Two kinds of sulfanilamide derivatives possessing diphenylene oxide nucleus were synthesized, i.e. 2-(p-aminobenzenesulfanilamide)-diphenylene oxide, m.p. 246-247°, and 2-(3′, 5′-dibromobenzenesulfanilamide)-diphenylene oxide, m.p. 199-200°.
Following sulfanilamide derivatives possessing diphenyl ether nucleus were synthesized in order to obtain antimalarial substances (I) m.p. 207-209° (II) m.p. 199.5-200° (III) m.p. 129-130° (IV) m.p. 183° (V) m.p. 147-148°
Azo derivatives of N-(α-diethylamino-δ-pentyl)-aniline were synthesized in order to obtain antimalarial substances. It was found that compounds (IV) and (V) possessed efficacy against malarial protozoa of monkeys.
1) By the hydrolysis of 2-methylmercaptopyrimidines by dil. H2SO4, 2-hydroxy compounds were obtained by almost quantitative yield. 2) By the reduction of 2, 6-dichloropyrimidines with 50% EtOH and Zn dust, or with benzene, 5% NH3-containing saturated NaCl solution and Zn dust, 2-chloro compounds were obtained. The yield is much better by the latter method.
Benzene solution of 6-chloropyrimidines with the addition of 5% NH3-containing satd. NaCl solution and Zn dust was boiled and reduction products of chlorine were obtained with a good yield. When the product is insoluble in water, a good result can be obtained by using dil. NH4OH or NH3-containing dil. EtOH instead of the satd. NaCl solution with NH3. 2-Amino-4-methyl-6-chloropyrimidine gives 2-amino-4-methyl-pyrimidine in good yield by 5% aqua ammonia and Zn dust.
The dehalogenation reaction of 2-amino-4, 6-dichloropyrimidine and 2-amino-4-methyl-6-chloropyrimidine by the heretofore used method of boiling with Zn dust was improved by making the solution alkaline with NH3 and adding metal salts as catalysts such as Cu, Bi, Ni, Cd, Sn, Mn, etc., which were added in an amount of ca. 0.01mol. per 1mol. of the pyrimidines. By the further addition of NaHCO3 when boiling with Zn dust, the yield on 2-amino- and 2-amino-4-methyl-pyrimidine was increased to 90%.
Hieraus kann man vermuten, dass C3 bzw. C5 des 4-Oxypyridin-N-oxydes gegen die Substitution mit den elektrophilen Reagenzien. aktiv sei. Die Vermutung wurde durch die Nitrierung bestätigt. Zuerst wurde es in Essigsäureanhydrid-Lösung mit Salpetersäure (d=1.39) bei 75° nitriert, wobei ein schwach gelbes nadelförmiges Krystall von Zp. 191-193° sich ausscheidet, welches beim Umkrystallisieren aus Wasser bzw. wasserhaltigem Methanol in nadelförmiges Krystall von Zp. 219-221° übergeht. Das Letztere wurde durch Analyse als ein Mononitro-4-oxypyridin-N-oxyd festgestellt. Es geht beim Behandeln mit Essigsäureanhydrid in das Erstere vom Zp. 191-193°, sodass das Erstere als das Monoacetat des Letzterens sich erwies. Die Ausbeute betrag ca. 90% der Theorie. Zur Konstitutions-ermittelung des Mononitroderivates wurde es man mit POCl3 durch Erhitzen auf dem Wasserbade in Mononitro-4-chlorpyridin-N-oxyd (gelbe Nadeln vom Zp. 147-149°) übergeführt und das Letztere katalytisch reduziert. Das Reductionsprodukt wurde sein Pikrat vom Fp. 195-198° sowie sein Monoacetat vom Fp. 129-132° als 3-Aminopyridin identifiziert.
Um die Nebenwirkung von Acetylnitrit zu beseitigen, hat der Verfasser Dimethylanilin als sein Acceptor versetzt und mit Essigsäureanhydrid analogerweise erhitzt. Aus der Reaktionsmischung, welche bald die grünliche Farbe von p-Nitrosodimethylanilin zeigt, wurde ausschliesslich 4-Oxypyridin-N-oxyd erhalten. Die Ausbeute betrug 63% der Theorie, sodass die Reaktion zur Darstellung desselbens geeignet ist.
Antiseptic power against soy sauce were tested with the follewing 6 compounds: (I) 2, 4-Dihydroxy-3-chloro-5-ethylbenzaldehyde, (II) 2, 4-Dihydroxy-3-chloro-5-n-butylbenzaldehyde, (III) 2, 4-Dihydroxy-3-chloro-5-n-amylbenzaldehyde, (IV) 2, 4-Dihydroxy-3-chloro-5-isoamylbenzaldehyde, (V) 2, 4-Dihydroxy-3-chloro-5-n-hexylbenzaldehyde, and (VI) 2, 4-Dihydroxy-3-chloro-5-n-heptylbenzaldehyde. The strength of antiseptic power was found to be in the order of II>III>I>IV>V>VI, of which I, II, III and IV possess stronger antisepsis than n-propyl p-hydroxybenzoate used as a control.
1) Reaction of acetylsulfanilylguanidine (I) and ethyl acetoacetate, ethyl methylacetoacetate or ethyl formylacetate, in isobutanol as a solvent with KOH or NaOH as a condensing agent results in the formation of a correspnding 2-acetylsulfanilylaminopyrimidine compounds. 2) By heating (I) and ethyl ethoxymethylene-acetoacetate (II), 2-acetylsulfanilylamino-4-methyl-5-carboxypyrimidine is obtained. This compound becomes acetylsulfamerazine by fusion with concurrent decarboxylation. Application of (II) to sulfanilylguanidine (III) results in an initial reaction of the amino radical at para-position and then the formation of a pyrimidine nucleus. 3) Reaction of (III) and ethyl acetoacetate, ethoxy methylene-malononitrile or ethyl cyanoacetate results in reaction with only the amino radical at para-position and there is no formation of a pyrimidine nucleus in any case.
Coclaurine is an alkaloid contained in Cocculus laurifolius D. C., and its structure is 1-(4′-hydroxybenzyl)-6-methoxy-7-hydroxy-1, 2, 3, 4-tetrahydro-isoquinoline. The authors synthesized coclaurine-4′-methyl ether from 3-methoxy-4-benzyloxy-phenylethylamine and 4-methoxyphenyl-acetic chloride.
According to experiments carried out by the anthor in 1937, 2 kinds of N-phthalyl derivatives are obtained by heating to 180-190°l(+)-glutamic acid and phthalic anhydride. One is phthalyl-l-glutamic acid, m.p. 163-4°, [α]D28.5=-40.73° (abs. EtOH), and the other, its dl-form, m.p. 207°, which showed no depression of m.p. when fused with an authentic product obtained from dl-pyrrolidone-carboxylic acid and phthalic anhydride. Phthalyl-l-phenylalanine, m.p. 183-4°, [α]D24=-213.71 (abs. EtOH), methyl ester, m.p. 110°, and phthalyl-l-tyrosine, m.p. 187°, [α]D26=-153.8° (abs. EtOH) were also obtained.
In order to synthesize pyridine from pyridine homologs, studies were made on the activities of methyl radical at α-and γ-positions and the fact that the corresponding carboxylic acids were easily decarboxylated. Experiments were carried out, accordingly, on the preparation of α, γ-carboxylic acid and its decarboxylation with α-picoline and its results were to be utilized. In order to obtain pyridine-carboxylic acid, hydrolysis after halogenation, oxidation by Se-H2SO4, chloric acid, H2O2, and electrolytic oxidation were attempted. Decarboxylation was attempted with heating in conc. H2SO4 and dry distillation of Ca, Cu, Na, NH4 salts and a hydrochloride.
Ethyl cyclohexylidenemalonate, obtained by treating ethyl cyclohexylidenecyanoacetate with H2SO4, was methylated, or H2O2 applied to ethyl cyclohexenylmethylcyanoacetate, to obtain ethyl cyclohexenylmethylmalonate. This was reacted with ethyl N-methylcarbamate under the presence of a mild condensing agent and 1-methyl-5-cyclohexenyl-5-methylbarbituric acid was obtained.
5, 5-Diethyl-2-thiohydrouracil (I), 1-methyl-5, 5-diethyl-2-thiohydrouracil (II), 5-isoamyl-5-ethyl-2-thiohydrouracil (III) and 1-methyl-5-isoamyl-5-methyl-2-thiohydrouracil (IV) were synthesized by the reduction of dialkylcyanoacetic ester or amide to α, α-dialkyl-β-aminopropionic ester or amide and condensation of Na-thiocyanate, CS2 or methyl isothiocyanate. Physiological tests of these compouuds showed that the somniferous action of (I) and (II) were approximately equal to that of barbituric acid used as a control but possessed slightly higher toxicity while (III) and (IV) showed weaker somniferous action and toxicity.