Starting from 7-hydroxy-coumarins and flavones the chloracetoxy compounds have been prepared and these have been converted into coumarino-7∶8-furanones and flavono-7∶8-furanones by means of the Fries reaction. Their properties have been studied and their benzylidine and acetyl derivatives obtained.

The lanthanum nitrate test for the acetate ion has been examined for use in the routine analysis of mixtures of inorganic substances including the acetate, oxalate and tartrate radicles. A distillation method for the preparation of the test solution and a modification of this procedure in the presence of sulphites and thiosulphates are described. The results obtained are quite satisfactory and the test is recommended for general use.

4-O-methyl ether of resorcylic aldehyde has been condensed with (I) acetophenone, (II) ω: 4-dihydroxy acetophenone, (III) ω∶3∶4-triacetoxy-and (IV) ω∶3∶4∶5 tetra-acetoxy-acetophenone to form pyrilium salts. Their properties and reactions are described. The first compound which has no hydroxyl groups in it undergoes change into the corresponding chalkone when its solution is treated with sodium acetate or when largely diluted with water. The reverse reaction takes place also rapidly in acid solution. The other compounds resemble closely pelargonidin, cyanidin and delphinidin though they exhibit a comparatively marked poverty of colour in solutions.

Addition of boric acid to O-hydroxy-carbonyl compounds dissolved in concentrated sulphuric acid, except in a few cases, brings about either a marked intensification or a change in colour of the fluorescence exhibited by them in daylight or under the lamp. In a few other cases fluorescence appears for the first time on the addition of boric acid. Since even the simpler O-hydroxy-carbonyl compounds yield these results with boric acid, it appears reasonable to conclude that this reaction will serve as a suitable method for the detection of O-hydroxy-carbonyl group. It must, however, be borne in mind that while the appearance of fluorescence, its intensification or a change in colour indicates the presence of a hydroxyl group ortho to the carbonyl, the non-appearance of the fluorescence effects described does not indicate the absence of this group.

Further work along these lines is in progress.

Flavylium salts containing γ- and α-pyrone rings have been prepared by condensing 7-hydroxy-3-methoxy-flavone-8-aldehyde and umbelliferone-8-aldehyde with hydroxy-aceto-phenones or their acetyl derivatives. They are found to have very feeble tinctorial properties and their fluorescence in concentrated sulphuric acid is not marked. The salts readily lose halogen and undergo conversion into colour bases.

A new fluorescence reaction for the detection of boric acid with resacetophenone and phosphoric acid has been described. None of the metallic radicles examined interferes while among the acid radicles chromate, bromate, chlorate, nitrite and fluoride do so to a limited extent. The reaction compares favourably with those described in the literature both as regards limit of identification and also interference. It has been shown that the test is applicable for the detection of micro-quantities of boric acid.

Addition of boric acid to aromatic compounds (C, H, and O only) of various types containing the, dissolved in concentrated sulphuric acid generally produces a marked intensification or a change in colour of the fluorescence exhibited by them in daylight or under the lamp In several cases the solution of the compound in sulphuric acid is itself non-fluorescent and fluorescence appears on adding boric acid

Further work is in progress.

Starting from γ-resorcylic aldehyde some typical 5-hydroxy and methoxy flavylium salts have been prepared and studied. They exhibit negligible fluorescence even in concentrated sulphuric acid. The structural factors that affect fluorescence in flavylium salts are discussed and comparison effected with coumarins.

Methyl ethers of 5∶6-dihydroxy-chalkones and flavanones have been prepared. 2∶5-Dihydroxy-6-methoxy acetophenone has been condensed with vanillin and 5∶6-dimethoxy-2-hydroxy-acetophenone with veratric aldehyde and anisaldehyde; the resulting chalkones have been converted into the flavanones. In the above reactions mixtures of chalkones and flavanones result.

The preparation of 3 ∶ 5 ∶ 6 ∶ 3′ ∶ 4′-pentahydroxy-flavone by Kostanecki's method and its properties are described. Its methyl ether and acetate have been prepared and characterised. These differ from patuletin and its derivatives.

The synthesis and properties of 6 ∶ 7 ∶ 3′ ∶ 4′-tetrahydroxy-flavonol and of its derivatives are described. ω ∶ 4-Dimethoxy-2-hydroxy-acetophenone is oxidised with persulphate in alkaline medium to yield ω ∶ 4-dimethoxy-2 ∶ 5-dihydroxy-acetophenone which is then condensed with veratric anhydride and sodium veratrate. The new flavonol and its methyl and acetyl derivatives differ from patuletin and its derivatives.

The methylation of patuletin has been reinvestigated. It forms two methyl ethers, one with five methoxyl groups and the other with six. Decomposition of the latter with alcoholic alkali yields quercetagetol-tetra-methyl ether and veratric acid. Demethylation of patuletin produces quercetagetin. Patuletin is shown to be a mono-methyl ether of quercetagetin; from a study of its properties and reactions and from a comparison with related compounds, the methoxyl is tentatively considered to be in the 6-position.

Starting from ε-methoxy-resacetophenone and adopting the procedure described in Part 1, 6:7-dihydroxy flavonols with 0,1 and 3 hydroxyls in the side-phenyl nucleus have been prepared. The characteristic properties of the group with reference to the hydroxy-compounds and their partial and complete methyl ethers are described. An alternative method starting with hydroxy-quinol has also been investigated and the simplest member of the group prepared by this method also.

A new and convenient synthesis of the flavonols of the quercetagetin series is described. ω: 4∶6-Trimethoxy-phloro-acetophenone has been prepared by two independent methods. By persulphate oxidation it is converted into the 2∶5-dihydroxy compound. Allan-Robinson condensation employing this ketone yields products containing a hydroxyl group in the 6-position. Subsequent demethylation and methylation yields the flavonols and their fully methylated ethers. Besides quercetagetin and tangeretin which occur in nature, 6-hydroxy galangin and 6-hydroxy myricetin which have not yet been discovered in natural products, have also been synthesised.

The synthesis of 3∶5∶ 6∶3′∶ 4′-pentahydroxy-flavone was already reported. The lower members of this group of 5∶ 6-hydroxy flavonols with one and no hydroxyl group in the side-phenyl nucleus have now been prepared by Kostanecki’s method. The characteristic properties are described.

The constitution of patuletin as 6-O-methyl quercetagetin has been finally established by the study of its penta-ethyl ether which yieldsO-diethyl-protocatechuic acid and ω∶4∶6-triethoxy-5-methoxy-2-hydroxy-acetophenone on degradation with alkali. The above ketone andO-pentaethylpatuletin have been synthesised by unambiguous methods starting from ω-ethoxy-phloroacetophenone.

A method of complete synthesis of 5∶6∶7∶8-hydroxy flavonols is described. It starts from ω∶3∶6-trimethoxy-2∶4-dihydroxy-acetophenone which is subjected to partial methylation (of the 4-hydroxyl group) and subsequently to persulphate oxidation. The product, 2∶5-dihydroxy-ω∶3∶4∶6-tetramethoxy-acetophenone is condensed with the anhydride and sodium salt of anisic acid and also of benzoic acid. The resulting 6-hydroxy-flavones yield on further methylation the fully methylated ethers of calycopteretin and 6∶8-dihydroxy-galangin and on demethylation, the free hydroxy-flavonols.

The simpler chromones having no side phenyl ring have poor toxic properties and resemble the simpler coumarins. Hydroxy isoflavones are more toxic than the corresponding flavones and the methoxy derivatives less toxic. In this there is resemblance to the hydroxy- and methoxy-phenyl coumarins. Among allyl-derivatives of chromones, flavones and isoflavones, ethers have high toxicity.

The possibility of orthor nuclear oxidation in the flavone series has been tested using 7-hydroxy-flavone and 3-methoxy-7-hydroxyl-flavone. By means of alkaline persulphate 7: 8-dihydroxy-flavone (10% yield) and 3-methoxy-7: 8-dihydroxy-flavone (20% yield) could be obtained. This seems to offer an easier method of preparing the flavonol, 3: 7: 8-trihydroxy flavone. The intermediate stage of the sulphate could be isolated pure from 7-hydroxyflavone.

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.

The synthesis and identity of karanjin-α-carboxylic acid reported earlier is now confirmed and karanjin obtained from it thus completing the synthesis of this flavono-furan by the process of building up a furan structure on a flavone system.

Two methods of synthesising isoflavonofurans of the angular type are examined. Starting from karanjic acid (VI) and passing through the intermediate (X), 2-methyl-isoflavono-7:8-furan (XI) is easily obtained. The alternative method which starts with 2-methyl-7-hydroxy-isoflavone (XII) and builds up the furan ring through the 8-aldehyde (XIII) is beset with difficulties. However if instead of the aldehyde, the corresponding ketone (8-acetyl derivative XVII) is employed the difficulties are eliminated and good yield of 2:β-dimethyl-isoflavono-7:8-furan (XIX) is secured.

Our thanks are due to the Imperial Chemical Industries, Ltd., and the National Institute of Sciences of India for the award of a Fellowship to one of us (L. R. R.).

Using methods of nuclear oxidation 7:8-dihydroxy-2-methyl isoflavone, 5:7:8-trihydroxyisoflavone and 5:7:8-trihydroxy-2-methyl isoflavone and their derivatives have been prepared. Demethylation of the 5:7:8-trimethoxy isoflavones with or without a 2-methyl group does not produce isomeric change in the trihydroxy product. It could therefore be concluded that a phenyl group in the 3-position prevents this isomeric change just like a methoxyl (hydroxyl) in the same position and that substitution in the 2-position has no influence.

Rutin was isolated in an yield of 4.6% from the flowers ofBauhinia tomentosa Linn. They contained quercetin also in small quantities.