α-Lipamide (IV) is obtained from α-lipoic acid (I) by application of ammonia to the reaction product of (I) and either ethyl chlorocarbonate, butyl chlorocarbonate, phosphoryl chloride, or diethyl phosphorochloridate. (IV) also forms on application of ammonia to α-lipoic anhydride (IX) or methyl α-lipoate (X). A new compound, 6, 8-dichloroöctamide (XV), was prepared by application of ammonia to methyl 6, 8-dichloroöctanoate (XI) or 6, 8-dichloroöctanoyl chloride (XIV), or to the reaction product of 6, 8-dichloroöctanoic acid (XII) and alkyl chlorocarbonate. (XV) is converted to α-lipamide (IV) by reaction with potassium thiocyanate or sodium disulfide.
A Mannich base was obtained in 70-80% yield by stirring a mixture of 4-hydroxyisoquinoline, 35% formaldehyde solution, and dimethylamine or piperidine in methanol. The free base is unstable but its dihydrochloride is stable. Catalytic reduction of this base over palladium charcoal afforded 3-methyl-4-hydroxyisoquinoline, m. p. 179-180°, in 60-70% yield and the Mannich base was established as 3-dialkylaminomethyl-4-hydroxyisoquinoline.
Application of the Grignard reagent to 2- or 3-alkyl-4-cyanopyridine afforded 2- or 3-alkyl(or aryl)-4-carbonylpyridine and the Bucherer reaction was attempted with these ketones. The reaction proceeded smoothly with the ketones possessing a substituent in the 2-position of the pyridine ring but the reaction did not occur at all in the ketones with a substituent in the 3-position. 4-(2-Thienylcarbonyl)-pyridine afforded the corresponding hydantoin in a low yield and the majority was recovered unchanged.
Glycerol 1-phosphate was obtained in 72% yield by the reaction of isopropylideneglycerol and bis(2, 4-dichlorophenyi) phosphonochloridite, in the presence of a tertiary amine, oxidation of its product with tert-butyl hydroperoxide, and final hydrolysis with an acid. In a similar manner, D-glucose 6-phosphate (in 71% yield) and D-galactose 6-phosphate (in 76% yield) were obtained respectively from 1, 2, 3, 4-tetra-O-acetyl-β-D-glucopyranose and 1, 2:3, 4-di-O-isopropylidene-D-galactopyranose. On the other hand, a 7:3 mixture of D-glucose 6-phosphate and 3-phosphate was obtained in 76% yield from 1, 2:5, 6-di-O-isopropylidene-D-glucofuranose.
The structure of the new coumarin compound, angelicone, isolated from the root of Angelica schishiudo KOIDZ. (Umbelliferae), was established as 5, 7-dimethoxy-8-(3-methyl-2-butenoyl)coumarin by the acid decomposition reported in the preceding paper and by alkali decomposition reported in the present paper. Consequently, angelicone is identical with glabra-lactone isolated from the root of A. glabra MAKINO, and it was decided to adopt the name of angelicone as the correct designation, with glabra-lactone as an alias. Infrared spectral analyses were made on angelicone, its alkaline decomposition product, and their related compounds. Color reaction to the Gibbs and Emerson reagent was also examined.
Microbiological oxidation of digitoxigenin (I) by Rhizopus arrhizus gives a kind of monohydroxydigitoxigenin (IIa) which does not agree with either digoxigenin, gitoxigenin, or sarmentogenin. Since (IIa) forms a diacetate, it is not 11β-hydroxydigitoxigenin and since the bis-dehydro compound (IV) obtained by oxidation of (IIa) with chromium trioxide is not digoxigenone, (IIa) does not have a hydroxyl in 12-position. Infrared spectrum of (IV) suggests the presence of two six-membered ring carbonyls and this suggests that the new hydroxyl introduced into (IIa) is not in D-ring. Since the ultraviolet spectrum and ferric chloride reaction of (IV) do not indicate the presence of α- or β-diketone, the new hydroxyl cannot be in the A-ring. Treatment of (VI) with hydrochloric acid does not cause isomerization to the 5α compound, which denies 3, 6-diketone structure for (IV). These experimental results suggest that the newly introduced hydroxyl is in 7-position. The presence of α, β-unsaturated ketone in the anhydro compound (V) of (IV) is indicated by its ultraviolet spectrum and this satisfies the above assumption. Application of carbonyl chloride to the 3-dehydro compound (IIIa) of (IIa) afforded 7β, 14β-carbonate (VI) and (IIa) was established as 7β-hydroxydigitoxigenin.
1-Arylamino-1-deoxy-D-glucuronamide was prepared from D-glucuronamide and arylamine and 1-arylamino-1-deoxy-2, 3, 4-tri-O-acetyl-D-glucuronamide (III) obtained by its acetylation was found to be the same as that obtained from 1, 2, 3, 4-tetra-O-acetyl-D-glucuronamide (α- and β-forms) (IV) and 1-bromo-l-deoxy-2, 3, 4-tri-O-acetyl-α-D-glucuronamide (V). It was revealed from these facts that (II) is an N-glucopyranoside with a pyranose ring.
Amadori rearrangement reaction was carried out on D-glucuronamide and arylamine and the amide of 1-arylamino-1-deoxy-D-fructouronic acid was obtained as crystals. The amide of 1-p-anisidino-1-deoxy-D-fructouronic acid was obtained as two kinds of inter-convertible crystals which were found from their infrared spectra to be the carbonyl type and the lactol type with a furanose ring.
As a general rule in analgesics, when a hydroxyl is introduced in the benzene ring, the potent compound has m-hydroxyl against the quaternary carbon bonded directly to the benzene ring. N-(2-tert-Aminoalkyl)propionanilides, possessing a hydroxyl in the benzene ring, were prepared and their analgesic action was examined. As a result, it was revealed that the most potent compound also has a hydroxyl in meta position against the tertiary nitrogen bonded directly to the benzene ring when in the meta position.
Application of acetaldehyde to threonine-copper chelate gives two kinds of crystals, α and β. In order to elucidate their structure and properties, measurement with thermobalance was carried out. Weight-loss curve at the time of heating of the substance showed ca. 9.5% loss in both α- and β-crystals, and this decrease was found to correspond to 2 moles of water of crystallization. The fact was also confirmed by recovery of the original weight by application of water vapor to the substance with decreased weight caused by heating. Dissociation pressure did not show a great value and dissociation energy was found to be similar to that of crystal water. Analysis of the volatile matter produced on heating showed it to be water.
In order to elucidate the chemical structure of two forms, α- and β-crystals, of threonine-copper-acetaldehyde compound, infrared spectral comparison was made on their anhydrates and rehydrated compound. The infrared absorption of the anhydrite showed the same spectrum in both forms. The anhydrite of β-crystal, when water vapor was allowed to be absorbed up to 0.4 specific pressure, showed the same spectrum as that of the β-crystal but when more water was allowed to be absorbed and then desorbed, its infrared spectrum was the same as that of the α-crystal. This showed that the β-crystal easily transited to the α-crystal in the presence of excess water. The ligand in both crystals is a Schiff base with acetaldehyde bonded to the amino group, the crystals possess two moles of water of crystallization, and their chemical structure is the same. The difference in their infrared absorption spectra was assumed to be due merely to the difference in crystal structure.
trans-Bis (N-ethylidene-DL-threoninato) copper (II) dihydrate comes in α- and β-form crystals, both melting at 202-203° with decomposition. The α-form crystal is a monoclinic holohedral class and the β-form crystal belongs to the triclinic holohedral class, the α-form crystal having C2h-2/m and β-form, Ci-1. These crystals were proved to be polymorphic forms by their comparative examination through X-ray powder and chemical methods.
In order to determine the structure of trans-bis(N-ethylidene-DL-threoninato)copper (II) dihydrate (α-form), X-ray crystal analysis was carried out on a single crystal, chiefly on (010) face, using Patterson and Fourier projection. This crystal has two molecules in unit lattice, is a monoclinic, and its space group is P21/c. The dimensions of the monoclinic cell are: a=11.41 Å, b=7.26 Å, c=10.63 Å, β=100°. From the electron density projection obtained from structural analysis, this chelate was found to have OH and COOH groups coordinating to the copper atom in a square planar and its ligand is a Schiff base with N-ethylidene group.
The structure of β-form of trans-bis (N-ethylidene-DL-threoninato) copper (II) dihydrate was presumed by the use of Patterson projection, P (UV). This crystal has one molecule in unit lattice and a projection close to that of electron density was obtained, making it easy to analyze its structure. The crystal is a triclinic, its space group is P1, and lattice constants are: a=9.90Å, b=8.91Å, c=5.54Å; α=102°, β=100°, γ=74°. The structure model obtained from crystal analysis of the α-form was found to place each atom at the maximum position on P(VU) merely by correcting slightly the inclination angle against (001) face. These facts showed that the chemical structure of β-form crystal is the same as that of the α-form.
Present series of work was carried out in order to prepare a hematopoietic with amino acid derived to iron (II) chelate. As reported in Parts I to V, trans-bis(N-ethylidene-DL-threoninato) copper (II) dihydrate is a special kind of a chelate with OH and COOH coordinated to the copper atom. This suggested that the same chelate may be formed with bivalent iron and examinations were made. It was thereby found that, of the requisite amino acids, α-amino acids possessing OH or SH group formed a stable chelate with iron (II). From its chemical properties and ultraviolet and infrared absorption spectra, this iron (II) chelate was assumed to have two molecules each of N-alkylidene-α-amino acid with OH or SH group and water molecule as the ligands, and coordinated with OH or SH and COOH groups.
1) Conditions necessary for the strongest specific coloration were examined for application of anthrone reagent to aqueous solution containing 50γ of D-glucose and 50γ of L-tryptophan, and the amount of reagent to be used, concentration of the reagent, and period of heating were determined. 2) In optimal conditions and in the presence of an equal amount of D-glucose and L-tryptophan, the optical density was found to become the maximum at 530mμ. 3) Optical density was measured in a solution of equal amounts of L-tryptophan and several kinds of sugars other than D-glucose. The result same as that described in (2) was obtained with hexoses and D-fructose showed the greatest absorbance. 4) Quantitative ratio of L-tryptophan and sugar in the sample solution was changed and variation in the absorbance at 530mμ was measured. When the amount of L-tryptophan was made constant and the amount of D-fructose varied, absorbance increased linearly in proportion to the increase of sugar but when the amount of D-fructose was made constant and the amount of L-tryptophan varied, absorbance did not increase proportionally unless the amount of L-tryptophan was twice that of D-fructose.
In order to prepare water-soluble derivatives of Phenobarbital and to examine their pharmacological activity, the compounds listed in Table I were prepared from the sodium salt of phenobarbital, using the reaction routes A, B, and C in Chart 1. Results of pharmacological tests on these synthesized compounds are shown in Table II.
The quinoline containing radioactive carbon, obtained by the reaction of aniline and acrolein [3-14C] diacetate, was derived through its 1-oxide to carbostyryl, oxidized with potassium permanganate to kynuric acid, and hydrolyzed into oxalic acid and anthranilic acid. The radioactive carbon was found to be in oxalic acid. This has revealed that the synthesis of quinoline from aniline and acrolein was effected by the mechanism (a) in Chart 1. The reaction of quinoline synthesis from aromatic primary amines and acrolein diacetate is affected by the acidity of the reaction mixture and the yield varies through the maximum with increasing acidity, In the case of p-nitroaniline, with weaker basicity than aniline, the optimal acidity is higher than that of aniline and this phenomenon can be explained by detailed analysis of the mechanism (a) shown in Chart 1.
Nitration of 1-methylphenazine 5-oxide (I) with potassium nitrate and sulfuric acid at a low temperature gives a mononitro compound (II), m. p. 210°. Refluxing of (II) with methanolic potassium hydroxide results in substitution of the nitro group with methoxyl and 1-methyl-x-methoxyphenazine 5-oxide (III) is formed. Polarization effect of the N-oxide group in (I) is assumed to appear at 3-, 7-, and 9-positions and synthesis of 1-methylphenazines with the methoxyl in 3-, 7-, or 9-position was attempted. The Wohl-Aue reaction of p-anisidine and m-nitrotoluene afforded 1-methyl-7-methoxyphenazine (VI), m. p. 147°, and its N-oxide (VII), m. p. 182°. The same reaction of o-anisidine and m-nitroanisole gave (VII) and 1-methyl-9-methoxyphenazine (IX), m. p. 164°, that of o-anisidine and m-nitrotoluene afforded (I) alone, and the reaction of o-nitroanisole and m-toluidine, (IX) alone. (VI) and (IX) did not agree with 1-methyl-x-methoxyphenazine (IV), m. p. 152°, obtained by deoxygenation of (III). Condensation of 3-methyl-4-nitroanisole and aniline was attempted in order to obtain a 3-methoxy compound but the objective compound was not obtained. Consequently, (IV) cannot be compared directly but it was assumed to be a 1-methyl-3-methoxy derivative since it did not agree with either of the known samples of 1-methoxy-6-methyl- and 1-methoxy-4-methylphenazines.
Oxidation of codeine and morphine with ceric ammonium nitrate and application of 2, 4-dinitrophenylhydrazine results in orange-red coloration. Thebaine, narcotine, and papaverine color yellowish to this reaction and can therefore be discriminated from the former two. Limit of detection is 1.5γ/0.05cc. In quantitative determination, interfering thebaine, narcotise, and papaverine must be removed. The procedure for determination of codeine is as follows: One cc. of aqueous solution of codeine (30-240 γ/cc.) is placed in a 5-cc. measuring flask, 2cc. of water is added, and the mixture is allowed to stand in crushed ice (0 to 2°) for 5 minutes. To this solution, 1cc. of 0.6% ceric ammonium nitrate (in N sulfuric acid), which had been stood in crushed ice for 5 minutes, is added, mixed well, and allowed to stand at that temperature for 25 minutes. To this mixture, 0.5cc. of 0.6% 2, 4-dinitrophenylhydrazine solution is added, the flask is removed from the ice bath, and allowed to stand at room temperature for 20 minutes. The mixture is diluted to 5cc. with water, shaken well, and transferred to a glass-stoppered centrifuge tube. Ten cc. of isoamyl acetate is added to the tube, shaken 100 times, and centrifuged for 3 minutes. Isoamyl acetate layer is discarded, 5cc. of fresh isoamyl acetate is added, and treated in the same manner. Absorbancy of the aqueous layer is measured at 500mμ. A blank test is carried out with the same reagent and in the same manner, using 1cc. of water in place of the test solution, and used as the control. In the presence of thebaine, the test solution is heated with N hydrochloric acid, basified with sodium hydroxide, and shaken with chloroform to transfer codeine into the chloroform layer. In the presence of narcotine and papaverine, the test sample is dissolved in 0.2% tartaric acid, shaken with chloroform, and the aqueous layer is submitted to determination of codeine as above.
Examinations ware made on the analysis of morphine by ceric ammonium nitrate-2, 4-dinitrophenylhydrazine method. The limit of detection by this method is 1.5γ/0.05cc. Thebaine and papaverine interfere in this determination and both must be removed by a simple separation procedure. Narcotine did not affect the resulting data but there is a fear of its having caused secondary reaction, so that its separation was also examined. The procedure for this determination is the same as that described for codeine, with ceric ammonium nitrate as 0.4% solution and period of reaction at 20 minutes. When codeine is present, the test solution is shaken with chloroform in the presence of sodium hydroxide, and morphine is determined with the aqueous layer, codeine with the chloroform layer. When thebaine is present, morphine is determined with the aqueous layer obtained by treatment as above. When both narcotise and papaverine are present, they are separated by treatment as in the case of codeine, and morphine is then determined.
Precipitation and coloration reaction of 5, 6-dihydroxy-1, 4-naphthoquinone (I) and 6, 7-dihydroxy-1, 4-naphthoquinone (II) with metal ions were examined and their limit of identification was sought. Of 26 kinds of common metal ions, (I) underwent sensitive precipitation and coloration with Ag+, Hg2+, Cu2+, and Fe3+ at pH 1 and formed precipitates or chelates at pH 5 with those ions and Al3+ and Cr3+, (I) produced color with Sn4+ and Sb3+ at pH 1-5. (II) reacted sensitively with Al3+ at pH 1-5, somewhat insensitively with Fe3+ at pH 5-8, and somewhat sensitively with Bi3+, Sn4+, and Sb3+ at pH 1, but (II) did not produce any precipitate. Patio of bonding between (II) and Sn4+ or Bi3+ in acid solution was measured by the continuous variation method and the composition of Sn4+: (II) of 1:1 and Bi3+: (II) of 1:2 was indicated.
In order to obtain synthetic high polymer enteric coating agent, various copolymers of methyl acrylate, acrylic acid, methyl methacrylate, and methacrylic acid were synthesized. These polymers were examined for their solubility in simulated gastric and enteric juice, permeability of water vapor through the film, and their viscosity and disintegrability were measured. Their availability as enteric coating agent was also examined and comparative examinations were made with shellac and cellulose acetate phthalate. It was thereby found that excellent enteric coating agent is found in methyl acrylate-acrylic acid system containing 9-42 molar % of free acid, methyl methacrylate-methacrylic acid system with around 70 molar % of free acid, and methyl acrylate-methacrylic acid system with 19-52 molar % of free acid. These polymers were also found to have better water vapor permeabilty and disintegrability than shellac or cellulose acetate phthalate.
Two Arndt-Eistert reactions were carried out on 3-phenylvaleric acid to prepare 5-phenylheptanamide. The Reformatsky reaction of propiophenone and ethyl 2-bromopropionate, followed by dehydration and reduction afforded a mixture of two isomers of 2-methyl-3-phenylvaleric acid, which were successfully separated by chromatography through silica gel. Attempted stereospecific preparation of one of the isomers alone failed. Each isomer was submitted to two Arndt-Eistert reactions and the corresponding ethyl 4-methyl-5-phenylheptanamide was obtained. The Reformatsky reaction of indanone and ethyl 2-bromopropionate, followed by dehydration, saponification, and catalytic reduction afforded only one isomer (XIIIa) of α-methyl-1-indanacetic acid. In this case, reduction with sodium and ethanol gave a mixture of two isomers and recrystallization of this mixture from petroleum ether afforded the other isomer (XIIIb). Two Arndt-Eistert reactions of (XIIIa) afforded 4-methyl-butyramide but this reaction did not take place in the case of (XIIIb), being accompanied by isomerization. α-Ethyl-5, 6, 7, 8-tetrahydro-2-naphthaleneacetonitrile (XVIII) was obtained from 5, 6, 7, 8-tetrahydro-2-naphthaleneacetonitrile and ethyl bromide. (XVIII) was derived to its methyl ester by the action of hydrogen chloride gas in methanol and its dehydrogenation reaction over palladium-carbon afforded α-ethyl-2-naphthaleneacetic acid, while saponification of (XVIII) afforded α-ethyl-5, 6, 7, 8-tetrahydro-2-naphthaleneacetic acid.
Reaction of propiophenone and ethyl succinate in tert-butanol, in the presence of potassium tert-butoxide, at below 10° afforded the half ester of 4-ethyl-4-phenylitaconic acid. The dibasic acid obtained by its saponification formed an anhydride with conc. sulfuric acid from which the ethoxycarbonyl and phenyl groups in the half ester are in trans. This trans-configuration was also revealed by comparison of ultraviolet absorptions of the half-ester of 4-ethoxy-4-phenylitaconic acid. One-sided addition of hydrogen to this half ester, its Hunsdiecker reaction, and reductive substitution of the bromine compound thereby formed with hydrogen, followed by saponification afforded threo-2-methyl-3-phenylvaleric acid.
The Reformatsky reaction of α-acetoxypropiophenone and ethyl 2-bromopropionate afforded 2-methyl-3-phenyl-4-methyl-Δ2-butenolide (I) as crystals. Catalytic reduction of (I) gave 2-methyl-3-phenyl-4-hydroxyvaleric acid γ-lactone (II), whose alkaline saponification resulted in partial isomerization to form a hydroxy acid (III), a mixture of stereoisomers. Warming of (III) in pyridine completed the isomerization and only one kind of γ-lactone (IX) was obtained, without contamination of an isomer. Saponifcation of (IX) afforded a hydroxy acid (III′) without being accompanied by isomerization. Methylation of (III′) with diazomethane to the methyl ester (IV′) and application of tosyl chloride to it in pyridine afforded the tosylate (V). Application of phenylmethanethiol to (V) to form the benzylthio compound (VI) and its desulfurization and saponification finally afforded erythro-2-methyl-3-phenylvaleric acid stereospecifically.
4-Ethyl-4-phenylitaconic acid was catalytically reduced to 2-(1-phenylpropyl)succinic acid and the reaction product of its anhydride and morpholine was identical with 2-(morpholinocarbonylmethyl)-3-phenylvaleric acid, prepared from the silver salt of 3-ethoxycarbonyl-4-phenylhexanoic acid according to the method of Salmon-Legagneur and Saudan. This fact indicates that the reaction of unsymmetric anhydride and amine took place by addition of the amine to the carbonyl with less substituent on the α-carbon atom. There seemed to be no change in the configuration throughout the whole course of this reaction.
Two electrodes of equal surface area are usually used for polarization titration and redox titration by D. C. and A. C. polarization methods was attempted with two electrodes of different surface area. Titration curve becomes distorted in D. C. polarization method and this is analyzed from controled current polarography. The titration curve in A. C. polarization method is almost the same as that in the use of minute electrodes and it was found that a D. C. titration curve is obtained by the commutating effect. In either case, a clear end-point is indicated in the titration curve.
Tetracaine and procaine undergo decomposition in an aqueous solution respectively into p-butylaminobenzoic acid and p-aminobenzoic acid. The compounds are more stable in acid range than in alkalinity and the extent of their decomposition cannot be measured correctly from the lowering of ultraviolet absorption alone. It was found that extraction of a sample at around the isoelectric point of p-butylamino-or p-aminobenzoic acid was the most effective in extracting these products and this was utilized for their determination (Charts 1-4). On the other hand, reaction velocity was examined with tetracaine by varying the pH from 0.29 to 11.08 and it was found that, at a definite pH, the reaction is a first-order reaction and the relationship between log kTC and pH was an acid-base catalyzed reaction, as shown in Fig. 3. This kTC was dissolved into each elementary reaction and equation (7) was obtained. Similar experiment was carried out with procaine at pH 2.5-6.0 and the relationship between log kPC and pH was found to be an acid-base catalyzed reaction, as shown in Fig. 5, giving equation (8).
Effect of glucuronic acid on the hemolysin of extracellular toxin from staphylococcus in vitro was examined and its reaction mechanism was considered. Toxicity of this toxin weakened or disappeared easily on contact with glucuronic acid and the toxicity was not recovered on dialysis. Similar weakening and disappearance of toxicity was observed with glucuronamide, sodium galacturonate, and sodium pyruvate as with sodium glucuronate, but the effect of sodium gluconate and glucose was not clear. Since the toxicity of this toxin disappeared rapidly by treatment with 2, 4-dinitrofluorobenzene, free amino group in the toxin protein may be responsible for this toxicity. Therefore, weakening or disappearance of toxicity by glucuronic acid may be due to the reaction of glucuronic acid with the free amino group in the toxin protein, i.e. formation of N-glucuronide.
Effect of glucuronic acid on the toxicity and antigenity of diphtheria toxin in vitro was examined and its reaction mechanism was considered. Toxicity of this toxin weakened or disappeared easily on treatment with glucuronic acid but not its antigenity. Consequently, this change is not accompanied by marked degeneration of the protein and may be termed as the formation of a toxoid. The weakening or loss of toxicity by glucuronic acid treatment is not recovered by dialysis to remove excess glucuronic acid so that the change cannot be considered as the formation of a mere mixture or a salt, the product being a comparatively stable substance. Since the toxicity and antigenity of diphtheria toxin are lost by its treatment with 2, 4-dinitrofluorobenzene, free amino acid is thought to take part in the toxicity and antigenity of this toxin. It was found by treatment with dinitrofluorobenzene to form dinitrophenylamino acid that ε-position in lysine had a free amino group. Therefore, weakening and disappearance of toxicity of this toxin by treatment with glucuronic acid is thought to be the result of reaction between glucuronic acid and free amino group in the toxin protein molecule, i.e. formation of N-glucuronide. Toxin free of toxicity by treatment with glucuronic acid was found to contain a definite quantity of glucuronic acid which could not be removed by salting out or dialysis.
Application of sodium sulfite to 4-chloropyridine 1-oxide and its methyl homologs afforded sodium 4-pyridine sulfonate 1-oxides. This salt turns into the free sulfonate by treatment with ion exchanger resin. Fusion of this salt with potassium cyanide afforded the corresponding 4-cyanopyridine 1-oxides and their yield was compared with that from N-oxygenation of 4-cyanopyridine with hydrogen peroxide and glacial acetic acid. The same reactions were carried out on quinolines.
D-Glucuronamide (I) was derived through 1, 2, 3, 4-tetra-O-acetyl-D-glucuronamide (II) and 1-bromo -1-deoxy-2, 3, 4-tri-O-acetyl-D-glucopyranuronamide (III) to methyl 2, 3, 4-tri-O-acetyl-D-glucosiduronamide (IV). The fact that (IV) is identical with methyl 2, 3, 4-tri-O-acetyl-β-D-glucopyranosiduronamide, obtained by acetylation of methyl β-D-glucopyranosiduronamide (VI) and that (II) and (IV) satisfy the pyranose structure of Hudson's isorotation rule proved that (I) has the pyranose structure.
In the ring-alkylation of acetanilide with alcohols, the yield is lower with sec-butanol than isopropanol. It was thereby found that this is not suitable as the method of preparation for 4′-sec-butylacetanilide (II) and that nitration of (II) with nitric acid and acetic anhydride resulted in liberation of the sec-butyl group, affording 4′-nitroacetanilide and not 2′-nitro-4′-sec-butylacetanilide (IV). It was confirmed that nitration with copper nitrate (trihydrate) and acetic anhydride is the best to obtain (IV).
The specific coloration of hexose with anthrone reagent, in the presence of tryptophan and changes in optical rotation were described in the preceding paper. The measure of optical rotation was carried out in the presence of amino acids other than tryptophan and it was found that other amino acid had almost no effect on this reaction.
Some of hexamethylenebis (trialkylammonium halide) for supporting electrolyte of polarography were prepared, whose depolarized potentials (tangent potentials) were measured polarographically, being reduced at different potentials from -1.91 to -2.23 volt vs. S. C. E.
As an application of A. C. polarography, silver nitrate titration with silver electrode and neutralization titration with antimony electrode were carried out. In the case of silver electrode, it is desirable that the surface area of the electrode be small, concentration of independent electrolyte be large, and the frequency be low. In the case of antimony electrode, it is desirable that the surface area of the electrode be small and frequency low, but inversely, concentration of independent electrolyte should be small. Sensitivity of both electrodes as inductive titration was not as good as that of platinum electrode. However, the two electrodes showed specific titration results and were successfully applied for A. C. polarography.
The object of the present work was to determine the utility of ion exchange memqrane for extraction or purification of alkaloids. The transport behavior of quinine in electrodialysis across the membrane, which was reported in the preceding paper, was particularly examined. The experiment was carried out at various pH's and current densities by the use of a five-compartment cell and following points were noted. 1) Quinine has greater permeability through weak-acid than strong-acid cation exchange membrane. 2) This permeability is maximum at about pH 3. 3) An electrodialysis of acidic aqueous extract of cinchona bark containing 2.458mg./cc., assuming all basic substances to be quinine, gives a solution which contains 4.741mg./cc., of quinine at pH 3 with 1.67A/dm2 for one hour.