Biscoclaurine-type base was prepared by the Ullmann reaction of two kinds of benzyl-tetrahydroisoguinoline-type base. One of the starting material, 1-(2-bromobenzyl)-2-methyl-6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline (VIII) was prepared by the route shown in Chart 1 and this was submitted to the Ullmann condensation with armepavine (1-(4-hydroxybenzyl)-2-methyl-6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline) (X) and a compound possessing the parent skeleton of the magnolaminetype base (I), dl-2, 4′-bis (2-methyl-6, 7-dimethoxy-1, 2, 3, 4-tetrahydro-1-isoquinolylmethyl) diphenyl ether (XI), was obtained.
Examinations were made on the Grignard reaction of N-methyl-4-anisoyl-10-hydroxy-decahydroisoquinoline (IVα) and its isomer (IVβ). (IVα) formed the Grignard reaction product (XIIα), while (IVβ) afforded (XIIβ) and its diasteromer (XIIβ′). Dehydration of (XIIα), (XIIβ), and (XIIβ′) in acetic acid with sulfuric acid resulted in the formation of identical substance (XIII) from any of them. From its analytical values, ultraviolet absorption spectrum, and the result of ozonolysis, (XIII) was found to have a styrene-type structure. Acetylation of the alpha-type (XIIα) was found to result in acetylation of only the angular hydroxyl to form (XVα), which easily underwent dehydration on being heated in acid medium and produced (XVI) with a styrene-type structure. Acetylation was not effected in the beta-type (XIIβ) and the starting material was recovered. A more drastic conditions of acetylation showed formation of (XIII). Such a difference in the reactivity of alpha- and beta-type compounds is probably due to the difference in their steric configurations. It was proved that it is impossible to effect mutual isomerization among the Grignard reaction products (XIIα), (XIIβ), and (XIIβ′), which endorses the appropriateness of the assumption made earlier regarding the mechanism of isomerization.
The plane structure of the substances previously synthesized and forming colorless plates (IVα), m. p. 153-154°, and colorless leaflets (IVβ), m. p. 110-113°, were found to be 10-hydroxy-decahydroisoquinoline compound (B) and not the Mannich base (A), as a result of consideration on the synthetic route, composition, chemical determination of each of the functional groups, and the assignment of infrared absorption spectra. In order to make further experimental proof of this fact, ring fission by the Hofmann degradation and steam distillation was attempted and degradation products indicated in Charts 1 and 2 were obtained. It was proved through this experiment that the position of the hydroxyl is also at C-10, that both (IVα) and (IVβ) are N-methyl-4-anisoyl-10-hydroxy-decahydroisoquinoline, the two being isomers with different steric configuration.
Infrared absorption spectra of the synthesized N-methyl-4-anisoyl-10-hydroxy-decahydroisoquinoline (IVα), its stereoisomer (IVβ), and their derivatives are indicated in Figs. 1-12. From the assignment of these infrared absorptions, it is clear that the alpha type (IVα) compounds take a configuration in which the side chain at C-4 and nitrogen in the parent ring are in sterical proximity and the beta type compounds (IVβ) take the steric configuration with the side chain in C-4 and the angular hydroxyl in close proximity. Such observations of infrared absorption spectra and examinations by the Stuart model suggested the structure (A) for the alpha type and (IVα) was assumed to be dl-2-methyl-4α (or β)-anisoyl-10β(or α)-hydroxy-trans-decahydroiso-quinoline. In the case of beta type, however, it was difficult to conclude the structure from their infrared absorption spectra and the possible structures (B), (B′), and (B″) were forwarded for (IVβ).
Comparative examinations were made on ultraviolet absorption spectra and pKa values between 2-methyl-4-anisoyl-10-hydroxydecahydroisoquinoline (IVα) and its isomer (IVβ), and sterecchemical considerations were made on their structure with the previously reported experimental results on their isomerization, dehydration, dehydration reaction of their Grignard-reaction products. It was finally concluded that it would be the most appropriate to assign dl-2-methyl-4α (or β)-anisoyl-10β (or α)-hydroxy-trans-decahydroisoquinoline for (IVα) and dl-2-methyl-4β (or α)-anisoyl-10β(or α)-hydroxy-trans-decahydroisoquinoline for (IVβ).
A new convenient volumetric method was established for the determination of quaternary ammonium salts using sodium tetraphenylborate, with Methyl Orange as the indicator. This method can be applied for quaternary ammonium salts with a long chain of alkyl group, such as cetyltrimethylammonium bromide, laurylbenzyldimethylammonium bromide, etc. It was found that Methyl Orange combined with the quaternary ammonium salts and did not show its acid color even in acid solution but the color appeared at the end point when titrated with sodium tetraphenylborate. Based on these facts, a procedure was established after examination of various conditions, such as the effect of pH, selection of an indicator, and concentration of the titrant and the indicator. In this procedure, 10-20cc. of M/20 to M/1000 sample solution is adjusted to the suitable pH with hydrochloric acid after addition of a drop of M/200 Methyl Orange solution and titrated with M/20 to M/50 sodium tetraphenylborate solution until the acid color appears. Results obtained with this procedure on various kinds of quaternary ammonium salts agreed with those obtained by the potassium cadmium iodide method.
Novel acetylenic alcohols were prepared by the Grignard reaction or with sodium amide in liquid ammonia. 1-Phenylhex-4-en-1-yn-3-ol and 1, 5-diphenylpent-4-en-1-yn-3-ol were prepared as the en-yne alcohols, 1-(2-thienyl)-but-2-yn-1-ol and 1-(2-furyl)-but-2-yn-1-ol as heterocyclic acetylenic alcohols, and 1-phenylhepta-2, 4-diyn-1-ol, 1-(4-chlorophenyl)-hexa-2, 4-diyn-1-ol, 1-(2-hydroxyphenyl)-hexa-2, 4-diyn-1-ol, 1-(3-methoxy-4-hydroxyphenyl)-hexa-2, 4-diyn-1-ol, and 1-(1-naphthyl)-hexa-2, 4-diyn-1-ol as the diyne alcohols. Symmetric diyne alcohols, 1-di-(1-naphthyl)-hexa-2, 4-diyne-1, 6-diol and 1, 6-diphenylhexa-2, 4-diyne-1, 6-diol, were obtained in two isomers each, in pure state.
3-Phenyl-1-propyn-3-ol was derived to its 3-nitrophthalate and submitted to optical resolution, affording A-ester of m.p. 152-153° (decomp.), [α]D25-56.8°, and B-ester of m.p. 152-153° (decomp.), [α]D25+55.7° Each was oxidized with potassium permanganate to mandelic acid nitrophthalate, affording A-acid of m.p. 178°, [α]D28+87.6°, and B-acid of m.p. 178°, [α]D28-90.7°. On the other hand, dl-mandelic acid was resolved into L(+)- and D(-)-mandelic acid by the use of D- and L-threo-3-(p-nitrophenyl)-2-aminopropane-1, 3-diol, both were derived to respective 3-nitrophthalates, and absolute configuration was determined as L-system for A-acid and A-ester, and D-system for B-acid and B-ester. A- and B-esters were each hydrolysed and derived to the corresponding A-alcohol of b. p18 118-119°, [α]D27-23.9°, and B-alcohol of b. p18 118-119°, [α]D28+22.6°, Each was submitted to oxidative coupling with cuprous chloride and corresponding 1, 6-diphenylhexa-2, 4-diyne-1, 6-diol were obtained; L-type, m.p. 120° (decomp.), [α]D26-27.6°, and D-type, m.p. 120°, [α]D26+26.7°. An equimolar mixture of these L- and D-forms gave the racemic compound which was identical with 1, 6-diphenylhexa-2, 4-diyne-1, 6-diol, m.p. 134°, described in the preceding paper of this series. Consequently, this was found to be the racemic compound and the compound melting at 113° to be a meso compound. Each was reduced to form 1, 6-diphenyl-hexane-1, 6-diol and the one of m.p. 134° was determined as the racemic compound and the other of m.p. 127° as the meso compound.
Reduction of hypoepistephanine (I:R=H), a kind of tertiary phenolic base contained in Stephania japonica MIERS (Menispermaceae), as a free base or its dihydrochloride, with sodium borohydride in methanol solution results in selective hydrogenation to form dihydrohypoepistephanine-B (V:R=H), m. p. 223-224°, [α]D24 +87.71°, alone. Methylation of this product gives N-methyldihydrohypoepistephanine-B (VI:R=H) (asymmetric centers: -, -), m. p. 257-258°, [α]D21+82.19°, an antipode of repandine (VII:R=H) (asymmetric centers, +, +), m. p. 248-250°, [α]D21-93.85°. Reduction of (I:R=H) with zinc dust and dil. sulfuric acid results in preferential formation of dihydrohypoepistephanine-A (VIII), m. p. 217-218°, [α]D20+263.15°, accompanied with dihydrohypoepistephanine-B (V:R=H). Formation ratio of A and B is 3:1. Methylation of (VIII) gives oxyacanthine (IX). Reduction of epistephanine (I:R=Me) or its dihydrochloride with sodium borohydride in methanol also results in selective hydrogenation and dihydroepistephanine-B (V:R=Me), m. p. 225-226°, [α]D25+101.01°, alone and its methylation gives N-methyl-dihydroepistephanine-B (VI:R=Me) (asymmetric centers, -, -), m. p. 213°, [α]D19+80.00, an antipode of O-methylrepandine (VII:R=Me) (asynmetric centers, +, +), m. p. 212-213°, [α]D19-79.93°.
In 1952, Takahashi and Senda revealed that a glycide-type compound, 4-(2-dimethylaminopropionamido) antipyrine had small toxicity and excellent properties as an antipyretic-analgesic. As a part of a search for new antipyretic-analgesic, amino acid amide-type compounds, which are in contrast to the former, were prepared from the point of solubility in water and pharmacological activity. The compounds prepared were the amides of N-(4-antipyrinyl) alanine derivatives (I, XI, XII), dimethylamides of N-arylalanine derivatives (II to IV), and amides of N-substituted N-acetylalanines (XIV to XVIII), N-dimethylaminoacetyl-alanines (XXII to XXIV), and N-methylalanines (XXV to XXVII). Some of these compounds showed high solubility in water.
A sharp and simple colorimetric determination of oxytetracycline was carried out. To 5cc. of the aqueous solution of oxytetracycline (2-15γ/cc.) was added 1cc. of p-nitrobenzenediazonium chloride reagent, prepared by the addition of 2cc. of 15% sodium cyanide solution and glacial acetic acid to the ice-cooled solution of 200mg. of p-nitroaniline dissolved in 5cc. of glacial acetic acid and 3cc. of conc. hydrochloric acid, with shaking, the mixture was warmed at 70° for 25 minutes, and the yellow color of the solution thereby produced has the absorption maximum at 440mμ, the absorption following the Beer's law. In the presence of tetracycline, the colorimetry as described above is carried out with the solution of a mixed sample and the value of E440-E530×k is calculated (where k is the value of E440/E530 of tetracycline). This value is compared with the calibration curve of oxytetracycline to obtain the potency and this enables the determination of oxytetracycline alone, excluding the effect of tetracycline. The value of determination carried out on a sample solution, which had been allowed to stand over a long period, by the present method was compared with the values obtained by biological method and a fairly good agreement was obtained.
Separatory determination of oxytetracycline from oxytetracycline preparation containing ascorbic acid was carried out by the use of a Permutit column. A solution (5cc.) of oxytetracycline preparation containing ascorbic acid (10-200γ/cc.) was passed through a column of acid-treated Permutit to effect adsorption of oxytetracycline on Permutit, the column was washed with five 10-cc. portions of distilled water to remove ascorbic acid from the column completely, and the column was eluted with 20cc. of 0.2N sodium hydroxide solution to desorb oxytetracycline. The effluent was received in a vessel containing 4cc. each of N hydrochloric acid and N acetic acid, and the total volume was brought to 50cc. To 5cc. of this solution, 1cc. of p-nitrobenzenediazonium chloride reagent is added and the mixture is warmed at 70° for 25 minutes. This is cooled in running water and the optical density of this solution is measured at 440mμ to obtained the potency of oxytetracycline. The values obtained by this method with oxytetracycline preparation containing ascorbic acid, the sample solution of which had been allowed to stand for a long time, were compared with that obtained by biological method and a fairly well agreeing result was obtained. In this case, aqueous solution containing oxytetracycline alone was allowed to stand under the same conditions and it was found that the rate of decomposition was somewhat higher in the sample containing ascorbic acid.
The potency determination of Fradiomycin had relied on biological method and the present studies were carried out in order to find a simple colorimetric method for its determination. To 5cc. of a sample solution placed in a glass-stoppered test tube, 5cc. of 2% isoamyl alcohol solution of lauric acid and 0.5cc. of 5% sodium carbonate solution were added, the mixture was shaken vigorously, and centrifuged. Four cc. of the isoamyl alcohol in the upper layer was transferred to a new glass-stoppered test tube, 5cc, of distilled water and 0.2cc. of 50% acetic acid solution were added, and the mixture was shaken for 5 minutes. Four cc. of the lower aqueous layer was transferred to a new test tube, 1cc. of 20% sodium carbonate solution was added, and shaken thoroughly. The mixture was cooled in ice water, 0.5cc. of 1% sodium 1, 2-naphthoquinone-4-sulfonate solution was added, and allowed to stand in ice water of 0° to 2° for 20 minutes. To this mixture, 2cc. of an equivolume mixture of acetone and ethanol was added, followed by 0.5cc. of 50% acetic acid solution. At the same time, blank test was carried out with distilled water in place of the sample solution and treated in the same way with the same reagents. Using this as the control, absorbancy was measured at 460 mμ and the potency of the sample solution was calculated from the calibration curve of Fradiomycin. Determinations were carried out by this method on the samples sterilized by boiling and treated with acid and alkali, and a sample solution allowed to stand for a long period. The values so obtained were compared with the values obtained by the cup method, given in the standard for antibiotic preparations and the two values showed good agreement.
Inorganic salts generally stabilize hyaluronidase and the action is especially strong in chlorides and bromides. Heavy metal ions, Cu2+ and Sn4+, inactivate the enzymatic action periodically while chelation agents inhibit this action of heavy metal ions, but also seem to act protectively on the enzyme directly. Protective colloids also has the stabilizing activity. The aqueous solution of hyaluronidase-procaine, added with sodium chloride, chelation agent, and protective colloid, is extremely stable.
Examinations were made on the method for preparation of thromboplastin for the determination of prothrombin concentration, using the brain and lung of bovine, horse, and rabbit as the material. The rabbit lung was found to produce stable thromboplastin of high potency by extraction in the presence of hydroquinone or gallic acid and lyophilization under mild conditions. This thromboplastin can be used for the determination of prothrombin concentration exactly the same as that heretofore prepared from rabbit brain.
Determination of opium alkaloid hydrochloride specified in the Japanese Pharmacopoeia VI does not specify the method of determinating secondary alkaloids. Determination of six main alkaloids, in opium alkaloid hydrochloride, morphine, narceine, narcotine, papaverine, thebaine, and codeine, was carried out by the separation of componental alkaloids by partition chromatography and non-aqueous titration with 0.005Np-toluenesulfonic acid. The separation was effected by the addition of the sample into the alkaline column (pH 12.5) and acid column (pH 2.2), placed vertically and connected above and below, and first extracted with ether, to be separated into amphoteric and non-amphoteric bases. The columns were disconnected and each alkaloid was separatory eluted out as shown in Table I.
Biological product of sulfisoxazole excreted in the urine after its oral administration was examined chiefly through paper chromatography and paper electrophoresis. It was thereby found that the substances excreted are sulfisoxazole, acetylsulfisoxazole, sulfanilamide, sulfisoxazole-N-sulfonate, and sulfisoxazole-N-glucuronide. Isolation of the substances excreted into the urine was carried out and sulfisoxazole, acetylsulfisoxazole, and an unknown substance were isolated. Other substances were in too minute a quantity or too labile to be isolated.
Condensation reaction was carried out among theophylline and benzimidazole with formaldehyde and various secondary amines (diethylamine, morpholine, piperidine) and the corresponding N-Mannich bases were obtained. These bases reacted easily with methyl iodide to form the methiodides of a quaternary salt.
The quaternary salt methiodide of the N-Mannich bases of theophylline has direct C-alkylating ability and, although the tertiary salts had no alkylating ability, the quaternary salt methiodide effected transaminomethylation. Reaction of indole and N-Mannich bases of benzimidazole afforded compounds (VI and III), in which aminomethyl group had been exchanged, and alkylated products. Detailed examination of the said reaction showed that transaminomethylation (a) occurred as the first step and, as a second step, the compounds (VI and VIII), formed by the said exchange reaction, underwent further reaction (b) to form 1-(3-indolylmethyl) benzimidazole (IX). The formation of (IX) was proved to be not the C-alkylation of the N-Mannich bases but N-alkylation of the Mannich base (VI) of indole by benzimidazole.
Pyruvic acid isonicotinoylhydrazone, the Schiff base of isonicotinic acid hydrazide (INAH) and pyruvic acid, was allowed to stand or heated in aqueous solution and the solution was submitted to paper partition chromatography, showing two spots with Rf values different from that of INAH. These spots appear more markedly on addition of Ca2+, Mg2+, and Ba2+. Development of these two spots by the two-dimensional paper chromatography resulted in further division of each into two spots. These two spots are considered to be of the same substance and are interconvertible.
Pyruvic acid isonicotinoylhydrazone the Schiff base of isonicotinic acid hydrazide (INAH) and Pyruvic acid, shows two spots on the paper chromatogram and these substances were assumed to be interconvertible isomers. In order to confirm this point, various related compounds were prepared and submitted to paper partition chromatography. It was thereby learned that the compounds of general formula (I) of the Schiff-base type give two spots when R1 and R2 are different, but only one spot when they are the same. From such facts, the two spots exhibited by pyruvic acid isonicotinoylhydrazone are its sym- and anti-forms.
Cleavage reaction with metallic sodium in liquid ammonia was carried out on O-methyldomesticine (III) and only one kind of phenolic base was obtained as the degradation product, isolated as its hydrochloride of needles, m.p. 255-256° (decomp.). This substance did not possess a methylenedioxy group and had only one methoxyl, its analytical values agreeing with the formula of C18H19O2N⋅HCl. The hydrochloride, m.p. 233-234°(decomp.), of its O-methylated compound possessed two methoxyls and its analytical values agreed with C19H21O2N⋅HCl, there being no evidence for the presence of phenolic hydroxyl in its infrared spectrum. It follows, therefore, that the cleaved base is monomethoxymonohydroxy-aporphine (IV) and its methyl ether would be dimethoxyaporphine (V). Hofmann degradation of (V) by the route shown in Chart 1, followed by oxidation and decarboxylation afforded dimethoxyphenanthrene (XI) which was identified through admixture and comparison of infrared spectra to be 3, 6-dimethoxyphenanthrene (XII). Consequently, the cleaved phenolic base (IV) obtained by the cleavage of O-methyldomesticine with metallic sodium in liquid ammonia is 2-hydroxy-10-methoxyaporphine (XIII) and its O-methylated compound (V) is 2, 10-dimethoxyaporphine (XIV). It is considered from these results that the methylenedioxy group in (III) is cleaved at 9-position by this reaction to produce a fresh hydroxyl in 10-position and the methoxyl in 1-positron is completely liberated. In general, the methoxyl bonded to the benzene ring is known not to change by cleavage reaction with alkali metal in liquid ammonia at a comparatively low temperature or undergoes demethylation in some cases to produce a new phenolic hydroxyl. Therefore, the loss of an aromatic methoxyl group by this cleavage reaction observed in the present series of experiments is an interesting new phenomenon.
2-Hydroxy-1-naphthaldehyde (I) combines with hydrazine giving aldazine (II) in diluted sulfuric acid, which shows a strong yellow-green fluorescence. This reaction may be used for the microdetection of hydrazine and isonicotinic acid hydrazide, which is easily hydrolysed to hydrazine by aqueous sodium hydroxide. The limit of detection of these compounds in one drop of water is 0.01γ and 0.1γ, respectively. The fluorescence of (II) has the maximum intensity at 534mμ. This intensity shows a linear correlation with the concentration of hydrazine in a range of 0.02-0.8γ/cc. and of isonicotinic acid hydrazide in a range of 0.4-12.5γ/cc. (Fig. 2). This method of estimation of the two compounds is interfered by only a few substances.
Transfer of 35S-labeled protein from the ghost protein to cytoplasmic protein was confirmed by the use of the labeled ghost formed by the supply of [35S] methionine to Pseudomonas fluorescens and non-labeled cytoplasm prepared separately. Since the transfer of 35S-labeled protein is hardly affected by the presence of [32S] methio nine, it was considered that the transfer is effected at the level of peptide. When using two kinds of ghost with different degree of destruction, transfer ability of labeled protein in the ghost (1:2) with smaller degree of destruction is much smaller than that of the ghost (1:10) with larger degree of destruction. In the ghost of mandelic acid-adapted cells, transfer ability of labeled protein in the ghost (1:2) was higher and it is assumed that the ghost of adapted and non-adapted cells are fairly different.
Incubation of the protoplast of Pseudomonas fluorescens was carried out by (1) preincubation in hypertonic bouillon containing l-madelic acid, ATP, and HDP, and (2) preincubation in hypertonic buffer solution containing l-mandelic acid and casamino acids, and it was found possible to produce mandelic acid oxidase adaptively. In the case of (1), formation of pyrocatecase was also noticed. In the formation of mandelic acid oxidase by the protoplast of Pseudomonas fluorescens, preincubation for 120 minutes resulted in disappearance of enzyme activity, which differs from the case of intact cells. Considerations were made on the necessity of supplying amino acid externally in the formation of mandelic acid oxidase by the protoplast of Pseudomonas fluorescens.
Mutual solubility of titanous sulfate-sulfuric acid-water system was measured and it was found that the crystal of 3Ti2(SO4)3⋅2H2SO4⋅26H2O was present in the lower layer, in the range of sulfuric acid concentration of ca. 30-77%, and that anhydrous Ti2(SO4)3 is present above the sulfuric acid concentration of ca. 77%.
Mutual solubility was measured in the diphenylhydantoin sodium-sodium hydroxide-water system and it was found that the diphenylhydantoin sodium in the lower layer consisted of 11-, 8-, 7-, 4-, and 1-water, and an anhydrite, these being present respectively in the range of sodium hydroxide concentration of up to ca. 10%, between 10% and 30%, between 30% and 35%, between 35% and 42%, and between 42% and 47%, and the anhydrate at above 47%.
Analysis of the proton magnetic resonance spectra of aromatic compounds possessing a methylenedioxy group showed that the methylenedioxy proton appeared as a strong singlet at around 50c.p.s. The signal originating in this can be determined separately from those of methoxyl and N-methyl groups. The effect of mono-substituted methylenedioxybenzene derivatives which give a positive shift to this singlet is in the order of CHO>COOCH3>CH3>CH2OH>CH2CN, while this order in 6-substituted piperonal derivatives is NO2>Br>Cl>CHO>NH2.
The 2- or 4-position of quinazoline is expected to be active to anionoid reagent. In fact, reaction of quinazoline with several anionoid reagents showed that the 4-position of quinazoline is extremely reactive. The reaction of quinazoline with sodium amide, Grignard reagent, phenyllithium, hydrogen cyanide, sodium hydrogensulfite, sulfurous acid, and hydrazine respectively afforded 4-aminoquinazoline (I), 4-methyl-3, 4-dihydroquinazoline (III), 4-phenyl-3, 4-dihydroquinazoline (VI), quinazoline-4-carbonitrile (VII), 3, 4-dihydroquinazoline-4-carbonitrile (X), 3, 4-dihydroquin-azoline-4-sulfonic acid (XII), and 4-hydrazinoquinazoline (XIII). The preparation of the starting quinazoline was made by the modified method. 4-Quinazolone was derived to the chloro compound, which was purified by passing through alumina column, and submitted to catalytic reduction in neutral medium, at ordinary temperature and pressure, using a catalyst of palladium on magnesium oxide carrier, affording quinazoline in a high yield.
The reaction of thionyl chloride with dl-erythro- and dl-threo-1-phenyl-1-p-tolyl-2-benzamido-1, 3-propanediol, the compound formed by substitution of hydrogen in 1-position of 1-phenyl-2-amino-1, 3-propanediol with p-tolyl group, results in formation of oxazoline accompanied with steric inversion. Hydrolysis followed by basification afforded N-benzoylated isomers with steric configuration different from that of the starting material. This has proved that mutual conversion between threo and erythro types is possible.
The reaction of dl-1-phenyl-1-p-tolyl-2-amino-1, 3-propanediol and benzimidic ester affords 2, 3-oxazoline, and the acyl migration of this propanediol by hydrogen chloride gas affords 2-amino-3-benzoyloxy compound. There is no change in the steric configuration in these reactions. Such a fact is the effect of steric factor of the substituent in 1-position in the migration state. Aminohydrin rearrangement of dl-erythro-1-phenyl-1-p-tolyl-2-amino-1, 3-propanediol by nitrous acid was carried out and a compound with the phenyl group migrated was obtained. This suggested that the report of Curtin and others could also be applied conveniently to this new compound.
In order to examine analgesic activity, dimethylaminoethyl and dimethylaminopropyl 6-chloro (methoxy or ethoxy)-2-benzothiazolecarboxylates were prepared. 2-Benzothiazolecarboxylic acids were obtained by the reaction of ethyl 4-chloro (methoxy or ethoxy)-oxanilate and phosphorus pentasulfide to form ethyl thioöxanilates, hydrolyzed with sodium hydroxide to thioöxanilic acids, and cyclized with potassium ferricyanide in alkaline aqueous solution. The acids were derived to the acyl chloride with phosphorus pentachloride and condensed with dimethylaminoethanol or dimethylaminopropanol. These esters underwent decomposition in the air to form 6-chloro-(methoxy or ethoxy)-benzothiazole. Dimethyl- or diethyl-aminoethyl and dimethyl aminopropyl 6-chloro- or 6-ethoxy-2-benzothiazolepropionate were prepared by the application of sulfuric acid in methanol to N-(p-chlorophenyl)- or N-(p-ethoxyphenyl)-succinimide to form methyl succinanilates, reacted with phosphorus pentasuifide to form N-phenylthiosuccinimides, and cyclized with sodium hydroxide to thiosuccinanilic acids, which was further cyclized with potassium ferricyanide to 2-benzothiazolepropionic acids, derived to aryl chlorides with thionyl chloride, and finally condensed with dimethylaminoethanol, dimethylaminopropanol, or diethylaminoethanol.
Mutual solubilities of chlorobenzene-, chloroform-, and carbon tetrachloride-alcohol-water systems were measured at 30°. The systems of ethyl-, propyl-, and isopropyl-alcohol-water-chlorobenzene (chloroform), mono- and di-ethyleneglycol-water-chloroform, and tert-butyl alcohol-water-carbon tetrachloride belonged to the Type I with continued binodal curve, and others to Type II. Selective power of the halogenated hydrocarbons to alcohol was measured and the halogenated hydrocarbons were found to be a good solvent for extraction of alcohols, but not for mono- and di-ethylene glycols.
Labeled sodium acetate [carbonyl-14C] was given to Mentha arvensis L. var. piperascens HOLMES, and its utilization rate and distribution in the plant were examined. Menthol was isolated from the radioactive mentha oil obtained therefrom and it was found that the carbon atoms in 3-, 1-, and/or 8- positions of menthol originated from the carbonyl-carbon in the acetic acid while those at 7-, 9-, and 10-positions had no radioactivity.