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. 2022 Nov 7;27(21):7649.
doi: 10.3390/molecules27217649.

Efficient Synthesis of Fluorescent Coumarins and Phosphorous-Containing Coumarin-Type Heterocycles via Palladium Catalyzed Cross-Coupling Reactions

Rumen Lyapchev  1 , Ana I Koleva  1 , Iskra Z Koleva  1 , Kristian Subev  1 , Ivelina Madzharova  1 , Kristina B Simeonova  1 , Nevena Petkova-Yankova  1 , Bernd Morgenstern  2 , Vesela Lozanova  3 , Petar Y Petrov  1 , Rositca D Nikolova  1
Affiliations

Efficient Synthesis of Fluorescent Coumarins and Phosphorous-Containing Coumarin-Type Heterocycles via Palladium Catalyzed Cross-Coupling Reactions

Rumen Lyapchev et al. Molecules. .

Abstract

Quantum-chemical calculations on the spectral properties of some aryl substituted 3-phosphonocoumarins were performed, and the effect of the substituents in the aryl moiety was evaluated. The structures possessing promising fluorescent properties were successfully synthesized via Suzuki and Sonogashira cross-coupling. The synthetic protocol was also applied for the phosphorous chemoisomer of 3-phosphonocoumarin, 1,2-benzoxaphosphorin, and their carboxylate analogues. The optical properties of the arylated and alkynylated products were experimentally determined. The obtained quantum-chemical and experimental results give the possibility for a fine tuning of the optical properties of phosphorous-containing coumarin systems by altering the substituent at its C-6 position.

Keywords: 1,2-benzoxaphosphorin; 3-phosphonocoumarin; DFT calculations; Pd-catalyzed reactions; Sonogashira reaction; Suzuki reaction; coumarin-3-carboxylates; cross-coupling; fluorescence; photophysical properties.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Suzuki reaction of 5-bromo-2-hydroxybenzaldehyde 1 with phenylboronic acid.
Scheme 2
Scheme 2
Knoevenagel condensation.
Scheme 3
Scheme 3
Suzuki coupling.
Figure 1
Figure 1
Pd-complexes used as catalyst in the studied reaction.
Scheme 4
Scheme 4
Suzuki coupling—optimizing the conditions.
Figure 2
Figure 2
ORTEP representation with thermal ellipsoids 40%—Crystal Data for C19H19O5P (M = 358.333 g/mol): monoclinic, space group P21/n (no. 14), a = 13.6869(9) Å, b = 8.5123(5) Å, c = 14.9033(9) Å, α = 90°, β = 90.726(2)°, γ = 90°, V = 1736.20(19) Å3, Z = 4, T = 133.00 K, μ(MoKα) = 0.185 mm−1, Dcalc = 1.371 g/cm3, 26,401 reflections measured (4.06° ≤ 2Θ ≤ 55.84°), 4155 unique (Rint = 0.0591, Rsigma = 0.0405) which were used in all calculations. The final R1 was 0.0390 (I > 2σ(I)) and wR2 was 0.1092 (all data). The crystallographic data could be found in the Supplementary Materials.
Scheme 5
Scheme 5
Suzuki coupling of 6-bromo-3-phosphonocoumarin 5.
Scheme 6
Scheme 6
Palladium-catalyzed arylation of 6-bromocoumarin-3-carboxylates 8a,b.
Scheme 7
Scheme 7
Palladium-catalyzed arylation of ethyl 6-bromo-2-ethoxybenzo[e][1,2]oxaphosphorine-3-carboxylate 6.
Scheme 8
Scheme 8
Palladium-catalyzed alkynylation of 3-substituted coumarin species—Sonogashira coupling.
Figure 3
Figure 3
Normalized fluorescent spectra of the phenyl substituted derivatives.
Figure 4
Figure 4
UV-VIS and normalized fluorescence spectra of 3a-b, 12a, and 12d phosphonocoumarins in acetonitrile.
Figure 5
Figure 5
UV-VIS and normalized fluorescence spectra in acetonitrile: (a) series of ethyl coumarin-3-carboxylates compounds 9a–e, 12b; (b) series of methyl coumarin-3-carboxylates compounds 10a–e; (c) series of ethyl 2-ethoxybenzo[e][1,2]oxaphosphorine-3-carboxylate 11a–d.
Figure 5
Figure 5
UV-VIS and normalized fluorescence spectra in acetonitrile: (a) series of ethyl coumarin-3-carboxylates compounds 9a–e, 12b; (b) series of methyl coumarin-3-carboxylates compounds 10a–e; (c) series of ethyl 2-ethoxybenzo[e][1,2]oxaphosphorine-3-carboxylate 11a–d.
Figure 6
Figure 6
Normalized fluorescence spectra in acetonitrile for derivatives bearing para-methoxyphenyl groups.
Figure 7
Figure 7
Fluorescence intensity in acetonitrile according to the pH: (a) coumarin 3a (c = 10−5 M) behavior in sulfuric acid, 1N; (b) coumarin 3c (c = 10−5 M) behavior in sulfuric acid, 1N; (c) coumarin 3a (c = 10−5 M) behavior in NaOH, 1N; (d) coumarin 3c (c = 10−5 M) behavior in NaOH, 1N. The green arrow is showing the changing of the fluorescence intensity depending on the H+ concentration.
Figure 7
Figure 7
Fluorescence intensity in acetonitrile according to the pH: (a) coumarin 3a (c = 10−5 M) behavior in sulfuric acid, 1N; (b) coumarin 3c (c = 10−5 M) behavior in sulfuric acid, 1N; (c) coumarin 3a (c = 10−5 M) behavior in NaOH, 1N; (d) coumarin 3c (c = 10−5 M) behavior in NaOH, 1N. The green arrow is showing the changing of the fluorescence intensity depending on the H+ concentration.
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