Compounds were tested for the activity of decreasing the capillary fragility by the prevention of pulmonary hemorrhage in mice under reduced pressure. Compounds effective were found to be natural, quercetin, 2, 3-dihydroquercetin, rutin, hesperidin, myricitrin and myricetin, and the synthetic 3′, 4′-dihydroxyflavonol, 6-chloro-3′, 4′-dihydroxyflavonol, 6-methyl-3′, 4′-dihydroxyflavonol and water-soluble 3′, 4′-dihydroxyflavonol-SO3Na, of which, 3′, 4′-dihydroxyflavonol was the most effective. It was assumed that for a compound to be effective as a capillary stabilizer, it was necessary for the flavonols or flavones to possess vicinal hydroxyls in the 3′- and 4′-positions, and a hydroxyl at 3-and a carbonyl at 4-position, since the methylation or acetylation of this hydroxyl decreases or obliterates this efficacy.
It was found that the most economical method for the preparation of 3′, 4′-methylenedioxyflavonol was by the alkaline condensation of heliotropin and o-hydroxyacetophenone, followed immediately, without isolating the 2′-hydroxy-3, 4-methylenedioxychalcone here formed, by the ring closure and oxidation with alkaline hydrogen peroxide. By the same method, 6-chloro-(m.p. 244-245°) and 6-methyl-3′, 4′-methylenedioxyflavonol (m.p. 195-196°) were obtained.
It was found that for the cleavage of methylenedioxy group in 3′, 4′-methylenedioxyflavonol, the addition of 2.3-2.5 moles of aluminum chloride in a solvent of nitro- or chlorobenzene gives the best results. This reaction can effectively be carried out when chloro or methyl radical is present in the 6-position. It was also found that the application of 5-6 moles of aluminum chloride, when there is a methoxy gronp present in the 4- and 7-positions of chromone nucleus, results in the concurrent cleavage of methylenedioxy radical and demethylation to quercetin.
It was found that the excretion of 3′, 4′-dihydroxyflavonol in urine and feces was very slight, being less than one-tenth of the amount administered. By paper partition chromatography, it was found that the urine contained three substances of different Rf values that must have been formed by physiological process. 3′, 4′-Dihydroxyflavonol was found to have no acute toxicity in mice, showing no histologic change in various organs after daily administration of the compound for 60 days.
Neutralization titration of weak acids was carried out using the high frequency volumetric analytical apparatus described in the previous report (This Journal 71, 705 (1951)). By the ordinary method, it is difficult to determine the end point but an excellent method was devised by the use of two procedures. One is the titration of definite amount of 0.1 N sodium hydroxide solution by the solution of weak acids to be tested, and the other is the addition of a very small amount of pyridine in the weak acid solution being tested. In the case of the latter, acids with a dissociation constants of around 10-7, i.e. acids with dissociation above that of the first dissociation of carbonic acid, can correctly be determined. In both cases, the solvent used is water. In the case of a mixture of two acids, as long as their dissociation constant is less than 10-3, they can separately be titrated without the addition of pyridine. Phenol, boric acids and others whose dissociation constant is less than 10-9 fail to react by this means even by the addition of pyridine that the presence of these compounds do not constitute a hazzard in this titration. It was found, however, that it was possible to titrate these very weak acids with dissociation constants less than 10-9 by the use of pyridine as the sole solvent.
Antibacterial action of various compounds possessing diphenyl ether as the fundamental nucleus was tested against human strain of Mycobacterium tuberculosis, Staphylococcus aureus and Escherichia coli. The results showed that none of the compounds possessed any remarkable growth inhibition against the tubercle bacilli although trilobine, one of the alkaloids of biscoclaurine type, showed a fair amount of antibacterial action far below that of p-aminosalycilic acid. Fairly high antibacterial action was shown by 2-hydroxydiphenyl ether against Staph. aureus and E. coli, by 3, 6-dibromo-4-hydroxydiphenyl ether against Staph. aureus, by 2, 2′-dihydroxydiphenyl ether against B. coli, and by diquinoline-6, 6′-oxide dimethiodide against Staph. aureus.
Antibacterial action of several derivatives of diphenylene dioxide, benzodioxane, phenoxthine and phenothiazine were tested against Mycobacterium tuberculosis (human strain), Staph. aureus and E. coli. Of the compounds tested, 2, 6-di-β-chloropropionyldiphenylene dioxide alone was found to possess a fairly high antibacterial action against these three microörganisms.
Antibacterial action of diphenyl sulfide, dipheny disulfide and thiazole derivatives were tested against human strain of Mycobacterium tuberculosis, Staphylococcus aureus and Escherichia coli. Of the compounds tested, 2, 2′-diaminodiphenyl disulfide was found to possess a strong antibacterial action against Staph. aureus.
Antibacterial action of alkyl- or cycloalkyl-resorcinols and their halogen derivatives were tested, in vitro, against Mycobaterium tuberculosis, Staphylococcus aureus and Escherichia coli. A group of compounds were found to have a strong antibacterial action against Staph. aureus, viz. decyl-, heptyl-, octyl- and hexyl-chlororesorcinols, in that order, strongly inhibited the growth of this microörganism.
By reacting phosphorus oxychloride on several 2-benzylamino-6-hydroxypyrimidines to 6-chloro compounds and by subsequent reduction, 2-benzylaminopyrimidines were obtained. Heating the 6-chloro compounds in alcoholic potassium hydroxide solution yielded 5-alcoxy compounds. 2-Benzylamino-4-methyl-6-hydroxypyrimidine was obtained by the condensation of benzylguanidine and ethyl acetoacetate. By the same procedure, 2-p-hydroxybenzylamino-4-methyl-6-hydroxypyrimidine was obtained from p-hydroxybenzylguanidine.
Having observed the formation of a large amount of o-methoxybenzylamine as a by-product during synthesis of p-methoxybenzylamine by the method of Herzberg and the others (D. R. P. 442, 774), examinations were made as to the best procedures for their separation and purification.
By the treatment of 3-[2′-methyl-4′-aminopyrimidyl-(5′)]-methyl-4-methyl-5-β-hydroxyethylthiothiazolone (2) (I) in acetic acid solution with oxidizing agents such as hydrogen peroxide, bromine, nitric acid, potassium chlorate, or potassium permanganate, or by electrolytic oxidation, sulfur outside the nucleus is oxidized to sulfuric acid and removed and vitamin B1 is formed. By the application of hydrogen peroxide in diluted sulfuric acid solution and by subsequent removal of sulfuric acid as barium sulfate, thiamine sulfate is obtained. In an acetic acid medium, thiochrome is partly formed. As has been described previously, the synthesis of (I) is very easy and the formation of thiamine from (I) is almost quantitative that the synthesis of vitamin B1 through (I) seems to be the best one of the known synthetic procedures.
In spite of the fact that the fatty acids constituting natural fatty oils generally possess even number of carbon atoms, the phenols obtained from plants generally possess alkyl side-chains composed of odd number of carbon atoms. Seizing on this fact, a biochemical formation of these phenols was assumed and based on that fact, a tentative structure of leprosol was proposed. In this assumption, one of the chain in the most probable structure, 4, 5, 6-trialkylresorcinol, was thought to be C17H35, and the remaining two of methyl groups, giving the empirical formula of (C6H)(OH)2(CH3)2(C17H35) This would be an isomer of nor-methyl-leprosol, C25H42(OH)2. Since it seemed interesting to find what properties the compounds would show compared to the natural substance, their A-type compound, 4, 6-dimethyl-5- and 4, 5-dimethyl-6-heptadecylresorcinols were synthesized.
Following the previous experiments, the two kinds of B-type compounds, 2, 6-dimethyl-5- and 2, 5-dimethyl-6-heptadecylresorcinols, and a C-type compound, 2, 4-dimethyl-6-heptadecylresorcinol, were synthesized. Coloration reactions according to the method of Butenandt and Stodola, and ultraviolet absorption spectra were made with these five kinds of resorcinol derivatives, including two A-types, and compared with those of nor-methyl-leprosol. As far as these comparisons went, the coloration was identical and the absorption spectra gave approximately similar curves. The melting point of 4, 6-dimethyl-5-heptadecylresorcinol was comparatively similar to that of nor-methyl-leprosol, but those of the others were far lower. The present set of model experiments has not given any determining factor in the assumption of which type most well represented nor-methyl-leprosol.
For one year between 1950 and 1951, specific weight of tissue powder of rhizomes without roots of Scopolia japonica Maxim., growing wild in a certain area, was measured by Koketsu's powder method and a marked seasonal variation was found to exist (Table I and Fig. 1). The cause of this variation was found to be due to the amount of starch accumulated (Table I and Fig. 2). Consequently, it was proposed that tne customary representation of its component content by the weight percentage was of little physiological significance. Therefore, the determined values of total alkaloid and total nitrogen were shown by the volume percentage calculated from specific weight of tissue powder (Table I and Fig. 3). From these values, a large seasonal variation of alkaloidal content could not be detected.
In order to examine the chemical activity of the phenanthridine nucleus, Claisen conversion of 2-allyloxy and 1-allyl-2-allyloxy-9-methylphenanthridine was carried out. From the manner of azo coupling and Mannich reaction of the conversion products, it was concluded that the phenanthridine nucleus possessed a naphthoid activity.
Pyrogen test of parenteral solutions that decreased the body temperature of normal rabbits was comparatively examined by the method described by the United States Pharmacopoeae and by the dorsal fixation, subcutaneous administration and calcium precipitation (sodium sulfate and carbonate) methods. Administration of calcium or sodium salicylate to rabbits fixed on its back, do not result in the decrease of their body temperature but administration of pyrogenous material results in temperature rise. It seems that the most suitable test method for pyrogens in parenteral solutions is by rabbits fixed on its back.
By reacting 2-methyl-4-amino-5-aminomethylpyrimidine (I) and γ-aceto-γ-thiocyanopropyl acetate (II) in butanol 3-[2′-methyl-4′-aminopyrimidyl (5′)]-methyl-4-methyl-5-β-acetoxyethylthiazolone imide (2) (V), m.p. 208° (picrate, m.p. 208° (decomp.)), was obtained with a concurrent formation of acetylthiochrome (IV). Hydrolysis of (V) with diluted hydrochloric acid yields 3-[2′-methyl-4′-aminopyrimidyl (5′)]-methyl-4-methyl-5-β-hydroxyethylthiazolone imide (2) (VI), m.p. 228°, which gives a hydrochloride of m.p. 267-268° (decomp.), and a picrate which melts once at 195° and decomposes with blackening and effervescence at 220°. (VI) can also be obtained by the reaction of 2-methyl-4-amino-5-bromomethylpyrimidine hydrobromide (VII) and 2-amino-4-methyl-5-β-hydroxyethylthiazole (VIII) in dioxane or butanol with subsequent liberation by alkalis. Both these processes, however, give poor yield of (VI) which inhibits the growth of Staphylococcus aureus and acts as an antagonist to thiamine.
By the application of cuprous cyanide to 4-methyl-2, 5-dibromothiazole (I) in nitrobenzene at 200-210°, 2-cyano-4-methyl-5-bromothiazole (II) and its acid amide (III) were obtained but with a very poor yield. (II) can also be obtained by the diazotization of 2-amino-4-methyl-5-bromothiazole followed by the application of cuprous cyanide to change to the nitrile. Hydrolysis of (II) yielded (III), 4-methyl-5-bromothiazole-2-carboxylic acid (VI) and its ammonium salt (V). (V) and (VI) easily liberate carbon dioxide by thermal decomposition to give 4-methyl-5-bromothiazole (VII).
In an attempt to find new antihistaminics of the Antergan type, the Beckmann rearrangement reaction was applied to 3, 4-methylenedioxy-α-dimethylaminopropiophenone oxime (IV) and α-piperidino derivative (VII), expecting the amide (VIII) and its analogs as the rearrangement products. 3, 4-Methylenedioxybenzonitrile (V), however, was obtained in nearly quantitative yield, either in chloroform-thionyl chloride or ether-phosphorus pentachloride procedure. A small amount of piperidine, but not dimethylamine, was traced in the reaction product as its picrate, the second half of the molecule of the oxime being largely converted into viscous, unidentifiable substance, probably a vinylamino polymer. The result is more or less simil ar to that of the Beckmann rearrangement of the second order. The action of toluenesulfonyl chloride upon the oxime in the presence of alkali again gave (V), but toluenesulfonyl chloride alone in pyridine or alkali solution (potassium hydroxide) only ended in recovery of the oxime.
In order to obtain asym. α-diketone derivatives, 4-alkoxy-4′-nitrodesoxybenzoin was synthesized by condensing p-nitrophenacetyl chloride with phenyl alkyl ether, in which the alkyl was methyl, ethyl, propyl, isopropyl or butyl. These substdnces were converted easily to benzilmonoöxime, except the isopropyl derivative, and then to p-nitroalkoxybenzil by hydrolyzing.
By the condensation of carbon disulfide with aminoacetonitrile (dl-α-amino-β-ethylidenepropionitrile) and benzaldehyde (p-acetaminobenzaldehyde), 2-mercapto-5-benzylidene, 2-mercapto-5-p-acetaminobenzylidene- and 2-mercapto-4-propenyl-5-p-acetaminobenzylidene-aminothiazoles were obtained. Alkyl, allyl and benzyl derivatives of these mercapto compounds were subsequently prepared.
By the respective condensation of carbon disulfide with aminoacetonitrile (dl-α-amino-β-ethylidenepropionitrile) and cinnamic aldehyde (p-dimethylaminobenzaldehyde), 2-mercapto-5-cinnamal-, 2-mercapto-5-p-dimethylaminobenzylidene- and 2-mercapto-4-propenyl-5-cinnamal-aminothiazoles were prepared and were led to their alkyl, allyl and benzylmercapto derivatives.
4-Methoxy-5-methylal-α-chlorotoluene and 3, 3′-dimethylal-4, 4′-dimethoxydiphenylmethane were obtained by the chloromethylation of 2-methoxybenzaldehyde with formaldehyde, hydrochloric acid gas and zinc chloride.
Following alkylisoquinoline derivatives were synthesized and their properties compared: 1-propyl-, 1-butyl-, 1-amyl, 1-hexyl-, 1-heptyl, 1-octyl-, 1-δ-methylamyl- and 1-α-ethylamyl-6, 7-methylenedioxy-3, 4-dihydroisoquinoline.
Following isoquinoline derivatives possessing alicyclic alkyl group in the 1-position were synthesized: 1-cyclohexyl-6, 7-methylenedioxy-3, 4-dihydroisoquinoline, 1-cyclohexyl-2-methyl-6, 7-methylenedioxy-1, 2, 3, 4-tetrahydroisoquinoline, 1-cyclohexylmethyl-6, 7-methylenedioxy-3, 4-dihydroisoquinoline and 1-cyclohexylmethyl-2-methyl-6, 7-methylenedioxy-1, 2, 3, 4-tetrahydroisoquinoline.
Acid amide was prepared from the amine obtained by the reduction of the oxime of benzyl propyl ketone. The isoquinoline cyclization of this acid amide yielded 1-phenyl-3-propyl-(3′, 4′, 5′-trimethoxyphenyl)-3-propyl-and 1-(3′, 4′-methylenedioxyphenyl)-3-propyl-3, 4-dihydroisoquinolines. These were then led to N-methyl-1, 2, 3, 4-tetrahydroisoquinolines.
Condensation of butyl and isoamyl bromides to benzyl methyl ketone yielded α-phenylamyl methyl ketone and α-phenyl-δ-methylamyl methyl ketone. Their respective oximes were reduced to amines, led to their acid amides which were used to synthesize 1-(3′, -4-methylenedioxyphenyl)-3-methyl-4-butyl-, 1-(3′, 4′, 5′-trimethoxyphenyl)-3-methyl-, 1-(3′, 4′-methylenedioxyphenyl)-3-methyl-4-isoamyl- and 1-(3′, 4′, 5′-trimethoxyphenyl)-3-methyl-4-isoamyl-3, 4-dihydroisoquinolines. These were led to N-methyl-1, 2, 3, 4-tetrahydroisoquinolines by the ordinary method.
Butyl and isoamyl bromides were respectively condensed with benzyl propyl ketone to yield α-phenylamyl propyl and α-phenyl-δ-methylamyl propyl ketones. Their oximes were reduced, led to their amines and then to acid amides, and finally submitted to isoquinoline cyclization yielding 1-(3′, 4′-methylenedioxyphenyl)-3-propyl-4-butyl- and 1-(3′, 4′-methylenedioxyphenyl)-3-propyl-4-isoamyl-3, 4-dihydroisoquinolines. The former was led to N-methyl-1, 2, 3, 4-tetrahydroisoquinoline by the usual method.
Benzyl and anisyl chlorides were respectively condensed with benzyl methyl ketone to yield α, β-diphenyl and α-phenyl-β-(p-methoxyphenyl)-ethyl ketones. Their oximes were reduced, led to amines, condensed with acid amides by the application of acid chloride and submitted to isoquinoline cyclization. Final products were: 1, 3-dimethyl-4-benzyl-, 1-phenyl-3-methyl-4-benzyl-, 1-styryl-3-methyl-4-benzyl- and 1-(3′, 4′, 5′-trimethoxyphenyl)-3-methyl-4-anisyl-3, 4-dihydroisoquinolines.
Condensation of isatin and phenoxyacetone by the Pfitzinger reaction yields 3-phenoxy-4-quinaldine-carboxylic acid and 2-phenoxymethyl-4-quinoline-carboxylic acid in a 3:1 ratio. It was found that the ether linkage of the phenoxymethyl group in the latter compound is cleaved comparatively easily.
By the replacement reaction of racemic methionine methyl ester hydrochloride with ammonium α-chloro-d-camphor-γ-sulfonate in aqueous solvent, L-methionine ester sulfonate, m.p. 153-154.5°, and the corresponding D-series compound, m.p. 160-162°, were obtained with respective yield of 85% and 73.4%. Hydrolyses of these with sodium hydroxide yielded L-methionine, in 73.5% yield, and D-methionine, in 72.1% yield. By the treatment of D-methionine with acetic anhydride and sodium hydroxide, acetyl-DL-methionine was obtained in 86% yield. Treatment of D-methionine with benzoyl chloride and sodium bicarbonate gave benzoyl-DL-methionine in 82.4% yield.
High pressure hydrogenation of matrine in dioxane with copper chromite as a catalyst gives matridine in a 95% yield. Matridine is obtained as white needles, m.p. 76°, b.p.5 153-154°, [α]D8=+28.8° (in absolute alcohol), and gives a dipicrate of needles, m.p. 265° (decomp.). These values are different from those of known sparteine and its isomer.
By the extraction of the fresh fruit of Rosa polyantha Sieb. et Zucc. (R. multiflora Thunb.) with ether, dark reddish fatty oil was obtained in 9.4% yield. The fatty acids were separated into saturated acids (39.7%), composed of palmitic (49.1%) and stearic (23.6%) acids, and unsaturated acids (60.3%), by Twitchell's method. The unsaturated acids were brominated and the presence of linoleic and linolenic acids was established. The pigments of pericarp consisted of lycopene and a small amount of α-carotene. Phytosterol, triterpenoid and quercetin were also isolated from the ethereal extract of the fruit.
Practical process of electrolytic manufacture of sugar was examined as to the electrolytic method and the effect of ξ potential of diaphragm in a two-chamber type. As a result, it was found that the three-chamber method in which acid saccharifying solution is placed in the middle chamber effected too large a ξ potential of the porcelain plate due to high voltage, and the movement of the acid saccharifying solution to the cathode chamber became greater before electrolytic neutralization could be expected. In a two-chamber process, using gelatine coated porcelain diaphragm, the passage of acid ions became slightly easier but on the other hand acid saccharifying solution (cathode solution) filtrated into the anode chamber resulting in too great a loss of sugar. This rules out the advisability of gelatine coating of the diaphragm. From the point of increasing monosaccharide by electrolysis it seemed most advantageous to employ a two-chamber process of electrolysis using a porcelain diaphragm.
1) Benzo-(h)-quinoline-N-oxide m.p. 123°, is formed when benzo-(h)-quinoline is heated with hydrogen peroxide and glacial acetic acid above 100°. Refluxion of this compound with acetic anhydride yields 2-hydroxybenzo-(h)-quinoline, m.p. 256°. 2) Benzo-(h)-quinoline-N-oxide gives a 2-cyano derivative, m.p. 161-162°, by the Reissert reaction, and is hydrolyzed to 2-carboxyl derivative, m.p. 181-182°. 3) Benzo-(h)-quinoline-N oxide differs from other aromatic amine-N-oxides in that it is partially reduced by SO2 gas to yield a small amount of benzo-(h)-quinoline. 4) Nitration of 2-hydroxybenzo-(h)-quinoline gives 7-nitro derivative.
Nitration of benzo-(h)-quinoline-N-oxide at 40°, 60°, 70° and 115° with conc. H2SO4 and KNO3 gives 7-nitro- (m.p. 220°), 9-nitro- (m.p. 242°), 10-nitro- (m.p. 238° (decomp.)) and dinitro- (m.p. 255° (decomp.)) derivatives and does not yield 4-nitro compound. This benzo-(h)-quinolino-N-oxide, differing from those of pyridine and quinoline does not show any polar effect of the N-oxide group against its para position.
By what mechanism and in what order the chemical reactions in high frequency titration are recognized were examined. The change in the condition of the solution was found to be transmitted by change in electric capacity, either when condenser or coil is used, followed in the latter case by the change in electric inductance. It was also found that the band in which both effects appeared markedly was automatically defined. From these results, it can be seen that the chemical reaction effects changes in the number of cycles and amplitude of the oscillator which, when received on a suitable receiver, are observed as a change in a direct current.
A simple apparatus was devised whereby amino acids and bases posseissng different electrical properties such as dissociation constants are separately detected by electrophoresis on a filter paper saturated with a buffer solution. By this means, separation of monoamino-monocarboxylic, monoamino-dicarboxylic and diaminomonocarboxylic acids was carried out. It was found possible to separate arginine, histidine and lysine from each other and glutamic and aspartic acids from their mixture separation of arginine and octopine, histidine and histamine, N-methylpyridinium hydroxide, N-methylnicotinic amide and homarine from an extract. Separation of trigonelline and homarine from each other was rather difficult. It was also possible to detect by this means albumin, α2-globulin β-and γ-globulin from serum proteins.
The existing method of detecting N-methylpyridinium hydroxide in animal extract involves the use of its aurate. A new method was devised whereby the base was adsorbed on cation exchange resin, Amberlite IRC-50 and a phenoxyacetic acid-formal-dehyde resin, KH-4B, and desorbed by hydrochloric acid. The acid residue is extracted with ohloroform and this is submitted to paper partition chromato graphy or paper micro-electrophoreris, and finally proved by the Dragendorff reagent. This allows detection of a minute amount of N-methylpyridinium hydroxide. Using the paper chromatographic method, 1.2mg. of this substance was detected per 1kg. of Corbbicula sandai Reinhardt.
Crystallographic constants of Tibione, p-acetylamino-benzaldehyde thiosemicarbazone, were determined by X-ray crystallography and goniometry. Some observations were also made on the molecular distribution of Tibione in its crystal. Crystallographic constants obtained were as follows: Crystalosystem: monoclinic Axial ratio: a:b:c=2.069:1:4.234 Unit cell: a0=13.16Å, b0=6.38Å, c0=27.01Å Axial angle: β=95°15′ Density: ρ=1.368 Space group: C2h5-P21/c No. of Tibione molecule in unit a unit cell: Z=8
Further examinations were made for substances which acted to reduce the body temperature of rabbits fastened on its back. In order to make pyrogene test of parenteral solutions, a rabbit is fastened on its back so as to control the lowering of body temperature, increase susceptibility to pyrogenous substances, and facilitate measurement of bodytemperature. By repeated operation of fastening a rabbit to its back, the temperature variation can be controlled to a minimum.
1) A few minutes' heating of acetylacetone and sulfanilamide or sulfaguanidine at 110° yields N4-(4′-oxo-amylidene-(2′))-sulfanilamide or -sulfaguanidine. 2) Reaction of acetylacetone or ethyl formylacetate with pyridine or 2-methylpiperidine gives piperidyl-vinyl-carbonyl compounds. 3) Heating piperidyl-vinyl-carbonyl cmpounds with sulfaguanidine results in the formation of sulfapyrimidines in good yields.
2-Phenoxypyrimidine was prepared from 2-chloropyrimidine and phenol. Application of benzylamine to the former yielded 2-benzylamino pyrimidine. In a similar manner, 2-phenoxy- and 2-β-naphthoxy-4-methylpyrimidines were prepared from 2-chloro-4-methylpyrimidine and reacted with amino compounds to obtain 2-benzylamino-, 2-p-methoxybenzylamino-, 2-anilino- and 2-(dimethylaminoethyl)-amino-4-methylpyrimidines. Application of benzylamine to 2-ethoxy-4-methylpyrimidine, obtained from 2-chloro-4-methylpyrimidine, by heating resulted in the formation of a small amount of 2-benzyl-amino-4-methylpyrimidine and N, N′-dibenzylurea.
N, N-Dimethyl-N′-benzylethylenediamine and N, N′-dimethyl-N′-(p-and o-methoxybenzyl)-ethylenediamine were obtained by the respective application of dimethylaminoethyl chloride hydrochloride to benzylamine, and p- and o-methoxybenzylamine. Six kinds of N, N′-dimethyl-N′-benzyl-N′-(2-pyrimidyl)-ethylendiamines were prepared by the respective reaction of 2-chloropyrimidine and 2-chloro-4-methylpyrimidine to the above substances.