Synthesis of isoquinolines from 2-phenylethylamines, amides, nitriles and carboxylic acids in polyphosphoric acid

Efficient One‐Pot Friedel–Crafts Acylation of Benzene and its Derivatives with Unprotected Aminocarboxylic Acids in Polyphosphoric Acid

“…[7,12] In a search of a new approach to isoquinolines we investigated the reaction of carboxylic acids, their esters, and anhydrides with 2-(3,4-dimethoxyphenyl)-ethylamine (homoveratrylamine) and its derivatives in PPA. [13] We found that this reaction afforded the corresponding 3,4-dihydroisoquinolines in good yields and purity.…”

One-Pot Synthesis of 1-(2-, 3- or 4-Aminophenyl)- and 1-(4-Aminobenzyl)-3,4-dihydroisoquinolines

“…9 The Friedel-Crafts acylation of activated benzene rings in the presence of polyphosphoric acid (PPA) is a very convenient method for direct synthesis of aromatic ketones. 13 This reaction was also applied to preparation of 1-substituted 3,4-dihydro-β-carbolines. 13 This reaction was also applied to preparation of 1-substituted 3,4-dihydro-β-carbolines.…”

“…-tetrahydroisoquinoline (5d): white solid, mp 142-143°C; 1 H-NMR (CDCl 3 ): 7.03 (2H, d, J=7.9 Hz, Ar), 6.67-6.58 (4H, m, Ar), 4.06 (1H, dd, J=4.3, 5.1 Hz, C-1), 3.84 (3H, s, OCH 3 ), 3.82 (3H, s, OCH 3 ), 3.50 (3H, m, NH and NH 2 ), 3.08 (2H, m, C-4), 2.84 (4H, m, C-3and CH 2 -Bn) 13. 13 C-NMR (CDCl 3 ): 147.4, 146.9, 145.5, 134.7, 129.7, 127.5, 114.9, 111.3, 110.9, 60.8, 55.7, 41.8, 29.2.…”

A Synthesis of N-Formylenamides of Isoquinoline

“…1,2 A few years ago we demonstrated a different approach, in which N-[2-(2-acyl-4,5-dimethoxyphenyl)ethyl]amides were obtained by acylation of N-acyl-3,4dimethoxyphenylethyl-amines with carboxylic acids in PPA and then cyclized in acidic media to provide various enamides of isoquinoline. 16 The success of this approach depends to an extent on the reaction conditions and on the nature of the N-acyl group in the starting compounds, since a cleavage of this group in the course of the reaction would lead to the formation 3,4-dihydroisoquinolines instead of enamides as end products. In this paper we report an extention of this method, allowing the synthesis of N-formylenamides of isoquinoline, which represent interest as intermediates in the synthesis of protoberberines, aporphines, dibenzopyrrocolines.…”