3-Phenyl-1,2,3,4-tetrahydroisoquinoline

The mechanism (Scheme 3) of a Cu-catalysed aerobic oxidative coupling reaction of A-phenyl tetrahydroisoquinoline (15) with isopropenyloxy(trimethyl)silane (16)... 

Substituted benzylaminoacetaldehyde diethylacetals and phenols react at room temperature in the presence of 6 TV hydrochloric acid to give 4-phenyl-tetrahydroisoquinolines. ... 

Radical vs. ionic mechanisms were described as possible routes to the formation of the iminium ion complex using similar mechanisms to those we have already encountered in this chapter. The radical processes were thought to involve HAT and SET in either order, and the ionic process was thought to involve elimination of water from a nitrogen-amine coordination complex (29). A copper-catalyzed CDC reaction between Al-phenyl tetrahydroisoquinoline (THIQ) and nitromethane was found to proceed in 70% yield when BHT was added, which was taken as evidence for the ionic mechanism. 

Phenyl tetrahydroisoquinoline scaffold was selected as it was proven to be a convenient peripheral site binder [27]. There is a growing interest in developing multitarget-directed drugs and particularly new potent dual-binding site, AChE inhibitors are able to exert a dual action [33] (inhibition of cholinesterase activity and inhibition of AChE-mediated Ap deposition) [34]. The results of the m-AChE-directed syntheses of heterodimeric huprine-based inhibitors are summarized vide Table 2.1). 

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). 

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>. 

Two molecules with comparable geometry in an asymmetric unit were found for 3,4-bis(4-fluorophenyl)-l,2,5-oxadiazole 2-oxide. The bond length of the dipolar N-O bond is 1.107 (7) A <2006AXEo4827>. In the molecule of 5-(6,7-dimethoxy-l,2,3,4-tetrahydroisoquinolin-2-yl)-4-phenyl-l,2,5-oxadiazole Ar-oxide, the six-membered heterocyclic ring has a flattened boat form. Intermolecular C-H- O hydrogen bonds link the molecules into dimers, which may be effective in the stabilization of the crystal structure <2006AXEo3130>. 

A number of nonnatural amino acids were resolved into individual enantiomers on 0-9-(2,6-diisopropylphenylcarbamoyl)quinine-based CSPby Peter and coworkers [48,90,113,114] after derivatization with Sanger s reagent, chloroformates (DNZ-Cl, FMOC-Cl, Z-Cl), Boc-anhydride, or acyl chlorides (DNB-Cl, Ac-Cl, Bz-Cl). For example, the four stereoisomers of P-methylphenylalanine, P-methyltyrosine, P-methyltryptophan, and P-methyl-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid could be conveniently resolved as various A-derivatives [113]. The applicability spectrum of cinchonan carbamate CSPs comprises also P-amino carboxylic acid derivatives, which were, for example, investigated by Peter et al. [114]. A common trend in terms of elution order of DNP-derivatized P-amino acids was obeyed in the latter study On the utilized quinine carbamate-based CSP, the elution order was S before R for 2-aminobutyric acid, while it was R before S for the 3-amino acids having branched R substituents such as wo-butyl, iec-butyl, tert-butyl, cyclohexyl, or phenyl residues. 

A parallel study [94] was performed by the same authors on the retention of model compounds (tryptophan, erythro- and t/ireo-P-methyltryptophan, A-carbobenzyloxy-tryptophan, A-(3,5-dinitro-2-pyridyl)-tryptophan, l-[5-chloro-2-(methylamino) phenyl]-l,2,3,4-tetrahydroisoquinoline, and y-phenyl-y-butyrolactone) on a ristocetin A-based CSP, using the three RP, POM, and NP elution systems. Also, in this case, the natural logarithms of the retention factors (In k) of the investigated compounds depended linearly on the inverse of temperature (1 /T). 

Racemic, cyclic and open-chain 1,2-diarylalkanes have been deprotonated under the regime of the sparteine protocoP . )V-Methyl-4-phenyl-l,2,3,4-tetrahydroisoquinoline (276) was deprotonated by i-BuLi/(—)-sparteine (11) and the intermediates 277 were quenched by MeOD. When performing the reaction in diethyl ether, (R)-278 was isolated with high ee values, up to 88% (equation 68). ... 

These alkaloids have a phenyl or phenylpropyl nucleus. The group includes simple phenyl amine (tyramine, hordenine), catecholamine (dopamine, noradrenaline, adrenaline), simple tetrahydroisoquinoline (mescaline, anhalamine, anhalonine, anhalonidine), benzylisoquinoline (e.g., papaverine), phthalideiso-quinoline (e.g., noscapine), phenethylisoquinoline (autumnaline, floramultine and kreysigine), tetrahydroisoquinoline (emehne and cephaeline) and terpenoid tetrahydroisoquinoline (secologanin and ipecoside) alkaloids. 

An attempt to utilize this conversion of amines into aldehydes in an isoquinoline synthesis was not successful.439 Instead, reaction between 2-(3,4-dimethoxyphenyl)ethylamine and isatin afforded only the spiro compound 150.439 Reaction between isatin and 2-(3-hydroxy-4-methoxyphenyl)ethylamine gave a mixture of two spiro compounds, while a reaction of isatin, this amine, and benzylamine gave 6-hydroxy-7-methoxy-l-phenyl-1,2,3,4-tetrahydroisoquinoline.439... 

Phenyl-2,3,4,6,7,l 16-hexahydro[l,3]thiazino[2,3-a]isoquinoline was obtained by the reduction of 4-phenyl-2//-[l,3]thiazino[2,3-a]isoquinolinium perchlorate and its 3,4-dihydro derivatives with KBH4 in methanol (74IJC1242). Reduction of 4-methyl-5,6-dihydro-2//-[l,3]thiazino[2,3-ajisoquinolinium perchlorate with either NaBH4 or sodium cyanoborohy-dride gave a mixture of 4-methyl-2,3,4,6,7,116-hexahydro[l,3]thiazino[2,3-a]isoquinoline and 1,2,3,4-tetrahydroisoquinoline [81IJC(B)372]. 

Although most ring-substituents on the 1-position of the natural tetrahydroisoquinolines are substituted benzyl groups or isobenzo-furanones, occasionally a phenyl group is observed, bound directly to the isoquinoline ring. An ortho (2,8) attack leads directly to the indino[l,2,3-ij]isoquinolines, known commonly as the azafluoranthenes. 

The reduction of 2-substituted-isoquinolinium salts has been reported by Torossian65 with potassium borohydride in water, by Mirza,68 and by Durmand et al.,87,68 using sodium borohydride in aqueous methanol to yield 1,2,3,4-tetrahydroisoquinolines. The reduction of the second double bond appears to arise from a mechanism similar to that leading to tetrahydropyridines from pyridinium ions (see Section I). Mirza66 (see also Bose60) found that the reduction of berberine (60) with sodium borohydride could be stopped at the 1,2-dihydro-intermediate (61), and Karrer and Brook70 showed that the 1,2-dihydroisoquinoline formed by the lithium aluminum hydride reduction of l-phenyl-2-methylisoquinolinium iodide (62) could be further reduced to the 1,2,3,4-tetrahydroisoquinoline (63) with sodium borohydride in methanol. Awe et al.71,72 and Huffman73... 

EUP161917,85EUP164247 91JMC19). l,3,4,6,7,116-Hexahydro[l,4]ox-azino[3,4-a]isoquinoline and its 4-oxo derivative were obtained by cycliza-tion of 3-[o-(2-chloroethyl)phenyl]morpholine and l-[(2-chloroethoxy)-methyl]-l,2,3,4-tetrahydroisoquinoline on the action of ferf-BuOK, and by cyclization of 2-[o-(3-morpholinyl)phenyl]acetyl chloride on the action of NEt3 (67BRP1094470,67NEP6611733). 

Pyrazino[l,2-5]isoquinolin-5-ium 2-oxide perchlorate and its 3-methyl and 3-phenyl derivatives were obtained by cyclization of the appropriate 3-oximidomethyl-l-acylmethylisoquinolinium salt (or its oxime) through heating in an acidic medium (72JHC177). Swern oxidation of 2-acyl-3-hydroxymethyl-l,2,3,4-tetrahydroisoquinolines (298) proceeded smoothly to yield a diastereomeric mixture of l-hydroxy-l,3,4,6,ll,lla-hexahydro-2//-pyrazino[l, 2-5] isoquinolin-4-ones 136 (87TL4065). Heating (3-carboxy-... 

The aromatic, tetramethoxy-substituted, tetrahydroisoquinoline alkaloid weberine has been isolated recently from extracts of the Mexican cactus Pachycereus weberi (38). The rare occurrence of four adjacent methoxy groups on an aryl moiety prompted the synthesis and examination by crystal-structure analyses of analogs and derivatives with four and five adjacent methoxy groups on the phenyl ring. In contrast to the problem with... 

In Tables I and II, the known types of 4-acetoxy-, 4-alkoxy-, and 4-hydroxy-l,2,3,4-tetrahydroisoquinolines are indicated. Table III summarizes the known 4-keto-l,2,3,4-tetrahydroisoquinolines. In Tables IV and V, the various classes of 1,2,3,4-tetrahydroisoquinolines and aromatic isoquinolines which have been made by the methods discussed in this article are given. In Tables VI and VII, the 4-phenyl-l,2,3,4-tetrahydroisoquinolines and bicyclic compounds made by nucleophilic displacement of the 4-hydroxy group are summarized. Twenty-four compounds e.g., (31-40) prepared from 30 with active CH,78 NH, and SH77 compounds have been reported details may be found in the references cited. 

The reaction of l-phenyl-6,7-diethox -l,2,3,4-tetrahydroiso-quinoline with benzoyl C3 anide in benzene-acetic acid gave rise to 54 which on basic hydrol3 sis yielded l-phenyl-6,7-diethoxy-l,2,3,4-tetrahydroisoquinoline-1 -carboxamide. ... 

Miyake and co-workers (40) have published a synthesis of ellipticine that features a novel reductive phenylation of nitroarenes (41) (Scheme 4). Nitration of 5,8-dimethyl-l, 2,3,4-tetrahydroisoquinoline (22) gave an inseparable mixture of nitro compounds 23. Treatment of this mixture with iron pentacarbonyl and triflic acid in the presence of benzene gave a 2 1 mixture of amines 24 and 25. Separation of these isomers and diazotization of each with nitrous acid, conversion to the azide, and thermolysis yielded ellipticine (1) and isoellipticine (27) (5,11-dimethyl-10f/-pyrido[3,4- )]carbazole), respectively, following Pd/C dehydrogenation of the initially formed nitrene insertion product (e.g., 26). The overall yield of ellipticine is 9%. 

The initial attack in the anodic oxidation of papaverine [75] probably involves a similar attack further oxidation and dimerization leads to the isolated product, 12,12 -bis-(2,3,9,10-tetramethoxyindolo[2,l-fl]isoquinolyl). An analogous reaction is the electrooxidation of a tetramethoxy-substituted 2-methyl-l-phenethyl-l,2,3,4-tetrahydroisoquinoline to a dibenzoquinolizinium derivative [76] and the oxidation of A,A -triphenyl-( -phenyle-nediamine to 9,10-diphenylphenazine [77]. Intramolecular Michel addition of nitrogen in a tetrahydroquinoline derivative to an o-quinone moity have resulted in the formation of a 5,6-dihydrodibenz[6,d]indolizine derivative [78]. A similar ring closure occurs during the oxidation of various catecholamines [79] and similar compounds [79] to indoles. Cyclic a-carbonylazo compounds, generated by anodic oxidation of the hydrazines, may be trapped by reaction with dienes to the expected heterocycles [80]. 

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