Crystallographic studies were made of pure santonin crystals to prepare its crystal system, facial indices and stereograph. The index of refraction, optic axial angle, sign of elongation and dispersion of optic axes were determined. These figures were compared with those of crystals obtained by microsublimation from Artemisia cina and A. monogyna Waldst. et Kit. in order to determine the presence of santonin. The same measurements were made of artemisin and temisin which are often present in crude drugs and have similar chemical structures to santonin, in order to facilitate observation.
The preparation of sodium citrate from calcium citrate involves initial preparation of citric acid by decomposition of calcium salt with H2SO4, neutralization with Na2CO3 and subsequent crystallization by evaporation. The reaction proceeds 98% even by applying Na2CO3 to calcium citrate while hot. However, sodium citrate so prepared contains pectin substance and is difficult to purify. By purification with concentrated NaCl solution, solubility of pectin substance is lowered, thereby decreasing the amount of the same in solution and lowering the solubility of sodium salt. Moreover, this NaCl solution can be used repeatedly which makes it economical. Although sodium citrate so prepared contains a small amount of NaCl, it can be brought up to the standard of Pharmacopoea by recrystallization.
By the sterilization of drugs having vitamin A as their important component, such as cod liver oil, by the standard method set by J. P. of 2hrs. at 120°, loss of about 10% vitamin A unit must be expected. This loss becomes ca. 20% if heated for 5hrs. Experiments on the effect of air and light showed that no great difference existed by the presence or absence of air and in colorless or brown glass ampules at 120°. Sterilization at 150-160° showed a loss of 8.4% average for 15 minutes, 10.5% average for 30 minutes' heating. After 2 hours' heating, the effect of air inside the ampule seemed to be marked, those in brown glass ampules being much more advantageous. However, no such difference exists between one and two hour heating which may be due to the definite amount of air sealed in an ampule which makes oxidation proceed in a short time. In any event, the change occurs lineally, especially when no air is present. This proves that the thermal decomposition of vitamin A cannot be prevented by either removal of air and water or by prevention of light. It follows, therefore, that the decrease of vitamin A unit must be sought by means of using drugs without heating.
In the nitration of quinoline-N-oxides having halogen in its benzene ring, such as 6-chloro-, 6-bromo- and 8-chloro compounds, effect of N-oxide radical on its C4 position is decreased by halogen radical and nitration occurs at C5 position.
2-Amino-4-phenyl-5-p-aminobenzenesulfone-thiazole was obtained by the condensation of ω-bromo-ω-p-acetaminobenzenesulfone-acetophenone and thiourea and subsequent hydrolysis. Bromination of p-acetaminobenzenesulfone-acetone in NaOH solution results in the substitution of Br in methylene radical situated between sulfone and carbonyl radicals. When this is condensed with thiourea and then hydrolyzed, 2-amino-4-methyl-5-p-aminobenzenesulfone-thiazole (methylpromizole) is obtained. Halogenation, if made in glacial AcOH solution, results in substitution of halogen atom in the methylene radical at the end so that, when this is condensed with thiourea and subsequently hydrolyzed, 2-amino-4-p-aminobenzenesulfone-methylthiazole is obtained.
Sulfide compounds obtained by reacting bromo-acetal to the sodium salts of p-thiocresol or p-nitrothiophenol is oxidized to sulfonacetal, brominated in glacial AcOH and condensed with thiourea to 2-amino-5-p-tolysulfone- and 2-amino-5-p-nitro-benzenesulfone-thiazole, respectively, Latter is reduced to Promizole (2-amino-5-p-aminobenzenesulfone-thiazole).
2-Chloro-5-(4′-diethylaminocyclohexyl)-amino-7-methoxyacridine, a new compound having N, N-diethylcyclohexylene-diamine (1, 4) radical instead of the basic side-chain of atabrin, δ-diethylamino-α-methylbutylamine, was synthesized by the condensation of N, N-diethylcyclohexylene-diamine (1, 4) and 2-chloro-5-phenoxy-7-methoxyacridine. This antimalarial having the side-chain which is more easily synthesized than that of atabrin, showed about the same (cis-form) or better (trans-form) therapeutic effect as atabrin by animal tests usiug innoculated canaries.
Ethyl acetaminocyano-acetate was synthesized by the reduction of ethyl isonitrosocyano-acetate to aminocyanoacetate and subsequent acetylation. This and the usual methods were compared. Some α-amino acids were synthesized by using ethyl acetaminocyanoacetate.
Addition of 1 mole EtI to N, N′-di-α-pyridylformamidine (I) obtained from α-amino-pyridine results in the formation of quarternary salt dye of pyridylformamidine. Further addition of 1 mole EtI results in decomposition to α-aminopyridine ethiodide (II). (I) reacts with cyclic ammonium salts containing active methylene forming quarternary salt of heterocyclic amino-ethenyl compound. Boiling (II) in anhydrous pyridine solution with ethyl orthoformate results in 1, 1′-diethyl-2, 2′-azomethinecyanine iodide, which is assumed to be a compound in which the 2 methine radicals of trimethinecyanine have been substituted by nitrogen. Spectroscepic studies of these dyes revealed that absorption maximum of pyridylaminoethenyl dyes is in a longer wave portion than the corresponding phenylaminoethenyl compounds, and that of azomethinecyanine in a shorter wave portion compared to the corresponding trimethinecyanine.
Anils obtained by the reaction of aromatic aldehydes and aniline or ammonia, e.g. Schiff's base, hydrobenzamide, etc., react with cyclic ammonium base possessing active methylene radical and form styryl dyes. This method has the advantage over the use of free aldehydes in that, formation of by-product isocyanines could be prevented by the elimination of condensation reagent, and that anils are more stable compared to free aldehydes. Trimethincyanine is formed by the reaction of cyclic ammonium salt possessing active methylene instead of formaldehyde on trimer-methylene-aniline and methylene-dianiline.
Esterificraion of organic acids using cation-exchange resin as a catalyst was experimented. In order to remove the water formed by the reaction, CCl4 was added with EtOH, thereby forming a ternary azeotropic mixture, allowing water to distill at a low temperature. This method is especially well-adapted for the esterification of aliphatic dicarboxylic and aromatic carboxylic acids. Sometimes, esterification does not proceed smoothy due to low temperature but, in such cases, use of higher alcohols such as butanol, will correct the fault. The advantage of ion-exchange resin over HCl and H2SO4 lies in the fact that the resin can be used over and over again for the same reaction, separation of the product from reactant solution is easy and that damage to reacting vessels in industries is minimized.
In the condensation of quinaldine methiodide and anils, the difference in the speed of dye formation by various substituents in aniline nucleus of anils was measured by colorimetry and following results were obtained. The reaction speed increases by the order of m-nitro>> o-carboxyl>H>p-methyl>p-hydroxyl radicals on aniline nucleus of piperonylidene-aniline but the order is p-nitro>> m-nitro->p-bromo->H>p-methyl>p-methoxyl in the case of p-dimethyl-aminobenzilidene-aniline. This fact seems to point that according to the polarization effect of these radicals on -CH=N- bond, they are proportionate to the speed of hydrolysis and so that radicals having strong polarity such as -NO2 promote the reaction whereas -OCH3 -OH which have inverse effect, tend to decrease the speed of reaction.
Acid product was obtained by the reduction of pulvinic anhydride (II) with Pd-coal as a cataylst but it did not solidify. Heating this product with acetic anhydride resulted in the formation of carboxycornicular lactone (IV), yellow needles, m.p. 218-9°, and vacuum distillation gave cornicular lactone (V), pale yellow leaflets, m.p. 136-6.5°. It follows, therefore, that this reduction product is dihydropulvinic acid (III). Methyl ester of (IV), yellow needles, m.p. 170-2°, gave, by reduction with PtO2, methyl diphenyladipiate, colorless leaflets m.p. 139-141°, and methyl tetrahydrocarboxy-cornicular lactone (VIII), white needles, m.p. 136°. Catalytic reduction of (V) with PtO2 resulted in obtaining α, δ-diphenylbutane-α-carboxylic acid (IX), colorless needles, m.p. 77-8°, cyclohexylphenyl-valerolactone (X), white needles, m.p. 66-7°, and α, δ-diphenyl-γ-valerolactone (XI), colorless needles, m.p. 67-9°. On the other hand, α, δ-diphenyl-γ-valerolactone of m.p. 72° is obtained by the catalytic reduction of α-phenyl-γ-benzyl-Δα, β-crotonlactone, colorless needles, m.p. 86-9°, with PtO2, or by the reduction of dihydrocorniculic acid. The above valerolactone was found to be identical with (IX) when fused with it.
By using diazomethane for the methylation of 5, 5-dimethyl-2, 4-dioxo-oxazolidine as a method of manufacturing 3, 5, 5-trimethyl-2, 4-dioxo-oxazolidine, a good yield was obtained. Methylation in good yield was obtained from 5, 5-dimethyl-2, 4-dioxo-thiazolidine, 2, 4-dioxo-thiazolidine and 2, 4-dioxo-oxazolidine as heterocyclic compounds of -CO-NH-CO-type.
It has been assumed that the synthesis of thioacetanilide by the reaction of K2S and P2S5 on acetanilide was essentially the reaction of acetanilide and K-thiophosphate formed. Conditions for the formation of maximum yield in this reaction was checked and thereby the formation rate of thioacetanilide as against acetanilide was increased to 80% of the calculated amount. The solubility of thioacetanilide in alkaline aqueous solution becomes zero when its concentration increases to over 25% and has a maximum solubility at 9% concentration.
Dissolution of thioacetanilide in aqueous alkali results in the solution of its sodium salt but in alkaline concentrations of over 2N, sodium salt formation is difficult by the effect of OH radical so that the solubility of thioacetanilide in this concentration range decreases. On the other hand, formation of 2-methylbenzothiazole from thioacetanilide in alkaline aqueous solution by the oxidation with K3Fe(CN)6, also decreases its rate of formation when the alkaline concentration is raised above 2N, which shows that the same relationship exists between the solubility of thioacetanilide and the concentration of its alikaline solution. This is due to the two tautomeric structures of thioacetanilide molecule which change according to the concentration of alkali. It is assumed that thio-enol form of thioacetanilide is more liable to form sodium salt and also is more liable to be oxidized.
p-Methoxy-nor-ephedrine was obtained by the condensation of anisaldehyde, nitroethane and KHCO3 and subsequent reduction with Fe or Zn and dil. H2SO4. Formation of normal and iso compounds was at a ratio of 1:3. Treatment of α-bromo-p-methoxypropiophenone with K-phthalimide and subsequent saponification gave aminoketone hydrochloride, m.p. 216°, which yielded a normal base when catalytically reduced with Adams' PtO2⋅H2. It was found that the reduction of anetholnitrosite with Zn+AcOH gives a normal compound, proving that the compound obtained earlier by Krámli and Bruckner by electrolytic reduction of acetyl anetholnitrosite and subsequent heating with 2N-HCl is an iso-form compound since saponification of acylamino-alcohol with mineral acid results in the conversion of normal to the iso compound.