DBU Catalyzed One-pot Four-component Synthesis of Benzo[a]pyrano[2,3-c]-phenazines and Spiro[benzo[a]pyrano[2,3-c]phenazine-1,3'-indoline] Derivatives
Authors: Banerjee Bubun , Singh Arvind , Kaur Manmeet , Priya Anu , Sharma Aditi 
Published: February 2025

aims:

To developed a simple, efficient and straightforward approach for the one-pot four component synthesis of a benzo[a]pyrano-[2,3-c]phenazines and spirobenzo[c]pyrano[3,2-a]phenazine derivatives from the equimolar reaction of 2-hydroxy-1,4-naphthaquinone, o-phenylenediamine, malononitrile and various aromatic as well aliphatic aldehydes or isatins respectively in the presence of a catalytic amount of DBU as catalyst in aqueous ethanol at 120 °C.

background:

Various phenazine derivatives are well known for their significant biological activities. Majority of them are available in natural sources. Many phenazine fused heterocycles especially benzo[a]phenazine derivatives possess immense biological efficacies which include antimicrobial, antifungal, anticancer, antileukemic, antitumor etc activities. To enhance the biological potential of benzo[a]phenazine skeleton, constant efforts have been made to fuse it with other biologically promising heterocycles. Among many others, benzo[a]phenazine fused with pyran skeleton reported to exhibit a wide range of pharmacological efficacies like anti-plasmodial, anticancer, antiangiogenic, antimalarial, anticancer etc activities.

objective:

Biological significance of benzo[a]phenazine skeleton motivated us to synthesize some benzo[a]pyrano[2,3-c]phenazine derivatives under greener conditions by following multicomponent reaction strategies.

method:

In a clean round bottom flask, a magnetic stir bar, 2-hydroxy-1,4-naphthaquinone (1; 0.5 mmol; 0.087 g), o-phenylenediamine (2; 0.5 mmol; 0.054 g), 20 mol

result:

We have developed a simple, efficient and straightforward approach for the one-pot four component synthesis of a benzo[a]pyrano-[2,3-c]phenazines and spirobenzo[c]pyrano[3,2-a]phenazine derivatives from the equimolar reaction of 2-hydroxy-1,4-naphthaquinone, o-phenylenediamine, malononitrile and various aromatic as well aliphatic aldehydes or isatins respectively in the presence of a catalytic amount of DBU as catalyst in aqueous ethanol at 120 °C.

conclusion:

In conclusion, we have developed a simple, efficient and convenient approach for the one-pot four component synthesis of a series of benzo[a]pyrano-[2,3-c]phenazines in excellent yields from the reactions of lawsone or 2-hydroxy-1,4-naphthaquinone, o-phenylenediamine, various substituted benzaldehydes and malononitrile in the presence of a catalytic amount of DBU as catalyst in aqueous ethanol at 120 °C. Butaraldehyde was also afforded the desired product in good yield. Under the same optimized reaction conditions, spirobenzo[c]pyrano[3,2-a]phenazine derivatives were also synthesized in excellent yields from the reactions of 2-hydroxy-1,4-naphthaquinone, o-phenylenediamine, isatin or substituted isatins and malononitrile. A multiple carbon-carbon and carbon-heteroatom bonds (two C=N, two C-C and one C-O) were formed to achieve the targeted products. The use of commercially available low-cost metal-free organocatalyst, less toxic solvent, excellent yields, short reaction times, no column chromatography, easy isolation procedure and gram-scale production are some of the notable advantages of this developed protocol.

other:

NA