Two simple methods were devised for evaluation of the effectiveness of antitussive drugs. A-method: A guinea pig, to which the drug had been administered subcutaneously before 30 min., is placed in a desiccator and allowed to inhale SO2-containing air for 1 min., the animal is taken out in open air, and the number of coughing observed for 5 min. In this method, the absence of cough response was regarded as effective. B-method: A guinea pig is anesthetized lightly by intraperitoneal injection of 15mg./kg. of pentobarbital sodium and fixed in a dorsal position. The trachea is exposed and a small hole cut in it. A stimulating hair is introduced through the hole for 3cm. and a violent cough is evoked. The stimuli were given at 15, 30, 60, 90, and 120 min. after injection of a drug and when no cough occurred even to one stimulus, the drug was regarded as effective. One animal can be used several times repeatedly with an interval of 10 or more days. In both methods ED 50 was calculated by the up-and-down method. The results from these two methods gave following values of ED 50, (mg./kg.): Morphine hydrochloride, 5.90 (A-method), 6.40 (B-method); codeine phosphate, 14.4 (A-method), 18.4 (B-method).
Antitussive activity of several opium alkaloids and their N-oxides was examined and the general pharmacological properties were studied of codeine N-oxide which is the most potent compound among them. Employing the two methods of assay for antitussive activity*1, it was found that codeine N-oxide possessed greater antitussive activity than codeine phosphate, whereas it was very weak in analgesic activity against pressure pain in mice. Furthermore, it was found that its acitons on blood pressure, respiration and heart, and its acute toxicity were definitely weaker than those of codeine phosphate. The constipating action and inhibition of gastrointestinal propulsion of codeine N-oxide were found to be less than those of codeine phosphate.
Antitussive and analgesic activity were examined of (+)-morphine, (+)-dihydromorphinone, and (+)-dihydrocodeine, which are the optical antipodes of natural alkaloids. It was concluded that these dextrorotatory compounds possessed significant antitussive activity, whereas their analgesic activity was negligible by pressure method in mice. Further, these dextrorotatory compounds did not depress the respiration of cat anesthetized with urethan. (+)-Morphine was found to be even antagonistic against the analgesic activity of (-)-morphine.
Starting with 1- and 2-naphthylamines, p- and m-phenetidine, m- and o-anisidine, and 2, 5-dimethoxyaniline, N-naphthylacetoacetamide, acetoacetophenetidide, anisidide, and anilide compounds were prepared and were cyclized to two kinds of carbostyril derivatives, 4-methyl-7-ethoxy- and 8-methoxy-carbostyril. These compounds were brominated with phosphoryl bromide to form 2-bromo-4-methyl-6-ethoxy-, -7-ethoxy-, 7-methoxy, 8-methoxy-, -5, 8-dimethoxy-, -benzo [h]-, and benzo[f]-quinolines, which were dimerized to 4, 4′-dimethyl-6, 6′-diethoxy-, -7, 7′-dimethoxy-, 7, 7′-diethoxy-, -8, 8′-dimethoxy-, -5, 5′, 8, 8′-tetramethoxy-, -benzo[h]-, and benzo[f]-2, 2′-biquinolines. Decomposition of 4, 4′-dimethyl-6, 6′- and-7, 7′-dialkoxybiquinolines with hydrobromic acid gave 4, 4′-dimethyl-6, 6′- and-7, 7′-dimcetoxy-2, 2′-biquinolines and 4, 4′-dimethyl-6, 6′-dibenzoyloxy-2, 2′-biquinoline via 4, 4′-dimethyl-6, 6′- and 7, 7′-dihydroxy-2, 2′-biquinoline.
2-Bromocinchoninic acid (I), and methyl and ethyl 2-bromocinchoninate (IV) were prepared by application of phosphoryl bromide to 2-hydroxycinchoninic acid and its methyl and ethyl esters. Application of phosphorus pentabromide to these compounds afforded 2-bromocinchoninoyl bromide (VII) and then 2-bromocinchoninamide (VIII). Dimerization of (I) gave 2, 2′-bicinchoninic acid (II) and its methyl, ethyl, and propyl esters were prepared. These esters could not be obtained by dimerization of (IV) and (II) was formed. Application of thionyl chloride to (I) gave 2, 2′-bicinchoninoyl chloride which was derived to 2, 2′-bicinchoninamide. This amide was also obtained by dimerization of (VIII). Nine kinds of acid amide compounds of 2, 2′-bicinchoninic acid were prepared by application of ethylamine, isopropylamine, butylamine, aniline, dimethylamine, diethylamine, diisopropylamine, dibutylamine, and methylaniline to the acid chloride of 2, 2′-biquinoline. Permanganate oxidation of 4, 4′-dimethyl-2, 2′-biquinoline gave 4′-methyl-2, 2′-biquinoline-4-carboxylic acid (XIII) and a small amount of 2, 2′-bicinchoninic acid (II). Methyl and ethyl esters (XIV) of (XIII) were also prepared.
Chemical behavior of N-(p-dimethylaminophenyl)-α-(1-oxido-pyridyl) nitrone (I) as the mashed aldehyde of picolinaldehyde 1-oxide (II) was examined. (I) undergoes smooth reaction with carbonyl reagents to form derivatives of (II). The aldoxime of (II) had syn configuration and its anti-isomer was not obtained. This aldoxime quite easily afforded the nitrile compound. Condensation of (I) and active methyl or methylene compounds was effected only in rhodanine and not in others. Isolation of (II) by hydrolysis of (I) with hydrochloric acid was not possible but (II) was obtained from phenylhydrazone, though in 15% yield.
In order to elucidate fundamental problems regarding preparations using aluminum soap, macrorheological examinations were made on the peptization of aluminum distearate-Nujol gel in concentrations used in preparations. Dependence of shear thixotropy on the concentration of various additives was examined by the improved McMichael viscosimeter and the result indicated that peptization decreased B coefficient of thixotropic breakdown with time. From the mode of this variation, this peptization was classified specifically into one kind of unpeptization type and three kinds of peptization type. At the same time, the same classification was derived from variation in equilibrium plastic viscosity. The optimal peptization concentration was at equimolar ratio of Al (OH) (OOCC17H35)2 and the equilibrium plastic viscosity markedly decreased at that concentration to show the minimum value. Compounds which act as a peptizer are those having free hydroxyl, carboxyl, or amino group, and they showed characteristic peptization type. The peptizer of hydroxyl system caused spinability in the gel and then a marked viscoelasticity, such as the Weissenberg effect. The foregoing phenomena were considered to be due to interaction between macromolecular micelle of aluminum stearate and peptizer compound, resulting in the severing or rearrangement of the micelle and destruction of gel in a network.
Infrared absorption spectra were measured of various kinds of non-peptized and peptized gel of aluminum distearate-Nujol gel and comparative examinations were made on characteristic absorption bands. Characteristic absorption bands of aluminum distearate gel were at 2.67, 6.28, and 10.17μ, respectively due to the free hydroxyl, carboxylate ion, and Al-O linkage. In the gel containing a peptizer of hydroxyl and amino series, the absorption at 2.67μ is no longer present and the absorptions of associated OH and NH appear at 2.7-3.0μ and that of fatty acid at 5.8μ, with disappearance of the absorption at 10.17μ. In the presence of carboxyl compound, the absorption due to Al-O linkage shifts to a somewhat shorter wavelength region and an absorption appears at 5.8μ. It is assumed, therefore, that the peptizer compound is bonded to Al-O octahedron in aluminum distearate and severs Al-O coordinating link, which is the main chain of gel structure (OH and NH2 compounds) or newly forms an aluminum salt (COOH compounds). This is considered to have endorsed appropriateness of rheological conclusion that peptization is due to destructive severance of macromolecular micelle of aluminum distearate by peptizer compound.
N-[5-(N-Methylanilino)furfurylidene]arylamine hydrohalide (A3) was prepared by application of methylaniline to N-(5-halofurfurylidene)arylamine (B) (Table I) and the corresponding base (C) was obtained by application of alkali to (A3) to effect dehydrohalogenation (Table II). Reacton of (C) with hydrazine, phenylhydrazine, or semicarbazide afforded the azine, phenylhydrazone, and semicarbazone of 5-(N-methylanilino) furfural. Reduction of (IX) with sodium borohydride and catalytic reduction of crude (XVI) so obtained gave 2-anilinomethyl-5-(N-methylaniline)tetrahydrofuran (XVII). The structure of (A3) was examined through ultraviolet, visible, and infrared absorption spectra.
Urine of rabbits administered with sulfathiazole, sulfanilamide, and sulfadiazine was examined by the same method as that reported in the preceding paper for detection of N-glucuronide as the metabolic product of sulfapyridine in rabbit urine*1. The Rf values of the N-glucuronides from rabbit urine were compared with the values of the N-glucuronides of the three kinds of sulfa drug. The rate of conjugation of N-glucuronides of these three kinds of sulfa drug was 6-20% of the drug administered, the value being lower than that of sulfapyridine. The fact that the amount of N-glucuronide does not increase in parallel with increased dosage of the sulfa drugs is different from the result obtained with sulfapyridine. The method devised by the present author for separatory determination of the free, acetylated, and N-glucuronide types of various sulfanilamides was applied to the rabbit urine after administration of sulfathiazole and sulfonamide. It was thereby assumed that the free sulfonamide is not necessarily in equivalent amount of free glucuronic acid but increases with the increasing dosage administered and that the substance which shows diazo coloration reaction only after hydrolysis with hydrochloric acid is nothing but N4-acetylated compound in the majority.
Reaction of 2-hydrazino-4-hydroxy-6-methylpyrimidine (I) and carbon disulfide afforded 3-mercapto-5-hydroxy-7-methyl-s-triazolo[4, 3-a]pyrimidine (II) and 3-mercapto-5-methyl-7-hydroxy-s-triazolo[4, 3-a]pyrimidine (VII). (VII) alone was obtained by pyrolysis of 1-(4-hydroxy-6-methyl-2-pyrimidinyl)-4-phenyl-3-thiosemicarbazide (XV), formed by the reaction of (I) and phenyl isothiocyanate. Heatingof (II) at 250-255° effects its isomerization to (VII). Reaction of 2-hydrazino-4, 6-dimethylpyrimidine (III) and carbon disulfide afforded 3-mercapto-5, 7-dimethyl-s-triazolo[4, 3-a]pyrimidine (XXIV) but (XXIV) easily underwent isomerization to 2-mercapto-5, 7-dimethyl-s-triazolo [2, 3-a]pyrimidine (XXVI). Similar mercapto compounds were obtained from 2-hydrazinopyrimidine (XXVII) and 2-hydrazino-4-methylpyrimidine (XXII).
Application of benzyl chloride to 5-amino-s-triazole (VI) in alkaline reaction afforded 1-(XI), 2-(XXV), and 4-benzylated (XVI) compounds. Decomposition of six out of seven kinds of N-benzyl-s-triazolopyrimidinones, obtained by benzylation of methyl-hydroxy-s-triazolo[4, 3-a]- and [2, 3-a]pyrimidines (I, II, and III), with 80% hydrazine hydrate or 5% potassium hydroxide clarified the structure of these compounds. It was also found that the heating of 5-methyl-8-benzyl-s-triazolo[4, 3-a]pyrimidin-7(8 H)-one (V) with piperidine effected its isomerization to 4-benzyl-7-methyl-s-triazolo[2, 3-a]-pyrimidin-5(4 H)-one (VIII).
The structure of the new glycoside, distichin, isolated from the methanolic extract of the leaves of Taxo diumdistichum, was determined as isorhamnetin 3-α-L-arabinoside. A glycoside of m. p. 250-252°, in which kaempferol is bonded to glucose, sequoyitol, end avicularin were isolated from the leaves of Glyptostrohus pensilis. Quercitrin was isolated from the leaves of metasequoia.
Thirty-six kinds of new and known derivatives of pyridazine with antifungal activity were prepared, while examining the relationship between changes in the chemical structure and antifungal activity. Antifungal activity of these derivatives was examined against phytopathogenic fungi and strong activity was found in 6-chloro-and 6-bromo-3-pyridazinethiols, 6-methoxy-3-pyridazinethiol, S, S-bis (6-chloro-3-pyridazinoyl) dithiocarbonate, bis (6-chloro-3-pyridazinyl) trithiocarbonate, and O-alkyl, O-phenyl, and O-benzyl S-(6-chloro-3-pyridazinyl) thiocarbonates.
The crude drug known as Tohoku-dai-kojutsu is the rhizome of a Manchurian Atractylodes plant which is anatomically related to Atractylodes japonica. Steam distillation of this rhizome afforded 1.0% of essential oil and the crystalline components isolated from this oil contained β-eudesmol as white needles, m.p. 79-80°, atractylon as white plates, m.p. 38°, and a new substance of extremely labile yellowish prisms, m.p. 52°, C13H10O. The last one was named atractylodin.
Experiments on the factors affecting the apparent density and strength of granules were carried out using calcium p-aminosalicylate (J. N. F. II) and light calcium carbonate, and (1) the amount of liquid added for compounding and particle size of a powder, (2) surface-chemical properties of the liquid, and (3) drying temperature were cited as the factors. Examinations were made on these factors. At the same time, wettability of a powder by the liquid was measured by the penetration method and it was found that granules with larger apparent density and greater strength would be obtained by the use of a powder with a large particle size, greater amount of liquid added to the powder, using a liquid which has low wettability to the powder used, and lowering the drying temperature.
Reissert reaction of lepidine (I) and 8-methyl- (II), 3-nitro-4-hydroxy-, and 3-carboxyethyl-4-hydroxy-quinolines resulted in the formation of the Reissert compounds (III and IV) from (I) and (II) alone, and the starting compounds were recovered with others. Application of cyanogen bromide to 6-chloro- (V) or 7-chloro- (VI), 8-chloro- (VII), 6-ethoxy- (VIII), and 8-hydroxy-quinolines in hydrous ether afforded (IX) and (X) respectively from (V) and (VIII), and (XI) from (VI), but the other compounds were recovered unchanged. Treatment of 3-nitro-4-amino- (XV), 5-nitro- (XVI), 6-nitro- (XVII), 7-nitro- (XVIII), and 8-nitro-quinolines (XIX) with hydrazine in ethanol, under pressure at below 100°, afforded the corresponding amino compounds (XX to XXIII), with the exception of (XVII) which was recovered. The same result was obtained by the use of a copper powder in this reaction. The same treatment of 4-nitroquinoline 1-oxide (XXIV) and 4-nitroquinaldine 1-oxide (XXVI) respectively afforded (XXV) and (XXVII). The reaction of (XXIV) and quinoline 1-oxide with hydrazine in ethylene glycol, in the presence of copper powder, gave quinoline, Reduction of (XVII) with lithium aluminium hydride produced (XXXIII).
The structure for sotetsuflavone was determined as (II), instead of (I), by relevant experiments. When treated with methanolic barium hydroxide solution, sotetsuflavone pentaethyl ether afforded 2-hydroxy-4, 6-diethoxyacetophenone, a phenolic acid (III), and p-ethoxybenzoic acid. The structure of (III) was confirmed by its oxidation to 3-carboxycarbonyl-4-ethoxybenzoic acid (V), which was newly prepared from a condensation product (VI).
A few of the amino acid derivatives with pyrolytic structure of antipyrine and acetophenetidine, prepared earlier, were found to have antipyretic and analgesic actions. Attempts were then made to introduce benzoic acid structure, having paralytic action, into the nitrogen in amino acid, in place of the pyrolytic structure, to examine the effect, if any, on increasing analgesic activity. N, N-Dimethyl-2-(ethoxycarbonylanilino) alkanamides and N, N-dimethyl-2-(dialkylcarbamoylanilino)-alkanamides were prepared. Preparation of N, N-dimethyl-2-(o-dialkylcarbamoylanilino) alkanamide was thought to be difficult due to the effect of a substitutent in the ortho-position but the objective compounds were obtained in a good yield by a new method of synthesis.
2-Phenyl-3-(5-nitro-2-furyl) acrylic acid and 2-phenyl-5-(5-nitro-2-furyl)-2, 4-pentadienoic acid were prepared by the Perkin reaction of 5-nitro-2-furaldehyde or 3-(5-nitro-2-furyl) acrolein with potassium phenylacetate. Comparative examinations were made on the effect of the nitro group in 5-position of the furan ring and the presence of conjugated double bond between the aldehyde group and furan ring on the yield of the product. It was thereby learned that the presence of a nitro group increased the yield, while participation of a conjugated double bond tended to lower the yield.
Infrared spectra of over 70 kinds of acetylenic, mainly phenylethynyl compounds were measured. Six absorptions, involving ≡CH and C≡C stretching, ≡CH bending, which split into two, and its overtone, and C6H5-C≡C- skeletal bending frequencies were assigned and discussed as the characteristic frequencies for substituted phenylethynyl and other monosubstituted acetylenes. The band near 1700cm-1 in propargyl alcohols which has been reported to be a characteristic absorption for this type of compounds was attributed to some impurities in the sample. The position, intensity, and, in particular, the splitting phenomenon of the C≡C stretching frequencies in a large number of disubstituted acetylenes were found to have distinct correlation to the structures, especially to those in the vicinity of C≡C bond in the molecule. Many regularities were found in the conjugation effect of acetylenic bond on the ketonic and other carbonyl stretching frequencies, and such effect was discussed in comparison with those of olefinic double bond.
Attempt was made to prepare N-dimethyl and N-monoisopropyl derivatives of homoleucinol. p-Nitrobenzoyl derivative of the OH group in N-isopropylhomoleucinol was obtained but not that of the NH group. L-Compound of N, N-diethylleucinol p-aminobenzoate was obtained as an oil of b. p. 170°, [α]D24+15°. Infrared spectrum of 2, 5-dimethyl-4-isobutyloxazole was measured and the absorptions at 1646 and 1586cm-1 were considered to be those of conjugated C=C and C=N, respectively.
Sensory test was carried out with modified Scheffe's method on 10 kinds of powders commonly used as a diluent in powdered medicinals. Each powder was evaluated for its flow property. Correlation between the scores thereby obtained and the result of various physical determinations was analyzed and it was found that there is a correlation between the result of sensory test and the results of angle of repose, revolving cylinder method, and vibrating spatula method.
Examinations were made on fatty liver caused by administration of ethionine by analysis of lipid in fatty liver and relationship between dose and period until appearance of fatty liver, from which the effect of various kinds of anti-fatty liver agents was compared. It was found that the amount of cholesterol and phospholipids in the plasma and liver tended to decrease 24 hours after administration of ethionine, conversely with increase of liver fats. Increase of liver fats caused by ethionine administration is due to increase in neutral fat. Orotic acid as well as methionine was found to have anti-fatty liver activity by administration of the test sample once with 500mg./kg. of ethionine to fasted rats. Fatty liver can be prevented sufficiently with methionine: ethionine ratio of 1:5. Examinations were also made with rats, not fasted but fed on a normal solid diet or on a low-protein diet lacking in anti-fatty liver factor. In this case, chondroitinsulfuric acid, glucuronic acid, orotic acid, and soya bean lecithin were effective in solid diet, and methionine was effective, and choline, vitamin B12, and the component of Alisma plantago were somewhat effective in low protein diet. Methionine, choline, and vitamin B12 were also able to improve liver dysfunction.
In order to examine if anti-fatty liver substances, known to be effective for dietary fatty liver, would have preventive effect against acute liver damage caused by carbon tetrachloride, bromsulfaphthalein retention in the plasma of normal rat was tested and dose-response curve of carbon tetrachloride was examined. Nine kinds of chemicals were administered to rats with liver damages caused by carbon tetrachloride and plasma bromsulfaphthalein retention, liver fats, and amount of cholesterol were examined. It was thereby found that orotic acid, soy bean lecithin, inositol, and the extract of Alisma plantago were effective, while vitamin B12 and sodium thioglycolate had no anti-fatty liver activity, although they were capable of effecting some improvement in hepatic functions, and DL-methionine, choline chloride, and glucuronic acid were entirely ineffective.
The extract fraction T-(1⋅1⋅1⋅1) from Alisma plantago L., now being examined as the new anti-fatty liver agent, was found to be effective not only in dietary fatty liver caused by low-protein diet added with cholesterol but also indicated the activity of lowering cholesterol in hypercholesterolemia caused under the same conditions, contrary to the action of choline and lecithin. This action is assumed to be advantageous in prevention of atherosclerosis and experiments were carried out with rabbits. Rabbits apparently grow normally on a diet added with 0.5% of cholesterol but after three months, the cholesterol value in the blood reached around 700mg%, with highly developed atheroma. Elevation of cholesterol value was stronger by the ester type than the free form, so that the F/T ratio decreased. Phospholipid value increased but not as much as the cholesterol value and the C/P ratio showed increase. On the other hand, addition of 0.5% of choline to above diet resulted in marked elevation of cholesterol and Phospholipid values, with increased worsening of atheroma. Lecithin also showed a slight choline-like tendency. On the contrary, addition of 0.5% of the fraction T-(1⋅1⋅1⋅1) clearly demonstrated appreciable inhibition of blood cholesterol elevation during the whole period of the experiment and tended to alleviate atheroma. Such a tendency was endorsed by comparative examinations among litter rabbits.
Optimal conditions for the analysis of methyl oleate by gas chromatography were determined and standard for measurement was prepared by selecting methyl myristate as the internal standard substance. Conditions for measurement, using a column of 2m. in length, with silicone grease, were a temperature of 226° and helium flowrate of 66cc./min. Standard methyl oleate and its ozonolysis product were submitted directly to gas chromatography. Result of analysis showed the rate of decrease in the peak of methyl oleate and that of increase in the peak of decomposition product of the ozonide were proportional to the amount of ozonization and that the determination of ozonide was possible within the accuracy of 5%. Direct gas chromatography of completely ozonized product of a fatty acid mixture was found to leave saturated acids without change, with disappearance of the peak of unsaturated acids which made it possible to determine the quantity of saturated and unsaturated acids in the mixture.
The earlier work on direct gas chromatography of the ozonide of methyl oleate failed to give any identity of the peaks a, b, and c, which appeared at a low Rt portion. It was determined through increase in the peak on addition of assumed substances that a is methyl aldehyde azelate (I), b is nonyl aldehyde (III), and c is the capronic aldehyde (V), a decomposition product of the ozonide of methyl linolate contained in the mixture. Similarly, the small peaks d, e, and f were respectively determined as methyl hydrogen azelate, nonylic acid, and caproic acid, the oxidation products of (I), (III), and (V). Stability of these substances was examined by the same method and it was found that methyl oleate and its ozonide are fairly stable at room temperature but that its decomposition product, aldehyde, is rapidly oxidized to the acid in air. These experimental results are thought to be of great help in elucidation of the mechanism for formation and decomposition of ozonides and deterioration of fats and oils.
Alkyl, aralkyl, and aryl derivatives substituted at the amide of undecylenamide were prepared and the effect of acid amide derivatives on increasing insecticidal activity of pyrethrin on fruit fly was examined. Among the 2-chloroisocaproic acid derivatives, those with 4-hydroxyphenyl, 4-hydrophenethyl, piperonyl, and vanillyl group had a strong effect. Majority of undecylenamides had fortifying effect, especially those with isopentyl, 2-methylpropyl, and cyclohexyl group, while the compound with 4-hydroxyphenyl group had no such activity.
Condensation of phthalaldehydic acid with nitromethane in alkaline state affords o-(2-nitrovinyl) benzoic acid in a good yield, Its reduction with phosphorus and hydriodic acid to form o-(2-aminovinyl) benzoic acid hydriodide and its treatment with alkali and hydrochloric acid gave isocarbostyril in 70% yield. After reduction of o-(2-nitrovinyl) benzoic acid with stannous chloride and hydrochloric acid, treatment of the reduction product with hydrochloric acid also afforded isocarbostyril.
A compact apparatus for catalytic hydrogenation, in which the reaction flask and gas burette are combined and easily mounted on usual magnetic stirrer, is described. When in use, the reaction mixture is placed in the reaction flask. combined with a gas burette of a suitable volume, and clamped to a magnetic stirrer. The water level in the burette is raised to almost the upper end and hydrogen is introduced from the cock S1 or S3, indicated in Figs. 1 and 2, to exchange the air inside the apparatus with hydrogen. The cock S2 or S4 is then closed, water level in the burette is lowered, the cock S1 or S3 is closed, and the reaction is started. When the Adams platinum is used, the sample is placed in a glass basket and hung on the hook at the lower end of the hydrogen-inlet tube. After hydrogenation over platinum oxide is completed, the apparatus as a whole is tilted 45°, and the basket is dropped into the reaction solution. This apparatus is simple, exchange of the air with hydrogen is easy, and the procedure is stable since there is no escape of hydrogen. A more accurate determination can be made by immersion of the reaction flask in a beaker filled with water at room temperature.
Application of alkaline hydrogen peroxide to sodium 2-cyanoethanesulfonate, obtained by reaction of acrylonitrile and sodium hydrogensulfite, afforded sodium 2-carbamoylethanesulfonate. Taurine (2-aminoethanesulfonic acid) was obtained in a comparatively good yield of 80-85% by reaction of the foregoing sulfonate and alkaline sodium hypochlorite.
Heterogeneous ion exchanger membranes were prepared and permeability of organic acids and bases, and alkaloids by eectrodialysis across the membrane was examined. Electrodialysis was carried out with a cell consisting of 3-4 compartments, each compartment being 7×8.5×5cm. in size, and platinum electrodes of 4×1.5cm. in size, at ca. 30V. Oxalate ion disappeared from 0.1N oxalic acid solution after 10 hours and from 0.1N sodium oxalate solution after 3 hours. Citrate ion also showed similar behavior. Permeation of aniline, caffeine, berberine, ephedrine, and nicotine through the membrane was confirmed. Electrodialyses of the aqueous extracts of coptis, tobacco, cinchona, scopolia, and areca also proved the permeability of their alkaloids.
The aporphine-type phenolic quaternary base, magnoflorine iodide (corytuberine methiodide) (I), when heated with ethanolamine at 160-170° for 15-30 minutes in an oil bath, undergoes cleavage of its tetrahydroisoquinoline ring to form the tertiary methine-type base (III). The same reaction of menisperine iodide (isocorydine methiodide) (II) results in ring-cleavage accompanied, with demethylation of the methoxyl in 1-position of the aporphine ring and the same base (III) is formed.
Considerable amount of hinokiflavone was obtained from the leaves of Cryptomeria japonica. This means that hinokiflavone is contained in the plants of all genera belonging to only two families, Taxodiaceae and Cupressaceae, without exception.
Plans were made for the synthesis of dinitrothianthrene. Condensation of 2-chloro-5-nitrobenzenesulfinic acid and nitrobenzenethiol afforded 2-(nitrophenylthio)-5-nitrobenzenesulfinic acids and their cyclization with conc. sulfuric acid gave 2, 8-, 1, 7-, and 2, 7(or 1, 8)-dinitrothianthrene. Their oxidation produced 1, 7- and 2, 8-dinitrothianthrene 5, 5, 10, 10-tetroxides. Reduction of the nitro group afforded 2, 8-diacetamidothianthrene and its 5, 5, 10, 10-tetroxide, and 2, 8-diaminothianthrene 5, 5, 10, 10-tetroxide.
Diazotization reaction of 3, 7-diaminodibenzothiophene 5, 5-dioxide was examined and 3, 7-diiodo- and 3, 7-dithiocyanato-dibenzothiophene 5, 5-dioxide were prapared. Several bis-azo dyes were synthesized by diazotization of 3, 7-diaminodibenzothiophene 5, 5-dioxide followed by coupling with 21 kinds of compounds of the phenol, amine, and sulfonic acid series as the β-component.
Analytical properties of 3, 7-diaminodibenzothiophene 5, 5-dioxide was examined and it was found that it is a promising reagent for the detection of NO2-, but inferior than benzidine for the detection of Pb, Mn, Co, Cr, and Cu ions.
Two methods were devised for comparing flow properties of powdered medicinals of poor fluidity. First method, indicated in Fig. 1, consists of a glass cylinder filled with the powder to a definite volume and the cylinder is allowed to roll over a slanted surface, fluidity of the powder being indicated by the area over which the powder spreads. The second method is for the powder whose angle of repose cannot be measured by the usual method due to poor fluidity. Glass beads (0.08mm. in diameter) are added to such a powder and nominal angle of repose is calculated by extrapolation by varying the volume percentage of glass beads, as shown in Fig. 3. As will be described in the following paper, the fluidity of powders measured by the above two methods seemed to have correlation with the flow property found by sensory test.