Tetramethylmagnolamine (-, -) (XI) was synthesized by the Ullmann reaction of l-6′-bromolaudanosine (IX) and l-armepavine (X), and it was proved that this synthesized base is the optical antipode of the natural tetramethylmagnolamine (+, +). It was thereby established that the structure of magnolamine itself and the optical rotation of its two asymmetric centers are represented by the structural formula (XII).

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In order to examine the action as antimetabolite of cyanocobalamine, 5-fluorobenzimidazole and 2-mercapto-5-fluorobenzimidazole were synthesized from commercial ethyl p-aminobenzoate. 5-Fluorobenzimidazole, colorless needles, m. p. 133°, was obtained by the condensation-cyclization of 4-fluoro-o-phenylenediamine and formic acid, and 2-mercapto-5-fluorobenzimidazole, colorless needles, m. p. 283° (decomp.), by the condensation-cyclization of 4-fluoro-o-phenylenediamine, carbon disulfide, and ethanolic potassium hydroxide.

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A crystalline component, C₂₂H₃₆O₇, m. p. 259-260°, was isolated from Rhododendron Metternichii var. typicum, Rh. japonicum, and Rh. Keiskei var. cardifolia. This substance was found to be identical with grayanotoxin I, isolated from the leaves of Leucothoe Grayana by Miyajima and Takei, and with andromedotoxin, isolated from the leaves of Rh. maximum by Wood and others. The name of andromedotoxin (=grayanotoxin 1) was adopted.

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An empirical formula of C₂₀H₂₉O (OCOCH₃) (OH)₄ was tentatively assumed for andromedotoxin (=grayanotoxin I) from the result of reactions represented in Chart 3 and the infrared spectral curve shown in Fig. 1.

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Drug preparations in general undergo change due to oxygen and moisture in the air with consequent decrease in the content, change in the preparative form, or coloration. Even with sugar- and gelatin-coated tablets, effect of moisture cannot be avoided during their preparation. In order to avoid such changes, it is desirable that drugs be coated perfectly with a substance which is water-resistant but which dissolves in gastric juice, so that the drugs will be protected from atmospheric moisture and other external effects while the preparation will easily crumble in gastric juice. As coating agents with such properties, aminocellulose derivatives were taken up and various derivatives were prepared by the applications of amines to methyl-, acetyl-, and ethylhydroxyethyl-cellulose p-toluenesulfonate. These derivatives were submitted to tests by coating tablets with each compound and measuring the time necessary for crumbling in distilled water and artificial gastric juice. It was thereby found that benzylamino- and diethylamino-methylcellulose, and 1-piperidyl- and benzylamino-ethylhydroxyethylcellulose were markedly good in water-resistance and solubility in gastric juice, and suitable as agents for a protective coating.

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Periodate oxidation was carried out on methyl 3, 6-anhydro-α-D-galactopyranoside (II), 3, 6-anhydro-D-galactose (III), 3, 6-anhydro-D-galactose diethylmercaptal (IV), and 1-deoxy-3, 6-anhydro-D-galactitol (1, 4-anhydro-L-fucitol) (V). (II) remained completely inert to this oxidation, while (III) consumed 2 moles of periodate and formed 1 mole of formic acid. About 3 moles of periodate was consumed by (IV) and 1 mole by (V). The oxidation product of (V) was obtained as bis-p-nitrophenyl-hydrazone (VII). From the foregoing results, it was confirmed that the anhydro sugar derived from methyl 6-O-tosyl-α-d-galactopyranoside (I) possesses the 3, 6-anhydro ring. The unexpected result obtained in the case of (IV) was found to be due to the consumption of periodate by the sulfur in mercaptal and was proved by the use of benzaldehyde diethylmercaptal.

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2-Alkoxy-1-naphthylamine derivatives were synthesized in order to test them for local anesthetic action. Alkoxynaphthalene (methyl, ethyl, butyl, isopentyl), prepared by the method of Williams, was nitrated by the method of Paul, reduced by the usual method to 2-alkoxy-1-naphthylamine, and reacted with chloroacyl chloride or bromoacyl bromide to obtain the corresponding 1-haloacylamido-2-alkoxy-naphthalene. The objective free bases were obtained by the application of dimethylamine or diethylamine and the free bases were reacted with hydrochloric acid to form the hydrochlorides. As a preliminary test for pharmacological effect of these substances, the compounds synthesized were submitted to rabbit cornea test and their time of duration was compared with that of cocaine.

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1) Utilization of various amino acids as the nitrogen source was tested with Escherichia coli No. 1. It was thereby found that aspartic acid is utilized best, followed in that order by asparagine, glycine, arginine, serine, glutamic acid, alanine, and leucine, while phenylalanine, tryptophan, valine, proline, lysine, isoleucine, histidine, threonine, and methionine are not well utilized. Periodical change of such utilization was examined by varying the length of culture and it was found that the utilization of asparagine and serine was greatly increased by prolongation of culture time.
2) The utilization of compounds related to arginine as a nitrogen source was found to be in the decreasing order of urea, citrulline, arginine, and ornithine, the utilization of urea being especially marked. Since ornithine was detected in the medium provided with arginine as the nitrogen source, it was assumed that E. coli No. 1 possesses an arginine-decomposing enzyme of arginine dihydrolase type.
3) The amino acid liberated into the medium during the growth of E. coli No. 1 in inorganic medium was examined by a two-dimensional paper chromatography and aspartic acid, glutamic acid, alanine, valine, histidine, and methionine were detected. There seemed to be no direct relationship between the amount of these amino acid appearing in the medium and the rate of utilization.
4) Deamination of various amino acids by E. coli No. 1 was examined and it was found that there is a parallel relationship between that and utilization of amino acids. The two were found to agree approximately in amino acids with low growth-promoting acitivity.
5) Oxygen uptake was measured with various amino acids as a substrate and it was found to be not stoichiometric with deamination reaction. It was therefore assumed that the deamination is other than oxidative.

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Electrolytic reduction of organic compound with the use of a cathode coated with hydrogenation catalyst is not new but it is theoretically possible than such electro-catalytic reduction of organic compounds has better effect that the direct electrolytic reduction or hydrogenation at ordinary pressure for the following reasons.
1) Over-voltage for hydrogen evolution at the catalyser electrode is extremely small and its cathode potential is quite close to the hydrogen electrode potential. Therefore, this process is very advantageous when a direct electrolytic reduction would interfere in the desired reduction and the desired reaction can progress only through catalytic reduction.
2) In this process, the reaction H⁺+e→H→1/2H₂ alone occurs on the surface of the catalyser electrode. This fact signifies that hydrogen is directly and sufficiently supplied to the cathode catalyst and that the hydrogen content of the catalyst is sufficiently large. Therefore, the reducibility of this catalyser cathode becomes extremely great as compared to ordinary hydrogenation reaction in which the rate-determining step is the supply of hydrogen to the catalyst, i.e. solubility of hydrogen gas in the solvent and its solubilization rate.
This electro-catalytic reduction was attempted with acetophenone, p-nitrosalicylic acid, p-nitroaniline, and nitrobenzene, and ethylbenzene, p-aminosalicylic acid, p-phenylenediamine and aniline were obtained in a good yield.
The reduction of acetophenone to ethylbenzene had not been effected by the conventional cathode of high-hydrogen over-voltage and catalytic reduction required hydrogen gas of medium pressure. The reduction of p-nitrosalicylic acid could not have been effected by direct electrolysis with lead cathode and was only possible by the use of surface chemical action of an electrode, like the use of a tin cathode. Catalytic reduction at ordinary pressure of a free p-nitrosalicylic acid resulted in decarboxylation and its sodium or ammonium salt had been usually used.

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Whereas the oxidation of ethyl 3-acetoxy-11-ethoxycarbonyleusantona-3, 5-dienate (II) with peracetic acid gives 3-oxo-6α-hydroxy-11-ethoxycarbonyleusanton-4-enic acid lactone (III), the same oxidation of the mixture (IX) of 3-acetoxyeusantona-3, 5-dienic acid and its C-11 epimer affords 3-oxo-6β-hydroxy-eusanton-4-enic acid lactone and C-11 epimer mixture (VII), which is also obtained on the oxidation of (IX) with chromium trioxide or potassium permanganate. (VII) is also obtained on the oxidation of a mixture (VI) of 3-oxoeusanton-4-enic acid and its C-11 epimer with mercuric acetate.

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When 2-bromo-3-oxo-6β-hydroxy-11-carboxyeusanton-4-enic acid lactone (I) is bóiled in pyridine, it undergoes stereospecific decarboxylation to form 2-bromo-3-oxo-6β-hydroxy-11-epi-eusanton-4-enic acid lactone (III), whose catalytic reduction gives 3-oxo-6β-hydroxy-11-epi-eusanton-4-enic acid lactone (V). The same compound (V) is also obtained by the catalytic reduction of (I) to form 3-oxo-6β-hydroxy-11-carboxyeusanton-4-enic acid lactone (IV) and boiling it in pyridine. It follows that the stereospecificity of the foregoing decarboxylation reaction is independent of the presence of bromine in 2-position and is a characteristic specific to these kinds of cis-lactone. The 11-epi structure of (III) and (V) was proved by boiling (III) in collidine to form 3-oxo-6β-hydroxy-11-epi-eusantona-1, 4-dienic acid lactone (II) and by the reduction of (III) with zinc dust to form 3-oxo-11-epi-eusanton-4-enic acid (VII).

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The properties of the alicyclic portion of a new fused heterocyclic compound, 7-methyl-4H-pyrimido [4, 5-d]-m-thiazin-2(1H)-one (I) was examined. Application of lithium aluminum hydride results in the reduction of carbonyl to methylene and not cleavage of the ring. Oxidation with hydrogen peroxide in glacial acetic acid results in the formation of 2-methyl-4-amino-5-pyrimidinylmethanesulfonic acid (XII) and not pyrimidine N-oxide. Heating with alkali hydroxide effects decarboxylation to form 2-methyl-4-amino-5-pyrimidinylmethanethiol hydrochloride (XV).
The previously reported disulfide compound (III) and the isothiuronium hydrogen carbonate (IV) also form sulfonic acid compound (XII) on oxidation with hydrogen peroxide in glacial acetic acid, while the thioether compound (VI) is oxidized first to a sulfone (VII) and then the pyrimidine ring is cleaved to form acetylurea.

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Methyl tetracosanate and methyl hexacosanate were each reacted in xylene, in the presence of sodium hydride and respectively formed methyl 2-docosyl-3-oxo-hexacosanate (I) and methyl 2-tetracosyl-3-oxoöctacosanate (I′), each in good yield. Each was reduced with sodium borohydride, saponified, and purified by chromatography, respectively affording 2-docosyl-3-hydroxyhexacosanoic acid (IIIα), m.p. 91-92.5°, (IIIβ), m.p. 86-88°, and 2-tetracosyl-3-hydroxyoctacosanoic acid (III′α), m.p. 92-93.5°, and (III′β), m.p. 87-89°. These compounds were identified by infrared spectra and through their acetates. 2-Docosylhexacosane-1, 3-diol (IV), m.p. 75.5-77°, and 2-tetracosyloctacosane-1, 3-diol (IV′), m.p. 78-79.5°, were isolated as the by-products of (III) and (III′). On the other hand, saponification of (I) and (I′) respectively afforded lignocerone (II) and cerotone (II′), which were identified by their oximes.

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Mutual solubility of the aliphatic primary amine-water-salt system at 30° was measured. The aliphatic amines used were propylamine, butylamine, amylamine, hexylamine, and heptylamine, and the salts used were potassium and sodium carbonate, sodium sulfate, and sodium and potassium chloride. It was thereby found that the conjugation curve, when represented as the molar fraction, was approximately experimentally linear within a certain concentration range. The dehydrating tendency of these amines was in the descending order of heptyl-, hexyl-, amyl-, butyl-, and propylamines with any of the salts, showing that higher the amine, the more easily it is dehydrated. The rearrangement is in the order of molecular weight and each of the straight lines was approximately in parallel. It was also found that there is a definite regularity in the dehydrative power of the salts.

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Visible absorption spectra of 30 kinds of phenylpyrazolone-azomethine derivatives were measured in methanol solution and examinations were made on the effect of a substituent (R′) in 1-position of the pyrazolone ring on absorption curve, as well as that (R) in the 3-position. When R′ is an electron acceptor, there is a tendency for increased contribution of ionic resonance structure in the excited state and the maximum absorption of x-band to shift to a longer wave-length side. Conversely, when R′ is an electron donor, the same shifts to a shorter wave-length side. The effect of R agreed entirely with the assumption drawn earlier and the same result was obtained of steric interference.

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The transmitted color of methanolic solution of 30 kinds of phenylpyrazolone-azomethine derivatives was compared with the CIE color chart, an international method of indicating the color tone, and observations were made on the relationship between chemical structure and dominant wave length. Calculation of trichromatic coefficients was made by the weight ordinate method, using C light source. It was found that when the substituent in 1-position of pyrazolone ring is an electron acceptor, the dominant wave length shifts to a longer wave-length side, while the same shifts to a shorter wave-length side when the substituent is an electron donor.

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Twenty-nine kinds of phenylpyrazolone derivatives were condensed respectively with N, N-diethyl-p-phenylenediamine by a photographic method, pyrazolone-azomethine dyes were formed on a photographic film, and trichromatic coefficients were calculated from their spectrometric transmission rate. These were compared with the dominant wave lengths calculated from the ultraviolet and visible absorption spectra of the dyes in methanol solution. The dominant wave length of the dyes formed on a film is generally more to a shorter wave-length side than that in methanolic solution, but the effect of each substituent on the dominant wave length and the order of the shift of dominant wave length among these compounds were found to be approximately similar to that in methanolic solution.

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Solvent effect on the ultraviolet and visible absorption spectra of 14 kinds of pyrazolone-azomethine derivatives was examined. These were compounds possessing a substituent with -SO₂NH- in 3-position of pyrazolone ring or those without such a substituent. In both, maximum wave length of the x-band tended to shift to a longer wave-length side with the increase of dielectric constants. The compounds with a substituent of -SO₂NH- in 3-position greatly affect the resonance system by the dissociation of -SO₂NH- in a basic buffer solution and the band makes a hypsochromic shift.

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Effect of a solvent on the ultraviolet and visible absorption spectra was examined in 12 kinds of pyrazolone-azomethine compounds, using solvents with widely varying dielectric constants. The maximum absorption of the x-band generally made a bathochromic shift with increasing dielectric constants, while that of compounds with a substituent containing -SO₂NH- bond in 3-position of the pyrazolone ring made a hypsochromic shift when the amount of water in the solvent exceeded a certain limit. Therefore, a transition curve with extinction ε at a specific wave length (550mμ) clearly agrees with the dissociation curve. Measurement of degree and constant of dissociation of these compounds indicated that compounds assumed to have a steric hindrance had larger dissociation constant and was less likely to be affected. Compounds with a substituent containing -SO₂NH₂ bond in 1-position of the pyrazolone ring had smaller dissociation constants than those not possessing such a substituent, while this state of dissociation was not observed in compounds other than those with -SO₂NH- bond in the substituent in 3-position.

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Effect of solvent pH on the ultraviolet and visible absorption spectra of 19 kinds of pyrazolone-azomethine compounds was examined. The maximum absorption of the x-band in these compounds generally shifts to a shorter wave-length side with increasing pH and by the comparison of extinction coefficient ε at 550mμ, these compounds were found to undergo dissociation between pH 8 and pH 14. Further, it was also found that compounds with a substituent containing -SO₂NH- in 3-position of the pyrazolone ring underwent a two-step dissociation at pH 2.1-4 and pH 4-7. Comparison of the effect of these substituents by measurement of dissociation constants showed that the order of dissociation at pH 8-14 is CH₃OC₆H₄SO₂NH-(p)>CH₃>C₆H₅SO₂NH>C₆H₅CONH, while it was in the order of CH₃OC₆H₄SO₂NH-(p)>NH₂C₆-H₄SO₂NH-(p)>CH₃C₆H₄SO₂NH-(p) in compounds assumed to have a steric hindrance. Compounds with a substituent containig NH₂SO₂ at 1-position of the pyrazolone ring had smaller dissociation constants than those without such a substituent. It was also found that compounds assumed to have a steric hindrance had larger dissociation constants than those without such hindrance and were less likely to be changed by the solvent pH.

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The metal chelate compounds of tetracyclines were prepared and their structure, solubility, and stability constants were determined. The ligands applied were the hydrochlorides of chlortetracycline and oxytetracycline, and the metal salts were chlorides, nitrates, and sulfates of Th⁴⁺, UO₂⁴⁺, Fe²⁺, Cu²⁺, Co²⁺, Al³⁺, and Zn³⁺.
The concentrated solution of the chelate compounds was mainly prepared with water, ethanol, and methylcellosolve with an excess of metal ion, the chelate compounds were then precipitated by adding ether or acetone to this solution, and purified by reprecipitation and repetition of washing. Recrystalization was not available here.
The compounds thus isolated are powder or vitreous solid with characteristic colors (yellow, orange, brown, etc.), most of which are soluble in water, while the UO₂²⁺ and Zr⁴⁺ chelates are somewhat sparingly soluble. These compounds are soluble in dilute acid and alkali, but their solubility decreases at pH 6-8. They are also sparingly soluble in organic solvents, e.g. ethanol and butanol, but insoluble in chloroform, benzene, and acetone.
The molar ratio of all the compounds (ligand: metal) is 1:1, but Zr⁴⁺ chelate compound, 1:2. These results hold true in aqueous solution. One exception is the ratio of ferric chelate which is 1:1 in solid, but 1:2 in aqueous solution.
By measuring the degree of dissociation colorimetrically, the stability constants can be obtained, the order of which is as follows: Fe³⁺>Zr⁴⁺>Th⁴⁺>UO₂²⁺>Al³⁺>Mg²⁺.
Adaptation of the displacement method with ferric chelate compound as standard is attempted with some chelate compounds and the result accordingly is Th⁴⁺>Cu²⁺>Co²⁺>Zn²⁺>Sr²⁺.

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Addition of hydrogen bromide to 2-allylanisole usually affords 1-(2-methoxyphenyl)-2-bromopropane by normal addition but the presence of a peroxide affords an abnormal addition product, 1-(2-methoxyphenyl)-3-bromopropane by peroxide effect. This product was identified by comparison with 2-(3-bromopropyl) anisole obtained by the bromination of 3-(2-methoxyphenyl) propanol formed by reduction of ethyl 2-methoxycinnamate. The 3-(2-methoxyphenyl) propylamines obtained by the amination of these bromo compounds possess physiological activity equal to or stronger than their isomers, α-methyl-2-methoxyphenethylamines, such as antihistamine actions.

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β-Methyl-2-methoxyphenethylamines, similar to α-methyl compounds, possess excellent sympathetic nerve stimulating action and these were prepared from 2-meth-oxyhydrotropaldehyde as the intermediate. Treatment of 1-(2-methoxyphenyl)-1, 2-dibromopropane with dilute acid results in concurrent hydrolysis and rearrangement to form 2-methoxyhydratropaldehyde and its reductive amination or amination by the Leuckart-Wallach reaction afforded β-methyl-2-methoxyphenethylamines. As one of related compounds, N, β-dimethyl-4-methoxyphenethylamine was prepared.

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Four different samples of Adams' platinum catalyst were prepared by changing the pyrolytic temperatures to 450°, 500°, 550°, and 600°, and specific surface area of these samples was measured by the gas and liquid adsorption methods. If the amount of thiourea added to the sample, at which hydrogen absorption of the catalyst becomes zero, is taken as the poisoning value, the greater the specific surface area, the greater will be the poisoning value, with consequent resistance to poisoning. Since the number of molecules adsorbed in liquid adsorption method and the number of molecules in poisoning value are in proximity, it was considered that the adsorpion of a poisoning molecule on Adams' platinum catalyst was preceded by the formation of a mono molecular layer.

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Examinations were made on the alkaloids of commercial crude drug “Moku-Boh-i” which originates from Cocculus trilobus DC. The chief alkaloid isolated was magnoflorine.
It had been impossible to separate and identify trilobine and isotrilobine from their mixture by the usual paper chromatography but it was found that the two bases could be separated by the use of a multi-buffered paper chromatography. By this method, the presence of a minute amount of trilobine and isotrilobine in “Moku-Boh-i” was proved.

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The following substances were synthesized by the diazotization of 7-aminocoumarin-3-carboxylic acid followed by the Gattermann, Sandmeyer, or Griess reaction and hydrolysis. 7-Chlorocoumarin-3-carboxylic acid, m.p. 189°. Ethyl 7-bromocoumarin-3-carboxylate, m.p. 124-125°. 7-Iodocoumarin-3-carboxylic acid, m.p. 218-219°, and its ethyl ester, m.p. 129-129.5°. Ethyl 7-hydroxycoumarin-3-carboxylate, m.p. 168-169°. The aqueous solution of these halocoumarin derivatives showed fluorescence under irradiation of ultraviolet rays, similar to 7-nitrocoumarin-3-carboxylic acid.

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Three kinds of crystalline component were isolated from the ethanolic extract of the whole herb of the fish-poison plant (Tephrosia obovata MEER.) of Leguminosae family obtained from the Pescadores, Taiwan. These crystals were found to be tephrosin, toxicarol, and rotenone.

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Oxidation of ethyl 3-halo-11-ethoxycarbonyleusantona-3, 5-dienate (IIa or IIb) with performic or peracetic acid and silver nitrate afforded 3-oxo-6α-hydroxy-11-ethoxy-carbonyleusanton-4-enic acid lactone (V).

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