8, 9-Dimethoxy-5, 6-dihydro-2-

DIMETHOXY-3,4-DIHYDRO-2-NAPHTHOIC ACID (2-Naphthoic acid, 3,4-dihydro-6,7-dimethoxy-)... 

Dimethoxy-3,4-dihydro-2-naphthoic acid can be dehydrogenated to give 6,7-dimethoxy-2-naphthoic acid. The yield of the latter was 85% after distillation and crystallization from alcohol. 

The system Ru2(OAc) Cl/O2/toluene/50°C oxidisedR CH NHR to imines R CH=NR converted 1,2,3,4-tetrahydroisoquinoline to the 3,4-dihydroisoquinoline with isoquinoline, and 6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline to 6,7-dimethoxy-3,4-dihydro-iso-qninoline (cf. mech. Ch. 1) [18], Such oxidations were also catalysed by TPAP/NMO/PMS/CH3CN, e.g. the conversion of indoline to indole (in which indoline nndergoes a donble-bond shift and aromatisation), and the oxidation of 1,2,3,4-tetrahydroqninoline to 3,4-dihydroquinoline (Fig. 5.1, Table 5.1) [19]. 

To a stirred solution of 6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline (3.00 g, 15.4 mmol, 1.00 equiv.) in anhydrous pyridine (100 mL) under argon at room temperature was added acetic anhydride (14.5 mL, 154 mmol, 10.0 equiv.) over 15 min. The resulting mixture was stirred at room temperature for 2 h, and then at reflux for 6 h. The volatiles were removed by rotary evaporation at 80°C under high vacuum. The residue was flash chromatographed on silica gel (MeOH-CH2CI2 8 92) to afford 3.21 g (89%) of l-(6,7-dimethoxy-3,4-dihydro-lH-isoquinolin-2-yl)ethanone as a viscous brown oil. The H-NMR spectrum reflected the presence of two slowly interconverting conformers in a ratio of 1.2 1 at room temperature. 

Synthesis of 2-[l-(6,7-dimethoxy-3,4-dihydro-lH-isoquinolin-2-yl)ethylidineamino]-4,5-dimethoxybenzonitrile ... 

To a solution of 2-(6,7-dimethoxy-3,4-dihydro-lH-isoquinolin-2-yl)-6,7-dimethoxyquinolin-4-ylamine (150 mg) in hot CH2CI2 (4.5 mL) and MeOH (1.5 mL) was added a solution of fumaric acid (22.8 mg, 0.196 mmol, 0.50 equiv.) in hot MeOH (3.0 mL). The resulting mixture was concentrated and the product was recrystallized from MeOH with hot filtration to afford, after filtration, 85 mg of light brown solid m.p. 239-240°C. 

In a procedure for the synthesis of 6,7-dimethoxy-3,4-dihydro-2-naphthoic acid (IV) by the method of G. P. Crowley and R. Robinson, ethyl y-veratrylbutyrate (I) is formylated with ethyl formate by dropwise addition of a solution of 1 and ethyl formate in ether to a suspension of sodium ethoxide in ether at —10°. After acidification, the formyl derivative II is collected by ether extraction and cyclized to III with a mixture of 90% phosphoric acid and concentrated sulfuric acid at 0-10°. Saponification gives the acid IV, m.p. 193°. 

Nakada and Nishihara (51) synthesized carnegine by suspending veratryl-acetoxime in toluene and treating with POCI3, obtaining 1-methyl-6,7-dimethoxy-3,4-dihydro-isoquinoline. Catalytic reduction of the methyl methosulfate of this compound yielded carnegine. 

Lawesson s reagent was found quite suitable to convert 6,7-dimethoxy-3,4-dihydro-l,2,3-benzotriazin-4-one 229 to the corresponding thione 230, which was methylated to 231a. Oxidation of the latter furnished the methylsulfone 231b, which in turn underwent displacement by several 4-substituted piperidines (Equation 89) <1990CPB2179>. 

A soln. of p-toluenesulfonyl chloride in abs. benzene added to a soln. of 3- (6,7-dimethoxy-3,4-dihydro-l-isoquinolyl) -8,9- dimethoxy-5,6-dihydropyrrolo[2,l-a] -isoquinolin-2-ethanol in the same solvent, and allowed to stand at room temp, overnight bisnorrubremetinium tosylate. Y 97%. Y. Ban and M. Terashima, Ghem. Pharm. Bull. 13, 775 (1965). 

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 ... 

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