Fatty oil was obtained in an 8.7-9.4% yield from the seeds of Nandina domestica Thunb. The fatty acids obtained were separated into saturated acids (32.3%), chiefly composed of palmitic and stearic acids, and unsaturated acids (67.7%), by Twitchell's method. The unsaturated acids were brominated and the presence of linolic and a small amount of oleic acids was established by oxidation with potassium permanganate. Linolenic acid was not found. Phytosterol was obtained in an 1.7% yield from the unsaponifiable fraction.
2-Mercapto-4-propenyl-5-aminothiazole was prepared by the condensation of dl-(α-amino-β-ethylidene)-propionitrile and carbon disulfide, and 2-mercapto-4-propenyl-5-benzylidene-aminothiazole, by the condensation of the above nitrile, carbon disulfide and benzaldehyde. Alkylmercapto- and benzylmercapto derivatives of these two thiazoles were also prepared.
p-Nitroacetophenone oxime was prepared by the application of sodium hydroxylamine disulfonate to p-nitroacetophenone. Corresponding p-tosyl ester was obtained by the reaction of p-tosyl chloride on the oxime under the presence of sodium alcoxide or hydroxide. The rearrangement of this ester, as described in the previous report, yielded p-nitro-α-aminoacetophenone hydrochloride which, upon reaction with dichloroacetyl chloride, gave p-nitro-α-dichloroacetaminoacetophenone. The addition of forma lin to the latter yielded p-nitro-α-dichloroacetamino-β-hydroxypropiophenone and its Pondorfreduction, dl-chloramphenicol.
1. Aldol condensation of p-nitrobenzaldehyde with benzaminoacetaldehyde or phenylacetylaminoacetaldehyde yielded α-benzamino- or α-phenylacetylamino-β-p-nitrophenyl-β-hydroxypropioaldehyde, whose Pondorf's reduction and subsequent hydrolysis yielded erythro-1-p-nitrophenyl-2-amino-1, 3-propanediol. 2. Reaction of aminoacetal and dichloroacetyl chloride yielded dichloroacetal whose hydrolysis gave dichloroacetaminoacetaldehyde.
α-Acylaminoacetophenone was synthesized from acetophenoxime p-tosyl ester by a reaction similar to the Beckmann rearrangement, from sodium hippurate by the application of benzoic anhydride, or from 2-phenyl-5 (4H)-oxazolone by the application of benzoyl chloride. Aldol condensation and the Pondorf reduction of the ketone compound yielded dl-threo-1-phenyl-2-acylamino-1, 3-propanediol.
p-Nitroacetophenone oxime, obtained by the reaction of p-nitroacetophenone and sodium hydroxylamine disulfonate, was reacted with p-tosyl chloride under the presence of sodium alcoxide or hydroxide, to prepare the tosyl ester of the oxime. Application of sodium methoxide to this ester yielded p-nitro-α-aminoacetophenone dimethyl acetal from which p-nitro-α-acylaminoacetophenone was prepared by acylation and subsequent hydrolysis.
Quinoline-7, 8-diol was synthesized by the following two courses: 1) 8-Hydroxyquinoline-7-sulfonic acid, m.p. 311-313°, prepared from 8-hydroxyquinoline, yielded the quinoline-diol when fused with KOH. Yield, 30% of the theory. 2) 2-Chloro-7, 8-dimethoxyquinoline, m.p. 94-95°, derived from 7, 8-dimethoxycarbostyril by treatment with POCl3, gave the quinoline-diol when boiled with phosphorus and hydriodic acid. Quinoline-7, 8-diol thus obtained is white microneedles, m.p. 286-287°; gives dark green coloration with FeCl3 in an alcoholic solution. Diacetate, white scaly crystals, m.p. 244-245°. Dimethyl ether, oily liquid which gives a picrate of yellow needles, m.p. 117-118°.
Chlorophenyl nitropyridyl ethers were prepared by the condensation of 2-chloro-5-(and 3)-nitropyridine with potassium salts of mono-, di- and trichlorophenols, and reduced to chlorophenyl aminopyridyl ethers in order to test the latter's antibacterial activities.
Nitration of 4-hydroxy-α-picoline-N-oxide in acetic acid solution with nitric acid free from nitrous acid yields two kinds of mononitro and one of dinitro compounds. Since the compounds obtained by the chlorination and catalytic reduction of the two mononitro compounds are 5-amino- and 3-amino-α-picoline, it became evident that the original nitro compounds were 4-hydroxy-5-nitro- and 4-hydroxy-3-nitro-α-picoline-N-oxides. Further nitration of the two mononitro compounds gave the same dinitro compound as obtained above which showed that the dinitro compound was 3, 5-dinitro-4-hydroxy-α-picoline-N-oxide. The constants of these compounds were: 4-hydroxy-5-nitro-α-picoline-N-oxide, m.p. 221° (decomp.); 4-hydroxy-3-nitro-α-picoline-N-oxide, m.p. 224-225°; 3, 5-dinitro-α-picoline-N-oxide, m.p. 215-217° (decomp.).
3-Guanylaminohydrocarbostyril and 3-glycocyamylaminohydrocarbostyril, which were prepared for the study of pharmacodynamic action of amyostatic poisons, have shown in mice a complicated poisonous action on the nervous system. Detailed studies on their biological actions have to be carried out subsequently.
2-Amino-5-(p-aminomethylbenzenesulfone)-thiazole, m.p. 216-216.5°, was prepared by the following process: 2-acetamino-5-(p-toluenesulfone)-thiazole was oxidized to 2-acetamino-5-(p-diacetylbenzylidenesulfone)-thiazole, m.p. 215-217°, by CrO3 and conc. H2SO4 in acetic acid solution, hydrolyzed and converted to its oxime by the addition of hydroxylamine. There are two forms of 2-amino-5-(p-benzaldoximesulfone)-thiazole, one of m.p. 223-224° and other of m.p. 233-234°, the former of which transits to the latter by being warmed and is more easily soluble in acetone than the latter. Reduction of this oxime with diluted acetic acid and zinc yielded the objective compound, the hydrochloride of which is very soluble in water.
The reactions and properties of gentiopicrin, a bitter glucoside of Gentian root, has been explained by the assumption of the presence of half acetal lactone in its molecule derived from β-aldehyde-ε-hydroxycarboxylic acid.
1) As a new method of preparing chemically pure isovaleric acid, the following process was worked ont: acetone→diacetone alcohol→mesityl oxide→β, β-dimethylacrylic acid→isovaleric acid. 2) dl-α-bromoisovaleric acid, prepared from such isovaleric acid, was resolved into optical isomers by the use of optically active 1-phenyl-2-methylaminopropane, and D(-)- and L(+)-α-bromoisovaleric acids were obtained. 3) From these optical isomers the two isomeric bromovalerylurea were prepared by the oridinary method as D(-)- bromovalerylurea, m.p. 158.5-159.5°, [α]D10-26.0 (c=3, EtOH), and L(+)-bromovalerylurea, m.p. 158.5-159.5°, [α]D10+26.0° (c=3, EtOH).
The total alkaloid of the Scopolia root was precipitated from its cold extract of 0.5% H2SO4 by the Dragendorf reagent and the bismuth compound of the alkaloid obtained by its filtration was decomposed by calcium hydroxide. The free alkaloid thus obtained was extracted with amyl acetate, shaken with diluted sulfuric acid and again precipitated by potassium carbonate. The precipitate was recrystallized from carbon tetrachloride and l-hyoscyamine, m.p. 102°, was obtained in an yield of 83% of the total alkaloid. l-Hyoscyamine easily underwent racemization by cold 0.2% sodium hydroxide solution to atropine.
Ethyl butyrylacetoacetate, prepared from the ethoxymagnesium compound of ethyl acetoacetate with n-butyryl chloride, was alcoholyzed to obtain ethyl butyrylacetate and its cyanoethylation by acrylonitrile yielded ethyl α-butyryl-γ-cyanobutyrate. Esterification of this compound gave the desired ethyl γ-butyrylbutyrate with an overall yield of 28.3% of the theoretical amount calculated from ethyl acetoacetate.
Dihydroresorcinols were prepared in a good yield by the cyclization of ethyl γ-acyl-butyrate by the dropwise addition of the ester on liquefied metallic sodium at a boiling point of xylene. The yield of dihydroresorcinol from ethyl γ-acetylbutyrate was 35.7%, and that of γ-ethyl-dihydroresorcinol from ethyl γ-butyryl butyrate was 50.0%.
The effect of nitrogen and potassium contents in the fertilizer upon the total alkaloidal content of the leaves of Datura Tatura L. was observed by the pot tests under the plans enumerated in Table I. Maximum yield of the alkaloidal content was found in plants cultivated in the soil containing 3g. nitrogen, 1.5g. K2O and 3g. P2O5 per 11kg. of soil. Interrelationship between the alkaloidal content and total nitrogen of the leaves was examined as well as the seasonal variation of the components by the cultivation tests to observe the most suitable conditions for harvesting.
Growth inhibitory action against tubercle bacilli in vitro was tested with 14 compounds of cinnamic acid series, 7 compounds of aminophenol series, 7 compounds of semicarbazone series, 3 compounds of biphenyl ether series, 3 compounds of phthalylacetic acid series, one compound of dibenzofuran series, 2 compounds of p-aminobenzoic acid series, 2 compounds of furfuracrylic acid series, 2 compounds of amino acid series, 12 compounds of phenolic acid series, and 11 kinds of organic reagents. Complete inhibition of growth was shown by the following at respective dilutions: 2, 4-dihydroxycinnamic acid at 100, 000; olivetonide at 80, 000; picrolonic acid at 160, 000-80, 000; 2-amino-4-methylphenol, 2-amino-4-chlorophenol, 2-amino-4, 6-dichlorophenol hydrochloride and 2-amino-4-chlorophenol hydrochloride at 160, 000; and 2, 4-dihydroxy-3-chloro-5-hexylbenzaldehyde semicarbazone at 80, 000. The effective dilutions in other compounds were 40, 000 or less.
Using lard, camellia oil, methyl oleate and triolein, as natural and synthetic fatty oils possessing oleic acid as a chief component, the progress of autoxidation was followed by an extended observation of their peroxide indices and iodine numbers. As a result, a differenee between the oxidative properties of ester and glyceride bonds and a far larger stability of natural fatty oils over the synthetic ones were realized. Influence of ultraviolet radiation on autoxidation was also examined. From the comparison of oxidizability of natural camellia oil, synthetic triolein and the latter containing the unsaponifiable matter from natural camellia oil, the effect of the presence of an antioxidant on oxidation curve in general was observed by which it seemed possible that this form of examination might be used as a means of judging potency of antioxidants.
Autoxidation under various conditions were carried out on methyl oleate, triolein and lard, possessing oleic acid as their fatty acid component, and the properties of their oxidation products and their oxidation mechanism were followed by polarography. As a result, one reduction wave due to the double bond in oleic acid was observed with all the materials besides two distinct waves and a maximum wave in one portion. From the chemical analysis of the peroxides and polarographic analyses, the two waves and the maximum wave were found to be due to unstab le peroxides that form at the initial stage of autoxidation of fatty oils, and some properties of these peroxides were learned. Some assumptions were drawn on a portion of the autoxidation reaction of fatty oils from the irregular relationship between the heights of the two polarographic waves and the chemical constants of the peroxides, the height of these two waves and the individually obtained maximum wave.
In the synthetic reaction of 4-hydroxyphenylarsonic acid by the Béchamp method, it was shown that zinc manifested a catalytic effect and gave good influence on the quality of the product. It was also assumed that the catalytic action of zinc promoted the velocity of rearrangement of the phenol ester of arsenic acid, which is initially formed from phenol and arsenic acid, to 4-hydroxyphenylarsonic acid.
It was found that 4-hydroxyphenylarsonic acid was formed by the thermal reaction of phenolsulfonic acid-(4) and arsenic acid. The compound can also be obtained from phenol by the consecutive application of sulfuric and arsenic acids. This reaction is affected by the time and temperature of the reaction, amount of arsenic acid used, amount of free sulfuric acid, and the presence of water. If the most suitable conditions can be adopted, the reaction can be utilized as the industrial preparative method for 4-hydroxyphenylarsonic acid.
Oxythiamine was obtained in a good yield by heating and boiling thiamine with 20% hydrochloric acid for two hours at an ordinary pressure. Oxythiamine was also obtained by heating 2-methyl-4-hydroxy-5-thioformaminomethylpyrimidine and γ-aceto-γ-chloropropyl acetate in dehydrated formic acid.
Heating of 6-methoxy-8-formaminoquinoline with pure 5-diethylaminopentanone-2 does not result in the formation of plasmochin, i.e. 6-methoxy-8-(4-diethylamino-1-methylbutylamino)-quinoline (Pamaquine), but the reaction does proceed by the addition of polyalcohols such as ethylene glycol, propylene glycol, glycerol and mannitol, phenols such as phenol and cresol, and amino alcohols, such as diethylaminoethanol and 5-diethylaminopentanol-2.
1. It was found that the convenient method to separate plasmochin from 6-methoxy-8-aminoquinoline was to shake the ethereal solution of the mixture with a pH 4.8-5.0 buffer solution of acetic acid and sodium acetate. 2. It was found that the condensation of 6-methoxy-8-formaminoquinoline and 5-diethylaminopentanone-2 with a mixture of ethylene glycol and diethylaminoethanol as an additive agent yields, besides plasmochin, 6-methoxy-8-(2-diethylaminoethylamino)-quinoline as a by-product. It follows, therefore, that the use of diethylaminoethanol is not indicated where a high purity plasmochin is desirable. 3. It was also found that the heating of 6-methoxy-8-formaminoquinoline with diethylaminoethanol, with or without ethylene glycol, resulted in the formation of 6-methoxy-8-(2-diethylaminoethylamino)-quinoline.
By the Leuckart reaction of 6-methoxy-8-formaminoquinoline and 5-diethylaminopentanone-2, with ethylene glycol as the reaction promoting agent, pure plasmochin can be obtained. Examination of reaction conditions wer mad to obtaine the maximum yield.
1). In the previous report, it was shown that compounds possesssing hydroxyl group, such as ethylene glycol and phenol, acted as a catalyst in the Leuckart reaction of aromatic amines. In order to show that the action was due to the hydroxyl group, mono- and di-ethers of ethylene glycol or ether of phenol were added and the yields compared. As a result, it was shown that the presence of a free hydroxyl group was necessary in promoting the reaction. 2). The fact that the velocity of the Leuckart reaction differred according to the kind and the amount of compounds containing hydroxyl group was shown by measuring, at defininite intervals, the amount of carbon dioxide gas generated.
It was made clear that plasmochin is formed by the reaction of 6-methoxy-8-aminoquinoline, 5-diethylaminopentanone-2 and ethyl or methyl formate, with or without ethylene glycol, in an autoclave. Examinations were made to find the reaction conditions that would give the maximum yield.
5, 6-Dimethoxy-8-(4-diethylamino-1-methylbutylamino)-quinoline was prepared by heating in autoclave 5, 6-dimethoxy-8-aminoquinoline and 5-diethylaminopentanone-2 with ethyl formate, or by heating the two compounds with ethylene glycol diformate at an ordinary pressure. Studies were made on the preparative method for the intermediate necessary for the above synthesis.