Using 2-mercapto-5-nitro- and 2-mercapto-3-nitro-5-amino-pyridines as starting materials, several alkyl (pyridyl)-mercapto derivatives were obtained. Pyridothiazoles were synthesized from 2-sulfocyano-3, 5-dinitropyridine and 2-mercapto-3-nitro-5-amino-pyridine.
1) Electrolytic reduction of benzalacetone derivatives were carried out in order to obtain their hydrogenated products. 2) Good results were obtained by the use of nickel plated copper wire as a cathode.
Piperonalmethyl ethyl ketone was prepared from piperonal and the double bond in piperonalmethyl ethyl ketone was reduced through electrolytic hydrogenation. Oxime of this reduced piperonylmethyl ethyl ketone was rearranged with P2O5 in toluene by means of Beckmann's rearrangement when 1-ethyl-nor-hydrastinine was formed, at the same time, by Bischler and Napieralsky's method. Methiodide of this compound, obtained by CH3I, was converted into methochloride by AgCl which was catalytically hydrogenated to 1-ethyl-hydro-hydrastinine. The previous report on the melting point of piperonylacetophenone has been corrected by the authors. 1-Phenyl-nor-hydrastinine prepared recently by the authors was reconfirmed with the reduced product, constants of which correspond to those appearing in literature.
There has been no evidence of a hydroisoquinoline compound having iso-propyl radical in its 8-position having been synthesized and this was accomplished by the authors by taking thymol as the starting material. This was led to thymotinaldehyde by the Gattermann's method, methylated with (CH3)2SO4, condensed with acetone and reduced by electrolytic hydrogenation. The oxime of this reduced product was treated with P2O5 or POCl3 in toluene solution to obtain 8-isopropyl-7-methoxy-1, 5-dimethyl-3, 4-dihydroisoquinoline.
1) Following were newly synthesized: β-Methylmyristic acid, γ-methylpalmitic acid, γ-ethylpentadecoic acid, γ-methyl-γ-myristolactone, γ-methyl-γ-palmitolactone, γ-ethyl-γ-palmitolactone, ε-methyllauric acid, ε-ethyllauric acid, ε-methylmyristic acid and ε-ethylmyristic acid. 2) Growth inhibitory action of 31 kinds of branched-chain and saturated or unsaturated straight-chain fatty acids were tested in vitro against avian type tubercule bacilli and following results were obtained: a) Maximum antibacterial actions were noticed in myristic acid derivatives with branched side-chains in all substitutions at α, β, γ and ε positions. b) In saturated, straight-chain fatty acids, lauric, myristic and palmitic acids showed great antibacterial power. c) In unsaturated, straight-chain fatty acids, linolenic acid gave remarkable results. d) Lactone compounds listed above also showed somewhat a fair amount of antibacterial action.
1) Electrolytic reduction of nitrobenzene in 82% H2SO4 resulted in the formation of p-aminophenol sulfate in a pure state with fairly good yield. 2) p-Hydroxyphenylurea was obtained with a good yield by heating together p-aminophenol sulfate and 2mol. urea over a water bath with Sn as a catalyst. 3) Several kinds of new compounds were obtained by the acylation of the OH-radical in p-hydroxyphenylurea with higher fatty acid residues.
In order to obtain dl-ephedrine possessing therapeutic value from dl-Ψ-ephedrine which is obtained as a by-product in synthetic procedure, experiments were carried out by the author. Application of PCl5 to dl-ephedrine and dl-Ψ-ephedrine results in Walden conversion in both cases and dl-Ψ-1-phenyl-1-chloro-2-methylaminopropane hydrochloride (I) and dl-1-phenyl-1-chloro-2-methylaminopropane hydrochloride (II), respectively, are formed. However, application of SOCl2 to dl-Ψ-ephedrine results in the formation of (I). Application of AgNO3 solution to (I) and (II) gives, in both cases, a mixture of dl- and dl-Ψ-ephedrine where the amount of the latter is always larger than the former. Heating (I) with NaOH solution gives N-methyl-1-phenyl-2-methylethylene-imine (III) which, when heated with 60% H2SO4, undergoes hydration and ring-cleavage, and gives about an equal mixture of dl- and dl-Ψ-ephedrine. Application of benzoyl or acetyl chloride to (III) results in their addition with concurrent ring-cleavage to give dl-Ψ-1-phenyl-1-chloro-2-benzoyl (or-acetyl)-methylaminopropane (IV and V).
dl-Ephedrine is quantitatively obtained by heating dl-Ψ-1-phenyl-1-chloro-2-benzoyl (or-acetyl)-methylaminopropane (IV or V) with NaOH solution with an intermediary formation of N-benzoyl (or-acetyl)-dl-ephedrine (VII or VIII). No by-product of dl-Ψ-ephedrine could be noticed. Heating (IV) or (V) with aqueous EtOH gives O-benzoyl (or-acetyl)-dl-ephedrine hydrochloride (IX or X) which, when saponified with dil. HCl, gives only dl-ephedrine hydrochloride. By these experiments, it became clear that when Cl is substituted with OH under the presence of N-acyl radical, Walden conversion from pseudo to normal system occurs. It is assumed that the formation of (IX) and (X) occurs with N→O transition of acyl radical by the liberated HCl after substitution and conversion.
Application of PCl5 to l-ephedrine (I) and d-Ψ-ephedrine (II) results in Walden conversion and formation of (+)-Ψ-1-phenyl-1-chloro-2-methylaminopropane hydrochloride (III) and (-)-1-phenyl-1-chloro -2-methylaminopropane hydrochloride (IV), respectively. Reaction of (II) and SOCl2 gives chiefly (III) which, when warmed with AgNO3 solution, gives a mixture of (I) and (II). Heating (III) with NaOH solution gives (-)-N-methyl-1-phenyl-2-methylethyl eneimine (V). Addition of AcCl to ethereal solution of (V) gives (+)-Ψ-1-phenyl-1-chloro-2-acetylmethylaminopropane (VI) which, when saponified with alkali, gives N-acetyl-1-ephedrine (VII) but gives l-ephedrine when saponified with acids with intermediate formation of O-acetyl-l-ephedrine hydrochloride (VIII). In the same manner, l-Ψ-ephedrine was treated to give optical antipodes which were finally led to d-ephedrine.
Examinations were made as to whether vitamin B1 when treated with alkali to cleave its thiazole nucleus takes the thiol form. As a model experiment, two kinds of thiazolium compounds were synthesized. Calculated amount of NaOH was added to each and 2, 4-dinitrochlorobenzene was respectively applied by which corresponding 2, 4-dinitrophenylmercapto compounds were formed. In order to determine the structure of these thioethers, they were hydrolyzed by mineral acids and the decomposition products (especially those containing sulfur) were examined and proved. Moreover, similar 2, 4-dinitrophenylmercapto compound was obtained in the case of vitamin B1 but its hydrolyzed product was an oily substance and the structure could not be determined. However, pyrimidine portion and formic acid were obtained. From these results, it has been made clear that the thiazole nucleus of vitamin B1 is cleaved by 3mol. NaOH to become Nasalt of a thiol compound.
Methyl α-benzoylamino-β, β-dimethylacrylate and 2-phenyl-4-isopropylidene-5-oxazolone were led from β-hydroxyvaline, and methyl α-benzoylamino-β, β-dimethylacrylate was led from β, β-dimethylacrylic acid through α-nitro-β, β-dimethylacrylate. Relationship between these compounds and penicillamine was determined.