4 Isoquinolones, 2,3-dihydro

The parent, unsubstituted isochromanone has been caused to react with a variety of aromatic amines to prepare Ar-substituted 1,4-dihydro-3(2.ff)-isoquinolones,4 and with amines to give amides.5 The 6,7-methylenedioxy-3-isochromanone was an intermediate in the synthesis of protopine and its allied alkaloids,6 and for the synthesis of the berberine ring system.7 The 6-methoxy analog was prepared as a potential intermediate in a camptothecin synthesis8 and 8-methoxy-4,5,6,7-tetramethyl-3-isochromanonc was an intermediate in the synthesis of sclerin.9 The compound herein described was the basis of a facile synthesis of ( l )-xylopmins,10 and its reaction with hydrazine has been reported.11... 

In a related type of reaction, the styryl isocyanates, readily available by Curtius rearrangement of cinnamoyl azides, undergo thermal cyclization to l-isoquinolones in good yield (equation 34) the reaction can also be carrried out using Friedel-Crafts catalysts. 2,3-Dihydro-4( 1//)- isoquinolones are obtained by Dieckmann cyclization of N- (o- carbalkoxy-benzyl)glycine ester derivatives (equation 35). The same reaction has been used for the synthesis of a range of non-aromatic heterocycles (equations 36 and 37). 

The transformation (190 — 191) exemplifies the use of transition metal reagents the reaction probably involves aminopalladation of the C = C bond (77JOC1329). 2,3-Dihydro-4(l//)isoquinolones are obtained by Dieckmann cyclization of 7V-(o-alkoxycarbonylbenzyl)glycine ester derivatives (192 - 193). 

Details of the sequence of steps in the thionyl chloride-mediated transformation of 4-carboxy-3,4-dihydro-3-phenyl-l(2//)-isoquinolines into indeno[l,2-c]isoquinolones have been elucidated62 and it is confirmed that the dehydrogenation precedes the electrophilic cyclization [of (56)]. 

A palladium-catalyzed three-component reaction with 2-iodobenzoyl chloride or methyl 2-iodobenzoate, allene and primary aliphatic or aromatic amines to prepare fV-substituted 4-methylene-3,4-dihydro-1 (27/)-isoquinolin-1 -ones was disclosed <02TL2601>. A synthesis of 1-substituted 1,2,3,4-tetrahydroisoquinolines via a Cp2TiMe2-catalyzed, intramolecular hydroamination/cyclization of aminoalkynes was also reported <02TL3715>. Additionally, a palladium-catalyzed one-atom ring expansion of methoxyl allenyl compounds 79 to prepare compounds 80 that can serve as precursors to isoquinolones was reported <02OL455,02SL480>. 

The 4-keto-l,2,3,4-tetrahydroisoquinolines are more systematically called 2,3-dihydro-4(l.ff J-isoquinolones, but the keto nomenclature would seem to be more descriptive of their properties. 

The alkylation of 2-(substituted amino)-9,10-dimethoxy-6,7-dihydro-4H-pyrimido[6,l-a]isoquinolon-4-ones usually led to a mixture of 2-(disubstituted amino)-6,7-dihydro and 2-(substituted imino)-3-alkyl-2,3,6,... 

Phthalide enolates (145), which can be viewed as dihomoenolates, add to Schiff bases to produce intermediate adducts (146) that cyclize to mixtures of cis and trans 3-aryl-4-hydroxy-3,4-dihydro-l(2W)-isoquinolones (147) and (148) (Scheme 30). As originally described by Dodsworth, Sammes and... 

Analogous condensations using lithium enolates of MA -diethyl-o-toluamide (149) have been described by Clark and Jahangir for the synthesis of 3,4-dihydro-l(2//)-isoquinolones (151 Scheme 31). It is fortunate that the enolate-imine addition-cyclization process occurs at low temperature, since warming the reaction mixture to room temperature, a common practice in many enolate-imine additions, leads to side reactions due to the instability of the 4-Iithiated derivative (150) formed by release of lithium diethylamide. The authors have exploited the in situ formation of (150) for the synthesis of 4-sub-stituted isoquinolones by trapping it with electrophiles. A cycloaddition mechanism via an... 

A patent for the preparation of quaternary salts of papaverine from C5, Ce, and Cg halides been published. N-Alkyl-papaverinium salts have been found to undergo oxidation by oxygen either photolytically or in the presence of cuprous chloride, to give the isoquinolones (25). The corresponding dihydro-papaverinium salts (26), with oxygen and cuprous chloride, do not suffer fission, and oxidation of the N-methyl compound (26 R = Me) in this way, followed by reduction of the product with sodium borohydride, affords a- and -hydroxy-laudanosines 21) The n.m.r. spectrum of laudanosine has been studied in detail. 

Ring expansion. A mixture of 2-benzyl-l,2-dihydro-7-methoxy-4(3H)-isoquinolone oxime, LiAlH4, and dry tetrahydrofuran stirred and refluxed 6 hrs. 4-benzyl-7-methoxy-l,3,4,5-tetrahydro-2H-l,4-benzodiazepine. Y 35%. R. I. Fryer et al., J. Org. Chem. 35, 2455 (1970). 

The synthesis and properties of i T-nitrosovalerolactam (II) and i T-nitroso-l,4-dihydro-6,7-dimethoxy-3(2 )-isoquinolone (III) are reported here along with directions for their use in the active site-directed inhibition of a-chymotrypsin. 

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