Chlorination of 6-chloro-4-cyclohexylresorcinol in ether solution with sulfuryl chloride results in the formation of an unstable intermediate, instead of the 2, 6-dichloro compound, and the recrystallization of the intermediate from benzene gives a white substance (I), m.p. 140-141.5° (decomp.), which shows a formula of C12H14O2Cl2⋅C6H6, possessing one mole of benzene and showing a phototropy. The crystals become tinted pink when directly irradiated by sunlight, and the melting point decreases in croportion to the duration of irradiation, finally yielding yellowish brown to brown prystals of m.p. 82-88°. The pink crystals of m.p. 131-133°, obtained by 18 minutes' irradiation, completely returned to the white substance after 24 hours, showing an m.p. 140-141.5°, but those that have changed to brown do not change color or return to the original white substance even after standing in the dark for some period. (I), when dried at 80° for 24 hours, in vacuum, or heated to over 70° for 1.5 hours, changes to a compound possessing a formula of C12H14O2Cl2 (II), m.p. 145° (decomp.), which is not greatly affected by light, only being tinted pale yellow. It seems that 6-chloro-4-alkylresorcinols generally yield by chlorination an unstable intermediate that shows phototropy but details on them have not been studied yet.
In order to obtain 2, 6-dichloro-4-cyclohexylresorcinol, 6-chloro compound was chlorinated with sulfuryl chloride but, instead of the objective compound, an unstable intermediate was obtained and its properties were studied. The intermediate shows phenolic properties but is totally different from chloroalkylresorcinols. Its absorption spectrum showed that the absorption curve has shifted to a longer wave-length range compared to those of 6-chloro- or 2, 6-dichloro-4-cyclohexylresorcinol. The compound yields a precipitate with methanolic silver nitrate solution which is not the case with the 6-chloro or 2, 6-dichloro compound. Methylation with diazomethane gives a monomethyl ether which no longer shows phenolic properties and which, by catalytic reduction, liberates one mole of chlorine and resumes the phenolic properties. Methylation of the latter yields 6-chloro-4-cyclohexylresorcinol dimethyl ether whose dehalogenation and subsequent permanganate oxidation give β-resorcylic acid dimethyl ether.
Chlorination of 6-chloro-4-cyclohexylresorcinol with sulfuryl chloride gives an unstable intermediate (I), possessing one phenolic hydroxyl radical. Its methylation with diazomethane, followed by catalytic reduction results in the formation of a mono-methyl ether (V) of 6-chloro-4-cyclohexylresorcinol. In order to determine the relative positions of the phenolic hydroxyl and the methoxyl group in (V), various reactions were carried out from which (V) was assumed to be 6-chloro-4-cyclohexylresorcinol-3-methyl ether, showing the phenolic hydroxyl to be present in the 1-position and the methoxyl at 3-position.
By the passage of a mixture of 2, 6-lutidine (I) and air over a catalyst, 6, 6′-dimethyl-α-pyridoin (II), C14H14O2N2, was obtained as orange red prisms, m. p. 200°. Unless (I) used for this catalytic vapor-phase oxidation is pure, the yield of (II) becomes very poor. The catalyst MoO3 (WO3 and V2O5 as promotors)-pumice stone was found to be better than V2O5 (WO3, MoO3 and CrO3 as promotors). (II), during its recrystallization, easily underwent autoxidation to 6, 6′-dimethyl-α-pyridil (III), C14H12O2N2, as yellow prisms of m. p. 173°. (II) is also easily oxidized to (III) by potassium permanganate or conc. nitric acid. Reduction of (III) with Pt-catalyst returns it to (II). A monoacetyl derivative of (II) was obtained as colorless prisms, m. p. 130°. Oxidation of (III) with hydrogen peroxide in dioxane gives, with a good yield, 6-melhylpicolinic acid. 6, 6′-Dimethyl-α-pyridil crystals are tinted green when exposed to light but the color changes back to the original yellow when allowed to stand in the dark.
By passing a mixture of quinaldine (I) and air over a catalyst of V2O5, MoO3 and WO3, heated to 450-480°, quinaldoin (III), C20H14O2N2, was isolated from the product as brown microprisms, m. p. 233° (decomp.), with a very small amount of quinoline aldehyde (II). During its recrystallization from a mixture of dioxane and alcohol, (III) undergoes autoxidation to give quinaldil (IV), C20H12O2N2, as yellow, long needles, m. p. 269°. Oxidation of (III) with potassium permanganate or conc. nitric acid easily changes it to (IV), which returns to (III) on catalytic hydrogenation with PtO2. This relationship is the same as that seen with 6, 6′-dimethyl-α-pyridoin and 6, 6′-dimethyl-α-pyridil. Catalytic vapor-phase oxidation of (I) failed to yield quinoline or quinoline-2-carboxylic acid. Oxidation of (I) With SeO2 in dioxane or alcohol, chiefly gives (II) with a small amount of (III), or vice versa, according to the reaction conditions. The yield ratio of (II) and (III) was found to be independent of the freshness or age of SeO2.
Flower wax was saponified with conc. alcoholic potash, and the unsaponifiable matter was fractionated by adsorption through a chromatographic column on alumina as a petroleum ether solution. From the most adsorptive portion, hentriacontanol, C31H63OH, was obtained as scaly crystals, m.p. 80.5-81.5°, and sitosterol, C29H49OH, was obtained as plate crystals, m. p. 135-136°, as the steroid. From the non-adsorptive portion, triacontane, C30H62, was obtained as scaly crystals, m. p. 64-65.5°, nonacosane, C22H60, as scaly crystals, m. p. 62.5-63.5°, pentacosane, C25H52, m. p. 53-54.5°, and as a triterpene, lupeol, C30H49OH, as needle crystals, m. p. 210°. It was also confirmed that an aromatic terpene alcohol (probably linalool or geraniol) was present as a substance of b.p.17 110-115° in the alcohol-soluble part of both portions.
1) Pentacyanoiron complex salts such as sodium nitroprusside, pentacyanoamminferroate and pentacyanoaquoferroate, react with hydroxylamine in NaOH or KOH solutions to give ruby red coloration which is not manifested in other alkali solutions (such as Na2CO3, NaHCO3, NH4OH, Ba(OH)2, Ca(OH)2). This allows distinction of these two kinds of alkalis. 2) To a very small amount of phenol compounds, or to 1 drop of its aqueous solution, 1 drop of 1% pentacyanoferroate solution is added, followed by l% solution of hydroxylamine hydrochloride and 1 drop of N-NaOH, by which green to blue coloration results. By this means, detection of phenol compounds is possible. Weakness of the coloration can be increased by slight heating.
Following compounds were synthesized as the derivatives of coumarin- and 6-nitro-coumarin-3-carboxylic acids: Butyl coumarin-3-carboxylate, m.p. 66-66.5°; butyl 6-nitrocoumarin-3-carboxylate, m.p. 153-154°; isoamyl 6-nitrocoumarin-3-carboxylate, m.p. 153-153.5°; coumarin-3-carboxylic urea, m.p. 255-255.5°; 6-nitrocoumarin-3-carboxylicurea, m.p. 243.5°. It was found, during this experiment, that the preparation of coumarin-3-carboxylic acid from salicylaldehyde by the Knoevenagel reaction gave better results when a solvent (alcohol) was not used.
Salicylaldehyde and nitrosalicylaldehydes were prepared as the starting material for the synthetic preparation of coumarin- and nitrocoumarin-3-carboxylic acids. Salicylaldehyde, 3-nitro-, 4-nitro- and 5-nitro-salicylaldehydes were obtained in a fairly good yield by the CrO3 oxidation of o-cresol and the monoacetates of corresponding nitrocresols in acetic anhydride and glacial acetic acid. The Reimcr-Tiemann reaction sometimes gave poor yields due to the effect of the nitro group, but this reaction had to be resorted to for 6-nitrosalicylaldehyde because of the availability of the original material. 4-Nitrosalicylaldehyde is obtained as yellowish white plates, m. p. 136-136.5°, recrystallized from a mixture of benzene and ligroin, and gives a phennyihydrazone of red needles. m. p. 174°, from alcohol.
Tuberculostatic action was examined with 29 kinds of p-nitrobenzoic acid derivatives and p-nitrobeozyl or p-nitrophenacyl-thiazolium compounds, in vitro against human H2 strain. None showed any remarkable growth inhibition as shown in Tables I and II.
Tuberculostatic action in vitro was examined of 10 kinds of p-nitrophenyl- and p-aminophenyl-imidazo compounds (cf. Table I) and some of the nitro compounds showed a more or less growth inhibitory action. The same action of 10 kinds of acid amides of p-nitro- and p-amino-salicylic acids examined (cf. Table II) showed that, although some efficacy was shown, the compounds obtained by the reaction of Girard P reagent on p-nitro- and p-acetamino-benzaldehyde were totally ineffective.
Fresh leaves and roots of Rhodea japonica Roth. were extracted, after preventing the action of enzyme by the Stoll method, treated in the usual manner, and the glycosides were separated by adsorption chromatography by which rhodexin A and rhodexin C were obtained in 0.008% and 0.03% yield, respectively. It was then found that rhodexin B was not present at all so that it was assumed that rhodexins A and C were contained in the plant organism as the true glycosides. The fresh fruits of Rhodea japonica were separated into pericarp and seed, and extracted separately to examine the presence of glycoside. It was found that glycoside was not contained in the pericarp, and about the same amount of rhodexins A and C were found to be present in the seeds as in fresh leaves and roots.
Periodic acid oxidation of trehalose and raffinose was carried out and the products were obtained as their p-nitrophenylhydrazones, that from trehalose being m. p. 160° (decomp.), [α]D=+70.00°, possessing only 2 phenylhydrazine groups against 4 aldehyde groups, while that from raffinose was m. p. 165° (decomp.), [α]D=+35.3°, with 3 phenylhydrazine groups against 6 aldehyde groups. The acid decomposition of the hydrazones yielded, from trehalose hydrazone, glyoxale, its p-nitrophenylosazone and glyceraldehyde, and from raffinose, phenylhydrazone, glyceraldehyde p-nitrophenylhydrazone besides the foregoing three. From these results, it was made possible to prove the bonding position of the p-nitrophenylhydrazine groups.
From the series of present experiments, it seems probable that the structure of glucosazone is cyclic, as was proposed by Percival, but its acetone adduct is in a straightchain structure so that it would not contain a bridged, oxygen.
Products obtained by the condensation of acetylene (I) and ammonia (II) invariably possess even-numbered carbon atoms, odd-numbered pyridine (IV) and lutidines not being formed at all. Even in compounds with even-numbered carbons, α-picoline, γ-picoline and 2, 3, 6-collidine are formed, but not β-picoline and 1, 3, 6-collidine. The present workers succeeded in obtaining pyridine as well as β-picoline and 3, 5-lutidine by the addition of methanol in the mixture of (I) and (II). Various catalysts were tried and Cd-phosphate, -chromate, -tungstate, -titanate and -vanadate were found to give the best yields of pyridine, with Fuller's earth used as the carrier. The best temperature range was found to be 350-425°, molar ratio of (I), (II) and MeOH at 1:1:1, the highest yield of (IV) being 23.7% calculated from the amount of (I) used.
Ullmann reaction was carried out on 5- and 7-bromoquinolines, obtained by the Skraup reaction of m-bromoaniline, by which 5- and 7-phenoxyquinolines were obtained. These were led to their respective tetrahydro and N-methyltetrahydro derivatives. Ullmann reaction of 8-hydroxyquinoline and phenol gave 8-phenoxyquinoline from which some derivatives were prepared.
By the Willgerodt reaction carried out on 4-acetyl- and 4, 4′-diacetyl-diphenyl ethers, with pyridine base as the solvent, corresponding diphenyl ether-4-acetic and diphenyl ether-4, 4′-diacetic acids were obtained in good yields.
It has been described by Friedman, et al. (U.S. Pat. 2, 500, 283, Brit. Pat. 625, 931), that the application of benzaldehyde and formic acid on 2-amino-4-methylpyrimidine results in the formation of 2-benzylamino-4-methylpyrimidine (III), but such formation was not witnessed by the reëxamination of this reaction by the present workers. In its stead, 2-amino-4-styrylpyrimidine (I) and 2-benzylamino-4-styrylpyrimidine (II) were obtained. (I) can also be obtained by heating 2-amino-4-methylpyrimidine and benzaldehyde to around 200°. The similar heating of (III) and benzaldehyde results in the formation of (II). Respective oxidation of (I) and (II) with potassium permanganate yields 2-aminopyrimidine-4-carboxylic acid (V) and benzoic acid, (V) yielding 2-amino-pyrimidine by decarboxylation.
It has been found by reëxamination that the formation of 2-p-methoxybenzylamino-4-methylpyrimidine (I) by the application of p-methoxybenzaldehyde and formic acid on 2-amino-4-methylpyrimidine, as described by Friedman, et al. (U.S. Pat. 2, 500, 283, Brit. Pat. 625, 931), is not correct, and the products obtained by the present workers were 2-amino-4-p-methoxystyrylpyrimidine (II) and 2-p-methoxybenzylamino-4-p-methoxystyrylpyrimidine (III). Oxidation of (II) yields 2-aminopyrimidine-4-carboxylic acid and p-methoxybenzoic acid. It was also found that by heating of 2-amino-4-chloro-6-methylpyrimidine with formic acid or with acetic anhydride, the chlorine atom at 4-position was easily replaced by a hydroxyl group.
In the synthetic preparation of 3-alkyl-4-methyl- or 4-alkyl-7-hydroxycoumarins by the condensation of resorcinol and ethyl α-alkyl- or γ-alkyl-acetoacetate in sulfuric acid, the reaction is somewhat obstructed when the ester possesses a higher alkyl group, resulting in the sulfonation of resorcinol with consequent decrease of the yield. By the decrease of sulfuric acid concentration and allowing longer hours for the reaction period, objective compounds with several long-chain alkyl groups were obtained with good yields.
Mold preventing action against soy sauce was tested with 23 kinds of synthetically prepared arylthioureas. Of the compounds tested, 2-hydroxyphenylthiourea showed the strongest action but was far weaker than that of butyl p-hydroxybenzoate used as the control.
Several dl-trans-2-diethylaminocyclohexyl esters were prepared from dl-trans-2-diethylaminocyclohexanol and aromatic acid chlorides (cf. Table I), and molar ratio and the solvents used were examined. A new synthetic procedure for the preparation of benzilate was also described. Of the compounds prepared, p-nitrobenzoate was obtained by Osterberg and Kendall who noted the melting point as 175°, 17° lower than that of the sample obtained by the author.
dl-trans-2-Dimethylamino- and -diethylamino-cyclohexyl benzhydryl ethers were prepared. The material, dl-trans-2-dimethylaminocyclohexanol, was obtained by heating cyclohexene oxide and dimethylamine in methanol at 180° under high pressure.
Determination of ascaridol in chenopodium oil was made by the infrared absorption spectrum. The wave-length of 10.69μ was chosen as the key band, and in the thickness of cell at 0.1mm., and in concentrations below approximately 8% by weight, the Beer's law was found to be applicable. Quantitative analyses with various samples could be made rapidly within an approximate error of 1-2%. This method could be used as a means of examining the method of chemical determination.
Dibenzalsorbitol which forms an organic gel is a mixture of di- and tri-compounds. Dibenzalsorbitol is obtained by the condensation of 2, 4-monobenzalsorbitol and benzaldehyde, gives an acetone adduct and a diacetate, and is oxidized by lead tetraacetate. It is concluded that the di-compound is 1, 3:2, 4-dibenzal compound, while the tri-com-pound is the 1, 3:2, 4:5, 6-tribenzal compound.
By carrying out paper chromatography of cardiotonic glycosides and aglycones of digitalis leaves, examinations were made as to their separate identification and of the purity of digitoxin preparations and their purification processes. The developing agent was a mixture of chloroform, methanol and water in 10:2:5 ratio, and the detection was made by utilizing fluorescence under ultraviolet ray with trichloroacetic acid. Pure digitoxin was obtained in a comparatively easy manner by the chromatographic purification on silica gel.
Separatory identification of gitoxigenin, diacetylgitoxigenin, oleandrigenin, 3-acetylgitoxigenin and 3-acetyl-Δ16-gitoxigenin was carried out by paper chromatography. Developing agent used was a mixture of chloroform, benzene and water in 1:9:2 ratio, and in the coloration the fluorescence by trichloroacetic acid was utilized under ultraviolet ray. It was thereby confirmed that partial acetylation of gitoxigenin yielded olean-drigenin alone, while partial hydrolysis of diacetylgitoxigenin yielded 3-acetylgitoxigenin alone. Therefore, the secondary alcohol groups in C3 and C16 were found to possess different properties, the latter being more reactive.
Respective condensation of α-bromo-3, 4-methylenedioxypropiophenone (IV) with acetamidine, phenacetamidine and thiourea yielded 2, 5-dimethyl-4-(3′, 4′-methylenedioxyphenyl)-imidazole (V), 4-(3′, 4′-methylenedioxyphenyl)-5-methylimidazole (VI) (in which a liberation of the benzyl group at 2-position had occurred), and 2-amino-4-(3′, 4′-methyl-enedioxyphenyl)-5-methylthiazole (VII), respectively. 2-Sulfanilamido-4-(3′, 4′-methylenedioxyphenyl)-5-methylthiazole (IX) and 2-(β-diethylaminoethylamino)-4-(3β, 4β-methylenedioxyphenyl)-5-methylthiazole (X) are obtained by the respective condensation of (VII) with acetosulfanilyl chloride and β-diethylaminoethyl chloride. Attempts on the cyclization of the amidine (III) and the condensation of (IV) with S-methyl isothiourea failed. Biological tests of (V), (VI), (VII), (IX), (X) and the methobromide of (X) are in progress.
Ortho, meta and para derivatives of 1-diethylaminoethoxyphenyl-3-methyl-6, 7-meth-ylenedioxyisoquinoline (V) and the dimethylamino compounds (VI) were prepared by reacting dimethyl- and diethyl-aminoethyl chlorides with 1-hydroxyphenyl-3-methyl-6, 7-methylenedioxyisoquinolines (IV), respectively, using sodium ethoxide as a condensing agent. Diethylaminoethyl 1-methyl-6, 7-methylenedioxyisoquinoline-3-carboxylate (VIII) was obtained by the trans-esterification between methyl 1-methyl-6, 7-methylenedioxy-isoquinoline-3-carboxylate (VII) and diethylaminoethanol. Biological tests of (V), (VI), (VIII) and methobromides of (V) and (VI) are now in progress.
It was found that, starting with industrially obtainable butyric acid, p-methoxy-α-hydroxybutyrophenone and p-methoxy-α-acetoxybutyrophenone were prepared after several processes, to which anisole was condensed, with conc. sulfuric acid as the condensing agent, to yield α, α-dianisyl-β-butanone. The preparation of 4, 4′-dihydroxy-α, β-diethylstilbene, which possesses an estrogenic activity, starting with butyric acid and using the above butanone as the intermediate, was successfully concluded. Condensation of anisole to α, α-dianisyl-β-ethylbutanol, obtained by reacting ethylmagnesium bromide to α, α-dianisyl-β-butanone, with conc. sulfuric acid as the condensing agent, resulted in the formation of 4, 4′-dimethoxy-α, β-diethylstilbene.
It was assumed that the preparation of testosterone via 3-hydroxy-17-amino-Δ5, 6-androstene was advantageous and therefore, Leuckart reaction was applied to trans-dehydroandrosterone by which 3-hydronxy-17-formamino-Δ5, 6-androstene was obtained in approximately 90% yield dy a hitherto unknown method. Its oxidation yielded 3-keto-17-formamino-androstene.
Utilizing the fact that 3-hydroxy-17-formamino-Δ5, 6-androstene is practically insoluble in ether, Leuckart reaction was applied to the neutral substance contained in the oxidation product of cholesterol by which 3-hydroxy-17-formamino-Δ5, 6-androstene, for the use of the synthetic preparation of testosterone, was easily isolated in pure form by the method hitherto unknown in literature.
It was assumed that the monochloro compound (I), m.p. 193-194°, obtained from dl-threo- and dl-erythro-1-phenyl-2-aminopropane-1, 3-diol hydrochloride is the threo compound. Acetylation (II) of this monochloro compound, followed by saponification (III→IV), yielded an N-acetyl erythro compound (V). The mechanism of this reaction was assumed to be one example of a participation of acyl group in replacement reaction, probably via oxozalidinium compound (III). By the reactions described in the Reports I and II, it has become possible for a reciprocal inversion to occur between an erythro and a threo compound, as shown in the accompanying Tables.
It was assumed that the monochloro compound (II), m. p. 201-202°, obtained by the respective application of thionyl chloride to L(-)-ephedrine and L(+)-ψ-ephedrine was the threo compound, and the mechanism of the ethylenimine cyclization and its cleavage are discussed. It was considered essential that the reaction which yielded N-acetyl L-ephedrine by the acetylation and saponification of this monochloro compound had to pass through an oxazolidinium compound. An advantageous rearrangement process whereby L (+)-ψ-ephedrine or a mixture of L(+)-ψ-ephedrine and L(-)-ephedrine was led to L(-)-ephedrine has been described.
By carrying out the acyl migration from N to O With N-acetyl-L-ψ-ephedrine, dl-threo-1-phenyl-2-acetylaminopropane-1, 3-diol, dl-threo-1-p-nitrophenyl-2-acetylaminopropane-1, 3-diol and chloramphenicol, it was confirmed that the compounds yielded O-acetyl or O-dichloroacetyl compound by the R-mechanism.
Matsukawa has already reported that acetylation of γ-aceto-γ-chloropropyl alcohol (V) with acetic anhydride gave three isomers, 2-methyl-2-acetoxy-3-chlorotetrahyd-rofuran (VIII), 2-methyl-2-hydroxy-3-acetyl-3-chlorotetrahydrofuran (II) and γ-aceto-γ-chloropropyl acetate (VI). However, authors confirmed from infrared absorption spectra that only (VI) would be obtained in this case. In a similar manner, the compound, obtained by the treatment of (V) with benzoyl chloride, is not 2-methyl-2-hydroxy-3-benzoyl-3-chlorotetrahydrofuran (XIII) but γ-aceto-γ-chloropropyl benzoate (XVIII). Following the procedure for α-aceto-γ-acetoxypropyl [2-methyl-4-aminopyrimidyl-(5)]-methyl-dithiocarbamate (VII), SB1 (IV) was synthesized from α-aceto-γ-benzoxypropyl [2-methyl-4-aminopyrimidyl-(5)]-methyl-dithiocarbamate (XIV) obtained from (XVIII)
An almost pure α-aceto-γ-hydroxypropyl [2-methyl-4-aminopyrimidyl-(5)]-methyl-dithiocarbarnate (VI) is obtained in an approximately quantitative yield by standing the aqueous solution of ammonium [2-methyl-4-aminopyrimidyl-(5)]-methyl-dithiocarbamate-(I), obtained by the condensation of CS2 and NH3, (NH4)2S, or (NH4)HS to 2-methyl-4-amino 5-aminomethylpyrimidine (IX), with the addition of an aqueous solution of γ-aceto-γ-chloropropyl alcohol (V). In this case, the use of O-acetate (II) or O-benzoate (VII) in place of (V) results in exactly the same reaction taking place to yield α-aceto-γ-acetoxy(or benzoxy)-propyl [2-methyl-4-aminopyrimidyl-(5)]-methyl-dithiocarbamate (III or VIII). The same result can be obtained by reacting together (V), (II) or (VII) with (IX), CS2 and NH3, but it seems more appropriate to assume that this reaction occurs by way of (I) as an intermediate.
An addition of 3 moles of hydrogen peroxide to the suspension of 1 mole of 3-[2′-methyl-4′-aminopyrimidyl-(5′)]-methyl-4-methyl-5-β-hydroxyethyl-thiothiazolone-(2) (I) in water, at 25-35°, results in generation of heat and hydration of the crystals. Evaporation of the reaction solution under a reduced pressure and addition of absolute alcohol to the residue result in the precipitation of thiamine sulfate (II). Treatment of the above reaction product with BaCl2 or Ba(NO3)2 yields thiamine hydrochloride (III) or thiamine nitrate (IV).
An addition of 3 moles of hydrogen peroxide to a suspension of 1 mole of O-acetyl, O-propionyl or O-benzoyl substituent (II, V or VI) of 3-[2′-methyl-4′-aminopyrimidyl-(5′)]-methyl-4-methyl-5-β-hydroxyethyl-thiothiazolone-(2) (I) in water, at 25-35°, results in generation of heat and in solvation of the crystals. Evaporation of the reaction mixture under a reduced pressure and addition of absolute alcohol to the residue yield acetyl-, propionyl- or benzoyl-thiamine sulfate (III, VII or VIII). Treatment of the reaction mixture with BaCl2 yields the hydrochlorides (IV, IX and X) of acylated thiamines. (II) and (V) can be prepared in a good yield by the respective boiling (I) with glacial acetic acid or propionic acid.
Antibacterial activities of isonicotinic acid hydrazide and isonicotinylglycine hydrazide, in vitro, against tubercle bacilli (human, bovine and avian types) were tested. The former was found to inhibit the growth of bacilli at 10, 000, 000 dilutions, while the latter showed the same activities at 30, 000-100, 000 dilutions, both against human and bovine types. Both compounds were totally ineffective against avian tubercle bacilli.
A new colorimetric method for the determination of m-aminophenol present in sodium p-aminosalicylate (PAS) has been devised. To a neutral solution containing 1mg. PAS and less than 50 γ of m-aminophenol in 1cc. of solution are added 0.2cc. of 27% ammonia water and 0.6cc. of 35% formaldehyde solution and, after about 5 minutes, 0.1cc. of quinone imide reagent (0.1% butanolic solution of 2, 6-dichloroquinone monochlorimide) is added. This mixture is diluted with distilled water to 5cc., shaken thoroughly and allowed to stand for 1.5hours. The extinction of this colored solution at 590 mμ is measured. The concentration of m-aminophenol in the sample solution is obtained by comparison with the extinction of a standard solution of PAS and m-aminophenol. When the amount of m-aminophenol in the sample is less than 5 γ against 1mg. of PAS, the sample solution is so adjusted as to contain 10mg. of PAS in 1cc. of solntion. In this case, 1.4cc. of formaldehyde solution is used, instead of 0.6cc., to minimize the effet of PAS on the coloration of m-aminophenol.