The 2-diethylaminoethylesters of heteroaromatic acid, such as 2-furoic acid (I), 2-thiophenecarboxylic acid (II), nicotinic acid (III) and quinaldic acid (IV) were synthesized and the rate of their hydrolysis was measured in an aqueous buffered solution. The same experiments were performed with 2-diethylaminoethylesters of benzoic acid (V) and 1-naphthoic acid (VI) for comparison. Esters of nitrogen-containing heteroaromatics, such as III and IV, differed in the pH-rate profile and were unstable compared with aromatic esters such as V and VI. The half-life of III and IV was calculated to be about 54.7 and 18.0 days, respectively, in an aqueous solution of pH 5.0 and at 25°.

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Reaction of trialkylboranes (I and II) with an aromatic aldehyde (III, IV and V) gave the styrene derivatives which were alkylated at the carbon atom of the aldehyde group. Reaction of I and II with carboxylic acid (XII to XV), carboxylic anhydride (XXIV to XXVII), and carbonyl chloride (XXVIII to XXXI) afforded the corresponding esters. In the reaction of trihexylborane (II) with benzoic acid (XII), the formation of hexyl benzoate (XX) was inhibited by the presence of a radical scavenger (phenothiazine).

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5-(3-Pyridyl)furfural (I) and 5-(3-quinolyl)furfural (II) were condensed with ο-aminophenol, ο-aminothiophenol, or ο-phenylenediamine, followed by oxidative cyclization with lead tetraacetate to the corresponding benzoazole derivatives. I and II gave 5-(3-pyridyl)- and 5-(3-quinolyl)-2-furylvinylene derivatives, respectively, by the Wittig reaction, and I reacted with 4-nitrobenzyltriphenylphosphonium bromide to give two geometric isomers.

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A newly designed laboratory for stability studies, "Artificial Climate Laboratory, " having an ability to reproduce an actual climate or any desirable climate conditions, was established. The temperature and humidity in this laboratory were controlled by the following processes : The climate data to be reproduced, i.e., the temperature and the dew point calculated from the actual temperature and relative humidity using a programmable computer, Deck Linc 8, were punched in a paper tape, a tape reader picked them up periodically, and the controlling devices sent a signal for operating the heat exchange valve and the humidifying valve simultanuously, and the temperature and humidity in each room of the laboratory were controlled full-automatically by the given data. The three actual climate conditions simulated in this laboratory were as follows : (1) A summer climate in Japan, measured in the company storehouse in Osaka, (2) a winter climate in Japan, measured by the meteorological observatory in Sapporo, and (3) a tropical climate, reported by the meteorological observatory in Bangkok, Thailand. Examinations were made on the stalility of retinol, thiamine, and ascorbic acid in a multivitamin liquid preparation, and changes in the appearance and consistency of cosmetic creams. The actual shelf-lives of the former, governed by the Arrhenius relation, agreed with that of the corresponding artificial climate condition. Therefore it was evidenced that the artificial climate well simulated the actual climate thermally. The changes of the latter, not following the Arrhenius relation, were hardly presumed by conventional accelerating method, but, nor repeating the Osaka condition of this system, changes to be expected for 1 or 1.5 years under actual climate were able to be reproduced in several months.

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4-Imino-6-methyl-4H-quinolizine derivatives (XIII) were easily obtained by the reaction of 6-methyl-2-pyridineacetate derivatives (XI) with ethoxymethylenemalononitrile (XII). The reaction of XI with ethyl ethoxymethylenecyanoacetate (XIV) afforded ethyl 4-substituted-2-cyano-4-(6-methyl-2-pyridyl)-crotonate derivatives (XV). New nitrogen-bridged [12]annulene heterocyclic systems, 1-azacycl[3, 3, 3]azine derivatives (XVII, XVIII) were obtained by the reaction of XIII or XV with XII or acetic anhydride.

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Semmler-Wolff reaction was examined with the oxime (I') of 5, 6, 7, 8-tetrahydro-quinolin-8-one (I), the oxime (II') of 5, 6, 7, 8-tetrahydroquinolin-5-one (II), the oxime (III') of 1, 2, 3, 4-tetrahydroquinolin-4-one (III), the oxime (IV') of 1, 2, 3, 4-tetrahydroacridin-4-one (IV), and the oxime (V') of 1, 2, 3, 4-tetrahydroacridin-1-one (V). The reaction was carried out under the condition of either (A) heating in 85% sulfuric acid at 140°for 4 hr or (B) heating in acetic anhydride at 140°for 4 hr. It was thereby proved that the products corresponding to the said reaction were obtained in all cases, except from III', by either of these conditions, although there was a difference in their yield. The products obtained from I' were 8-aminoquinoline (VI) by method (A) and 8-acetamidoquinoline (VI') from method (B) ; those from II' were 5-aminoquinoline (VII) by method (A) and 5-acetamido quinoline (VII') by methdo (B) ; those from IV' were 4-aminoacridine (VIII) by method(A) and 4-acetamidoacridine (VIII') by method (B) ; and those from V' were 1-aminoacridine (IX) by method (A), and 1-acetamidoacridine (IX') and 1-diacetamidoacridine (IX") by method (B). In the case of III', method (A) afforded the hydrolyzed product, III, and the acetylated compound (III") of III' was obtained from method (B).

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A new sensitive method for selective detection of phenylpyruvic acid in urine is presented. This is based on the finding that diazotized p-chloroaniline reacts with phenyl-pyruvic acid in sodium hydroxide solution, in the presence of sodium sulfite and sodium hypophosphite, to give a coloring matter which is extracted with cyclohexane to show a pink color. In this method, 1.0 ml of urine is treated instead of aqueous phenylpyruvic acid solution. The detection limit of the acid was 0.3-0.5 mg/dl in usual and faintly colored urine of an infant, and about 1 mg/dl in fairly colored urine. The method was not affected by the tested substances other than the acid. The coloring matter in the method was isolated in crystalline form and its structure was determined as the red form of 1, 5-di(p-chlorophenyl)-3-phenylformazan.

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The reaction of 2'-bromomethyl-2-biphenylcarbaldehyde (V) with sodium cyanide was carried out under different conditions. The reaction in a polar protic or aprotic solvent at a low temperature (-60°) gave 5-cyano-5, 7-dihydrodibenz[c, e]oxepin (VI), in an aprotic solvent at room temperature it gave VI and 9-cyanophenanthrene (IX), and in an aprotic solvent at high temperature (55-65°), it gave VI, IX, and diphenide (II). The diphenide was found to be formed by autoxidation of VI. Mechanisms are proposed for the formation of VI, IX, and II.

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On hydrolysis with dilute mineral acid, Ginseng saponins, ginsenosides-Rb₁, -Rb₂, -Rb₃, -Rc, and -Rd yielded panaxadiol (IV), and ginsenosides-Re, -Rf, -Rg₁, and -Rg₂ and 20-glucoginsenoside-Rf afforded panaxatriol (X). The optimal condition of saponinhydrolysis for the quantitative analysis of IV and X was studied. The crude hydrolysates of methanol extract of Ginseng were trimethylsilylated with N-trimethylsilylimidazole and the saponin content was calibrated by the gas chromatographic determination of TMS-panaxadiol and TMS-panaxatriol, using diacetylhederagenin methyl ester as the internal standard. This procedure was applied to the evaluation of the commercial "Ginseng Tea" and "Ginseng Extract."

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The tannin of Geranium thunbergii was extracted with acetone/H₂O at room temperature, and the solution was extracted with EtOAc. This extract was fractionated using droplet countercurrent chromatography to yied tannin 1 and tannin 2. The relative astringency measurement and quantitative determination of ellagitannin by ultraviolet absorption of the solutions colored with NaNO₂-AcOH showed that the tannin activity of this plant is mainly due to the substances in the EtOAc extract in which tannin 1 and tannin 2 are the main constituents, and also that ellagitannins are the main constituents of the tannins in this plant. When treated with boiling water, tannin 1 was fairly rapidly hydrolyzed, and the resulting solution gave, upon fractionation after methylation, corilagin, hexahydroxydiphenoic acid, and gallic acid as their methylated derivatives. Glucose was also detected. An additional hydrolysis product, in which another galloyl group was presumed to be linked to corilagin, was obtained by treatment with boiling water for a short period. Tannin 1, therefore, would be one of the main original substances which yielded previously reported corilagin and other compounds related to tannin, which were obtained from the hot water extract.

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Identification of components in pharmaceutical preparations was rapidly and easily performed by the combination of thin-layer chromatography and infrared diffuse reflection method. A sample solution extracted by methanol was separated on a thin-layer microplate of silica gel containing a mixed fluorescent substance. The colored portions on the plate were separated while irradiating with a wide wave ultraviolet lamp, and extracted with methanol. The extracts were mixed with KBr, dried, and its infrared spectrum was measured. The spectra thus obtained were compared with standard spectra. Even 25 μg of a component gave a distinct spectrum by the diffuse reflection method.

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Titanium phosphates were prepared by the reaction of titanium dioxide (anatase, rutile), titanyl hydroxide, or titanium metal with phosphoric acid, and their formation conditions and acidic properties were examined. Titanium (IV) pyrophosphate, TiP₂O₇, was the main product in the reaction of titanium dioxide or titanyl hydroxide with phosphoric acid. TiP₂O₇ was formed in the system of Ti-H₃PO₄, but titanium (III) tetra-metaphosphate, Ti₄(P₄O₁₂)₃, was additionally formed. This tetrametaphosphate was easily obtained by heating the primary product of Ti/P (R)=1/6-1/10 in a nitrogen stream (50 ml/min) or vacuum (0.01 mmHg) at 500-700°. Titanium phosphate produced in this study was a solid acid, its acidity being mainly concentrated at acid strength of H₀=+1.5. Titanium phosphate made from anatase had the largest amount qf acid (4.3 mmol/g) at the reactant ratio of R=1, while that prepared from rutile or titanyl hydroxide had a large acidity (0.6 mmol/g) at R=1/2. It was clear that the amount of acid in titanium phosphate was closely related to its water content.

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Some derivatives of aminobenzoic acid were examined for their inhibitory activity against immune hemolysis and heat-induced hemolysis. Of the compounds tested, bis(salicylamido)benzoic acids were proved to have a potent inhibitory effect on both hemolytic reactions. In immune hemolysis, inhibitory activity of 2, 4- and 2, 5-bis(salicylamido)benzoic acid was a little weaker than that of sodium copper-chlorophyllin, but stronger than that of sodium citrate, dipotassium ethylenediaminetetraacetate, and non-steroidal anti-inflammatory drugs used as active controls. In heat-induced hemolysis, 2, 4-, 3, 5-, and 2, 5-bis(salicylamido)benzoic acid inhibited hemolytic reactions more pronouncedly than non-steroidal anti-inflammatory drugs. Structure-activity relationships and possible use of these active compounds as new drugs were discussed.

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Color reaction of O, O-dimethyl 2, 2-dichlorovinyl phosphate (I) and various ketones in alkaline ethanol solution was examined, and acetophenone (II) was found to be the most advantageous reagent. I was determined in insecticidal preparations. Dipterex, dibrom, and dichloroacetaldehyde (III) showed similar absortion spectra. Dipterex and III were removed by extraction. Several cormmercial preparations have been analyzed by this method with a precision of 1-2%. Mechanism of this color reaction was suggested to be dehydrative condensation reaction of II and III produced from I by hydrolysis in alkaline ethanol solution. Among various kinds of aldehydes, acetaldehydes showed characteristic absorption spectra with two intense peaks at 480 and 600 nm.

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A modified method of the Chichibabin amination reaction was carried out on 1, 5-, 1, 6-, and 1, 8-naphthyridines and their aminated compounds (II, VI, and VIII) were obtained in a high yield. A modified Skraup reaction was carried out on these aminated compounds, and on 3, 4- and 2, 6-diaminopyridines, in the presence of sulfo-mix, and using ferrous sulfate and boric acid as a catalyst. This reaction gave the objective pyridonaphthyridines of the angular type, 4, 5, 9-triazaphenanthrene (III), and its methyl derivative (IV) but not the linear type.

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1, 2-Diaminopyridinium mesitylenesulfonate (I) reacts, in the presence of potassium carbonate, with a variety of α, β-unsaturated carbonyl compounds such as benzoylacetyllenes, benzalacetophenones, ethoxymethylenepentane-2, 4-dione, and diethyl ethoxymethylenemalonate to give s-triazolo[1, 5-a]pyridine derivatives, presumably via 1-amino-2-imino-1, 2-dihydropyridine (VIII). Reaction of I with diphenylcyclopropenone in ethanol in the presence of potassium carbonate afforded ethyl 3-amino-2, 3-diphenylacrylate, whereas reaction of VIII in an aprotic solvent (benzene) gave 3-amino-2, 3-diphenyl-N-(2-pyridyl)acrylamide.

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Thinchrograph analysis was established for simple quantitative analysis. Seasonal variation in the content of stevioside and its content in the samples cultivated at 12 different places in Japan were examined by this method. In addition, 24 samples of classified by their morphological characteristics were examined for their stevioside productivity.

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Color reaction between hemin and pyridine in acetic acid was spectrochemically studied. Hemin sensitively reacts with pyridine in acetic acid to form pyridine hemichrome. A hemin solution in a mixture of pyridine and acetic acid (15 : 85, by vol.) shows a stable red orange color which gives an absorption maximum at 407 nm. A linear relationship was observed between the hemin concentration. in the range of 0-8.5 μg/ml and the absorbance at 410 nm in the solution. This color reaction can be used as a simple and rapid technique for the qualitative and quantitative analysis of hemin.

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Hydrolysis of stevioside (I) with crude hesperidinase afforded its genuine aglycone, steviol (III) quantitatively. Rebaudioside-A, which was newly isolated from Stevia rebaudiana along with I, yielded isosteviol (II) on acid hydrolysis, was hydrolyzed partially, and did not give III with this crude enzyme. The optimal condition for the enzymic hydrolysis of I and quantitative analysis of the resulting III by gas chromatography were studied to establish the selective determination of I in Stevia leaves. This procedure can be applied to the simple determination of I in orange juice without any pretreatment.

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It has been found that a reaction of the cyclic imino ether in gardneramine (I) with MeI afforded N-methylated oxindole (III). Synthesis of a compound (XIV)) having a cyclic imino ether system and its reaction with MeI are described. An alcohol (X) was prepared by the Michael reaction of N-acetyl-3-ethyloxindole (VII) with ethyl acrylate, followed by LiA1H₄ reduction. On treatment with p-toluenesulfonyl chloride in pyridine, X afforded a tosylate (XI) and a chloride (XII). The imino ether (XIV), synthesised by the reaction of XII with potassium t-butoxide in dimethyl sulfoxide-benzene (1 : 1), reacted with MeI to afford N-methyl-3-(3-iodopropyl)oxindole (XX). The reductive dehalogenation of XX with NaBH₄/Me₂SO gave N-methyl-3-ethyl-3-propyloxindole (XXI), which was identical with the authentic sample prepared from XII by a different route.

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By the use of gas chromatography and gas chromatography-mass spectrum, camphor was detected from the water of Lake Inbanuma, which is one of the sources of Chiba Prefecture water supplies, and camphor and p-methylacetophenone were detected from the water of the Southern Basin of Lake Biwa, which is the source of Kyoto City water supplies. These compounds would be partly responsible for objectionable odor and taste occuring in water supplies.

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