Convenient Synthesis of Fluorescent Chromeno[4,3-d]pyrimidines from Electron-Deficient 3-Vinylchromones

Abstract

We report an easy and powerful approach to the synthesis of novel chromeno[4,3-d]pyrimidine-5-acetic acids through ANRORC reaction of electron-deficient 3-vinylchromones and 1,3-N,N-binucleophiles. The reaction proceeds under mild conditions (EtOH, rt) and is applicable to a wide range of substrates. The described compounds show fluorescence in the violet-blue range (390–460 nm) with Stokes shift of 40–80 nm and moderate quantum yield (0.15–0.20). As the electron-withdrawing group is conserved in the form of an acetic acid fragment, these compounds may readily be functionalized or conjugated to a required substrate for (bio)analytical purposes.

Synthesis and Reactivity of Electron-Deficient 3-Vinylchromones

“…In the reaction of acetamidine with 3-vinylchromone 10c, containing two ester groups that increase its electrophilicity compared to chromones 2, in addition to the expected chromenopyrimidine 72, 5-salicyloylpyrimidine 73 is formed as a result of the attack at the C-2 and C-1' atoms, followed by the cleavage of the malonic ether. 54 An analogous behavior of chromone 10c, similar to that of 3-formylchromone, was also observed in the formation of pyrimidine 75 from toluamidine and 3-vinylchromone 74 with two phosphonate groups (Scheme 32). 55 Scheme 32 Reactions of chromones 10c and 74 with amidines 4.3 Reactions with other 1,3-and 1,4-dinucleophiles 3-Vinylchromones 11b obtained from 3-formylchromones 1a and malononitrile react with cyanoacetohydrazide as a 1,3-C,Ndinucleophile on the acrylonitrile fragment, giving chromonylpyridones 77.…”

“…A simple and effective approach to the new chromeno[4,3d]pyrimidines 71 was developed through the ANRORC reaction of electron-deficient 3-vinylchromones 2 and such 1,3-N,Ndinucleophiles as amidines and guanidine. 54 The reaction proceeds under mild conditions (EtOH, ~20 °C), is complete within a few hours, and is applicable to a wide range of substrates (Scheme 31). This transformation proceeds following the pathway characteristic for chromones, i.e.,…”

Fluorescent 5H‐Pyrano[3,2‐c]chromenes: Synthesis, Photophysical Properties and Sensing of Nucleophilic Anions

“…Melting points were determined on a capillary point apparatus and are uncorrected. Ethyl 3‐(4‐oxo‐4 H ‐chromen‐3‐yl)acrylates 1 a – r were synthesized through Knoevenagel condensation [12b] …”

Конструирование Конденсированных Гетероциклических Систем На Основе Реакции Электронодефицитных 3-Винилхромонов С Цианацетамидом

“…3-Винилхромоны 1, содержащие в винильном фрагменте электроноакцепторную группу (EWG), зарекомендовали себя как многоцелевые структурные блоки для построения на их основе конденсированных гетероциклических систем [1,2]. В частности, наличие в их структуре нескольких электрофильных центров с резко отличающейся реакционной способностью позволило создать эффективный метод синтеза хромено [4,3-d]пиримидинов [2]. При этом известно, что данные фенантреноподобные соединения часто проявляют анальгезирующую и антиагрегантную активность [3].…”