Benzaldiphenyl-hydroxyethyl amine, obtained by the action of benzaldehyde under the presence of alcoholic potash on phenylalanine, tyrosine, glutamic acid, leucine and alanine, was hydrolized to diphenylhydroxyethyl amine. Normal and iso-derivatives of the latter were determined and transition of normal to iso-compd. was made clear. The compound obtained by Rabe, Hartung and Corrab is the normal compd.

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Treatment of N-benzoyl derivative of n-dianisylhydroxyethyl amine with HCl results in benzoyl transition to benzoate and, at the same time, dehydration occurs to give β-p-nitrobenzoylamino di-p-methoxystilbene as a by-product. Deamination of normal base gives n-hydro-anisoine. Dipiperonylhydroxyethylamine, obtained by treatment of tyrosine and glycine by piperonal under the presence of alcoholic potash solution and subsequent hydrolysis, seems to be iso-compound from the results of its de-amination and benzoyl transition. Iso-hydroxypiperoine, obtained by de-amination coincides with the substance obtained by Fittig-Reusen.

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The preparation of sulfamino-pyridine, s fusing p-acetamino-benzene-sulfochloride with amino-pyridines, had formely been published in this journal; and also sulfamino-pyridothiazoles had been yielded by fusing the sulfochloride with amino-pyridothiazoles such as S, N-amino-methenyl-(2-amino-3-mercapto)-5-chloro-pyridine.
On the application of this fusing method to the preparation of p-amino-benzene-sulfamino-benzene, p-amino-benzene-sulfamino-pyridine and 4-methyl-2-(p-amino-benzene)-sulfamino-thiazole, we obtained the following results.
The mixture of aniline (2 moles) and p-acetamino-benzene-sulfochlorde (1 mole) were fused for about 1 hour at 130-140° and the crude product of p-acetamino-benzene-sulfamino-benzene, warming with dilute hydrochloric acid, were hydrolyzed to p-amino-benzene-sulfamino-benzene. Yield: 83% of the theory. When fused the mixture of 2-amino-pyridine (1 mole) and p-acetamino-benzsne-sulfochloride (1 mole) for about 40 minutes at 130-140°, 2-(p-amino-benzene)-sulfamino-pyridine was formed. Yield: 45% of the theory. After fusing 4-methyl-2-amino thiazole (1 mole) with p-acetaminobenzene-sulfochloride (1 mole) for about 50 minutes at 110-112°, the reaction mixture was treated with dil. hydrochloric acid. The yield of 4-methyl-2-(p-amino-benzene)-sulfamino-thiazole was 64% of the theory.

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Heating quinoline-N-oxide with Ac₂O at 1 0-140° gives carbostyril with an yield of 20-30%. At the same time, orange-red powder (acetate: colorless prisms, m.p. 330-331°; experimental formula C₈H₇NO₂), a small amount of quinoline and fluorescent yellow needles, (C₉H₆N)₂ 0. 1/2 H₂O, m.p. 254°, are formed. Similar treatment with Ac₂O of 3-, 4-, 5-, 6- and 7-bromoquinoline-N-oxide give corresponding bromocarbostyril with about 70% yield.

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dl-N-Methylene-glutamic-pyrrolidone carboxylic acid, m.p. 147-148°, was obtained by the action of formaldehyde and formic acid on optically active or inactive pyrrolidone carboxylic acid. The principle of the formation of this acid was utilized in presence of pyrrolidolne carboxylic acid mixed in glutamic acid.

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N-Methylene-bis-l(+)-pyrrolidone carboxylic acid m.p. 287°, [α]_D²¹=+85.73°, was obtained by the application of methylal and 2N HCl on l(+)-glutamic acid. Diethyl ester of the former has m.p. 117°, [α]_D²⁰=+55.64°. The principle of the formation of this stable acid was utilized in the detection of l(+)-glutamic acid mixed in rac-glutamic acid.

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5-Methyl-3-methylaminohexane was obtained by catalytic reduction with PtO₂ or PdO₂ of a product obtained by applying methyl amine on 5-methlhexanone-(2).

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2, 3′-Dipyridyl and β-3, 4-methylenedioxyphenetyl bromide gave only one addition product of 1:1 under any working conditions so far tevted. From the weak basicity of α-substituted pyridines, the constitution of the product should be β-(pyridyl-α)-pyridine-3, 4-methylenedioxyphenetyl bromide. This substance was readily oxidized to the corresponding pyridone derivative by means of alkaline K₃Fe(CN)₆. Ring-closure followed by hydrogenation gave 6-piperidyl-2′1′-(2′) 4′, 5′-methylenedioxy-3, 4, 5, 6, 7, 8-hexahydro-(2′1′:1, 2-benzoquinolizine), which was identified only by its crystalline Pt-salt.

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4, 4-Dipyridyl and β-3, 4-methylenediroxyphenethyl bromide in excess gave two kinds of addition product: one consists of 1:2 of the two reactants and the other of 1:1, with the former predominating. 1:2 Additive product is very sparingly soluble in alcohol while 1:1 product is soluble. Both substances gave corresponding pyridone derivatives only when oxidized with faintly alkaline K₃Fe(CN)₆ in very dilute aqueous solution. Though the pyridones were not obtained free from inorganic matter, their ring-closure and subsequent hydrogenation proceeded smoothly, giving correspondiug bis-benzoquinolizine and piperidyl-benzoquinolizine. The former gives stable dihydrochloride and its emetine activity is now being investigated.

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Bacteriostatic activities were determined of 3-chlorobutenylamine derivatives obtained by the reaction of various amines such as NH₃, monomethyl, dimethyl or diethyl amines, on 1, 3-dichlorobutene-(2). Primary, secondary or tertiary amines having chlorobutenyl radical possess no bacteriostatic activty, while quarternary ammonium salts of invert soap type, 3-chlorobutenyl-cetylammonium chloride, possess strong antibacterial power against staphylococcus aureus.

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In the condensation of 2-amino-5-carbethoxythiazole and acetosulfanilyl chloride, 2-acetosulfanilamido-5-carbethoxythiazole (I), m.p. 194°, is obtained if the reaction proceeds at a low temperature in pyridine, but a saponification product of ethyl carbonate, i.e. sulfacarboxythiazole acetate (II), m.p. 227°, and bis-sulfanilyl compd., are obtained if the reaction proceeds in ace one with the addition of NaHCO₃. Alkaline saponification of (I) gives, first, sulfacarboxy hiazole acetate, which is finaly deacetylated to sulfacarboxy-thiazole, m.p. 215°.

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The present experiments were undertaken in order to obtain 2-amino-4-methylpyrimidine from 2-amino-4-methyl-6-chloropyrimidine. Use of Zn for the dehalogenation of this reaction gives a very poor yield but addition of NaOH to Zn powder increases the yield to 75%. Use of methanol or 60% methanol as soevent in this reaction gives 2-amino-4-methyl-6-methoxypyrimidine, m.p. 158°, with a good yield, and the objective compound cannot beobtained.

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Relation between molar ratio and the rate of formation of bis- acetosulfanilyl compound was obtained in the condensation of 2-aminothiazole and acetosulfanilyl chloride in pyridine, acetone and dioxane as solvents. There are two kinds of bis acetosulfanilyl compound, one with m.p. 132° and the other with m.p. 190-240°, the former transiting to the latter when heated in alcohol. Productive experimentations were made with bis-acetosulfanilyl compounds of 2-amino-4-methyl, 2-amino-4, 5-dimethyl-, 2-amino-4-phenyl- and 2-amino-4-phenyl-5-methyl-thiazoles and it was definitely proved that phenyl radical obstructed formation of bis-acetosulfanilyl compound.

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Bromoquinine-mono-N-oxide and hydroquinine-ar-mono-N-oxide were each heated with Ac₂O-AcOH at 120-130° and 2′-oxyquinine and 2′-oxyhydroquinine, respectively, were obtained. Similar transition occurs when the reaction is made with benzoic anhydride.

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2′-Hydrooxyquinine was benzoylated in order to protect the OH radical at 9-position and then chlorinated with PCl₅ and finally treated with Na-butoxide which resulted in the synthesis of 2′-butoxyquinine.

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Direct comparison of 2′-hydroxyquinine synthesized by Ochiai and others, with the new metabolic product of quinine obtained by treating quinine with rabbit liver as experimented by Kelseyetal., proved two compounbs to be identical, Similar treatment of quinoline with rabbit liver gives carbostyril with yield of ca 20%. No metabolic product was obtained from quinoline-N-oxide.

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Two kinds of equipment were designed for vacuum distllation of a small amount of substances. One of them, especially, was adapted for distillation of viscuous substance with a small loss. Basic substance (C₁. C₁′) obtained from charred locust (drug) was distilled with this equipment but no effective component could be isolated from its distillate. Distillation of the latter with a very effective semimicro distillation apparatus gives a small amount of crystals of isocaproic amide which does not have antispasmodic effect. The effective component is assumed to be confined in the portion with higher boiling point and does not distillate out.

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Assuming that the antispasmodic action of the base contained in charred (locust) was formed by the thermal decomposition of insect protein, charred substances of several proteins made and tested for antispasmodic effect but all proved to be negative. Its effect could not be increased even by the thermal decomposition of proteins after mixing them with alumina or anthracene Charred chitine substance has no antispasmodic action.

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Synthesis of 2-chloroquinoline-4-carboxylic acid chloride as the starting substance for the synthesis of percaine was made as follows: Lepidine-N-oxide was oxidized with KMnO₄ to quinoline-N-oxide-4-carboxylic acid, then treated with inorganic chloride and the objective was obtained with a good yield.

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Treatment with alkholate or phenolate of 4-nitro-α-picoline-N-oxide in corresponding alcoholic or phenolic solution gives respective OCH₃, OCH₂ or O-φ derivatives, reaction proceeding smoothly. Treatment with acetyl chloride or acetyl bromide gives corresponding 4-Cl- or 4-Br-derivatives. 4-Cl-derivative can be obtained by heating 4-nitro compound with concentrated HCl.

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20 kinds of sulfide and sulfone compouds containing benzothiazolyl were synthesized. A 1 rge part of these compounds are being tested with animals for effectiveness against typhoid fever.

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Sulfide and sulfone compounds having nitro or aminophenyl radicals and oxyquinaldyl or oxylepidylradicals were synthesized. Animal tests of these compounds have not been made as yet.

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During the course of the prepartion of styryl- and isocyaninedyes with 4-phenoxyquinaldine methiodide, the reaction does not occur when the amount of the catalyst amine is small. In an aqueous solution, only the phenoxy radical at 4-position is substituted by the secondary amine, but in alcoholic solution, methyl radicals at both 2- and 4-positions are activated. Use of excess of tertiary amine decomposes styryl dye which transits to isocyanine dye.

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In the application of piperonal on 4-phenoxyquinaldine methiodide under the presence of triethyl amine, the amount of the formation of styryl dyes decreases and that of cyanine dyes incrases with the increasing amounts of the amine, the former reaching its minimum and the latter its maximum at 1/2 mole of the amine. This fact proves that the stryl dye formed is decomposed by the excess of amine and transits to cyanine dye form. This hydrolysis of the double bond was also proved by the fact that phenylethenyl-quinaldine is formed when wet diphenylfomamidine is applied to quinaldine-stryl dye not having phenoxy radical at 4-position; that this anilino compound transits to cyanine dye form; and that heating of 4-phenoxyquinaldine stiryl dye with Na-picrate in alcohol gives the picrate of 4-phenoxyquinaldine methiodide.

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Ionic reactions of 4-nitroquinoline-N-oxide revealed that, similar to the case of 4-nitropyridine-N-oxide, ionic reactions were more active where number of carbon atoms were smaller in chain-form alcohols. Comparison of activities of phenols and alcohols gave conclusion that the reactivity was larger when acidity of OH radical was stronger.

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