1) 2-Methylmercapto-4-methylpyrimidine, 2-hydroxy-4-methyl-pyrimidine hydrochloride and 2-chloro-4-methylpyrimidine were synthesized. 2) 2-Sulfanilamido-4-methylpyrimidine (Sulfamerazine) was synthesized with a good yield by the condensation of N4-acetyl-sulfanilamide and 2-chloro-4-methylpyrimidine under the presence of alkali carbonate.
1) 2-Chloropyrimidine was synthesized. 2) 2-Sulfanilamido-pyrimidine (sulfadiazine) and 2-sulfanilamido-4, 6-dimethylpyrimidine (sulfamethazine) were synthesized with good yields by the respective condensation of N4-acetylsulfanilamide and 2-chloropyrimidine or 2-chloro-4, 6-dimethylpyrimidine.
Nitration of 4, 5-dimethyl-carbethoxyaminobenzene with nitrosulfuric acid chiefly gives 2-nitro-4, 5-dimethyl-carbethoxy-aminobenzene with some 6-nitro and 2, 6-dinitro derivatives. Hydrolyses of these nitro compounds give 2-nitro-, 6-nitro- and 2, 6-dinitro-4, 5-dimethylaniline, respectively. Acetylation of 6-nitro-4, 5-dimethylaniline with a mixture of acetic anhydride and glacial AcOH gives a mono-acetate of m.p. 106-7° and a diacetate of m.p. 114-5°.
Basic phenol alkyl ethers were synthesized by the condensation of methyl 3-allyl-4-hydroxyphenyl ether and methyl 4-allyl-5-hydroxyphenyl ether with β-diethylamino-ethyl chloride. Application of magnesium-ethyl bromide on diethylamino-acetone gives 1-diethylamino-2-methylbutanol-(2) which was changed to 1-diethylamino-2-methyl-2-chlorobutane. Condensation of C-allylguaiacol to the latter gave (β-diethylamino-α-methyl-α-ethyl)-ethyl 2-methoxy-6-allylphenyl ether.
Distilled water radiated with supersonic waves obstructs colloidal formation of sulfur formed from Na2S2O3 and HCl, and prolongs the time required for its formation. This is due to the formation of nitrous acid by supersonic wave radiation, the acid oxidizing hyposulfate to sulfurous acid which contributes to the equilibrium system of H2S2O3⇔H2SO3+S.
From the seeds of Nandina domestica Thunb., 0.68% non-phenolic and 0.04% phenolic bases were obtained. 0.02% Alkaloid was obtained from its pericarp. Protopine, m. p. 206°, was obtained from the fraction of crude methyl ether of domesticine in 0.044% yield against the seeds.
A synthetic procedure for vitamin B1 was formulated in which 2-methyl-4-amino-5-formaminomethyl-pyrimidine hydrochloride, γ-aceto-γ-chloropropyl acetate and H2S are used. Good results can be obtained by this reaction by the addition of ca. 15% active charcoal or active charcoal to which metals, such as ferric hydroxide or nickel hydroxide, have been adsorbed in 1% amount. It is assumed that in this reaction, the 3 component compounds undergo condensation in one stage and is peculiarly different from the methods heretofore used. It is necessary, in this reaction, that there be an amino radical at 4-position of pyrimidine nucleus.
As a result of studies on the reaction mechanism involving the formation of p, p′-dinitro-diphenyl disulfide (II) and p, p′-dinitro-diphenyl sulfide (III) from the reaction of 2mol. p-nitro-chlorobenzene (I) and 1mol. Na2S2, it was found that the compound (II), formed from (I) and Na2S2, was reduced further by Na2S2 to Na-salt of p-nitrothiophenol (IV) to which (I) again reacted to form (III). By the application of above theory, 2mol. (I) and 1mol. Na2S were reacted in the presence of a small amount of Na2S2 and (III) was obtained with a good yield. In this case, (II) is first formed from (I) and Na2S2, to which Na2S reacts to form (IV) and at the same time, Na2S2 is produced, this substance being repeatedly used in the first reaction. (IV) and (I) react to form (III).
Ten isosteric compounds of sulfanilamide were synthesized by replacing one or both of the two amino groups by CH3, OH or Cl (instead of F). Their comparative bacteriostatic activities were tested against E. coli und Staphylococcus aureus. The order of the precedence of the compounds are given in Table I. These facts indicate that sulfanilamide is most active among compounds tested but it is only a matter of comparison and compounds physically similar also possess considerable activities.
Twelve isosteric compounds of p-aminobenzoic acid were prepared by replacing the NH2- and OH- groups with CH3, NHOH- or Cl- radicals and their respective bacteriostatic activities were tested against E. coli and Staph. aureus. The relative bacteriostatic efficacies of the groups in positions R4 and R1 of R4-C6H4-SO2-R1 and R4-C6H4-CO-R1 type compounds are discussed (Cf. Tables)
Antagonistic effects of the isosteric compounds of p-aminobenzoic acid against p-aminobenzoic acid on the growth of E. coli were studied. It was found that, while the 4-amino compounds were remarkably antagonistic against p-aminobenzoic acid, 4-hydroxyl and 4-methyl compounds were less effective and no such effect was found in 4-chloro compounds. Antagonistic properties of 4-nitro compounds against p-aminobenzoic acid are also discussed.
The mechanism of the specific action of sulfanilmide type compounds characterized by competition with p-aminobenzoic acid are discussed. In order to antagonize p-aminobenzoic acid, it is necessary for the molecule to possess on the one end, a radical which forms a hydrogen bond, and on the other, an ionizable radical such as the sulfonyl, carbonyl or arsenyl, in the para position to the former one, as well as the size and the shape of the whole molecule.