Chemistry of Coumarins. ‐ Nucleophilic Substitutions of 4‐Chloro‐3‐nitrocoumarin with Hard and Soft Nucleophiles

Abstract

Reactions of 4-chloro-3-nitrocoumarin with a variety of nucleophiles produced a number of novel substituted coumarins. Hard and borderline nucleophiles exclusively substitute chlorine in position 4, while soft nucleophiles substitute the nitro group in position 3 (except for iodide) of the title compound. This result of the nucleophilic substitution of 4-chloro-3-nitrocoumarin is rationalized in terms of the HSAB model. Chemie der Cumarine. -Nucleophile Substitutionen an 4-Chlor-3-nitrocumarin mit harten und weichen NucleophilenUmsetzungen von 4-Chlor-3-nitrocumarin mit verschiedenen Nucleophilen ergaben zahlreiche ncue substituierte Cumarine. Harte Nucleophile und solche im Ubergangsbereich zu den weichen substituieren ausschliefllich das Chlor in Position 4, wahrend weiche Nucleophile (mit Ausnahme von Iodid) die Nitrogruppe in Position 3 der Titelverbindung ersetzen. Dieses Ergebnis wird mit Hilfe der Theorie von den harten und weichen Sauren/Basen diskutiert.Compounds containing a coumarin subunit possess a wide range of biological activities and show an interesting chemical reactivity' -9 ) . This is the consequence of the rich electronic structure of coumarin which offers abundant possibilities for diversified activity and reactivity of the system. In the course of our studies"."' on the chemistry of coumarins and related structures we have investigated reactions for the preparation of a number of differently 3,4-substituted coumarins. We found that Pearson's HSAB (hard and soft acids and bases) concepti2-") of preferred interactions of hard acids (acceptors) with hard bases (donors) and soft acids (acceptors) with soft bases (donors) may be used in the case of nucleophilic attack on 4-chloro-3-nitrocoumarin (1) as a guiding principle for predicting the effect of substitution. The nucleophilic substitutions of 4-chloro-3-nitrocoumarin with a variety of nucleophiles, classified as hard, soft, and borderline"), led t o a number of novel substituted coumarins.

Potential antiproliferative effect of isoxazolo- and thiazolo coumarin derivatives on breast cancer mediated bone and lung metastases

“…Based on the »hard and so (Lewis) acids and bases« (HSAB) concept that electrophiles a ack the coumarine ring (19), the eight heterocyclic amines, isoxazoles and thiazoles, were derivatized to obtain diazonium ions which would be further used as electrophiles to a ack the coumarine ring at position 3. Isoxazole and thiazole substituents were used based on the literature data pointing to the antiproliferative and tumour vascular-disrupting activity of their derivatives (20)(21)(22)(23), with isoxazole and thiazole rings being important pharmacophores.…”

Influence of the aryl substituent identity in 4-arylamino-3-nitrocoumarins on their antimicrobial activity

“…HRMS(EI): M + (C16H12N2O4) 296.0815, requires 296.0797 (= +1.8 mmu). IR and 1 H and 13 C NMR (in CDCl3) previously published (Tabaković et al, 1983;Dekić et al, 2010c 2H, H-6, H-8), 7.00-7.20 (m, 4H, H-2', H-3', H-5', H-6'), 2.31 (s, 3H, CH3).…”

An Improved Synthesis of 4-Chlorocoumarin-3-sulfonyl Chloride and Its Reactions with Different Bidentate Nucleophiles to Give Pyrido[1',2':2,3]- and Thiazino[3',2':2,3]-1,2,4-Thiadiazino[6,5-c]Benzopyran-6-one 7,7-Dioxides

“…25 %) (Scheme 2). Modification of this step was based on the report that the chlorine atom at position 4 cannot be attacked by water [29]. Also, it was found that in general the sulfonyl chlorides are insoluble and stable in water [31].…”

“…Based on these facts we wanted to combine the coumarinic system with 1,2,4-thiadiazines in the hope that the resulting novel heterocycles would be biologically active, especially as anticancer and anti-HIV agents. Also, we designated positions 3 and 4 of coumarin for annellation, because these positions are mainly attacked by electrophiles and nucleophiles, respectively [29].…”