Cyclization of dialkyl(4-hydroxy-2-butynyl)-(3 isopropenylpropargyl)ammonium salts and intramolecular recyclization of the resultant products

Abstract

Keywords: dialkyl(4-hydroxy-2-butynyl)(3-isopropenylpropargyl)ammonium salts, dialkyl(6-methyl-1,3-dihydro-4-isobenzofuranylmethyl)amines, intramolecular cyclization, base catalysis, recyclization.In previous work [1, 2], we showed that dialkyl(4-hydroxy-2-butynyl)(3-phenylpropargyl)ammonium chlorides and bromides or dialkyl(4-hydroxy-2-butynyl)(3-vinylpropargyl)ammonium chlorides and bromides cyclize under base catalysis conditions to give 2,2-dialkyl-4-hydroxymethylbenz[f]isoindolinium or 2,2-dialkyl-4-hydroxymethylisoindolinium salts, respectively. The intramolecular recyclization of these salts was discovered in a study of the stability of these products under aqueous alkaline cleavage conditions using a twofold molar excess of KOH [2, 3]. OH R 2 N O H R 2 N OH R 2 N O R 2 N O OH 1a-e 2a-e 1-3 a R = Pr; b R = C 4 H 9 ; c R+R = (CH 2 ) 4 ; d R+R = (CH 2 ) 5 ; e R+R = (CH 2 ) 2 O(CH 2 ) 2 3a-e 1 3 5 7 --Cl -+ + + Cl -Cl --__________________________________________________________________________________________

Synthesis and intramolecular recyclization of 2,2-dialkyl-6-chloro-4-hydroxymethyl-benzo[f]isoindolinium salts

“…Here, as before [2][3][4][5], the products from recyclization of compounds 2a-c -4-dialkylaminomethyl-8-chloro-1,3-dihydronaphtho[1,2-c]furans 3a-c -are also obtained with yields of 10-15%. The latter are formed with yields of 62-68% from the salts 2a-c by the action of a twofold molar excess of KOH in aqueous solution with heating (80-85°C), and with subsequent cyclization and recyclization without isolation of the salts 2a-c the total yields of the amines 3a-c amount to 75-82% [2][3][4].…”

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In the presence of 0.2 mol of aqueous KOH to 1 mol of the initial salt dialkyl(2-butynyl-4-hydroxy)-(3-R 1 -propargyl)ammonium salts (R 1 = Ph, vinyl, or isopropyl) undergo cyclization, forming 2,2-dialkyl-4-hydroxymethylisoindolinium and 2,2-dialkyl-4-hydroxymethylbenzo[f]isoindolinium salts [1][2][3].While studying the question of the stability of the above-mentioned salts under the conditions of aqueous alkaline cleavage we discovered intramolecular recyclization, which included a stage with cleavage of the isoquinoline ring by the action of the alkoxide ion formed in the alkaline medium and the formation of a dihydrofuran ring [2][3][4][5]. It was established that the recyclization process was facilitated by increase in the number of aromatic rings and by the presence of a methyl substituent in the benzene ring.

…”

“…In the presence of 0.2 mol of aqueous KOH to 1 mol of the initial salt dialkyl(2-butynyl-4-hydroxy)-(3-R 1 -propargyl)ammonium salts (R 1 = Ph, vinyl, or isopropyl) undergo cyclization, forming 2,2-dialkyl-4-hydroxymethylisoindolinium and 2,2-dialkyl-4-hydroxymethylbenzo[f]isoindolinium salts [1][2][3].…”

“…While studying the question of the stability of the above-mentioned salts under the conditions of aqueous alkaline cleavage we discovered intramolecular recyclization, which included a stage with cleavage of the isoquinoline ring by the action of the alkoxide ion formed in the alkaline medium and the formation of a dihydrofuran ring [2][3][4][5]. It was established that the recyclization process was facilitated by increase in the number of aromatic rings and by the presence of a methyl substituent in the benzene ring.…”

“…The ease of recyclization of the salts with substituents in the aromatic ring [3] and the salts with the phenanthrene ring [5] compared with the 2,2-dialkyl-4-hydroxymethylisoindolinium analogs is explained by the higher aromaticity of the benzene ring.…”