Isoquinoline, hydro

Hydrolysis and subsequent oxidation of 2-methyl-4,6,7,l Ifi-tetra-hydro[l,3]oxazino[2,3-n]isoquinoline-4-one (42) afforded ring opened product 43 (99TL8269). 

The rhodium(II) acetate catalyzed reaction of 2-(3-oxo-2-diazobutyryl)-1,2,3,4-tetrahydroisoquinoline in boiling toluene yielded 2-methyl-4,6,7,l 16-tetra-hydro[l, 3]oxazino[2,3-n]-isoquinoline-4-one in 72% yield (99TL8269). 

The mass spectral fragmentations of 9,10-dimethoxy-2,3,4,6,7,ll/)-hexa-hydro-l//-pyrimido[6,l-n]isoquinolin-2-ones 140 and -2,4-diones 141, under electron ionization (at 70 eV) were examined by metastable ion analysis, a collosion-induced dissociation technique and exact mass measurement (97RCM1879). Methyl substituent on N(3) in 140 (R = Me) had a larger effect on both the fragmentation and on the peak intensities, than a methyl substituent on C(6) (R = Me). The ionized molecules of 140 (R = H) were rather stable, whereas 4-phenyl substitution on C(4) of 140 (R = Ph) promoted the fragmentations of the molecular ions. The hexahydro-1//-pyrimido[6,l-n]isoquinoline-2,4-diones 141 were more stable, than the hexahydro-l//-pyrimido[6,l-n]isoquinolin-2-ones 140, and the molecular ions formed base peaks. 

Isoquinoline, 2-acetyl-l, 2,3,4-tettahydro-6,7-dimethoxy-l-inethylene-, 4 Isoquinoline, 2-benzoyl-l -benzy 1-1-cyano-1,2-dihydro- [1-Isoquinolinecarbo-mtrile, 2-benzoyl-l, 2-dihydro-l -(phenjlmethyl)-), 23 Isoquinoline, 2-benzoyl-l -cyano-1,2-di-hydro l-Isoquinohnecarbomtrile, 2-ben2oyl-l, 2-dihydro-], 20 ISOQUINOLINE, 1-BENZYL- [ISOQUINOLINE, HPHENYLMFTHYL)-], 19 Isoquinoline, 3,4-dihydro-6,7-dimethoxy-l-methyl-, 4... 

Dihydropyridines have also been starting points for stereospecific syntheses of hydro-phenanthridines and isoquinolines. Interest exists in these compounds because of the occurrence of this structural feature in alkaloids. For example, isoquinuclidine (263), derived from JV-alkoxycarbonyl-l,2-dihydropyridine, undergoes a Cope rearrangement to give the isoquinoline derivative (264) (80JA6157). Further chemical transformations of (264) provided a formal total synthesis of reserpine (Scheme 50). 

Isoquinoline, 2-acetyl-l,2,3,4-tetrahydro-6,7-dimethoxy-1-methylene-, 56, 4 Isoquinohne, 2 benzoyl 1-benzyl 1 cyano 1,2-drhydro-, 56, 23 Isoquinohne, 2-benzoyl-l-cyano-l, 2-di-hydro-, 56, 20... 

Synthesis. The starting material for the synthesis of levallorphan is 1-(4-Methoxy-benzyl)-1,2,3,4,5,6,7,8-octa-hydro-isoquinoline 6 (preparation see levorphanof) (Schnider and Griissner, 1951 Hellerbach, 1956 Ehrhart and Ruschig, 1972 Patron, 1979 Kleemann etal., 1999) ... 

Catalytic hydrogenation of 6-chloro-8-nitro-3,4-dihydro-2//-pyrimido-[l,2-a]isoquinoline in ethanol over Pt02 for 69 h afforded 8-amino-3,4-di-hydro-2H-pyrimido[l,2-a]isoquinoline (67IJC403). 

Treatment of 2-(2-methylphenyl)-5,5-dimethyl-l,4,5,6-tetrahydropyrimi-dine (279) with butyllithium in the presence of /V,/V,Al, /V -tetramethyleth-ylenediamine (TMEDA) in tetrahydrofuran at 0°C under nitrogen, then with methyl benzoates at -50°C gave 6-aryl-6-hydroxy-3,4,6,7-tetrahydro-2//-pyrimido[2,l-a]isoquinolines (280), which gave 6-ary 1-3,4-di hydro-2//-pyrimido[2,l-a]isoquinolines (281) with heating in toluene in the presence of p-toluenesulfonic acid (93JMC3098). 

The treatment of a diastereomeric mixture of 1-hydroxy-1,2,3,4-tetra-hydro-6H-pyrazino[l,2-fc]isoquinolin-4-one 236 with Et3SiH and TFA gave pentacyclic derivative 237 (08BMC9065). 

The 13C spectra of several 1-phenyl-3,4-dihydro-, l-phenyl-l,2,3,4-tetra-hydro-, and 1-naphthyl-3,4-dihydroisoquinolines have been reported in the compilation of Shamma and Hindenlang (7). The chemical shifts that have been assigned to the isoquinoline moieties in these molecules agree with those of similar systems discussed in previous sections of this article. The chemical shifts of the carbon atoms in the 3,4-dimethoxyphenyl groups are remarkably similar to those of the same unit in laudanosine (28). In the 1-naphthyl series the spectra of three compounds differently substituted in the naphthalene unit were recorded and assignments made to all carbon atoms. 

Treatment of 2-benzoyl-l,2,3,6,7,l lh-hexahydro-4//-pyrazino[2,l-a]-isoquinolin-4-one with NaNH2, then with ethylene oxide yielded the 3-(2-hydroxyethyl) derivative (76GEP2441261). 4-Thioxo and 2-(cyclohexyl-thiocarbonyl)-4-thioxo derivatives were prepared from 1,2,3,6,7,116-hexa-hydro-4//-pyrazino[2,l-a]isoquinolin-4-one and its 2-cyclohexylcarbonyl derivative by treatment with P4Si0. 

Heteroaromatic cations undergo reduction when treated with 1,4-dihydronicotinamide. An early study showed that the 10-methylacridinium ion (87) was rapidly reduced in a redox reaction to the 9,10-dihydro adduct by 1,4-dihydronicotinamides (M Scheme 18). A variety of systems including py-ridines, isoquinolines, quinolines and phenanthridines have been studied using this and related procedures. The selective reduction of pyridinium and quinolinium salts with 1-benzyl-1,2-dihydro-isonicotinamide (89) has been achieved. The selective conversion to the thermodynamically more stable 1,4-dihydro species (90 Scheme 18) is rationalized by the reversibility in the formation of the kinetic products (i.e. the 1,2-adducts) in the presence of pyridinium ions. In the pyridinium case 1,6-di-hydro adducts were also observed in some cases. Reactivity in such systems is sometimes hindered due to hydration of the dihydropyridine system. This is particularly so in aqueous systems designed to replicate biological activity. Dihydroazines derived from isoquinolines and 3,5-disubstituted pyridines have been reported to overcome some of these difficulties. ... 

Photochemically induced ring contraction of novel 4-iminodi-hydro-1,2,3-triazoles to the corresponding ( )- and (Z)-aziridin-imines has also been reported. A different pathway is followed in the 6-(l -triazolyl)uracils (24) which on irradiation in acetonitrile were converted into the pyrrolo[2,3-d]pyrimidines (25) via triplet biradical intermediates a novel cyclisation leading to the formation of pyrimido[4,5-c]isoquinolines is observed, however, when C-5 phenyl substituents are present on the triazole ring. Rate constants for the cycloaddition f diarylnitrilimines, generated by photoelimination of nitrogen from diaryl 2H-tetra-zoles, to various dipolarophiles have been determined experiment-... 

NMR data on 2-oxo-, 3-methyl-, and 3-phenyl-2,4-dioxo-l,3,4,6,7,l Ih-hexahydropyrimido[6,l-a]isoquinolines have been measured in CDCI3 (91MRC10 ). The structures of 3-amino-4-substituted 1,3,4,6,7,llh-hexa-hydro-2//-pyrimido[6,l-a]isoquinoline-2-ones have similarly been investigated by means of NMR spectroscopy (90JHC957). 

Quinoline, Isoquinoline, and their Benzo- and Hydro-derivatives. - Relatively few syntheses of quinolines are based on 2,3-disubstituted pyridines a recent addition to their number is illustrated in Scheme 33. The essential steps are Michael addition, intramolecular acylation, and aromatization via loss of toluene-p-sulphenic acid. ... 

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