Application of cyclohexylamine, in an amount 1.5-2 times the theoretical quantity, to ammonium nitridotrisulfate and heating the mixture at 170° for 3 hours results in formation of cyclohexylammonium cyclohexanesulfamate in over 90% yield. The amount of ammonia evolved was examined in the reaction of ammonium nitridotrisulfate and cyclohexylamine at 120° and this reaction was considered to be in a following manner:
N(SO₃NH₄)₃+C₆H₁₁NH₂=N(SO₃NH₄)₂(SO₃HC₆H₁₁NH₂)+NH₃
N(SO₃NH₄)₂(SO₃HC₆H₁₁NH₂)+3C₆H₁₁NH₂=NH(SO₃HC₆H₁₁NH₂)₂+C₆H₁₁NHSO₃HC₆H₁₁NH₂+2NH₃

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Reaction of ammonium imidodisulfate and cyclohexylamine at 170° results in quantitative formation of cyclohexylammonium cyclohexanesulfamate according to the following equation:
HN(SO₃NH₄)₂+4C₆H₁₁NH₂=2C₆H₁₁NHSO₃HC₆H₁₁NH₂+3NH₃
If this reaction is carried out at refluxing temperature and ordinary pressure, cyclohexylammonium imidodisulfate is obtained according to the following equation:
NH(SO₃NH₄)₂+2C₆H₁₁NH₂=HN(SO₃HC₆H₁₁NH₂)₂+2NH₃
In this reaction, if ammonium chloride, ammonium nitrate, or cyclohexylamine hydrochloride is added during the reaction, cyclohexylammonium cyclohexanesulfamate is obtained by the first equation.

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Metal nitridotrisulfate and cyclohexylamine are comparatively difficult to react than ammonium nitridotrisulfate and cyclohexylamine. Reaction at 170° under high pressure afforded 3 moles of cyclohexanesulfamate from 1 mole of ammonium nitri-dotrisulfate, but only 1 mole of cyclohexanesulfate was obtained from 1 mole of metal nitridotrisulfate.
Three new kinds of analogous compounds, C₆H₁₁NH₂HN(SO₃HC₆H₁₁NH₂)₂, C₆H₁₁NH₂-HN(SO₃Na)₂, and C₆H₁₁NH₂HN(SO₃)₂Ca, were prepared and their properties were examined.

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Hydrolysis and cyclohexylammonolysis of nitridotrisulfate were comparatively examined. In the reaction of sodium nitridotrisulfate and cyclohexylamine, addition of the acid of cyclohexylammono system, such as ammonium chloride, ammonium sulfate, cyclohexylamine hydrochloride, or cyclohexylamine sulfate, afforded cyclohexanesulfamate in a good yield.

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Reaction of cyclohexylamine with the acid of hydroxylaminesulfonic acid system was examined and it was considered that only the N-sulfonic acid took part in the formation of cyclohexanesulfamate and that O-sulfonic acid group did not take part in this rection.

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Thermal decomposition of sodium cyclohexanesulfamate results in its decomposition according to the following equation in the presence of moisture:
2C₆H₁₁NHSO₃Na+H₂O=C₆H₁₁NHSO₃HC₆H₁₁NH₂+Na₂SO₄
and according to the following equation in the absence of moisture:
2C₆H₁₁NHSO₃Na=C₆H₁₁NHSO₂NHC₆H₁₁+Na₂SO₄

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Medicinal tablets of compounds containing water of crystallization often show variation in disintegration time by passage of time and various examinations are being made to solve this problem but no reports are available for fundamental reasons for this phenomenon.
Assuming that the moisture during preservation might be the reason for this phenomenon, relationship between the amount of crystal water in a compound and pressure-tabletting was examined from measured values in thermobalance, differential thermal analysis, specific gravity, and X-ray diffraction methods, using calcium p-aminosalicylate heptahydrate (PASCa⋅6H₂O).
PAS-Ca⋅6H₂O loses its water of crystallization according to atmospheric conditions. In this case, gram-volume decreases as indicated in Table I and, at the same time, the substance takes an amorphous state, not forming a crystal lattice even after a long period of time, as shown in Fig. 5. As indicated in Table II, supply of water to this anhydrate results in retention of crystal water in transition state but its X-ray diffraction pattern is still that of an amorphous state and lattice formation is observed only after a long period of time.
These facts suggest that when tablets are formed from a compound in partially amorphous state, the tablets absorb moisture during passage of time and gradually transits to crystal lattice of a hydrate, resulting in volume change of the crystal and promotion of tablet disintegration. This also results in decreased amount of retained air and gradual lengthening of disintegration time (Table III).

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Syntheses and cleavage reaction were attempted with 4, 5-disubstituted isoxazoles with a furan ring. In order to obtain the starting α-formyl ketone compound, usual formylation with ethyl formate was carried out on deoxyfuroin (I), acetyl-furan (II), furfuryl benzyl ketone (III), and furyl benzyl ketone (IV). (I) failed to undergo this reaction, the formyl compounds of (II) and (III) were so labile that they easily underwent resinification, and only the α-formylbenzyl furyl ketone (IV′), m.p. 100-101°, was sufficiently stable. (IV′) colored reddish violet with Fe³⁺ in 2γ/0.05cc. concentration and this color is an iron complex salt (V) of m.p. 179-180°, with a molar ratio of (IV′) to iron of 3:1.
Reaction of (IV′) with equivalent of hydroxylamine hydrochloride in ethanol afforded 4-phenyl-5-furylisoxazole (VI), b. p₃ 145-146°, and its reaction with sodium ethoxide in ethanol solution resulted in cleavage to furoyl-phenylacetonitrile (VII), m.p. 89-89.5°. On heating with 25% sodium hydroxide at 100° for 30 minutes, (VII) was decomposed into 2-furoic acid and benzyl cyanide. Oxidative decomposition of (VII) in dilute sodium hydroxide with hydrogen peroxide resulted in preferential cleavage of the furan ring and benzoic acid was obtained as one of the acid components but not 2-furoic acid. Amidation of (VII) with 95% sulfuric acid gave 2-furoyl-2-phenylacetamide (VIII), m.p. 184-185°, whose hydrolysis with dilute sulfuric acid gave the starting compound (IV).
It was revealed from these experimental results that the series of reactions used for syntheses and cleavage for 4, 5-substituted isoxazoles with aromatic ring carried out in the past is also applicable for the present comparatively stable starting compound, the α-formyl ketone compound with a furan ring.

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It has been found that the use of benzene gives better result than methanol as a solvent in the high-pressure catalytic reduction of 4-phenyl-3-propenonitrile (III) to obtain 1-phenyl-4-amino-1-butene (IV). When methanol is used, a fair amount of 1-amino-4-phenylbutane was found to be formed as a by-product. A few kinds of unsaturated nitrite (I, VII, and IX) were submitted to reduction under these conditions and the corresponding unsaturated amines (II, VIII, and X) were obtained in a good yield.

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Measurement was made on the temperature of crystallization of various concentrations of calcium pyruvate isoniazone from its supersaturated aqueous solution. Supersolubility curves of crystals A and B were approximately parallel to their solubility curves. Examinations on the effect of solution concentration, rate of cooling, stirring, and other conditions on crystallization showed that these conditions affected not only the crystallization temperature but also the shape of crystals and the quantity. Further examinations were made on the conditions and mechanism of crystallization of calcium pyruvate isoniazone.

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Measurement of sedimentation volume is often used in the study of suspension solvent and attempt was made to calculate this value theoretically. First, results obtained by modifying the calculation for volume, d, when spherical granules undergo aggregation, are described.
Spheres which were given axis and order from the random rigid were dropped perpendicularly into a vessel having a definite bottom area to calculate the sedimentation volume and volume fraction was obtained from it. It was thereby learnt that, when the width of the vessel was taken as 100, calculation with 400-600 granules of spherical model with radius of 7-10 would eliminate the effect of bottom area of the vessel and volume fraction would become constant. If the effect of granules lining the outer sides of the vessel was taken into account, calculation of a small range gave calculated values for the vessel as a whole. The volume fraction obtained from these calculations was 0.183 and it was concluded that the value of 0.128 obtained by Vold was not correct.

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Fluorine analysis was examined by burning organofluorine compound in a quartz combustion tube, trapping the silicon tetrafluoride evolved in an absorption tube for carbon-hydrogen analysis, and calculating the amount of fluorine from increase in its weight. When a sample consists of carbon, hydrogen, oxygen, and fluorine, burning of the sample in nitrogen stream, using the apparatus for oxygen analysis, should produce carbon monoxide, hydrogen, and silicon tetrafluoride. Detailed examinations were made on this combustion gas and reagents capable of absorbing silicon tetrafluoride alone at ordinary temperature were examined.

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When organofluorine compound is burned in apparatus for direct determination of oxygen, a part of silicon tetrafluoride thereby formed was found to be adsorbed on the platinized carbon granules and not all of silicone tetrafluoride flows out during the analytical period. Thermal decomposition of platinized carbon granules, when the layer is shortened, was examined and periodical flow of silicon tetrafluoride during this time was measured by the alternate use of two absorption tubes. It was found that the amount of silicon fluoride remaining on platinized carbon granules was the same and this was not in proportion to the fluorine content in the sample but varied according to the adsorptivity of platinized carbon granules and flow rate of nitrogen gas. Based on these observations, analysis of organofluorine compound was carried out by the combustion method using absorption tube filled with silica gel.

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Natto is manufactured by cultivation of Bacillus natto, a strain of B. subtilis, on the surface of boiled soy-beans, and has a viscous substance. Slightly sticky powder was obtained after extracting the viscous substance successively with aqueous solution of trichloroacetic acid, phenol, and pyridine, and was purified by dialysis and electrodialysis. This substance was isolated as electrophoretically single compound, positive to the Molish reaction, negative to the biuret reaction, and contained phosphorus but not nitrogen or sulfur. Hydrolysis of this polysaccharide gave three monosaccharides, arabinose, xylose, and galactose.

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Acetylation of viscous polysaccharide, extracted from Natto, containing D-galactose, L-arabinose, and D-xylose, afforded an acetylated polysaccharide of molecular weight of 10000, CH₃CO content of 42.99%, and not containing any ash. Deacetylation of this polysaccharide afforded electrophoretically single polysaccharide with molecular weight of ca. 5300 per one terminal group. The content of these three kinds of componental sugars is approximately equal and it was assumed that the polysaccharide has a molecular weight of 5300-5900 and contains approximately equimolar amount of L-arabinose, D-xylose, and D-galactose.
Methylation of the acetylated compound afforded a methylated polysaccharide with 43.28% of CH₃O. Hydrolysis of this methylated polysaccharide afforded 3, 5-O-dimethyl-arabinose, 2, 4-O-dimethylxylose, 2, 4-O-dimethylgalactose, 2, 3, 4-O-trimethylgalactose, and 2, 3, 4, 6-O-tetramethylgalactose. It therefore follows that the original polysaccharide is composed of arabinose, xylose, and galactose bonded with each other at 1- and 2-positions of L-arabofuranose, 1- and 3-positions of D-xylopyranose, and 1- and 6-positions of D-galactopyranose, having branched chain bonded at 3-position of the galactose residue, and the non-reducing terminal sugar is considered to be galactose.

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Following the preceding report on the structure of the viscous polysaccharide extracted from Natto, content ratio of methyl sugars was determined and the polysaccharide was found to have three branched chains. The structure of this polysaccharide was presumed from various data obtained in the present series of work such as periodate consumption of 24 moles, formic acid formation of 12 moles, detection of glyoxal and glyceraldehyde from the hydrolyzate of the polyaldehyde formed by periodate oxidation of the polysaccharide, and detection of glycerol, arabinose, xylose, and a minute amount of galactose from the hydrolyzate of polyhydric alcohol obtained by reduction of the foregoing polyaldehyde with sodium borohydride.

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Podophyllotoxin, picropodophyllin, β-apopicropodophyllin, kaempferol, quercetin, and a new substance were isolated from the root of Diphylleia Grayi. The new substance was isolated as pale yellow needles, m. p. 291°, C₂₁H₁₆O₇, and its structure was assumed as (III) from its infrared and ultraviolet spectral data, giving the name of diphyllin. It was assumed that picropophyllin and β-apopicropodophyllin had been formed secondarily from podophyllotoxin during the course of their separation, as indicated in Chart 1. Another substance was isolated as colorless needles, m. p. 229-233°, and this was assumed to have a 4-arylnaphthalene skeleton.

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The pyridoquinolines and pyrroloquinolines obtained by the Skraup and Conrad-Limpach-Knorr e quinoline cyclization and Fischer's indole cyclization carried out on 4, 6-diaminoquinoline and 4-methyl-6-aminocarbostyril were all found to be angular cyclized product. Skraup's quinoline cyclization was carried out newly on 5-methyl-6-aminocarbostyril, protecting the 5-position with an alkyl group, to find whether angular and linear cyclizations took place. The starting 5-methylcarbostyril was prepared by the rearrangement reaction of 5-methylqui noline 1-oxide with tosyl chloride and the intermediate tosyl derivative was hydrolyzed to 5-methylcarbostyril. Since the rearrangement of quinoline 1-oxide with tosyl chloride results in variety of reactions, it was important that the tosyl derivative was obtained as an intermediate. Nitration of 5-methylcarbostyril gave the 6-nitro compound and 5-methyl-6-aminocarbostyril derived from it was submitted to the Skraup cyclization. The product was chromatographed through alumina and three kinds of product were obtained; pale yellow needles (A) of m.p. 316-317°, pale yellow needles (B) of m.p. 303-304°, and colorless needles (C) of m.p. 124°. From the comparison of their ultraviolet spectra and preparation of their derivatives, it was confirmed that (A) is the linear cyclized product, (B) the angular cyclized product, and (C) is the hydrate of (A).

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Following the formation of a linear cyclization product by the Skraup reaction of 5-methyl-6-aminocarbostyril in affording pyrido [2, 3-g] quinoline, indole cyclization by the Fischer process was carried out and it was found that a linear product is formed, as in the case of the Skraup reaction, affording pyrrolo [2, 3-g] quinoline derivative. These results revealed that the benzene portion of quinoline shows benzenoid activity when α-position of the pyridine portion is substituted with a group with a large +M effect.

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Thirty-seven kinds of various new derivatives of N-substituted pyrazinamide, aminopyrazine, pyrazinoic acid hydrazide, and pyrazinealdehyde were synthesized and their antibacterial and antifungal action were tested with tubercle bacilli H₃₇RV strain, Aspergillus niger, and Penicillium notatum. All the derivatives tested showed better antituberculosis action than pyrazinamide used as the control, especially 1-isonicotinoyl-2-pyrazinoylhydrazine and pyrazinealdehyde isonicotinoylhydrazone completely stopped the growth of tubercle bacilli in a respective concentration of 0.156 and 0.0625γ/cc. Antifungal test did not reveal any better derivatives.

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Internal gland number existing at 1mm² of cross section in stipes of ferns containing phioroglucides was studied stochastically. The results are shown in Table I. This specific value varies by kinds of ferns, and does little by localities and individuals, so that it seems to be one distinctive point in anatomy.

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Examinations were made on the electrode reaction of the first group of sulfanilamide derivatives and following points were noted as their polarographic behavior:
1) The wave height was higher, the greater the acidity of the aqueous solution of such derivatives. Reduction wave did not appear in the presence of more than equimolar amount of alkali hydroxide and the sodium salt of such derivatives did not show any reduction wave. The wave height is greatly affected by the amount of dissolved oxygen.
2) The first group sulfanilamide derivatives behave more like acetic acid than hydrochloric acid in the effect of kind and content of organic solvent and in relationship between the concentration of sulfanilamide and half-wave potential.
3) Constant-voltage electrolysis results in increase of pH value with decrease of current density, and there is no change in the molecular structure of the sulfanilamide derivatives before and after electrolysis. Reduction wave of the first group sulfanilamide derivatives cannot be considered as the contact wave in which the amino group in para-position takes part.
From such a behavior, it was assumed that the reduction wave of the first group sulfanilamide derivatives was due to the dissociation of hydrogen from a weak acid, as in the case of acetic acid.

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A colorimetric determination of INAH was devised by application of 2-bromo-1′-acetonaphthone to INAH to form 1-(1-naphthylcarbonylmethyl)-4-hydrazinocarbo-nylpyridinium bromide and its coloration by basification. This procedure is as follows: A mixture of 1cc. of ethanol containing 1-40γ of INAH and 0.5cc. of 0.25% solution of 2-bromo-1′-acetonaphthone is refluxed in a boiling water bath for 25 minutes, 0.1% ethanolic solution of sodium ethoxide is added, and the whole volume is brought accurately to 5cc. with ethanol. After standing this solution for 3 minutes, its absorbance is measured at 470mμ and the concentration is calculated from the calibration curve.
In the presence of isonicotinic acid, nicotinic acid is measured at 500mμ by which INAH in the range of 4-70γ can be determined selectively in the presence of 15γ of isonicotinic acid, 30γ of nicotinic acid and nicotinamide, and 200γ of 3-pycoline and 4-pycoline. Determination error is within 2.5%. 2-Pycoline and picolinic acid do not undergo coloration under these conditions.

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Methanolic extraction of the fresh whole herb of Lobelia sessilifolia LAMB afforded a new glucofructan besides melissic acid, nonacosane, ursolic acid, and potassium chloride. Recrystallization of this glucofructan gave inulin-like crystalline powder which did not show a definite melting point, became semi-fused with slight foaming at 173°, colored at 180-190°, and underwent decomposition at around 205°. The hydrate crystal also behaved analogously with [α]_D¹²-29.2° (H₂O). It does not reduce the Fehling solution, does not color to iodine, and corresponds to the molecular formula of C₄₂H₇₂O₃₆⋅10H₂O as crystallized from water, and is a heptasaccharide consisting of 2 moles of glucose and 5 moles of fructose. Since it does not form formic acid on oxidation with periodic acid, glucose is not present as the terminal sugar.

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In order to obtain 2-methyl-5(or 6)-alkylbenzimidazoles, synthesis of 2′-nitro-4′-alkylactanilides (II) via 4′-alkylacetanilides (I) was examined. Of the numerous methods for preparation of (I), the process of nitration of alkylbenzene, followed by reduction and acetylation, was applied to alkylbenzenes such as ethylbenzene, butylbenzene, etc., and satisfactory result was obtained, except in the case of isopentylbenzene (prepared from benzylmagnesium chloride and isobutyl bromide) which failed to form the objective compound. The process of reduction of p-acylaniline by the Wolff-Kischner method to p-alkylaniline and its acetylation was applied to isopentyl and pentyl derivatives, and the objective compounds were obtained in a good yield. The nitration of (I) to obtain (II) gave results indicated in Table I. Reaction conditions of this nitration were found to differ according to the size and shape of the alkyl group, each requiring individual attention.

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Alkaloidal components were examined in the cortex of Xanthoxylum schinifolium SIEB. et ZUCC. (Fagara schinifolia (SIHB. et ZUCC.) ENGL.) (Rutaceae) (Japanese name “Inu-zansho”) growing on Mount Ibuki. Besides a tertiary base, skimmianine (I), a neutral substance, aesculetin dimethyl ether (II), was isolated. On the other hand, presence of a comparatively large amount of quaternary base was detected but the base seemed to be extremely labile and underwent decomposition during extraction.

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It has been reported^*1 that the Chinese drug _??__??__??_ (Shan-dou-gen), the radix of Sophora subprostrata, had anti-tumor activity and examinations were made on its components in order to elucidate its pharmaceutical effect. Presence of matrine, oxymatrine, anagyrine, methylcytisine, β-sitosterol, and lupeol was confirmed and two other substances were isolated; one of m. p. 145° (decomp.) and the other of m. p. 158°. The components of this radix were compared by paper partition chromatography with those of Euchresta japonica, Sophora flavescens, and Sophora japonica and a markedly fluorescent spot (spot K), considered to be due to the characteristic component of this radix, was detected.

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Derivation of α-cyanoketones to dicarboxylie acids was attempted by the use of decomposition of α-cyanoketones with hydrogen peroxide in dilute alkali hydroxide solution, reported previously. The reaction carried out on α-cyanocyclohexanone and 2-cyano-α-tetralone afforded the corresponding adipic acid and 2-carboxyhydro-cinnamic acid in 21-22% yield. Although this reaction does not give a good yield of the product, it is a simple process and is not accompanied by formation of by-products that it seems to be possible for use as a synthetic process for some kinds of dicarboxylie acid.

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The extracts of 117 kinds of plants were examined for the antitumor activity against Ehrllch ascites tumor by the cylinder-plate method and the following plants (solvents) were found to be effective: Cinchona succirubra (water), Gardenia jasminoides (acetone, ether), Trachelospermum asiaticum (water, methanol, acetone, ether), Gentiana lutea (water), Arctostaphylos Uva-Ursi (water, methanol, acetone, ether), Aucuba japonica (water, ether), Panax repens (ether), Trapa natans (ether), Phellodendron amurense (water, methanol, acetone), Rhanunculus glaber (methanol, acetone, ether), Paeonia albiflora (water, methanol), Paeonia suffruticosa (ether), Coptis japonica (water, methanol), Zingiber officinale (methanol), Allium sativum (methanol, ether).

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Following the isolation of phenolic bases, nuciferine and roemerine, and a phenolic base, nornuciferine (I), from the leaves and petioles of lotus (Nelumbo nucifera GAERTN.), another base was isolated from the mother liquor left after separation of nornuciferine. The base was isolated as a crystalline oxalate of m. p. 211-212° and this was proved to be dl-armepavine (III).

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Four kinds of coumarin derivatives were isolated from Angelica Keiskei KOIDZUMI (Umbelliferae) by the process shown in Chart 1, these being psoralen (I), m. p. 161-162°, angelicin (II), m. p. 139-140°, bergapten (III), m. p. 187.5-188.5°, and xanthotoxin (IV), m. p. 146-147°. Besides these, angelic acid (V), m. p. 47-48°, and behenic acid (VI), m. p. 75-76°, were obtained as acid substances. Good results were obtained by the use of silica-gel chromatography for isolation of each of these substances but no new derivative of coumarin was obtained. Psoralen had hitherto been isolated from Leguminosae, Moraceae, and Rutaceae plants, and Hata and others had isolated it from the root of Angelica japonica A. GRAY among the Umbelliferae plants. The present result seems to suggest that psoralen might be distributed widely in the Umbelliferae plants also.

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Some derivatives of 3-aminopyrazinoic acid were prepared and their aryl derivatives were obtained by application of benzoyl, p-nitrobenzoyl, p-aminobenzoyl, p-chlorobenzoyl, furoyl, p-hydroxybenzoyl, nicotinoyl, or isonicotinoyl chloride. Various carboxamide and carboxahydrazide derivatives were also obtained from the foregoing derivatives. Antituberculosis and antifungal activity of these compounds were tested with tubercle bacilli H₃₇Rv strain, Aspergillus niger, and Penicillium notatum. All the compounds tested showed better antitubercular action than pyrazinamide used as the control but none had better antifungal activity.

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