N-Diethylglycine hydrazide, b.p.2 105°, was prepared by the reaction of N-diethyl-glycine ethyl ester and hydrazine hydrate. The hydrazide gave a sulfate of m.p.118° as recrystallized from alcohol, which is not hygroscopic and is stable in the air. For the general isolation of carbonyl compounds from a mixture, N-diethylglycine hydrazide is applied to the mixture in acetic acid acidity, the reaction mixture shaken with ether to remove substances other than carbonyl compounds, and the aqueous solution is alkalized with sodium bicarbonate by which the carbonyl compound precipitates out as the hydra-zone. To regenerate the carbonyl compound, the hydrazone is dissolved in 1N hydrochloric acid, the mixture allowed to stand for 12-24 hours, and the carbonyl compound is liberated.
Eight kinds of coumarin derivatives were prepared, their anthelmintic action determined, and following relationships were found to exist between their chemical structure and anthelmintic action. 1) No outward change occurred on the addition of arabic gum and Tween 80 to the modified Locke-Ringer solution. 2) The action of coumarin was slightly different in the Locke-Ringer modified solution and in the Bunge solution. 3) The anthelmintic action decreased when the double bond between 3- and 4-positions of coumarin, 2-thiocoumarin, and 4-methylcoumarin were hydrogenated to their respective dihydro compounds. 4) No anthelmintic effects were found in ethyl coumarin-3-acetate, methyl isocoumarin-3-carboxylate, and ethyl coumalin-5-carboxylate, but a good effect was found in methyl coumalin-5-carboxylate. 5) There seemed to be no relation between hypnotic and anthelmintic action although both coumarin-3-carboxylic diethylamide and soluble barbital excited the ascaris. 6) It seemed that the compounds melting between 70° and 100° possessed comparatively good efficacy.
1) Pyridinium halides possessing a carbamyl group in the 3-position and methyl, isopropyl, benzyl, phenacyl, or p-bromophenacyl group in the 1-position were prepared, and their absorption spectra of the oxidation and reduction types were compared. The difference between the two types were not so large as at DPN. 2) Whether these synthetic compounds substituted with DPN in a few dehydrogenase system was examined but no such substitution was found to occur. 3) Cultural examinations were made with these compounds as to whether they possessed vitamin action towards Staphylococci and dysentery bacilli. It was found that phenacyl and p-bromophenacyl derivatives substituted with nicotinamide in 10-5-10-6 molar concentration to show a vitamin action. 4) Few considerations were offered as to the cause of the phenomenone as given in (3), in spite of experimental results obtained as iterated in (1) and (2).
A new synthetic method for the preparation of N1-3, 4-dimethylbenzoylsulfanilamide (Irgafen) by the combination of the following processes: An oily substance, Camphren, is obtained by the steam distillation of 1 part of camphor with 4 parts of conc. sulfuric acid; oxidation of Camphren with sodium hypochlorite to 3, 4-dimethylbenzoic acid, which is derived to the phenyl ester; fusion of phenyl 3, 4-dimethylbenzoate, sulfanilamide, and alkali carbonate, or phenyl 3, 4-dimethylbenzoate and alkali salt of sulfanilamide, to obtain the objective Irgafen.
A new kind of condensation of diazonium salts with isonitrosoacetophenones was found. Several kinds of α-diketone monoximes were prepared by this condensation and subsequently hydrolyzed to α-diketones.
3- and 4-ω-Isonitrosoacetylpyridines and their N-oxides were prepared by the reaction of the respective acetyl compounds with isoamyl nitrite. These isonitrosoacetylpyridines underwent condensation with diazonium salts to give several kinds of p-substituted α-isonitrosobenzyl pyridyl ketones. In the case of their N-oxides, such condensation was not seen to occur.
Anion exchange resin was successfully used as a catalyst in the Michael condensation (1:4-addition) of acrolein with ethyl acetamidomalonate or ethyl nitromalonate from which γ-acetamido-γ, γ-dicarbethoxybutyraldehyde or γ-nitro-γ, γ-dicarbethoxybutyraldehyde was obtained in a good yield. Several kinds of thiols were similarly allowed to undergo addition with acrolein by the use of anion exchange resins to yield β-thiopropaldehyde derivatives. These experiments have shown that the use of anion exchange resins as a catalyst in such reactions is advantageous and has opened a new field of use for ion exchangers.
Six kinds of thiazole-carboxylic acid hydrazides and their allied compounds were prepared and their antibacterial action against Mycobacterium tuberculosis bacilli H 37 Rv was tested in Proskauer-Beck's modified medium but none were found to inhibit the growth of the bacilli at 20, 000 dilution.
As a result of studies on the components of flea bane, Erigeron annuus L. and E. macranthus, white crystals (I), m.p. 117-118°, were obtained from the chloroform-soluble portion of the methanolic extract of the flowers, and these were identified as hydroxy-γ-pyrone, i.e. pyromeconic acid, C5H4O3. The yield was approximately 0.7% of the dried flower. This acid was found only in trace amounts in the stem, and about one-fifth of the amount of flower content in the leaves. This is the first instance of the indication of the presence of this acid in plants. The ether-soluble portion of the said methanolic extract yielded some yellow crystals, and the ethyl acetate-soluble portion yielded a kind of flavone.
The yellow crystals (II) obtained from the ether-soluble portion, and the crystals (III) from the ethyl acetate-soluble portion, of the methanolic extract of the flowers of Erigeron annuus and E. macranthus, were further examined and (II) was found to be quercetin. The flavone compound (III) yielded apigenin as the aglycone and was found to be bonded to glucuronic acid. The bonding ratio was one molecule each and the position of the bonding was the C7 of apigenin which indicated the glucuronide to be apigenin-7-glucuronide. This is a new flavone glucuronide never previously found in nature.
Antibacterial activity of various compounds were tested in vitro. 2, 5-Dimethyl-4'-hydroxydiphenyl ether and some lichen components such as anziaic acid, microphyllic acid, protocetraric acid, α-collatolic acid, collatolon, rangiformic acid, l-protolichesterinic acid, and sphaerophorol, were able to inhibit the growth of Micrococcus pyogenes var. aureus in 80, 000 dilutions, and anziaic acid, microphyllic acid, protocetraric acid, α-collatolic acid, collatolon, rangiformic acid, β-collatolic acid, and stictinic acid, all lichen substances, were also able to inhibit the growth of Escherichia coli communior in 80, 000 dilutions. Anziaic acid, microphyllic acid, protocetraric acid, α-collatolic acid, sphae-rophorol, divaricatic acid, and sphaerophorin, the lichen substances, and 2, 5-dimethyl-3-hydroxydiphenyl ether, and 3, 7-dihydroxy-1, 9-dimethyldibenzofuran were able to inhibit the growth of Bacillus subtilis in 80, 000 or more dilutions. Of these compounds, anziaic acid, microphyllic acid, protocetraric acid, and α-collatolic acid were all effective against the three kinds of microorganisms tested, in 80, 000 dilutions.
Hydrolysis of 2-amino-5-benzamido-4-phenylthiazole with dil. hydrochloric acid resulted in the formation of a new substance, 5-phenyl-2-thiohydantoin, which was confirmed by its preparation from α-phenylglycine.
Ionization constants and absorption spectra of 4-aminopyridine (A), its N-oxide (B), 4-aminoquinoline (C), and its N-oxide (D), were determined in water and in sulfuric acid as solvents. Results obtained are given below: 1) As shown in Table II, the N→O compounds were generally bathochromic compared to the N+-H type, in either solvent. 2) The pKa of the equilibrium such as (II) in aqueous solution was found to be 3.54 for (B) which is extremely small compared to that of 9.17 for (A) and (C). 3) The pKa of the equilibrium such as (VIII) in conc. sulfuric acid was: (A)=-6.55, (B)=-6.27, (C)=-7.11, (D)=-6.55, which showed that the values for the N-oxide compounds were larger in both cases. The above results were explained from the resonance effect of the substituents, and the resonance energy contributed by the amino radical in (I) and (IV) were calculated as 22-23 kcal. per mole.
A powerful antihistamine had previously been obtained in ethylenediamine series, are γ-substituted derivatives of pyridine homologs. In a similar manner, 18 kinds of compounds were obtained including N, N-dimethyl-N′-furfuryl-N′-4-(2, 6-lutidyl)-ethylenediamine, N, N-dimethyl-N′-(p-chlorobenzyl)-N′-4-pyridylethylenediamine, N, N-dimethyl-N′-phenyl-N′-4-(2, 6-lutidyl)-ethylenediamine, and allied compounds.
Starting with 4-chlorolutidine, 4-phenyl-4-[4-(2, 6-lutidyl)]-6-dimethylamino-3-hexanone (V) was prepared via α-phenyl-α-4-(2, 6-lutidyl)-acetonitrile (II) and 2-phenyl-2-[4-(2, 6-lutidyl)]-4-dimethylaminobutyronitrile (IV). Animal tests showed that the compound (V) possessed a somewhat remarkable action of killing pain.
Using mature male rabbits, following facts were found: 1) When the time elapsed between the drawing of blood was comparatively short (2 hours), and the amount of blood drawn was over about 3cc., the serum protein concentration was found to decrease whereas when the amount of blood drawn was limited to below one cc., no significant change was observed. 2) When the interval between the drawing of blood was lengthened (approx. 6 hours), there was found no significant change in the concentration of serum protein, irrespective of the amount of blood drawn. 3) Administration of parotin was found to lower the concentration of serum protein in comparison to the control animal irrespective of the amount of blood drawn.
Mold preventing action against soy sauce was tested with 16 kinds of compounds comprising two groups: First Group composed of phenylacetic acid derivatives, and Second Group of p-aminosalicylic acid derivatives. Compounds of both groups were found to possess only a very weak mold preventing action in approximately 0.001-0.01% concentration with the exception of sodium o-cresyl-p-aminosalicylate which managed to prevent the growth of molds for 22.5 days in approximately 0.01% concentration.
Fungistatic and sporostatic effects of some mercury compounds were tested against pathogenic fungi, such as Trychophyton interdigitale and Achorion Schoenleinii. The best effects were found in Merthiolate and phenylmercuric acetate which were able to completely inhibit the growth of fungi in 1:1, 024, 000 and 1:258, 000 dilutions, respectively. On the other hand, Mercurochrome and Salyrgan were totally ineffective. It was additionally found that the bacteriostatic and fungistatic actions were more or less parallel in mercurial compounds.
Growth inhibitory action in vitro of 27 kinds of compounds was tested against H2 strain of human tubercle bacilli. Some effects were found in the condensation products of isonicotinic acid hydrazide and aromatic aldehydes, 2-hydrazino-4-methyl-6-hydroxy-pyrimidine, 2-hydrazino-4-methylpyrimidine, and Girard P reagent.
2-Imino-3-(p-aminosulfonylbenzene)-4-thiazolidon was obtained from p-chloroacet-aminobenzenesulfonamide and potassium thiocyanate, and its heating with hydrochloric acid under a pressure resulted in the formation of ammonium p-aminosulfonylbenzene-dithiocarbamate. The latter yielded with sodium chloroacetate 2-thio-3-(p-aminosulfonylbenzene)-4-thiazolidone. By the condensation of 4-thiazolidones, possessing imino, sulfur, or oxygen in the 2-position, and p-acetaminobenzaldehyde, 2-imino, 2-thio, or 2-oxo derivatives of 5-acetaminobenzal-4-thiazolidones were obtained.
A series of compounds in which the 2-position of the thiazole ring was bonded to sulfanilamide through hydrazino group were prepared in order to obtain effective antitubercular preparations. Deacetylation of thiazole compounds, obtained by the condensation of p-acetaminobenzenesulfonyl thiosemicarbazide with α, β-dichloroethyl ether, monochloroacetone, ω-bromoacetophenone, ethyl bromoacetoacetate, and ethyl chloroacetate, respectively yielded 2-(p-aminobenzenesulfonyl)-hydrazino-thiazole, -4-methylthiazole, -4-phenylthiazole, -4-methyl-5-carbethoxythiazole, and -4-thiazolidone. Of these compound, the 4-thiazolidone derivative showed a remarkable action in inhibiting the growth of tubercle bacilli in vitro.
The fatty acids comprising the fatty oil obtained by the ether extraction of the fruits of Litsea japonica Mirb. were chiefly lauric acid, with capric acid, a small amount of myristic acid and traces of lindellic acid, tsuzuic acid and oleic acid. The fatty oil can be used in place of theobroma oil JP VI.
Acrylonitrile reacts with 4-methyl-5-β-acetoxyethyl-2-mercaptothiazole or 4-methyl-5-β-hydroxyethyl-2-mercaptothiazole, in the presence of sodium hydroxide, to give a substance, C12H15N3OS2, m.p. 62-63°, which was proved to be 3-β-cyanoethyl-4-methyl-5-β-cyanoethoxyethyl-2-thiono-4-thiazoline by its synthesis by the cyanoethylation of 3-β-cyanoethyl-4-methyl-5-β-hydroxyethyl-2-thiono-4-thiazoline in dioxane solution with acrylonitrile, in the presence of sodium hydroxide. 3-β-Cyanoethyl-4-methyl-5-β-hydroxyethyl-2-thiono-4-thiazoline, m.p. 78-78.5°, was obtained from β-aminopropionitrile by the action of γ-aceto-γ-chloropropyl alcohol and carbon disulfide, or by the deacetylation of 3-β-cyanoethyl-4-methyl-5-β-acetoxyethyl-2-thiono-4-thiazoline, m.p. 79-79.5°. This latter compound was prepared from β-aminopropionitrile, γ-aceto-γ-chloropropyl acetate, and carbon disulfide.
Condensation of the salts of N-[2-methyl-4-aminopyrimidyl-(5)]-methyldithiocarbamic acid, such as its ammonium salt (I), or 2-methyl-4-amino-5-aminomethylpyrimidine (II), with carbon disulfide, and ammonia with γ-aceto-γ-chloropropyl chloride (III), results in the initial formation of α-aceto-γ-chloropropyl N-[2-methyl-4-aminopyrimidyl-(5)]-methyldithiocarbamate (IV) which, being extremely unstable, immediately undergoes intramolecular rearrangement to transit to its isomer, 2-methyl-2-chlorotetrahydrofuryl-(3) N-[2-methyl-4-aminopyrimidyl-(5)]-methyldithiocarbamate (V). However, the use of 2-methyl-2, 3-dichlorotetrahydrofuran (VI), the cyclic isomer of (III) instead of (III), resulted in total failure to form (V).
From the measurement of constants and the components obtained by the saponification of the leaf wax from 38 kinds of Confiferales examined, it was found that the Coniferal wax could be divided into two groups, A and B. A Group consists of Juniperus, Chamaecyparis, Thujopsis, Thuja, Biota, Cunninghamia, Cryptomeria, Taiwania, Pinus, Cedrus, Abies, Tsuga, Picea, and Torreya, while the B Group consists of Sciadopitys, Larix, Pseudolarix, Pseudotsuga, Cephalotaxus, Podocarpus, and Taxus. The wax from the A Group possesses a large ester number and the chief component is estolides of juniperic and sabinic acids. The wax from the B Group does not contain these estolides as a chief component or is totally devoid of them. There is no instance that two groups of plants are present in one genus. 1, 12-Dodecanediol, 1, 16-hexadecanediol, 10-nonacosanol, and melissyl alcohol were detected from the non-saponifiable matter.
1) Oil of egg yolk was saponified with alcoholic potash and separated into non-saponifiable matter and acid substance. 2) A ketosteroid was obtained from the non-saponifiable matter as white needle crystals, m.p. 142-143°, which gave a semicarbazone of m.p. 258-260°, and an oxime of m.p. 188-190°. 3) The above ketosteroid gave a positive vaginal smear reaction in young female mice, and caused the increase of the weight of seminal vesicles and prostatic glands in castrated male mice. 4) The acid portion was composed of liquid acids containing oleic, linolic, and higher unsaturated fatty acids, and solid acids containing palmitic and stearic acid.
The alcoholic solution of formyldesoxybenzoin (F. D. B.) gives purplish brown precipitate with trivalent iron and seems to offer possible specific coloring reagent for Fe+++. The limit of determination is 1γ per drop (0.05cc.). This color reaction is not affected by the concurrent presence of 100 volumes of Ni++, Co++, and Cu++. Attempt to derive F. D. B. to its oxime with hydroxylamine resulted in the formation of 4, 5-diphenylisoxazole, instead of the oxime, which indicated the structure of F. D. B. in alcoholic solution. In other words, F. D. B. was proved to be in a stable β-type and that the colored precipitate with trivalent iron was formed by the intramolecular complex salt of this β-type.
The chromium oxide formed by the thermal decomposition, at 350°, of ammonium chromium chromate prepared from chromium salt and chromate, is a mixture of chromium oxides which can be indicated by CrO2. This chromium oxide was used as a catalyst in the high pressure acid reduction of camellia oil in nichrome autoclave but the oxide did not seem to possess any catalytic activity. However, under the present experimental conditions, the inner wall of the autoclave seemed to induce some side reactions so that the above conclusions should be checked by different experimental apparatus. Infrared absorption spectral measurements indicated the presence of a fair amount of ketones and hydrocarbons as the products of side reaction.
In order to remove the influence of the conditions of the inner wall of the autoclave, glass lining was devised by which high pressure acid reduction of camellia oil and ethyl laurate was carried out. The results showed that chromic oxide possessed no catalytic ability in this reaction. The experimental results described in the present and the previous papers have revealed that the conclusion drawn by Miyake should be corrected.
The content of berberine in the barks of trunk, branches, and twigs from one tree, as a condition for collection, was determined with phellodendron obtained from Phellodendron japonicum. The content in these three parts was found to decrease in that order, approximately in proportion to the diameter of the particular portion examined. The relationship between the time of collection and berberine content was found to be independent of each other, the content being the maximum in July at 3.09%, that in June being 2.68%, in August, 2.88%, and an average of 2.28-2.44% in other months. It follows, therefore, that collection of barks from large trees during the summer would furnish materials of excellent quality.
Houttuynia, a widely used crude drug, is the dried stems and leaves of Houttuynia cordata Thunb. (family Saururaceae) collected during the flowering season. The crude drug has been used from olden times as diuretic and the leaves have been found to contain quercitrin. Studies were carried out to determine the suitability of the collecting season. The floral spike and fruit spike were collected separately from both of which isoquercitrin, and not quercitrin, was confirmed. The leaves contained quercitrin but not isoquercitrin. Both quercitrin and isoquercitrin are 3′, 4′-dihydroxyflavonol and possess mild laxative and diuretic action. According to Ozawa, this compound also possesses rutin-like action. It follows, therefore, that if the terrestrial plant is collected during the flowering season, the additive pharmacological action of the two chemicals could be expected.
The mucuous substance from Gloiopeltis furcata has been found to inhibit blood coagulation, both in vitro and in vivo, tested with rabbits, although some toxicity was found. In diluted solutions, toxicity was not apparent, and the lasting effect was much better than heparin. It also took more than 24 hours for the blood to regain normal coagulation time. The amount of calcium and protein in blood were determined and calcium was assumed to influence to some extent the coagulation inhibition.
Based on the theory of synergic effect of sulfa drugs, three new salts of p-aminomethylphenyl methyl sulfone with sulfanylthiourea, sulfacetamide, and sulfathiazole were prepared, and their X-ray diffraction data and physical constants were determined. The antibacterial effects in vitro of these compounds were compared with those of basic components in artificial medium. No significant synergism was found in in vitro experiment, as compared to each component, but it was expected that the remarkably increased solubility of these salts might produce some effect on the mode of action in vivo.
Hypericin was isolated as crystals from Hypericum erectum Thund. Since hypericin dissolves in pyridine and gives dark red coloration, this method can be utilized in detecting the presence of hypericin in plant samples viewed under a microscope. The presence of hypericin was detected in 23 out of 29 plants of Guttiferae family.