Phenols methoxylation

One step in the synthesis of morphine by Gates and Tschudi involved elimination of a keto group from an intermediate having two phenolic methoxyl groups, and under usual Huang-Minlon conditions extensive demethylation occurred. A high yield was achieved by operating at 150-155° for 1 hr. 

The Martin modification is generally applicable but may require slight adjustment. Thus if the ketone is very sparingly soluble in water, addition of a small amount of acetic acid may be required (3-5 ml. per 50 g. of ketone). A substance containing phenolic methoxyl groups may suffer some demethylation, and remethylation may be required. 

Hawthorne, S. B., Miller, D. J., Langenfeld, J. J., and Krieger, M. S. (1992) PMi0 high volume collection and quantification of semi- and nonvolatile phenols, methoxylated phenols, alkanes, and polycyclic aromatic hydrocarbons from winter urban air and their relationship to wood... 

Electrochemically active compounds are typically aromatic and contain hydroxyl (phenols), methoxyl or amine moieties. Some aliphatic compounds, notably thiols... 

Renfrew et al. [597] carried out the alkylation of 2-ethoxycarbonyl-4-methoxylcyclohexanone (522) with o-methoxyphenethyl bromide (523) with subsequent decarboxylation and Grignardization, leading to the tertiary alcohol (524). Without being isolated, the latter was dehydrated and cy-clized to a mixture of isomers of the tricyclic dimethoxy derivative (525) [597]. A study of the stereochemistry of this type of cyclization has shown that in all cases the cis-A/B isomers predominate in the mixture of products [598, 599]. Selective hydrolysis of the phenolic methoxyl led to the free phenols (529) [597]. Separation of the epimeric mixture (529) gave three isomers, from which the cis-ketone (532) and the trans-ketone (533) were obtained in four stages [600, 601], Their configurations were shown by independent synthesis from the ketone (535) obtained by the scheme BC -- A [602], Chapter HI, Scheme 57. 

A simple synthesis of tetrahydroxyben2oquinone by methoxylation—hydrolysis of chloranil has been reported (265). Similarly, tetraar5ioxyben2oquinones have been prepared from chloranil and alkali salts of phenols (266). 

Corypalline, CnHijOjN (Corydalis spp. Nos. 9, 22 list, p. 170). This phenolic base, m.p. 168°, picrate, m.p. 178°, contains one methoxyl group and on methylation yields 2-methyl-6 7-dimethoxytetrahydrof5oquinoline, Ci2Hi,02N, m.p. 82°, and on ethylation, 2-methyl-6-methoxy-7-ethoxy-tetrahydrofsoquinoline, m.p. 65°, whence the free hydroxyl appears to be at C and this has been confirmed by the synthesis of corypalline by a method analogous with that used by Spath, Orekhov and Kuffner. Corypalline is therefore hydrohydrastinine (XII) with the methylenedioxy group replaced by MeO at C and. OH at C (Manske). ... 

The three alkaloids concerned, morphine, codeine and thebaine, all behave as tertiary bases. Morphine contains two hydroxyl groups of which one is phenolic and the other a secondary alcohol group. On methylation of the phenolic hydroxyl codeine results. On oxidation, codeine is transformed into codeinone by conversion of the secondary alcohol group into a carbonyl group, and when thebaine is boiled with A-sulphuric acid for a few minutes, it is hydrolysed into codeinone and methyl sulphate, and in other ways thebaine has been shown to contain two methoxyl groups. That the relationship between the three alkaloids is close may be illustrated by the following slightly extended formula —... 

Floripavidine, CjjHjgOjN. This occurs in the crude mixture of non-phenolic bases, and is separated from fioribundine by repeated crystallisation of the mixed hydrochlorides from water. The base crystallises from alcohol in prisms, has m.p. 241-2°, and [a]n — 156-25° (MeOH) the hydrochloride, m.p. 209-10°, hydriodide, and methiodide, m.p. 228-30°, were prepared. The alkaloid contains no hydroxyl group (Zerewitinoff), but a methoxyl, a dioxymethylene, and a methylimino group are present. 

EtOH), is insoluble in benzene or ether, and sparingly in chloroform, but dissolves readily in alkali, the solution darkening in air. The salts are crystalline but unstable. The base forms a crystalline metbiodide and contains two methoxyl and two phenolic hydroxyl groups. On methyla-tion it yields a mixture of corydine and fsocorydine. On exhaustive methylation corytuberine yields eventually trimethylamine and 3 4 5 6-tetramethoxy-8-vinylphenanthrene, m.p. 69°. 

Chrycentrine, CigHigOBN (item 34 list, p. 172), m.p. 216°, non-phenolic, contains a dioxymethylene, but no methoxyl groups. 

Oxyacanthine contains three methoxyl groups, and one phenolic hj droxyl group is indicated by the preparation of an 0-benzoyl derivative, a potassium derivative and a methyl ether (identical with trilobamine methyl ether, p. 357) yielding a hydroehloride,. 2HC1, m.p. 

Chondrofoline, CgjHgjOjNj, 2H2O, crystallises from methyl alcohol in triangular plates, m.p. about 135°, [ajffg — 280-6° (dry base N/10. HCl). It is a phenolic base, contains three methoxyl groups, does not give a Millon reaction, but in methyl alcoholic solution gives a faint, pink-purple colour with ferric chloride. The nitrate forms needles m.p. 225° (dec.). 

The base boiled in methyl alcoholic solution with methyl iodide and potassium hydroxide, forms a gelatinous methiodide, which was converted by silver chloride into the methochloride. The latter when boiled with 20 per cent, solution of sodium hydroxide, produced a mixture of methine bases, which were separated as the methiodides into 0-methylbebeerine-methine methiodide B, m.p. 237° (cf. p. 375), and a lasvorotatory form, m.p. 190°, which proved to be the lasvo-enantiomorph of d-O-methyl-bebeerinemethine methiodide (form C, p. 375). Chondrofoline therefore belongs to the bebeerine type represented by formula (III). In it R = H, the single phenolic hydroxyl is at ORj or OR4 and the remaining groups, OR2, OR 3, OR or alternatively ORj, OR2, OR 3 are methoxyl groups (King,i 1940). 

Galipoline, C19H19O3N. A process for the extraction and separation of the angostura bark alkaloids was described by Spath and Eberstaller,i and from the phenolic bases obtained Spath and Papaioanou isolated this alkaloid. It crystallises from water, has m.p. 193°, contains two methoxyl groups, and on methylation by diazomethane yields galipine. 

S. Henningsii (S. Africa). Two crystalline alkaloids (1) 23 28 5 2> m.p. 280-5-282°, [a]], ° — 80° (EtOH) contains one methoxyl, but no methylimino group and is possibly phenolic (2) 24 3305 2> m.p. 214-5-215°, contains two methoxyl groups and gives a violet coloration with Frohde s reagent. The alkaloids are possibly mono-and di-methoxy derivatives of the same parent base. Amorphous alkaloids are also present and possibly a third crystalline base (Rindl, S, Afr. J. Sci., 1929, 26, 50 Trans. Boy. Soc. S, Africa, 1931, 20, 59 (with Sapiro), ibid., 1936, 23, 361). 

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