It has been found that, besides the two kinds of yellow and red crystals of fluorescein, there was another kind of orange crystals, containing one mole of the water of crystallization, that precipitate out at above pH 5 of the solution, and that there exist yellow crystals of m.p. 191-193°, besides the known colorless crystals of m.p. 200-202°, for fluorescein acetate. In the present series of experiments, the structure of three kinds of fluorescein in solution was observed by the determination of absorption spectra and polarography. It was thereby concluded that the three kinds of fluorescein took up the same structure in a state of solution and the o-quinone type (formula V) was assumed for it in solution below pH 2, p-quinone type (formula IV) at above pH 5, and lactone type (formula VI) at pH 3-4.
The three kinds of fluorescein crystals, red, yellow, and orange, were assumed to be those of o-quinone type (I), lactone type (II), and p-quinone type (III) from the results of comparative examination of formation conditions, absorption and manner of liberation of dry ammonia and dry hydrogen chloride gas, with the ethyl derivative of fluorescein. The X-ray powder photograph also gave different reflection lines for the three kinds. It was also assumed that the colorless and yellow diacetates were respectively that of the lactone type and o-quinone type.
In continuation of the cultivation tests carried out in 1950 and 1951, cultivation tests on Chenopodium ambrosioides L. var. anthelminticum A. Gray were carried out in cooler regions, i.e. highlands of Nagano Prefecture, Tohoku districts, and in the Hokkaido, during 1952. Distillation tests and determination of ascaridol were carried out on the crop and the summarized results of tests carried out during the three years are as follows: 1) Growth, yields of crop and fruits, content of essential oil, and content of ascaridol during 1952 are shown in Table I. Atmospheric temperature and rainfall in various regions during this year are shown in Table II. 2) It was found that the growth, especially at the outset, is retarded in the cooler regions, compared to that in the standard plot, but the yields of crop and fruits are not necessarily inferior to those of the warm region. 3) The contents of essential oil and ascaridol are also not necessarily inferior in the crop from the cooler regions to those from the warm region.
In spite of the fact that the presence of the carbonyl group is naturally assumed in α-aceto-γ-hydroxypropyl (IV) and α-aceto-γ-acetoxypropyl N-[2-methyl-4-aminopyrimidyl-(5)]-methyldithiocarbamate (VII), neither of these compounds show the absorption band around 5.85μ that is generally attributed to this group in infrared absorption spectrum. In order to compare with these compounds acetonyl and phenacyl N-[2-methyl-4-aminopyrimidyl-(5)]-methyldithiocarbamate (X and XI) were prepared and their infrared absorption spectra were determined. These compounds also were found to be devoid of absorption bands around 5.85μ. The cause of this phenomenon was assumed to be either due to the fact that the absorption of carbonyl has shifted to the longer wave length and overlaps with the absorption due to C=N bond at around 6μ, or that these compounds exist in their enolized form and thereby lack the absorption due to C=O group. However, no chemical basis for either has yet been obtained.
Yoshida and others determined infrared absorption spectra of α-aceto-γ-hydroxypropyl (I), α-aceto-γ-acetoxypropyl (II), and α-aceto-γ-ethoxypropyl N-[2-methyl-4-aminopyrimidyl-(5)]-methyldithiocarbamate (V), and assumed that the absorption band that appears around 9μ is due to the C-O-C bond of the tetrahydrofuran nucleus. From such a conclusion, they assumed that the above dithiourethanes were respectively 2-methyl-2-hydroxytetrahydrofuryl-(3) (I′), 2-methyl-2-acetoxytetrahydrofuryl-(3) (II′), and 2-methyl-2-ethoxytetrahydrofuryl-(3) N-[2-methyl-4-aminopyrimidyl-(5)]-methyl-dithiocarbamate (V′). The analysis of the absorption band around 9 μ is extremely difficult and it is dangerous to make the above conclusion from this fact alone. The present writers carried out examination of the reactivity of these compounds and pointed out that the results would be extremely irrational if the compounds were given the formulae (I′), (II′), and (V′), and that the chemical changes could be clearly explained by giving them the formulae (I), (II), and (V).
3-Dimethylamino-1, 1-di (2′-thienyl)-butene-1 was first synthesized by Adamson by the dehydration of the carbinol (I) prepared from thiophene and ethyl β-dimethylamino-butyric acid ester by the lithium method. In the present series of experiments, the carbinol (I) was obtained in approximately 50% yield from 2-thienyl sodium at a low temperature of -20° to -40°, without the use of expensive and difficult to obtain lithium. Dehydration of (I) with acetyl chloride gave the objective (II) in a good yield of approximately 70%.
Eight kinds of hitherto unknown phenoxymethyl ethers were prepared and the influence of the kinds, position, and number of the substituents was tested against mice. It was found, as expected from the structure, that the compounds were all unstable to acids in vitro and gave characteristic coloration with sulfuric acid. None of the compounds showed any degree of effect in vitro, only the nitro compounds showing a slight effect such as standing of hair, uneasiness, and teary eyes. These compounds were all tasteless and odorless that they were easily administered.
With acetamide or acetanilide as the addition agent, 1-phenyl-3-methylpyrazolone or thiobarbituric acid was reacted with orthoformic ester and symmetrical methineoxonol dyes were obtained. Similarly, oxonol dyes were prepared from barbituric acid or 3-ethylrhodanine with cyanoacetic ester as the addition agent or from 4-imidothiobarbituric acid and orthoformic ester with malonic dinitrile as the addition agent. Merocarbocyanin dyes were obtained by the reaction of the oxonol dyes obtained above from the cyclic diketomethylene compound and quaternary salt of heterocyclic bases possessing the methyl group in the 2-position.
By the application of orthoformic ester and p-anisidine, m-aminophenol, p-toluidine, N, N′-diphenylhydrazine, or phenylhydrazine, respectively on barbituric or thiobarbituric acid, corresponding anilidomethylene or hydrazinodimethylene compounds were obtained. Application of orthoformic ester and benzidine or m-phenylenediamine on barbituric acid yielded the corresponding diaminomethylene compounds.
As one step in the preparation of procainamide, electrolytic reduction of the nitro group in β-diethylaminoethyl-p-nitrobenzamide was carried out with diluted hydrochloric acid as the electrolytic solution with tin as the cathode or lead as a cathode and stannous chloride as the carrier, and procainamide was obtained in a good yield.
By the condensation of aromatic aldehydes and carbon disulfide with aminoacetonitrile or dl-α-amino-β-ethylidenepropionitrile in ethyl acetate, corresponding 2-mercapto-5-arylideneaminothiazoles and 2-mercapto-4-propenyl-5-arylideneaminothiazoles were obtained. Application of alkyl halides, allyl bromide, or benzyl chloride, on the sodium salt of these mercapto compounds yielded the corresponding 2-alkyl (allyl or benzyl)-mercapto derivatives.
Application of acetyl or benzoyl isothiocyanate on aminoacetonitrile or dl-α-amino-β-ethylidenepropionitrile, in ether or a mixture of ether and ethyl acetate, resulted in the formation of 2-acetamino- and 2-acetamino (or benzamino)-4-propenyl-5-aminothiazoles. Condensation of aromatic aldehydes with these 5-aminothiazole derivatives gave the Schiff bases. The same Schiff bases were obtained by the application of acetyl or benzoyl isothiocyanate on aminoacetonitrile or dl-α-amino-β-ethylidenepropionitrile in ethyl acetate or a mixture of ether and ethyl acetate.
2-Hydroxy-5-benzalaminothiazole was obtained by the application of COS on benzal-aminoacetonitrile in alcohol. 2-Hydroxy-5-arylideneaminothiazoles are formed when COS is applied on aminoacetonitrile and aromatic aldehydes in a mixture of alcohol and ethyl acetate. Condensation of alkyl halides, allyl bromide, or benzyl chloride with the sodium salts of these 2-hydroxy compounds gave the corresponding alkoxy (allyloxy or benzyloxy)-5-arylideneaminothiazoles. Of the latter, 2-ethoxy-5-benzalaminothiazole was also obtained by the application of benzalaminoacetonitrile on ethylxanthoacetic acid.
1) Application of potassium thiocyanate and bromine on β-naphthol, in accordance with the formula of Kaufmann or Neu failed to give the expected 1-thiocyano compound, contrary to the original report and in its stead, substances assumed to have been formed secondarily from the expected thiocyano compound, i.e. 1-mercapto-2-naphtholcarboxylate and 2, 2′-dihydroxy-1, 1′-dinaphthyl sulfide, were obtained. 2) Warming of 1-mercapto-2-naphtholcarboxylate with alkali yielded 2, 2′-dihydroxy-1, 1′-dinaphthyl sulfide and disulfide. 3) The structure of the foregoing three compounds were proved by their respective preparation from 2-chloro-2-naphthol.
In the previous report, it was assumed from the examination of the reaction of aromatic aldehydes with α-amino acids possessing a primary amino group by paper chromatography that C-type and D-type bases of (I) were formed besides the existing data. In the present series of experiments, isolation and identification of the C-type base in the reaction between benzaldehyde and glycine, alanine, or α-aminoisobutyric acid were made and the assumption made in the previous report was thereby confirmed.
In continuation of previous reports on the reaction of aromatic aldehydes and α-amino acids, α-aminophenylacetic acid was used in place of the previous aliphatic acids. It was found that the reaction also occurred in this case as in equation (1) but there was seen a tendency for the formation of a larger amounts of A-type and C-type bases of formula (I), contrary to the case of aliphatic amino acids. It was also proved by the present series of experiments that water was formed during the reaction when the amino group in the α-amino acid was primary or secondary. A reaction mechanism was proposed for the formation of numerous bases from the present and two preceding experiments by enlarging upon the considerations made in a previous paper.
A paper chromatography of alcohols was devised. A solution decanted from a wellshaken mixture of 0.5cc. of an alcohol, 0.1-0.4cc. of ether containing 20% of carbon disulfide, and 1g. of powdered potassium hydroxide, is evaporated to dryness and the residue wetted with a drop of water is spotted on the start line of a filter paper. This is developed with butanol saturated with 2% aqueous solution of potassium hydroxide or sodium carbonate, and the finished papergram is examined under an ultraviolet light or with the Grote's reagent. This method was found to be applicable to the detection of methanol in ethanol and wine.
Compounds which possess hydroxyl groups in a vicinal position undergo change in their electrical conductivity in boric acid solution by forming some kind of a complex salt of boric acid. Based on this fact, sugars and flavonoids can be separated by paper electromigration using boric acid or borax solution as the electrolyte. Sugars which could not be separated by paper partition chromatography could be separated easily by this method. In the case of flavonoids, the distance of migration was found to be proportional to the number of the vicinal hydroxyl groups in their molecule. Coloring agent used for sugars was aniline biphthalate, and lithium aluminum hydride was found to be the most sensible color reagent for flavonoids.
A group of milking cows in a farm in the suburb of kobe died in July, 1952, and this was followed by a death or slaughter of a total of 79 heads of cattle during about one month. As a result of investigation, this was found to be due to the toxic substance produced by a kind of Penicillium velutinum attached in the dry malt in the feed given to these cattle. This strain of the fungus was found to be different in cultural form and type from any of the known, similar toxic strain of fungus that, pending decision of a formal scientific name, it was tentatively designated as the Hori-Yamamoto strain. This Hori-Yamamoto strain was found to multiply aerobically only on a medium containing sugars and produce toxic substance. For example, 0.1cc. of the culture filtrate from the Sabouraud medium, cultivated at 25-27°C; for 10 days, was able to kill mice of 15-17g. weight in 10-15 hours. A residue obtained by the evaporation of this culture filtrate is a hygroscopic brown powder which dissolves easily in hydrated organic solvents and aqueous alkali solutions, and possesses a toxicity of 50mg./kg. mouse, which failed to decrease by boiling at 100° for 30minutes.
The Fries rearrangement of ω-chloroacetoguaiacol (I) was found to give mainly ω-chloroisoacetovanillone (II) with a small amount of ω-chloroisoacetovanillone chloroacetate (II′). The expected ω-chloroacetovanillone was not detected in the reaction mixture. The best result was obtained when 2.2 moles of aluminum chloride was used with 1 mole of (I) in carbon disulfide at an ordinary temperature (25°). When the reaction was carried out in benzene or toluene, the only ketonic product isolated was ω-chloroacetophenone and its p-methyl derivative which showed that the Fries rearrangement occurs intermolecularly and not intramolecularly as was earlier assumed. (II′) was obtained in a good yield from (I) and chloroacetyl chloride by a Friedel-Crafts type reaction. A mechanism for the formation of (II) and (II′) was also postulated.
Solubilities of lipophilic vitamins and hormones were compared by dissolving them in various concentrations of (12)-oxyethylenesorbitan monolaurate, a nonionic surface active agent. It was found that the solubilizing ability increased extremelyin a conc entration range of 65% of the surfactant and above that concentration. Inorder to clarify the cause of this phenomenon, partial specific volume, viscosity, electricconducti vity of the salts added, and vapor pressure were measured of various concentration of the solution of surface active agents. It was found that the values of these constants also showed a sudden change at the same concentration range as above. It is assumed, from these results, that sudden increase in the solubilization power is due to some abrupt change in the internal structure of the surfactant solution.
Heating of diethanolamine hydrochloride at 200-230° results in the formation of morpholine alone, but the same at 230-240° gives morpholine and piperazine. The product from the heating at 250-260° is chiefly piperazine and only a small amount of morpholine is formed. N-Alkyldiethanolamine hydrochloride also forms N-alkylmorpholine and N-alkylpiperazine by heating. Both morpholine and N-alkylmorpholine undergo partial decomposition when heated at a high temperature to form piperazine and N-alkylpiperazine, respectively. By heating a mixture of diethanolamine hydrochloride and monoalkylamine hydrochloride at 250-260° for 3-4 hours, N-monoalkylpiperazine is obtained in 20-30% yield of the theoretical amount. Similar heating of the mixture of the hydrochloride of diethanolamine and dialkylamine also yields N-monoalkylpiperazine. Heating of a mixture of the hydrochloride of diethanolamine or N-alkyldiethanol-amine and ammonium chloride also results in the formation of the corresponding piperazine or N-monoalkylpiperazine in 20-25% yield of the theoretical amount. Morpholine, piperazine, and N-alkylmorpholine are formed as by-products in these reactions.
Reaction of the sodium salt (II) of vitamin B1 and sodium alkyl thiosulfate (III) in aqueous solution results in the formation of vitamin B1 alkyl disulfide (I) and the yield is rather poor when the product (I) is water-soluble. This was assumed to be due to the destruction of (I) by sodium sulfite that is formed as a by-product during this reaction. The fact that the following four equilibria existed in the reaction mixture when (II) and (III) or (I) and sodium sulfite were reacted was confirmed: (II) + (III) ⇔ (I) + Na2SO3, (I) + Na2SO3 ⇔ (VI) + (VII) (II) + (VI) ⇔ (V) +Na2SO3, (III) + (VII) ⇔ (IV) + Na2SO3 in which (IV) is dialkyl disulfide, (V), vitamin B1 disulfide, (VI), sodium thiaminyl-thiosulfate, and (VII), sodium mercaptide.
From the water-soluble fraction of the dried leaves of Digitalis purpurea, a primary glycoside, purpurea glycoside B, and a substance tentatively designated as Substance IIA were isolated. Acetylation of the latter substance gave Digitalinum verum hexaacetate and hydrolysis of IIA yielded dianhydrogitoxigenin, glucose, and digitalose. This, however, showed extremely stronger toxicity than the digitalinum verum prepared from the digitalis seeds. This Substance IIA is assumed to possess Digitalinum verum as a chief constituent but is probably accompanied by a different cardiac glycoside containing gitoxigenin as the aglycone.
From the water-soluble fraction of the leaves of Digitalis purpurea, gitorin (gitoxigenin monoglucoside) was isolated. This substance was found to be present in a state which made it extremely difficult to separate from Digitalinum verum. Gitonin was obtained by fractionating the acetyl compound of the mixture of these substances and by subsequent saponification with potassium bicarbonate.
The methyl group in 2-methyl-5-phenylthiadiazole (I) shows approximately the same reactivity as that in 2-methylthiazole and undergoes dehydration-condensation with aromatic aldehydes in the presence of anhydrous zinc chloride. The reactivity increases when (I) is derived to the methiodide and easily undergoes condensation with aromatic aldehydes or p-nitrosodimethylaniline in the presence of piperidine. Formation of cyanine dyes can also be detected.
Sobel prepared pyridonium cholesteryl sulfate. The present authors found that the compounds of a similar type were formed generally by the reaction between pyridine-type alkaloids, R3N, and a triterpene alcohol, R′-OH. To a chloroform solution of pyridine, quinoline, or nicotine, is added in drops chlorosulfonic acid, under ice-chilling, and the product thereby formed is reacted with β-amyrin in a solvent containing acetic anhydride, by which a triterpene sulfate of the alkaloid is formed by the following reaction formulae: R3N+SO3HCl→R3N⋅SO3 (HCl) R′OH+R3NSO4→R′SO3H⋅R3N Such substances are easily soluble in water and the solution foams like saponin. Paper chromatography of these substances was also studied.
Attempts were made to introduce the nitro group into the 5-position of some furan derivatives possessing a substituent in the 2-position of the furan nucleus by the application of acetic anhydride and conc. nitric acid (sp. gr. 1.44), in order to determine optimum conditions of reaction and suitable catalyst. Furfural diacetate (I), ethyl furoate (II), furfuryl acetate (III), and furylacrylic acid (IV) were the furan derivatives used, and conc. sulfuric acid, stannous chloride, orthophosphoric acid, boric acid, phosphorus pentoxide, oxalic acid, and p-toluenesulfonic acid, were selected for the catalyst. (I) formed 2-(5-nitro)-furfural diacetate in 73% yield from a mixture of (I): HNO3:Ac2O in weight ratio of 1:1.5:5.3, and in 78% yield when conc. sulfuric acid and p-toluenesulfonic acid were used as the catalyst. When orthophosphoric acid was used as the catalyst, (II) gave ethyl 2-(5-nitro)-furoate in 72% yield, (III) gave 2-(5-nitro)-furfuryl acetate in 78% yield, and (IV) gave 2-(5-nitro)-furylacrylic acid in 58% yield.
By warming acetylacetoacrylic acid (II), m.p. 28.5°, with acetic anhydride in glacial acetic acid, with sulfuric acid as a catalyst, protoanemonin (I), b.p.0.1 32-36°, was obtained as needle crystals (m.p. -5°), in 57% yield. The yield form levulinic acid was 18%. The pH and antibacterial activities remained unchanged for a few months when 0.2% propylene glycol solution of (I) was allowed to stand at around 5° with the addition of 0.005% of hydroquinone or propyl gallate.
Ca3 (P32O4) 2 was obtained in 83% yield from radioactive phosphoric acid. Radioactive phosphoryl chloride, P32OCl3, was prepared in 41% yield by the passage of phosgene over a mixture of this radioactive calcium phosphate and activated carbon heated to 350°.
Equine serum was purified by the ammonium sulfate fractional salting out method and crystalline albumin and β- and γ-globulin were obtained as a uniform, pure product by electrophoresis. The yield thereby obtained was 8-10g. of crystalline albumin, 0.75g. of β-globulin, 5-6g. of γ-globulin, and 1.0g. of equine serum lipoproteine, from 1L. of serum. α-Globulin could not be obtained as a uniform product. Each fraction of equine serum precipitating by the stepwise concentration of ammonium sulfate was comparatively examined by electrophoresis.