the reaction was carried out in aqueous acid [161,164] ... 

Upon treatment with HF-SbFj, para-substituted phenols (or their methyl ethers) can be diprotonated [66], first on the oxygen atom and then on the meta carbon [67]. The resulting dipositively charged species are exceedingly reactive towards a variety of arenes [67], 4-Arylcyclohexanones, the primary products of the reactions, can be further transformed to 3-arylcyclohexanones. The ratio of the two isomers depends on conditions such as the reaction time, amount of acid, and the nature of the substrates. For example, when p-cresol is reacted with benzene in the presence of HF-SbFs, 4-methyl-4-phenylcyclohexenone and 3-phenyl-4-methylcyclohexenone are obtained in yields of 29 and 33 %, respectively, after 90 s. By increasing the reaction time to 15 min, the yield of 3-phenyl-4-methylcyclohexenone is increased to 90 % whereas that of 4-methyl-4-phenylcyclohexenone decreased to 2-3 % (Eq. 27). 

The rearrangement occurs also when nitro benzene is electrolytically reduced by immersing the cathode in nitro benzene and sulphuric acid and the anode in sulphuric acid. Phenyl hydroxyl amine is first produced and by the above rearrangement is converted into para amino phenol. This rearrangement is analogous to the one occurring when phenyl methyl nitrosamine goes over to para-nitroso methyl aniline (P- S59)-... 

It was also of interest to gain insight into the source of the methyl substituents in the dechlorinated products. Several patents have described the ortho /para methylation of phenolic substrates by methanol over metal oxide catalysts at elevated temperature (6-8). An alternate source of the methyl groups in the products might be the SCCO2 mobile phase. Carbon dioxide can be reduced at iron surfaces in the presence of water to form short chain alkanes. Approximately 90% of the products consisted of methane (9). A possible probe mi t be to use a different solvent to dissolve the substrate PCP. Table 3 records... 

The para-protonated methylated phenols, when irradiated in their absorption band ( max 330 nm), were converted into the respective 2-hydroxybicyclo[3.1,0]hexenyl cations, for example ... 

Alternative Names/Abbreviations Ortho/meta/para-creso/s, cresylic acid, tricresol, methyl-phenol, hydroxytoluene... 

Hindered phenols, like 2,6-di-rert-butyl-p-cresol, which in an oxidizing environment and at high concentrations transforms to stilbenequinone. This species absorbs visible light, and therefore adds to discoloration. It has also been found that hindered phenols, containing ortho or para methyl groups react with natural rubber latex in the presraice of free radicals. This bound antioxidant is much more efficient than conventional antioxidant [123]. 

Some Amaryllidaceae plants possess a group of alkaloids containing a Cg— C2-N-C1-C6 unit. In this unit, the C6-C2-N moiety is derived from tyrosine or tyramine, and the C -Ci part is derived from phenylalanine through cinnamic acid, p-coumaric acid, and protocatechualdehyde [1]. Tyramine (C6-C2-N unit) and protocatechualdehyde (C -Ci unit) are then combined and methylated to form O-methylnorbelladine, which is a common biosynthetic precursor of various Amaryllidaceae alkaloids. Through para,ortho -, ortho,para - and para,paw-phenol coupling of norbel-ladine, the lycorine, galanthamine, and crinine type alkaloids are formed, respectively [2]. 

The introduction of substituents containii a-hydrogens into the para-position of phenol sharply changes the EPR spectra splitting on these protons appears. Thus, the radicals of 2,6-di-tert-butyl-4-methyl-phenol (ionol) (IV)... 

Cyclodextrins have had valuable industrial uses for a considerable time, particularly as agents to bind or release volatile molecules. Accurate predictions concerning the selectivity and stability of cyclodextrin-guest complexes are therefore of considerable interest both academically and practically." MD was used to simulate cyclodextrin hydrates" as a test of the applicability of the GROMOS program package to systems beyond proteins and nucleic acids. Other early MD simulations focused on interactions with guests such as enantiomers of methyl-2-chloropropionate. Comparisons between calculated thermodynamic properties for complexes formed by O -cyclodextrin with para-substituted phenols and the results of MM simulations led to improvements in force fields that described the interactions. MM2 simulations were used to support NMR data for the -cyclodextrin inclusion complex with benzoic acid. " The well-known catalytic effect of cyclodextrins has been modeled. For example, the relative rate increase of hydrolysis of S over R phenyl ester stereoisomers in the presence of -cyclodextrin... 

The para and ortho positions of phenols condense at the carbonyl group of acetone to make bisphenols, eg, bisphenol A, 4,4 -(l-methylethyhdene)bisphenol [80-05-07]). If the H atom is activated, CICH— compounds add to the carbonyl group in the presence of strong base chloroform gives chloretone (l,l,l-trichloro-2-methyl-2-propanol [57-15-8]). 

The shikimate pathway is the major route in the biosynthesis of ubiquinone, menaquinone, phyloquinone, plastoquinone, and various colored naphthoquinones. The early steps of this process are common with the steps involved in the biosynthesis of phenols, flavonoids, and aromatic amino acids. Shikimic acid is formed in several steps from precursors of carbohydrate metabolism. The key intermediate in quinone biosynthesis via the shikimate pathway is the chorismate. In the case of ubiquinones, the chorismate is converted to para-hydoxybenzoate and then, depending on the organism, the process continues with prenylation, decarboxylation, three hydroxy-lations, and three methylation steps. - ... 

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