6.7- Dimethoxy-3,4-dihydroisoquinoline

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). 

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... 

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-... 

Hydrogenation of ethyl A -[2-(2-pyridyl)ethyl]carbamate in ethanol over Raney Ni at 130°C and 120 atm gave perhydropyrido[l,2-c]pyrimidin-1-one (67YZ663). Cyclization of ethyl Y-[2-(l,2,3,4-tetrahydro-2-quinolyl)ethyl]carbamate at 190-200°C afforded 2,3,4,4a,5,6-hexahydro-l//-pyrimido[l,6-a]quinolin-l-one (60YZ1414), whereas that of l-(2-benzamidoethyl)-6,7-dimethoxy-3,4-dihydroisoquinoline in boiling toluene with phosphoryl chloride led to 4-phenyl-9,10-dimethoxy-6,7-dihydro-2//-pyrimido[6,l-fl]isoquinoline (63YZ1043). 

O-demethylation and reetherification or methylenation of the liberated phenolic groups (346-348). The alkaloid corypalline (lc) can be conveniently prepared from 6,7-dimethoxy-3,4-dihydroisoquinoline (349). The first step is partial demethylation of the methoxyl at C-7. It gives rise to the monomethoxy derivative which on hydrogenation affords corypalline (Scheme 1). 

Scheme 1. Transformation of 6,7-dimethoxy-3,4-dihydroisoquinoline into corypalline (1 iff (349).

A soln. of 0-benzylanhalamine in methanol treated with 17.2%-NaOGl-soln., stirred 1 hr. at room temp., solid NaOH added, and refluxed 45 min. 8-ben-zyloxy-6,7-dimethoxy-3,4-dihydroisoquinoline. Y 98%. A. Brossi, F. Schenker, and W. Leimgruber, Helv. 47, 2089 (1964). 

Derivatives of l,3-bis-[6,7-dimethoxy-3,4-dihydroisoquinoline-(l))-2-arylpropane reduce platelet adhesiveness, aggregation, retraction and liberation of biogenic amines from cells in idiich these CMqpounds have accumulated Derivatives of 3-alkyl-3-carbalkoxy-6,7-dimethoxy-3,4 dihydro-isoquinolines also have the same effect on platelets ... 

Platelets treated with l-p-chlorostyryl-3Hnethyl-3-carbomethoxy-6,7-dimethoxy-3,4 dihydroisoquinoline (SSDHI) lose their ability to spread, adhere, aggregate and retract. They cannot undergo the morphological and biochemical cluuiges of viscous metamorphosis produced by thrombin ... 

Z)-ferf-Butyl l-(3-chlorobenzylidene)-6,7-dimethoxy-3,4-dihydroisoquinoline-2(l//)-carboxylate (4b) Colorless crystals, mp 146-147 °C reaction time 6 h yield 86%... 

A stirred mixture of l-(5-benzyloxy-4-methoxy-2-nitrobenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline, 10%-Pd-C, and p-cymene heated 4.5 hrs. at 140-145° in the presence of air l-(5-benzyloxy-4-methoxy-2-nitrobenzoyl)-6,7-dimethoxyiso-quinoline. Y ca. 50%. M. P. Cava and I. Nogudii, J. Org. Chem. 37, 2936 (1972). 

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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