In order to test the bacteriostatic activity, some compounds related to 4H-1-benzothiopyran-4-one 1, 1-dioxide, a kind of isoster of 1, 4-naphthoquinone, were prepared as illustrated in Chart 1. Contrary to expectations, none of these compounds showed strong activity in vitro against Mycobac. tuberculosis and E. coli. It is supposed that the redox potential of quinones plays an important rôle in their bacteriostatic activity. The half-wave potentials of some typical derivatives were measured by polarography. It was clarified that these compounds, which possessed 3-oxopropenylsulfonyl (-CO-CH=CH-SO2-) structure, showed comparatively positive reduction potential. This result agreed with the fact that 2-(phenylthio)thiochroman-4-one 1, 1-dioxide was easily produced from 3-bromo-4H-1-benzothiopyran-4-one 1, 1-dioxide and thiophenol in alkaline medium.
Cleavage reaction with sodium in liquid ammonia was examined with 1, 6-dimethoxy-3, 8-dimethyldibenzo-p-dioxin (I), which possesses a methyl group in the position para to the ether linkage. One of the two cleaved products was found to be 2-hydroxy-4, 5′-dimethyl-6, 3′-dimethoxydiphenyl ether (II) and the other, 2, 2′-dimethoxy-4, 4′-dimethyl-6, 6′-dihydroxybiphenyl (III). The presence of this methyl group in the para-position was found to inhibit the progress of normal cleavage reaction, resulting in increased formation of (III). The yield of (II) was found to increase by lowering the reaction temperature and by addition of ammonium chloride during the reaction. This conclusion agrees with the result obtained in the previous work.
Examination was made on the cleavage reaction of dibenzofuran (II), phenoxathiin (III), thianthrene (IV), and 2, 7-dimethylthianthrene (V) with alkali metal in liquid ammonia and results thereby obtained are listed in Table I. The ether linkage in dibenzofuran (II) is comparatively difficult to be cleaved and reduction of the ring takes place preferably when ammonium chloride is added. In phenoxathiin (III), the sulfur linkage is cleaved first to form o-phenoxybenzenethiol and a mercapto group is newly formed in the ortho-position, making it difficult for subsequent cleavage of the ether linkage, as in the case of 2-hydroxydiphenyl ether. In the case of thianthrene (IV) and dimethylthianthrene (V), however, the two sulfur linkages are easily cleaved, forming two moles of thiophenol.
Treatment of 1-deoxy-1-p-toluidino-D-fructose (N-p-tolyl-D-isoglucosamine) (I) with a mixture of acetone and conc. sulfuric acid afforded 1-deoxy-l-p-toluidino-4, 5-O-isopropylidene-D-fructopyranose (II), m.p. 123-124°, whose periodate oxidation gave 2, 3-O-isopropylidene-4-O-(N-p-tolylglycyl)-D-erythrose (VIII) as a syrup. Hydrolysis of (VIII) with alcoholic potassium hydroxide produced 2, 3-O-isopropylidene-D-erythrose (X) and the potassium salts of N-p-tolylglycine. Deacetonation of (X) with Amberlite IR-120 (H+) gave D-erythrose. The yield of (X) and (XII) was 43% and 36%, respectively, from D-glucose.
In photometric titration of iron (II) ion with potassium permanganate in sulfuric acidity, the equivalence point can be determined as the cross point of two straight lines if the spectrophotometer is set between 280 and 300mμ. Since the extinction of titanium (III) and titanium (IV) ions is far smaller than that of iron (III), titration of iron (III) with potassium permanganate, with addition of excess titanium (III) sulfate, followed by photometric titration at 280-300mμ, would give a curve in which the distance between the first and second break would correspond to the amount of iron. This method will make it possible to determine a minute amount of iron of 0.1-1mg. in 50cc. of a sample taken into the titration cell. Moreover, this eliminates the conventional reduction procedure by merely adding titanium (III) sulfate, and this method is more rapid and sensitive than the existing method when handling a large number of samples containing about the same amount of iron.
Infrared spectra of cyanopyridine derivatives having various substituents were examined. The C≡N stretching absorption of the nitrile bonded directly to the ring appears at 2239±4cm-1, while that of cyanomethylpyridine derivatives appear at 2257±4cm-1. Introduction of an electron-attracting group into the ring shifts the C≡N stretching absorption to a higher wave-number region, with marked decrease in its intensity. This absorption band splits into two in 2- and 3-cyano-pyridine 1-oxide, appearing respectively at 2237 and 2245cm-1 and at 2241 and 2249cm-1. The C≡N stretching absorption in 4-cyanopyridine 1-oxide derivatives shifts to a lower wave number than those of 4-cyanopyridine derivatives, with marked increase in their intensity. Relationship between the Hammet's σ value and wave number, molecular extinction coefficient, and integrated absorption intensity is generally linear. The wave number and intensity of C≡N stretching absorption in 2- and 4-cyanopyridine 1-oxides are markedly different from those of 2- and 4-cyano-pyridines, indicating that the electron-donating property of the N-O bond in 4-cyano-pyridine 1-oxide is considerable, and appropriateness of this fact is also suggested by the result of nitration reaction of pyridine 1-oxide.
Solubilization of vitamin A-alcohol, -acetate, and -palmitate, and ergocalciferol in water by mixing with sucrose monomyristate results in different viscosity of the solubilized solution according to the kind of solubilizates when the ratio of sucrose myristate to water is kept constant and concentration of the solubilizates is varied. In vitamin A-alcohol and ergocalciferol, relative viscosity increases with increasing concentration until the solution becomes turbid and the viscosity then falls. On the other handy viscosity of the solubilized solution hardly changes with increasing concentration of vitamin A-palmitate and -acetate. This phenomenon is assumed to be connected with polarity of the solubilizates. Viscosity of the solution in which lauryl alcohol has been solubilized is similar to the former and that of cetane is similar to the latter. The fact that the viscosity of a solution in which polar substance has been solubilized shows a maximum at a certain concentration of the solubilizate has already been observed in other surface-active agents and the foregoing phenomenon is assumed to be related to the structure of solubilized micelle formed by sucrose myristate and the substance to be dissolved.
In order to solubilize vitamins A and D for fortification of foodstuff, substances which are allowed for use in foodstuff, such as sucrose ester, must be used as a solubilizing agent. However, some of sucrose esters suited for solubilization have unpleasant odor or taste and their use is limited. In order to improve this point, raffinose esters were prepared, and their properties and solubilization power were examined. Raffinose palmitate, oleate, and myristate are practically odorless and tasteless, dissolve well in water, and are able to solubilize vitamins A and D to form a transparent solution, thereby showing that they have solubilization power equal to the known solubilizing agents such as Tweens. Oral and parenteral toxicity of these raffinose esters showed that the former is very small and their possible use for foodstuff was suggested. However, these esters were fairly toxic by intravenous injection and this was assumed to be due to their hemolytic action, same as that of sucrose esters. Aqueous solution of vitamins A and D solubilized with raffinose ester is stable and does not become cloudy on heating.
Assuming that antiviral compounds might be obtained by introduction of a higher alkyl group into the structure of barbituric acid, 28 compounds of this series were prepared and their in vivo effect against Nakayama strain of Japanese B encephalitis virus was examined in mice. It was thereby found that the compound effective on this virus are 3-methyl-5-propyl-, 3-allyl-, 3-benzyl-5-methyl-, and 3-butyl-5-methyl-5-lauryl-barbituric acids, and 3-benzyl-5-ethyl-5-phenyl- and 3-benzyl-5, 5-diethyl-barbituric acids.
In order to find better antiviral compounds than PANS-610, 15 compounds of alkyl N-acetylnaphthionate and 16 compounds of N-alkyl-4-acetamido-1-naphthalenesulfon-amide related PANS-610 were prepared and their in vitro and in vitro activity against the Nakayama strain of Japanese B encephalitis virus were examined. However, the decyl, undecyl, and dodecyl derivatives of the two series of compounds were found to have only in vitro activity weaker than PANS-610.
It has been reported that some organophosphorus compounds possess antimitotic property and it was thought that antiviral compounds might be obtained by introduction of a higher alkyl group into the structure of such compounds. Thus, 16 compounds of N-alkyl-P, P-bis(1-aziridinyl)phophinic amides were prepared and their in vitro activity was examined with the Nakayama strain of Japanese B encephalitis virus. N-Nonyl and N-decyl derivatives found to have in vitro activity against the virus, almost equal to that of PANS-610.
It has been found that several compounds of N-alkyl-P, P-bis(1-aziridinyl)phosphinic amide series have in vitro antiviral activity and, therefore, 12 compounds of Alkyl P, P-bis(1-aziridinyl)phosphinate series were prepared and their in vitro activity tested against the Nakayama strain of Japanese B encephalitis virus. N-Decyl, N-undecyl, and N-dodecyl derivatives were found to be effective against this virus.
o-Aminophenol was given orally to a rabbit and substances in the urine originating from the aminophenol were examined. The presence of o-aminophenol, o-amino-phenyl glucosiduronic acid, o-aminophenyl hydrogensulfate, and o-acetamidophenol were confirmed by individual isolation. 1-o-Hydroxyanilino-1-deoxyglucuronic acid was not isolated directly but its presence was proved indirectly, while o-hydroxy-phenylsulfamic acid and 3-aminophenoxazin-2-one were not detected. Quantitative examination of these substances in the urine after oral administration of 1g. of o-aminophenol showed that approximately 7.6% of the administered aminophenol was excreted per se, 26% as o-aminophenyl glucosiduronic acid, 18% as o-aminophenyl hydrogensulfate, and 1.2% as o-acetamidophenol.
Reaction of acetophenone with aromatic primary amines, in the presence of sulfur, failed to afford the anticipated phenylthioacetanilides, differing somewhat from the reaction of heterocyclic compounds, and only phenylacetanilides were obtained. In order to examine this reaction, the same reaction was carried out with thioacetophenone, sulful, and aniline, from which only 2, 4-diphenylthiophene (XXII) and a small amount of styrene (XXIV) were obtained. Desulfurization reaction gave 1, 3-diphenylbutane (XXIII) from (XXII) and 2, 3-diphenylbutane (XXVI) from thioacetophenone. These experiments have given interesting example that the reaction of thioacetophenone and aromatic primary amines is preceded by complicated condensation reaction of thioacetophenone molecule itself. The foregoing 2-phenylacetanilides were derived by the usual process into 2-phenylthioacetanilides and 2-benzylbenzothiazoles.
Reaction of active methyl group and aromatic primary amines, in the presence of sulfur, easily affords the compounds of thioanilide-type and benzothiazole type. Examinations were made on the behavior of thioanilide-type compounds during this reaction and a new kind of substitution reaction was found to take place. The reaction of thiopicolinanilide (I) and aniline afforded N, N′-diphenylpicolinamidine (II) which was proved by synthesis through a different route. In order to obtain a mixed-type amidines by the same procedure, thiopicolinanilide was reacted with aromatic primary amines carrying electron-releasing group in the para-position but, contrary to expectations, formation of mixed-type amidines was not observed and a substituted products were obtained. A small amount of 6-substituted 2-(2-pyridyl) benzothiazoles was also obtained. According to such a result, in order to clarify the order of substitution by the effect of para-substituent in the amines, reactions were carried out in various combinations and the order of substitution by this reaction was found to be as follows: H2N- -COOC2H5<H2N- H2N- -CH3<H2N- -OCH3<H2N- -OC2H5<H2N- -OC3H7 This order of substitution agrees with the order of electron-donating nature of the substituent para to the amino group in benzene ring and the Hammett's rule would probably apply in this case.
The substitution reaction confirmed in thiopicolinanilide was examined in N-phenylthioisonicotinamides, thiobenzanilides, and thioacetanilides, in order to extend the range of this reaction. It was thereby found that this substitution reaction is not instigated by the effect of nitrogen atom in the pyridine ring but is a general reaction for thioanilide-type compounds. Examinations were also made to see if this reaction also occurs in oxaanilide-type compounds, having oxygen atom in place of sulfur atom, but the substitution reaction was found not to occur in the case of phenylacetanilides, benzanilides, picolinanilides, and acetanilides. It follows, therefore, that this is a substitution reaction characteristic to thioanilide-type compounds.
Examinations were made on the formation of sulfisoxazole N-glucuronide, one of the biological metabolites of sulfisoxazole. The increased excretion of N-glucuronide into the urine after oral administration of sulfisoxazole and further increase in the N-glucuronide by the combined use of glucuronolactone were observed. Formation of sulfisoxazole N-glucuronide was recognized in the aqueous solution, blood, and urine when allowed to stand at 37° for 8 hours after addition of sulfisoxazole and glucuronic acid. It was also found that addition of sulfisoxazole to normal urine and allowing this to stand at 37° for 8 hours resulted in increased formation of the N-glucuronide and this was accompanied with the corresponding decrease of approximately equal amount of free glucuronic acid. From these results, it is pointed out that bioformation of sulfisoxazole N-glucuronide is non-enzymatic as well as being enzymatic, and the effect of (administered) glucuronolactone on detoxication of sulfisoxazole is chiefly acceleration of N-glucuronide-type detoxication process.
Method of assay for antihistamines in official formularies is difficult when used for assay of preparations and the values obtained are often inaccurate. The colorimetric determination of organic bases by the sulfophthalein dyes was applied to the assay of antihistamines of propy famine series and a good result was obtained by the use of Bromocresol Green and Bromothymol Blue. At the same time, effect of substances blended in the preparations was also examined and it was found that chlorpheniramine maleate (I) alone can be selectively determined by the use of Bromothymol Blue and ethylene dichloride when aminopyrine is compounded in (I) and by the use of Bromocresol Purple or Bromophenol Blue and benzene when ephedrine hydrochloride is compounded in (I).
It has been found that diphenhydramine undergoes fairly rapid decomposition in the presence of a strong acid and, in order to find its decomposition in gastric juice and its stability in a preparation, kinetic studies were made of its decomposition in aqueous solution. Diphenhydramine is hardly decomposed in alkaline solution. The decomposition in acid solution was found to be due to hydrolysis of the ether linkage and the reaction velocity constants were calculated at 40.0°, 50.0°, 59.6°, and 95.0°, between pH 0.7 and pH 4.7. It was found that this decomposition is a pseudofirst-order reaction and that it was catalyzed by hydrogen ion in the range of pH measured. The hydrogen ion catalytic constant, kH, could be represented by the following equation: kH=8.63×1015⋅e-23, 900/RT (L./mole/hr.) Rates of decomposition during digestion in the stomach, during sterilization at pH 5.5, and during storage were calculated from the above equation and all were found to be below 0.4%, negligible from the point of compounding. It is assumed, therefore, that the rapid decomposition of diphenhydramine in the body is mainly due to their decomposition in the organs and tissues.
An interesting desulfurization reaction was discovered by the formation of hydrazone (III) by the reaction of bis(p-nitrobenzyl) disulfide (I) and hydrazine hydrate. As a supplementary means for examining this reaction mechanism, reaction of (I) with other basic substances was examined and it was found that the oxime (XIII) and semicarbazone (XIV) were also formed with hydroxylamine and semicarbazide. As to the mechanism of this reaction, it was assumed, from the evolution of hydrogen sulfide and ammonia, and resistance of bis(p-nitrobenzyl) sulfide (VI) to desulfurization, that (I) forms thioaldehyde compound (XI) and thiol (XII), the former (XI) reacts with hydrazine to form the hydrazone (III) and hydrogen disulfide, and the thiol (XII) formed at the same time gradually changes into the disulfide (I), causing the chain reaction to progress, chiefly forming a hydrazone (III). It was also observed that various amines, such as methylamine, ethylamine, trimethylamine, aniline, and pyridine, also undergo similar desulfurization reaction but the reaction rate was slow in this case and the yield of the product was so poor that only a few of the products were identified. Further examinations are under way.
2-Acylpyridines (acyl=CH3CO, C2H5CO, C3H7CO, C4H9CO) with alkyl (methyl or ethyl) in the 4-position were prepared by the following route: 2, 4-Lutidine 1-oxide was submitted again to rearrangement by the Boekelheide method to 4-methylpicolin-aldehyde (B), oxidized with silver oxide, and esterified to ethyl 4-methylpicolinate (C). The Claisen condensation of (C) to (D) and ketonic decomposition of (D) afforded 2-acetyl-4-methylpyridine (I). Application of methyl, ethyl, or butyl iodide to (D) and ketonic decomposition of the respective products afforded 2-propionyl- (II), 2-butyryl- (III), and 2-valeryl-4-methylpyridine (IV). Application of methyl iodide to 4-ethylpyridine 1-oxide and reaction of the resultant 1-methoxy-4-ethylpyridinium iodide (E) with potassium cyanide gave 4-ethyl-2-pyridinecarbonitrile (F). Application of the Grignard reagents obtained from methyl iodide, ethyl bromide, propyl iodide, and butyl iodide to (F), afforded 2-acetyl- (V), 2-propionyl- (VI), 2-butyryl- (VII), and 2-valeryl-4-ethylpyridine (VIII).
Determination of 5α-cholestan-3α-ol (I) was carried out by the use of its absorption at 1002cm-1 in its infrared spectrum (Fig. 2) as the key band, in chloroform solution and as KBr pellet. From the route of its synthesis, (I) was expected to be contaminated with cholesterol (II), 5α-cholestan-3β-ol (III), and 5β-cholestan-3-one (IV), and their effect on the determination of (I) was also examined. Presence of (II) and (IV) was found not to affect the determination but (III) was found to interfere, and, therefore, determination of (I) in a mixture of (I) and (II) was attempted. As the results indicated in Tables I and II show, the standard deviation presumed according to the method of Youden was 0.55% by the solution method and 0.58% by the pellet method.
N-(p-Methoxyphenyl)glycine ethyl ester and N-(p-ethoxyphenyl)glycine ethyl ester were each reacted with benzenesulfonyl or p-toluenesulfonyl chloride in pyridine to form N-(p-alkoxyphenyl)-N-(arylsulfonyl)glycine ethyl esters (II) and these were reacted with hydrazine to form N-(p-alkoxyphenyl)-N-(arylsulfonyl)glycine hydrazine (III). Application of arylsulfonyl chloride to (III) or N-(p-alkoxyphenyl)glycine hydrazide (V) in pyridine affords 1-[N-(p-alkoxyphenyl)-N-(arylsulfonyl)glycyl]-2-(arylsulfonyl)hydrazine (IV). Reaction of (V) and arylsulfonyl chloride in dehyd. ethanol affords (IV) and 1-[N-(p-alkoxyphenyl)glycyl]-2-(arylsulfonyl)hydrazine (VI). Further application of arylsulfonyl chloride to (VI) in pyridine affords (IV).
The corresponding 1-[(N-p-alkoxyphenyl)glycyl]-2-benzylidenehydrazines (II) were obtained by condensation of N-(p-methoxyphenyl)- or N-(p-ethoxyphenyl)glycine hydrazide (I) with salicylaldehyde, p-nitrobenzaldehyde, m-nitrobenzaldehyde, p-chlorobenzaldehyde, 3-nitro-4-chlorobenzaldehyde, piperonal, p-(dimethylamino)benzaldehyde, p-acetamidobenzaldehyde, and p-aminobenzaldehyde, in ethanol containing acetic acid. Similarly, treatment of N-(p-methoxyphenyl)- and N-(p-ethoxyphenyl)-N-(benzenesulfonyl)glycine hydrazide (III) with the foregoing aromatic aldehydes afforded 1-[N-(p-alkoxyphenyl)-N-(benzenesulfonyl)glycyl]-2-benzylidene hydrazines (IV). Reaction of (II), other than 1-[N-(p-alkoxyphenyl)glycyl]-2-(p-aminobenzylidene)-hydrazine (II), with benzenesulfonyl chloride in pyridine also afforded (IV). Reaction of benzenesulfonyl chloride with (II) and 1-[N-(p-alkoxyphenyl)-N-(benzenesulfonyl)-glycyl]-2-(p-aminobenzylidene)hydrazine in pyridine gave 1-[N-(p-alkoxyphenyl)-N-(benzenesulfonyl)glycyl]-2-(p-benzenesulfonamidobenzylidene)hydrazine, and application of hydrazine hydrate to 1-[N-(p-alkoxyphenyl)-N-(benzenesulfonyl)glycyl]-2-(p-acetamidobenzylidene)hydrazine and 1-[N-(p-alkoxyphenyl)glycyl]-2-(p-acetamidobenzylidene)hydrazine respectively gave (III) and (I).
1-[N-(p-Methoxyphenyl)glycyl]-2-isopropylidenehydrazine (II), obtained by the reaction of N-(p-methoxyphenyl)glycine hydrazide (I) and acetone, reverts to the original (I) by treatment with hydrazine hydrate. Heat treatment of (II) in ethanol containing a small amount of hydrochloric acid does not afford the anticipated (I) but an unknown substance (V) is obtained which, on reaction with benzenesulfonyl chloride, changes into the compound (VI) containing a benzenesulfonyl group. From the qualitative reactions, elemental analytical values, and determination of molecular weight of these substances, (V) was assumed to be 1, 2-bis[N-(p-methoxyphenyl)glycyl]hydrazine and (VI), 1, 2-bis[N-(p-methoxyphenyl)-N-(benzenesulfonyl)glycyl]hydrazine. On the other hand, application of thionyl chloride to the ethyl ester of N-(p-methoxyphenyl)-N-(benzenesulfonyl)glycine to form the acid chloride and its reaction with N-(p-methoxyphenyl)-N-(benezenesulfonyl)glycine hydrazide (IV) gives (VI). Reaction of (IV) and monochloroacetyl chloride to form 1-[N-(p-methoxyphenyl)-N-(benzenesulfonyl)glycyl]-2-(chloroacetyl)hydrazine and its reaction with p-anisidine gives 1-[N-(p-methoxyphenyl)-N-(benzenesulfonyl)glycyl]-2-[N-(p-methoxyphenyl)glycyl]hydrazine which also produces (VI) by reaction with benzenesulfonyl chloride.
Cleavage reaction of norcoralydine (I) by application of metallic sodium in liquid ammonia affords one kind of a phenolic base (cleaved base A), whose hydrochloride melts at 249-250° with decomposition. The same reaction with metallic lithium in place of sodium, under exactly the same conditions, affords two kinds of phenolic bases, the same cleaved base A and another base B of m. p. 232-234°. Of these cleaved bases, base A was found to be 11-hydroxy-2, 3, 10-trimethoxy-5, 6, 13, 13a-tetrahydro-8H-dibenzo [a, g] quinolizine (II) by its synthesis through the route shown in Chart 1. The cleaved base B was found identical with 2, 10-dimethoxy-3, 11-dihydroxy-5, 6, 13, 13a-tetrahydro-8H-dibenzo[a, g] quinolizine (III) which had earlier been synthesized by the present writers.
Cleavage reaction of laudanosine (IV) by metallic lithium in liquid ammonia, using dehyd. dioxane as a solvent, results in the demethylation of methoxyl in 3′-position of benzyltetrahydroisoquinoline ring to form the phenolic base, laudanine (V). When the same reaction is carried out in tetrahydrofuran as a solvent, with increased amount of metallic lithium used, the reaction progresses further to demethylation of the methoxyl in the 6-position as well, forming 4′, 7-O, O-dimethyllaudanosoline (VI).
Dissociation constants of 10 kinds of sulfanilamides (I to XIV) were measured and it was observed that a large dissociation constant means that N1-acetyl derivative is easily obtained, i.e, it is one of the factors for selective acetylation of N1-position. Ultraviolet absorption spectra of acetyl derivatives of sulfanilamides were examined and some regularity was found to be present.
The reaction whereby the acetyl group in N1-position undergoes rearrangement to N4-position in N1-acetyl-N1-(3, 4-dimethyl-5-isoxazolyl) sulfanilamide (I), N1-acetyl-N1-(5-methyl-3-isoxazolyl) sulfanilamide (III), and N1-acetyl-N1-(2-phenyl-3-pyrazolyl)-sulfanilamide (IV) is considered to be an intermolecular rearrangement since the reaction of sulfanilamide (VII) with (I) produces N4-acetyl-N1-(3, 4-dimethyl-5-isoxazolyl)-sulfanilamide (II), N4-acetylsulfanilamide (VIII), and N1-(3, 4-dimethyl-5-isoxazolyl) sulfanilamide (IX), and the same products are similarly obtained from (III) and (VII). The fact that N4-acetyl-N1-(3, 4-dimethyl-5-isoxazolyl) sulfanilamide is obtained in a good yield from N1, N4-diacetyl-N1-(3, 4-dimethyl-5-isoxazolyl) sulfanilamide (XI) and (IX), and that a similar reaction takes place with N1, N4-diacetyl-N1-(5-methyl-3-isoxazolyl)-sulfanilamide (XII) indicate that this rearrangement reaction is preceded by the formation of (IX) from 2 moles of (I) and one mole of (XI), and (XI) thereby formed acetylates the N4-position of (IX) to produce two moles of (II). It is assumed that, in the case of (III) and (IV), the acetyl group in N1-position undergoes rearrangement to N4-position by a similar mechanism.
N-(p-acetamidobenzenesulfonyl)-2-methylthioacetamide (IX) was prepared from methyl 2-methylthionoacetoacetate (V) and N4-acetylsulfanilamide (III), and reactivity of 2-methylacetoacetimidic ester (I), 2-methylacetoacetic ester (II), and (V) with (III) was examined. The reactivity was thought to be in the descending order of (I), (V), and (II). Effect of α-alkyl group in acetoacetic ester (VI) in the condensation of (III) and derivatives of (VI) was examined and the reaction was found to become difficult as the number of carbon atoms in the α-alkyl increased. Further, effect of various alcohols in the solvent on the condensation of (I) and (III) was examined and the yield of condensation was found to increase as the polarity became larger.
Photochemical change of methyl oleate, linoleate, and linolenate was examined by gas chromatographic procedure described in the preceding report. Determination standard of these acids, when exposed to direct sunlight, showed a change which appeared as a peak same as in the case of the ozonide of these acids. This change did not occur at all in the absence of oxygen and the light of 3200-5000 Å was found to give the greatest photochemical change. Velocity of photochemical change under the same conditions of sunlight irradiation was found to be approximately proportional to the square of the number of double bonds in unsaturated fatty acids. It was thereby concluded that the position of this unsaturated bond becomes the factor for acceptor element for attack of oxygen molecule.
Xi-xin is a crude drug using a subterranean portion of a few plants of Asiasarum genus (Asaraceae family). The most important of its component has been reported as methyleugenol which makes up about 50% of its essential oil but this was found to vary greatly according to habitat of the plant. Some plants contained safrole, eucarvone, and 1, 8-cineol as the chief components. Xi-xin oil from Manchurian plant was proved to contain elemicin, an isomer of cis-asaron. Tu-xi-xin is the dried root of Hetehotropa genus of the same family and used as a substitute for Xi-xin. The chief component of its essential oil had been reported as safrole but elemicin was found to be present as the chief component in some of the crude drug.
Several dosage of o-aminophenol was administered orally to human subjects and rabbits, and the amount of conjugated glucuronic acid and sulfuric acid excreted into the urine was examined. It was found that a living organism had the ability to change o-aminophenol into O-glucuronide and ethereal sulfate according to the amount of o-aminophenol administered but detoxication by O-glucuronide was found to take place preferentially over that of ethereal sulfate.
In order to examine the reaction of 3-substituted 1-methoxypyridinium salts and potassium cyanide, reaction of 1-methoxy-3-cyano-, 1, 3-dimethoxy-, and 1-methoxy-3, 5-dibromopyridinium methylsulfates with potassium cyanide was carried out in water or ethanol-water mixture. The respective reaction products thereby obtained were 2, 3-dicyanopyridine in 27.8% yield, 2, 5-dicyanopyridine in 17.6% yield, 2-cyano-3-methoxypyridine in 67.8% yield, and 2-cyano-3, 5-dibromopyridine in 70% yield.
Alkaloids contained in Magnolia grandiflora L. var. lanceolata AIT. of North American origin were examined and the main base was found to be magnoflorine (I), one of the water-soluble quaternary bases, same as in the domestic Magnolia gradiflora L. (Japanese name “Taisanboku”). This North American plant was found not to contain salicifoline (II) which is contained in the domestic M. grandiflora and a new base, whose chloride melted at 203.5-207°, was found to be present.
In order to determine by a simple and micro-method the amino acids in protein hydrolyzate and to identify the amino acid composition in proteins, amino acids separated by paper partition chromatography were submitted to colorimetry, using the modified Ninhydrin reagent described in the preceding paper. It was thereby found that the determination is possible with an error of within 2-5% when using the calibration curve obtained by the two-dimensional, ascending chromatography. A good result was obtained by the use of Toyo Roshi No. 51 A filter paper. Actual determination using whale insulin gave approximately the same precision as the determination by the Stein-Moore method using ion exchange resin.
Catalytic hydrogenation of (diethylamino) acetonitrile was carried out over Raney nickel W-7 catalyst and without a solvent. The desired N, N-diethylethylenediamine was obtained in a yield of about 40% of the theoretical. This method was adapted to other disubstituted amino-acetonitriles and -propionitriles such as dimethylamino, morpholino, and piperidino compounds. In contrast to the experiments previously reported, relatively moderate conditions were employed for the hydrogenation and the yields were more or less improved. Raney nickel W-7 catalyst may be the most suitable for the hydrogenation of this type of compounds.
The main alkaloids of opium, morphine, codeine, papaverine, narcotine, and dihydrocodeine, form a salt with various organic and inorganic acids. The water-soluble salts of these alkaloids have a strong bitter taste and are disliked for oral use. The artificial sweetening, saccharin, is a kind of acid and salt-formation of these alkaloids with saccharin was attained by heating a mixture of the alkaloid and saccharin in organic solvent. The salt thereby formed has a sweet taste, the sweetness of saccharin shielding the bitterness of the base, and is a water-soluble salt of uniform composition.