YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
75 巻 , 7 号
選択された号の論文の37件中1~37を表示しています
  • 志甫 伝逸, 高林 昇
    1955 年 75 巻 7 号 p. 773-775
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    4-Hydrazino-6-methylpyrimidine was prepared in a good yield by the reaction of 4-chloro-6-methylpyrimidine and hydrazine hydrate. 2-Amino-4-hydrazino-6-methylpyrimidine was prepared in a similar manner from 2-amino-4-chloro-6-methylpyrimidine and the latter was used further for the preparation of 2-amino-4-thiosemicarbazido- and 2-amino-4-(4′-methyl-5′-β-hydroxyethylthiazolyl-2′) hydrazino-6-methylpyrimidine, and 2-amino-4-aminoguanidyl-6-methylpyrimidine dihydrochloride.
  • 志甫 伝逸, 高林 昇
    1955 年 75 巻 7 号 p. 776-778
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    3-Methyl-6-hydrazinopyridazine (I) was prepared from 6-chloro compound (III) and hydrazine hydrate, almost in a quantitative yield. Reaction of the hydrochloride (m.p. 231° (decomp.)) of (I) and potassium thiocyanate gave the thiosemicarbazido compound, while that and cyanamide gave the hydrochloride of the aminoguanidino compound. Monochloroacetone and the former yielded 3-methyl-6-[N′-(4′-methylthiazolyl-2′)] hydrazinopyridazine, while γ-chloro-γ-acetopropyl alcohol and the same compound yielded 3-methyl-6-[N′-(4′-methyl-5′-β-hydroxyethylthiazolyl-2′)] hydrazinopyridazine, both as hydrochlorides.
  • 高林 昇
    1955 年 75 巻 7 号 p. 778-781
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Eight kinds of 3-alkoxy-6-chloropyridazine and 3 kinds of 3-alkylthio-6-chloropyridazine, and their derivatives prepared and their behavior to anionoid substitution was examined. 3-Alkylthio-4- and -5-methyl-6-chloropyridazines were also prepared.
  • 石黒 武雄, 古賀 直文, 高村 恭治, 丸山 哲生
    1955 年 75 巻 7 号 p. 781-785
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    The flowers of Osmanthus fragrans Lour. var. aurantiacus Makino were soaked in petroleum ether immediately after collection, digested for one week, and filtered with pressing. The aqueous layer of the filtrate was extracted with ether. The residual flowers were then digested with warm dehydrated ethanol for 16 hours.
    1) The portion soluble in petroleum ether is composed of concretes amounting to 0.214% of the original flowers and its treatment with cold dehydrated ethanol separates it into 0.163% of absolutes and 0.043% of flower wax, which is chiefly composed of triacontane, C30H62.
    2) The ether solution was chromatographically purified and p-hydroxyphenethyl alcohol C8H10O2, was isolated.
    3) The ethanol-soluble portion yielded D-mannitol.
    4) The water-soluble portion was fractionated with lead acetate and basic lead acetate. D-Mannitol was isolated from the filtrate and the presence of D-glucose and D-fructose was detected by paper chromatography. The precipitate obtained by lead acetate and the portion soluble in ethanol, yielded succinic acid.
  • 金庭 延慶
    1955 年 75 巻 7 号 p. 785-788
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    1) Nitration and bromination of resacetophenone and its monomethyl and dimethyl ethers were concluded to occur at 5-position.
    2) 5-Bromoresacetophene can be obtained by the hydrolysis of a substance (m.p 84°) of the product obtained from the bromination of resacetophenone monoacetate and melts at 171°.
    3) During the methylation of 5-bromo- and 5-nitro-resacetophenone with dimethyl sulfate, the hydroxyl in the ortho-position of the nitro or bromine group was more easily methylated than that ortho to the acetyl group.
  • 金庭 延慶
    1955 年 75 巻 7 号 p. 788-791
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    1) Nitration and bromination of 4-nitroresorcinol and their monomethyl and dimethyl ethers showed that the nitro or bromine group is introduced into the 6-position.
    2) As for the position of the bromine in the brominated 4-nitroresorcinol and its monomethyl and dimethyl ethers, Hodgson and Dyson had carried out the structural determination of 4-bromo-6-nitroresorcinol 3-methyl ether that this substance was taken as the standard. Methylation of this ether with dimethyl sulfate affords dimethyl ether of m.p. 139°. Methylation of 4-bromo-6-nitroresorcinol 1-methyl ether, m.p. 162°, with dimethyl sulfate affords the dimethyl ether of m.p. 139°. The same methylation of 4-bromo-6-nitroresorcinol yields a monomethyl ether, m.p. 114°, which is further derived to the dimethyl ether of m.p. 139°. Admixtute of all the substances of the same melting point showed no depression of m.p.
    3) 4-Bromo-6-nitroresorcinol crystallizes with the water of crystallization, and shows m.p. 134° when dried over sulfuric acid. Its methylation with dimethyl sulfate has shown that the hydroxyl in the ortho-position to bromine is more easily methylated than that ortho to the nitro group.
  • 金庭 延慶
    1955 年 75 巻 7 号 p. 791-794
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    1) Nitration and bromination of β-resorcylic acid and its 4-methyl ether revealed that the nitro or bromine group is introduced into the 5-position.
    2) Methylation of 5-bromo- and 5-nitro-β-resorcylic acid with dimethyl sulfate showed that the hydroxyl in the ortho-position of bromine or nitro group is more easily methylated than that ortho to the carboxyl group, apart from the behavior of the carboxyl.
    3) Orientation of the β-substituted compound of resorcinol was discussed, with emphasis on the aromaticity of resorcinol in the case of free hydroxyl, monoether, and diether.
  • 木下 弥兵衛, 森山 繁隆
    1955 年 75 巻 7 号 p. 795-798
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Using the apparatus described in the previous paper, electrophoreses of barbital, phenobarbital, ethylhexabital, methylhexabital, allobarbital, isomytal, and pentobarbital were carried out. Figs. 1 and 2 show the relationship between migration distance and the voltage or time. The migration distances of these compounds at respective pH values are shown in Table I and Figs. 3-12. Detection of the phoretic images were effected by spraying nitric acid solution of mercuric nitrate and alkaline hypobromous acid by which the images appeared as white spots on yellowish brown background. This method of detection was devised by the writer and was found to enable detection of up to 2γ of barbital, 10γ of methylhexabital, and 5γ of other compounds. The mixtures of these compounds were easily separated by using the Kolthoff buffer solution of pH 9.2 and the Sörensen buffer of pH 9.6, and migrated twice at 400V., 10°, for 60minutes.
  • 増田 亨, 澤 陽一, 浅井 満子, 桑田 智
    1955 年 75 巻 7 号 p. 799-801
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    When FAD was decomposed with hydrochloric acid, the product developed on a paper with butanol: acetic acid: water (4:1:5), and examined under ultraviolet light, absorption band, in regions corresponding to Rf 0.44-0.46, was detected at the borderline between adenosine and adenine, besides the bands of FAD, FMN, riboflavin, AMP, and lumiflavin. In the same chromatogram a benzidine-positive band with Rf 0.11 was detected, but it does not correspond to that of the ribose produced by the decomposition of FAD because ribose shows Rf 0.28 under the same conditions. Although many bands positive to phosphate ion reaction were detected in the chromatogram, the benzidine-positive band is also positive to the reaction. It is reasonable to suppose, therefore, the benzidine-positive band to be ribophosphate and that with Rf 0.44-0.46 for adenine. From the result, it became necessary to correct the authors' previous report on the decomposition of FAD by hydrochloric acid.
    Decomposition of FAD by alkali is very complicated, and is, therefore, not suitable as a tool for the identification of FAD prepared by the authors.
  • 増田 亨, 澤 陽一, 浅井 満子, 桑田 智
    1955 年 75 巻 7 号 p. 802-803
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    To examine the stability of FAD solution, FAD was dissolved in Theorell buffer solution (pH 3.0-9.0) and heated at 100° for 1-5hrs. in fused, coloress ampules. The solution was then developed on paper with butanol:pyridine: water (4:3:7) and the chromatogram was observed under a ultraviolet light to detect the band of FAD. The band was cut out and eluted with phosphate buffer and from the absorption value at 450mμ of the eluate, the residual percentage of FAD was estimated. The residual percentage was 95% immediately after one hour's heating at 100° (pH 7.0). When the same solution in ampules is illuminated with 100-W. electric lamp from a distance of 30cm. for 5hrs., there was observed no change in the quantity of FAD. When the solution was exposed to the October sunlight for 4 or 8hrs., paper chromatography of the solution in both cases showed the bands of FMN, riboflavin, AMP, and lumiflavin, besides that of FAD, but the residual percentage of FAD was as high as 88% even after 8-hr. exposure, contrary to expectations.
  • 生熊 晋
    1955 年 75 巻 7 号 p. 804-806
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    L-threo-1-p-Nitrophenyl-2-benzamido-3-benzoyloxypropan-1-ol (II) was converted with thionyl chloride to L-erythro-O, O-dibenzoyl-1-p-nitrophenylserinol hydrochloride (IV), which was derived to L-erythro-1-p-nitrophenyl-2-benzamido-3-benzoyloxypropan-1-ol (V), and finally hydrolyzed with alkali to L-erythro-1-p-nitrophenyl-2-benzamidopropan-1, 3-diol (VI). These compounds were identified with those obtained by the Moersch method.
  • 上農 義雄, 那波 速男, 上柳 次三郎, 森本 浩, 中守 律夫, 松岡 敏郎
    1955 年 75 巻 7 号 p. 807-811
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Kainic acid (I) comes as colorless needle crystals of m.p. 251° (decomp.), [α]D29: -14.8° (c=1, H2O); it is soluble in water and acetic acid, sparingly soluble in methanol, insoluble in ether, petroleum ether, and benzene, and soluble in acids and alkalis; pK′ of the aqueous solution are 2.05, 4.30, and 10.08; it discolors bromine and poassium permanganate solutions; forms a salt sparingly soluble in water with heavy metals and barium. Its ninhydrin reaction is yellow, coloration with sodium naphthoquinone-4-sulfonate is orange red, and with ferric chloride, yellowish brown. Its infrared absorption curve shows the absorption peculiar to acidic amino acid. Molecular formula corresponds to C10H15O4N, molecular weight 213, and does not contain N-methyl, carbonyl, acetyl, or methoxyl group. In order to examine the properties of the functional groups in (I), the following derivatives were prepared by the routes shown in Fig. 1. Dihydrokainic acid (II), m.p. 272° (decomp.), C10H17O4N. Zinc kainate (III), m.p. over 300°, C10H13O4NZn⋅H2O. Dimethyl kainate (IV), b.p4 145°, C12H19O4N. Dimethyl N-methylkainate methiodide (VI), m.p. 188-194° (decomp.), C14H24O4NI. Monomethyl kainate (V), m.p. 250-252° (decomp.), C11H19O4N. Kainic acid betaine (VII), m.p. 205-210° (decomp.), C13H21O4N. Picrate of (VII), m.p. 174° (decomp.). Dimethyl dihydrokainate (VIII), b.p3 125°, C12H21O4N. Hydrochloride of (VIII), m.p. 158°. Diethyl dihydrokainate (IX), b.p13 105°, C14H25O4N. From the properties of these derivatives, it was seen that (I) possessed one unsaturated group and two carboxyl groups.
  • 上農 義雄, 那波 速男, 上柳 次三郎, 森本 浩, 中守 律夫, 松岡 敏郎
    1955 年 75 巻 7 号 p. 811-814
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Following the previous series of experiments, various derivatives of kainic acid (I) were prepared. N-Acetylkainic acid (XI), m.p. 161-162°, C12H17O5N. Dimethyl N-acetylkainate (XII), b.p4 191-193°, C14H21O5N. N-Acetylkainic diamide (XIII), m, p. 256-258° (decomp.), C12H19O3N3. N-Acetyldihydrokainic acid (XIV), m.p. C12H19O5N. Dimethyl N-acetyldihydrokainate (XV), b.p3 177°, C14H23O5N. N-Acetyldihydrokainic diamide (XVI), m.p. 252-253° (decomp.), C12H21O3N3. Dimethyl dihydrokainate phenylisocyanate (XVII), m.p. 154°, C19H26O5N2. Dimethyl N-ethoxycarbonyldihydrokainate (XVIII), b.p1 160°, C15H25O6N. Dimethyl N-nitrosokainate (XXI), b.p3 178°, C12H18O5N2. N-Acetylkainic anhydride (XIX), m.p. 186°, C12H15O4N. N-Acetyldihydrokainic anhydride (XX), m.p. 182-183°, C12H17O4N. From the properties of these derivatives, the nitrogen in (I) was found to be a secondary amine.
  • 上農 義雄, 那波 速男, 上柳 次三郎, 森本 浩, 中守 律夫, 松岡 敏郎
    1955 年 75 巻 7 号 p. 814-821
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Dry distillation of kainic acid (I) with soda lime afforded C7H11N (II), b.p24 78-80°, which formed pyrrole blue (III), C15H14ON2, on application of isatin. Chromic acid oxidation of (II) yielded C7H9O2N (IV), m.p 83°, whose catalytic reduction gave C7H11O2N (V), m.p. 61°, agreeing with the melting point of isopropylsuccinimide. Dry distillation of (I) and of dihydrokainic acid (VIII) afforded (II) and (C8H9ON)2 (VI), m.p. 156-157°, whose saponification gave C8H11O2N (VII), m.p. 178° (decomp.). Both (II) and (VII) give postive pine splinter and Ehrlich reactions, and (II), (IV), and (V) show peculiar absorption for pyrrole, maleinimide, and succinimide, respectively, in the ultraviolet region. (VI) also shows absorption of >C=O and >C=C. From the analyses of their infrared spectral curves and their mutual relations, (II), (IV), (V), and (VI) were respectively assigned the structures of β-isopropylpyrrole, isopropylmaleinimide, ring dilactam of 2-carboxy-4-isopropylpyrrole, and 2-carboxy-4-isopropylpyrrole. They were identified by admixture with synthetic samples and from infrared absorption curves. Comparison of the infrared spectra of (II) and of α- and α′-methyl-β-isopropylpyrrole, proposed for (II) by Miyazaki, et al. showed them to be different. From the foregoing results and other considerations, it was assumed that kainic acid is 2-carboxy-4-isopropylpyrrolidine, possessing an acetic acid group and one double bond in or outside the ring.
  • 上農 義雄, 那波 速男, 上柳 次三郎, 森本 浩, 中守 律夫, 松岡 敏郎
    1955 年 75 巻 7 号 p. 821-825
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Dimethyl kainate (II) and dimethyl dihydrokainate (V) were each submitted to reduction with lithium aluminum hydride and derived respectively to kaininediol (III) and dihydrokaininediol (VI). From the analyses of the infrared curves of (III) and (VI) and of kainic acid (I) and dihydrokainic acid (IV) with fluorinated paraffine as the solvent, the double bond in (I) was attributable to the isopropenyl group. Oxidation of N-acetylkainic acid (VII) with potassium permanganate yielded formic acid as the volatile matter, and saponification of the non-volatile portion afforded C9H13O5N (IX), m.p. 205° (decomp.). Ozonization of (VII) yielded formaldehyde (identified as the dimedone) and C11H15ON (VIII), m.p. 185°, whose saponification gave a product (IX), identical with that obtained with formaldehyde by the ozonization of (I). (IX), m.p. 205° (decomp.), forms a polymorphic crystals of m. p. over 280°. It gives yellow coloration by the ninhydrin reaction, does not discolor bromine, gives a positive iodoform reaction, and shows single ketone absorption in the ultraviolet region. It absorbs 1 mole of hydrogen on catalytic reduction and forms a semicarbazone (X), m.p. 235-236° (decomp.), C10H16O5N4. From the foregoing results, it was concluded that (I) and (VII) possessed an isopropenyl side chain and formed (IX) and (VIII) possessing the methyl ketone group, together with formic acid or formaldehyde, by the oxidation. It follows, therefore, that (I) is 2-carboxy-4-isopropenylpyrrolidine, with -CH2-COOH group outside the ring.
  • 上農 義雄, 那波 速男, 上柳 次三郎, 森本 浩, 中守 律夫, 松岡 敏郎
    1955 年 75 巻 7 号 p. 825-828
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Catalytic reduction of dihydrokainic acid (I) was carried out under the presence of formaldehyde to prepare N-methyldihydrokainic acid (II), m.p. 100-110°, C11H19O4N⋅1/2H2O, whose esterification afforded dimethyl N-methyldihydrokainate (III), b.p4 123°, C13H23O4N. (III) or dimethyl dihydrokainate was derived to the methiodide (IV), m.p. 159-161°, C14H26O4NI, by he application of methyl iodide. The Hofmann degradation of (IV), using either silver carbonate or oxide, afforded dihydrokainic acid betaine (VI), C13H23O4N⋅H2O, as an intermediate which underwent rearrangement to (III) on heating. The Hofmann degradation of dimethyl N-methylkainate methiodide only gave N-methylkainate.
  • 上農 義雄, 那波 速男, 上柳 次三郎, 森本 浩, 中守 律夫, 松岡 敏郎
    1955 年 75 巻 7 号 p. 828-832
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    N-Methyldihydrokaininediol methiodide (XI), m.p. 194°, C12H26O2NI, was prepared from dimethyl N-methyldihydrokainate (III) or dihydrokaininediol by the method indicated in Fig. 1. The Hofmann degradation of (XI) with silver carbonate or silver oxide, or sodium hydroxide solution, yielded N-methyldihydrokaininediol methine (XII), C12H25O2N. Since (XII) does not undergo catalytic reduction or ozonolysis, it was found to be a compound possessing an epoxy linkage and not the methine with a double bond, formed by the regular Hofmann degradation. Second-stage Hofmann degradation with silver oxide, after deriving (XII) to its methine methiodide (XIII), m.p. 179-180°, C13H28O2NI effected decomposition with liberation of trimethylamine, and yielded the initial fraction of b.p20 115° (XIV-i) and a main fraction of b.p20 120-122° (XIV-ii). Both agree with the composition of C10H18O2 and from their respective infrared absorption curves, (XIV-i) was found to be the des-N compound possessing two oxide rings, the majority having formed the oxide rings by the second-stage degradation, while (XIV-ii) was mainly the des-N compound formed by the regular degradation. Ozonization of (XIV-ii) yielded formaldehyde (identified as the dimedone) and a ketone-like compound of b.p20 130-135°. From the foregoing results and considering the experimental facts described in preceding papers, the structure of dihydrokainic acid was assumed to be (I-A) or (I-B), shown in Fig. 2.
  • 上農 義雄, 那波 速男, 上柳 次三郎, 森本 浩, 中守 律夫, 松岡 敏郎
    1955 年 75 巻 7 号 p. 832-835
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    In order to derive kainic acid to a more simpler compound and submit it to the Hofmann degradation, the carboxyl was substituted with a methyl group. Dihydrokaininediol was led through N, O, O-tritosyldihydrokaininediol (XVI), m.p. 120°, C31H39O8NS3, to N-tosyldihydrokainine diiodide (XVII), m.p. 97°, C17H25O2NSI2. Dimethyl N-benzoyldihydrokainate (XVIII), m.p. 94°, C19H25O5N, was prepared from dimethyl dihydrokainate hydrochloride, reduced to N-benzyldihydrokaininediol (XIX), b.p2 188°, C17H27O2N, and chlorinated to N-benzyldihydrokainine dichloride hydrochloride (XX), m.p. 186°, C17H26NCl3. Dehalogenation was attempted by several methods on (XVII) and (XX) but the attempt failed. N-Methyldihydrokaininediol (X) was chlorinated to N-methyldihydrokainine dichloride hydrochloride (XXI) which was treated with alkali after zinc powder reduction, in acid medium, and the oil (XXII) of b.p16 86° thereby obtained was catalytically reduced to form the objective N-methylmethylethylisopropylpyrrolidine (XXIII-i), b.p16 91°, [α]D18: +40°, C11H23N; picrate, m.p. 94°; methiodide (XXIV-i), m.p. 197°. From the results of ozonization, catalytic reduction, and infrared absorption spectrum, (XXII) was assumed to be N-methylmethylvinylisopropylpyrrolidine. High temperature-high pressure reduction of dihydrokaininediol in ethanolic solution, with copper-chromium catalyst, afforded two substances, (a) b.p22 75-80° and (b) b.p27 140-145°. (a) is N-ethylmethylethylisopropylpyrrolidine formed by N-ethylation with ethanol while (b) is a compound in which one of the -CH2OH group had been left intact in this reaction. Based on these findings, N-methyldihydrokaininediol was similarly treated in methanol solution and afforded (XXIII-ii), b.p21 90-95°, which formed a picrate of m.p. 124-125° and a methiodide (XXIV-ii) of m.p. 187°, [α]D17: +5°. It was assumed that (XXIII-ii) was racemized during the high temperature-high pressure reduction.
  • 上農 義雄, 那波 速男, 上柳 次三郎, 森本 浩, 中守 律夫, 松岡 敏郎
    1955 年 75 巻 7 号 p. 836-840
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    The methiodides (XXIV-i and -ii) of the N-methylalkylpyrrolidine compounds were each submitted to the Hofmann degradation with silver oxide and the methine (XXV-i), b.p16 84°, [α]D15: +14.5α, and (XXV-ii), b.p21 85-86°, were respectively obtained. Ozonic oxidation of (XXV-i) and (XXV-ii) afforded, from (XXV-i) the dimethylamino ketone compound (XXVI-i), b.p19 105-106°, [α]D16: +30°, which formed semicarbazone of m.p. 115-116°, [α]D15: -27.5° (MeOH), [α]D20: -38° (AcOEt); picrate of m.p. 106-108°, [α]D19: +17° (MeOH), and from (XXV-i), (XXVI-ii), b.p19 100-104°, forming a semicarbazone of m.p. 109-110°, [α]D20: 0° (MeOH or AcOEt), picrate of m.p. 114-115°, [α]D18: 0° (MeOH). Since the foregoing two semicarbazones gave identical infrared absorption curves in carbon tetrachloride, (XXVI-ii) must be the racemate of (XXVI-i). Secondstage Hofmann degradation was then carried out on the syrupy methiodide of (XXV-i) with silver oxide or on the methiodide (XXIX-i), m.p. 207°, C13H30NI, of the dihydromethine compound (XXVIII-i), b.p16 85-86°, obtained by the catalytic reduction of (XXIV-i), with silver oxide or conc. sodium hydroxide solution, or both but the anticipated objective compound was not obtained, recovering (XXVI-i) or (XXVIII-i). Such results only endorsed the previous conclusion and failed to give conclusive evidence as to which of the proposed formulae, given in the preceding paper, is correct.
  • 上農 義雄, 那波 速男, 上柳 次三郎, 森本 浩, 中守 律夫, 松岡 敏郎
    1955 年 75 巻 7 号 p. 840-844
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Chromic oxidation of dihydrokainic acid afforded a compound (VI), m.p. 171°, C9H11O4N, with a small amount of acetic acid and isobutyric acid. Catalytic reduction of (VI) yielded two isomers, (IV-i) of m.p. 146° and (IV-ii) of m.p. 93-95°, corresponding to the formula C9H13O4N. Saponification of these two isomers afforded a compound (VII) of m.p. 170°, C9H14O6, from (IV-ii), with liberation of ammonia. From the fact that (VI) shows ultraviolet curve peculiar to maleinimide, and (IV-i) and (IV-ii) that of succinmide, and from the mutual relationship of (VI), (IV), and (VII), which are all acid substances, it was assumed that (VI), (IV), and (VII) are respectively carboxymethylisopropylmaleinimide, carboxymethylisopropylsuccinmide, and isopropyltricarballylic acid. (VI) and (VII) were prepared according to the method shown in Fig. 4 and identified by mixed fusion and from infrared absorption curves. Some considerations were made on the formation mechanism of (VI).
    Summarizing the experimental results described from the first paper of this series to the present one, kainic acid was assumed to be 2-carboxy-3-carboxymethyl-4-isopropenylpyrrolidine.
  • 須川 利男, 三野 安, 栗田 章
    1955 年 75 巻 7 号 p. 845-850
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    A process for preparing 1-amino-3-methylbutan-2-one (IV) easily and in a good yield was devised. Condensation of (IV) and ethyl oxalylacetate yielded 2-carboxy-3-ethoxy-carbonyl-4-isopropylpyrrole (VIII) which was derived to 2-carboxy-4-isopropylpyrrole (XI) on heating with potassium hydroxide solution. Decarboxylation of (VIII) followed by saponification with sodium hydroxide solution afforded 3-carboxy-4-isopropylpyrrole (XIII). Dry distillation of (XI) yielded β-isopropylpyrrole (XVI) which was identical with the pyrrole obtained by Ueno, et al. By the soda lime or zinc dust dry distillation of kainic acid. The pyrrole-carboxylic acid formed by the hydrolysis of pyrocol was found to be identical with (XI). Condensation of (IV) with ethyl acetoacetate afforded 2-methyl-3-ethoxycarbonyl-4-isopropylpyrrole (XVII) whose saponification with potassium hydroxide afforded 2-methyl-3-carboxy-4-isopropylpyrrole (XVIII). Dry distillation of (XVIII) gave 2-methyl-4-isopropylpyrrole (XIX).
  • 那波 速男, 中守 律夫, 松岡 敏郎
    1955 年 75 巻 7 号 p. 850-853
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Ethyl isobutyrylisonitrosoacetate (II) was prepared by the isonitrosation of ethyl isobutyrylacetate (I), used by Miyazaki et al. for the preparation of 2-methyl-4-isopropylpyrrole (V), the substance assumed by them as the zinc dust-distillation product of kainic acid. Condensation of (II) and ethyl acetoacetate yielded 2-methyl-4-isopropyl-3, 5-diethoxycarbonylpyrrole (III), C14H21O4N. Hydrolysis of (III) with 10% sodium hydroxide solution or conc. sulfuric acid followed by treatment with 10% potassium hydroxide solution afforded the same crystals (IV), m.p. 134°, in either case, and agreed with 2-methyl-3-carboxy-4-isopropylpyrrole, m.p. 134°, prepared by a different route. It follows, therefore, that in both cases the ester at the α-position was saponified and decarboxylated and this is a different behavior from that of 2-methyl-4-propyl-3, 5-diethoxycarbonylpyrrole (VIII) and Knorr's pyrrole. Decarboxylation of (IV) hereby obtained gave the objective (V), b.p15 84°, C8H13N.
  • 本庄 美喜男, 宮本 益雄, 上柳 次三郎, 那波 速男, 内林 政夫
    1955 年 75 巻 7 号 p. 853-856
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Isobutyronitrile (IV) was prepared from isobutyric acid (I) through isobutyryl chloride (II) and isobutyramide (III), and was led to isopropyl ketone by the Grignard reaction with ethyl iodide or bromide. Isonitrosation of (V) yielded 2-isonitroso-4-methylpentan-3-one (VI) which was reduced and acetylated to 2-N-acetylamino-4-methylpentan-3-one (VII) and followed by hydrolysis with hydrochloric acid to 2-amino-4-methylpentan-3-one (VIII), obtained as the hydrochloride. (VIII) was condensed with ethyl oxalylacetate by the method of Corwin et al. to afford 2-methyl-3-isopropyl-4-ethoxycarbonyl-5-carboxypyrrole (IX) which was hydrolyzed with potassium hydroxide and decarboxylated to (XII). This substance formed a picrate of 2 moles of (XII) and 1 mole of picric acid, as in the case of 2, 3-dimethylpyrrole.
  • 須川 利男, 三野 安, 栗田 章
    1955 年 75 巻 7 号 p. 856-860
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Condensation of 1-amino-3-methylbutan-2-one and ethyl acetone-dicarboxylate yielded 2-ethoxycarbonylmethyl-3-ethoxycarbonyl-4-isopropylpyrrole (I) during which 2-methyl-3-ethoxycarbonyl-4-isopropylpyrrole (II) formed as a by-product by the hydrolysis and decarboxylation of the ethoxycarbonyl group at the 2-position. Respective application of ethyl diazoacetate, in the presence of copper powder, to 2-methoxycarbonyl-(IV), 2-methyl-3-ethoxycarbonyl-(X), and 2-methoxycarbonyl-3-ethoxycarbonyl-4-isopropylpyrrole (XI) resulted in the introduction of an acetyl radical at the 5-position to form 2-methoxycarbonyl-4-isopropyl-5-ethoxycarbonylmethylpyrrole (VII), 2-methyl-3-ethoxycarbonyl-4-isopropyl-5-ethoxycarbonylmethylpyrrole (XII), and 2-methoxycarbonyl-3-ethoxycarbonyl-4-isopropyl-5-ethoxycarbonylmethylpyrrole (XIII). Application of 1 mole of ethyl diazoacetate to 2-methyl-4-isopropylpyrrole (XV) yielded 2-methyl-4-isopropyl-5-ethoxycarbonylmethylpyrrole (XVI) and further application of ethyl diazoacetate to (XVI) afforded 2-methyl-4-isopropyl-3, 5-diethoxycarbonylmethylpyrrole (XVII).
  • 那波 速男, 上柳 次三郎, 中守 律夫, 松岡 敏郎, 木全 清一
    1955 年 75 巻 7 号 p. 860-865
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Syntheses of 2, 5-dimethyl-(III), 3-ethyl-(VII), 2-methyl-3-ethyl-(XIV), and 2-methyl-5-ethyl-4-isopropylpyrrole (XVIII), and 2-ethyl-3-isopropylpyrrole (XI) were attempted. (III) was prepared, first by the condensation of 2-amino-4-methylpentan-3-one (I) and ethyl acetate to form 2, 5-dimethyl-3-ethoxycarbonyl-4-isopropylpyrrole (II) which was hydrolyzed by heating with potassium hyroxide and decarboxylated, and confirmed as its picrate. (VII) was prepared by the condensation of 1-amino-3-methyl-butan-2-one (IV) and ethyl acetopyruvate to form 2-carboxy-3-acetyl-4-isopropylpyrrole (V) and, per se or after decarboxylation to 3-acetyl-4-isopropylpyrrole (VI), submitted to the Wolff-Kischner reduction. The structure of (VII) was confirmed by its oxidation to ethylisopropylmaleinimide (VIII). (XI) was prepared by the Friedel-Crafts reaction to 2-methoxycarbonyl-4-isopropyl-5-acetylpyrrole (X) and its subsequnt reduction by the Wolff-Kischner method. This was confirmed as the picrate and also by deriving it to isopropylmaleinimide (XII) by oxidation. In an attempt to obtain (XIV), (IV) and acetylacetone were condensed to form 2-methyl-3-acetyl-4-isopropylpyrrole (XIII) and submitted to the Wolff-Kischner reduction from which a pyrrole compound was obtained whose infrared absorption spectrum was identical with that of the pyrrole compound obtained by the Friedel-Crafts reaction of 2-methyl-3-ethoxycarbonyl-4-isopropylpyrrole (XV) to form 2-methyl-3-ethoxycarbonyl-4-isopropyl-5-acetylpyrrole (XVI) and submitted to the Wolff-Kishner reduction, per se or after saponification and decarboxylation. The two were respectively submitted to N-methylation and reduction to form the N-methylpyrrolidine compounds (XXI) and were found to be identical by the agreement of their infrared absorption curves and the picrates. Dehydrogenation of the pyrrolidine compound hereby obtained gave the original N-methylpyrrole compound. No detailed examinations have been as to the structure of the pyrrole compounds obtained during these syntheses.
  • 村上 信三, 竹本 常松, 鄭 然昌, 醍醐 皓二
    1955 年 75 巻 7 号 p. 866-869
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    If the structure of kainic acid, the anthelmintic principle of Digenea simplex Ag., is as shown below, various reactions listed in Table I would be explained well.
  • 村上 信三, 竹本 常松, 鄭 然昌, 醍醐 皓二
    1955 年 75 巻 7 号 p. 869-873
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Examination of various properties of kainic acid and its derivatives, and their infrared absorption spectra produced conclusive evidence that 2-carboxy-3-carboxymethyl-4-isopropenylpyrrolidine, the structure determined by the Takeda Research Laboratory and privately shown to the present writers, would be the most appropriate structure for kainic acid and that it enabled explanation of various reactions listed in Table II.
  • 高原 篤夫, 谷口 繁
    1955 年 75 巻 7 号 p. 873-877
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    An electrophotometer was devised and manufactured for the determination of each component developed on a filter paper, without dissolving out the component. Determination conditions using this photometer were examined with picric acid. The use of this devise has eliminated the long procedures necessary for dissolving out the component and the individual differences in such direct determination, and effected increased accuracy.
  • 青木 大, 福田 友昭
    1955 年 75 巻 7 号 p. 878-880
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    In order to clarify the effect of granular size on weight variations during tabletting, changes in weight variations by the different combinations of granular sizes and tablet sizes were examined through stochastics. It was thereby concluded that, in the practicable size of granules,
    1) in tabletting tablets of a definite size, the larger the diameter of the granuler, the larger became the weight variation, the ratio of its increase being linear; and
    2) in tabletting tablets of different sizes with the granules of the same size, greater the weight of tablets, smaller became the weight variation, the ratio of decrease being linear.
  • 高取 吉太郎, 山田 保雄, 川島 治
    1955 年 75 巻 7 号 p. 881-883
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    1) Starting with 3, 4-dimethylbenzoic acid, pure 3, 4-dimethylaniline, free from other isomers, was obtained in 70-79% yield by the Schmidt reaction and in 40-43% yield by the Snyder reaction.
    2) 3, 4-Dimethyl-1-ethoxycarbonylaminobenzene was obtained in a good yield by the Curtius reaction of 3, 4-dimethylbenzoic acid. Karrer and others described this substance as an oil but this was obtained as colorless prismatic crystals of m.p. 54-55°.
    3) Nitration of 3, 4-dimethylaniline with a mixture of copper nitrate and acetic anhydrided afforded 6-nitro compound in a good yield.
    4) 5, 6-Dimethyl-2-mercaptobenzimidazole and 5, 6-dimethylbenzimidazolyl-2-mercaptoacetic acid were also synthesized.
  • 和田 俊洋
    1955 年 75 巻 7 号 p. 883-885
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    There are two possible structures for the 3-enol benzoate of progesterone but all references to it in the literature give only one kind of a melting point and no mention is made of its structure. Further, there is no clear description of the 3-monosemicarbazone of progesterone. One kind of the 3-enol benzoate, pregna-3, 5-dien-3-ol-20-one 3-benzoate, and progesterone 3-monosemicarbazone were synthesized and their melting points were confirmed as being respectively at 227-231° and at 226-229° (decomp.), the structures being confirmed from ultraviolet absorption spectra and other analytical data.
  • 阿部 久二
    1955 年 75 巻 7 号 p. 885-888
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Three compounds of the thiobarbituric acid series, containing a cyclohexenyl group, were synthesized and their intravenous anesthetic effect was compared with that of sodium methylhexabital.
    1) Sodium 5-allyl-5-(Δ2-cyclohexenyl)-2-thiobarbiturate is better than sodium methylhexabital and this is the first compound with Δ2-cyclohexenyl group to possess hypnotic action.
    2) Δ1-Cyclohexenyl derivative is somewhat inferior.
    3) Sodium 5-ethyl-5-(Δ1-cyclohexenyl)-2-thiobarditurate was found to be unsuitable as the intravenous anesthetic.
  • 阿部 久二, 石坂 哲夫, 恩田 政行, 久慈 光亮, 開 誠治, 塚本 義二
    1955 年 75 巻 7 号 p. 888-891
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Pure 2-halopentane can be obtained by the application of sodium halide to 2-pentanol tosylate but the reaction takes a long period and the yield is poor. A new advantageous method was devised so as to eliminate the use of expensive 2-halopentane by the condensation of methyl propyl ketone (III) and ethyl cycanoacetate (IV) and followed by the reduction by which ethyl (1-methylbutyl) cyanoacetate (VI) was obtained in approx. 64% yield. Thiopental Sodium is obtained from (VI) by the ordinary procedures.
  • 阿部 久二, 石坂 哲夫, 塚本 義二
    1955 年 75 巻 7 号 p. 891-892
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Thiamyal Sodium can be prepared in accordance with preparative method for Thiopental Sodium and their respective yield is about the same. Thiamylal Sodium is somewhat better than Thiopental Sodium in hypnotic action but causes stronger side-actions.
  • 阿部 久二, 加藤 信幸, 開 誠治
    1955 年 75 巻 7 号 p. 893-896
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Ethyl (1-methylbutyl) ethylmalonate (XII) is an important intermediate for the preparation of Thiopental Sodium and is obtained by the pentylation of ethyl ethylmalonate (IX) but in a poor yield. Improvement was effected by carrying out the reaction in benzene series solvent and in the presence of metallic sodium, greatly increasing the yield. There are many methods of preparing Thiopental Sodium but the most advantageous is that through (VII)→(IX)→(XII)→(XIII)→(XIV). Hypnotic effect of Thiopental Sodium is far stronger than that of sodium 5-allyl-5-(Δ2-cyclohexenyl)-2-thiobarbiturate and sodium methylhexabital, and is most well adapted for intravenous anesthetic.
  • 阿部 久二, 松井 和夫
    1955 年 75 巻 7 号 p. 896-897
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
    Sodium 5-(2-methylthioethyl)-5-(1-methylbutyl)-2-thiobarbiturate is a compound in which the ethyl group in Thiopental Sodium has been substituted with a 2-methythioethyl group and can be prepared as Thiopental Sodium, in about the same yield. This compound shows methionine action in vivo by the formation of methionine. It is said to be more rapid in effect than Thiopental Sodium as an intravenous anesthetic and its pharmacological action is now being examined.
  • 志甫 伝逸, 高林 昇, 金岡 又雄, 後藤 実
    1955 年 75 巻 7 号 p. 898-899
    発行日: 1955/07/25
    公開日: 2010/02/19
    ジャーナル フリー
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