It has been previously observed that ethyl 2-bromo-4, 5-dimethoxyphenylacetate was produced by the reaction between 2-bromo-4, 5-dimethoxyphenylacetic acid hydrazide and either chloral or bromal in ethanol. Accordingly, the reactions between benzoic, phenylacetic, hydrocinnamic acid hydrazide and either chloral or bromal in various alcohols were attempted and respective esters have been obtained. Hydrogen cyanide, carbon dioxide and ammonium chloride were produced in the dehydrazination reaction. The condensation products, prepared by reacting benzoic and phenylacetic acid hydrazide with chloral were refluxed in ethanol, giving respective ethyl ester. Therefore, this reaction was considered that the intermediates produced by the condensation between acid hydrazide and either chloral or bromal were formed and in the alcoholysis, the -CO-N< bond will be cut off by the electron attractivity of either trichloro- or tribromo-ethylidene radicals.

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According to the Chart 1, various carboxylic acids have been prepared, in order to examine an influence of the substituting radicals upon the decarboxylation of 2-oxazolecarboxylic acids (Table I, II and III). The temperature of the decarboxylation of these carboxylic acids was measured with a silica spring thermo-balance on its loss of weight by heating every 1° per minute and the calculation was made with the linear portion of the curves obtained from the temperature and the loss of weight (Fig. 1). The temperature of the decarboxylation observed becomes higher in the following order. NO₂<H<CH₃O<HO<NH₂ with p-substituted phenyl compounds, NO₂<H<NH₂ with p-substituted biphenyl compounds and except a few cases, it is found to be in accordance with the order from electron-acceptor to electron-donor. Moreover, from the residues after the temperature measurements of the decarboxylation of carboxylic acids, oxazoles have been obtained in a rich yield (Table IV).

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In the measurement of the velocity of the decarboxylation of 5-(p-substituted phenyl)-2-oxazolecarboxylic acids, an influence by the solvents and the substituting radicals have been examined.
In the case of solid, it did not show the first order reaction and the velocity became greater as the time elapsed. In the hydrated solvent of ethanol, they showed the first order reaction and the velocity became greater as the content of ethanol increased. By an addition of hydrochloric acid, it became a little greater but the decarboxylation was hardly taken place, when pyridine was added. Either in quinoline or in dichloroacetic acid as a non-aqueous solvent, they showed the first order reaction and the velocity in quinoline was much faster than in dichloroacetic acid. Therefore, the Hammett law has been established among H, CH₃S, CH₃O and NH₂ radicals in quinoline and among Cl, H, CH₃S, C₆H₅, CH₃O and OH radicals in dichloroacetic acid. The reaction mechanism was also investigated.

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Zephyranthine reacts with periodate faster than dihydrolycorine (XI), and gives an isopropylidene derivative, C₁₉H₂₃O₄N, m.p. 156-157° (decomp.). Therefore, it seems that the two hydroxyl groups in this alkaloid are vicinal and cis each other. Diacetylzephyranthine was oxidized with permanganate to give a lactam diacetate C₂₀H₂₁O₇N, m.p. 252-253° (decomp.), whose infrared spectrum in chloroform showed a peak at 1639cm^-1, characteristics of a six-membered lactam ring. The lactam, C₁₆H₁₇O₅N, m.p. 268-270° (decomp.) which was obtained by alkaline hydrolysis of the lactam diacetate, gave a dialdehyde on periodate oxidation. The dialdehyde, C₁₆H₁₃O₅N, m.p. 210-211° (decomp.); [α]_D²³ +83.52° (c=0.54, CHCl₃), was shown to be identical by the mixed melting point and infrared spectral comparison with the authentic dialdehyde (VIII) prepared from lycorine. Since this dialdehyde has the same direction and value in the optical rotation as those of the dialdehyde from lycorine whose absolute configuration had been established, the hydrogen at 3a-position should be in an α-configuration.
These results indicate that zephyranthine (III) is an alkaloid with a lycorane skeleton, and its two hydroxyl groups are situated at C-1 and C-2.
A treatment of zephyranthine monotosylate (XVIII), C₂₃H₂₅O₆NS, m.p. 178-179° (decomp.) with lithium alminum hydride gave monodeoxy derivative (XIX), m.p. 169-170°, [α]_D²⁵ -100.00° (c=0.96, CHCl₃), which was characterized as its hydrochloride, C₁₆H₁₉O₃N⋅HCl, m.p. 264-265° (decomp.). This monodeoxy derivative was identical with the known α-dihydrocaranine. Based on this finding and the fact that the two hydroxyl groups in zephyranthine are cis, zephyranthine can be formulated as XVII which has been proved to be identical with α-dihydro-2-epilycorine (XXIV), derived from lycorine.

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Based on degradative and synthetic investigations, the structure of nerinine isolated from Zephyranthes candida HERB. has been shown to be represented by the formula (XXV).
It was verified that nerinine is related to albomaculine and in the same manner lycorenine is also related to homolycorine. Accordingly, structure (XXVI) was assigned to albomaculine.

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By the direct reaction of alkylamine, D-glucuronolactone (I) afforded N-alkyl-1-alkylamino-1-deoxy-D-glucuronamide (II) and N-alkyl-D-glucuronamide (III), and the structures of both (II) and (III) have been determined to be a pyranose type. To presume its reaction mechanisms, 1-p-nitroanilino-1-deoxy-D-glucuronolactone and alkylamine were reacted and N-alkyl-1-p-nitroanilino-1-deoxy-D-glucofuranuronamide (XII), α- and β- anomer (XIV, XIII) of N-alkyl-1-p-nitroanilino-1-deoxy-D-glucopyranuronamide were prepared. These facts suggested the reaction mechanism of producing II or III from I.

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Synthesis of D-glucuronic acid by the reaction between either D-glucurono-3, 6-lactone (I-III) or -6, 1-lactone (XXV) and arylamine was investigated. Glucuronic acylchoride (XX) gave also an expecting compound of D-glucuronic acid arylamide (XXI-XXIII).

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When D-glucuronolactone (I) was reacted with ammonia, depending on the reaction condition, various products such as 1-amino-1-deoxy-D-glucuronamide (II), 1-(glucuronylamino)-1-deoxy-D-glucuronic acid (IV), D-glucuronamide (III) and NH₄-D-glucuronate (VI) have been afforded and every structure of the products was determined to be in a pyranose structure.

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On treating with phosphoryl chloride, acyl derivatives of 6-aminoisosafrole gave quino lines. A new synthesis of quinoline derivatives has been described.

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When organic reagents with chelating functional groups was analysed by thin-layer chromatography, a better result can not be obtained because of the tailing. The investigation revealed that traces of metallic elements coexisted in adsorbents chelated with the reagents. In order to prevent this inconvenience, EDTA⋅2Na which is more than an amount consumed by the water-insoluble components of the adsorbent (Kieselgel G.) was added in advance to the chromato-plate for the better chromatography.

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Potassium 1, 2-naphthoquinone-4-sulfonate gives a coloration of the absorption maximum at 490mμ with sulpyrine and the chromogen produced can be extracted with chloroform, which shows an absorption maximum at 474mμ. Interferences caused by coexisting substances were investigated and the presence of reducing substances like ascorbic acid was found to exert no influence by using 0.5% potassium 1, 2-naphthoquinone-4-sulfonate solution under adequate conditions. The interferences by the presence of aliphatic primary amines like amino acid may be eliminated by chloroform extraction. Based on these facts, method of determination of sulpyrine with a high selectivity has been established.

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Colorimetric determination of aminopyrine in mixed anti-cold pharmaceutical preparations was studied, and a highly selective and precise method has been established. The mechanism of color development was found to be due to the oxidative condensation of 4-aminoantipyrine produced from aminopyrine by oxidative demethylation with phenol in a weak alkaline medium yielding an indophenol type pigment. Optimum conditions for color development were investigated thoroughly, and the different effects in various buffer solutions on the color development have also been studied. N-Methylaminoantipyrine produced by the dissociation of sulpyrine gave the same coloration as aminopyrine, but the interference of N-methylaminoantipyrine could be eliminated by its acetylation. Conditions of the acetylation were also discussed. The acetylation gave satisfactory result both in aqueous medium and in chloroform.

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Colorimetric determination of ethoxybenzamide in mixed anti-cold pharmaceutical preparations was studied, and a new method with high accuracy and selectivity has been established. Hofmann rearrangement was carried out for ethoxybenzamide to yield o-phenetidine, which gave orange red coloration by diazotizing with sodium nitrite, followed by diazo-coupling with β-naphthol. The coloration shows its absorption maximum at 510mμ. Optimal conditions for Hofmann rearrangement and diazo-coupling were investigated and it was found that Hofmann rearrangement had to be carried out under cooling in ice-water. At the ordinary temperature and above, the calibration curve of ethoxybenzamide does not go through the origin, probably because some amount of the o-phenetidine produced would be decomposed further.

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In connection with the water soluble papaverine related compounds, syntheses of 6 kinds of 1-dihydroxybenzyl-6, 7-dimethoxy-3, 4-dihydroisoquinoline derivatives (IIa-f) were attempted. In the case of 2, 3-, 2, 4-, 2, 5- and 2, 6-dihydroxybenzyl derivatives, a resinification in benzylation of [bis (benzyloxy) phenyl] acetic acid (VIa-d), starting materials of amide (VIIIa-d) were found to be remarkable, therefore, instead of the preparation of amide by the condensation of VIIa-d and homoveratrylamine, the amide, mentioned above and 7-, 6-, 5- and 4-hydroxybenzofuran-2-one (IXa-d) were condensed to amides (Xa-d), which were later benzoylated to VIIIa-d. These amides were dehydrated to ring closure into 4 kinds of 1-[bis (benzyloxy) benzyl] derivatives and a further debenzylation gave two kinds of the expected compounds IIIa-b. In the case of 3, 4- and 3, 5-dihydroxybenzyl derivatives, their amides (VIIIe-f) were prepared by the usual Schotten-Baumann method. However, the former compound produced 1-[3, 4-bis (benzyloxy) benzyl] isoquinoline derivative (IIe) and (IIIe). The latter did not give any expected compound of either IIf or IIIf.

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A new method of determining berberine together with palmatine as well as the other accessory alkaloids in Coptis japonica MAKINO by spectrophotometric measurements has been deviced, after the seperation by TLC.
0.05 gram of powdered Coptis japonica MAKINO was extracted with methanol, which was chromatographed on the Kieselgel plate with a developer of a solvent mixture of butanolacetic acid-water=7:1:2. From the chromatogram (Fig. 1), berberine portion was scratched out and extracted with methanol. The absorption was measured through the filter of 420-440mμ and the berberine content was determined according to the calibration curve (Fig. 2) previously prepared. This manipulation takes about 9-10 hours and the recovery rate was found to be more than 95% in average (Table II, III). Considering from the seperation of berberine from the other accessory alkaloids completely, it is considered to be superior to the other method. This data was also compared with that by ionexchange resin method.

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The alkali decomposition of thioxolone was reported previously and the decomposition reaction of 5-chlorothioxolone (I) and 5, 7-dichlorothioxolone (I′) in alkaline solution was examined. Both I and I′, similar to thioxolone, became unstable as it became alkaline and were decomposed to 4-chloro-2-mercaptoresorcinol (II) and 4, 6-dichloro-2-mercaptoresorcinol (II′) respectively. The thiol compounds were oxidized to 2, 2′-dithiobis[4-chlororesorcinol] (III) and 2, 2′-dithiobis [4, 6-dichlororesorcinol] (III′). These reaction becomes slow as chlorine radical was introduced. These disulfide derivatives showed its reduction wave in acidic media by polarography, being supposed to be n=2.

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2, 5-Dimethoxyaniline and α-acetyl-γ-butyrolactone were reacted to 2-[1-(2, 5-dimethoxyphenylimino) ethyl]-γ-butyrolactone (I), which was later treated with phosphorous oxychloride to give 2-methyl-3-(2-chloroethyl)-4-chloro-5, 8-dimethoxyquinoline (II). Treatment of (II) with either acetic acid or thiourea afforded the corresponding 4-methyl-6, 9-dimethoxy-2, 3-dihydrofuro [3, 2-c]-quinoline (III) and 4-methyl-6, 9-dimethoxy-2, 3-dihydrothieno [3, 2-c] quinoline (VI), respectively. (III) and (VI) were treated with 47% hydrobromic acid to give 4-methyl-2, 3-dihydrofuro [3, 2-c] quinoline-6, 9-diol hydrobromide (IV) and 4-methyl-2, 3-dihydrothieno [3, 2-c] quinoline-6, 9-diol hydrobromide (VI) which were converted to 4-methyl-2, 3-dihydrofuro [3, 2-c] quinoline-6, 9-dione (V) and 4-methyl-2, 3-dihydrothieno [3, 2-c] quinoline-6, 9-dione (VIII) respectively by the oxidation of potassium permanganate in sulfuric acid.

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11-Iodo-10-undecynoic acid was prepared by the reaction of both 10-undecynoic acid and iodine in the presence of sodium hydroxide and its salts, phenylesters, amide and anilides were also synthesized.

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An investigation of the alkaloidal constituents of the stems of Formosan Croton cumingii MUELL. et ARG. (Euphorbiaceae) was led to the isolation of the water soluble quaternary alkaloid magnoflorine (I). This is the first instance of the occurrence of the aporphine alkaloid in the quaternary type from the Euphorbiaceae family.

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