Methoxyl groups determination

Methylated phenols very often form part of the molecule of natural products, in particular, of alkaloids. In the elucidation of their constitution the quantitative determination of the methoxyl groups is of great importance. This determination is carried out by the excellent method of Zeisel, in which the methyl group is removed as methyl iodide by the action of concentrated hydriodic acid. This method (directions, p. 80) should be practised with the anisole already prepared. 

Conversion to phenolates coupled with NMR analysis has been used in determining the relative locations of the hydroxyl and methoxyl groups in phenolic pavines (1,25). Moreover, changes in chemical shifts of neighboring aromatic protons when going from a CDCI3 solution to a DMSO solution had been useful in assigning the correct position of the phenol (25,112). 

Jansen and Lindberg162 have determined the effect on various aldosides of 10% sodium hydroxide at 170° the rate constants are given in Table XI. The aldofuranosides are much less stable in alkali than are the corresponding aldopyranosides, and the (rans-l, 2-anomers are less resistant than the ct s anomers. The lower stability of the Irons-glycosides has been attributed to the formation of a 1,2-anhydride, with elimination of the methoxyl group. 

Filippov, M.P. and Kuz minov, V.l. 1971. Photometric determination of methoxyl groups in pectic substances. J. Anal. Chem. USSR (Zhurnal Analiticheskoi Khimii). 26 143-146. 

In reversed-phase HPLC separation of polyphenolics on the basis of polarity, the elution order of polyphenolics may be predicted. The more-polar polyphenolics are generally eluted first under reversed-phase conditions. Glycosylation in flavonoids increases their polarity and therefore their mobility in the re-versed-phase system. The elution order of benzoic acids, hydroxycinnamic acids, and agly-cones of flavonoids can normally be determined on the basis of the number of polar hydroxyl groups and lipophilic methoxyl groups. For additional information about elution order for various classes of polyphenolics, see Background Information. 

One recent related study has been reported, tying together isomescaline and schizophrenia. Through the use of radioactive labelling, the extent of de-methylation (the metabolic removal of the methyl groups from the methoxyls) was determined in both schizophrenic patients and normal subjects. When there was a loading of the person with methionine (an amino acid that is the principal source of the body s methyl groups), the schizophrenics appeared to show a lesser amount of demethylation. 

Estimating the reactivity of various aromatic nuclei in lignin involves studies to determine the protodedeuteration rates of certain selectively deuterated model compounds. The combined effects of hydroxyl, methoxyl, and side-chain substituents are approximately additive in guaiacyl models while syringyl models show significant deviation from the predicted behavior. The reactivity of the position meta to methoxyl groups is higher while those of the ortho and para positions are lower than anticipated on the basis of combined substituent effects. 

Partial Rate Factors for Protodedeuteration in Perchloric Acid Solution. All lignin model compounds studied contained hydroxyl, methoxyl, and methyl groups as the only substituent groups. Table II summarizes what the authors believe are the most reliable partial rate factors for these substituents in perchloric acid solution. All partial rate factors are based on determinations in 57% perchloric acid solutions. The partial rate factors for ortho and para positions of methyl and methoxyl groups are based on later work by Suzuki (21). The partial rate factors for phenol were calculated from data on 2, 4, 6-trideuterophenol (6) using the value 9.1 X 10-5 hr.-1 for monodeuterobenzene by Suzuki (21) and assuming 1 3.2 ortho to para ratio. 

In order to determine the applicability of the additivity principle for polysubstituted models, the rate data in Table III have been expressed in terms of partial rate factors of individual substituent groups in Table IV. The partial rate factors for polysubstituted compounds are calculated on the same basis as those of monosubstituted ones. For instance, the partial rate factors in guaiacol refer to the factors by which the rate constants of phenol are modified in positions 3, 4, 5, and 6 by introducing a methoxyl group in position 2. Likewise, the partial rate factors for methoxyl in 4-hydroxy-3,5-dimethoxytoluene indicate how the protodedeuteration rates of 4-hydroxy-3-methoxytoluene at positions 2 and 6 are modified by inserting a methoxyl group at position 5. 

The stereochemistry at C-3 in the 1,6-diene series can be determined from the value of J23. In all cases this value is small, about 2 Hz, suggesting that the proton at C-3 is quasi-axial and hence that the methoxyl group is equatorial. This assignment is supported by the observation of diaxial couplings (/3ax 4ax w 10 Hz) between protons at C-3 and C-4 (19-21, 55, 56). 

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