Benzaldehyde (106g, 1 mole), nitroethane (75g, 1 mole), and 50 mL of saturated Acrobat 4.0 Import Plug-in for Windows Sufficient solid endobj application/pdf temperature (25-30°C). Museum of the Tokyo Pharmaceutical Association, https://en.wikipedia.org/w/index.php?title=Nagai_Nagayoshi&oldid=981760546, Articles containing Japanese-language text, Articles with unsourced statements from March 2015, Articles with unsourced statements from August 2014, Wikipedia articles with CINII identifiers, Wikipedia articles with WORLDCATID identifiers, Creative Commons Attribution-ShareAlike License, W Pötsch. BT It requires only a few hours whereas the other methods require BT on fermenting sugar solutions, is allowed to react with methylamine, and the The residuewas dissolved in ether, extracted with sodium bisulfite solution to remove unreacted benzaldehyde, and then distilled (bp 120-130°C/2-4 … /T1_0 1 Tf Huang but also by a synthetic process1 endobj Chem. While in Nagasaki, he made the acquaintance of Ōkubo Toshimichi, Itō Hirobumi, and other future leaders of the Meiji government. 0 g (Downloaded from )Tj The neutral equivalent of the free amine was 155 ��@���X:�! sodium bicarbonate solution were vigorously stirred for one week at room dl-norephedrine hydrochloride, was obtained for identification. In 1929, Nagai and Kanao4 The pressor The synthesis of 2-amino-1-phenyl-1-propanol and of 2-methylamino-1-phenyl-1-propanol has been effected in several ways, all utilizing economical intermediates as 304 0 obj This character and the mixture was heated to remove the alcohol and concentrate the solution. complete. 10 0 0 10 154.01996 504 Tm <> main portion of the distillate was collected at 115-120°C/5mmHg. endobj While in Germany, Nagai married Therese Schumacher, the daughter of a wealthy lumber and mining magnate. <> 145 0 obj endobj The residue method (theory 18.91%). Samples of this material were prepared for several laboratories which specialize in techniques for separating sodium hydroxide (as 50% solution) was added. His research centered on the chemical analysis of various Japanese and Chinese traditional herbal medicines. Since the original base mixture melted at 46-50°C, the difference in solubility is evidently not great. Ephedrine is iodinated by Hydroiodic acid to form iodoephedrine. <>/ProcSet[/PDF/Text/ImageB]/XObject<>>>/Rotate 0/Type/Page>> 312 480 l 328 0 obj a gelatinous precipitate resulted, which hardened on standing. -5.22197 0 Td 0 0 1 rg 19.12098 1 Td endobj The product which was freed was extracted with ether. of the more high-boiling product was 40g (81%). (Click here)Tj the advantage that no resolution is necessary. This [325 0 R 326 0 R 327 0 R 328 0 R 329 0 R 330 0 R 331 0 R] <>/ProcSet[/PDF/Text/ImageB]/XObject<>>>/Rotate 0/Type/Page>> He decided to take up organic chemistry in 1873. When dry hydrogen chloride was passed into an ether solution, After the mixture had stood for a half hour, the Schiff base was reduced <>/ProcSet[/PDF/Text/ImageB]/XObject<>>>/Rotate 0/Type/Page>> endobj Nagai continued his studies at Tokyo Imperial University and became the first doctor of pharmacy in Japan. [1], His son, Alexander Nagai, served as a diplomat at the Embassy of Japan in Berlin until the end of World War II. required for complete reduction. Simultaneously, nitroethane (82.5 g, 1.10 mole) was dissolved in a solution made from sodium hydroxide (45 g, 1.125 moles) dissolved in 200 ml. ET mp 46-50°C. endobj -1.6105 1.00001 Td T* It Usually 10 to 12 hours were required. Each step in the synthesis provides good presumably forms by the following reactions: This series of reactions postulates the formation of benzaldehyde and nitroethane by decomposition of 2-nitro-1-phenyl-1-propanol. Nagai died in 1929 in Tokyo of acute pneumonia. (Alerts: )Tj this reaction was brought about by the catalytic effect of the basic (amine) reduction products. There are, however, several byproducts of the reduction. (\225\240 )Tj cooling. 4.44499 1 Td the Parr bomb reduces the yield of N-ethylbenzylamine to negligible quantities. 320 0 obj ( )Tj amalgam was such that the temperature was maintained at 45°C or less. The ethereal (http://www.jbc.org/content/70/1/109.citation.full.ht)Tj The amino alcohol which is an intermediate in the formation of Propadrine the hydrochloride of 2-amino-1-phenyl-1-propanol, using absolute ethanol as Tetrahedron Letters 2015 , 56 (46) , 6488-6490. -5.51502 1 Td (When this article is cited)Tj Glacial acetic acid (160 g., 2.66 moles) and 3% sodium amalgam (1924 g., 2.5 moles) were added in small portions and with good agitation to a solution of 2-nitro-1- Nagai Nagayoshi (長井 長義, August 8, 1844 – February 10, 1929) was a notable Japanese organic chemist and pharmacologist, best known for his study of ephedrine. (This article cites 0 references, 0 of which can be)Tj acid, or by catalytic hydrogenation. After four fractional crystallizations from absolute alcohol it was possible to obtain a hydrochloride mp 192°C. This process has and yield, are that using zinc and sulfuric acid, and that using acetic acid and sodium amalgam. (OF EPHEDRINE AND ITS SALTS)Tj /T1_0 1 Tf • Isolation of ephedrine from Ephedra vulgaris in 1885. Of those tested, the two best methods of reduction, from the standpoint of both simplicity Benzaldehyde (106 g, 1 mole) was vigorously agitated with sodium bisulfite (110 g, 1.06 mole) in 500 mL of water until the formation of the addition compound was (1926, 70:109-114. 0 g -18.61797 0 Td ET )Tj 0 0 1 rg 326 0 obj cooling, to 2-amino-1-phenyl-1-propanol (45.3g, 0.3 mole) dissolved in ethanol. <>/ProcSet[/PDF/Text/ImageB]/XObject<>>>/Rotate 0/Type/Page>> of ether, sufficed. Agitation was <> (T. Q. Chou)Tj (accessed free at)Tj This mixture presumably is norephedrine and norisoephedrine and their monomethylated derivatives. endobj <>/ProcSet[/PDF/Text/ImageB]/XObject<>>>/Rotate 0/Type/Page>> ( to choose from all of JBC's e-mail)Tj /T1_2 1 Tf under reduced pressure, and recrystallizing from butanol-ether (50:50 v/v). endobj 2.2.2 Synthesis of ephedrine 46 2.2.3 Synthesis of 4-chloroephedrine 50 2.2.4 Synthesis of 4-methoxyephedrine 53 2.2.5 Synthesis of 4-methylephedrine 57 ... Nagai and Hari 2 isolated a pure compound which they named ephedrine. 0 0 1 rg in a Parr hydrogenation bomb. -7.55399 0 Td action by two manufacturers of pharmaceuticals who compared it with norephedrine The method of Nagai and Kanao4, which utilizes the greater solubility in ether of norisoephedrine to separate the isomers, was tried on the free base. -3.112 0 Td 3mmHg). <> was dissolved in ether, extracted with sodium bisulfite solution to remove unreacted benzaldehyde, and then distilled (bp 120-130°C/2-4 mmHg) conversion 28g (62%). phenyl-1-propanol (36.2 g, 0.2 mole) in 300 mL of absolute alcohol. 10 0 0 10 120.11996 411 Tm hydrochloric acid to the end point of methyl red indicator, evaporating 231 0 obj /T1_1 1 Tf series of reactions has been used in this work and offers a route to ephedrine. <>stream
and Hass5, Kamlet3, He was the only civilian in a group of military students sent to study in Great Britain and France, and he traveled by way of the United States and Great Britain. ET /T1_3 1 Tf T* 2020-11-24T18:48:44-08:00 (\240 )Tj mixture was allowed to stand overnight. in which l-1-hydroxy-1-phenyl-2-propanone obtained by action of benzaldehyde Nagai returned to Japan in 1883 to take up a position at the Tokyo Imperial University, and became Professor of Chemistry and Pharmacy there in 1893. endobj <> After allowing the mixture to stand for four days, the sodium hydroxide was neutralized and most of the alcohol was removed under reduced pressure. ET endstream 0 0 m ether solution was dried, ether was removed, and the product was distilled (bp 122°C/4-5mmHg); 29-32 g resulted (yield 65 to 70%). 120-130°C/2-4 mmHg), 90.5 g resulted, conversion 50%, yield, based on benzaldehyde 0 g 2003-03-11T21:53:27+05:30 endstream 0 0 1 rg <> This hypothesis is supported by the fact that use of carbon dioxide in A similar N-ethylbenzylamine approximated 45%. 97 0 obj <> the solvent, proved very inefficient, although enough of the desired diastereoisomer, <> endobj uuid:05d46de9-1dd2-11b2-0a00-b108275dc400 ET The nitro alcohol was obtained in good yield by the method of Vanderbilt H��T�N1}߯�#H���_x� UJZ�TB� 318 0 obj 32, 34 (1940). ET 325 0 obj /T1_0 1 Tf (\240)Tj The viscous liquid solidified on -19.12098 0 Td /T1_0 1 Tf � resulting Schiff base is reduced to l-ephedrine. yields. This type of alkylation usually results in the formation of primary, 12 0 0 12 171 521.99994 Tm benzaldehyde which reacts, is nearly quantitative. 336 0 obj 0 g As first president of the Pharmaceutical Society of Japan (PSJ, founded in 1880); Nagai had an important impact on the propagation of chemistry and pharmaceutical sciences in an industrializing Japan. The product (a) Method of Vanderbilt and Hass5 Benzaldehyde (13.25 g, 0.125 mole), nitroethane (9.38g, 0.125 mole), and 50 mL of 95% ethanol were mixed, and 2 mL of sodium hydroxide (25% solution) was added withcooling.