Central nervous system active compounds. VI. Reissert compounds as precursors of 1-(3-phthalidy1)isoquinolines

Abstract

The reactions of isoquinoline and phthalazine Reissert compounds with phthalaldehydic acids and their derivatives have been investigated as a means of synthesizing 1-(3-phthalidyl)isoquinolines. Of a variety of conditions tried those involving phase transfer were found, in general, to be the most suitable. The products, which are analogues of the convulsant alkaloid bicuculline, showed weak central nervous system depressant activity.

Phthalides and Phthalans: Synthetic Methodologies and Their Applications in the Total Synthesis

“…151c In the similar vein, Reissert compounds 438 react with phthalaldehydic acids 437 in the presence of KOH and benzyl triethylammonium chloride to give isoquinolylphthalide 439 (Scheme 109). 152 Such reactions are not applicable to 3-ethoxy or 3-bromophthalides.…”

Synthesis of Phthalides and 3,4-Dihydroisocoumarins Using the Palladium-Catalyzed Intramolecular Benzannulation Strategy

“…Phthalides and 3,4-dihydroisocoumarins are a class of naturally occurring substances exhibiting biological activities. , They are also attractive intermediates for the synthesis of more complex heterocyclic and carbocyclic compounds, various drugs, and naturally occurring compounds . Although various methods have been developed for the synthesis of phthalides and dihydroisocoumarins, only a limited number of papers are known for the construction of phthalide and dihydroisocoumarin skeletons from acyclic, acetylenic compounds in a one-step procedure. − For example, the Alder−Rickert reaction, nickel-catalyzed 8 or mediated 9 [2 + 2 + 2] cocyclization of alkyne moieties, and rhodium-catalyzed carbocyclization reaction of diazocarbonyl with tethered alkynes 10 are known as a one-step synthetic procedure.…”

The Recent Impact of Solid-Phase Synthesis on Medicinally Relevant Benzoannelated Oxygen Heterocycles

“…Strategy I (Scheme 17) is the addition of ortho-metalated esters 125 (X ) OR), amides 125 (X ) NR 2 ), or their synthons to aldehydes 126 and cyclization to 130. Strategy II is the treatment of formylsubstituted benzoic acids 129 with organometallic reagents, such as alkyllithium, 69 alkylzinc, 70 alkylsodium, 71 alkyltitanium 72 or Grignard reagents. 73 The corresponding lactones 130 are formed during or after acidic workup.…”