In order to test their antibacterial action, following derivatives of p-gnanylphenyl-sulfonamides and their related compounds were synthesized: N1-methyl, -pyridyl, -dimethylpyrimidyl, -thiazolyl, -methylthiazolyl, and -thymol. The physical constants of these compounds are given in Tables.
Methyl benzoate and benzoic acid were chloromethylated in concentrated sulfuric acid by paraformaldehyde and hydrochloric gas. It was found that in both compounds the chloromethyl radical was introduced into the meta-position.
2-Methylbenzoic and 4-chlorobenzoic acids were treated with paraformaldehyde and hydrochloric gas in a concentrated sulfuric acid solution. The chloromethylated compounds obtained in this case were 2-methyl-5-chloromethylbenzoic acid from the former, and 4-chloro-3, 5-dichloromethylbenzoic acid from the latter.
Conditions of reaction during synthesis of 2-methyl-benzothiazole through thioacetanilide was found to be as follows: 8% alkaline solution of thioacetanilide is added dropwise into supersaturated solution of potassium ferricyanide, with violent agitation. Extraction of the base following the reaction is preceeded by salting out with anhydrous sodium carbonate by which the yield on the base could be raised to 70% of the theory. This improved method of synthesis gives satisfactory results in the oxidation of thioacetanilide derivatives possessing anionoid group (e.g. methoxyl, methyl, chloro, etc.) in the para position, but those in which these groups are present in the ortho position or those possessing cationoid group (e.g. nitro) in the para position did not give as satisfactory an yield.
Antibacterial power in vitro of 10 kinds of newly synthesized thiocarbocyanine were examined. It was found that benzothiocarbocyanine possessing a substituent at 8-position had powerful bactericidal power against Staphylococcus aureus Terashima. Of such compounds, the one with 2, 4-dihydroxyphenylvinyl radical at 8-position showed complete inhibition of growth of Staph. aureus in a concentration of 10. exp (-6.7)g. per cc.
In the manner similar to the case of the nitriles as reported in II, oximes were hydrogenated over nickel catalysts at high temperature and high pressure in the presence of formamide or ethyl formate. Experiments were carried out used as oximes benzaldoxime, p-sulfonamidobenzaldoxime, acetaldoxime, n-butyraldoxime, acetoxime and acetophenoxime. Corresponding formylamino derivatives were regularly obtained but the yield was not as good as in the case of nitriles, except in the case of aromatic aldehydes.
Hydrogenation of carbonyl compounds over Raney nickel at high temperature and high pressure in the presence of ammonia and formamide gave formylamino derivatives. The carbonyl compounds used were benzaldehyde, p-sulfonamidobenzaldehyde, n-butyraldehyde, acetophenone and phenylacetone. The yield of formamides was good in aromatic carbonyl compounds, side reaction being suppressed. Yield of formylamino derivatives were comparatively poor from aliphatic carbonyl compounds.
Experimental data on the reductive acylamination of nitriles with amides or esters other than formic acid are given. Experiments conducted include acylamination of benzonitrile with acetamide and ethyl acetate, p-sulfonamidobenzonitrile with urea, and 2-methyl-4-amino-5-cyanopyrimidine with ethyl lactate, by which the corresponding acylamino derivatives were obtained. However, results were comparatively poor.
Various types of aliphatic amines were formylated by formamide and ethyl formate. Acylation of benzylamine was carried out with formylmethylamine, formylethylamine, acetamide, n-butyl formate and ethyl acetate.
Reductive formylamination of benzonitrile by formylmethylamine, n-butyl formate and formamide was carried out at a temperature below that of the formylation of amines. The results of experiments are given in the text together with the author's opinion on its reaction mechanism.
p-Benzoxybenzene sulfochloride and 2-amino-4-methylpyrimidine, 2-aminopyridine, or 2-aminothiazoles were reacted in pyridine and corresponding N1-heterocyclic substituted 2-p-benzoxybenzene sulfonamides were synthesized. These were led to 2-p-hydroxy-and 2-p-acetoxy-benzene sulfonamide-N1-heterocyclic substituted derivatives.
Basic phenol alkyl ethers such as β-diethylaminoethyl 2-methoxy-4-propenylphenyl ether, β-diethylaminoethyl 2-methoxy-4-propenyl-6-allylphenyl ether, and β-diethylaminoethyl 2-allyl-6-carhomethoxy (ethoxy, allyloxy)-phenyl ether, were synthesized using allyl derivatives of isoeugenol, resorcinol and salicylic acid as the starting materials.
Abnormal structures were observed in the stems of Tricosanthes japonica Regel, in the radial margin of the xylem plate and around the inner phloem, as well as in the tissue of cortex. In these abnormal structures in the margin of the xylem and in the inner phloem there exist small vessels differentiated as a result of activity of secondary cambium cells. Such type of abnormal thickening does not correspond to any type hitherto described.
Folium Ketsumei, the dried leaves of Cassia Tora L., was extracted with MeOH and a flavonol glycoside was obtained from the concentrated extract as light yellow needles, m.p. 225-6°, corresponding to the formula C27H30O16⋅2H2O. On hydrolysis with 5% H2SO4, it gave one mol. of kaempferol, m.p. 273-4° (tetracetate, m.p. 181-2°), and two mol. of glucose (phenylosazone, m.p. 212°). In order to determine the position of the hydroxyl group bonded to the sugar residue, the glycoside was methylated with CH2N2. The reaction product, on hydrolysis with 5% H2SO4, gave small needles, m.p. 148-150°, which did not show any depression of the melting point when fused with 3-hydroxy-5, 7, 4′-trimethoxyflavone, m.p. 150-151°. Thus the original glycoside was proved to be kaempferol-3-diglucoside.
It has been found from present experiments that, of the two kinds of crystals known to exist of bis-acetosulfanilylthiazolone-imide-(2), i.e. of m.p. 190-240°, and of m.p. 130-3°, the one with higher m.p. gives crystals of m.p. 245° after treatment with anhydrous acetone, and that the same changes into crystals of m.p. 130-3° upon addition of glacial AcOH or water, these being crystals of a dihydrate. Observations were also made on the reaction of bis-acetosulfanilylthiazolone-imide-(2) and guanidine carbonate and it was found that the use of chlorobenzene as a solvent gave the best yield of acetosulfathiazole and acetosulfaguanidine (Cf. Table I.).
A new strain of acetone-ethanol fermenting bacteria which gives crystalline dextrin was isolated. Examination of its microbiological characteristics showed the new strain of bacteria to be very similar to Bacillus macerans. By a few days of culture at 40° in 10% potato gruel medium, and by addition of acetone to the fermenting liquid to 50%, amylase is precipitated. The optimal pH of this enzyme is 5.4, and the temperature, 50°. Digestion of starch paste with this enzyme gives crystalline dextrin with a 50% yield.
Digestion of starch by the newly isolated bacteria gave a new crystalline dextrin hexasaccharide which was methylated. This methylation by ordinary means gave a crude methyl compound containing 32% of CH3O radical, which was brought to a completely methylated compound by treatment with metallic sodium in liquid ammonia to Na saccharate with subsequent treatment with CH3I. The methyl compound wes obtained as needle crystals containing 1.5mol. ether of crystallization when recrystallized from ether. This crystal gradually effloresced in air. Crystals not containing ether melted at 98-103°, with [α]D=+160.5° (in CHCl3).
Chemical structure of the methylated compound of the new hexasaccharide (new crystalline dextrin) was examined and it was found to be a oligosaccharide in which 6mol. of 2, 3, 6-trimethylglucopyranose were bonded in a ring form, similar to the previously reported hexasaccharide. Treatment of the completely methylated compound of the new saccharide with conc. HCl at a low temperature gives trimethylglucose, which can be assumed to be its structural components, in a 93% yield. This compound gives an m.p. of 114°, [α]D=+90°. Its chemical examination revealed that it posseses an oxygen bridge between C1 and C5, and a free OH radical at C4, so that the structure was proved to be 2, 3, 6-trimethyl-glucopyranose. Changes in the αD value of the saccharide was examined by its hydrolysis with 50% H2SO4 at a room temperature and a temporary increase in αD value was observed which is the specific characteristics of cyclic polysaccharides as stated by Freudenberg. From these facts, the new compound was assumed to be a cyclic hexasaccharide.
Both the previously reported saccharide (Schardinger's dextrin) and the new saccharide (new crystalline dextrin) were found to be oligosaccharides composed of 6mol. of glucose and no difference in their respective chemical structures could be observed. Observations were made in the present experiment from the point of enzymatic chemistry on their α- and β-bonding, and a difference between the two saccharides was revealed. By respective treatment of the two substances with maltase, which cleaves at α-bonding, and β-amylase, which cleaves at β-bonding, following results were obtained: 1) The hexasaccharide (Schardinger's dextrin) is decomposed only by maltase. 2) The new hexasaccharide forms glucose and maltose by the respective action of maltase and β-amylase. From these results, it has become clear that, in the hexasaccharide (Schardinger's dextrin), the glucose molecules are bonded in α-bonding alone, while in the new saccharide, they are bonded both in α- and β-bondings. It can therefore be assumed that the only difference existing in the two saccharides is the difference in the manner of bonding.