Title : Synthesis of derivatives of 4-hydroxymethylisoindolinium chlorides and their intramolecular recyclization
Base catalyzed intramolecular cyclization, discovered by acad. A.T. Babayan, prof. E. O. Chukhajian with coauthors, is a absolutly new direction in organic and fine organic chemistry and includes excellent possibilities for the synthesis of di-, tri- and tetracyclic condensed isoindolinium and also linearly annulated benzo[f] isoindolinium salts. In continuation of the research, it was found that in the base catalysed conditions -(4-hydroxybut2-ynyl)(3-alkenyl- or 3-aryl-prop-2-ynyl)ammonium chlorides undergo intramolecular cyclization. For cyclization of above mentioned salts in contrast of the propargylic analogs the reaction mixture is heated at 40–45 °C during 10–15 min, then takes place cyclization with self-heating. The cyclic products - chlorides of -4-hydroxymethylisoindoliniumand –benzo[f]isoindolinium were obtained with high yields. In 2003 it was established that the above mentioned salts in water-base cleavage reaction conditions undergo intramolecular recyclization. As a result are formed derivatives of 1,3-dihydroisobenzo[c]furan, the formation of which include nucleophilic attack of the alkoxy ion on the partially positively charged carbon atom of the isoindolinium cycle. This leads to breaking of N-C bond of the isoindolinium as well as to formation of new C-O bond.
Recently it was established that the cyclization of dialkyl(4-hydroxybut-2-ynyl)(3--bromphenylprop-2-ynyl)ammonium chlorides in water-base condition is accompanied by the subsequent recyclization of cyclic products.
In the case of piperidinium and morpholinium analogs it was possibile to isolate the corresponding salts: chlorides of 2,2-pentamethylen-4-hydroxy-6-brombenzo[f]isoindolinium and spiro[4-hydroxymethyl-6-brombenzo[f]isoindolin]- 2,4’-morpholinium. The recyclization of these salts under the conditions of water-alkali cleavage is realized at the room temperature. The observed phenomenon is unique in the field of intramolecular recyclization.
The study revealed the influence of substituents at nitrogen atom, in aromatic ring and the number of aromatic rings on the base-catalyzed cyclization as well as the intramolecular recyclization of cyclic products. For the first time revealed by us intramolecular recyclization is a domino process and, in contrast to intermolecular recyclization, is not accompanied by a narrowing or an increase of the cycle, and instead of a five-membered isoindolinium cycle, a dihydrofuran cycle is formed.
Audience Take Away:
- The audience will learn how to expand the area of base catalized intramolecular Cyclization and Recyclization for synthesis of new bioactive nitrogen-containing heterocycles, 1,3-dihydrobenzo[c]furans and their condensed analogs.
- These compounds have proved to be very attractive and useful for the synthesis and design of molecules of potential drugs.
- The involvement of new dienes and dienophiles in base catalized intramolecular Cyclization and Recyclization will Page 106 Catalysis and Green Chemistry 4th Edition of International Conference on ICG 2019 help to synthesize compounds, the synthesis of which by another methods is difficult.