Synthesis of benzyl substituted tetrahydropyridines and 1,2,3,4-tetrahydroisoquinolines via acid catalyzed cyclization of γ,δ-unsaturated N-formyl-N-styryl amines (original) (raw)
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Russian Chemical Bulletin, 2010
A three step method for the preparation of CF 3 substituted 1,2,3,4 tetrahydroisoquino lines and 1,2,3,6 tetrahydropyridines has been suggested. The first step includes alkylation of isoquinoline or 4 methylpyridine at the nitrogen atom with the formation of salts, which are involved into the reaction with Grignard reagent or lithium triethylborohydride to give en amines. The enamines undergo nucleophilic trifluoromethylation upon the action of Me 3 SiCF 3 under acidic conditions.
Journal of Heterocyclic Chemistry, 1986
Cyclocondensation of 6-amino-2,4-dioxopyrimidine or 2,4,6-triaminopyrimidine with 1-cyclohexenecarboxaldehyde 13 afforded regiospecifically, tricyclic, angular 1,3-disubstituted tetrahydropyrimido[4,5-~]isoquinolines 5 and 6 respectively. In addition, 2,4,6-triaminopyrimidine when condensed with 2-chloro-1-cyclohexenecarboxaldehyde 14, regiospecifically afforded the angular isomer 6. However, the cyclocondensation of 2,6-diamino-4-oxopyrimidine with 13 was regioselective and afforded a mixture of the linear and angular tetrahydrcpyrimidoisoquinolines 2 and 4. The growth of leukemia L-1210 cells in culture were inhibited 50% by 6 at 9 x 10.' M. Compounds 4 and 5 were not significantly active.
A new approach towards the synthesis of pyrrolo[2,1- a]isoquinolines
Tetrahedron Letters, 2010
Reaction of 5-bromo-2-methyl-8-nitro-1,2,3,4-tetrahydroisoquinoline with activated alkynes affords stable tetrahydropyrrolo[2,1-a]isoquinolin-4-ium ylides. Further reactions of ylide 2 gives access to substituted dihydropyrrolo[2,1-a]isoquinolines in good yields.
Tetrahedron, 2010
Knoevenagel products formed by the condensation of N-monoalkyl barbituric acids with o-tert-amino benzaldehydes undergo tert-amino effect reactions (T-reactions) yielding 1-alkyl-2,4,6-trioxoperhydropyrimidine-5-spiro-3 0-(1 0 ,2 0 ,3 0 ,4 0-tetrahydroquinoline) derivatives as a mixture of (S*,S*)-and (S*,R*)diastereomers. Mostly, the major diastereomer has the S*,S*-configuration. According to X-ray diffraction data in the solid form and NOE data in solution, diastereoselectivity of the T-reactions can be associated with the structure of the Knoevenagel products whose conformation is fixed by the strong intramolecular CeH/p interaction.
A Synthesis of N-Formylenamides of Isoquinoline
HETEROCYCLES, 2006
N-Formylenamides of isoquinoline (6) were obtained from N-[2-(2acyl-4,5-dimethoxyphenyl)ethyl]formamides (5) by cyclization in the presence of catalytic amount of p-toluensulfonic acid. The starting keto formamides (5) were obtained by acylation of a N-[2-(3,4-dimethoxyphenyl)ethyl]formamides (1) with carboxylic acids or their anhydrides in polyphosphoric acid (PPA).
The Journal of Organic Chemistry, 2005
The stereoselective outcome of Pd(II)-or Ag(I)-catalyzed intramolecular N-alkylation to afford 1,3disubstituted 1,2,3,4-tetrahydroisoquinolines was examined. In the absence of additional substituents, Pd(II) allows a facile access to the cis isomers, while Ag(I) favors formation of the trans isomers. The same observation was made for the synthesis of 2,5-disubstituted pyrrolidines.
Tetrahedron, 1994
Absbrmr: ~AUryl-3-(2-hy&~)-3,~~y~~l(2~-~u~o~one4~~c acids (SJ3) were prepared from homophthalic anhydride (1) and N-(2-hydroxyarylidene)akylammea (2J8). The acids SJ3 showed a tendency towards cyclodehydration to give isoquinoline derivatives with fused [l]benropyrane (8) or naphthopyrane (12) ring system. The relative cordigurations of the novel fused heterocyclic compounds 5,8,l2,l3 and related compounds were determined by NMR studies, and in the case of l3 also by means of X-ray analysis. Some MM2 force field molecular mechanica calculations on some selected fused heterocycles were executed. The naphtho[l',2':5,6]pyrano[4,3-clisoquinoline ring system incorporated in the lactone 12 is hitherto unreported. Reactions of homophthalic anhydrides with imines were used previously for synthesis of hetero-cycIes. Recently we showed that the reaction of homophthaiic anhydrides with o-chloro-imines leads to the formation of furo[3,4-c]isoquinolinediones.' As a continuation of our studies on the preparation of isoquinolines with annelated lactone ring, we examined as a first stage the reaction of homophthalic anhydride 1 and N-(2-hydroxyarylidene)allqdamines 2a.e and the hitherto undescribed 2b (Scheme 1).
To prepare new N-(1,2,3,4-tetrahydroquinolin-4-yl) pyrrolidin-2-one molecules and to characterize them by spectroscopic methods. Materials and methods. All reagents were purchased from Aldrich, commercial grade. The purity of the products and the composition of the reaction mixtures were monitored by thin layer chromatography over Silufol UV254 chromatoplates (0.25 mm). Product isolation and purification were performed by column chromatography (SiO2) using ethyl acetate. Results. Preparation of new N-(2-nitrophenyl-1,2,3,4-tetrahydroquinolin-4-yl) pyrrolidin-2-ones has been achieved via the one-pot synthesis, based on a BiCl3-catalyzed imino Diels-Alder cycloaddition reaction of toluidine, N-vinylpyrrolidin-2-one and 4-nitro- or 3-nitrobenzaldehydes. The structure of the pyrrolidine derivatives was confirmed by 1H nmr and 13C nmr studies, in addition to inverse-detected 2D NMR experiments and monocrystal X-ray diffraction. Conclusions. An efficient, economic, and fast synthetic route (multi-component imino Diels-Alder reaction) was employed in the construction of several new tetrahydroquinoline derivatives, useful and attractive rigid skeleton with well-defined stereochemistry.