1) By the Application of quarternary ammonium salts, such as diethyl-β-hydroxyethyl-benzyl-ammonium chloride or dimethyl-phenyl-benzyl-ammonium chloride on 6-methoxy-8-aminoquinoline, 6-methoxy-8-benzylamino-quinoline was obtained. 2) By the application of β-diethylaminoethyl-pyridinium p-toluenesulfonate on 6-methoxy-8-aminoquinoline, 6-methoxy-8-(β-diethylaminoethyl)-aminoquinoline was obtained.
p-Isoamylphenyl orthoformate and 2-hydroxy-5-isoamylbenzaldehyde were obained by the Tiemann-Reimer reaction of p-isoamylphenol but the objective compound, 4-dichloromethyl-4-isoamyl-Δ2: 5-cyclohexadienone, could not be obtained.
The amount of myoglobin in whales is extremely large compared to land animals and this is assumed to assist in supplying oxygen during submarine navigation. There is also a large amount of iron compounds, other than hemoglobin form, in whale blood.
4-Chloropyridine or quinoline-N-oxide forms per molar addition product with thiourea. Decomposition of these addition products with NaOH or NH4OH in cold or hot state gives 4-substituted mercapto compounds, 4, 4′-substituted sulfides and 4, 4′-substituted disulfide-N, N′-dioxides. Conversion of 4-mercapto compounds to 4, 4′-substituted sulfides and that of 4, 4′-diquinolyldisulfide-N, N′-dioxide to 4, 4′-diquinolylsulfide-N, N′-dioxide are also described.
By the application of p-nitrothiophenol, 4-mercaptoquinoline-N-oxide, 2-mercapto-4, 6-dimethylpyrimidine, 2-mercapto-4-methyl-thiazole and 2-mercapto-4, 5-dimethylimidazole to 4-chloropyridine- or quinoline-N-oxide easily gave corresponding sulfides which were then oxidized to sulfones. (However, sulfone of 4, 6-dimethylpyrimidine were not obtained). p-Nitrophenyl derivative was reduced to p-aminophenyl-pyridyl- or -quinolyl-sulfone. Antibacterial action of these compounds are being tested. Decomposition of p-nitrophenyl-pyridyl-(4)-sulfide-N-oxide by Na-ethoxide is also described.
a) Iodine oxidation of Vitamin B1 hydrochloride with application of 3mol. NaOH gave “aneurin disulfide”, which containes 2mol. of crystal water and has no certain melting point. However, treatment absolute EtOH or drying for a long period of time, gives an anhydride of decompn. 179°. Acetylation with acetic anhydride gives diacetate, decompn. 155°. An attempt to synthesize this diacetate by other method to determine its structure was unsuccessful. b) Air oxidation of Vitamin B1 with application of 3mol. NaOH gave, instead of “Aneurin disulfide”, Vitamin B1 half-chloride, m.p. 125-6°, 2-methyl-4-amino-5-aminomethyl-pyrimidine and crystals of unknown structure with m.p. 224°. The same process with the application of 2mol. NaOH on Vitamin B1 hydrochloride gave crystals of m.p. 239° instead of “Aneurin disulfide”. The former crystals give positive thiochrome reaction when cysteine is applied.
Esters of p-toluenesulfonic acid of aminoalcohols such as α-diethylamino-δ-pentanol which has a tertiary nitrogen atom of strong basicity cannot be prepared by the ordinary method of esterification for p-toluenesulfonic acid. It is necessary, in these cases, to close the basicity of its tertiary nitrogen atom by salt formation and then reacting for a long period of time at a comparatively high temperature. The author has found that the α-diethylamino-δ-pentylation of the amino group of aniline or 6-methoxy-8-aminoquinoline by the use of this ester cannot be carried out by the method described in D.R.P. and that it is necessary to use a much higher temperature and a longer reacting time.
1) The reaction mechanism by which 2mol. p-nitrochlorobenzene is applied with 1mol. Na2S under the presence of a small amount of Na2S2 to form p, p′-dinitrodiphenyl sulfide was observed and it was found that the reaction proceeded as far as the formation of p-nitrothiophenol upon completion of which, the reaction occurrs between this newly formed compound and p-nitrochlorobenzene. It follows, therefore, that when 1mol. p-nitrochlorobenzene is used the reaction stops with the formation of p-nitrothiophenol so that the application of o, p-dinitrochlorobenzene easily gives o, p, p′-trinitrodiphenyl sulfide, m.p. 158-160°. 2) Application of Na2S3 on p-nitrochlorobenzene, as in the case of Na2S2, gives a mixture of p, p′-dinitrodiphenyl disulfide and sulfide although the formation of the latter is much lower than in the case of Na2S2. 3) Application of Na2S to o-nitrochlorobenzene under the presence of Na2S2 hardly formed o, o′-dinitrodiphenyl sulfide which showed that the reaction takes a different course from that in the case of (1). 4) Application of Na2S2 on o-nitrochlorobenzene gives solely o, o′-dinitrodiphenyl disulfide and no monosulfide is formed. However, it was found that the application of Na2S2 on o, p-dinitro chlorobenzene gave a small amount of monosulfide as well as o, o′, p, p′-tetranitrodiphenyl disulfide.
This work was undertaken in order to study the relationship between the methods of preparing 3-amino-4-hydroxyphenylarsene-oxide hydrochlorides and their therapeutic activities. The hydrochlorides were considered form the points of toxicity, activity, stability and solubility. It has been found that soluble hydrochloride anhydride, or its hemihydrate, was the best among the hydrochlorides from the point of pharmaceutics.
p-Ethoxyphenyl-cyanamide was obtained by an ordinary method from p-phenetidine, H2Se was applied to give p-ethoxyphenylselenurea which was oxidized by Br2 to 6-ethoxy-2-aminobenzoselenazole, m.p. 147°. The hydrochloride of the compound possesses strong local anesthetic actions. 2-Sulfanylamidobenzoselenazole, decmopn. 310°, is obtained from 2-aminobenzoselenazole according to general method for sulfonamide compounds.
2-Alkylaminoselenazole can be prepared by; (i) the preparation of alkylcyanamide from primary or secondary amines, application of H2Se to this to alkylselenurea and application of halogenoketone, or (ii) alkylation of the K-salt of 2-acetaminoselenazole and its subsequent hydrolysis. 2-Amino- and 2-mono-alkyl-selenazole form prototropy with selenazolone-imide (2) and the structural difference with 2-dialkylaminoselenazole can only be determined by the similarity and difference in absorption spectra. The C5-position of 2-diethylamino-4-methylselenazole possesses a strong activity, couples with phenyldiazonium chloride so that it can easily be nitrated under comparatively mild conditions. It condenses with benzaldehyde, and also gives a beautiful violet coloration upon warming with orthoformic ester and anhydrous ZnCl2. It condenses with formaldehyde but does not form any crystalline substance and the attempt to synthesize ketone compounds by both Friedel-Crafts' and Gattermann's methods was unsuccessful.
Dimethylacrylic acid was used as the material which, together with Br2, were dropped into methanol under the presence of AgNO3 to give (I). This was treated with 28% NH4OH in a sealed tube by heating to 90-100° to give (II). The methyl ester of (II) was prepared into benzoyl derivative (III) with benzoyl chloride in an ordinary manner. This benzoyl derivative was heated over a water bath with POCl3 in anhydrous benzene solution and methyl 2-phenyl-5-dimethyl-(5, 4)-dihydro-oxazole-4-carboxylate (IV) was obtained as the cyclized product. Saponification of this ester with 2% alcoholic potash gave the corresponding carboxyli cacid (V). Application of P2S5 to (IV) to obtain the corresponding sulfur compound, 2-phenyl-5-dimethy-(5, 4)-dihydrothiazole-4-carboxylic acid (VI), was attempted but ended unsuccessfully.