Isoquinolin-l-ones

Isoquinolin-1 -one, 3-(4-methoxyphenyl)-1,2-dihydro-synthesis, 3, 685 Isoquinolin-l-one, 3-methylthio-synthesis, 2, 403 Isoquinolin-l-one, 3-thiomethyl-syn thesis... 

Treatment of (11 aS)-3-isopropyl-11 a-methyl-4-phenyl-1,6,11,11 a-tetrahy-dro[l,4]oxazino[4,3-6]isoquinolin-l-one (243) with 6N HCl in a pressure tube, then the reaction of the work-up residue with propylene oxide gave (3S)-3-methyl-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (244) (99S704). 

Additions of stabilized carbanions to imines and hydrazones, respectively, have been used to initiate domino 1,2-addition/cyclization reactions. Thus, as described by Benetti and coworkers, 2-subshtuted 3-nitropyrrolidines are accessible via a nitro-Mannich (aza-Henry)/SN-type process [165]. Enders research group established a 1,2-addition/lactamization sequence using their well-known SAMP/ RAMP-hydrazones 2-308 and lithiated o-toluamides 2-307 as substrates to afford the lactams 2-309 in excellent diastereoselectivity (Scheme 2.72) [166]. These compounds can be further transformed into valuable, almost enantiopure, dihydro-2H-isoquinolin-l-ones, as well as dihydro- and tetrahydroisoquinolines. 

N-Substituted 4-methylene-3,4-dihydro-l-(2H)-isoquinolin-l-ones are synthesized by means of a palladium-catalyzed three-component process (Scheme 16.5) [9]. 

Attaching cyclic, bidentate 1-hydroxy-177-pyridin-2-thione, 1-hydroxy-177-pyridin-2-one (1,2-HOPO) and 2-hydroxy-277-isoquinolin-l-one (1,2-HOIQO) ligating units via their C-6 carbon to TREN template produced 19 , 20 and 21 , respectively. 

For the bicyclic compounds the differences in aromaticity between the two possible forms were smaller, about 8 and about 18 kJ mol-1 for the quinolin-2-one and isoquinolin-l-one systems respectively. Similar values were found for the corresponding bicyclic thiones. 

The aromatic energy differences between the aminopyridine and pyridinone imine form (jE yridine -Epyridineimine) can be found as detailed previously (see Section 2.04.4.2) (72JCS(P2)1295). The pyridinone imine form retains much aromaticity, but less so than in the case of the oxygen compounds, as can be seen from the following figures for the above quantity 2-aminopyridine/pyridin-2-one imine, 42 4-aminopyridine/pyridin-4-one imine, 61 2-aminoquinoline/quinolin-2-one imine, 21 1-aminoisoquinolinone/isoquinolin-l-one imine, 26 kJ mol-1. 

Isocoumarins react with aqueous ammonia or alkylamines to give good yields of isoquinolin-l-ones for example 3-(4-methoxyphenyl)-l,2-dihydroisoquinolin-l-one (282). A 7-nitro group in the isocoumarin may be reduced by treatment with hydrazine and Raney nickel to the corresponding 7-amino derivative (284), but with hydrazine alone a 2,3-benzodiazepin-l-one (283) is formed (68JCS(C)2205,57JGU2342,81CPB249). 

Two mechanisms (i.e. direct hydrolysis and alternatively a path via an unstable acyl phosphate intermediate) are involved in the hydrolysis in phosphate buffer of N-arylsulfonyl / -lactams such as (130).107 The acyl phosphate intermediate can be trapped with hydrazine. The alkaline hydrolysis of some torsionally distorted lactams, i.e. the bridged benz[rfe]isoquinolin-l-ones (131), in 70% (v/v) DMSO-water has been compared under the same conditions with the hydrolysis of AvA-dimethyl-1 -naphthamide (132). The relative rates of reaction and activation parameters indicate the effect of torsional distortion.108 The reaction of the tricyclic azetidinones (133) with trifluoroacetic acid gives the bicyclic thioesters (135). The mechanism may involve acid-catalysed elimination of methanethiol to give an azetinone intermediate (134) which, after nucleophilic attack of the thiol, is converted into (135).109... 

JA11707), 4-cyano-3-phenyl-3-trifluoromethyl-2,3-dihydro-lH-pyrido [l,2-c]pyrimidin-l-one (05MI1), and 10-(ferf-butyl)-3-methylene-3,4,4fl,5-tetrahydro-3H-[l,3]oxazino[3,4-b]isoquinolin-l-one (07EJ02015) under either acidic or basic conditions. 

Reaction of tetrahydroisoquinoline-3-carboxylic acid 434 with primary amines and isonitriles provided 1,2,3,4, 1,11 -hexahydro-6H-pyrazino [l,2-b]isoquinolin-l-ones 435 (06HEC107). 

Mcthyl-2//-isoquinolin-l-one derivatives 41 are accessible by the reaction of substituted o-bromobenzamides 40 with carbanions. One such example is... 

Oxidation of 8,9-dihydroxy-l, 3,4,6,11,1 la-hexahydro [1,4]oxazino[4,3-6]isoquinolin-l-one with Se02 in hot AcOH afforded 8,9-dihydroxy-l-oxo-... 

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