3‐aryl‐6‐methoxy‐2‐oxo‐1,2‐dihydroquinoline‐4‐carbonitriles as Solvent and pH Independent Green Fluorescent Dyes

Abstract

Highly fluorescent and stable 3‐aryl‐6‐methoxy‐2‐oxoquinoline‐4‐carbonitriles 6 (λexc = 408 nm and λem = 510 nm) were synthesized starting from appropriate arylmalonates 2. Ring closure reaction with p‐anisidine gave 4‐hydroxyquinolones 3, which could be bis‐chlorinated to yield quinolines 4. Regioselective hydrolysis produced reactive 4‐chloroquinolones 5, which were converted to green fluorescent 4‐cyano quinolones 6 using toluenesulfinates as catalysts.

Syntheses and Fluorescent Properties of 6‐Methoxy‐2‐oxoquinoline‐3,4‐dicarbonitriles and 6,7‐Dimethoxy‐2‐oxoquinoline‐3,4‐dicarbonitriles

“…In all investigated cases, N‐alkyl derivatives have the same or very similar fluorescence properties, which means that the introduction of linker groups such as N‐acetates do not change these properties and allows an easy linking to biological material. This fact complies with the results we found in earlier investigations .…”

“…A regioselective hydrolysis in 2‐position with ethanolic methanesulfonic acid gave the desired reactive intermediate, 4‐chloro‐6‐methoxyquinolone 3 , in excellent yields. The introduction of the cyano group in position 4 was planned using a similar procedure as described in refs by reaction with potassium cyanide in a sodium p‐toluenesulfinate mediated reaction. Under these conditions at 130°C, after 27 h a mixture of two strongly green fluorescent compounds, 6‐methoxy‐2‐oxo‐1,2‐dihydroquinoline‐4‐carbonitrile ( 5 ) together with 6‐methoxy‐4‐[(4‐methylphenyl)sulfonyl]quinolin‐2(1H)‐one ( 4 ) was obtained, which had to be separated by fractionated crystallization from dioxane.…”

“…For the further use of fluorophores such as 5 or 6 having N‐alkyl linker groups for fluorescence labeling purposes, we studied N‐methyl derivatives as model compounds because they are known to show similar fluorescence properties as compounds with linker groups . Path A started from p‐anisidine, which was methylated either via a two‐step synthesis using an adapted text book procedure for similar structures : in a Chapman rearrangement with trimethyl orthoformate N‐(4‐methoxyphenyl)‐N‐methylformamide was obtained, which was then hydrolyzed with 10% hydrochloric acid to give 4‐methoxy‐N‐methylbenzenamine 10 in an overall yield of 52%.…”

“…6,7‐Dimethoxy‐carbostyrils having a 4‐trifluoromethyl or a 4‐cyano substituent as acceptor group are highly fluorescent compounds with emission values up to 510 nm and high quantum yields up to 0.6. Further properties such as high thermal and photochemical stability and no oxygen quenching make them very useful as new fluorophores (e.g.…”

“…) suitable to outclass similar and widely used coumarin derivatives . Attempts for a fine‐tuning of these values in 4‐cyano‐6,7‐dimethoxycarbostyrils by introduction of additional acceptor or donor groups gave, with substituted aryl groups in position 3, no significant effects ; surprisingly, substituents such as 3‐chloro, 3‐nitro or 3‐amino groups were replaced in all cases during the introduction of the cyano group in position 4 by a further cyano group in position 3 .…”