6-Methoxy-l,2,3,4-tetrahydroisoquinoline

In order to locate the secondary amino group, the alkaloid was N-acetylated, and the X-acetyltrilobine was subjected to cleavage with sodium-sodium hydride and liquid ammonia (102, 107). The phenolic base CXLVII, obtained by partial cleavage, was methylated and the resulting compound (CXLVIII) was submitted to a second-stage cleavage with sodium in liquid ammonia. There was obtained l-(4 -methoxy-benzyl)-2-methyl-6-methoxy-l,2,3,4-tetrahydroisoquinoline (XXXIII) and l-(4 -methoxybenzyl)-2-acetyl-6-methoxy-8-hydroxy-l,2,3,4-tetra-hydroisoquinoline (CL). These results show that trilobine is represented by CXLII (Ri=H). 

SCHEME 9. Electrolysis of l,2-dimethyl-7-hydroxy-6-methoxy-l,2,3,4-tetrahydroisoquinoline... 

A mixture of N-methyl-10-acetoxy-6-methoxy-7-oxo-J5,6,8,9-hexahydroisoquino-line, coned. H2SO4, and acetic anhydride allowed to stand 2hrs. at room temp. -> N-methyl-4,7-diacetoxy-6-methoxy-l,2,3,4-tetrahydroisoquinoline. Y 46.7%. -The acetoxy group migrates to the 4-position instead of the normal 5-position. B. Umezawa, O. Hoshino, and Y. Terayama, Chem. Pharm. Bull. 16, 180 (1968). 

Electrochemical oxidation of racemic l,2-dimethyl-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline (22) gives a number of dimers (cf. Vols. 2 and 4) but of the three possible racemic C-8—C-8 dimers (cf. Scheme 2) only one, the racemate corresponding to (23), was obtained.Evidently only molecules of (22)... 

The mixture of 2.48 g guaiacol (0.02 mol), 3.0 g 40% aqueous formaldehyde (0.04 mol), and 3.6 g methylaminoacetaldehyde dimethyl acetal (0.03 mol) in 25 mL ethanol was stirred at room temperature for 24 h. The solvent was removed on a rotary evaporator and the resulting thick oil was dissolved in 50 mL cold 6 N HCl and washed with ether. The acidic solution was stirred at room temperature for 15 h. The last traces of ether were removed on a rotary evaporator and the solution was hydrogenated over 4 g of 5% palladium on carbon at room temperature and atmospheric pressure until no more hydrogen was absorbed (about 0.02 mol). The catalyst was removed by filtration and the solution was concentrated on a rotary evaporator to a yellow syrup. The syrup was treated with 50 mL of hot ethanol and cooled. Crystals formed and were collected to yield 1.20 g of the crude hydrochloride of 2-methyl-6-hydroxyl-7-methoxy-l,2,3,4-tetrahydroisoquinoline, in a yield of 26%, m.p. 281-284°C. The mother liquor after the removal of 2-methyl-6-hydroxyl-7-methoxy-l,2,3,4-tetrahydroisoquinoline hydrochloride was concentrated and cooled to yield 3.12 g of crystalline crude hydrochloride of 2-methyl-7-methoxy-8-hydroxyl-l,2,3,4-tetrahydroisoquinoline, in a yield of 68%, m.p. 208-212°C. 

Vanillin allowed to react with equimolar amount of aminoacetal in abs. ethanol, hydrogenated with PtOg, filtered, coned, in vacuo, taken up in 6 iV HCl, extracted with ether, allowed to stand overnight, and hydrogenated with 5%-palladium-on-carbon 6-hydroxy-7-methoxy-l,2,3,4-tetrahydroisoquinoline. Y 71%. — This new synthesis is simple and relatively trouble-free. F. e. s. J. M. Bobbitt, K. L. Khanna, and J. M. Kiely, Ghem. Ind. 1964, 1950 J. Org. Chem. 50,2247 (1965). 

A soln. of 530 g. of l-carbethoxy-2-(a-ethyl-/ ,y -dicarbethoxypropionyl)-6,7-di-methoxy-l,2,3,4-tetrahydroisoquinoline in alcohol allowed to stand overnight with 10%-NaOH in a melting ice bath, acidified with dil. H2SO4 at 0°, and the resulting crude carboxylic acid heated 4 hrs. at 100° in xylene until the calculated amount of GOg has evolved -> 380 g. l-carbethoxy-2-(a-ethyl-y -carb-ethoxypropionyl)-6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline. A. Griissner et al., Helv. 42, 2431 (1959). 

Noscapine (Nectadon ), 2-methyl-8-methoxy-6,7-methylenedioxy-l-(6,7-di-methoxy-3-phtha-lidyl)-l,2,3,4-tetrahydroisoquinoline, is also one of the isoquinoline derivatives present in opium. Next to morphine, it is the most abundant of the opium alkaloids, present to the extent of 6% in the seed capsules. This drug was formerly known as narcotine but, because it is neither chemically nor pharmacologically related to the narcotics, is more appropriately designated as noscapine. 

The thermal condensation of p-benzyloxyphenylacetic acid and of 3-methoxy-4-hydroxyphenethylamine occurs and gives, with a yield of 86% to 92%, the N-(3-methoxy-4-hydroxyphenethyl-p-benzyloxyphenyl)acetamide from this latter, by cyclization according to Bischler-Napieralski with phosphorus oxychloride in acetonitrile, followed by reduction with sodium borohydride, there is obtained with a yield of 75% to 80% the l-(p-benzyloxybenzyl)-6-methoxy-7-hydroxy-l,2,3,4-tetrahydroisoquinoline, which is methylated with... 

Methylation with diazomethane afforded (— )-norcoralydine. The location of the hydroxyl at C-3 was ascertained from the isolation of 6-ethoxy-7-methoxy-l-keto-l,2,3,4-tetrahydroisoquinoline (XL) from the... 

The Faltis theory, which postulates that bisbenzylisoquinoline alkaloids originate in the plant through enzymatic dehydrogenation of the benzylisoquinoline units l-(4 -hydroxybenzyl)-6-methoxy-7-hydroxy-l,2,3,4-tetrahydroisoquinoline (coclaurine) or l-(4 -hydroxy, benzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (norcoclaurine), has been accepted and refined. This theory has played a role in influencing... 

The alkaloid was synthesized by the Ullmann condensation of l-(3 -bromo - 4 - benzyloxybenzyl) - 2 - methyl - 6,7 - dimethoxy -1,2,3,4 - tetra-hydroisoquinoline (XXXIV) and l-(4 -benzyloxybenzyl)-2-methyl-6-methoxy-7-hydroxy-l,2,3,4-tetrahydroisoquinoline (IX) followed by removal of the benzyl groups (40). 

Alkaloid isolations and structural elucidations are summarized in Table 3. Reduction of a new quaternary alkaloid isolated from Berberis oblonga gave 6-hydroxy-7-methoxy-2-methyl-l,2,3,4-tetrahydroisoquinoline and the alkaloid was deduced to... 

Pschorr aporphine synthesis, Kupchan el al.2 have reported an improved synthesis of aporphines by using (1) for condensation with o-nitrotoluenes (2) in the presence of potassium t-butoxide in DMA to give l-(2-nitrobenzyl)-6-methoxy-7-hydroxy-l,2,3,4-tetrahydroisoquinolines (3) in yields of 88-95%. These are hydrogenated to the... 

Salsoline. 1,2,3,4-Tetrah ydro- 7-methoxy-l -meth-yl-6-isoquinolinol 6 -hydroxy -7 -methoxy -1 -methyl -l,2,3,4-tetrahydroisoquinoline. CMH13NO, mol wt 193.24. C 68.37%, H 7.82%, N 7.25%, O 16.56%. In Salsota riehterl Karel.. Chenopodiaceae. Extraction procedure Orechoff,... 

Oxidation of codamine ethyl ether (LXVI) cleaved the benzylisoquinoline system to 4-methoxy-5-ethoxyphthalic acid (LXVH) and veratric acid (VT). While the formation of these two acids precluded the location of the phenolic hydroxyl in the benzyl residue, LXVTI could have arisen from either a 6- or 7-ethoxy-substituted isoquinoline system. This question was settled by repeating the potassium permanganate oxidation of 0.0085 g. of codamine ethyl ether (LXVI) under gentle conditions. This time, 1-ke-to-2-methyl-6-methoxy-7-ethoxy-l, 2,3,4-tetrahydroisoquinoline (LXVIII) was isolated its structure was confirmed by synthesis, and therefore codamine is XXII. 

Final proof of the structure of tetrandrine came when the alkaloid was subjected to the sodium in liquid ammonia reaction (127, 133). The two products d-l-(4 -methoxybenzyl)-V-methyl-6,7-dimethoxy-l, 2,3,4-tetra-hydroisoquinoline (XXXIX) and d-l-(4 -hydroxybenzyl)-iV-methyl-6-methoxy-7-hydroxy-l,2,3,4-tetrahydroisoquinoline (XL) were isolated. It is thus evident that the structure of tetrandrine must be represented by XXX. However it was also proved (126) that isotetrandrine is represented by the same structure (XXX) and that its cleavage products are... 

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