2- Methylisoquinoline derivative

Decahydroquinoline and decahydroisoquinoline are dehydrogenated over palladium to the corresponding (>z-tetrahydro derivatives, a valuable procedure for making these compounds. 1-Methylisoquinoline is prepared by refluxing its 3,4-dihydro derivative with excess Raney nickel until the temperature reaches 248°, the boiling point of the desired product (75%). 

An interesting synthesis was developed for bostrycoidin (283) and its 8-0-methyl derivative (282). From 1,2-addition of 1,1-dimethoxyethene to 3-methylisoquinoline-5,8-dione, a mixture (7 1) of the regioisomers 284 and 285 was obtained. The latter could also be prepared in a Minisci-type reaction with subsequent ring closure. After photochemical hydroxylation and demethylation with BClj, 283 was obtained (80TL5089 82AJC1439). 

Ancisirocladus is the only genus of the Ancistrocladaceae and comprises some twenty species of lianas and shrubs found in the tropical rain forest of Asia and Africa. Examination of the bark extract of Ancisirocladus lectorius (Ancistrocladaceae) collected in Johore. Peninsular Malaysia, resulted in the isolation of a new simple isoquinoline, 6,8-dimethoxy-3-hydroxymethyl-1 -methylisoquinoline (1) and a new naphthylisoquinoline derivative, 4 -O-demethylancistrocladine (4), together with the known isoquinolines, 6,8-dimethoxy-l,3-dimethylisoquinoline (2) and (5)-6,8-dimethoxy-l,3-dimethyl-3,4-dihydroisoquinoline (3) [24, ... 

Photolysis of the mixture of the isomeric Z- and E- enol acetates (123, Ar = 3,4(MeO)2CgH2) derived from 4-(3,4-dimethoxypheitylacetyl)-2-methylisoquinolin-l-one gives a... 

Oxygenated isoquinolinium derivatives (34) have been prepared by isomerization of dihydroindeno-azirinones (33). Studies are reported on the Birch reduction of l,2,3,4-tetrahydro-2-methylisoquinoline and its 6- and 7-methoxy-analogues. ... 

Method (a) usually gives only trichloro or tribromo derivatives of N-hetero-cycles that contain active CH3 groups and it is not applicable to 3-methyl-pyridine, 3- or 4-methylquinoline, or 1-, 3-, or 4-methylisoquinoline further, 2- and 4-methylpyridine cannot be brominated by this method, although they can be thus chlorinated.755,757... 

The picolinium salts (216) obtained by reactions of the picolines (215) with a-halogenoketones, and also with a-halogenoesters and a-halogenoni-triles (and even those from benzyl halides), react with a-dicarbonyl compounds in the presence of base to give quinolizinium salts (217) as shown in Scheme 50 salts derived from 1-methylisoquinoline similarly gave... 

A mixture of p-tolylacetonitrile, phosgene, dry HCl, and chlorobenzene heated 4 days at 100-105° in a sealed glass tube placed in an autoclave 1,3-didiloro-7-methylisoquinoline. Y 65.3% based on phosgene consumed. - This is a general one-step synthesis of 1,3-didiloroquinoline derivs. F. e. s. S. Yanagida, M. Ohoka, and S. Komori, J. Org. Chem. 34, 4127 (1969). 

The initial approach to evaluate substituent effects involved the synthesis of a series of 5-substituted derivatives of (1) [34], Nitration of I-methylisoquinoline (58) produced only one isomer (59), which was reduced to give the amino analogue (60). Acetylation of (60), followed by oxidation, acid hydrolysis and reaction with thiosemicarbazide produced the corresponding thiosemicarbazone... 

Several possible mechanisms including ionic [39] and free radical [40] formation have been proposed for the analogous rearrangement of 2-picoline N-oxide. In the case of the isoquinoline series, where no rearrangement products at position 3 were isolated, an intermediate (74) resulting from abstraction of an active H from the 1-methyl by AcO would be reasonably expected to predominate in the transformations. Such an intermediate cannot be formed from 3-methylisoquinoline since it would result in the disruption of the aromaticity of the benzene ring. Conversion of (74) to the 1-acetoxymethyl derivative (75, pathway a) may result from an intramolecular rearrangement, analo-... 

Oxidation of 4-acetoxy-l-methylisoquinoline (76) with selenium dioxide produced the corresponding 1-carboxaldehyde, which upon acid hydrolysis yielded the 4-hydroxy derivative. Treatment of heterocyclic aldehydes with thio-semicarbazide produced the desired thiosemicarbazones. In general, the 4-substituted derivatives were less effective than (1) as antineoplastic agents against Sarcoma 180 ascites cells in mice however, the sodium salt of the 4-hydroxy derivative was considerably more efficacious than (1) against the L-1210 lymphoma. 

Thiosemicarbazones of 3-, 4-, and 5-methylisoquinoline-1-carboxaldehyde have also been synthesized [18] to assist in a definition of molecular dimensions compatible with biological activity. The syntheses of the methyl-substituted derivatives were accomplished by rearrangement of the N-oxides of 1,3-, and 1,4-dimethylisoquinoline with acetic anhydride followed by acid hydrolysis of the ester and subsequent oxidation of the carbinol with manganese dioxide. However, 1,5-dimethylisoquinoline (77) was selectively oxidized with selenium dioxide to the corresponding 1 [Pg.337]

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