Synthesis and Photo-oxygenation of Some Substituted 1-Benzyl-3,4-dihydroisoquinolines. Mechanism of Enamine Photo-oxygenation

The synthesis of a series of substituted 1-benzyl-3,4-dihydroisoquinolines by Bischler-Napieralski cyclization is described. Competitive methylene blue sensitized photo-oxygenation experiments allowed the determination of relative rates of photo-oxygenation of 1-benzyl-3,4-dihydroisoquinolines, Substituents were shown to affect both the equilibrium concentration of the tautomeric enamine and the overall photo-oxygenation rate. After correcting for differences in enamine concentration, the relative rate data provided a diagnostic probe of the reaction mechanism, which involves transfer of charge in the rate-limiting step.     

Reactions of 1,3,3-trimethyl-3,4-dihydroisoquinolines with polyhaloalkanonitriles

The reactions of 1,3,3-trimethyl-3,4-dihydroisoquinolines with halogenated nitriles afford -aminovinylimines, which undergo acid hydrolysis to form 1-(polyhaloacylmethylene)-3,3-dimethyl-3,4-dihydroisoquinolines.     

Direct heterocyclization of tetrahydroisoquinolin-1-ylideneacetic acids by the action of 5-arylfuran-2,3-diones

Aroylketenes generated in situ by thermolysis of 6-aryl-2,2-dimethyl-4H-1,3-dioxin-4-ones reacted with 3,3-dialkyl-1-methyl-3,4-dihydroisoquinolines to give (1Z,3Z)-4-aryl-4-hydroxy-1-[3,3-dialkyl-3,4-dihydroisoquinolin-1(2H)-ylidene]but-3-en-4-ones. The crystalline and molecular structure of (1Z,3Z)-4-hydroxy-1-[6,7-dimethoxy-3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-ylidene]-4-phenylbut-3-en-2-one was studied by X-ray diffraction.     

Etude en RMN: Couplages a Longue distance dans les Perfluoro-alkyl-1 Dihydro-3,4 Isoquinoléines et Perfluoro-alkyl-1 Isoquinoléines

The ¹H and ¹⁹F NMR spectra of 1-(perfluoroalkyl)-3,4-dihydroisoquinolines and 1-(perfluoroalkyl)isoquinolines have been investigated. Several long distance couplings were observed: the α-fluorine atoms of the perfluoroalkyl chains exhibit in the 1-(perfluoroalkyl)-3,4-dihydroisoquinolines homoallylic coupling with the methylenic protons in position 3, and in the 1-(perfluoroalkyl)-4-methylisoquinolines interbenzylic coupling with the methyl groups in 4, respectively. Furthermore the α-fluorine atoms of the perfluoroalkyl chains are, in all the compounds, coupled with the H-8 proton. To our knowledge, this is the first time that such a ⁵J coupling of an aromatic proton and a fluorine atom has been demonstrated. The various long distance couplings are interpreted using geometric, steric and electonic effects.     

Synthesis and spectral properties of 6,7-dimethoxy-1-[(ortho; and para-R)-phenyl]-3,4-dihydroisoquinoline

The preparation of eleven novel 6,7-dimethoxy-1-[(ortho, and para-R)-phenyl]-3,4-dihydroisoquinolines with possible pharmacological activity is described. The structure of all products was corroborated by ir, ¹H-nmr, ¹³C-nmr, and ms.     

Reaction of 1-methylthio-3,4-dihydroisoquinolines with amines

A study was carried out on the reaction of 1-methylthio-3,4-dihydroisoquinolines with aromatic and aliphatic amines, thiourea, semicarbazide, and thiosemicarbazide. The reactions with anthranilic acid and 2-amino-3-carboethoxy-4,5-dmeurylthiophene give 6,6-dmethyl-5,6-dihydro-8H-isoquino[1,2-blquinazolin-8-one and 6, 6, 9,10-tetramethyl-5,6-dihydro-8H-benzo[i]thieno[2,3-b]quinolizin-8-one, respectively. 1-Semicarbazido-and 1-thiosemicarbazido-3,4-dihydroisoquinolines were shown to undergo thermal elimination of ammonia to give substituted 1, 2, 4-triazolo [3, 4-a]isoquinolin-3-ones and 1, 2, 4-triazolo[3, 4-ajisoquinoline-3-thiones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 800-806, June, 1996. Original article submitted June 19, 1995; revision submitted March 14, 1996.     

Synthesis of substituted bis(3,3-dialkyl-3,4-dihydro-1-isoquinolyl)methanes

Symmetrical and non-symmetrical substituted bis(3,4-dihydro-1-isoquinolyl)methanes were synthesized by fusion of substituted 1-methylthio-3,4-dihydroisoquinolines with 1-methyl-3,4-dihydroisoquinolines and by the Ritter reaction of 1,1-dialkyl-2-arylethanols with 1-cyanomethylidene-1,2,3,4-tetrahydroisoquinoline or malononitrile.     

[3+3] Cyclocondensation of 1-alkyl-substituted 3,4-dihydroisoquinolines with 2-aminomethylenecycloalkane-1,3-diones or aminomethylene malonates: A novel annelation reaction in the series of cyclic Schiff's bases

A new approach to the construction of polycyclic skeletons of fused azines with nitrogen at the bridgehead based on a novel reaction of cyclic Schiff's bases (1-alkyl-substituted 3,4-dihydroisoquinolines) with α-aminomethylenecarbonyl compounds (2-aminomethylene-cyclohexane-1,3-diones or aminomethylenemalonic ester) was developed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1358–1360, July, 1997.     

Symmetrical and Unsymmetrical Bis-1,1′-(3,4-dihydroisoquinolines)

3,3,-Dialkyl-1-cyano-3,4-dihydroisoquinolines were prepared by Beckmann defragmentation of ethyl α-(3,3-dialkyl-3,4-dihydroisoquinol-1-yl)-α-hydroximinoacetates and they take part in a Ritter reaction to form substituted bis-1,1′-(3,4-dihydroisoquinolines).__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 558–563, April, 2005.     

Mild and Efficient Syntheses of 1-Aryl-3,4-dihydroisoquinolines and 1-Aryl-3,4-dihydro-β-carbolines via Regiospecific β-Eliminations of the Corresponding N-Tosyl-1,2,3,4-tetrahydroisoquinolines and N-Tosyl-1,2,3,4-tetrahydro-β-carbolines

Treatment of N-tosyl-1-aryl-1,2,3,4-tetrahydro-isoquinolines or N-tosyl-1-aryl-1,2,3,4-tetrahydro-β-carbolines with a strong base such as NaOH or KOH at 70 °C in dimethylsulfoxide (DMSO) produced 1-aryl-3,4-dihydroisoquinolines or 1-aryl-3,4-dihydro-β-carbolines in good yields via mild and regiospecific β-eliminations. A dramatic solvent effect was observed, DMSO was crucial for the reactions. The temperature is also crucial for the reactions and should be kept between 60 and 80 °C.     

Ritter reaction. Synthesis of 1-substituted 3,3,7,9-tetramethyl-2-azaspiro[4.5]deca-6,9-dien- and -1,6,9-trien-8-ones and 7-methoxy-3,3,6,8-tetramethyl-3,4-dihydroisoquinolines

1-(4-Methoxy-3,5-dimethylphenyl)-2-methylpropan-1-ol reacted with nitriles [MeSCN, PhCN, MeCN, EtOC(O)CH₂CN] in the presence of concentrated sulfuric acid to give both 1-R-3,3,7,9-tetramethyl-2-azaspiro[4,5]deca-6,9-dien- and -1,6,9-trien-8-ones and 1-R-7-methoxy-3,3,6,8-tetramethyl-3,4-dihydroisoquinolines. The reaction with 3,4-dimethoxyphenylacetonitrile afforded 10,11-dimethoxy-1,3,6,6-tetramethyl-1,5,6,12b-tetrahydrodibenzo[d,f]indole-2,8-dione. Three-component condensation of 2-methoxy-1,3-dimethylbenzene with isobutyraldehyde and nitriles led to the formation of spirocyclic systems and 3,4-dihydroisoquinoline derivatives in lower yield.     

A Novel Synthesis of Aporphines via 3-Phenylphenethylamines

rac-1,2,10-Trimethoxy-aporphine ( 14 ) and rac-2-ethoxy-10,11-dimethoxyaporphine ( 27 ) have been synthesized from the 3-phenylphenethylamines 9 and 22 by a new route. The 8-phenyl-3,4-dihydroisoquinolines 11 and 24 , the oxo-aporphines 12 and 25 and the rac-nor-aporphines 13 and 26 were obtained as intermediates.     

New type of recyclization in 3,4-dihydroisoquinolines in the synthesis of β-(o-indazolylaryl)ethylamines and their 7-azaindazolyl analogues

1-(2-Hydrazinoaryl)-3,4-dihydroisoquinolines and their hydrazinopyridyl analogues undergo recyclization affording novel (7-aza)indazolyl-β-arylethylamines. The products are expected to possess neurotropic activities.     

Application of the Intermolecular α-Amido-alkylation Reaction for the Synthesis of Tertiary Amides and 1-Substituted 2-Acyltetrahydroiso-Quinolines. Synthesis of (±)-Carnegine

Adducts 4 of Schiff bases and 3,4-dihydroisoquinolines with acyl chlorides react with Grignard reagents 5 in an intermolecular α-amidoalkylation reaction to the corresponding tertiary amides or 1-substituted 2-acyltetrahydroisoquinolines.     

An AB + D → ABCD approach to the construction of the 8-azasteroid skeleton by [3+3] cyclocondensation of 3,4-dihydroisoquinolines with ethyl 2-oxocyclopentanecarboxylate as a new annelation reaction for a series of cyclic Schiff"s bases

A new approach (AB + D ABCD) to the construction of tetracyclic 8-azagonane (cyclopenta[5,6]pyrido[2,1-a]isoquinoline or benzo[a]cyclopenta[f]quinolizine) structures was developed and exemplified by cyclocondensation of 1-alkyl-3,4-dihydroisoquinolines with ethyl 2-oxocyclopentanecarboxylate.     

Reactions of the nitrosonium ion. VII. Syntheses of dihydroisoquinolines and oxazoles from azides in nitrile solvents

N-Alkylnitrilium salts are cleanly produced from alkyl azides by reaction with nitrosonium salts in nitrile solvents. Syntheses of 3,4-dihydroisoquinolines from nitrilium ions formed in this method from 2-phenylethyl azide are described. Oxazoles are readily formed from phenacyl azides by this general method; the advantages of oxazole syntheses through azide nitrosation are discussed.     

Ternary condensation of cyclic azomethines,aromatic aldehydes,and barbituric acid: A new approach to the synthesis of 8,15,17-triaza-d-homogonanes

New fused heterocyclic compounds of the 8,15,17-triaza-d-homogonane series have been obtained by ternary condensation of cyclic azomethines (1-methyl-3,4-dihydroisoquinolines) with aromatic aldehydes and barbituric acid in DMF.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2353–2355, September, 1996.     

Oxiranes in the Ritter Reaction. Synthesis of 6,7- and 5,8-Dimethoxy-3,3-dialkyl-3,4-dihydroisoquinolines by a Tandem Alkylation-Cyclization Reaction

The interaction of 1,2- or 1,4-dimethoxybenzene with isobutylene oxide and nitriles RCN leads to 1-R-6,7- or 1-R-5,8-dimethoxy-3,3-dimethyl-3,4-dihydroisoquinolines. In the case of 1,2-dimethoxybenzene and cyclohexene oxide the similar reaction is accompanied by rearrangement and 1-R-3,3-tetramethylene-3,4-dihydroisoquinolines are formed in low yield. On using cyanoacetic acid ester and any oxide derivatives of tetrahydroisoquinolylideneacetic acid are formed.     

Saturated heterocycles. Part 209. Synthesis of 1-cyclohexyl-substituted isoquinoline derivatives

In contrast with earlier literature data [7], both acrylic esters and acrylonitrile underwent Michael addition to l-methyl-3,4-dihydroisoquinolines 1-4 to yield the diesters 5-9 or the dinitrile 10 , respectively. Compounds 5-10 were converted by Claisen condensation to 1-[(3′-methoxycarbonyl- or 1-[(3′-ethoxycarbonyl-4′-oxo)-l'-cyclohexyl]-3,4-dihydroisoquinoline derivatives 11-16 . Several derivatives of 12 were prepared. The new compounds possess various pharmacological actions.     

A simple synthesis of the pentacyclic lamellarin skeleton from 3-nitro-2-(trifluoromethyl)-2H-chromenes and 1-methyl(benzyl)-3,4-dihydroisoquinolines

The basic structural framework of lamellarin alkaloids, 8,9-dihydro-6H-chromeno[4′,3′:4,5]pyrrolo[2,1-a]isoquinoline derivatives, has been obtained in good yields via Grob synthesis between 3-nitro-2-(trifluoromethyl)-2H-chromenes and 1-methyl-3,4-dihydroisoquinolines in refluxing isobutanol. In the case of 1-benzyl-3,4-dihydroisoquinolines, a dynamic NMR effect was observed in the ¹H and ¹⁹F NMR spectra of the products as a result of restricted rotation about the single bond linking the benzene ring and the heterocyclic system. When the reaction was carried out with 3-nitro-2-(trichloromethyl)-2H-chromenes in toluene at room temperature, only Michael adducts, as a mixture of two diastereomers, were isolated.