Phenylations isoquinoline

In 1968, the aforementioned reaction was repeated and found to produce a rearranged product (11). This was the first report of aryl migration with the Pictet-Gams conditions. The expected product was l-methyl-3-phenyl isoquinoline, but only 1-methyl-4-isoquinoline (11) was observed. Interestingly, the authors did not suggest a mechanism for the formation of the isolated product. 

There has been little systematic study of the chemistry of 1,4-oxazepines. Vigorous acid hydrolysis cleaves the amide linkage in (369 R1=Ph, R2 = H) and recyclization gives 2-o-hydroxyphenyl-5-phenyloxazoline and l,2,3,4-tetrahydro-l,8-dihydroxy-3-phenyl-isoquinoline. The l,4-benzoxazepin-5-one (353) can be alkylated at N but on treatment with triethyloxonium fluoroborate it is converted to 5-ethoxy-3-phenyl-l,4-benzoxazepine — one of the very few examples of a fully unsaturated 1,4-oxazepine ring. This product is isomerized to l-ethoxy-4-hydroxy-3-phenylisoquinoline when boiled in methanol. The 4,l-benzoxazepine-2,5-diones (348) are converted to quinazolines by reaction with ammonia. The dihydro-l,4-oxazepin-5-one (343) can be acetylated at nitrogen and bromi-nated at the 6-position. 

Chemical Name 8-Amino-l,2,3,4-tetrahydro-2-methyl-4-phenyl-isoquinoline maleate... 

Ar = Indole, p-carboline alkaloids Ar = Phenyl, isoquinoline alkaloids... 

The absolute configurations of (If , 4R)-l,2,3,4-tetrahydro-4-hydroxy-6-methoxy-2-methyl-l-phenylisoquinoline (31) and its epimer (IS, 4R), synthesised fromD-(+)-2-amino-l-(3-hydroxyphenyl)ethanol, have been determined with the aid of n.m.r. spectral and o.r.d. and c.d. measurements.42 These results may prove to be useful in the determination of the absolute configuration of 1-phenyl-isoquinoline alkaloids. In this regard, another report on the conformation and configuration of differently substituted tetrahydroisoquinolines may be consulted.43... 

Fig. 11.18 left Current-brightness-voltage characteristics of a single-layer red-emitting device based on (l-(phenyl)isoquinoline)2lr(acetylacetonate) piq2lr(acac) (see inset for the chemical structure). The structure of the device was PEDT/PVK PBD piq2lr(acac)/CsF/AI. 

Among the amines that have been resolved with (-)-DAG are a-phenylethylamine (a-methylbenzenemethanamine), [R-(R, R )]-2-amino-l-(4-nitrophenyl)-l,3-propanediol, 1,2,3,4,5,6,7,8-octahydro-l-(4-methoxyphenylmethyl)isoquinoline, 3-methoxymorphinan, 1,2,3,4-tetrahydro-7-methoxy-4-phenylisoquinoline, 3-hydroxy-i 7-methyl-morphinan, l,2,3,4-tetrahydro-6,7-dimethoxy-l-[3,4-(methylenedi-oxy)phenyl]isoquinoline, l,2,3,4-tetrahydro-6,7-dimethoxy-l-(3,4,5-tri-methoxyphenyl)isoquinoline, 2-[4-(phenylmethoxy)phenyl]-2-(3,4-di-methoxyphenyl)ethanamine, A-norlaudanosine (tetrahydropapaver-ine), and l,2,3,4-tetrahydro-6,7-dimethoxy-l-[3-methoxy-4- phenyl-methoxy)phenyl]isoquinoline. 

Rickborn and co-workers ° ° isolated the cycloadduct 164 from 4-phenylox-azole through careful manipulation of the experimental conditions (Fig. 3.50). They generated benzyne at 0°C from 1-aminobenzotriazole and lead tetraacetate. Compound 164 was stable at room temperature but, on heating, eliminated benzo-nitrile to give isobenzofuran 162, which could be trapped with A -methylmaleimide to afford a quantitative yield of the tetracyclic derivative 166 as an 88 12 mixture of endo and exo isomers. The cyclic aminal 164 was also sensitive to acid and rearranged to 4-hydroxy-3-phenyl-isoquinoline 165 on exposure to silica gel or a catalytic amount of trifluoroacetic acid. The benzyne cycloadditions were also carried out on 4-(4-nitrophenyl)oxazole and 4-(4-methoxyphenyl)oxazole. A fourfold rate increase was seen for the cycloaddition of the nitrophenyl-substituted oxazole relative to the methoxyphenyl analog, indicating a concerted process with little contribution from a polar intermediate. 

The only reactions of this type noted in the pyridopyridazine series are two classic Bischler-Napieralski type closures in benzo fused systems in which 3- or 4-benzamidopyridazines are cyclized to an adjacent phenyl group to give a 6-aryIpyridazino-[3,4-c]- (e.g. 361—> 362) or -[4,5-c]- isoquinoline respectively (59JCS1, 59JCS6). 

Reaction of 1-chloroisoquinoline with 5-phenyltetrazole gave 3-phenyl[l,2,4]triazolo[3,4-n]isoquinoline (428). It has been suggested that the initial 2-tetrazolylisoquinoline (425) underwent ring opening to (426) which readily lost N2 giving (427). This nitrilimine is a 1,5-dipole, and on cyclization the [l,2,4]triazolo[3,4-n]isoquino-line (428) is formed (70CB1918). 

To understand the unpredictable nature of the Pictet-Gams reaction, Hartwig and Whaley conducted the first mechanistic studies in 1949. Their work focused on substituent effects when directly attached to the ethylamine side chain. They also investigated a variety of dehydration agents in order to identify optimal reaction conditions. It was determined that formation of the isoquinoline structure was virtually impossible when alkyl or phenyl substituents were placed in the 4-position of the ethylamine side chain. 

The amino group of 3,4-dihydro-2//-pyrimido[2,l-n]isoquinoline 421 (R = H) was acylated with different isocyanates and phenyl isothiocyanate (98JMC1050). 

It is difficult to treat the effect of a heteroatom on the localization energies of aromatic systems, but Brown has derived molecular orbital parameters from which he has shown that the rates of attack of the phenyl radical at the three positions of pyridine relatively to benzene agree within 10% with the experimental results. He and his co-workers have shown that the formation of 1-bromoisoquinoline on free-radical bromination of isoquinoline is in agreement with predictions from localization energies for physically reasonable values of the Coulomb parameters, but the observed orientation of the phcnylation of quinoline cannot be correlated with localization ener-... 

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. 

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). 

Aminothiocarbonylphenyl)methoxy] derivative 384 was obtained from 8-[(4-cyanophenyl)methoxy]-2-cyclohexy 1-2,3,4,6,11,11 a-hexahydro-l/7-pyrazino[l,2-i]isoquinoline-l,4-dione by treatment with (EtO)2P(S)SH and one drop of H2O at room temperature for 17 h, then followed by addition of more H2O (98MIP7). Reaction of 8-[(4-aminothiocarbonylphe-nyl)methoxy] derivative 384 and MeCOCH2Cl yielded 8- [4-(4-methylthia-zol-2-yl)phenyl]methoxy derivative 385. 7-Bromomethyl derivative was prepared from the 8-hydroxymethyl-8-[(4-cyanophenyl)methoxy]-2-cyclo-pentyl-2,3,4,6,11,1 la-hexahydro-177-pyrazino[l, 2-i]isoquinoline-1,4-dione with PBr3 in CH2CI2 at room temperature. 7-[(l-Pyrazolyl)methyl] derivative was obtained from 7-bromomethyl derivative by treatment with pyrazole in the presence of NaH in DMF at 50 °C. 

Substituted 4-aryl-1 -oxo-1,2-dihydropyrazino[l, 2-i]isoquinolinium salts 402 were obtained when 3-substituted isoquinolines 401 were cleaved from a polymer by treatment 25% TFA (00MIP5). c/i-3,lla-H-3-Phenyl-1,2,3,4,11,11 fl-hexahydropyrazino[l, 2-i]isoquinoline-1,4-dione (404) formed when isoquinoline derivative 403 was cleaved from a resin with 25% TFA during an automated solid-phase synthesis (98BMCL2369). 

Thermolysis of the vinyl azide 11 in toluene furnishes a mixture of ethyl 2-phenyl-l//-3-benz-azepine-4-carboxylate(12), ethyl 4-(2-phenylvinyl)indole-2-carboxylate(13) and ethyl 1-benzyl-isoquinoline-3-carboxylate (14).82... 

Ethyl 1 -phenyl-1,8b-dihydroazirino[2,l- ]isoquinoline-3-carboxylate (2), obtained by decomposition of azide 1 (see Section 3.2.1.1.1.1.) in the presence of triethyl phosphite, on heating under reflux in toluene, rearranges quantitatively to the 3//-3-benzazepine 3.82... 

S )-(L-asparaginylamino)-2(/f)-hydrosy-4-phenyl-butyl]-7V-tert-butyldecahydro-(4aS,8aS)-isoquinoline-3(S)-carboxamide... 

CjjHjjNjOgS 191226-98-9) see Amprenavir Ar-(crt-butyI-2-[2(t )-hydroxy-4-phenyl-3(S)-phthalimido-butyI]decahydro-(4a5,8aS)-isoquinoline-3(S)-carbox-amide... 

Stereostructures of a co-crystal of (li )-l- 4-[(9aA)-perhydropyrido[l,2- ]pyrazin-2-yl]phenyl -2-phenyl-7-hydroxy-l, 2,3,4-tetrahydroisoquinoline with ERa-LBD301-553/C — S triple mutant <2005JME364> and iV-[2-(4-hydroxyphenyl)ethyl]-a-propyl-3-[(4-hydroxyphenyl)methyl]-l,4-dioxo-l,2,3,4,ll,l la-hexahydro-67/-pyrazino[l,2- ]isoquinoline-3-acetamide with fructose-1,6-biphosphatase <2003JBC51176> were determined by X-ray crystallography. The structure of a complex formed from 3-[( -methylphenyl)amino]-4-[(4-methylphenyl)imino]-4//-pyrido[l,2-tf]pyrazine with sodium bis(trimethylsilyl)amide and (norbornadiene)Mo(CO)4 in THF was characterized by single crystal X-ray diffraction <1995JPR38>. 

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