In continuation of Part VIII, members of the 3-methoxy-7-hydroxyflavone series with one, two and three methoxyl groups in the side phenyl nucleus are subjected to ortho-oxidation with alkaline persulphate; the yield of the corresponding 7∶8-hydroxy compounds is 10 to 15%. On the other hand, attempts at ortho-oxidation by this method in the side phenyl nucleus have failed just as in several cases of simpler benzene derivatives. It is suggested that ortho-oxidation in nature should be considered to take place in multiple stages and this has been verified using a convenient example in the flavone series. 3-Methoxy-7-hydroxy-flavone undergoes change into the corresponding 8-aldehyde by the action of hexamine and this is converted into 3-methoxy-7∶8-dihydroxy flavone by means of alkaline hydrogen peroxide, the yields being very good.

The experiments described in this paper show that a pure sample of oroxylin-A melts at 219–20° (acetate, 139–40°), that the substance melting at 231–32° is a mixture of it with chrysin and that this mixture could be separated by fractionation of the acetates. The constitution of oroxylin-A as the 6-methyl ether of baicalein is confirmed by ethylating it to the diethyl ether and showing that the product is identical with a synthetic sample of 6-methoxy-5 ∶ 7-diethoxy flavone. The details of the synthesis are given.

The use of ethylation in the study of naturally occurring glycosides and partial methyl ethers of hydroxy flavones is discussed. This procedure renders the work simpler and more definite. Starting from ω-ethoxy res-and phloracetophenones, the preparation of mixed ethyl methyl ethers of the flavonols, fisetin, kæmpferol, and quercetin, with an ethoxyl in the 3-position and methoxyls in the other positions, is described and it is shown that these compounds are useful in the study of the 3-glycosides of these flavonols. The case of rutin has been used as a typical example.

As an illustration of the synthesis of fully ethylated compounds fisetin tetraethyl ether is made and as an example for the use of ethylation in the study of both 7-glycosides and 7-methyl ethers, O-3∶3′∶4′-triethyl-7-methyl-fisetin is synthesised.

The use of ethylation for establishing interrelationship between glycosides and partial methyl ethers of hydroxy flavones is illustrated with the case of quercimeritrin and rhamnetin. Quercimeritrin has been ethylated with diethyl sulphate and the ethylated glucoside hydrolysed and methylated. The product is a mixed ether of quercetin and is shown to be identical with O-tetraethyl rhamnetin.

The trimethyl ether of fisetin with a free hydroxyl group in 4′-position yields the 5′-aldehyde readily by the action of hexamine. Subsequent oxidation with hydrogen peroxide gives rise to good yields of robinetin trimethyl ether. Its methylenation leads to the synthesis of kanugin and demethylation to the formation of robinetin. This constitutes another example of the two stage ortho-oxidation of the side phenyl nucleus of the flavonols.

Employing the two stage process of ortho-oxidation eugenol is converted into 5-hydroxy eugenol. Methylation of this yield elemicin and methylenation myristicin. This constitutes the most convenient synthesis of these naturally occurring compounds and is highly significant from the point of view of biogenesis.

3-Methyl-gallic and myristicic acids have been synthesised by new methods. For this purpose vanillic acid is converted into its 5-aldehyde and oxidised with alkaline hydrogen peroxide to yield 3-methyl-gallic acid. Esterification, methylenation and hydrolysis give rise to a good yield of myristicic acid.

Based on considerations of biogenesis asarone is now synthesised from isochavibetol by para nuclear oxidation with alkaline persulphate and subsequent methylation. Isochavibetol needed for this purpose is conveniently prepared by the condensation isovanillin with propionic anhydride and sodium propionate.

It is suggested that umbelliferone is a fundamental compound in the biogenesis of coumarins and that other important hydroxycoumarins involve further stages of oxidation. In support of this idea experiments are described for the preparation from umbelliferone of æsculetin byp-oxidation and daphnetin byortho-oxidation. From either of these dihydroxycoumarins, 6:7:8-trihydroxycoumarin can be prepared. Limettin would, however, appear to have a different origin. The possible evolution of fraxinol from limettin byp-oxidation is supported by persulphate oxidation experiments using 4-methyl limettin. 4-Methyl fraxinol has also been synthesised from 2:6-dimethoxyquinol and acetoacetic ester.

The methyl ethers of morin, resomorin and resodatiscetin have been made by different methods in order to examine the possible resistance of the 2′-hydroxyl group to methylation. No such resistance is found. 8-Hydroxy derivatives of morin, datiscetin and resodatiscetin have been prepared by employing methods of nuclear oxidation.