2-Phenylcinchonic acid hydrazide (I), m.p. 227°, and p-aminosalicylic acid hydrazide (II), m.p. 199-200°, were prepared by the method of Curtius and Struve, and their toxicity, LD50, against mice, in vitro antibacterial action against human type Aoyama strain tubercle bacilli and non-pathogenic acid-fast bacteria No. 920 were tested in Proskauer and Beck modified medium (10% bovine serum added). (I) was able to inhibit the growth of Aoyama strain at 1000γ/cc. concentration in a 4-weeks test but possessed no antibacterial power against No. 920 strain. LD50 by subcutaneous injection in mouse was found to be 12mg./10g., the toxic symptoms being sedation, difficulty of walking, drowsiness, convulsion of the limbs, difficulty of breathing, and respiratory paralysis. LD50 of (II) by subcutaneous injection in mouse was 1.5mg./10g., the toxic symptoms being excitement, unrest, paralysis of hindlimbs, difficulty of breathing, spasm, and respiratory paralysis. (II) was able to inhibit growth, of Aoyama strain at 10γ/cc. concentration, and in 1000γ/cc. concentration against acid-fast bacteria No. 920 in a 4-week test.
2-β-Acetylhydrazinothiazoles were prepared by the application of α-haloketones to 1-acetylthiosemicarbazide and the hydrolysis of the thiazoles thereby obtained with diluted hydrochloric acid gave several kinds of 2-hydrazinothiazoles. However, the corresponding 2-hydrazino compound could not be isolated from 2-β-acetylhydrazino-4-methylthiazole, and the evaporation of the hydrolyzed solution under a diminished pressure to dryness afforded 2-amino-5-methyl-1, 3, 4-thiadiazine hydrochloride in a good yield. These compound were prepared in order to test their activities against tubercle bacilli.
Growth inhibition of Micrococcus pyogenes var. aureus was tested in 73 kinds of compounds of which the following were able to inhibit growth in 80, 000 dilutions: Isobutyl β-orcinolcarboxylate, butyl 3, 6-dimethyl-5-aldehyde-2, 4-dihydroxybenzoate, ethyl olivetolcarboxylate, isopropyl olivetolcarboxylate, methyl olivetonate, and olivetonide. Propyl olivetolcarboxylate was especially effective, having inhibited growth in 320, 000 dilution. Isobutyl β-orcinolcarboxylate and olivetonide inhibited growth of Bacillus subtilis in 80, 000 dilutions. All these compounds possessed only a weak growth inhibitory action against Escherichia coli communior.
1) Potency determination of antispasmodics was efficiently made by improving the apparatus so as to make it possible to record simultaneously eight tracings of small intestinal movements on one smoked paper. 2) Antispasmodic potencies of diphenylalkanolamines synthesized were examined with atropine sulfate and papaverine hydrochloride as standards. Results are given in Table I.
By the use of the improved apparatus, the usual method was examined statistically with the following results: 1) When intestinal specimens obtained from the same animal on the same day were used in four different baths, the values obtained corresponded within experimental error. 2) The largest reason for the extreme variation of potency ratio by the usual method is assumed to be the difference in animals used. 3) The potency of 3-piperidino-1, 1-diphenylbutanol hydrochloride obtained by the application of Bliss-Finney method was 33.5% of that of atropine sulfate, and its confidence interval (level of significance 5%) was 14.9-52.3%.
1) Fusion of O-benzoyl-p-aminophenol results in the isolation of the rearrangement product, N-benzoyl-p-aminophenol, and a rearrangement intermediate, O, N-dibenzoyl-p-aminophenol. Such intramolecular substitutions are reported. 2) Fusion of a mixture of O-benzoyl-p-hydroxybenzenesulfonamide and alkali carbonate also results in the isolation of the rearrangement product, N-benzoyl-p-hydroxy-benzenesulfonamide, and a rearrangement intermediate, O, N-dibenzoyl-p-hydroxybenzenesulfonamide. This intramolecular substitution is also explained.
Catalase acion of iron salt solutions at a constant temperature of 25° and at varied pH ranges was studied and it was found that the curve of pH and catalatic activity showed a maximum and minimum points. At pH 1.8, the intensity of catalase activity were the same for the ferric and ferrous ions at concentrations below 10-3g. ion, whereas they were different above this concentration, the intensity of catalase activity being stronger in the ferrous than in the ferric ions. As a result, it was seen that by making a standard curve of ion concentration and catalase activity at pH 1.8 and a constant temperature, the cause of catalase activity of mineral springs could be found by comparison with such curves.
Catalase activity of iron salt solution was examined as to the addition of Mn++, an important catalyst in mineral springs, and of Cu++, co-catalase pointed out by the present authors. It was found, however, that the catalase action of Mn++ is independent of iron salts whereas Cu++ acts as a co-catalase to iron ion, and shows the maximum in the curve between log Cu++ and activity ratio. It was also found that there was an approximately definite relationship between the concentration of Cu++ and Fe+++, but not necessarily between Cu++ and Fe++. Vanadate ion was also found to show co-catalase activity against iron salts at around 10-2g. ion, Cu++ also shows co-catalase activity against sodium ferric-phthalocyanine-tetrasulfonate but its excess tend to inhibit the activity. Iron bipyridyl complex delays the catalase action of iron salts but such action is rapidly recovered when the bipyridyl comlex begins to decompose.
Twenty-eight kinds of methyl, methoxy, and hydroxy derivatives of coumarin were prepared and the variation in their anthelmintic action by the kinds, position, and number of the substituents present was examined. Physiological action was observed in a glass tube filled with 2, 000 dilutions of coumarin derivatives in revised Locke's solution at 38°. The results obtained were as follows: 1) The order of potency due to different kinds of substituents was methyl>methoxy->hydroxy-coumarin. 2) The potency decrease by different position of the substituents was parallel in methyl-and methoxy-coumarins but not parallel in hydroxycoumarins. 3) The potency decreased when methyl was introduced in 4-position or when two or more hydroxyl or methoxyl groups were introduced. 4) 7-Methyl- and 3-methyl-coumarins were especially powerful, Ascaris suilla dying within 20-30minutes. Pointing to the similarity in the structures of 3-methylcoumarin and santonin, importance of the methyl group attached to the carbon atom neighboring the carbonyl group of the lactone ring was proposed. 5) It was pointed out that potent compounds were found among those with melting points below 130°.
With the increase of vitamin A unit as the objective, primary hot saponification and secondary cold saponification were carried out in hydrogen stream on cod liver oil from tuna (Thynnus orientalis) of 100, 000 I.U. of vitamin A1, in accordance with the method of saponification of quantitative determination. As a result, high unit of 700, 000 I.U. and 1, 600, 000 I.U., respectively, was obtained. Esterification of the unsaponifiable matter from these two was reëxamined and it was found that the purified secondary unsaponifiable substance invariably yielded a phosphate by phosphoryl chloride when submitted to dehydrochloride catalysis with pyridine. Spectral analysis shows that the absorption maximum of the purified phosphate was in the range of 300mμ.
Typical receptum that calls most rational the low temperature, short-period synthesis of phosphatization of the unsaponifiable substance from cod liver oil, i. e. application of phosphoryl chloride with anhydrous pyridine as the catalyst, was reëxamined literally and experimentally from the point of view of the so-called productive optimum function by analysis from two functional points. Ratio of affinity and reaction velocity were reëxamined and, in order to study the activation energy necessary and sufficient for monoesterification, the temperature variation from the beginning to the latter part of the synthetic reaction was followed. As a result, it was found that, under the optimum conditions, good results could be obtained by beginning the reaction at -10° and majority of the reaction concluded around 0°C. It was also confirmed that the most rationalized method would be to utilize the initial generation of heat as the activation energy needed for the last half of the reaction. It was found that the productional function was limited by the amount of the initial material used and it was concluded that sigmated productive units of plant for the unit of optimum quantity for esterification was necessary.
1) Content of vitamin A in raw liver oil used as standard for vitamin A assay, in the phosphate of unsaponifiable matter, and in vitamin A preparations were determined physicochemically from which it was found that (i) vitamin A is easily autoxidized in an aqueous solution, (ii) phosphate showed no measurable change before and after saponification, and (iii) preparations should be subjected to preliminary purification treatment by saponification. 2) Simple and complex parenteral solutions were prepared and their stability were examined from which complex solution was found to be stable provided that the ampule is sealed enitrely without oxygen, and glycerol or glucose are used for isotonic preparation. Tablet forms should be given some preventive method for oxidation, but oral drops and chocolate coated pills were found to physically prevent oxidation. 3) It was found that for stabilization, it was necessary to exclude air during granulation of tablet preparations. It was also found that (i) mixing with hydrated substances accelerated oxidation, (ii) caseine and gelatine gave some degree of protection but emulsification and drying should be made in nitrogen or carbon dioxide stream, (iii) mixing with succrose powder is disadvantageous, and that (iv) internal cleavage due to weathering decreases protection against periodical change. Its prevention could be effected by the use of cetanol or cacao butter, or by the addition of a small amount of raw liver oil.
Burden assays were carried out on the sodium and calcium salts of vitamin A phosphate and it was found that these were excreted into urine during saturation of vitamin A, 1 hour after subcutaneous injection of the sodium salt and within 3 hours of the oral administration of the calcium salt. The substance excreted was confirmed to be the partially oxidized substance of the phosphate. However, further examination would be necessary to determine whether all the vitamin A compounds are excreted into urine in a similar form. Comparative examination with other vitamin A preparations showed that the phosphate form gives a more rapid and reliable effects and would be valuable for the diagnosis of vitamine A deficiency.
Aminovinyl compounds were prepared by the application of orthoformate and p-toluidine or m-aminophenol on α-picoline methiodide, 2, 6-lutidine methiodide, quinaldine methiodide, ethiodide, and 2-methylbenzothiazole ethiodide. The ethiodides of quinaldine and 2-methylbenzothiazole easily reacted with orthoformate and p-aminoacetophenone or p-aminosalicylic acid to form corresponding aminovinyl compounds. 2-Amino-4-methylthiazole, 2-acetamino-5-aminothiazole, and 2-amino-4-methyl-6-hydroxypyrimidine failed to yield aminovinyl compounds on reacting dye parent compounds and orthoformate, only forming carbocyanines.
Carbocyanine dyes were formed by the application of orthoformate and oximes or semicarbazide to the parent compound of a few dyes. Application of orthoformate and N-ethylphenylhydrazine or phenylhydrazine to the methiodide and ethiodide of quinaldine gave N-ethylphenylhydrazinovinyl and anilinovinyl compounds. Application of orthoformate and N, N′-diphenylhydrazine or N, N′-ditolylhydrazine to quinaldine methiodide, quinaldine ethiodide, and 2-methylbenzothiazole ethiodide respectively yielded N, N′-diarylhydrazinodivinyl compounds.
Corresponding merocarbocyanine dyes were obtained by the respective application of 3-phenyloxazolone-5, 3-ethylrhodanine, 3-phenylrhodanine, 1-methyl-3-phenylpyrazolone, or 3-hydroxythionaphthenone to 2, 2′-ω, ω′-(N, N′-diphenylhydrazino)-divinylquinoline dimethiodide and diethiodide, and 2, 2′-ω, ω′-(N, N′-ditolylhydrazino)-divinylbenzothiazole diethiodide.
Several kinds of pyrimidylhydrazines and their derivatives, and pyrimidine-carboxylic acid hydrazides were prepared and their growth inhibition, in vitro, of H37 Rv strain of tubercle bacilli was tested. However, there were no compounds that showed any noticeable results.
Several kinds of hydrazinopyridines, hydrazinopyrimidines, hydrazinothiazoles, and their derivatives were prepared and their growth inhibition, in vitro, of H37 Rv strain of tubercle bacilli was tested. Some effect was seen in isonicotinylhydrazones and 2-β-acetylhydrazinothiazoles.
Crude fatty acids, in an approximate yield of 11%, were obtained from the fruits of Angelica polyclada Franch. Derivation of the acids to methyl ester and its fractional distillation at 3mm-. pressure yielded three fractions, (A), (B), and (C) (cf. Table I). Each fraction was separated into solid and liquid acids by the lead salt method by which palmitic acid, m. p. 61-62°, was obtained from (A) fraction, crystals of m. p. 28-53° from (B) fraction, and crystals of m. p. 32-33° from (C) fraction as solid acids. 9, 10, 12, 13-Tetrahydroxystearic acid was obtained as the liquid acid from both the (B) and (C) fractions as the oxidation product by the Hazula method, from which it can be seen that linolic acid is present in the fruit. As the method of separatory estimation of petroselic, petroselidic, palmitic, oleic, and linolic acids that constitute the fatty acids obtained from the fruit oil of the Umbellifera family, chromatography employing circular filter paper was devised (cf. Table II). Utilizing this method, the crystals of m. p. 28-53° were found to be a mixture of palmitic and petroselic acids and those of m. p. 32-33° were petroselic acid with a trace of petroselidic acid. From these experimental results, it was confirmed that the acids constituting the fruit oil of Angelica polyclada were petroselic, petroselidic (trace), palmitic, and linolic acids.
Crude fatty acids, in an approximate yield of 18%, were obtained from the fruit of Phellopterus littoralis Benth. Derivation of the acids to the methyl ester and its fractional distillation at 3-mm. pressure gave two fractions, (A) and (B). The two fractions were respectively separated into solid and liquid acids by the lead salt method. As a solid acid, palmitic acid, m. p. 60-61°, was obtained from (A) fraction, and crystals of m. p. 27.5-28.5° from (B) fraction. As a result of estimation by the circular paper chromatography (cf. preceding paper) and elaidination, the latter crystals were found to be a mixture of petroselic and petroselidic acids. As a liquid acid, 9, 10, 12, 13-tetrahy-droxystearic acid was obtained as the oxidation product of the Hazula method from both the (A) and (B) fractions from which the presence of linolic acid in the fruit oil was clarified. The fatty acids constituting this fruit oil were confirmed to be petroselic, petroselidic, palmitic, and linolic acids.
Crude fatty acids, in an approximate yield of 12%, were obtained from the fruit of Heracleum nipponicum Kitagawa. Derivation of the acids to methyl ester and its fractional distillation under 3-mm. pressure gave three fractions, (A), (B), and (C). No acid substance was obtained from (A) fraction. (B) and (C) fractions were respectively separated into solid and liquid acids. As a solid acid, palmitic acid, m.p. 60-61°, was obtained from (B) fraction, and crystals of m.p. 25-28° from (C) fraction. Estimation by the circular paper chromatography and elaidination showed these crystals to be a mixture of petroselic and petroselidic acids. As a liquid acid, 9, 10-dihydroxy- and 9, 10, 12, 13-tetrahydroxystearic acids were obtained as the oxidation product by the Hazula method from (B) and (C) fractions from which the presence of oleic and linolic acids was clarified. Foregoing results have confirmed that the fatty acids constituting the fruit oil of this plant were petroselic, petroselidic, palmitic, oleic, and linolic acids.
Crude fatty acids, in an approximate yield of 15.6%, were obtained from the fruit of Ligusticum acutilobum Sieb. et Zucc. Derivation of the acids to methyl ester and its fractional distillation under 3-mm. pressure gave four fractions, (A), (B), (C), and (D). Fraction (A) failed to yield any acid substance. The remaining three fractions were resepctively separated into solid and liquid acids by the lead salt method. As a solid acid, palmitic acid, m.p. 60-61°, was obtained from (B) fraction, and crystals of m.p. 24-25° from (D) fraction. (C) Fraction failed to yield any solid acid. The crystals from (D) fraction were estimated by the circular paper chromatography, by elaidination, and by oxidation by the Hazula method, and were found to be a mixture of petroselic and petroselidic acids. As a liquid acid, 9, 10-dihydroxy- and 9, 10, 12, 13-tetrahydroxy-stearic acids were obtained as the oxidation product by the Hazula method from (B), (C), and (D) fractions from which the presence of oleic and linolic acids was clarified. Foregoing results confirmed that the fatty acids constituting this fruit oil were petroselic, petroselidic, palmitic, oleic, and linolic acids.
Removal of pyrogen from parenteral solutions was experimentally examined by the ordinary purification method on the degree of pyrogen removal. In this case, the coloration tests was made with TBP reagent which is said to indicate proportional relationship between pyrogen and febrifuge in rabbits. Market product of glucose injection, having positive TBP reaction was recrystallized, treated with various absorbents, oxidative agents, or reducive agents. Fungal culture filtrate, containing pyrogen, was also treated with anion and cation exchange resins and conc. hydrochloric acid. Degree of coloration with TBP reagent was examined on each sample before and after treatments. Experimental results have shown that recrystallization and treatment with oxidation agent were able to decrease substance that gave positive TBP reaction (pyrogen), but not to make it entirely negative. Treatment with ion exchange resins and reductive treatment were found to be practically ineffective.
Treatment with various chemicals was made for the removal of substances giving positive TBP reaction (pyrogen×) and it was found that series of quinone compounds, such as p-quinone, toluquinone, p-xyloquinone, α-naphthoquinone, anthraquinone, and chloranil, wereextremely effective. Quinone treatment of marketed unsuitable glucose injections and fungal culture filtrate, containing pyrogen, was found to be clearly effective in removing pyrogen, confirmed by the decrease of pyrogen both by TBP reaction and animal tests, which coincided.
Fatty oil was obtained in 14.9% yield from the seeds of Ligustrum japonicum Thunb. (Oleaceae) by extraction with ether. The fatty acids obtained were separated into saturated acids (19.5%), composed of palmitic and stearic acids, and unsaturated acids (80.5%) by Twitchell's method. The unsaturated acids were chiefly composed of oleic acid and 11.5% of linoleic acid. Linolenic acid was not found. By the extraction of the seeds with methanol, the presence of glucose (as glucosazone) and mannitol (as tribenzal derivative) was comfirmed. From the ethereal extract of pericarp, crude triterpenoid (1.4%) was obtained and from which oleanolic acid was isolated. Pericarp contains a tolerable amouns of glucose. The amount of reducing sugar (as glucose) of epicarp, pulp, and seed average 22.5%, 40.85%, and 15.5%, respectively.
Heating of 2-[2′-methyl-4′-aminopyrimidyl-(5′)]-methyl-formamino-5-hydroxy-Δ2-pentenyl-(3) alkyl disulfide (vitamin B1 alkyl disulfide) (I) in cyclohexanol results in its decomposition to thiochrome (III) and 3-[2′-methyl-4′-methylpyrimidyl-(5′)]-methyl-4-methyl-5-β-hydroxyethylthiazole-3-thione (SB1) (IV). Heating of vitamin B1 disulfide (II) in ethylene glycol results in its decomposition to (III) and 3-[2′-methyl-4′-methyl-pyrimidyl-(5′)]-methyl-4-methyl-5-β-hydroxyethylthiazol-2-one (vitamin B1-thiazolone) (V), with a minute amount of (IV) as a by-product which was confirmed by the paper partition chromatography. Heating of (I) in alkaline medium results in the formation of vitamin B1 (VI), (II), (III), (IV), and (V), while the similar heating of (II) yields (VI), (III) (IV), and (V). These components were all proved by the paper partition chromatography. Heating of (I) with hydrochloric acid results in its decomposition into formic acid, 2-methyl-4-amino-5-aminomethylpyrimidine, (VII), and α-aceto-γ-hydroxypropyl alkyl disulfide.
Determination of infrared absorption spectra have shown together with few other facts that the compounds previously reported as α-aceto-γ-hydroxy (or acetoxy, benzoxy)-propyl N-[2-methyl-4-aminopyrimidyl-(5)]-methyldithiocarbamate (IVa, IVd, IVe) or α-aceto-γ-[2-methyl-3-chlorotetrahydrofuryl-(2)]-oxypropyl N-[2′-methyl-4′-aminopyrimidyl-(5′)]-methyldithiocarbamate (IVf) should actually be 2-methyl-2-hydroxy (or acetoxy, benzoxy) tetrahydrofuryl-(3) N-[2-methyl-4-aminopyrimidyl-(5)]-methyldithiocarbamate (Va, Vd, Ve) or 2-methyl-2-[α-methyl-β-chlorotetrahydrofuryl-(α)-oxy]-tetrahydrofuryl-(3) N-[2′-methyl-4′-aminopyrimidyl-(5′)]-methyldithiocarbamate (Vf). It is assumed that, during the formation of these compounds, (IVa, IVd, IVe) or (IVf) is formed as an intermediate which undergo cyclizational rearrangement due to instability and transit to (Va, Vd, Ve) or (Vf). Formation of (V) and formation of thiothiazolone from (V) were explained by the aniotropy, and the formation of (X) from (IX) by prototropy.
Respective condensation of ethylene bromohydrin (VI) with the sodium salts of acetylacetone (Va), propionylacetone (Vb), and benzoylacetone (Vc) results in the formation of γ-acetopropyl acetate (IIIa), γ-acetopropyl propionate (IIIb), and γ-benzoylpropyl acetate (IIIc). It is assumed that γ-diacetopropyl alcohol (IIa), γ-propionyl-γ-acetopropyl alcohol (IIb), and γ-benzoyl-γ-acetopropyl alcohol (IIc) primarily formed as intermediates are extremely unstable and immediately undergo rearrangement to transit to (IIIa), (IIIb), and (IIIc), in which acyl radical with small +E effect migrates and the radical with large effect remains. This shows that the rearrangement efficiency is reverse of the +E effect, i.e. C2H5CO>CH3CO>C6H5CO. (IIIc) was treated with sulfuryl chloride to γ-benzoyl-γ-chloropropyl acetate (VIc) which was prepared, by the previously reported method, into 2-phenyl-2-acetoxytetrahydrofuryl-(3) N-[2-methyl-4-aminopyrimidyl-(5)]-methyldithiocarbamate (VIIIc), N-[2′-methyl-4′-aminopyrimidyl-(5′)]-methyl-4-phenyl-5-β-hydroxyethylthiothiazolone-(2) (IXb), and N-[2′-methyl-4′-aminopyrimidyl-(5′)]-methyl-4-phenyl-5-β-hydroxyethylthiazolium chloride hydrochloride (XI).
It has been found that 2-nitramino-4-methyl-6-hydroxypyrimidine (IV) and 2-hydrazino-4-methyl-6-hydroxypyrimidine (I) which Shiho and others claimed to have synthesized are actually 2-amino-4-methyl-5-nitro-6-hydroxypyrimidine (V) and 2, 5-diamino-4-methyl-6-hydroxypyrimidine (VI), respectively. (IV) was synthesized by the present author and (I) was obtained by the application of hydrazine hydrate to (IV). (I) was found to be identical with the specimen obtained by the authors by another method and its identity was confirmed by various reactions.
2-Hydrazino-4-methylpyrimidine (I) prepared by Shiho, et al. and by the present authors differed in their respective melting points. The one prepared by the author gave 4-methylpyrimidine (X) by copper sulfate, 2-hydroxy-4-methylpyrimidine (XI) by oxidation with KMnO4, and hydrazine and (XI) by hydrolysis with hydrochloric acid so that this compound could not be other than (I).
Application of benzaldehyde to 2, 5-diamino-4-methyl-6-hydroxypyrimidine (II) results in condensation, not at 2-amino group but at 5-amino group, to form 2-amino-4-methyl-5-benzylideneamino-6-hydroxypyrimidine (III). The fact that the reaction product of (II) and benzoyl chloride is 2-amino-4-methyl-5-benzoylamino-6-hydroxypyrimidine (IX) was confirmed by the synthesis of the latter by another method.
A small crucible (ca. 35mm. diameter, ca. 22mm. high) in which 50-100mg. of crude powdered drug is placed is covered with filter paper wetted with water, and placed in a metal bath (or air bath) of about 220° for 5 minutes. On the filter paper, on which the sublimate from the crude drug is attached, is dropped aqueous solution of 5% potassium hydroxide by which bright carmine to violet coloration occurs if anthraquinone is present in the crude drug. This method can be utilized for all crude drugs containing anthraquinones.
By the Fischer method (glacial AcOH+conc. HCl or ZnCl2 in EtOH) methyl propyl ketone phenylhydrazone gave exclusively 2-methyl-3-ethylindole which gives a strong magenta coloration by the Ehrlich reagent and formed a picrate of brown red crystals, m.p. 150-150.5°. 2-Propylindole, prepared from butyroyl-o-toluidide by the Madelung-Verley reaction, gives reddish purple coloration by the Ehrlich reagent, quite different from the foregoing compounds. The latter forms a picrate of orange red crystals, m.p. 148-149°, which melted at about 130° when admixed with the above picrate.
Price and his collaborators reported that 2-amino-4-methyl-5-carbethoxypyrimidine (I) does not give the corresponding hydrazide by hydrazine hydrate but it was found that if the above ester (I) is heated with a large excess of hydrazine hydrate, or if hydrazine hydrate is reacted in purified pyridine or purified tetraline as solvent, the objective 2-amino-4-methylpyrimidine-5-carboxylic acid hydrazide (II) is obtained with a good yield. (II) was found to be devoid of antitubercular action in vitro.
The synthesis of 3-dimethylamino-1, 1-di(2′-thienyl)-butene-1 by the Adamson method gives a poor yield due to the formation of a resinous substance during the dehydration process. Various examinations have revealed that if the condensation product of thiophene and ethyl β-dimethylaminobutyrate, without isolation, is treated with conc. hydrochloric acid at 95-100° for 15minutes, the objective is obtained in 61% yield.
As a substance that heightens the cardiotonic and diuretic action of Senso, the Chinese crude drug of toad excretions, a free amino acid, arginine, is present in Senso. As a protein hydrolyzate, aspartic acid and leucine were detected as the amino acid.
Polarographic studies of meconic acid indicated the presence of an ideal reductive wave in a buffer solution of pH 1-4, containing 0.1 N potassium chloride. This was utilized for the determination of meconic acid in opium and good results were obtained. The effect of the co-presence of meconic acid during polarographic determination of morphine was also examined.
Polarographic studies of the sweetenings of m-nitraniline series indicated the presence of an ideal reductive wave in a buffer solution of pH 5, containing 0.1 N potassium chloride. Qualitative estimation of a series of these compounds by dissociation index was also attempted and this method was used for the determination and estimation of the sweetenings of m-nitraniline series.
Various conditions regarding hydrolysis of diacetylmorphine were examined and good results were obtained with attempted quantitatine determination of diacetylmorphine. To 1cc. of 10-2-10-4 molar solution of diacetylmorphine hydrochloride, 1cc. of 20% sulfuric acid is added, boiled on a boiling water bath for 10 minutes to effect hydrolysis, and morphine determined by the methods described in the previous report.
Polarographic analysis was utilized for the determination of sulfur compounds in mineral water, for the sake of speeding and simplifying the analysis. 1) SO4-- strong alkali→ Fe(OH)3ppt. pH3-5→Pb(NO3)2 PbSO4 3N AcONH4→Pb++→Polarography 2) S, S2O3--, H2S, etc. Br→NaOH SO4-- → (Same as above) → Polarography 3) H2S (AcO)2Cd→acidity CdS 3N HCl→ H2S↑ Cd++ → Polarography 4) S2O3-- 1% CuSO4→H2SO4(acid) CuS hot→HNO3 Evaporation to dryness → Cu++ → Polarography
A dried legume of Gleditschia horrida Makino (Leguminosae) is known to contain saponin but no studies have been made as to its non-saponifiable matter. Experiments by the present author resulted in isolation of various substances. Oil of Gleditschia horrida is a wax-like substance of dark greenish color, obtained in 1.2% yield. It gives an acid value of 127.6, saponification value of 228.8, iodine value of 87.9, contains 0.7% of sterol (by digitonin method) and 64.8% of non-saponifiable mater. The latter yielded ceryl alcohol, m.p. 78°, nonacosane, m.p. 63-64°, stigmasterol, sitosterol, and a structurally unknown sterol of m.p. 158-159°. Besides the foregoing, minute amount of substances assumed to be sitostene, heptacosane, and terpene-like matter were isoleted. Majority of the solid non-saponifiable matter were ceryl alcohol and nonacosane.