Vapor-phase ammoxidation of 3-picoline over 5% Cr2O3-Al2O3 catalyst was carried out at 400° and the mechanism of its reaction was studied. The reaction rate of the ammoxidation of 3-picoline depended on the partial pressure of 3-picoline and oxygen, but was not affected by that of ammonia. The reaction therefore is controlled by oxidation process. Nevertheless the kinetic behavior was different from the oxidation of 3-picoline over the same catalyst. In order to clarify this phenomenon, the ammoxidation and oxidation of 3-picoline over γ-Al2O3, 2% or 5% K2O-5% Cr2O2-Al2O2, and 10% Cr2O3-Al2O3 were examined, and the oxidation of pyridine with and without ammonia was studied. From these experiments the following results were obtained. In the absence of ammonia, the total oxidation proceeds, because chromium is in the higher oxidation state and the carrier, γ-Al2O3, takes part in the reaction. In contrast, in the presence of ammonia, Cr2O3-Al2O3 becomes moderately active so that the total oxidation does not proceed and 3-cyanopyridine is obtained selectively.
The kinetics of heterogeneous vapor-phase ammoxidation of 3-picoline to 3-cyanopyridine was carried out over a Cr2O2-Al2O3 catalyst in a flow system. The reaction was carried out at atmospheric pressure and over the temperature range of 380° to 440°. The reaction rate was influenced by the partial pressure of 3-picoline and oxygen, but was not influenced by that of ammonia, 3-cyanopyridine or water. Experimental rate data were well interpreted by the Langmuir-Hinshelwood mechanism, where the rate-determining step was the surface reaction between adsorbed 3-picoline molecules and adsorbed oxygen atoms. The parameter values in the rate expression were estimated by nonlinear least squares analysis. The energy of activation for the ammoxidation of 3-picoline was ca. 36 kcal/mole, and the heats of adsorption for 3-picoline and oxygen were ca. 4.6 and 6.0 kcal/mole, respectively.
Hygroscopicity and thermal stability of inorganic pharmaceutics in the Japanese Pharmacopoeia (VIIth Edition) were examined by thermogravimetry using samples stored over three months at a temperature of 30° and relative humidity of 32% or 75%. Weight-loss curve was similar under these conditions in some but majority of the samples showed increased weight loss of 1-12% when stored at a relative humidity of 75%, indicating that storage under this condition is not desirable. With the use of resulting data obtained from the above examination, analysis by chemical kinetics was carried out by the method of Freeman and Carroll, and activation energy and reaction order were calculated.
Reaction of the conjugated 1, 2-diimines with isocyanates was investigated. 6, 6', 7, 7'-Tetramethoxy-3, 3', 4, 4'-tetrahydro-1, 1'-biisoquinoline (I) reacted with several phenyl isocyanates (Ila-e) and benzoyl isocyanate (IIf), giving criss-cross type 1 : 2-adducts (IIIa-f). Behavior of N, N'-bis(cyclohexyl)ethylenediimine (VII) was different depending on reaction conditions. Reaction of VII with IIf at room temperature afforded 1 : 2-adduct (VIII) through 1, 2-cycloaddition to C=N bond of VII, presumably due to the contribution of 1, 4-dipolar structure of IIf, while in boiling xylene gave criss-cross type 1 : 2-adduct (X). On the other hand, although addition of N, N'-bis(cyclohexyl)butylene-2, 3-diimine (XV) to IIf was not found to take place at room temperature, XV reacted with IIf in boiling xylene to give a criss-cross adduct (XVI) as VII.
Reaction of indole derivatives with ketenethioacetals, in the presence of sodium hydride or sodium hydroxide, results in the formation of 3-(2-cyano-1-methylthiovinyl)indole derivatives (III). Reaction of these compounds (III) with various nucleophilic reagents (amines, active methylene compounds, sodium cyanide) resulted in the formation of products by substitution of the methylthio group.
Reaction of 2-methyl-3-aminoisocarbostyril (I) with benzaldehyde gave the corresponding Schiff base, 2-methyl-3-benzalaminoisocarbostyril (II) and 6, 8-dimethyl-14-phenyl-5, 6, 8, 9-tetrahydropyrido[2, 3-c ; 6, 5-c']diisoquinoline-5, 9-dione. (Va) in 23% and 58% yield, respectively. This pyridodiisoquinoline (Va), which was a novel pentacyclic ring system containing three nitrogen atoms, could be synthesized by another route.
Reaction of 3-aminio-2-methylisocarbostyril with an aromatic aldehyde generally gave the corresponding Schiff base and the corresponding novel pyrido[2, 3-c ; 6, 5-c']diisoquinoline-5, 9-dione derivatives. In order to examine the generality of this reaction, the reaction was carried out under various conditions using several aromatic aldehydes having electron-releasing or electron-attracting substituents (-CH3, -OCH3, -Cl, -NO2) in the para-position. The reaction mechanism was presented from these results.
Metabolic fate of mannan, which is known as one of anti-timor polysaccharides, was investigated with 3H-mannan in the mice. 1) After a single intraperitoneal injection of 3H-mannan, the radioactivity was predominantly incorporated into the liver and spleen, indicating selective retention of the polysaccharide in reticuloendothelial system cells. The distributed radioactivity showed a maximum level during rather a long period between 6 and 15 hours and decreased slowly thereafter maintaining a high level even after 1 week. On the other hand, the level of radioactivity in the kidney and blood was low and dropped rapidly. 2) By the examination of the forms of the radioactive substance in the liver, using the gel filtration method, it was clarified that the radioactivity remained mainly in large-molecule fractions.
Disodium monolauryl phosphate was synthesized by the pyrophosphoric acid method. The surface tension of its solution was measured in aqueous sodium chloride and sodium hydroxide by changing its concentration. The surface excess was calculated by applying the Gibbs adsorption equation. Szyskowski equation was verified using the activity of disodium monolauryl phosphate, a, and it was confirmed that the values of surface excess agreed with those calculated from the Langmuir adsorption equation using the activity, a, instead of the concentration. The activity, a, was defined as a=γ±(2C+C')2 C where γ±is the mean activity coefficient calculated from the Debye-Huckel equation, C is the concentration of disodium monolauryl phosphate, and C' is the added salt concentration. On the basis of the discussion of micelle formation, it was also concluded that the micelle formation occured at the constant activity independent of the added salt concentration.
The structure of the new base isolated from Stephania Sasakii HAYATA was revealed as 1, 2-methylenedioxy-4-hydroxyporphine (III) from ultraviolet, infrared, nuclear magnetic resonance and mass spectra. Absolute configuration of the 6a-position was found to be R from the result of.optical rotatory dispersion, but the steric configuration of the alcoholic hydroxyl in 4-position still remains to be clarified.
Hydroxyethyl-starch, whose DS is 0.51 by Lortz method and intrinsic viscosity is 0.22 dl/g, was hydrolyzed with sulfuric acid to monosugar units. These monosugars were separated by paper chromatography and then by thin-layer chromatography to five fractions, which were identified as D-glucose, 6-O-hydroxyethyl-D-glucose (6-HEG), 3-O-hydroxyethyl-D-glucose (3-HEG), 2-O-hydroxyethyl-D-glucose (2-HEG), and cis-1, 2-O-ethylene-D-glucofuranose (1, 2-EGF). Molecular concentration ratio of the fractions determined by spectrophotometry using anthrone was 0.479 : 0.103 : 0.029 : 0.299 : 0.090 for D-glucose : 6-HEG : 3-HEG : 2-HEG : 1, 2-EGF. DS calculated from the molecular concentration of D-glucose was about 0.52, showing coincidence with DS by Lortz method. Since 1, 2-EGF, a dehydro isomer of 2-HEG, also showed the substitution at C-2 position of glucose unit in hydroxyethyl-starch, distribution ratio of hydroxyethyl groups on the C-2, C-6, and C-3 was calculated to be about 75%, 20%, and 5%, respectively.
Reaction of diketene with glycinamide (IIIa) and its N-substituted derivatives (IIIb-f) afforded 2-acetoacetamidoacetamide (IVa-f) in a good yield. Treatment of IVa-e with sodium methoxide in methanol gave several cyclization products (II, V, VI, VII, , VIII). In the case of IVa-c, the main product was II which is obtainable by the cyclization of ethyl acetoacetylglycine3)(Ia). On the other hand, disubstituted derivative such as IVd, e gave 3-hydroxy-3-methyl-5-oxopyrrolidine-2-carboxamide (VI, VII) as a main product.
Reaction of diketene with α-aminonitrile and β-aminonitrile afforded their N-acetoacetate (VI, VII) in a good yield. VI was easily cyclized with triethylamine or sodium methoxide giving 3-acetyl-4-amino-3-pyrrolin-2-one (VIII), while treatment of VII with sodium methoxide gave 1-substituted 3-acetyl-4-amino-5, 6-dihydro-2(1H)-pyridone (X) and 1-substituted 4-methyl-1, 2-5, 6-tetrahydro-6-oxonicotinonitrile (XI).
Permeabilities through the gelatin membrane were measured with three electrolytes, KSCN, KCl, and K2SO4, and the effect of gelatin content was studied. The permeability coefficient in the membrane, P*, decreases along the sigmoid curve with increasing gelatin content. The rate constant of permeation at the interface, k, remains constant even when gelatin content varies. The values of k in the case of KSCN, KCl, and K2SO4 were individually 0.89, 0.80, and 0.57×10-3, respectively. With increasing gelatin content of the membrane, the corresponding membrane thickness, L*(=P*/k), decreases, expressing the resistance at the interface to diffusion. L* of three electrolytes are on the identical curve. The parameters of interaction between gelatin and electrolytes were calculated from the apparent membrane constant, f*, with reference to that of KCl. In the low content of gelatin, there are no differences in the affinity between three electrolytes and gelatin, but differences appear with increasing gelatin content. The affinity of KSCN becomes greater and that of K2SO4. less than that of KCl. The relation between the porosity and tortuosity of the membrane was also calculated.
The distribution of d- and l-ephedrine[α-14C] in rats was studied by whole body autoradiography, and the metabolites in organs, in which high radioactivity was detected, were identified by the reverse isotope dilution analysis. Amount of radioactivity at 2.5 hr after subcutaneous injection decreased in the order of liver, kidney>brain, spleen, adrenal, lung, contents of stomach and intestine. In addition, it was found that the levorotatory isomer has a stronger affinity for organs and is more slowly excreted in urine than the dextrorotatory isomer. In the liver, norephedrine, p-hydroxyephedrine, and glucuronides of ephedrine and p-hydroxyephedrine were identified as the metabolites together with unchanged ephedrine, while almost all radioactivity in the brain and the spleen was explained as that of the substrate itself. From the comparison of recovered metabolites, it was found that the d-isomer is less liable to be metabolized than the l-isomer. Moreover, it was revealed that deaminaiton and p-hydroxylation are greatly affected by configuration in the α-position and so require greater stereospecifisity than N-demethylation reaction.
Peripheral effects of gardneramine and gardnerine on circulatory and digestive systems were examined. Gardneramine and gardnerine produced a hypotensive effect in the rabbit, which seemed to be derived from their peripheral vasodilataion, direct depressive action on myocardium, and central depressive action. Both alkaloids produced vasodilatation in the hind limb preparation of the dog and depressive action on atria isolated from the guinea pig. They produced a weak preventive effect on stress in the mouse, Gardneranine inhibited the movement of smooth muscle organs such as stomach of the rat and intestine of the mouse. On the contrary, gardnerine accelerated it with lower doses, inhibited with higher doses. Both alkaloids decreased slightly the pH value of gastric acidity in the rat and also produced a weak papaverine-like antispasmodic action in the intestine isolated from the mouse. From these results, it may be concluded that gardneramine and gardnerine have a weak papaverine-like action on peripheral organs, the former being weaker than the latter. However, it is of interest to note that gardnerine accelerated the movement of smooth muscle of gastrointestinal tract with lower doses.
Benzyne reaction of 2, 3-xylidine with o-halogenobenzoic acids (IV) gave mefenamic acid (I) and its isomer, 3-(2, 3-dimethylanilino)benzoic acid (II). The same reaction of m-halogenobenzoic acid with V also gave I ana II. Further, the benzyne reaction of methyl m-halogenobenzoate afforded benzamide (XI) and XII. In the above reaction, 3-aryne derivative (VII) seems to be the intermediate. Investigation of the effect on plantar edema induced by carrageenin in the rat was carried out, but compounds more effective than mefenamic acid was not found.
It was found that the substance produced by B.subtilis H inhibits gastric acid secretion in a rat. This substance is precipitated at pH 3.0 from the culture medium and is extracted with acidic ethanol, then purified with silica gel, Sephadex LH-20 column chromatography, and thin-layer chromatography. The inhibitory substance is crysta1lized from ethanol to needle-crystals. The substance contains five kinds of amino-acids, Asp 3, Glu 3, Val 3, Ile 2, and Leu 9, and fatty acid. The substance inhibits gastric acid secretion stimulated by tetragastrin in a rat, as well as contraction of the guinea-pig duodenum and the rat descending colon induced by drugs. This substance is pyrogenic and is present in the cytoplasm in the subcellular fraction of B.subtilis H.
The reductive cyclization of 3, 6-dichloro-4-(o-nitrophenyl)pyridazine in excess triethyl phosphite afforded 1, 4-dichloro-5-ethylpyridazino[4, 5-b]indole as a sole product and its structure was confirmed from its spectrometric data and by synthesis.
3-Phenacylidenebenzofuran-2-one (IIIa) was obtained by the application of triphenylphosphinebenzoylmethylene (IIa)to coumarandione (I). The reduction of IIIa with Na2S2O4 in EtOH-H2O yielded the corresponding dihydro compound (IV). Reaction of IV with hydrazine hydrate in AcOH afforded a pyridazinone derivative (V) which was a recyclization product. Treatment of V with P2O5 in decalin afforded 3-phenylbenzofuro-[2, 3-c]pyridazine (VII).
β-Sitosterol (I), scopoletin (II), and a sesquiterpene lactone (compd. C) were isolated from the ratoons of Artemisia feddei collected in Kochi Prefecture. Besides compd. C, I was also found in the mature plant.