Morphine, codeine, thebaine, narcotise, and papaverine were determined in opium from India, Turkey, and Yugoslavia, and it was found that the determination is possible with ca. 1g. of a sample as fresh opium. Recovery rate of each of these alkaloids was 95-106%. Indian opium contained comparatively small amount of morphine and a large amount of codeine and narcotise. The procedure of determination was as follows: Preparation of test solution: An accurately weighed ca. 0.8g. of a sample (corresponding to ca. 1g. as fresh opium) is continuously extracted with 25cc. of methanol for 5 hours, ammonia is added, followed by ethyl acetate, and insoluble matter is removed. The solution is evaporated to dryness, the residue is dissolved in methanol, 0.5N hydrochloric acid is added, and methanol is evaporated in a reduced pressure. The residual solution is brought to a definite quantity with 0.5N hydrochloric acid, centrifuged, and the supernatant is used as the test solution. Separatory determination: 8N Sodium hydroxide solution is added to a part of the test solution, shaken with chloroform, and the alkaline layer is acidified with hydrochloric acid. This is shaken with chloroform, the aqueous layer is basified with ammonia water, and extracted with ethyl acetate. The residue obtained after evaporation of ethyl acetate is submitted to the determination of morphine by the method described in Part XII of this series. The chloroform layer is shaken with 0.2N tartaric acid to transit codeine and thebaine into the acid layer. Thebaine is determined with a part of this acid solution and another part is treated as described in Part XI of this series to separate thebaine for determination of codeine. A portion of the test solution in basified with ammonia water, extracted with chloroform, and papaverine and narcotise are separatory determined with this chloroform solution by the method described in Part VIII and XI of this series.
Starch oxidized with nitric acid was neutralized with alkali and boiled, from which formation of glucuronic acid was detected. This reaction was found to progress even at room temperature by the use of excess alkali. The solution after alkali treatment does not indicate increased formation of glucuronic acid even after acid hydrolysis and this fact suggests that oxidized starch undergoes complete change by alkali treatment. The amount of glucuronic acid formed by the action of alkali was larger in oxidized starch which was considered to contain greater degree of oxo structure by secondary oxidation. Consequently, formation of glucuronic acid by alkali treatment was found to be closely related to intramolecular structure, especially oxo structure.
Isonicotinic acid hydrazide (INAH) easily forms a Schiff base with keto acids such as pyruvic and mesoxalic acid. The toxicity of this base, pyruvic acid isonicotinoyl-hydrazone, is 1/29 that of INAH in LD50 by subcutaneous injection in mice and this decrease in toxicity is more marked in mesoxalic acid isonicotinoylhydrazone, its LD50 being less than 1/40 that of INAH. Even by comparison between benzoic acid hydrazide, which has a structure similar to INAH, and its Schiff base, pyruvic acid benzoylhydrazone, toxicity of the latter was found to be 1/8 that of the former, when compared by LD50 by subcutaneous injection in mice. This decrease in toxicity by derivation to a Schiff base was found to be due to absence of inhibition of glutamic decarboxylase activity in the brain. Clinical tests have shown that Schiff bases of INAH have less side effects and this is also considered to be due to absence of inhibition against glutamic decarboxylase which requires pyridoxine as the coenzyme.
Reaction of thiourea with DL-trans- and DL-cis-2-chlorocyclohexylamine (trans- and cis-I) hydrochloride in the hot was examined. cis-(I) formed cyclohexanone and a small amount of DL-trans-2-iminoperhydrobenzothiazolidine (trans-III), which are presumably products formed respectively by trans-elimination and SN2, followed by ring closure, trans-(I) formed trans-(III), probably by thermal ring-closure of DL-trans-2-(2-aminocyclohexyl)-2-thiopseudourea hydrochloride formed as an intermediate via cyclohexanoaziridine. A general method for synthesis of 2-(2-aminoalkyl)-2-thiopseudourea is proposed on the basis of the mechanism of trans-(I) reaction; an aziridine is treated with thiourea and an acid in the cold to give the corresponding 2-thiopseudourea. This method is advantageous for obtaining any salt of 2-thiopseudourea salt.
Treatment of 2-(2-aminoethyl)-2-thiopseudourea (AET) sulfate with 1 equiv. of Ba(OH)2 was introduced to the isolation of 1-(2-mercaptoethyl)guanidine (MEG) sulfate which has been supposed by Doherty, et al. to be the active principle of AET, the protector of radiation sickness. A method for detection of aziridines color by reaction was devised on the basis of the fact that an aziridine reacts with thiourea and an acid in the cold to yield the corresponding 2-(2-aminoalkyl)-2-thiopseudourea salt which is converted to 1-(2-mercaptoalkyl)guanidine by neutralization.
Two moles of o- or p-aminophenol undergoes condensation with 1 mole of terephthalaldehyde to form the Schiff base which has a maximum absorption in ethanol at 380mμ. This absorption makes a bathochromic shift to 445mμ in ethanolic alkali hydroxide solution by formation of a quinoid structure. Aromatic primary amines having, methyl, carboxyl, carboxylic ester, or nitro group, and hydroxyl in meta-position also undergo condensation with terephthalaldehyde but their Schiff bases do not show bathochromic effect due to quinoid structure in an alkaline medium. This fact can be utilized for colorimetric determination of o- and p-aminophenol in the presence of aniline, toluidines, aminobenzoic acids, and procaine by condensation of the phenol in ethanol, basification of the reaction mixture, and colorimetry of the orange-yellow solution. Presence of p-nitroaniline and m-aminophenol gives positive deviation. This determination can be carried out with an error of within ±2%.
Examinations were made on chelates of 47 kinds of 2, 2′-biquinoline derivatives, including three known compounds, and copper (I) on the effect of changes in the kind and position of the substituent and changes in spectrophotometric constants (ε, λmax). Examinations were made with 2, 2′-biquinolines with substituents in 4- and 4′-positions, presence of substituents in 6, 6′-, 7, 7′-, and 8, 8′-positions in the 4, 4′-dimethyl compound, presence of methyl groups in 6, 6′-, 7, 7′- and 8, 8′-positions in 4, 4′-dimethyl compound, and presence of substituents in 6, 6′-, 7, 7′-, and 8, 8′-positions in 4, 4′-diphenyl compound, as well as with polysubstituted compounds. The maximum sensitivity was found in 4, 4′-diphenyl-6, 6′-dimethyl-2, 2′-biquinoline (ε 11030) and (2, 2′-biquinoline)-4-carboxylic acid and -4, 4′-dicarboxylic acid were found to undergo this reaction in aqueous solution. Further introduction of a substituent in 6, 6′- or 7, 7′-position in 4, 4′-substituted compounds indicated that the absorbency is greater in 6, 6′-substituted compounds, being hyperchromic, while maximum absorption is batho-chromic in 7, 7′-substituted compounds. 8, 8′-Substituted compounds and N-oxides lost the ability to undergo coloration reaction with copper (I) due to steric hindrance.
Following the preparation of porous granular silver for use in the determination of oxygen, porous block silver and porous copper were devised. Porous copper is a novel form and no reports are found on its use in chemical reaction. The use of porous copper in nitrogen gas for removal of oxygen was found to have seven times the ability of copper wire and absorptivity of iodine in nitrogen gas was found to be twice that of porous silver. A new observation was made on the reaction of copper wire and sulfur compounds.
Analysis of carbon and hydrogen in organic compounds was carried out by the use of a novel porous copper oxide and porous silver as the reaction agents and the sample was heated rapidly in air stream flowing at the rate of 20-25cc./min., the air passing over copper oxide layer heated at 750-800° to effect oxidative combustion in a short period. Porous copper oxide has a large catalytic oxidative power in a small amount and porous silver hasa larg e absorbability for halogens and sulfur at a low temperature. Period required for one rapid analysis of carbon and hydrogen in organic compounds is 23-25 minutes.
A tertiary phenolic base, coclanoline, had been isolated from Cocculus laurifolius DC. (Japanese name “Kosyu-uyaku”) and Kusuda proposed the structure (II) for it.*3 On the other hand, Govindachari had isolated reticuline from Anona reticulata LINN. and proposed the formula (II) as its chemical structure. In order to clarify the relationship between these two bases, dl-1-(3-hydroxy-4-methoxybenzyl)-2-methyl-6-methoxy-1, 2, 3, 4-tetrahydro-7-isoquinolinol (II) was synthesized and its infrared spectrum was found to agree with that of natural reticuline but not perfectly with that of natural coclanoline. Therefore, an isomer of (II) with two phenolic hydroxyls and two methoxyls in different positions, dl-1-(3-methoxy-4-hydroxybenzyl)-2-methyl-7-methoxy-1, 2, 3, 4-tetrahydro-6-isoquinolinol (IIa), was synthesized and compared with natural coclanoline but identification was not established. It is therefore considered that coclanoline is a laudanosoline dimethyl ether-type base other than (II) or (IIa).
It was found, as reported in the preceding paper, that the synthesized dl-1-(3-hydroxy-4-methoxybenzyl)-6-methoxy-1, 2, 3, 4-tetrahydro-7-isoquinolinol (dl-reticuline) (I) and 1-(3-methoxy-4-hydroxybenzyl)-2-methyl-7-methoxy-1, 2, 3, 4-tetrahydro-6-iso-quinolinol (Ia) did not agree with coclanoline, the tertiary phenolic base isolated from Cocculus laurifolius DC. (Japanese name “Koshu-uyaku”). In the present series of work, two more isomers having two methoxyls and two phenolic hydroxyls in positions different from (I) and (Ia) were synthesized, i.e. 1-(3-methoxy-4-hydroxybenzyl)-2-methyl-6-methoxy-1, 2, 3, 4-tetrahydro-7-isoquinolinol (II) and 1-(3-hydroxy-4-methoxybenzyl)-2-methyl-7-methoxy-1, 2, 3, 4-tetrahydro-6-iso-quinolinol (IIa). Comparison with natural coclanoline showed that neither of them agreed with the natural base. Consequently, it has become necessary to reëxamine the chemical structure of natural coclanoline.
Four kinds of laudanosoline dimethyl ether-type base (I to IV) were synthesized but none of them agreed with coclanoline isolated by Kusuda from Cocculus laurifolius DC. Separation and isolation of this tertiary phenolic base was carried out with freshly collected plant material and reëxamination was made on the coclanoline fraction. It was thereby found that the coclanoline reported to date was a mixture of two kinds of base. Of these two, coclanoline-A formed an oxalate of m. p. 143.5-144.5° (decomp.) and permanganate oxidation of its O, O-diethyl compound afforded p-ethoxybenzoic acid and 4-methoxy-5-ethoxyphthalic anhydride. Comparison of the oxalate of the original base with the oxalate of d-N-methylcoclaurine (VII) showed that they agreed completely in various properties, and the two substances were identified by mixed fusion and infrared spectral comparison. From the mother liquor left after separation of coclanoline-A oxalate, coclanoline-B was isolated as crystals of m. p. 152-160° but detailed examinations could not be made due to the small amount of the sample available. However, its properties were in good agreement with those of laudanine (XIII). It follows, therefore, that coclanoline first isolated by Kusuda from Cocculus laurifolius must have been a mixture of d-N-methylcoclaurine (VII) and laudanine (XIII).
The paper electrophoretic separation of phloroglucinol derivatives in aspidium extract was carried out by a double migration method, using the Kolthoff buffer solution added with a small quantity of surface-active agent. Filicinrc acid was used as the standard and MFC values (distance moved by Aspidium constituent/distance moved by filicinic acid) were calculated. In the first migration at pH 7.0, flavaspidic acid was separated and the other constituents were separated in the second migration at pH 8.6. The spots were detected by coloring with diazotized sulfanilic acid, after pencil-marking of the fluorescence under ultraviolet rays.
Paper electrophoretic separation of phloroglucinol derivatives was examined in the rhizomes of 35 species of Dryopteris growing in Japan and the results are listed in Table I. In this work two substances which have not been reported before were detected. One of them was detected from D. austriaca, D. tokyoensis, D. championi, and D. kinkiensis, and it was identified as desaspidin. The other substance detected from D. crassirhizoma, D. lacera, and D. uniformis is similar to filixic acid in melting point, which was prepared from Extractum Aspidii (Merck), but different in MFC value and Rf value of paper chromatography. Examination of this substance is now under way.
Synthetic route for 2, 3-dihydrofuro-[2, 3-b] quinoline was reëxamined and following observations were made. 1) The high-melting substance formed during the synthesis of dihydrofuroanilide, the starting compound for the above synthesis, was examined in detail and, from its reactions, molecular weight, elemental analyses, and ultraviolet and infrared spectra, it was assumed to be a dimer formed by hydrative polymerization of 2 moles of dehydrofuroanilide and 1 mole of water. 2) Reaction of dihydrofuroanilide, 3-(2-hydroxyethyl) carbostyril, and dihydrofuro-quinoline with polyphosphoric acid, phosphoryl chloride, conc. sulfuric acid, conc. hydrochloric acid, and acetic acid was examined. 3) 3-(2-Hydroxyethyl) carbostyril forms 3-(2-chloroethyl)-6-chlorocarbostyril by treatment with thionyl chloride and further treatment of this carbostyril gives 6-chloro-2, 3-dihydrofuro [2, 3-b] quinoline.
Crude drugs containing berberine-type alkaloids are used extensively as an anticonvulsant, sedative, antiphlogistic, and hemostatic but their therapeutic effect varies. Comparative examinations were therefore made on the relationship between their chemical structure and their direct action on mouse intestine and uterus, and anticonvulsant action. Tests were made of quaternary bases of berberine (I), palmatine (II), jatrorrhizine (III), dihydroberberine (IV), and dihydropalmatine (V), and tertiary bases of dl-tetrahydroberberine (VI), dl-tetrahydropalmatine (VII), and dl-tetrahydrojatrorrhizine (VIII). In the case of intestines, neither the dehydro type (I to III) nor dihydro type (IV and V) showed any marked action but tetrahydro type (VI to VII) showed strong papaverine-like action. The compounds (I) to (V) showed marked contraction of uterus but the action of (VI) to (VIII) was transitory and anti-acetylcholine action was more evident. It was found that these actions became stronger as the substituent on the side chain changed from methylenedioxy to methoxyl to hydroxyl.
A hydroxyl group in organic compounds was acetylated with acetic anhydride and pyridine, excess reagent was decomposed with sodium carbonate solution, and the ester thereby formed was derived to acetohydroxamic acid by treatment with hydroxylamine. This acid was colorimetrically determined as the iron complex salt. The method was applied to numerous alcohols, phenols, and sugars and it was found to have repeatability of ±0.6% and reproducibility of 1.3%. The feature of this method is that no special apparatus or reagents are needed and a semimicro amounts of a sample can be determined in a simple manner. Since a large excess of acetic anhydride is used, the method is adapted for samples containing a large amount of water and also for those which are easily hydrolyzed and alkali titration cannot be used. Only one calibration curve can serve for almost any kind of compounds, and amines and carboxylic acids do not interfere in this determination. For colored samples or samples which might color during the procedure, a suitable correction was devised. This determination cannot be used for tertiary alcohols and sublimable substances.
Polarographic behavior of 15 kinds of commercial sulfanilamide derivatives was examined and the compounds were classified into four groups. The polarography was carried out with tetramethylammonium bromide as the supporting electrolyte. The compounds which showed one-step reduction wave in non-buffered solution containing 10% of dioxane were classed in Group 1 and it included N1-(3, 4-dimethyl-5-isoxazolyl) sulfanilamide, N1-(1-phenyl-5-pyrazolyl) sulfanilamide, N1-(5-methyl-3-isoxazolyl) sulfanilamide, and N1-acetylsulfanilamide. Group 2 included the compounds which showed perfect wave in a solution containing around 80% of dioxane and these were N1-2-pyridylsulanilamide, N1-2-thiazolylsulfanilamide, and N1-(3, 4-dimethylbenzoyl) sulfanilamide. The compounds which showed one- to two-step waves in a solution containing 10% of dioxane and also a reduction wave in buffered solution were classed into Group 3 and included N1-(5-methyl-1, 3, 4-thiadiazol-2-yl) sulfanilamide, N1-(2, 6-dimethyl-4-pyrimidinyl) sulfanilamide, N1-(2, 6-dimethoxy-4-pyrimidinyl)-sulfanilamide, N1-2-pyrimidinylsulfanilamide, N1-(4-methyl-2-pyrimidinyl) sulfanil amide, and N1-(6-methoxy-3-pyridazinyl) sulfanilamide. The compounds which failed to show reduction wave in any of these conditions were sulfanilamide and N1-amidinosulfanilamide, and these were classed in Group 4. Conditions for measurement of sulfanilamide derivatives in Group 1 were examined and it was found that their determination is possible within a concentration range of 0.2-1.0 mM. Method for this determination was also established.
Investigations on the actual state of analytical process of alkoxyl group utilizing the apparatus recommended by the Committee of Microchemical Apparatus in American Chemical Society were described, The blank value due to the incomplete elimination of hydriodic acid vapor in the scrubber of this apparatus within the distillation time of 45 minutes and carbon dioxide flow of 10cc./min. (slightly less than 2 bubbles per second in the receiver) was at least 0.10cc. of 0.01N sodium thiosulfate which corresponds to 0.17% of methoxyl and 0.25% of ethoxyl group in 3mg. of a sample. On the other hand, the most accurate results were obtained at this distillation time in which the blank value was included, agreeing with the results of statistical study by the above committee. Therefore, it is supposed that some alkyl iodide was retained in the apparatus under the standard procedure. Comparisons between several wash liquids indicated that distilled water was not actually inferior to any other wash solutions in regard to this apparatus. The commercially available phenols added for dissolving the sample occasionally contained some alkoxyl impurities causing very high blanks. The use of Kirstens's reaction mixture from which the alkoxyl impurities were completely swept away by preliminary treatment appeared to be the best to be recommended.
A new titrimetric method was devised by utilization of the difference in dielectric constants of acid, base, and salts in non-self-dissociating solvent of low dielectric constant, such as p-dioxane. This is a kind of nonaqueous titration and is similar to high-frequency titration, since it uses a high-frequency circuit but its mechanism is dependent on the changes in dielectric constant, without changes of the electric conductivity of a solvent. This method was therefore named dielectrometric titration. It is possible to make rough calculation of the dipole moment from the titration values obtained by this method. Satisfactory results were obtained by titration of amines with picric acid. Titrable range is around pKb 7 and accuracy is around 1%.
Titration of amines with p-toluenesulfonic acid and trichloroacetic acid caused a phenomenon not observed by titration with picric acid. Titration curves of primary and secondary amines and that of tertiary amines were different and this difference was found to be common to sulfonic and carboxylic acids. The calculated and titration values of tertiary amines agreed within an error of around 1% but primary and secondary amines showed titration values specific to each individual amine, the values being scattered in the range of 82-100% of the theoretical values. Titration range of sulfonic acid is much wider than that of picric acid, and aniline and Schiff bases can be titrated with sulfonic acid.
Differentiation titration of a mixture of primary and secondary amines and tertiary amines was effected by utilization of the difference in titration curves of primary, secondary, and tertiary amines by p-toluenesulfonic acid. Differentiation titration of primary and secondary amines can be effected by the addition of benzaldehyde.
Differentiation titration using p-toluenesulfonic acid was carried out on a mixture of primary, secondary, and tertiary amines. It was found in a titration of a mixture containing two kinds of amines that a simple fnnctional relationship existed between the calculated value y and titrated value x of quantitative ratio of the amines expressed as y=a+bx. By the use of this relative equation, two kinds of amines can be separatory determined with good accuracy.
4, 6-Diaminoquinoline was derived to 4-amino-6-hydrazinoquinoline and this was condensed with various ketones and aldehydes to form the hydrazones listed in Table I. Indole cyclization reaction of acetone hydrazone (X) by the Fischer process afforded the corresponding (XVI) as colorless needles, m.p. 117°, which transited to (XVII) on being heated with 25% alkali hydroxide. (XVII) is the indole-cyclized product corresponding to (X) but its structure could be either (XVIIa) or (XVIIb). In this connection, Huisgen carried out indole cyclization of acetone 6-quinolylhydrazone by the Fischer process and proposed the structural formula (XV) for the product. This structure (XV) seems appropriate in view of the naphthoid activity of quinoline but it cannot be concluded from this fact that the indole-cyclization product of (X) possessing an amino group in 4-position must necessarily be (XVIIa). Since the yield of the cyclization product of (X) was unsatisfactory (29%), (XII) was submitted to indole-cyclization reaction by Huisgen's process in order to compare ultraviolt absorption spectra, and two kinds of products were obtained; one of colorless prisms, m.p. 198°, and the other of pale yellow needles, m.p. 268° The latter was found to be the double salt of the former with zinc chloride and its heating with 25% alkali hydroxide solution afforded the compound of m.p. 198°. The ultraviolet absorption spectra of these compounds are compared in Fig. 1 with those of (XV), (XVII), and 3H-pyrrolo [3, 2-f]quinoline, presumed by Horner, and there is a great possibility that (XVII) takes the pyrroloquinoline form of a similar type and an angular configuration like (XV). Confirmation of this point must await further detailed work.
The Conrad-Limpach-Knorr cyclization reaction was carried out on 6-amino- and 4, 6-diaminoquinolines and the products thereby obtained are listed in Table I. Heating of 6-aminoquinoline with ethyl acetoacetate afforded an anilide compound (I), m.p. 125-126°, which was heated with conc. sulfuric acid to form the 2-hydroxylepidine compound (II) and derived to a chloro compound (III) of colorless needles, m.p. 204°, by treatment with phosphoryl chloride. There is no doubt that an angular cyclization took place due to the naphthoid activity of quinoline since there is no substituent in the pyridine portion. 4-Methyl-6-aminocarbostyril (VII) was prepared by the route shown in Chart I and (VII) was submitted to the Skraup reaction to form the corresponding derivative (VIII), m.p. 312° (decomp.). The chlorolepidine compound, obtained by chlorination of (VIII), came as colorless needles, m.p. 204°, undepressed on admixture with (III). Similar Conrad-Limpach cyclization of 4, 6-diaminoquinoline afforded the corresponding pyrido [f] quinoline derivatives (X and XII). For elucidation of the structure of (X), (VIII) obtained by the Skraup reaction of (VII), was derived to its N-oxide and catalytic reduction of its nitro compound (XIV) over palladium-carbon finally afforded (X).
Phenylmercuri-, (p-tolylmercuri)-, (o-hydroxyphenyl)mercuri-, (o-hydroxymethyl-phenyl)mercuri-, (p-hydroxymethylphenyl)mercuri-, (o-acetamidomethylphenyl)mercuri-, [p-(3-hydroxypropyl)phenyl]mercuri-, and (p-chlorophenyl)mercuri-theophyllines were prepared. The position of the substituent in theopylline was proved to be at 7 by comparison of ultraviolet and infrared spectra of these compounds with those of 7-allyltheophylline, 7-(3-acetoxymercuri-2-methoxypropyl)theophylline, and 7-(3-chloromercuri-2-methoxypropyl)theophylline prepared from 7-allyltheophylline, mercuric acetate, and phenylmercury acetate.
Preparation of 2-amino-5-nitro-1, 3, 4-thiadiazole was unsuccessful by the rearrangement of nitro group in the side chaine at 2-position of 2-nitramino-1, 3, 4-thiadiazole and also by direct nitration of 2-acetamido-1, 3, 4-thiadiazole with a mixture of potassium nitrate and conc. sulfuric acid at various temperatures. The reaction of 2-nitramino-5-R-1, 3, 4-thiadiazoles (R=H, CH3, C2H5, C3H7, and iso-C4H9) with benzylamine in boiling xylene afforded 2-benzylamino-5-R-1, 3, 4-thiadiazole (except in the case of R=H) and 3-mercapto-4-benzyl-5-R-4H-1, 2, 4-triazole. The former was also prepared by the reaction of 2-chloro-5-R-1, 3, 4-thiadiazole (R=H, CH3, C2H5, n-C3H7, and iso-C4H9) with benzylamine in methanol. 3-mercapto-4-benzyl-5-R-4H-1, 2, 4-triazoles (R=H, CH3) were prepared from 1-acyl-4-benzyl-3-thiosemicarbazides by cyclization with 10% sodium carbonate solution, which were synthesized by using 80% formic acid, and a mixture of acetic acid and its anhydride with 4-benzyl-3-thiosemicarbazide, respectively. Recation of 4-benzyl-3-thiosemicarbazide with 99% formic acid gave 2-benzylamino-1, 3, 4-thiadiazole.
Components of the ovaries of Japanese toad (Bufo vulgaris), 2-3 days after being caught, were examined by paper chromatography by the Zaffaroni system and gamabufotalin, γ-sitosterol, and palmitic acid were isolated. Paper chromatography with the Zaffaroni system indicated the presence of desacetylcinobufagin, desacetylcinobufotalin, cinobufotalin, telocinobufagin, and hellebrigenin. Water-soluble components appeared as three spots on paper chromatogram but they could not be isolated and identified.
Reëxamination was made on the components of the skin of domestic toad (Bufo vulgaris) and the following were isolated and identified: Gamabufotalin, resibufogenin, cinobufagin, cinobufotalin, bufalin, hellebrigenin, telocinobufagin, desacetylcinobufagin, desacetylcinobufotalin, and γ-sitosterol. A new bufogenin was isolated which corresponded to molecular formula of C26H36O6, with one each of acetyloxyl, secondary hydroxyl, and tertiary hydroxyl groups, and not having an epoxide ring at 14-15. Its acetate had the molecular formula of C28H38O7, and the bufogenin was named gamabufotalininol.
The formation of 2-phenylindole by heating of 1-phenacylpyridinium bromide and aniline at high temperatures was confirmed. Examination of reaction conditions showed that the reaction of 1 mole of 1-phenacylpyridinium bromide and 2 moles of aniline in N, N-dimethylaniline, by heating at 200° for 2 hours, gave the product in 83% yield. It was revealed through the use of various amines in place of aniline that 2-phenylindole derivatives are formed from aromatic primary amines in which the ortho position of amino group is not substituted.
1, 5-Bis(5-nitro-2-furyl)-3-pentadienone guanylhydrazone hydrochloride was treated in organic solvent with warming and two kinds of product (A) and (C), having strong antibacterial action against gram-negative bacteria, were obtained. (A) was found to be 3-amino-6-[(5-nitro-2-furyl)vinyl]-as-triazine and (C), 3-amino-5-(5-nitro-2-furylmethyl)-6-[(5-nitro-2-furyl)vinyl]-as-triazine.
Starch oxidized with nitric acid shows ketone absorption at 285mμ but this absorption disappears after its reduction with sodium borohydride, while the absorption remained after catalytic reduction. Since this reduction product of the oxidized starch does not indicate high formation of uronic acid by acid decomposition, this ultraviolet absorption is considered to be a measure of reduction effect. Acid decomposition of the reduction product indicated the presence of mannuronic acid and an unknown non-lactonized uronic acid, which was considered to be either allouronic or altronic acid.
Photodecomposition of leucoriboflavin 10-ethylformate was carried out. Irradiation of light on neutral aqueous solution resulted in liberation of ethylformyl group under aerobic condition and lumichrome was formed via riboflavin. Under anaerobic condition, the compound was entirely stable. Irradiation of light on alkaline aqueous solution caused decomposition, both under aerobic and anaerobic conditions, and lumiflavin was formed but the rate of decomposition was smaller under anaerobic condition.
Examination of alkaloids in Phelloaendron amurense RUPR. var. japonicum OHWI. (Japanese name “Ke-kihada”) (Rutaceae) proved the presence of a water-soluble quaternary base, similar to P. amurense RUPR. (Japanese name “Kihada”) and P. amurense var. sachalinanse FR. SCHM. (Japanese name “ Hiroha-kihada”) reported previously (cf. Table I).
It was found that heat treatment of 1, 5-bis(5-nitro-2-furyl)-3-pentadienone guanylhydrazone hydrochloride converted it into a compound which showed marked antibacterial action against gram-positive and -negative bacteria. Therefore, this original compound was treated in butanol at 130° for 2 hours and the residue obtained by evaporation of butanol afforded two kinds of products, named A and C, with different chemical and antibacterial behavior. Product A showed bactericidal effect against dysentery bacilli in a dilute solution of 0.1γ/cc. and this action was found to be 1000 times greater than that of the parent hydrochloride.
Of the various kinds of phenylmercurated theophylline compounds, the representative one, 7-(phenylmercuri)theophylline, was given as a subcutaneous injection in mice and its acute toxicity (LD50) was 0.095±0.005mg./g. body weight. The diuretic effect of this compound was found to be better than that of theophylline, there being a significant difference. Effect of the subcutaneous injection of 7-(phenylmercuri)theophylline and theophylline in mice on the amount of urine excreted was examined and the maximum amount of urine was found to be excreted one hour after the injection.
p-[(3-Acetoxymercuri-2-methoxypropyl)carbamoyl]phenoxyacetic acid (IV) was synthesized and preparative method for its starting materials, N-allyl-4-hydroxybenzamide (II) and p-(allylcarbamoyl)phenoxyacetic acid (III), was compared with that of Whitehead and others. The structure of (II), (III), and (IV) was confirmed through elemental analyses and infrared spectral data.
The alkylation of 2-p-toluenesulfonamido-1, 3, 4-thiadiazole with alkyl halide or dialkyl sulfate in alkaline medium yielded 4-alkyl-5-p-toluenesulfonimido-Δ2-1, 3, 4-thiadiazolines (R=CH3, C2H5, C3H7, iso-C3H7, iso-C4H9, sec-C4H9, C6H5⋅CH2-). Ultraviolet absorption spectra of these compounds exhibited the maximum absorption at about 225 and 270mμ.
A new photometric method of analysis for 2-Phthalimidoglutarimide is described. It is based on the formation of a hydroxamic acid derivative by treatment with 2N hydroxylamine hydrochloride and 3.5N sodium hydroxide for 60 minutes at room temperature, and this derivative, after neutralization with 3.5N hydrochloric acid, undergoes complex formation with iron (III) ion to show a brownish purple color.
Glutethimide is easily decomposed into 2-ethyl-2-phenylglutaramide (I) in alkaline solution. This decomposition occurs in sodium hydroxide or carbonate solution by the second-order reaction, but not in sodium hydrogen carbonate solution. The degradation velocity constants at 20°, 30°, and 40° in 0.01N sodium hydroxide solution were 7.66×10-1, 1.67, and 3.56, and those in 0.01M sodium carbonate solution were 3.56×10-1, 7.50×10-1, and 1.83, respectively. The activation energies in 0.01N sodium hydroxide and 0.01M sodium carbonate solution were 14.3 and 14.6 kcal., respectively.