d-Sesamin and Paulownin, colorless crystals, C20H18O7⋅CH3OH, m. p. 84°, were isolated from the wood of Paulownia tomentosa STEUD. Paulownin afforded protocatechuic acid by alkali fusion, piperonylic acid by potassium permanganate oxidation, and 1, 2-methylenedioxy-4, 5-dinitrobenzene and oxalic acid by nitric acid oxidation. The above facts and UV, IR and NMR spectra suggest that paulownin could be formulated as II.
Leaf wax of Hinoki (Chamaecyparis obtusa ENDL.) was saponified, alkanes alone were extracted from its neutral component, and submitted to low-pressure distillation. Its distillate of a mixture of comparatively lower alkanes was submitted to gas chromatography and 11 kinds of alkane were detected. Six of these were found to be n-pentadecane, n-hexadecane, n-heptadecane, n-octadecane, n-nonadecane, and n-eicosan, and remaining five were assumed to be isoalkanes.
Sodium N-cyclohexylsulfamate (Sodium Cyclamate) forms cyclohexylamine by hydrolysis with hydrochloric acid with addition of hydrogen peroxide and the product colors with quinhydrone. The coloration differs according to whether an aqueous solution or organic solvent was used in the reaction. This was utilized in devising methods A and B for colorimetric determination of sodium N-cyclohexylsulfamate according to its concentration. Method A: Hydrogen peroxide solution and hydrochloric acid are added to the test solution (containing 1-10mg./ml.), the mixture is heated in a boiling water bath for 2 hours, cooled, and neutralized with sodium hydroxide. Hydrogen peroxide is decomposed with an excess of manganese dioxide, the mixture is centrifuged, and the supernatant is adjusted to pH 9.0 with a buffer solution. Quinhydrone reagent is added to it, the mixure is warmed, acidified with acetic acid, and extracted with chloroform. The absorbancy of this extract solution is read at 355mμ. Method B: Hydrogen peroxide solution and hydrochloric acid are added to the test solution (containing 50-600γ/ml.), the mixture is heated in a boiling water bath for 1.5 hours, cooled, and neutralized with sodium hydroxide. This is adjusted to pH 12.0 with a buffer solution and extracted with chloroform. Ethanol and quinhydrone reagent are added to the extract solution, the mixture is warmed, and its absorbancy is read at 495mμ.
In order to use the colorimetric methods A and B for the determination of sodium N-cyclohexylsulfamate (sodium cyclamate) for various foodstuffs, effect of coexisting substances to be found in the food was examined. Dulcin, putrefying amines, and some of artificial coloring matter were found to interfere in this determination but they could be removed by preliminary treatment with ion-exchange resin or by solvent extraction. These determination methods were applied to liquid, semi-solid, and solid foodstuffs and a good result was obtained with the exception of a few.
Thiazolidinecarboxylic acid derivatives were synthesized as the agents against radiation injury. Their protective and restorative effects were examined by the mortality of mice exposed to the lethal dose of X-ray. Of these derivatives, Nos. 11 and 13 were found to be protective and restorative, Nos. 1 and 16 protective, and No. 4 restorative. Nos. 4, 11, and 13 had no restorative effect on the hematologic injury of rats caused by X-ray irradiation. These substances protected the mice injected with otherwise lethal dose of sodium arsenite from death and diminished protectively the necrosis of liver caused by carbon tetrachloride.
General pharmacological activities were examined with coumarin (A-1) and five kinds of coumarin derivatives, 4-methylcoumarin (A-3), 2-thiocoumarin (B-1), 6-aminocoumarin hydrochloride (E-2), 6-aminocoumarin coumarin-3-carboxylic acid salt (G-22), and 6-chlorocoumarin (J-2). Acute toxicity (LD50) by oral administration decreased in the order of G-22, A-1, J-2, E-2, B-1, and A-3, and the order of A-1 and J-2 was reveresed by subcutaneous injection. Of various central effects, antipyretic action was the strongest and some of them, notably A-3, B-1, E-2, and J-2, also showed hypnotic action but none of them showed any significant analgesic or antipmetic action. Majority of these compounds showed inhibitive action on the cardiovascularr system, as well as hypotensive and adrenolytic actions. G-22 had a comparatively strong hemolytic, anticoagulant, and erythrocytopenic actions. These compounds did not have any local anesthetic, mydriatic, spasmolytic, or antihistamine actions.
Many kinds of amino derivatives of [2-(5-nitro-2-furyl)vinyl]quinoline compounds were prepared and their chemical properties were examined. Application of these compounds as a chemotherapeutic was also examined and the following new watersoluble nitrofuran derivatives were obtained: 2-Amino-4-[2-(5-nitro-2-furyl)vinyl]-quinoline lactate (I), 4-amino-2-[2-(5-nitro-2-furyl)vinyl]quinoline lactate (II), and 4, 6-diamino-2-[2-(5-nitro-2-furyl)vinyl]quinoline hydrochloride. Of these, II is structurally similar to Acrinol, known as the penetrating antiseptic, and the antibacterial action of II is greater than that of Acrinol. This fact seems to suggest its practical use.
Aspect of phase inversion of an emulsified system of nonionic surfactant by temperature variation was examined by measuring electric resistance. For this purpose, some modifications were made on the apparatus reported previously (Fig. 1). Characteristic electric resistance-temperature curve (Fig. 2) is obtained from the values of electric resistance of the system corresponding to the temperature variation. The system undergoes phase inversion from O/W type to W/O type with the rise in temperature and the values of its electric resistance show gentle decrease (S1°) at first, then increase rapidly to the peak (G°), decrease again (S2°), and rapidly increase again. These results showed that the Winsor theory can be applied to the emulsified system of nonionic surfactant, as in the case of the solubilized system. It was also clarified that a linear relationship is established between the temperature of phase inversion and HLB value of nonionic surfactant in the emulsified system (Fig. 4). The HLB value of nonionic surfactant was shown to be easily measured from the measurement of electric resistance-temperature curve.
Aluminum stearates of various compositions were prepared and the structural viscosity of their benzene solutions was measured. Structural viscosity increased with the increase of St/Al ratio when the ratio was smaller than 2 and decreased when the ratio was greater than 2. Intrinsic viscosity [ηN], calculated from ηr(1/Q→0), had a maximum at the St/Al ratio a little smaller than 2 and then decreased abruptly with the decrease of St/Al ratio, and was nearly equal to zero when St/Al was smaller than 1.8. In the range of 2-2.4 of St/Al, ratio [ηN] was nearly constant and decreased abruptly to zero with the approach of St/Al ratio to 2.5. It has become clear that [ηN] did not depend on the lot of Al-St nor on the method of the extraction of free acid, but only on the composition of aluminum stearate. The value of k, calculated according to Staudinger's equation, (ln ηr)/c=[η]-k[η]2c(at 1/Q→O), remained nearly constant in the range of 1.9-2.5 of St/Al, and was highly different from that in other ranges. It has, therefore, been considered that the soaps whose St/Al ratio is 1.9-2.5 are different from the soaps of the other compositions in the degree of polymerization or in the structure of polymer.
Viscosity of aluminum stearate in benzene solution was measured for the specimens treated thermally under various conditions. When the disoap was heated at 110°, the viscosity of its solution increased with the weight loss of the soap, and when it was heated at 150° the viscosity initially increased and then decreased. When the monosoap was heated at a temperature higher than 110°, the viscosity of its solution decreased with the weight loss of the soap. Infrared absorption and X-ray diffraction of aluminum stearate were measured. The absorption band due to the Al-O linkage vanished in the infrared spectrum of the heated monosoap and the X-ray diffraction patterns of the disoap tended to that of monosoap with a thermal treatment. It was concluded that the structural change of St-Al-(OH)2 to St-Al=O occurs in the monosoap with heating. The molecular weight of disoap increases with heating at 110° because of the coordination of another disoap molecule to the position where the terminal molecule has been lost from the disoap molecule by the thermal treatment. At 150°, the chain of disoap is broken by the separation of one molecule of water from the two monomer units or one molecule of stearic acid from one monomer unit, resulting in the decrease of the molecular weight.
The volume fractions of each component in the dilute phase (υ′1, υ′2, υ′3) and concentrated phase (υ1″, υ2″, υ3″) were calculated according to Flory's and Scott's theoretical equations, in the ternary system, solvent, nonsolvent, and polymers, for the polymerization degree of 1000, 5320, and ∞. In these treatments it was assumed that P1=P2=1, P3>>1 for the polymerization degree Pi; and A=X13/P1=X31/P3=O, B=X12/P1=X21/P2=O, C=X32/P3=X23/P2≠O for the interaction parameters. For further calculation, two cases were considered; in one, volume of the solution is kept constant by overflow of the excess solution such as in turbidimetric titration, and in the other, the whole solution is kept in a large vessel, such as in the case of the fractionation of a polymer. For these two cases, the volume fraction of the condensed phase Φ, the quantity of the precipitated polymer Φv3″, the ratio of the quantity of the precipitated polymer to the total quantity of the polymers in the system Φυ3″/υ3 were calculated as functions of the relative volume of the nonsolvents added to the system (V/V0). These treatments were made under the conditions where the interaction parameter C was 2.27 and the initial concentration υ30 was 0.0125, 0.0100, 0.0075, 0.0050, and 0.0025. For each polymerization degree and each initial concentration, the volume of the nonsolvent, to be added to the system (V/V0)p before the precipitation starts, was also calculated.
Phenol is known to color red with xanthydrol in hydrochloric acetic acid solution and a method for the determination of phenol using this reaction was examined. In this method, 1ml. of xanthydrol reagent solution (120mg, of xanthydrol dissolved in glacial acetic acid, 30ml. of hydrochloric acid added, and the whole volume brought to 100ml. with glacial acetic acid) is added to 1ml. of glacial acetic acid solution of phenol (5-60γ/ml.), the mixture is heated on a water bath for 8 minutes, and diluted to 10ml. with glacial acetic acid. Absorbance of this solution is measured at 503mμ, with the blank test using glacial acetic acid in place of the test solution. Acetone may be used to dilute the reaction mixture. The calibration curve is a straight line passing the original point and the coefficient of variation is around 1.0-1.5%. This method of determination can be applied to that of o-cresol, pyrocatechol, and guaiacol by modifying the reaction time and the wave-length of the optical measurement.
As the mechanism for the color reaction between phenol and xanthydrol, formation of 9-(p-hydroxyphenyl)xanthylium salt (II), through the intermediate 9-(p-hydroxyphenyl)xanthene (I) was presumed and, in order to prove this reaction, II was synthesized by the known process and II was found to be identical with the pigment formed by the color reaction between phenol and xanthydrol. Measurement of the reaction rate showed that the formation of I followed the second-order reaction formula and the formation of II, in which I and xanthylium ion took part, followed the second-order reaction formula. Formation reaction of I was slower than that of II, so that the former is the rate determining step in the color reaction between phenol and xanthydrol. Decomposition of I, i.e. reverse reaction of the formation of I, also takes place but the rate is much slower than the formation reaction of I and II, and can therefore be neglected.
In the reaction of phenol and xanthydrol in hydrochloric-acetic acid solution, 9-(p-hydroxyphenyl) xanthene (I) is formed as the intermediate of a pigment formation but when the reaction is allowed to proceed in glacial acetic acid solution, 9-(o-hydroxyphenyl) xanthene (II) is formed in about an equal amount with I. I and II can be separated by alumina chromatography and can be discriminated easily by the marked difference in their coloration behavior to the Gibbs reagent. When hydrochloric acid is present the reaction participated by the free-type phenol is predominant and, since its activation energy is comparatively high, difference between ortho and para substitution is thought to be rather marked. On the other hand, in the glacial acetic acid solution, the reaction participated by the phenoxide anion becomes predominant and its activation energy would be lower than that in the former case, resulting in a small difference between ortho and para substitution. This assumption is endorsed by the fact that para-substitution alone takes place in the case of anisole, which would not form a phenoxide anion, irrespective of the presence or absence of hydrochloric acid.
Based on the antitubercular and hypoglycemic action of coumarin derivatives, seven kinds of following derivatives of sulfonamide system were synthesized. 6-Tolylsulfonamidocoumarin (L-1), 6-(4-acetamidophenylsulfonamido) coumarin (L-2), 6-(4-aminophenylsulfonamido) coumarin (L-3), 4-methyl-6-tolylsulfonamidocoumarin (L-4), 4-methyl-(4-acetamidophenylsulfonamido) coumarin (L-5), 4-methyl-5-(4-aminophenylsulfonamido) coumarin (L-6), and 3-ethyl-6-tolylsulfonamidocoumarin (L-9). Of these compounds, hypoglycemic action of L-2 and L-3 has already been reported by Ito, et al. although its activity is not as marked as that of 2-(4-aminophenylsulfonamido)-5-isopropylthiadiazole. Antituberculosis action of these compounds were tested and reported by Mitani, and the antituberculosis action was found to be stronger when the substituent in 6-position of the coumarin ring is p-aminophenylsulfonamide group than when it is p-acetamidophenylsulfonamide group. None of the compounds synthesized were found to have stronger action than 4-methyl-7-(4-aminophenylsulfonamido) coumarin reported by Bersch, et al.
In connection with the previous report that psoromic acid, one of depsidone series compounds of lichen substances, has antitumor action against Ehrlich ascites tumor, several kinds of depsidone of comparatively simple structure were synthesized in order to progress this work to a more complicated compounds of depsidone series. The compounds synthesized were as follows: 11-Oxo-11H-dibenzo[1, 4-b, e]dioxepin-8-car-boxaldehyde, 11-oxo-11H-dibenzo[1, 4-b, e]dioxepin-7-carboxaldehyde, 6-hydroxy-, 6-methyl-, 7-methyl-, and 8-methyl-11H-dibenzo[1, 4-b, e]dioxepin-11-one, and dibromo- and dibromo-8-propyl-11H-dibenzo[1, 4-b, e]dioxepin-11-one.
Fusion reaction of 3-arylpropanols, 3-aryloxy-1, 2-propanediols, and ethylene glycol with urea was carried out and over ten kinds of derivatives of carbamates (I to VII) and 5-substituted 2-oxazolidinones (IX to XIX) were synthesized. Examinations were made especially on the formation and decomposition process of 5-(2-methoxy-4-allyl-phenoxymethyl)- and (2-methoxy-4-propylphenoxymethyl)-2-oxazolidinones among these synthesized products, as well as their reactivity with hydrogen and anhydrous hydrazine. Thermodynamic activity measured with guppy showed the greatest activity in IV of the carbamate group and XII in 2-oxazolidinone group.
3-Methyl-2-benzothiazolinone hydrazone was found to undergo reaction with acrinol in the presence of ferric chloride to produce reddish violet color which has absorption maximum at 545mμ and this reaction was applied to quantitative determination of acrinol. Presence of 5-nitrofurfurylideneaminoguanidine, chloroprophenepyridamine maleate, and berberine hydrochloride does not interfere in this reaction. Procedure: One ml. of the test solution (containing 120μg./ml. of acrinol) is accurately measured into a 20ml. measuring flask, 1ml. of 0.5% 3-methyl-2-benzothiazolinone hydrazone solution is added, followed by 1ml. of 1.2% ferric chloride solution. The mixture is shaken well, warmed in a water bath of 60° for 10 minutes, and cooled. Ethanol (95%) is added to bring the whole volume to 20ml. Blank test is carried out with 1ml. of water in place of the test solution. The absorbance is measured at 545mμ, referred to this blank.