1) Heating of alkylenediamine with various glycols at a high pressure in an autoclave, using Raney nickel as a catalyst, affords C-alkylated piperazines in good yield. The reaction of propylenediamine with ethylene glycol, propylene glycol, and 2, 3-butanediol respectively affords 2-methylpiperazine, cis- and trans-2, 5-dimethylpiperazine, and α-, β-, and γ-2, 3, 5-trimethylpiperazine. In the case of 2, 3-diaminobutane with the same glycols, cis- and trans-2, 3-dimethylpiperazine, α- and γ-2, 3, 5-trimethylpiperazines, and α- and β-2, 3, 5, 6-tetramethylpiperazines are obtained. 2) C-Alkylated piperazines were also prepared by cyclization of N-(2-hydroxyalkyl) alkylenediamines under a high pressure and in the presence of a catalyst. 3) Condensation of diacetyl with propylenediamine and 2, 3-diaminobutane respectively afforded 2, 3, 5-trimethyl- and 2, 3, 5, 6-tetramethyl-5, 6-dihydropyrazines which were hydrogenated with sodium and ethanol to the corresponding C-alkylated piperazines. These were compared with isomers of C-alkylated piperazines obtained by the foregoing two routes.
Synthesis of dl-homoarmepavine was attempted in order to confirm the structure of l-homoarmepavine, which was assumed to be l-1-(3-methyl-4-hydroxybenzyl)-2-methyl-6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline (II), a phenolic base obtained by cleavage of insularine (I) with metallic sodium in liquid ammonia. The racemic compound obtained by the route shown in Chart 1 exhibited infrared absorption spectrum in chloroform identical with that of l-homoarmepavine, obtained by cleavage of insularine (I), and the Rf values in paper chromatography were also the same in the two substances, establishing that the structure of l-homoarmepavine is represented by the formula (II). Thus, even from the reaction with sodium in liquid ammonia, insularine was proved to be one of a specific biscoclaurine-type bases with a depsidan ring.
The Friedel-Crafts reaction of 1, 6-dimethoxydibenzo-p-dioxin (I) with acetyl chloride, in the presence of anhydrous aluminum tribromide affords the diacetyl derivative of m.p. over 300°, C18H16O6, whose Clemmensen reduction gives a diethyl derivative of m.p. 163-165°, identical with 1, 6-dimethoxy-4, 9-diethyldibenzo-p-dioxin (II), obtained by the Ullmann condensation of 1-ethyl-2-bromo-3-hydroxy-4-methoxybenzene (IId). Therefore, the diacetyl compound obtained by the Friedel-Crafts reaction of (I) must be 1, 6-dimethoxy-4, 9-diacetyldibenzo-p-dioxin (IV) formed by the introduction of two acetyl groups respectively in position para to the methoxyl group.
Reduction of 3-nitroquinoline 1-oxide (I) was examined and it was found that reductive deoxygenation of the N-oxide group in the 3-nitro compound was much more facile than that in the 4-nitro compound. From the various data of reduction in solvents listed in Table I, it was found that this reduction was effected, as in the case of the 4-nitro compound, through 3-hydroxyamino- (II) and 3-amino-quinoline 1-oxide (III) to 3-aminoquinoline (IV). It was therefore considered that the facility of deoxygenation of the N-oxide group in 3-nitro and 4-nitro compounds could be explained as the difference in the electron density in the corresponding aminoquinoline 1-oxides.
Conductometry was applied to the quantitative determination of maleic hydrazide (1, 2-dihydropyridazine-3, 6-dione). An accurately measured 0.2-0.3g. of maleic hydrazide is dissolved in distilled water to make 100cc., 10-20cc. of 0.1N sulfuric acid is added, this solution is titrated with N sodium hydroxide, and conductance at various points is measured. This is plotted on a graph. The value derived by subtracting the number of cc. of 0.1N sulfuric acid divided by 10 from the number of cc. of the alkali required to the 1st breaking point corresponds to one-half the amount of impurities, and the number of cc. corresponding to this half amount of impurities subtracted from the number of cc. of the alkali required to the 2nd breaking point corresponds to the amount of N sodium hydroxide corresponding to maleic hydrazide. By the use of this correction, titration can be made with good accuracy. In diethanolamine solution, there will be no effect of impurities and diethanolamine and, with the addition of 0.1N sulfuric acid, the space between the 1st and 2nd breaking points is the number of cc. of N sodium hydroxide corresponding to maleic hydrazide. Comparison of this method with that of ultraviolet spectrophotometric method with the market product showed good agreement. It follows therefore that the present method is suitable as industrial analytical method since it allows a more simpler determination.
When acetyl, benzoyl, and phenylacetyl derivatives of ethyl dl-4-(2-piperidyl) butyrate are dry distilled with the same or twice the amount of soda lime, 4-methyl-, 4-phenyl-, and 4-benzyl-Δ3-dehydroquinolizidines are obtained in respective yield of 97%, 93%, and 95%, with generation of slight ammonia odor. These bases are unstable and colored in the air but their picrates and perchlorates form stable dehydroquinolizidinium salts and do not undergo any change even when heated in air at 120-130°. Catalytic reduction of these bases in ethanol with palladium-carbon catalyst easily afforded 4-alkyl- or 4-arylquinolizidines in quantitative yield. It was found from these facts that this kind of cyclization reactions reported to date do not necessarily require the formation of enol type by the carbonyl group of the acid amide.
Acyl derivatives of ethyl dl-3-(2-piperidyl) propionate and dl-3-(2-pyrrolidinyl)-propionate were dry distilled with soda lime from which 3-substituted Δ2-dehydroindo-lizidines and Δ2-dehydropyrrolizidines were obtained in around 95% yield. Catalytic reduction of these bases with palladium-carbon easily afforded the corresponding indolizidine and pyrrolizidine derivatives. The Δ2-dehydro bases obtained by dry distillation were extremely labile, coloring immediately in air but their picrates and perchlorates were stable. Reaction of the aqueous solution of the perchlorates of 3-methyl-Δ2-dehydroindolizidine and Δ2-dehydropyrrolizidine with potassium cyanide afforded 3-cyano-3-methyl-indolizidine and -pyrrolizidine derivatives which formed respective picrates. Recrystallization of the picrates from ethanol resulted in genration of hydrogen cyanide and the substances reverted to the original 3-methyl-Δ2-dehydroindolizidine and -pyrrolizidine picrates. These reactions are the same as those of the Δ3-dehydroquinolizidines described in the preceding paper and are clearly confirmed by infrared absorption spectra.
As the new thiol-type thiamine derivatives, disulfide derivatives of thiamine and higher alkyl, 2-hydroxyalkyl, 2-hydroxy-3-alkoxypropyl, alkoxycarbonylmethyl, ω-hydroxyalkyl, tetrahydrofurfuryl, 3-(2-tetrahydrofuryl) propyl, and tetrahydro-2-pyra-nylmethyl were synthesized.
Tetramethylmagnolamine (-, +) (Ic), the diastereoisomer of natural tetramethylmagnolamine (+, +) (Ib) and of synthesized tetramethylmagnolamine (-, -) (Ia), was prepared by the Ullmann reaction of d-armepavine (V) and l-6′-bromolaudanosine (VI), the two 1-benzyltetrahydroisoquinoline-type bases that form its structural components. The properties of the compound so obtained are listed in Table I.
A new reaction was found by heating quinoline 1-oxide with tosyl chloride in dimethylformamide, with boron trifluoride as a catalyst, which effected dimethylamination of the 2- and 4-positions in 29% yield. In the case of isoquinoline, the same reaction afforded 1-dimethylaminoisoquinoline in 39% and 2-(1-isoquinolyl) isocarbostyril as a by-product in 25% yield.
Application of tosyl chloride and dimethylformamide to quinaldine and lepidine 1-oxides did not effect dimethylamination and chloromethylquinoline was obtained in both cases. The yield from this reaction was greatly increased by the presence of boron trifluoride. Presence of water in the reaction of lepidine 1-oxide and tosyl chloride results in the formation of a carbostyril and not chlorine substitution.
p-Aminobenzoates of saccharides and polyhydric alcohols were prepared and their utility as the protective coating agent was examined. p-Aminobenzoates were prepared by the application of p-nitrobenzoyl chloride to saccharides and alcohols to form p-nitrobenzoates which were catalytically reduced in the presence of Raney nickel. The p-aminobenzoates of sucrose, lactose, glucose, fructose, and mannitol are resistant to the action of water, dissolve in gastric juice, and form protective films. Glucose p-aminobenzoate was insoluble in various organic solvents except dioxane that its utility as the coating agent was somewhat questionable. These p-aminobenzoates were tested by coating starch-lactose tablets and submitted to measurement of the time taking for disintegration in distilled water and simulated gastric juice to examine their water resistance and solubility in gastric juice. It was thereby found that these compounds could be used as protective coating agent.
Glycine esters of cellulose derivatives, their N-substituted compounds, and p-aminobenzoates were prepared and their utility as protective coating agent was examined. Methyl-, acetyl-, and ethylhydroxyethyl-cellulose were chloroacetylated with chloroacetyl chloride and reacted with various amines to form glycine esters and their N-substituted derivatives. p-Nitrobenzoates of cellulose derivatives were prepared with p-nitrobenzoyl chloride and subsequent reduction. Glycine esters were all slightly soluble in organic solvents and artificial gastric juice, and were not suitable as coating agents. p-Aminobenzoate of methylcellulose formed semilucent coating and ethylhydroxyethylcellulose derivatives had low solubility in organic solvents, that these were not suited for the present purpose. p-Aminobenzoate of acetylcellulose was found to have good properties as the protective coating agent.
The reactivity of the double bond in 2-position of thiachromone 1, 1-dioxide, considered to be isosteric compound of 1, 4-naphthoquinone, was examined. Hydrogen (zinc dust and acetic acid), bromine, 2, 3-dimethylbutadiene, hydrogen bromide, and thiophenol underwent addition to this double bond to form 4-thiachromanone 1, 1-dioxide and their derivatives but in the case of two latter reagents, bromo and phenylthio groups were respectively introduced into the 2-position. Additive condensation of thiophenol with 3-bromothiachromone 1, 1-dioxide in the presence of alkali afforded 2-phenylthio-thiachromone 1, 1-dioxide. These facts indicate the double-bond characters of 2-position and it is concluded that the addition of a nucleophilic reagents is controlled by the α, β-unsaturated ketone system (-CO-CH=CH-) according to the difference in polarization of CO>SO2. On the other hand, dibromination of 4-thiachromanone 1, 1-dioxide and formation of 1, 1-dioxide from 3, 3-dibromo-4-thiachromanone by oxidation did not give the anticipated result and this was considered to be due to the steric hindrance of polar-bonded bromine and sulfonyl group.
Riboflavin 5′-phosphate was reacted with 14 kinds of carbodiimide and the formation of riboflavin cyclic 4′, 5′-phosphate and N-riboflavinphosphoryl-N, N′-dialkylurea was observed. Formation of the latter was especially marked in the case of aliphatic carbodiimide. Riboflavin cyclic 4′, 5′-phosphate reacts with primary alcohols in the presence of hydrochloric acid to form riboflavin 5′-alkylphosphate.
It had earlier been reported that the alkylation of 2-sodioformyl-3-alkoxypropionitrile (II or III) with dialkyl sulfate afforded cis- and trans-2-alkoxymethylene-3-alkoxypropionitrile (IV, V, and VI) but later examinations revealed that the substances obtained in this reaction were still impure. Further purifications showed that besides the cis and trans isomers of the foregoing nitriles, another isomer of low boiling point has been formed. This new isomer was found to have C=C bond from the Raman spectra although this point was not clear from its infrared spectrum. Ozonolysis of this isomer afforded formaldehyde, proving the presence of endo-methylene group. Catalytic reduction resulted in the rapid absorption of one mole of hydrogen to form 2-dialkoxymethyl-propionitrile (X and XI). The latter was confirmed from its infrared spectrum and formation of 2, 5-dimethyl-4-aminopyrimidine (XII) by condensation with acetamidine. These experimental results have proved that the new-type isomer obtained by the foregoing reaction is 2-dialkoxymethyl-acrylonitrile (VII, VIII, and IX).
Application of alcohol to cis- and trans-2-alkoxymethylene-3-alkoxypropionitrile and 2-dialkoxymethyl-acrylonitrile, with acid or alkali as a catalyst, was found to effect facile addition of the alcohol to form the acetal-type compounds, 2-dialkoxymethyl-3-alkoxypropionitriles, evidenced by their elemental analytical values and infrared absorption spectra. In this reaction, some 2-dialkoxymethyl-acrylonitriles formed and transetherification of the starting 2-alkoxymethylene-3-alkoxypropionitriles and the formed 2-alkoxymethylene-3-alkoxypropionitriles was observed.
Formation of 2-dialkoxymethyl-acrylonitrile, formed together with 2-alkoxymethylene-3-alkoxypropionitrile by the alkylation of 2-sodioformyl-3-alkoxypropionitrile with dialkyl sulfate, was revealed to result by the catalytic effect of unreacted dialkyl sulfate on the 2-alkoxymethylene-3-alkoxypropionitrile first formed. This catalytic reaction is also effected, besides the dialkyl sulfate, by conc. sulfuric acid, p-toluenesulfonic acid, H acid, and ammonium sulfonate. When a few drops of conc. sulfuric acid is added to 2-dialkoxymethyl-3-alkoxypropionitrile and this is submitted to low-pressure distillation at 100° and 30mm.Hg, alcohol liberates immediately to form 2-alkoxymethylene-3-alkoxypropionitrile, while elevation of the bath temperature to around 170° results in the formation of 2-dialkoxymethyl-acrylonitrile. It follows, therefore, that the choice of reaction conditions will easily afford 2-dialkoxymethyl-3-alkoxypropionitrile, 2-dialkoxymethylene-3-alkoxypropionitrile, or 2-dialkoxymethyl-acrylonitrile.
Reëxaminations were made on the reaction of acetamidine with cis- and trans-2-alkoxymethylene-3-alkoxypropionitrile, 2-dialkoxymethyl-acrylonitrile, or 2-dialkoxymethyl-3-alkoxypropionitrile. It was thereby found that this reaction with 2-alkoxymethylene-3-alkoxypropionitrile in ethanol affords 2-methyl-4-amino-5-alkoxymethylpyrimidine while other two substances afforded 2-methyl-4-amino-5-acetamidomethylpyrimidine via 2, 7-dimethyl-5, 6-dihydropyrimido [4, 5-d] pyrimidine. The same 2-methyl-4-amino-5-acetamidomethylpyrimidine is obtained by the reaction of 2-alkoxymethylene-3-alkoxypropionitrile in methanol or in the presence of sodium ethoxide. This reaction course was followed by ultraviolet absorption spectrum and it was revealed through this means that acetalization occurred first by the action of the alcohol on 2-alkoxymethylene-3-alkoxypropionitrile and this was followed by cyclization to a pyrimidine ring.
Utility of various N-substituted polyvinylamines and N-substituted vinylaminevinyl acetate copolymers as a protective coating agent was examined. The N-substituted derivatives were prepared by the application of primary or secondary amines to the p-toluenesulfonate of polyvinyl alcohol and vinyl alcohol-vinyl acetate copolymer. Of these, all the polyvinylamine derivatives were sparingly soluble in organic solvents and were found to be unsuitable as a protective coating agent. On the other hand, derivatives of the copolymer were all well soluble in organic solvents, and N, N-diethyl, N-benzyl, N-hydroxyethyl, and piperidino derivatives were insoluble in water but soluble in simulated gastric juice, and easily formed a film from organic solvent solution. These four were submitted to the measurement of disintegration time in distilled water and simulated gastric juice after coating on starch-lactose tablets. They all showed resistance to disintegration in distilled water for over 4 hours but disintegrated within 10-20 minutes in simulated gastric juice, showing suitability as protective coating agents.
Utility as protective coating agent was tested with polyvinyl aminoacetacetals and their N-substituted derivatives, polyvinyl p-dimethylaminobenzacetal, and their copolymers with vinyl acetate, . Polyvinyl aminoacetacetal and the N-substituted derivatives were prepared by the application of various amines to polyvinyl bromoacetacetal and polyvinyl p-dimethylaminobenzacetal by the application of p-dimethylaminobenzaldehyde to polyvinyl alcohol. Copolymers with vinyl acetate were prepared similarly. The compounds soluble in organic solvents, insoluble in water, and soluble in simulated gastric juice were diethylaminoacetacetal, benzylaminoacetacetal, and 1-piperidylacetacetal of polyvinyl, and copolymers of vinyl diethylaminoacetacetal-vinyl acetate and of vinyl piperidinoacetacetal-vinyl acetate. These were coated on tablets and tests showed that they had resistance of over 4 hours in distilled water but disintegrated within 10-20 minutes in simulated gastric juice. Therefore, these would probably prevent the action of moisture on the drug and show protective action, as well as rapidly undergoing disintegration in gastric juice, and would be very useful as a protective coating agents.
In order to introduce a substituent in the 8-position of coumarin-3-carboxylic acid, 3-acetamidosalicylaldehyde, m.p. 152°, was first prepared. Both 3-nitrosalicylaldehyde and 1-diacetoxymethyl-2-acetoxy-3-nitrobenzene formed 3-acetamidosalicylaldehyde on catalytic reduction over palladium-carbon in acetic acid-acetic anhydride mixture. This aldehyde was used as a starting material for the preparation of the following compounds: 8-Aminocoumarin-3-carboxylic acid, m.p. 223° (decomp.). Its ethyl ester, m.p. 115-116°. The ethyl ester of N-acetylated compound, m.p. 169-170°. Ethyl 8-aminocoumarin-3-carboxylate was also obtained by catalytic reduction of the corresponding nitro compound. Hydrolysis of 2-hydroxy-5-acetamidobenzylidene-aniline afforded 5-acetamidosalicylaldehyde, m.p. 149°, whose thiosemicarbazone melted with decomposition at 312-314°.
Amination of 3-alkylpyridines with sodium amide in decalin or xylene was not effected except in the case of methyl derivative, which afforded 2-amino-3-methylpyridine. This compound was submitted to consecutive bromination, cyanation, and saponification to prepare 3-methylpicolinic acid. Condensation of 1-acyl-2-iminopropane with 3-ethoxyacrolein diethyl acetal gave 2-methyl-3-acylpyridine, which was reduced by the Wolff-Kishner method, derived to N-oxide, and submitted to the Boekelheide rearrangement. The acetoxymethyl derivatives so obtained were hydrolyzed with hydrochloric acid, and oxidized with activated manganese oxide (Ball reaction). As in the first case mentioned, the 3-alkyl derivatives afforded 3-alkyl-2-pyridinealdehyde in better yield (54.6-62.3%) than that (45%) of non-substituted pyridines. Their mild oxidation gave the objective 3-alkylpicolinic acid with alkyl from methyl to pentyl. 5-Methylpicolinic acid was prepared from 2-methyl-5-ethylpyridine via 2, 5-lutidine but the yield from the Ball reaction was 37.7%, less than that from the 3-alkyl derivatives.
2, 6-Lutidine was derived to its N-oxide by the usual method, submitted to Boekelheide's rearrangement to form 2-acetoxymethyl-6-methylpyridine, deacetylated by boiling with hydrochloric acid to 6-methyl-2-pyridinemethanol, which was changed to 6-methyl-2-pyridinealdehyde by the Ball reaction, and oxidized mildly with silver oxide to form 6-methylpicolinic acid. 6-Alkylpicolinic acids, with alkyl above ethyl, were prepared in the following manner: The methyl groups in 2- and 6-positions were changed to a larger group by the application of phenyllithium and alkyl halide to 2, 6-lutidine and this was submitted to the same reactions as above. The 2-(1-acet-oxyalkyl)-6-alkylpyridines so obtained were submitted to pyrolysis to form 2-alkylvinyl-6-alkylpyridine and its oxidation with cold potassium permanganate afforded 6-ethyl-, 6-propyl-, 6-butyl-, and 6-pentyl-picolinic acid. Use of sulfuric acid in place of pyrolysis resulted in poor yield.
Antibacterial activity in vitro of 21 kinds of alkylpicolinic acid differing from one another in the size and position of their alkyl groups and of picolinic acid against Staphylococcus aureus, Salmonella typhi, and Esherichia coli was examined. The relationship between the chemical structure of these compounds and their antibacterial activity was studied.
1) Substances possessing a dibenzo-p-dioxin (diphenylene dioxide) structure show blue to bluish green coloration in sulfuric-nitric acid or conc. sulfuric acid solution when added with potassium nitrate, sodium nitrate, potassium chlorate, or other oxidation agents. This reaction was discovered by Tomita more than 20 years ago and it was applied to the detection of dibenzo-p-dioxin derivatives by paper chromatography in the present series of work. 2) Coloring reagent was an ethanolic solution of potassium nitrate followed by spraying of conc. sulfuric acid. 3) Paper chromatography was carried out on several dibenzo-p-dioxin derivatives with ordinary and silicone-treated filter paper (Toyo Roshi No. 50), using various solvent systems. Results obtained are listed in Table I. 4) This coloration method can be applied to the paper chromatograpay of alkaloids possessing a dibenzo-p-dioxin structure such as trilobine, isotrilobine, and menisarine.
Present series of experiments were carried out in order to obtain 4, 9-dimethoxydibenzo-p-dioxin-2, 7-dicarboxylic acid (VI). The Ullmann reaction of the potassium salt of 5-bromovanillin in coal gas atmosphere, with “Natur Kupfer C” as a catalyst did not afford a substance giving positive reaction of dibenzo-p-dioxin which should color blue to sulfuric and nitric acid mixture. The Ullmann reaction of the potassium salt of methyl 5-bromovanillate (IV) with the same catalyst afforded methyl 4, 9-dimethoxydibenzo-p-dioxin-2, 7-dicarboxylate (V), m.p. 278°, whose hydrolysis finally gave the objective acid (VI) which crystallized from N, N-dimethylformamide as colorless needles, m.p. over 300°.
Optical resolution of dl-N-methylcoclaurine was successfully effected with di-p-toluoyl-d-tartaric acid and -l-tartaric acid as the resolution agents and in a mixed solvent of methanol and ethyl acetate. The optically active compounds thereby obtained are listed in Table I. Optical rotation of d- and l-N-methylcoclaurine differs greatly by the solvents used, as indicated in Table II.
Tertiary bases were obtained from the root of Caulophyllum robustum MAXIM., which formed a picrate of yellow needles, m.p. 228-230° (decomp.), a styphnate (A) of pale yellow prisms, m.p. 201-203° (decomp.), and another styphnate (B) of yellow needles, m.p. 132-136°, all in small amounts. A large amount of an aporphine-type magnoflorine (I) was obtained as the water-soluble quaternary base but the plant did not contain any berberine-type quaternary base.
Growth inhibition in vitro against human type tubercle bacilli H37Rv was tested with alkyl and aryl esters of 4-succinyl-, 4-maleyl-, and 4-phthalyl-amidosalicylic acid. Alkyl esters, including the esters of p-aminosalicylic acid, showed only a weak activity and comparison of bacteriostatic activity was difficult and aryl esters of p-aminosalicylic acid were far stronger than the others. p-Tolyl ester and o-and p-methoxyphenyl esters of 4-phthalylamidosalicylate showed growth inhibition 6.57-12.77 times that of p-aminosalicylic acid when the ratio of molecular weights is taken into consideration.
Capillary analysis of xylene extract of crude drugs indicated that the relationship between the height, y, of elevation of crude fats extracted and concentration, x, of crude fats in the extract solution could be represented by y=2m-n/x, and that quantitative determination of crude fats in the crude drugs could be made by this means.
As a model compound in which -SH group is bonded to asymmetric carbon atom through a methylene group, (+)- and (-)-2-dimethylamino-3-phenylpropanethiol were synthesized and asymmetric synthesis of methyl mandelate from phenylglyoxal was attempted, using the foregoing compound as the catalyst. It was thereby found that the asymmetric synthesis is possible and dextrorotatory product was obtained by the use of a levorotatory catalyst, but its yield was extremely poor.
The method of Brewster-Ciotti was applied to dibasic acids and monoamide and imide were obtained from phthalic, homophthalic, and succinic acids, indicating that the intermediates are intramolecular anhydride. The imide formed here is considered to have been produced by dehydration of the monoamide first formed by the byproduct benzenesulfonic acid and also by heating. The same reaction of glutaric and adipic acids afforded monoamide and diamide which indicates that the intermediates in this case are intermolecular anhydride.
The unknown derivatives of coclaurine, dl-N-methylisococlaurine (VIII), dl-4′-methyl-N-methylcoclaurine (IX), and dl-demethylcoclaurine (X) were prepared (cf. Table I). Methylation of dl-coclaurine (I) with excess of diazomethane was found to form dl-O, O, N-trimethylcoclaurine (VII) (picrate, m.p. 170-171°) as a by-product besides dl-O, O-dimethylcoclaurine (V) (m.p. 202-203°) (oxalate, m.p. 206-207°).
Rabbit ears receiving irradiation of a single dose of X-rays above a certain limit undergoes delapidation (Fig. 1). Figs. 2 and 3 indicate effect from change of a few conditions. This irradiation delapidation was thought to be applicable for the test of drugs for preventing irradiation damage of the skin. Fig. 4 shows that sodium nitrite, as other compounds tested, was ineffective in preventing X-ray delapidation.
Quinolinediol, which was reported previously as 7, 8-diol, prepared from oxine and its 5-sulfonic acid by alkali fusion was found to be identical with 8-hydroxycarbostyril by obtaining 8-benzoyloxycarbostyril, m.p. 212-214°, and from the result of infrared spectrum.