6.7- Dimethoxy-1-methyl-3,4-dihydroisoquinoline

Dimethoxy-1-methyl-3,4-dihydroisoquinoline was prepared according to an Organic Syntheses procedure Brossi, A. Dolan, L A. Teitel, S. Org. Synth., Coll. Vol. V11988, 1. 

A. N-(tert-Butoxycarbonyl)-6,7-dimethoxy-1 -mathylenff-1,2,3,4-tetrahydroiso-quinoline. A 1 -L, three-necked, round-bottomed flask is equipped with a thermometer, magnetic stirring bar, nitrogen inlet with gas bubbler, and a pressure-equalizing dropping funnel (Note 1). The flask is charged with 102.6 g (500 mmol) of 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline (Note 2) and 150 mL of alcohol-free... 

Knabe et al. (271-274) later observed that 6,7-dimethoxy-2-methyl-1,2-dihydroisoquinolines (175), possessing either a free or a substituted benzyl group in position 1, readily rearrange to 3,4-dihydroisoquinoline salts (176) on treatment with dilute acids. 

Methyl-1,2-dihydropapaverine (175, R = OMe) rearranges to the 2-methyl-3-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinolin-ium salt (176, R = OMe) under very mild conditions (treatment with 2% hydrochloric acid). A similar rearrangement of l-(3,4-methyl-enedioxybenzyl) - 2 - methyl - 6,7 - dimethoxyisoquinoline (175, R, R = —O—CHj—O—) affords 3-(3,4-methylenedioxybenzyl)-2-methyl-6,7-di-methoxy-3,4-dihydroisoquinolinium chloride (176, R, R = O—CHj—O—) (256). The reaction was shown to be an allylic rearrangement with internal return (275,275). 

A solution of 50 grams of N-(a-methylhomoveratryl)-3-methoxy-4-ethoxyphenylacetamide, prepared as set out above, in 200 cc of benzene, is treated with 8 cc of phosphorus oxychloride. The mixture is refluxed for about 3 hours, cooled and then is shaken with a solution composed of 15 grams of sodium hydroxide dissolved in 60 cc of water. The aqueous layer is removed, and the benzene solution is washed with water. The washed benzene solution is dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The low-melting solid residue is 6,7-dimethoxy-3-methyl-1-(3 -methoxy-4 -ethoxybenzyl)-dihydroisoquinoline base. 

To a solution of 50 grams of 6,7-dimethoxy-3-methyl-T(4 -ethoxy-3 -methoxybenzyl)-dihy-droisoquinoline base in 200 ml of dry benzene are added 150 ml of decalin, and the mixture is distilled until its temperature reaches 180°C. 1.5 grams of 5% palladium on carbon are then added. The mixture is stirred under reflux for about 6 hours to dehydrogenate the dihydroisoquinoline. On cooling, the reaction mixture is diluted with petroleum ether and the precipitated 6,7-dimethoxy-3-methyl-1-(3 -methoxy-4 -ethoxybenzyl)-isoquinoline is filtered off and recrystallized from dilute ethanol. 

The submitters, working on a kilogram scale without purification of reagent or solvent and with no precaution against moisture, obtained 6,7-dimethoxy-l-methyl-3,4-dihydroisoquinoline hydrochloride,2 m.p. 202-203°, instead of the dichlorophosphate at this stage. The checkers obtained this hydrochloride by either treating the free base with... 

The photolytic and thermolytic decomposition of emetine have been studied. Photolysis has been shown to involve oxidation and fragmentation, whilst thermolysis involves only oxidation. Compounds identified were emetamine, O-methylpsychotrine, l, 2 -didehydroemetine, tetradehydroemetinium bromide, rubremetinium bromide, 6,7-dimethoxy-3,4-dihydroisoquinoline, 6,7-dimethoxy-l-methyl-3,4-dihydroisoquinoline, 3-ethyl-9,10-dimethoxy-l,4-dihydrobenzo[a]quinolizinium chloride, its 2-methyl-derivative, and the dimerized compound (112).141... 

Similar methodology was used in the synthesis of 3-methyl derivatives of the alkaloids thalactamine, doryanine, and 6,7-dimethoxy-A-methyl-l(2//)-isoquinolone652. The S l reaction between 0rr/20-halogenobenzylamines and enolates derived from a series of ketones and aldehydes affords 1,2-dihydroisoquinolines, from which the isoquinoline derivatives can be obtained by dehydrogenation and the 1,2,3,4-tetrahydroisoquinolines by reduction653. The products of the S l reactions of (2-halo-4,5-dimethoxyphenyl)acetic... 

Af-Methyl-6,7-Dimethoxy-1,2-Dihydroisoquinolin-1 -one 6,7-Methylenedioxy-1,2-Dihydroisoquinoline-1 -one //-Methylthalidaldine Noroxyhydrastinine Thalactamine Thalflavine Thalifoline Morphinans... 

The cyclisation of appropriately substituted iV-benzyi quaternary salts of 3,4-dihydroisoquinolines has afforded tetrahy-droberberines. For example the electrolytic reduction of the salt (219, R=CH2Br) and the treatment of -the salt (219, R=CH2 SiMe2) with sodium fluoride yields xylopinine (220, R =H, R = OMe) (T. Shono et al.. Tetrahedron Letters, 1978, 4819 S. Takano, H. Numata and K. Ogasawa, Heterocycles, 1983, 2, 417). The condensation of 6,7-dimethoxy-3,4-dihydroisoquinoline with methyl 2,3-dimethoxy-6-bromomethylbenzoate in acetonitrile in the presence of zinc as a reducing agent affords tetrahydro-palmatine (220, R =0Me, R =H) (H. Hamaguchi et al. J.org. Chem., 1983, 1621) and the condensation of the same dihy-... 

Michael addition of 6,7-dimethoxy-l-methyl-3,4-dihydroisoquinoline to the unsaturated ester (76) and the product converted into... 

Dimethoxy-l -methyl-3,4-dihydroisoquinoline Isoquinoline, 3,4-dihydro-6,7-dimethoxy-1-methyl- (8,9) (4721-98-6)... 

A study of the benzylisoquinoline bases showed that, on heating with acetic anhydride, l-(3,4-dimethoxybenzoyl)-6,7-dimethoxy-3-methyl-3,4-dihydroisoquinoline (14) gives an intensive green color reaction which is due to compound 15 (383). The mechanism of a reaction for the demonstration of the presence of papaverine, giving rise to coralyne (73) (Scheme 30), was described (384). 

A soln. of 2-methyl-4-piperonyl-6,7-dimethoxy-l,2-dihydroisoquinoline in acetic acid containing coned. HCl refluxed 1.5 hrs. under Ng 3,4-dimethoxy-6-methyl-8,9-methylenedioxy-5,6,12,13-tetrahydro-l lH-indeno[l,2-c]isoquinoline. Y 75%. 

Pseudocyanides. 6,7-Dimethoxy-2-methyl-l-allyl-l,2-dihydroisoquinoline dissolved in N H(5i, heated 0.5 hr. at 80° bath temp., cooled, made alkaline with NaHCOj, and treated with coned. NaCN-soln. pseudocyanide. Y 92%. F. rearrangements s. J. Knabe and H.-D. Holtje, Ardi. Pharm. 303, 404 (1970) Pharmazie 25, 313 (1970). 

A mixture of l-acetonyl-6,7-dimethoxy-3,4-dihydroisoquinoline and POClg in benzene refluxed 20 min. on a steam bath crude 2-methyl-8,9-dimethoxy-5,6-dihydro-2H-isoxazolo[3,2-a]isoquinoline (Y ca. 100%), 1 g. dissolved in ethanol, acidified with HCl, and hydrogenated 0.5 hr. with PtOg 1 g. l-(2-hydroxypropyl)-6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline. N. Itoh, Chem. Pharm. Bull. 8, 441 (1960). 

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