Photochemical synthesis of 1,2,3,4-tetrahydroisoquinolin-3-ones from N-chloroacetylbenzylamines

When N-chloroacetyl-3-hydroxybenzylamine (37) in aqueous acetonitrile was irradiated, both ortho and para photocyclizations with reference to the OH group occurred to give 7- and 5-hydroxy-3-oxo-1,2,3,4-tetrahydroisoquinolines (52,53). Similarly, 1-methylisoquinoline derivatives (54,55) were synthesized. N-Chloroacetyl-3,5-dihydroxybenzylamine (39) gave a single photoproduct, 5,7-dihydroxy-3-oxo-1,2,3,4-tetrahydroisoquinoline (56). These photocyclizations were smoothly extended to the synthesis of 1-benzyl, 1-(4′-methoxybenzyl)- and 1-(3′,4′,5′-trimethoxybenzyl)-isoquinoline derivatives (58～64).     

Stereochemical studies on the synthesis of 1,2,3,4-tetrahydroisoquinolin-4-ols

The stereoselectivity of the acid catalyzed promoted cyclization of adequately substituted α-aminoaldehydes to afford a series of tetrahydroisoquinolin-4-ols is studied. The results illustrate the effect of the substituents at C-1 and/or C-3 in the target heterocycle. The required precursors 5 and 10 were synthesized from the enantiomerically pure (−)-imines 1 by two different routes, and reacted with conc. HCl.     

Solution-phase parallel synthesis of novel 1,2,3,4-tetrahydroisoquinoline-1-ones as anticonvulsant agents

Following our previous studies in the field of anticonvulsant agents, we planned a one-pot solution-phase parallel synthesis (SPPS) of a small library of new 1,2,3,4-tetrahydroisoquinoline derivatives. The activity against audiogenic seizures in DBA/2 mice of the newly synthesized compounds has also been evaluated.     

Synthesis of New 1,2,3,4-Tetrahydroisoquinoline Derivatives. 2-(2,3,3-Trimethyl-1,2,3,4-tetrahydroisoquinolin-1-yl)anilines

A four-step procedure has been developed for the synthesis of new 2-(2,3,3-trimethyl-1,2,3,4-tetrahydroisoquinolin-1-yl)anilines by acylation of 2-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)anilines at the amino group with isobutyryl chloride, reduction of the endocyclic C=N bond in N-[2-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)phenyl]isobutyramides, N-alkylation of N-[2-(3,3-dimethyl-1,2,3,4-tetrahydroisoquinolin-1-yl)phenyl]isobutyramides to N-[2-(2,3,3-trimethyl-1,2,3,4-tetrahydroisoquinolin-1-yl)phenyl]isobutyramides, and acid hydrolysis of the latter.     

New approach to the synthesis of 1,2,3,4-tetrahydroquinolin-4-ones

The reaction of aromatic amines with complexes of N,N-dimethylacrylamide and N,N-dimethylmethacrylamide with trifluoromethanesulfonic anhydride leads to the formation of tetrahydro-4-quinolones and 3-methyltetrahydro-4-quinolones respectively. M. V. Lomonosov Moscow State University, Moscow 119899. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 503–508, April, 1997.     

A novel convenient synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones via 4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones

A novel four-step methodology for the synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones has been developed. The reaction of readily available N-[(1-acetoxy-2,2,2-trichloro)ethyl]ureas with Na-enolates of 1,3-diketones or β-oxoesters followed by heterocyclization-dehydration of the oxoalkylureas formed gave 5-acyl-4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones. The latter, in the presence of NaH, eliminate CHCl₃ to give the target compounds.     

Synthesis of 5-substituted 6-methoxy-1,2,3,4-tetrahydro-β-carbolin-1-ones

The nitration and bromination of 6-methoxy-1,2,3,4-tetrahydro--carbolin-1-one were studied. 5-Nitro and 5-bromo derivatives were obtained. 5-Acetyl-1,2,3,4-tetrahydrocarbolin-1-one oxime was obtained, and its Beckmann rearrangement was studied. The use of lithium aluminum hydride leads to reduction of the 5-acetyl group to give an alcohol group, whereas reduction of the acetyl group to an ethyl group occurs in the case of reduction with a palladium catalyst. Saponification of 5-substituted carbolin-1-ones with alcoholic alkali makes it possible to obtain 4-substituted tryptamines with a carbonyl group in the 2 position. The structures of the compounds were established by means of the PMR and mass spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 80–85, January, 1979.     

Cleavage of 2-(1,2,3,4-tetrahydroisoquinolin-1-yl)-2-phenyl-1,3-dithianes with HgO/BF3

Summary The title compounds (5) were prepared by addition of 2-phenyl-1,3-dithiane anion (2-lithiated10) to adequately substituted N-alkyl-3,4-dihydroisoquinolinium salts (7a–7g). Cleavage of compounds5 with HgO/BF₃ affords S-benzoyl-1,3-propanedithiol (4a) and the corresponding disulfide4c, benzaldehyde, and Hg(I) ions. In contrast to the title compounds, 2-(-dialkylaminobenzyl)-2-phenyl-1,3-dithianes (6) yield benzil under these conditions.In commemoration of the late Prof. Dr. Dr. h.c. mult.Horst Böhme, Marburg/Germany, an outstanding representative of Pharmaceutical Chemistry     

Experiments on the total synthesis of Lysolipin I. Part III. Preparation and transformations of substituted 1,2,3,4-Tetrahydrodibenzofuran-1-ones

1,2,3,4-Tetrahydrodibenzofuran-1-ones were obtained by Michael addition of 1,3-cyclohexadione ( 2 ) to o-benzoquinone ( 3 ) and to p-benzoquinones 8 and 11 (Scheme 2). In addition to the expected 7,8-disubstituted adduct 14 , the ZnCl₂-catalyzed reaction of dione 2 with methoxy-p-benzoquinone ( 11 ) afforded a small amount of the 6,8-disubstituted regio-isomer 13 (Scheme 2). The projected cleavage of these dibenzofuranones to 3-methoxy-2-phenyl-2-cyclohexenone 22 could be effected by treatment with NaOH followed by methylation (Scheme 3). Attempted acetalization of such dibenzofuranones resulted in a retro-Claisen-type cleavage, giving the benzofuryl-butyrate 16 . Other transformations include reduction of the ketone, of the C(4a)=C(9b) bond, and alkylation with Li-ethoxyacetylide (Scheme 3). Oxidation of 8-hydroxy-7-mehoxydibenzofuran derivatives led to o-quinones instead of the desired ring cleavage to p-quinones (Scheme 4).     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

1,2,3,5-Tetrahydro-4H-1,5-benzodiazepin-4-ones and 1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-ones from the reaction of hydrazoic acid on 1,2,3,4-tetrahydroquinolin-4-ones

The Schmidt reaction on 1,2,3,4-telrahydroquinolin-4-ones (1) gave 1,2,3,5-telrahydro-l,5-benzodiazepin-4-ones (II) and 1,2,3,4-tetrahydro-1,4-benzodiazepin-5)-ones(III). The ratio of II and III is dependent upon substituents present on the nitrogen ring atom of the quinolinones.     

Stereoselective synthesis of cyclohexa-2,4-dien-1-ones and cyclohex-2-en-1-ones from phenols

A convenient synthetic method for the synthesis of substituted cyclohex-2-en-1-ones by the direct alkylation of phenols has been developed. Furthermore, enantiomerically enriched 2,6-dimethyl-6-(3-methylbut-2-enyl)-cyclohexa-2,4-dienone was prepared by the deprotonation of 2,6-dimethylphenol with a sparteine–lithium complex followed by alkylation with 1-chloro-3-methylbut-2-ene. 2,6-Dimethyl-6-(3-methyl-but-2-enyl)-cyclohex-2-enone was prepared from the corresponding cyclohexa-2,4-dien-1-one by selective hydrogenation of the 4,5-double bond. The method was extended to 2-methyl-naphthalen-1-ol and 1-methyl-naphthalen-2-ol resulting in 2-(R)-methyl-2-(3-methylbut-2-enyl)-2H-naphthalen-1-one and 1-(S)-methyl-1-(3-methylbut-2-enyl)-1H-naphthalen-2-one, respectively.     

New convenient one-step synthesis of 4-arylphthalaz-1 -ones

4-Arylphthalaz-1-ones (2a–e) are prepared by the hitherto unknown reaction of N-aminophthalimide (1) with aromatic hydrocarbons under Friedel-Crafts conditions. The reaction of N-aminophthalimide with Grignard reagents presents another convenient method for the synthesis of 4-alkyl or 4-arylphthalaz-1-ones.     

一种铜催化合成异吲哚啉-1-酮的方法

本文设计了一种以邻苯甲腈和苯乙炔为原料,在铜催化剂的作用下环化生成异吲哚啉-1-酮的反应方法.以邻溴苯腈和苯乙炔作为反应模板,对溶剂、碱添加剂、催化剂、反应时间和温度做了探索,确定最佳反应条件为:碘化亚铜(0.02 mmol),去氧水(0.6 mmol),叔丁醇钾(0.3 mmol),1,4-二氧六环(0.2 mol·L^-1),100℃反应6 h.在最优反应条件下,对不同的反应底物进行了一系列的研究,底物适用性良好.     

Asymmetric synthesis of 3-hetero-substituted 2,3-dihydro-1H-isoindol-1-ones

An efficient asymmetric synthesis of highly enantioenriched 3-hetero-substituted 2,3-dihydro-1H-isoindolinones is reported. The key step is a diastereoselective nucleophilic addition on N-acylhydrazonium intermediates generated by acidic treatment of hemiaminal precursors bearing an (S)-2-alkoxymethyl-pyrrolidin-1-yl type auxiliary. The auxiliary is removed by an oxidative N,N-bond cleavage with magnesium monoperoxyphthalate.     

Mass spectra of trisubstituted 1,2,3,4-tetrahydro-1,5-benzodiazocin-2-ones

The mass spectra of 1,5-benzodiazocin-2-ones are characterized by multiline character due to the large number of pathways of fragmentation of the molecular ions. In a number of cases the same signal in the high m/e region corresponds to ions with different compositions. The principal fragmentation pathways were determined by high-resolution mass spectrometry. The possible structures of the fragment ions and the mechanisms of their formation are discussed. The mass spectra of model compounds were also investigated for this purpose.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 529–536, April, 1977.     

The synthesis of bicyclic 1,2,3,4-tetrahydro-1,4-benzodiazepin-5-ones from 2-(o-nitrobenzoyl)-1,2-thiazine-1-oxide precursors

Sulfinylation of o-nitrobenzamide and subsequent hetero Diels-Alder reaction gave a series of 2-(o-nitrobenzoyl)-1,2-thiazine-1-oxides. The 2-(o-nitrobenzoyl)-1,2-thiazine-1-oxides undergo a ring opening reaction with phenyl magnesium bromide to give allylic sulfoxides, which, after [2,3]-sigmatropic rearrangement and desulfurisation, furnish unsaturated vicinal N-(o-nitrobenzoyl)-1,2-amino alcohols. Oxidation of the alcohol and reductive ring closure gave a series of bicyclic 1,2,3,4-tetrahydro-1,4-benzodiazepin-5-ones, a subset of the ‘privileged’ 1,4-benzodiazepine structure. A 4-hydroxy-1,2,5-benzothiadiazepin-1,1-dioxide was synthesised by the same route starting from o-nitrobenzenesulfonamide.