1) Condensation of (III) with ammonia, dimethylamine, piperidine, aniline, p-chloroaniline, and 2, 4-dichloroaniline in ethanol gave the compounds (IV to IX) which were reduced to (X to XII), and acetylated to (XIII to XV). Application of phenol, p-nitrophenol, and p-cresol to (III) gave the compounds (XVI to XVII). Similar condensation of 4, 8-dichloroquinaldine with aniline, p-chloroaniline, p-nitroaniline, and anisidine in ethanol gave the compounds (XIX to XXII). 2) Similar condensation of 2-chlorolepidine or 2-chloro-5-nitrolepidine with p-chloroaniline, p-nitroaniline, and p-anisidine gave (XXIII to XXV) and (XXVI to XXVII). The compound (XXIX), obtained by nitration of 2-hydroxylepidine followed by chlorination, was identified with 2-chloro-6-nitrolepidine. Similar condensation of (XXIX) and 2-chloro-8-nitrolepidine with p-aminoaniline, p-chloroaniline, and p-anisidine gave the compounds (XXX to XXXV). These compounds were submitted to antifungal test with Candida.
1) Application of aniline to 2-chloro-6- and -8-nitrolepidines (I and IV) in ethanol afforded 2-phenylamino-6- and -8-nitrolepidines (II and III). Application of p-nitroaniline to (I), (IV), and 3-nitro-4-chloroquinaldine (V) afforded 3-nitro-4-(p-nitrophenyl) aminoquinaldine (VI) from (V) but (I) or (IV) were recovered unchanged. Fusion of (I) and (IV) with p-nitroaniline finally afforded 2-(p-nitrophenyl) amino-6- and -8-nitrolepidines (VII and VIII). Similar application of p-acetanilide to (V) and aniline to 2-chlorolepidine respectively afforded 3-nitro-4-(p-acetaminophenyl) amino-quinaldine (XI) and 4-(p-nitrophenyl) aminolepidine (XIII). 2) Hydrogen sulfide was applied to (VI), (VII), and (VIII) in ethanolic ammonia and the amino compounds thereby formed were derived to (IX), (XII), (XIV). Acetylation of (IX) gave the acetyl compound (X) which showed depression of the melting point on admixture with (XI). Deamination of (XII) and (XIV) afforded the same compound which was identical with (XIII). 3) Treatment of (II), (VI), and (XIII) with hydrazine hydrate in ethanolic solution resulted in reduction of (II) alone to 2-phenylamino-6-aminolepidine (XV) and others were recovered unchanged. Reduction of (XIII) was effected by treatment with tin (II) chloride and hydrochloric acid to form 2-(p-aminophenyl) aminolepidine (XVI). Polarographic examination of the reduction of the foregoing compounds (VI, VII, VIII, and II) showed the same result as by chemical experiment. The compounds (III), (VI), and (VII) are insoluble in and their antifungal test with Candida sp. could not be carried out.
From the decomposition products of D-glucuronolactone isonicotinoyl hydrazone (II) at room temperature, D-glucuronic acid isonicotinoyl hydrazone isonicotinoyl hydrazide (III) was isolated, which has been identified to produce when the water solution of (II) was heated. Furfralaldehyde isonicotinoyl hydrazone (IX) was also isolated from the reaction solution. (III) has been recognized to be produced from 1-deoxy-1-(2-isonicotinoylhydrazino)-β-D-glucopyranosiduronic acid (VII) and ethyl 1-deoxyisonicotinoylhydrazino)-β-D-glucopyranosiduronate (VIII). As to the mechanism of production of (III), the reaction, one molecule of glucuronolactone was released from 2 molecules of (II), may be considered to be taken place in the similar reaction to disproportionation.
By heating the aqueous solution of D-glucuronolactone salicyloylhydrazone (II), D-glucuronic acid salicyloylhydrazone salicyloylhydrazide (III) was obtained. 1-Deoxy-1-(2-salicyloylhydrazino)-β-D-glcopyranuroic acid salicyloylhydrazide (VI) was synthesized from ethyl D-glucuronate (IV). (VI) was also obtained from methyl 2, 3, 4-tri-O-acetyl-α-D-glucopyranuronate (VII) and 2, 3, 4-tri-O-acetyl-β-D-glucopyra-nurono-6, 1-lactone (X) and (VI) was proved to have the β-pyranose structure.
By the Michael condensation of ethyl cyanoacetate and ethyl crotonate, diethyl α-cyano-β-methylglutarate was prepared and its hydrolysis followed by dehydration gave β-methylglutaric anhydride. Its condensation with homoveratrylamine, derivation to the imide and then to the lactam through electrolytic reduction, and dehydrative cyclization of its product, followed by reduction with sodium borohydride or by catalytic reduction in the presence of Adams platinum catalyst afforded two isomers of 2-methyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-11bH-benzo [a] quinolizine. Infrared spectra of the two isomers were comparatively examined.
The Friedel-Crafts reaction of γ-methylresorcinol and 3, 5-dimethoxyphthalic anhydride gave 2-(3-methyl-2, 4-dihydroxybenzoyl)-3, 5-dimethoxybenzoic acid and dehydrative cyclization of its methyl derivative afforded 1-hydroxy-2-methyl-3, 6, 8-trimethoxyanthraquinone in a good yield. This anthraquinone compound was derived to 1, 3, 6, 8-tetramethoxy-2-anthraquinonecarboxylic acid in five steps. The position of the hydroxyl groups in this acid was confirmed with tetrahydroxyanthraquinone formed by its demethylation.
Starting with 2-methyl-1, 3, 6, 8-tetrahydroxyanthraquinone (III), formed by demethylation of 1-hydroxy-2-methyl-3, 6, 8-trimethoxyanthraquinone, attempt was made to synthesize rhodacladonic acid by (1) introduction of CH2OH group into the 7-position of (III); (2) oxidation of CH2OH group in 2-hydroxymethyl-1, 3, 6, 8-tetrahydroxyanthraquinone (VII), derived from (III); and (3) introduction of CH3 or CHO group into 7-position of (VII). However, none of these reactions progressed.
Application of p-toluenesulfinyl chloride (II) to butylurea (I) in pyridine results in the formation of thiourea (IV) and sulfonylurea (V), together with p-toluenesulfinylurea (III). Behavior of (III) on being left under various conditions was examined and (III) was found to be considerably unstable, undergoing facile hydrolysis to form sulfonic acid (VII) and thiolsulfonate (VIII). It was also found that (III) formed (IV) and (V) by disproportionation in pyridine. These experimental results suggest that the reaction of (I) and (II) are fairly complicated by the formation of (III) and its decomposition, accompanied by disproportionation of (III) into (IV) and (V). Some considerations were made on the mechanism of formation of (IV) and (V) from (III) and on hypoglycemic action of (III).
Depletion of thiamine during hyperthyroidism was assumed to be due to the inhibition of phosphorylation of thiamine or acceleration of its decomposition and excretion by thyroid hormone. In order to examine this problem, mice, rats, and rabbits were administered with thyroid stimulating hormone, thyroxine, diiodotyrosine, dried thyroid gland powder, 2, 4-dinitrophenol, and the synthesized thyroxine and O, N-di-(2, 4-dinitrophenyl) derivative of diiodotyrosine, and variation in the amount of thiamine excreted into urine was examined. Thyreotropic hormone effected increase of thiamine in the rat liver while thyroxine and dried thyroid gland powder markedly decreased thiamine. Diiodotyrosine decreased the thiamine content of the heart and its action remained unchanged on dinitrophenylation. 2, 4-Dinitrophenol itself increased the liver thiamine content but 2, 4-dinitrophenol compound of thyroxine decreased the thiamine content in the liver and kidneys, same as thyroxine itself, and also that of the heart. Thyroxine effected decrease of thiamine in the liver and kidneys of a rabbit. Excretion of thiamine in this case increased markedly for a time and decreased later. Thyroidectomy was found to effect gradually decrease of thiamine excretion into the urine.
5-Alkylamino-2-thiobarbituric acid derivatives containing a p-substituted phenyl group in the nitrogen were synthesized in order to examine the presence of analgesic action in a compound by the introduction of two kinds of atom group, one having a pyrolytic and the other hypnotic activity, in one molecule. Attempt for further introduction of an alkyl group in the carbon atom at 5-position failed. Pharmacological test of 19 kinds of the barbituric acid derivatives synthesized showed that none of them had a strong analgesic action.
Some time ago, Tomita and Kunitomo derived l- and d-N, O, O-trimethylcoclaurine (II and IIa) from D-(-)- and L-(+)-laudanosine, whose absolute configuration had already been elucidated, and determined the absolute configuration of coclaurinetype bases. Based on this result, absolute configuration of the two asymmetric centers in the majority of biscoclaurine-type bases was also clarified. Of these, the oxyacanthine-type base having methylenedioxy as the characteristic atom group in the molecule, cepharanthine (IV), was submitted to cleavage reaction with metallic sodium in liquid ammonia, by Tomita and Sasaki, and d-1-(p-hydroxybenzyl)-2-methyl-7-isoquinolinol (V) and D-(-)-N, O-dimethylcoclaurine (VI) were obtained as the cleaved bases. This proved that the absolute configuration of one (in B) of the two asymmetric centers in cepharanthine was a D type but that of the other (in A) had not been confirmed. In order to elucidate this point, cleavage reaction with metallic lithium in liquid ammonia was carried out on D-(-)- and L-(+)-N, O, O-trimethylcoclaurine (II and IIa), whose absolute configuration had been clarified in a previous work. (II) and (IIa) were respectively derived to D-(-)- and L-(+)-N, O-dimethylisococlaurine (VII and VIIa), formed by demethylation of the methoxyl group in the 6-position of the isoquinoline ring, and the Ullmann reaction of (VII) and (VIIa) afforded the phenyl ethers (VIII and VIIIa), which were again submitted to cleavage reaction with metallic sodium in liquid ammonia to be derived respectively to l- and d-1-(4-methoxybenzyl)-2-methyl-7-methoxy-1, 2, 3, 4-tetrahydroisoquinoline (IX and IXa) (cf. Table I). The O, O-dimethyl compound of (V), one of the bases obtained by cleavage reaction of cepharanthine (IV), was found to be identical with the above (IXa). This has proved that the absolute configuration of the unidentified asymmetric center at A in cepharanthine (IV) is the L type. It therefore follows that the absolute configuration of the two asymmetric centers in cepharanthine is indicated by (L, D) or (S, R), as shown in formula (IV).
Reaction between 1, 2-dihydro-3H-pyrido [3, 2, 1-kl] phenothiazin-3-one and aromatic aldehydes was examined and 2-benzylidene-1, 2-dihydro-3H-pyrido [3, 2, 1-kl] phenothiazin-3-one derivatives and their isomers, 2-benzyl-3H-pyrido [3, 2, 1-kl] phenothiazin-3-one derivatives, were obtained. Relationship between the structure of these products and their ultraviolet and infrared spectra were clarified. Reduction of 2-benzyl-3H-pyrido [3, 2, 1-kl] phenothiazin-3-one with lithium aluminium hydride afforded 2-benzyl-1, 2-dihydro-3H-pyrido [3, 2, 1-kl] phenothiazin-3-one and -3-ol.
Reduction of 3-hydroxyimino-1, 2-dihydro-3H-pyrido [3, 2, 1-kl] phenothiazine with lithium aluminium hydride afforded 3-amino-1, 2-dihydro-3H-pyrido [3, 2, 1-kl] phenothiazine as the normal reduction product and 1, 2, 3, 4-tetrahydro-[1, 4]-diazepino [3, 2, 1-kl] phenothiazine as the rearrangement product. The structure of these compounds was confirmed through their synthesis.
Reaction of one mole of sodium methoxide with 4-methyl-3, 6-dichloropyridazine (I) gave 3-methoxy-4-methyl-6-chloro- (III) and 3-chloro-4-methyl-6-methoxy-pyridazine (IV), the structure of both being confirmed. Dehalogenation of (III) to 3-methoxy-4-methylpyridazine (VII), its N-oxidation to 3-methoxy-4-methylpyridazine 1-oxide (VIII), and its nitration with mixed acids gave 3-methoxy-4-methyl-6-nitropyridazine 1-oxide (X), whose structure was proved from the result of various reactions. The position of the N-oxide group in the N-oxides obtained by oxidation of 4-methyl-3, 6-dimethoxypyridazine (II), (III), (IV), and (VII) was also clarified.
The polymers formed in the combination between acrylic acid and methacrylic acid group, and methyl acrylate and methyl methacrylate group are adhesive each other during the coating process, therefore plasticizer is necessary. In order to improve this properties, internal plasticization was examined. Eight varieties of internal plasticizers, such as octyl and cetyl acrylate, dodecyl and cetyl methacrylate, vinyl laurate and caprate, vinyl octyl ether and vinyl cetyl ether were applied to two groups of polymers with methyl acrylate-methacrylic acid and methyl methacrylate-methacrylic acid at the proportion of 1, 5 and 10%. Their solubility, viscosity and spinnability of the solutions, elasticity and water vapor permeability of the film have been measured. In addition, disintergration test of coated tablet was also carried out. The results showed that the properties was impoved by the internal plasticization and the coating has been made easily without using the other additive materials and it was found to be desirable enteric coating agents.
By the use of the properties of Neutral Red to react with sulfate-type and sulfonate-type anionic surface active agents to forma complex compound sparingly soluble in water but easily soluble in organic solvents, various conditions were examined for the determination of sodium laurylsulfate. The method thereby established was as follows: A sample solution containing 5-100γ/cc. of sodium laurylsulfate, 1cc. of buffer solution (pH 5), and 2cc. of 0.01M Neutral Red solution, measured accurately, are placed in a glass-stoppered test tube and shaken for about 1 minute. To this mixture, 10cc. of dichloroethylene is added, the mixture is shaken for 2 minutes, and centrifuged. The supernatant is filtered through a cotton plug and absorbance of the filtrate is measured at 530mμ. A blank test is carried out with the same quantity of the same reagents, using 1cc. of distilled water in place of the sample solution. This method can be used to a certain extent in the presence of potassium stearate and nonionic surface active agents, and the presence of sodium sulfate does not interfere in this reaction. If 10cc. of the sample solution is used, this method can be applied to solutions of 1/10 the concentration. The accuracy of this method is below 1%.
The plant of Leonurus sibiricus L. (Japanese name “Yakumoso” or “Mehajiki”) (Labiatae) was colleted during the flowering season and extracted as shown in Chart 1. The alkaloid, leonurine, was obtained in 0.02-0.04% yield. Free leonurine, m.p. 238°(decomp.), C14H21O5N3⋅H2O; hydrochloride, m.p. 194° (monohydrate); styphnate, m.p. 214-215°; oxalate, m.p. 191-192°. At the begining of flowering, content of leonurine is small and 0.03% of fumaric acid was obtained from the fruiting season of the plant. Glucoside and rutin were obtained in 0.1% yield from the whole herb during the fruit-bearing season. Leonurine (I) possesses two methoxyls and is positive to phenolic and alcoholic hydroxyl. It gives positive Dragendorff and Sakaguchi reactions and negative Meyer reaction. Hydrolysis of (I) with hydrochloric acid gives syringic acid (II), m.p. 206°, C9H10O5, the acid and its ethyl ester, m.p. 90.5°, agreed with the synthesized specimens. The mother liquor of this hydrolysis afforded the picrate of (III), C5H13ON⋅C6H3O7N3, m.p. 155°. Hydrolysis of (I) with sodium hydroxide or barium hydroxide afforded (II) as well as ammonia and a C4-amino alcohol as a benzoate of m.p. 74.5°, C11H15O2N, and p-nitrobenzoate of m.p. 163°, C18H17O7N3 (Chart 2).
The NMR of the benzoate, m.p. 74.5°, of the C4-amino alcohol obtained by alkaline hydrolysis of leonurine was examined and it was assumed to be 4-amino-1-butanol. Therefore, its benzoate, m.p. 74.5°, and N, O-bis (p-nitrobenzoate), m.p. 163°, were synthesized, as well as (4-hydroxybutyl) guanidine picrate. These were compared with the respective derivatives obtained by the decomposition of the natural product and were identified as the same substances. Bonding position of syringic acid and the guanidine compound was assumed from a model substance and the structural formula (b′) was proposed for leonurine.
1, 4-Dihalogen compounds like (XI) and (XIII), prepared from α-formyl-γ-butyrolactone or α-acetyl-γ-butyrolatone, were found to form the corresponding condensed dihydrothiophenes easily by the action of thiourea or alkali hydrosulfide. Such a reaction was found to be fairly common and the reaction was utilized for the preparation of dihydrothienoquinoline and dihydrothienopyrimidine derivatives.
When 6-chloro-2, 4-dimethoxypyrimidine (I) was reacted with sodium amide in liquid ammonia, 2-amino-4, 6-dimethoxypyrimidine (III) was afforded in 47% yield, besides a small amount of by-products, such as 4-methoxy-2, 6-diaminopyrimidine (VIII), 2-methoxy-4, 6-diaminopyrimidine (IX), as well as 6-amino-2, 4-dimethoxyprimidine (II), which has been expected to be main product. It was found that in liquid ammonia, (I) was reacted with sodium methylate to 2, 4, 6-trimethoxypyrimidine (VII) and that (VII) was reacted with sodium amide to (III) in better yield, respectively. 2-Amino-4-methoxy-6-chloropyrimidine (VI) was reacted with sodium amide to (VIII) in liquid ammonia. Considering from the results, the reaction mechanism from (I) to (III) has been suggested that the CH3O- group which was attacked by sodium amide at either 2 or 4 position of (I) was reacted with the non-reacted (I) to yield (VII), followed by the secondary reaction between (VII) and excess sodium amide into (III).
The substitution reaction of pyrimidine derivatives having methoxyl groups with sodium amide in liquid ammonia are described. That is, 2-amino-4-methoxy-6-pyrimidinethiol (II) (50%) and 2-amino-4, 6-dimethoxypyrimidine (III) (1.6%) from 2, 4-dimethoxy-6-pyrimidine thiol (I), 2-amino-4-methoxy-6-methylthiopyrimidine (V) (50%) from 6-methylthio-2, 4-dimethoxypyrimidine (IV) which was produced by the methylation of (I), 2-amino-4-methoxypyrimidine (VII) (65%) and 2-methoxy-4-amino-pyrimidine (VIII) (10.4%) from 2, 4-dimethoxypyrimidine (VI), 2-aminopyrimidine (X) (19%) from 2-methoxypyrimidine (IX), and finally 4-amino-6-methoxypyrimidine (XII) (85%) from 4, 6-dimethoxypyrimidine (IX) were synthesized. In addition, the condensation between (XII) and N-acetylsulfanilylchloride gave N1-(6-methoxy-4-pyrimidyl)-N4-acetylsulfanilamide (XIII), followed by the hydrolysis to N1-(6-methoxy-4-pyrimidyl)-sulfanilamide, being approved to be superior sulfa drug.
N1-(6-Substituted 4-pyrimidinyl) sulfanilamide (VIa: ethoxy, VIb: isopropoxy, IVc: methylthio, and VId: ethylthio) were synthesized by the condensation between N-acetylsulfanil chloride and 4-aminopyrimidine (IIIa-d) which provided, ethoxy, isopropoxy, methylthio and ethylthio at 6-position, followed by the hydrolysis. 4, 6-Dichloropyrimidine and sodium sulfanilamide were condensed in either dimethyl sulfoxide or dimethylformamide into N1-(6-chloro-4-pyrimidinyl) sulfanilamide (VII). N1-(6-methyl-4-pyrimidinyl) sulfanilamide (VIII) was prepared by the condensation between 4-chloro-6-methylpyrimidine (X) and sodium N4-acetylsulfanilamide in dimethylsulfoxide, followed by the deacetylation of the product. The antibacterial properties of the compounds synthesized, in vitro test, showed that (VIc), (VII) and (VIII) gave nearly as same activities as (I), namely that was more powerful than that of sulfadimethoxine and that (VIa) and (VId) showed the same power, though (VIb) was inferior.
Direct acetylation of either N1-(6-methoxy-4-pyrimidinyl) sulfanilamide (II) or its sodium salt gave N4-acetyl and N1, N4-diacetyl derivatives but any expected N1-acetyl derivative (I) has not been produced. Therefore, (I) was synthesized by the reaction between alkali metal salt of N-(6-methoxy-4-pyrimidinyl)-4-nitro-benzenesulfonamide (IV) and either acetic anhydride or acetyl chloride to N-acetyl-N-(6-methoxy-4-pyrimidinyl)-4-nitrobenzenesulfonamide (VII), which is followed by the catalytic reduction. (IV) was obtained by the condensation between 4-amino-6-methoxypyrimidine (III) and p-nitrobenzensulfonoyl chloride, or by the reaction of N-(6-chloro-4-pyrimidinyl)-4-nitrnbenzenesulfonamide (VI) and sodium methylate. Furthermore, (II) was prepared by the catalytic reduction of (IV) or usual reduction with iron and HCl.
The exchange reaction between various ketonic isonicotinoylhydrazone and D-glucuronlactone in methanol was examined and D-glucuronolactone isonicotinoylhydrazone was obtained. As the alkyl group of the ketone residue become higher, its reaction velocity become slower, as well as its yield become poor. The investigation of the analogous reaction has been also done with D-glucuronic acid and D-glucose.
Condensation of D-glucuronolactone with 13 kinds of aromatic acid hydrazides and 3 kinds of aliphatic acid hydrazides afforded D-glucuronolactone acylhydrazones. These acylhydrazones were heated in an aqueous solution and the corresponding D-glucuronic acid acylhydrazone acylhydrazides were obtained. Antituberculosis action of these compounds in vitro was examined but none was found to be effective.
An investigation of the decomposed product of glucuronic acid amide in water solution has been carried out and pyrrol-2-carboxaldehyde (I) has been confirmed to be produced as one of the decomposed substances.
On the synthetic study of water soluble papaverin-like compounds, 2, 4-, 3, 4- and 2, 5-dihydroxy derivatives out of the six kinds of the compounds which provide two hydroxyl groups attached to phenyl radical at 1 position were already synthesized. In this report, acid chloride of α-resorcylic acid dibenzyl ether was condensed with α-methyl-β-methoxy-3, 4-methylenedioxyphenethylamine to the amide compound, which was cyclized with POCl3 to the isoquinoline derivatives, which was followed by the debenzylation in ethanolic hydrochloric acid to give the expected 1-(3, 5-dihydroxyphenyl)-3-methyl-6, 7-methylenedioxyisoquinoline.
Dehydrative cyclization of N-[(3, 4-dimethoxyphenethyl) carbamoylmethyl] benzamide or -furamide by the Bischler-Napieralski reaction results in dehydration from two molecules to form 3-phenyl- or 2-furyl-8, 9-dimethoxy-5, 6-dihydroimidazo [5, 1-a]-isoquinoline. In order to examine the reaction mechanism of this dehydrative cyclization, 1-benzoylaminomethyl- and 1-furamidomethyl-6, 7-dimethoxy-3, 4-dihydroisoquinolines and 1-(3, 4-dimethoxyphenethyl)-2-phenyl-2-imidazolin-5-one were synthesized and submitted to the same cyclization reaction from which the objective imidazo-isoquinoline derivatives were obtained. This has proved that the products obtained in the past by the cyclization of N-(3, 4-dimethoxyphenethyl)-2-acylamino-acetamides are not formed by monomolecular dehydration and that they are imidazoisoquinoline derivatives formed by bimolecular dehydration.
Pyrogen test method in four kinds of pharmacopoeiae (Japanese 7th edition, U. S. 16th edition, British 1958 edition, and International 2nd edition) was comparatively examined by the statistical treatment of its efficiency from the standard of assay by the Monte Carlo method. The variance (σ2=0.0179), obtained by the administration of glucose injection, was found to be a good measure having sensitive discriminatory power. The British method was especially good but it required the largest number of animals per unit test. The variance (σ2=0.0835), obtained by the administration of a pyrogenic substance, showed a fair difference in the efficiency among the four methods and the American method was found to be the most rational, there being less chance of making false judgement of positive result than by the Japanese or International method, although there was no likelihood of over-looking the pyrogenic substance in any of the methods. The British method had a greater chance of missing the pyrogenic substance than the other methods, in spite of the use of a larger number of animals per unit test. It was concluded that, if the American pharmacopeal method is followed, individual difference of animals tested for the rise of body temperature must be below ca. 0.09 in variance, and there would be an increasing danger of over-looking the contamination of minimum pyrogenic substance of 0.6° by the British method if this variance of the individual difference is over ca. 0.02.
Previously, the bitter component of Petasites japonicus was examined and crystals of m.p. 99.5-100° were isolated. In the present series of work, aromatic components were separated from this plant. A neutral essential oil, which seemed to be the main component of its aroma, was separated from the ether extract of this plant and the oil was found to be 1-nonene. The oil also contained angelic, caproic, and caprylic acids as the acidic substances, and butyraldehyde as the neutral substance.
Comparison was made between chelatometry and permanganometry for the determination of calcium salts as pharmaceutics. A more simpler, rapid, and accurate determination was found to be as follows: The sample (taken as a×10-1g.) solution is added with magnesium ethylenediaminetetraacetate is directly titrated with standard solution of 0.05M ethylenediaminetetraacetic acid, with eriochrome black T as the indicator or the solution added with excess of ethylenediaminetetraacetic acid and magnesium ethylenediaminetetraacetate is back-titrated with calcium chloride solution, with eriochrome black T as the indicator. This method seemed to give better result than by permanganometry.
6-Methoxy-2-quinolinecarbonitrile was obtained by application of potassium cyanide to 6-methoxyquinoline 1-oxide. In accordance with this reaction, potassium cyanide was applied to dihydroquinine N, N-dioxide bis (methosulfate) in hydrous solvent and 2′-cyanodihydroquinine was obtained in a good yield. This is a new method for the preparation of 2′-cyano compound of quinine bases.
A more practicable and convenient method for the preparation of 2-(2-chloroethyl)-benzoxazin-4(3H)-one was found to be the treatment of salicylamide and 3-chloro-propionaldehyde with phosphoryl chloride, in the absence or presence of an inert solvent.