The antibacterial action of the extracts of 50 kinds of crude drugs were tested against Escherichia coli and Bacillus dysenteriae by the Bouillon dilution method. It was found that Cortex Magnoliae obovatae, C. Myricae, C. Quillaiae, Fructus Gleditschiae, Semen Euryales and Flos Caryophylli were found effective against E. Coli, and the above and 15 others were found effective against B. dysenteriae, effective minimum concentration against the latter being: Semen Euryales 1:800, Flos Caryophylli 1:400, Lignum Picrasmae 1:200, Cortex Quillaiae 1:100. The effective dilution against E. Coli being: Semen Euryales 1:200, Cortex Quillaiae 1:100. Others were all ineffective at less than 1:50.

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Antibacterial action against Staphylococcus aureus and Escherichia coli, and insect repellent action against Attagenus piceus were tested with 34 kinds of compounds, chiefly of dihydroxydiphenylmethanes and their chloro derivatives. An approximately parallel relationship was found to exist between the two actions. In regard to the relationship between the actions and chemical structure against Staph. aureus, the presence of hydroxyl radical was found to be important with emphasis on the ortho position rather than the para. As to the effect of substituents, the introduction of organic groups such as alkyl, phenyl, halogens and nitro, was found to strengthen the effect while inorganic groups such as sulfones and carboxyls tended to decrease the action. The most strongest action against staphylococci were found in 2, 2′-dihydroxy-3, 5, 3′, 5′-tetrabromodiphenylmethane and 2, 2′-dihydroxy-3, 5, 3′, 5′-tetrachlorodiphenyltrichloroethane, both of which were effective up to 1:60, 000, 000 dilution. 2, 2′-Dihydroxy-3, 5, 3′, 5′-tetrachlorodiphenylmethane was effective against E. coli up to 1:500, 000 dilution.

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4′, 5′-Dimethoxy-3, 4, 5, 6, 7, 8-hexahydro-(1, 2:1′, 2′-benzoquinolicine) (III) was synthesized from δ-valerolactone and β-3, 4-dimethoxyphenethylamine via N-β-3, 4-dimethoxyphenethylpiperidone (V), followed by ring closure to (II) and hydrogenation to (III). The results obtained are shown in the accompanying table. This synthetic method adds another one to the existing methods as described by Child and Pyman, and by Sugasawa and Sakurai, whose descriptions do not agree entirely.

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In vitro tests of growth inhibition against tubercle bacilli were carried out with 14 kinds of thiosemicarbazones, 5 kinds of cinnamic acid and coumarin derivatives, 10 kinds of nitro, nitroso and amino derivatives of phenols such as phenol, cresol, resorcinol and thymol, and four other compounds. As a result, it was found that thiosemicarbazones of p-thymotinaldehyde, 2, 4-dihydroxy-3-chloro-5-ethylbenzaldehyde, 2, 4-dihydroxy-3-chloro-5-butylbenzaldehyde, 2, 4-dihydroxy-3-chloro-5-hexylbenzaldehyde and p-nitrobenzaldehyde showed a similar antibacterial action as Tibione. Although 2-hydroxy-5-nitrocinnamic acid, β-methyl-7-aminocoumarin and p-nitrosothymol showed antibacterial action of around 64, 000 dilution, there were no compounds which showed antibacterial action equal to streptomycin, p-aminosalicylic acid and usnic acid.

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2-(p-Aminobenzenesulfonamido)-4, 5-dimethylpyrimidine (VIII) was prepared by the condensation of methyl α-formylethyl ketone (II) or its sodium salt (I) with sulfaguanidine by means of alkaline condensing agent. N⁴-Acetylsulfaguanidine undergoes similar condensation only in acetic acid solution giving 2-(p-acetaminobenzenesulfonamido)-4, 5-dimethylpyrimidine (VII). Better results were obtained when acetals of methyl α-formylethyl ketone such as (III), (IV) or (V) was used in place of (I) and (II). 2-(p-Dimethylaminobenzenesulfonamido)-4, 5-dimethylpyrimidine was also synthesized.

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A new method for the industrial preparation of sulfamerazine was established, based on Sugasawa's method using formylacetone acetal and sulfaguanidine as the starting material. β-Acetylvinyl ether and formylacetone ethylene acetal are also available for the same purpose. The reaction mechanism between β-acetylvinyl chloride and sulfaguanidine in the synthesis of sulfamerazine is also discussed.

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The preparation of 5-(p-aminobenzenesulfonamido)-3, 4-dimethylisoxazole (sulfaisoxazole) was studied. When 5-amino-3, 4-dimethylisoxazole (aminoisoxazole) was condensed with acetosulfanilyl chloride, two kinds of bis-acetosulfanilyl derivatives were obtained, the two showing different stability against alkali. The less stable compound furnished two moles of acetosulfoisoxazole when fused with one mole of aminoisoxazole, while the other, more stable, remained unchanged under similar treatment. The aminoisoxazole was then condensed with p-toluenesulfonyl chloride, followed by acetosulfanilyl chloride, and vice versa. By studying the properties of 5-[N, N-(p-toluenesulfonyl)-(p-acetosulfanilyl)-amino]-3, 4-dimethylisoxazole thus produced, it was deduced that the more stable bis-compound is 5-[bis-(p-acetosulfanilyl)-amino]-3, 4-dimethylisoxazole (V), and the other, 2-acetosulfanilyl-3, 4-dimethylisoxazolone-acetosulfanilylimide-5. The isolation of the latter compound, which is less stable, is now under progress.

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β, β-Dichloropropionaldehyde acetal, prepared from 1-bromo-3, 3-dichloropropyl acetate and appropriate alcohol, was condensed with acetylsulfaguanidine in acetic acid solution in the presence of sodium acetate, giving acetylsulfadiazine in 28% yield. When the condensation was carried out in conc. sulfuric acid, 2-aminopyrimidine was the only product isolated which owes its formation to guanidine sulfate, the degradation product of acetylsulfaguanidine by sulfuric acid.

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Guanidine salts were condensed with 1-bromo-3, 3-dichloropropyl acetate (I) or β, β-dichloropropione acetal (II) in conc. sulfuric acid or in alcohol containing hydrochloric acid by which 2-aminopyrimidine was obtained in a good yield. A small amount of 2-amino-5-bromopyrimidine was formed at the same time when (I) was used as the starting material.

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Of the thiosemicarbazones of benzaldehyde with substituent in the para position which were said to be as effective as Tibione, p-ethylsulfonylbenzaldehyde thiosemicarbazone was prepared by the condensation of thiosemicarbazide and ethylsulfonylbenzaldehyde. This aldehyde was obtained from the corresponding methyl derivative, i.e. p-tolylethyl sulfone, by its oxidation with chromic and sulfuric acids in acetic anhydride to aldehyde diacetate, followed by hydrolysis.

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1) By the thiocyanation of 2-amino-, 2-acetamino-, 4-methyl-2-amino- and 4-methyl-2-acetamino-thiazoles, their 5-thiocyano derivatives were obtained in a good yield.
2) Thiocyanation of 2-benzoylaminothiazole and 4-methyl-2-benzoylaminothiazole was examined. These materials were prepared by the fusion of phenyl benzoate with 2-aminothiazole and 4-methyl-2-aminothiazole.
3) 5-Thiocyano- and 5-thiocyano-4-methyl-2-benzoylaminothiazoles were prepared.

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1) Reaction conditions were examined for the preparation of phenosulfazole and 2-(p-hydroxybenzenesulfonamido)-4-methylthiazole by the respective diazotization of sulfathiazole and sulfamethylthiazole, followed by decomposition with hot, diluted sulfuric acid.
2) Properties of phenosulfazole and 2-(p-hydroxybenzenesulfonamido)-4-methylthiazole were clarified.

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1) A new method of benzoylation in which phenyl benzoate and aromatic or heterocyclic amines are heated in or without a solvent to effect condensation was examined.
2) By this method of benzoylation, heterocyclic compounds of nitrogen that contain an amino group in the α-position of nitrogen and are likely to give mono- and di-benzoyl compounds, such as 2-amino-pyridine, -thiazole, -pyrimidine, -quinoline and -benzothiazole, all give monobenzoyl compounds.
3) By this method of benzoylation, compounds containing amino and hydroxyl groups inside a molecule, such as m-amino- and p-amino-phenols, give only the N-benzoylated compounds.
4) 2-Benzoylamino compounds of pyridine, thiazole and pyrimidine, differing from other benzoylated compounds, are soluble in cold, diluted caustic alkalis. This specificity was assumed to have some relationship to the possession of strong antibacterial power by sulfapyridine, sulfathiazole and sulfadiazine.

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1) A new method of benzoylation in which the N-benzoylated aromatic sulfonamides are obtained by the fusion of a mixture of phenyl benzoate, aromatic sulfonamide and anhydrous alkali carbonates, or of phenyl benzoate and alkali salts of aromatic sulfonamides, was examined.
2) By this method of benzoylation, p-amino- and p-hydroxybenzenesulfonamide give only their N¹-benzoylated products in good yields.
3) By extensive application, this method can be used as a novel acylation of aromatic sulfonamides by the use of phenyl esters of aliphatic, aromatic and heterocyclic carboxylic acids.

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Nine kinds of new antihistaminics of pyridine series were synthesized. N, N-Diethyl-N′-γ-lutidyl-N′-benzylethylenediamine (VI) (picolyl- (VIII), pyridyl-(X)) and N-benzyl-N-γ-lutidyl-β-(1-piperidyl)-ethylamine (V) (picolyl (VII), pyridyl (IX)) were obtained by the respective condensation of 4-benzylamino-lutidine (IIa), -picoline (IIb), and -pyridine (IIc) with diethylaminoethyl chloride and N-β-chloroethylpiperidine (III). Schiff's bases, obtained from anisaldehyde and dimethyl- or diethyl-aminoethylamine, were reduced to give N, N-dimethyl-N′-p-methoxybenzylethylenediamine (XIII) and N, N-diethyl compound (XIV). The use of furfural instead of anisaldehyde gave N, N-diethyl-N′-furfurylethylenediamine (XV). N, N-Dimethyl-N′-γ-lutidyl-N′-p-methoxybenzylethylenediamine (XVI) was obtained from (XIII) and 4-chlorolutidine, N, N-diethyl-N′-γ (α-picolyl)-N′-furfurylethylenediamine (XVII) from (XV) and 4-chloropicoline, and N, N-dimethyl-N′-γ (α-picolyl)-N′-phenylethylenediamine (XVIII) from N, N-dimethyl-N′-phenylethylenediamine and 4-chloro-α-picoline.

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The lutidine fraction in the lower boiling fraction and quinoline fraction in the medium boiling fraction of the coal-tar bases were treated with hydrogen peroxide and glacial acetic acid to obtain N-oxide compounds. The lutidine fraction thereby yielded 2, 6- and 2, 4-lutidine-N-oxides and β- and γ-picoline-N-oxides, while the quinoline fraction yielded quinoline- and isoquinoline-N-oxides. These compounds were respectively treated with phosphorus trichloride in chloroform to give the original bases in a good yield. 2, 6- and 2, 4-lutidine, β- and γ-picoline, quinoline and isoquinoline were all obtained in a pure state.

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Replacement reactions of quinoline and its N-oxides possessing halogen or nitro group in the 4-position with various carbon anion groups were examined. In most cases, orginal materials were recovered, or resulted in the formation of resinous products of unknown structure. However, some success were obtained by the reaction of 4-bromoquinoline and cuprous cyanide in which the two compounds were mixed and distilled under reduced pressure and yielded cinchonic nitrile. Condensation of 4-bromoquinoline with benzyl cyanide in the presence of sodium amide gave, in a good yield, α-(4-quinolyl)-phenylacetonitrile. Since 4-bromoquinoline can easily be obtained in a good yield from 4-nitroquinoline-N-oxide, its reaction with cuprous cyanide would be the most suitable method of preparing cinchonic nitrile and lepidylamine.

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The authors compared the paper chromatograms of hydriodies of organic bases obtained by developing with butanol with those of the quarternary ammonium iodides. On the latter could be observed either a spot of iodine which coincided with the spot of the base colored by Dragendorff's reagent, or two spots of iodine one of which coincided with that of the base while the spot of iodine of the former did not coincide at all.

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Heating aromatic sulfonamides with phenyl or naphthyl esters of carboxylic acids in the presence of alkali carbonate gives easily and in a good yield N-acyl derivatives of sulfonamides.

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By heating 1-p-nitrophenyl-2-amino-1, 3-propanediol (aminodiol) (I) with an excess of dichloroacetic acid by themselves at 130-140° or in toluene, N, O, O-tri(dichloroacetyl)-aminodiol, m.p. 142-143°, is obtained. In the case of heating in butanol, N-dichloroacetylaminodiol (chloramphenicol), m.p. 150-151°, is obtained in a 47% yield irrespective of the amount of dichloroacetic acid used. Boiling aminodiol with an excess of acetic acid gives N, O-diacetylaminodiol, m.p. 170°, while heating with equimolar amount of acetic acid in toluene, or with 1-5 molar quantity of acetic acid in butanol gives N-acetylaminodiol, m.p. 162-163°, in 50-60% yield. Heating (I) in butanol with formic, menthoxyacetic and mandelic acids in butanol gives, respectively, N-formylaminodiol, m.p. 180°, in 80-90% yield, N-menthoxyacetylaminodiol, m.p. 138-140°, in 30% yield, and N-mandelylaminodiol, m.p. 182-184°, in 15% yield. Heating (I) with excess of benzoic acid at 130-140° gives N-benzoylaminodiol. From these results, it is seen that, although the yields vary according to the acid used, heating aminodiol with organic acid in butanol results in selective N-acylation, the reaction mechanism of which is assumed to be dehydration of organic salts of aminodiol.

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By the extension of the reaction reported in the previous paper, organic acid was reacted with 1-p-nitrophenyl-2-amino-1, 3-propanediol (aminodiol) (I). By the heating of aminodiol benzoate (II) with excess of acetic acid in butanol, N-acetylaminodiol (III) was obtained in a 69% yield. The use of equimolar amount of acetic acid, in this case, results in the decrease of the yield to 10% with recovery of unreacted (II). Application of equimolar amount of acetic acid and excess of benzoic acid to (I) gives (II) alone and no formation of (III) was detected. By the application of dichloroacetic acid to d- and l-aminodiol tartrate in butanol, the natural-form chloramphenicol (d-V) and its antipode (l-V) were obtained with 40% yield. d-Compound, [α]_D²²=+19.07° (c=1.52% EtOH); antibacterial power 1000u/mg.

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By heating dl-, d- and l-1-p-nitrophenyl-2-acetylamino-1, 3-propanediol (II) and excess of dichloroacetic acid in butanol, dl-, d- and l-1-p-nitrophenyl-2-dichloroacetylamino-1, 3-propanediol (chloramphenicol) (I) was obtained in 31% yield. In the same manner (I) was obtained in 37% yield from dl-1-p-nitrophenyl-2-formylamino-1, 3-propanediol (III). The same reaction on dl-1-p-nitrophenyl-2-benzoylamino-1, 3-propanediol (IV) ended in the recovery of the unreacted material.

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Acetylation of the hydrochloride (III) of 1-p-nitrophenyl-2-amino-1, 3-propanediol (aminodiol) (I) with acetic anhydride results in the acetylation, first, of the hydroxyl in the 3-position, then of the hydroxyl in the 1-position, and finally, that of the amino group with liberation of hydrochloric acid, to yield O³-acetylaminodiol hydrochloride (IV), O, O-diacetylaminodiol hydrochloride (V) and N, O, O-triacetylaminodiol (VI). Alkalization of (IV) and (V) results in acyl rearrangement from O to N giving N-acetylaminodiol from (IV) and N, O-diacetylaminodiol from (V). By the application of this method, the hydrochloride (III), and methanesulfonate (IV) of (I) and d-camphor-β-sulfonate of d- and l-compounds were respectively heated with dichloroacetic acid at 100° by which the hydrochloride, methanesulfonate, and d-camphor-β-sulfonate of O³-dichloroacetylaminodiol were obtained whose alkalization results in aryl rearrangement to yield chloramphenicol (II). By heating (I) and d- and l-aminodiol tartrate with dichloroacetic acid at 100°, O³-dichloroacetylaminodiol dichloroacetate was obtained whose acyl rearrangement also gave (II).

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By the acyl rearrangement of chloramphenicol (II) with hydrochloric acid, O-dichloro-acetylaminodiol hydrochloride (III), m.p. 166-168° (decomp.), was obtained in 63% yield. The same rearrangement of (II) with methanesulfonic acid gave two kinds of O-dichloro-acetylaminodiol methanesulfonate, one being the compound (IV), m.p. 151-152°, [α]_D¹⁹=-45° (MeOH), (yield, 55%) in which the acyl group had migrated to the hydroxyl in 1-position, while the other (V), m.p. 180-181°, [α]_D¹⁹=+11° (MeOH) (yield, 17%), a compound acylated in the 3-position. (III) was assumed to be the compound in which the rearrangement occured at the hydroxyl in 1-position from the specific rotation, [α]_D¹⁸=-48° (EtOH). The products obtained by the acyl rearrangement of dl-N-acetylaminodiol (VI) by the application of d-camphor-β-sulfonic acid, d-and l-O-acetylaminodiol d-camphor-β-sulfonate (VII) (d-, m.p. 140-141°; l-, m.p. 172-173°), were resolved, alkalized to effect acyl rearrangement and optically active compound (VI) was obtained. The same resolution of dl-chloramphenicol (II) gave l-compound of O-dichloroacetyl-aminodiol d-camphor-β-sulfonate (l-VIII), m.p. 178-179°, which was isolated, the same acyl rearrangement carried out and l-compound of (II) was obtained. The mother liquor obtained after separation of (l-VIII) was also alkalized for acyl rearrangement to yield a mixture of dl-(II) and d-(II) from which d-(II) was obtained by recrystallization.

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1) Several kinds of 2-aryloxypyrimidines were prepared by the reaction of 2-chloropyrimidines and phenols or naphthols.
2) Heating aromatic sulfonamides with 2-aryloxypyrimidines or pyridines in the presence of alkali carbonate easily yields sulfapyrimidines or sulfapyridines.

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Application of pyridine to thiamine hydrochloride in aqueous solution in the presence of sulfurous acid at a room temperature results in exchange of 4-methyl-5-β-hydroxyethylthiazole (I) and pyridine to yield N-(2-methyl-4-aminopyrimidyl-(5))-methylpyridinium compound (II). Contrariwise, application of (I) to the hydrochloride of (II) in aqueous solution in the presence of sulfurous acid results in its conversion to thiamine. These reactions occur according to the law of mass action and is greatly influenced by the pH of the medium, the most suitable being pH 5-6 for the reaction of thiamine to (II), and pH 4-5 for the reverse reaction. The products of both reactions were obtained and confirmed as crystals although a by-product was found to have been formed as 2-methyl-4-aminopyrimidyl-5-methylsulfonic acid. (II) was coincidental with the hydrochloride obtained by the condensation of 2-methyl-4-amino-5-bromomethylpyrimidine hydrobromide with pyrimidine followed by treatment with silver chloride. (II) changes to 2-methylpyrichromine by alkaline oxidation with ferricyanide, and its butanolic solution shows bluish green fluorescence which can be distinguished from the fluorescence of thiochrome. These reactions are quite similar to reactions occuring by the thiamine decomposing enzyme.

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Reactions of 2-amino-, 2-amino-4-methyl- and 2-amino-4-phenyl-thiazoles with esters of acetoacetic, malonic and monochloroacetic acids, and with monochloroacetic acid were examined.

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Isoquinoline derivatives possessing alkyl group in the 8-position of benzene nucleus, i.e. 1-phenyl-5-methoxy-8-ethyl-3, 4-dihydroisoquinoline and 1-methyl-5-methoxy-8-butyl-3, 4-dihydroisoquinoline, were synthesized from p-ethyl- and p-butylanisol.

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Pharmacognostic studies were made of Cinnamomum daphnoides S. et Z., C. Loureirii Nees, C. Japonicum S., and C. Camphora S. (Family Lauraceae) and a fruit of each plant was determined by their morphological and anatomical specificities. The fatty oils show similar melting points except that of C. Camphora that they could be used in place of Oleum Nikkei specified in Japanese Pharmacopoeae V.

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By the application of sodium hydroxide, 2′-amino-6-chloro (methoxy, ethoxy) pyrido-2, 3:5′, 4′-thiazole was decomposed to 2-mercapto-3-amino-6-chloro (methoxy, ethoxy)-pyridine and treated with acetic anhydride to obtain 2-acetylmercapto-3-acetamino-6-chloro (methoxy, ethoxy) pyridine and 2′-methyl-6-chloro (methoxy, ethoxy) pyrido-2, 3:5′, 4′-thiazole. 2-Acetylmercapto-3-acetamino-6-chloropyridine is hydrolyzed by cold sodium hydroxide solution to 2-mercapto-3-acetamino-6-chloropyridine which is then oxidized by ferric chloride to 3, 3′-diacetamino-6, 6′-dichloropyridine-2, 2′-disulfide.

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2′-Styryl-6-chloro (methoxy, ethoxy)-pyrido-2, 3: 5′, 4′-thiazole and its derivatives were prepared by the respective condensation of 2′-methyl-6-chloro (methoxy, ethoxy) pyrido-2, 3: 5′, 4′-thiazole with benzaldehyde, m-and p-nitrobenzaldehydes and p-dimethylaminobenzaldehyde.

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1) 2-(β-Chloroethyl)-mercapto-6-nitrobenzothiazole was prepared by the condensation of 2-mercapto-6-nitrobenzothiazole and ethylene chloride and was led to its 6-acetamino derivative. 2-Propyl (isoamyl) mercapto-6-nitrobenzothiazole were reduced to the 6-amino derivatives.
2) Alkyl and allyl 6-nitrobenzothiazolyl-(2) sulfones were reduced to 6-amino derivatives which were acetylated to 6-acetamino derivatives.

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1) In the preparation of pyridine from α-picoline with V₂O₅-pumice stone as a catalyst, studies were made to find the relationship between the amount of catalyst and the yield. Using reaction tube with section area of 2.0cm², a mixture of α-picoline and air are passed at a flow rate of 0.05cc/min., and 300cc/min., respectively, and the best yield of pyridine was obtained at the thickness of catalyst layer of 7.5-15cm. Catalyst layer of more or less than this thickness decreased the yield.
2) If the methyl group in α-picoline alone received partial oxidation to give pyridine, then the amount of oxygen necessary would be 1.5mol. oxygen per mol. of picoline. Actually, however, partial oxidation of pyridine ring occurs at the same time that the amount of air most suitable is 3.5-6 liter per 1cc. of α-picoline, i.e. about 2-3.5 times more air than the theoretical amount.
3) Comparison of resistance to oxidation between α-picoline and pyridine showed that the former is more liable to oxidation at a lower temperature.

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Several derivatives of 3-methoxydiphenyl ether were synthesized. 3-Methoxy-4-nitrodiphenyl ether, needles, m.p. 109° (from methanol), and 3-methoxy-6-nitrodiphenyl ether, needles, m.p. 89° (from alcohol) were obtained by the Ullmann reaction from 3-bromo-6-nitro- and 3-bromo-4-nitro-anisol, respectively. Both were converted to corresponding amines by reduction with sodium disulfide in alcohol. 3-Methoxy-4-aminodiphenyl ether hydrochloride, m.p. 230° (decomp.) (from chloroform). 3-Methoxy-6-aminodiphenyl ether hydrochloride, m.p. 156° (decomp.) (from benzene). By direct bromination of 3-methoxydiphenyl ether, monobromo and dibromo derivatives are easily formed. The substituent positions of these bromo derivatives are assumed to be in 4- and 6-positions. Monobromo compound, b.p._0·4 105-110°; dibromo compound, b.p._0·08 137-140°. By benzoylation of the dibromo compound following demethylation, white needles, m.p. 118° (from chloroform and alcohol) were obtained which was found identical with 3-hydroxydibromodiphenyl ether benzoate prepared by dibromination and subsequent benzoylation of 3-hydroxydiphenyl ether.

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The addition of quinoline, nicotinic acid or nicotinic amide to the aqueous solution of thiamine hydrochloride in the presence of sulfurous acid and allowing the mixture to stand for a few days at a room temperature or at 30° result in the substitution of these amines with the thiazole portion (I) of thiamine to yield N-(2-methyl-4-aminopyrimidyl-(5′))-methylquinolinium chloride hydrochloride (QB₁), N-(2′-methyl-4′-aminopyrimidyl-(5′))-methyl-3-carboxypyridinium chloride hydrochloride (V) or its 3-carbamino compound (VI). Application of 4-methyl-5-β-hydroxymethylthiazole (I) or pyridine to aqueous solution of (QB₁) in the presence of sulfurous acid respectively gives thiamine- or N-(2-methyl-4-aminopyrimidyl-(5))-methylpyridinium chloride hydrochloride (PB₁). (PB₁) returns to (QB₁) by the action of sulfurous acid and quinoline. (QB₁) is oxidized by alkaline iodine or ferricyanide to form 2-methylquinochromine (IV) that shows yellowish green fluorescence in alcoholic and isobutanolic solutions. By alkaline ferricyanide oxidation, (V) and (VI) form 2-methyl-9-carboxypyrichromine (VII) and 9-carbamino compound (VIII), respectively, which show violet fluorescence in aqueous solution and dull bluish green fluorescence in alcoholic and isobutanolic solutions. Hydrobromides of (QB₁), (V) and (VI) can easily be obtained by the condensation of 2-methyl-4-amino-5-bromomethylpyrimidine hydrobromide and quinoline, nicotinic acid and nicotinic amide, respectively. As shown above, it is interesting to note that thiamine undergoes replacement reactions with nicotinic acid or amide which are growth factor in animal body.

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As a compound similar to amidone, 4-phenyl-4-Δ¹-cyclohexenyl-6-diethylaminohexanone-3 (I) was prepared. From the facts that the substitution of one phenyl in 1-diphenyl-3-piperidinopropane (II) increases the analgesic activities of both musculotropic and neurotropic types and that the double bond in morphine is between C₇ and C₈ of the phenanthrene nucleus, the synthesis was carried out to find the pharmacological action of (I). (I), b.p.₁ 159-161°, was obtained in a good yield from α-phenyl-α-Δ¹-cyclohexenyl-γ-diethylaminobutyronitrile (IV) with ethylmagnesium bromide. Oxalate, m.p. 132-134°; succinate, m.p. 99-100°; ethobromide, m.p. 120-121°. No crystalline salts were obtained of hydrochloride, sulfate, perchlorate, tartrate, camphor-sulfonate and picrate.

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Following four kinds of phenylpyrazolone derivatives were prepared: 1-p-Sulfophenyl-3-pentadecyl-, 1-p-phenoxy-m-sulfophenyl-3-pentadecyl-, 1-m-carboxyphenyl-3-p-palmitinoylaminophenyl- and 1-p-carboxyphenyl-3-m-palmitinoylaminophenyl-5-pyrazolones.

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Dimethyl and diethyl ethers of resorcinol and the diazonium salts prepared from 2, 4-dinitroaniline were coupled in glacial acetic acid or nitrobenzene by which coupling was effected together with liberation of the alkyl group. A better result was obtained in the case of glacial acetic acid. The liberation of the alkyl group takes place at the alcoxyl in the para-position of the coupling.

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Pectin obtained from Bryophyllum calicinum Salisb. contains a large amount of calcium which was removed by ammonium oxalate and the pectin precipitated by alcohol containing hydrochloric acid. This pectin differs in its component parts, is composed of 75% galacturonic acid, gives 7.3% methoxyl value, and is chiefly composed of galacturonic acid and glucose. Part of the acid was confirmed to be methyl ester from the fact that its oxidation yielded mucic and saccharic acids and glucosazone.

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1) From the ether extract of the fruits of Neem tree (Melia azedarach L. var. japonica Makino) five neutral oil fractions were obtained by chromatographic adsorption. Their saponification values were 188.22-209.22, and iodine values, 135.82-146.93.
2) The adsorbability of the oil was found to be dependent on the number of double bonds rather than on the molecular weight.
3) By the estimation of Reichert-Meiszl and Polenske values of the total neutral oil, 6.67% of the consituent fatty acids was found to be volatile.
4) The volatile fatty acids were led to hydroxamic acids and paper-chromatographed by which acetic and caproic acids were obtained which were also confirmed as silver salts and p-bromophenacyl esters.
5) In case hydrated butanol was used as a solvent at 24-25°, the Rf value of valerohydroxamic acid was slightly smaller than that of isovalerohydroxamic acid, the reverse of which was true in the case of using hydrated ethyl acetate as a solvent.

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Application of p-chlorobenzene to sodium p-toluene sulfinate (I) yields p-methyl-p′-nitrodiphenyl sulfone (II) which, when oxidized with chromic acid in acetic anhydride and hydrolyzed, gives 4-(p-nitrobenzenesulfonyl)-benzaldehyde (IV). Condensation of thiosemicarbazide with (IV) followed by reduction gives 4-(p-aminobenzenesulfonyl)-benzaldehyde thiosemicarbazone (VI) whose acetate (IX) is obtained by its treatment with acetic anhydride. The acetate is also obtained by treating (IV) with sodium bisulfite to sodium bisulfite adduct of 4-(p-aminobenzenesulfonyl)-benzaldehyde followed by the application of acetic anhydride and glacial acetic acid to p-acetamino compound (VIII) and finally condensed with thiosemicarbazide.

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Paper partition chromatography of inorganic cations were carried out with potassium, sodium, ammonium, magnesium and lithium chlorides in neutral solutions of propyl alcohol containing 10% by volume of methanol. After evaporation of the solvent, the strip was sprayed with 5% solution of silver nitrate, exposed to diffused light and washed with water. A good separation of all five metals was always obtained. A number of other solvents including butanol: methanol in 3:7 ratio and amyl alcohol: methanol in 3:7 ratio also gave good results. However, the separation of magnesium from lithium was found to be more difficult and the addition of 2% oxine to these solvents gave better results. Since the separation by this means can be achieved even in absolute dryness, the mechanism of separation was assumed not to be totally dependent on partition between immiscible solvents but rather on selective adsorption between the paper used and the metal halides. Examples of such separation of amino acids with dried solvents of propyl and methyl alcohol suggest such posibility. There is no theoretical grounds for such mechanism and absorption seems to be the only explanation. Müller and Clegg attributed the diffusion velocity of a solvent to the surface tension, density and viscocity but the present experiments indicated that the paper chromatographic separation depends on the equilibrium of absorption potential of surface active substances and their force of solvation towards the flowing potential plane.

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N-Disubstituted sulfonamide derivatives, such as ArSO₂N (R or Ar) (CH₂X) or Ar-SO₂N-(CH₂X)₂ type compounds (R=alkyl, Ar=aryl, X=negative group) which contain a negative atomic group such as the aryl, carboalcoxyl and carbonyl group, bonded through the methylene to the nitrogen of aromatic sulfonamides, such as p-toluenesulfodibenzylamide and p-toluenesulfosarkosine ethyl ester, decompose by the action of alkali alcoxides to form aromatic sulfinic acids. The reactivity of these compounds is proportional to the negativity of the negative atomic group present.

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Some of the compounds of azo dyes of benzidine series are known to possess antiviral and antitripanosomal actions and the benzidine residue is believed to be responsible for the appearance of these activities. Based upon this assumption, about 20 kinds of compounds of sulfanilamide, p-aminobenzamide and p-hydroxybenzenesulfonamide types containing the benzidine residue were prepared and their antibacterial actions against Escherichia coli were examined. Those that showed any antibacterial action were 4, 4′-bis(p-acetamino- and p-amino-benzenesulfonamido)-diphenyl, the former approximately equal to that of sulfanilamide and the latter about that of sulfadiazine. 2-Nitro-4-(p-acetamino- and p-amino-benzenesulfonamido)-4′-acetaminodiphenyl showed similar antibacterial action as that of sulfanilamide.

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Reaction of aryl sulfochloride on 2-amino-5-methyl-, 2-amino-5-mercapto- and 2, 5-diamino-thiazoles, and reaction of acetoacetic and malonic esters on 2-amino-5-methylthiazole were attempted.

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In order to determine the structure of quercetin dimethyl ether, m.p. 232-235°, obtained by the methylation of quercetin with diazomethane in the presence of 2 moles of NaH₂BO₃, its alkaline decomposition was attempted but only protocatechuic acid was confirmed and no phenolic portion was obtained in a pure form. Therefore, Allan and Robinson's synthetic method was followed and methoxyphloroacetophenone (V), 3, 4-dibenzyloxybenzoic anhydride (VI), m.p. 128-129°, and potassium 3, 4-dibenzyloxybenzoate were fused to obtain 5, 7-dihydroxy-3-methoxy-3′, 4′-dibenzyloxyflavone (VII), m.p. 189-190°. (VII) was boiled with 1 mole of dimethyl sulfate and potassium carbonate in acetone to yield 5-hydroxy-3, 7-dimethoxy compound (VIII), m.p. 122-123° (acetate, m.p. 162-163°), which was debenzylated by heating in glacial acetic acid with conc. hydrochloric acid to 3′, 4′, 5′-trihydroxy-3, 7-dimethoxyflavone or quercetin-3, 7-dimethyl ether (I), m.p. 234-235° (acetate, m.p. 163-164.5°), which was found to be identical by mixed fusion with the above-mentioned dimethyl ether.

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Various flavone and flavonol derivatives were prepared (cf. Tables I and II) and their solubilization by borax solution was examined (cf. Tables III and IV), in which + denotes soluble (less than 10% insoluble), -denotes insoluble (less than 10% solute), and ± denotes intermediate. From these results, flavone and flavonol are both insoluble showing that the pyrone ring has no effect in solubilization. Compounds not possessing phenolic hydroxyls in 3′- and 4′-positions are also insoluble but those possessing them in 3′-, 4′ -and 5-positions become soluble. The presence of hydroxyl at 7-position does not seem to have any direct bearing on solubilization. Fisetin is an exception since it is soluble with absence of hydroxyl at 5-position. However, since 3′, 4′-dihydroxyflavonol is an intermediate (±), the hydroxyl in the 3-position cannot substitute for that in the 5-position. Such solubilization tests can be an auxiliary means in the determination of natural flavone and flavonol derivative. Such compounds that are soluble can be utilized in extraction with borax solutions or in isolation from other flavones.

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Treatment of aminoacetonitrile with sodium hydroxide yielded a sodium solution of glycocoll to which p-nitrobenzoyl chloride was reacted to obtain p-nitrohippuric acid. In this instance a monohydrate of pale yellow prisms, m.p. 130-132°, is obtained at pH 1.0-1.5 and that of white needles, m.p. 190-192°, at pH 4.0-4.5. These two transit to each other by the correction of pH. Catalytic reduction of p-nitrohippuric acid yielded p-aminohippuric acid.

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Synthesis of β-diethylaminoethyl-α-naphthylamine, a coloration reagent for microdetermination of sulfa drugs, was attemted. Reaction of α-naphthylamine and diethylaminoethyl chloride in pyridine by heating for a few hours gave the desired compound in a 56% yield. By the same procedure of aniline, o-toluidine and p-phenetidine, diethylaminoethyl derivatives were obtained in 40-50% yield.

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