Tag: 167.6354

Syntheses in the phenanthrene series. VI. Synthesis of morphinane was written by Grewe, Rudolf;Mondon, Albert. And the article was included in Chemische Berichte in 1948.Quality Control of 3-Chloro-5,6,7,8-tetrahydroisoquinoline This article mentions the following:

Et cyclohexanone-2-carboxylate (225 g.), 170 g. NCCH₂CO₂Et, 23 g. NH₄OAc, 72 g. AcOH, and 300 cc. C₆H₆ are refluxed 6-7 hrs. at 160° with simultaneous separation of the H₂O formed (45 cc.). After addnl. heating for 1 hr., 200 cc. ether is added to the cooled mixture, the ether layer washed with NaHCO₃ and H₂O, and the ether evaporated Distillation of the residue gives 75% 1,2-C₆H₉(CO₂Et):C(CN)CO₂Et (I), b₁ 160-70°, b_0.3 155°, in addition to a small amount of Et tetrahydroanthranilate, m. 73.5°. I (300 g.) is refluxed 7 hrs. with 1.2 l. concentrated HCl with stirring and, after addition of 300 cc. more HCl, another 2 hrs., giving 73% 2-carboxy-1-cyclohexene-1-acetic acid (II), m. 165°. The mother liquor is concentrated over the free flame until the crystallization of NH₄Cl begins, neutralized with NaHCO₃, and 12% 1,3-dihydroxy-5,6,7,8-tetrahydroisoquinoline (III), m. 205°, is filtered off. An intimate mixture of 140 g. II and 250 g. (NH₄)₂CO₃ is slowly heated in an oil bath at 230° until the NH₃ evolution has ceased, giving 92% III, pale yellow crystalline powder from 70% AcOH. Heating 115 g. III and 200 cc. POCl₃ 3 hrs. at 200°, pouring the reaction mixture onto ice, and distilling the reaction product give 95% 1,3-dichloro-5,6,7,8-tetrahydroisoquinoline (IV), b_0.8 134°, crystals from EtOH, m. 87°, insoluble in dilute HCl, volatile with steam. Reduction of IV in EtOH with Raney Ni in the presence of 2 equivalents Na in EtOH at 50° and 80 atm. gives 100% 5,6,7,8-tetrahydroisoquinoline (V). V is also obtained in 83% yield on addition of 75 g. Raney Ni in small portions over a period of 0.5 hr. to 20 g. IV in 600 cc. 10% NaOH at 90°, or in 100% yield by addition of 100 g. Zn dust to 60 g. IV in 400 cc. concentrated HCl at not over 40° with vigorous stirring, concentrating the reaction mixture over a free flame, making it strongly alk. while warm, and extracting it with ether, giving the 3-mono-Cl analog (VI) of IV, b₁₃ 143°, which is reduced with H in the presence of Pd-charcoal, thus giving 100% V, b₁₂ 102-4° (picrate, yellow leaflets, m. 144°). To V.MeI is added 1.6 mols. PhCH₂MgCl in ice-cold ether; after the exothermic reaction is over, the product is decomposed with NH₄Cl and extracted with ether, giving 83% 2-methyl-1-benzyl-1,2,5,6,7,8-hexahydroisoquinoline (VII), b_0.3 128-30°. VII readily decompose and gives no crystalline derivatives Hydrogenation of VII in N HCl with Adams catalyst gives 93% of the 1,2,3,4,5,6,7,8-octahydro derivative (VIII), b_0.5 136° (picrate m. 134°). Heating 33.6 g. VIII with 336 g. H₃PO₄ (d. 1.7) 3 days at 150° and extracting the diluted and alkalized mixture with ether give 50% N-methylmorphinane (IX), crystals from petr. ether (b. 30-60°), m. 61°. IX can also be isolated as the picrate, golden yellow leaflets, m. 174°. From the mother liquor 2 isomeric IX picrates, m. 203° and 201°, are isolated. IX.HCl m. 231-3°; IX sulfate m. 205°; IX.MeI (X) m. 253°. Heating 1.5 g. X with 10% NaOH gives 95% of the des-base (XI), an oil (picrate m. 217°). Dehydrogenation of 0.7 g. XI with 0.2 g. Pd-charcoal 0.5 hr. at 320° gives 80% phenanthrene, m. 97-8° (picrate m. 143°). Cyclization of 3 g. of the carbinol base (XII) as described earlier (4b-(2-dimethylaminoethyl)-4b,5,6,7,8,8a,9,10-octahydrophenanthrene (XIII), b_0.2 150° (picrate m. 185°). Hydrogenation of XI with PtO₂ catalyst gives XIII (picrate m. 185°). Refluxing 3.5 g. IX with 2 g. BrCN in CHCl₃ gives 2 g. N-cyanomorphinane (XIV), b_0.05 162°, fine needles, m. 104°. Refluxing 1 g. XIV with 6 N HCl until a sample remains clear on addition of H₂O gives 0.7 g. morphinane (XV), b_0.05 115° (HCl salt m. 229°; sulfate m. 195°; picrate m. 207°). Methylation of XV with MeI and NaOH gives X, m. 251°. In the experiment, the researchers used many compounds, for example, 3-Chloro-5,6,7,8-tetrahydroisoquinoline (cas: 875249-27-7Quality Control of 3-Chloro-5,6,7,8-tetrahydroisoquinoline).

3-Chloro-5,6,7,8-tetrahydroisoquinoline (cas: 875249-27-7) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline motif is often present in natural products with a broad range of biological and pharmacological activities. The dopamine-derived tetrahydroisoquinolines (TIQ) synthesized endogeneously from aldehydes and catecholamines have shown to modulate neurotransmission, central metabolism and motor activity.Quality Control of 3-Chloro-5,6,7,8-tetrahydroisoquinoline

Referemce:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem