Asymmetric meso-CF3-dipyrromethanes with amino- and heterocyclic functions from trifluoro(pyrrolyl)ethanols and pyrroles

Journal Pre-proof Asymmetric meso-CF3 -dipyrromethanes with amino- and heterocyclic functions from trifluoro(pyrrolyl)ethanols and pyrroles Denis N. Tomilin, Lyubov N. Sobenina, Olga V. Petrova, Elena F. Sagitova, Arsalan B. Budaev, Igor A. Ushakov, Andrey V. Ivanov, Boris A. Trofimov

PII:

S0022-1139(20)30006-3

DOI:

https://doi.org/10.1016/j.jfluchem.2020.109455

Reference:

FLUOR 109455

To appear in:

Journal of Fluorine Chemistry

Received Date:

4 November 2019

Revised Date:

26 December 2019

Accepted Date:

26 December 2019

Please cite this article as: Tomilin DN, Sobenina LN, Petrova OV, Sagitova EF, Budaev AB, Ushakov IA, Ivanov AV, Trofimov BA, Asymmetric meso-CF3 -dipyrromethanes with aminoand heterocyclic functions from trifluoro(pyrrolyl)ethanols and pyrroles, Journal of Fluorine Chemistry (2020), doi: https://doi.org/10.1016/j.jfluchem.2020.109455

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Asymmetric meso-CF3-dipyrromethanes with amino- and heterocyclic functions from trifluoro(pyrrolyl)ethanols and pyrroles Denis N. Tomilin, Lyubov N. Sobenina, Olga V. Petrova, Elena F. Sagitova, Arsalan B. Budaev, Igor A. Ushakov, Andrey V. Ivanov, Boris A. Trofimov* A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Science, 1 Favorsky Str., 664033 Irkutsk, Russian Federation,

tel/fax: + 7(3952) 41-93-46; e-mail: [email protected]

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Graphical abstract

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Highlights

AlCl3 is the new effective catalyst for the synthesis of asymmetric meso-CF3dipyrromethanes

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Approach to new dipyrromethanes – precursors of BODIPY dyes and metal complexes – was described

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Excess of catalyst could cause disproportionation

Abstract

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Asymmetric meso-CF3-dipyrromethanes with amino- and nitrogen heterocyclic functions, a new family of the BODIPY dye precursors, have been synthesized in 70-90% yield by condensation of trifluoro(pyrrolyl)ethanols with pyrroles in the presence of AlCl3. This catalyst, for the first time, was shown to be more efficient than commonly used P2O5, which was entirely inactive in the condensation of pyrroles having basic substituents (amino group and pyrazole moiety). Keywords

Trifluoro(pyrrolyl)ethanols, pyrroles, meso-CF3-dipyrromethanes, aluminum chloride, condensation 1. Introduction Dipyrromethanes attract a steady interest as important powerful building blocks and auxiliaries in organic and bioorganic chemistry, catalysis and high-tech material science [1-5].

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They are particularly widely utilized for the assembling of porphyrins and porphyrinoids, like corroles, chlorins, porphyrins with extended π-system, calix[4]pyrroles [6-10]. Also, they are indispensable for the construction of boron dipyrromethene fluorophores (BODIPYs) [11-14], highly effective fluorescent labels, PDT agents and promising photonic organic materials [1520]. Dipyrromethanes are precursors of sensitive detectors of phosphate-anions [21]. Complexes of dipyrromethanes with tetracyanoquinodimethane are known as highly selective sensors for aniline [22], cysteine [23], phosphate [24], carbonate [24], and fluorine [25] anions. Metal complexes with dipyrromethane ligands catalyze hydrogenation reactions [26] and hydroamination of alkenes and alkynes [27]. Polymers containing dipyrromethane units exhibit

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electrochromic properties and can be useful for “smart” glasses and films [28].

Among the meso-substituted dipyrromethanes, those with the trifluoromethyl (CF3) group are of special interest because this substituent essentially improves the useful properties of BODIPY dyes therefrom. In particular, the CF3-substituent as strongly electron-withdrawing one

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facilitates the chemical modification of the dye molecules adjusting them for fluorescent protein labeling [29]. Such meso-CF3-substituted BODIPY dyes demonstrate a deeper bathochromic

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shift compared to fluorine-free congeners [30-36] and can be employed as fluorescent sensors for in vivo imaging systems and in photodynamic therapy [37-41]. These fluorinated dipyrromethanes are key intermediates in the synthesis of electron-

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deficient porphyrins, which themselves and their metallic complexes show unique properties when applied in catalysis, material science, and medicine [42-45].

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A general method for the synthesis of such dipyrromethanes consists of the acid-catalyzed condensation of pyrroles with perfluoroalkyl aldehydes or its derivatives (trifluoroacetaldehyde methyl hemiacetal [29, 46] or trifluoroacetaldehyde hydrate [47]). A disadvantage of this

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approach is the competitive formation of tripyrromethanes and their higher oligomers. Besides, this method allows obtaining exceptionally symmetrical dipyrromethanes that significantly

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restricts its application. Meso-CF3-dipyrromethane was also prepared by condensation of pyrrole with 1-bromo-1-chloro-2,2,2-trifluoroethane in the presence of a sodium dithionite [48, 49]. Evidently, a further progress in this field requires more structural diversity and functional

complexity in the dipyrromethane series. In this context, asymmetric representatives of the mesoCF3-dipyrromethanes with different amino and heterocyclic substituents could cardinally contribute to potential of these compounds as synthetic building blocks and ligands for biometal catalysts, drug precursors and components for optoelectronic materials. The recently pioneered methodology for the synthesis of meso-CF3-substituted dipyrromethanes that comprises trifluoroacetylation of pyrroles with trifluoroacetic anhydride,

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reduction of trifluoroacetylpyrroles to trifluoro(pyrrolyl)ethanols and condensation of the latter with pyrroles in the presence of P2O5 [30], substantially paves the way to reach the above goal. Although this methodology can provide the synthesis of asymmetric molecules, our preliminary experiments show that it is inefficient for preparation of meso-CF3-dipyrromethanes containing basic functions, like amino group and some nitrogen heterocycles, obviously due to the neutralization of the P2O5 catalyst and acidic P-OH species therefrom. Consequently, the purpose of this work is to modify this methodology in order to make it suitable for construction of both asymmetric meso-CF3-dipyrromethanes and those bearing various basic functions. Such compounds should be not only additionally polarized owing to their asymmetry but also capable of extra-complexing and donor/acceptor interacting with

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diverse environmental chemicals.

2. Results and discussion

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As mentioned above, the reaction of 2,2,2-trifluoro-1-(4,5,6,7-tetrahydroindol-2-yl)ethan1-ol (1a) with pyrroles, bearing basic functions (aminophenyl and pyrazole substituents), 3-

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phenyl-5-(pyrrol-2-yl)pyrazole (2a) and 2-(4-aminophenyl)pyrrole (2b), in the presence of equimolar amount of P2O5, a common condensing agent for such reactions, failed to produce any quantitates of the expected dipyrromethanes 3aa and 3ab, only the starting materials being

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recovered.

The P2O5-promoted condensation also does not take place when a basic function is located

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in the trifluoroethanol component, e.g., with 2,2,2-trifluoro-1-(4,4,6,6-tetramethyl-4,5,6,7tetrahydropyrrolo[3,2-c] pyridin-2-yl)ethan-1-ol (1c). During the further investigation of this cross-coupling we have found that the excellent

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catalyst for this process proved to be AlCl3, which until now have never been employed in the dipyrromethane syntheses.

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Indeed, when trifluoropyrrolylethanol 1а and pyrrolyl-pyrazole 2а were stirred in the presence of AlCl3 (10 mol%) at room temperature for 16 h dipyrromethane 3аа was selectively formed with 76% yield, the conversion of the starting pyrroles being complete (Scheme 1). Under similar conditions, the reaction of trifluoro(pyrrolyl)ethanol 1a with 2-(4-

aminophenyl)pyrrole (2b) proceeded slower: after 16 hours the conversion of the starting reagents did not exceed 70%. The complete conversion of the reactants was achieved with 20 mol% of AlCl3 in 36 hours to provide dipyrromethane 3ab in 90% yield (Scheme 2). An increased loading of AlCl3 (50 mol%) allowed the process duration to be reduced to 16 hours securing 58% yield of the target product 3ab. However, the latter, under these conditions,

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undergoes partial (15-17%) disproportionation to give symmetric dipyrromethanes 4aa and 5bb (Scheme 2). Formation of symmetrical products in similar process was previously reported [50]. Symmetric dipyrromethanes 4 and 5 in trace amounts were also detected in the crude product obtained from trifluoro(pyrrolyl)ethanol 1b and aminophenylpyrrole 2b in the presence of 50 mol% of AlCl3 within 3.5 hours (Scheme 3), whereas the yield of the pure target asymmetric dipyrrometane 3bb was 82%. The negligible symmetrisation of the synthesised dipyrromethanes is likely resulted from insignificant reversible decomposition of the protonated asymmetric molecules to release trifluoromethylpyrrolyl cations A, B and corresponding pyrroles (Scheme 4), which can be

Noteworthy,

that

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combined in a symmetric mode, as shown on the example of dipyrromethane 3ab. 2,2,2-trifluoro-1-(4,4,6,6-tetramethyl-4,5,6,7-tetrahydropyrrolo[3,2-

c]pyridin-2-yl)ethan-1-ol (1с), having higher basic (cycloaliphatic amine) moiety, is condensed with pyrroles, e.g., 2-phenylpyrrole (2с), much slower as compared to above reactions (Schemes

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1, 2, 3).

Experimentally, with 10 mol% of AlCl3 for 16 hours (like in Scheme 1) no condensation

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was observed, while with 50 mol% of the catalyst (like in Scheme 2) during the same time the reactant conversion was only 59%. A preparatively suitable result (72% yield of dipyrromethane for 5 hours) at complete conversion has been attained only when 100 mol% of AlCl3 was used

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(Scheme 5).

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This fact is in keeping with the rationale, that the acidic condensing agents (AlCl3 in this case) are neutralized (hence deactivated) by basic substituents. Thus, unlike condensing agent Р2О5, widely used for synthesis of dipyrromethanes, a

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newly found here catalyst AlCl3 efficiently permits to manage with the synthetic challenge associated with the design of asymmetric meso-CF3-dipyrromethanes having basic functions.

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To determine the coverage of new catalyst we have carried out a series of reactions

between trifluoro(pyrrolyl)ethanols 1d-f and pyrroles 2c,d, when both reactants have no noticeable basic functions. As seen from Table 1, in this case the catalyst displays much higher efficacy: with 10 mol% of AlCl3 the reactions takes 1-2 hours only, providing 89-90% yields of the target dipyrromethanes, that surpassed (by 6-10%) the yields obtained with P2O5. The high purity of dipyrromethanes synthesized with this catalyst is another advantageous feature.

3. Conclusion:

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A new family of dipyrromethanes, namely, asymmetric

meso-CF3-dipyrromethanes

bearing basic functions (amino group, pyrazole) have been synthesized by cross-coupling of trifluoro(pyrrolyl)ethanols with pyrroles in the presence of AlCl3. This catalyst, employed for first time for this condensation allowed to overcome the difficulties associated with deactivation of convential condensing agents by the basic reactions. The synthesized dipyrromethanes due to enhanced polarity and extra capacity for complexing and docking to biotargets are promising building blocks for fluorescent sensors, biolabels, porphyrins, porphyrinoids and metal complexes of diverse catalytic activity. The extra basicity of the synthesized dipyrromethanes (aminophenyl, pyrazolyl, tetrahydropyridine moieties) will be further explored for extending and

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diverisfying of functionalities decorating the main scaffold of boron dipyrromethene dyes including condensation with carbonyl compounds (Schiff base synthesis), alkylation with organic halides or addition to the activated multiple bonds.

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4. Experimental section

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H,

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C and

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4.1. General information

F NMR spectra were recorded in CDCl3 and DMSO-d6, using a Bruker Avance

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400 NMR spectrometer (400.1, 100.6 and 376.5 MHz, respectively). The chemical shifts (δ) are given in ppm and referenced to residual solvent: 7.27 ppm (CDCl3) and 2.50 ppm (DMSO-d6) for 1H, 77.1 ppm (CDCl3) and 39.50 ppm (DMSO-d6) for

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C. The

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F chemical shifts were

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referenced to CFCl3. Coupling constants in hertz (Hz) were measured from one-dimensional spectra and multiplicities were abbreviated as following: br (broad), s (singlet), d (doublet), dd

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(doublet of doublets), m (multiplet). The chemical shifts were recorded in ppm, coupling constants (J) in Hz. IR spectra were obtained on a Varian 3100 IF-IR spectrometer (400-4000 cm-1, KBr pellets or films). The (C, H, N) microanalyses were performed on a Flash EA 1112

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СHNS-O/MAS (CHN Analyzer) instrument. Fluorine content was determined on a SPECOL 11 (Carl Zeiss Jena, Germany) spectrophotometer. Melting points (uncorrected) were determined with melting point SMP3 (Stuart Scientific). Trifluoro(pyrrolyl)ethanols 1a-f and their precursors, trifluoro(pyrrolyl)ethanones, were synthesized according to the procedures given in the paper [30]. Their spectral characteristics are presented in the Supporting Information. Method of dipyrromethanes synthesis from trifluoro(pyrrolyl)ethanols and pyrroles in the presence of P2O5 was published in [30].

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4.2. Synthetic procedures 4.2.1. Synthesis of dipyrromethanes 3 in the presence of AlCl3 (General procedure) A mixture of 2,2,2-trifluoro-1-(1H-pyrrol-2-yl)ethan-1-ol 1a-f (1.00 mmol), 2-aryl/hetarylpyrrole 2a-d (1.00 mmol) and AlCl3 (0.10-1.00 mmol) in dried CH2Cl2 (40 ml) was stirred at rt for 1-36 h. Then the NaHCO3 (2 mmol) was added and the mixture was stirred 30 min, the precipitate formed was filtered off, washed with CH2Cl2 (2 x 8-9 mL). The residue after removing solvent was purified by flash chromatography (SiO2, n-hexane:CH2Cl2 1:1) to give dipyrromethane 3.

4.2.1.1. 2-{2,2,2-Trifluoro-1-[5-(3-phenyl-1H-pyrazol-5-yl)-1H-pyrrol-2-yl]ethyl}-4,5,6,7-

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tetrahydro-1H-indole (3aa)

The dipyrromethane 3aa (0.312 g, 76%) was obtained in the presence of 0.10 mmol (0.013 g) of AlCl3 for 16 h as light pink solid; mp 90-95 oC. IR (film): 3429, 3360, 3192, 2928, 2851, 1605, 1527, 1450, 1390, 1334, 1255, 1161, 1105, 909, 768, 732, 694 cm-1.

H NMR (400.1 MHz, CDCl3): δ = 9.42 (br. s, 1 H, NH), 7.67 (br. s, 1 H, NH), 7.58-7.56 (m, 2

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H, Ph), 7.46–7.38 (m, 3 H, Ph), 6.65 (s, 1 H, H4, pyrazole), 6.51–6.49 (m, 1 H, H3’), 6.33–6.31

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(m, 1 H, H4’), 5.94 (d, 1 H, 3JNH = 1.7 Hz, H3), 4.75 (q, 1 H, 3JHF = 8.0 Hz, CHCF3), 2.46–2.44 (m, 4 H, CH25,6), 1.75–1.72 (m, 4 H, CH24,7).

С NMR (100.6 MHz, CDCl3): δ = 146.4, 144.9, 129.8, 129.1 (2C), 128.7, 128.1, 125.7 (2C),

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125.3, 125.3 (q, 1JCF = 279.9 Hz, CF3), 124.8, 120.7, 117.5, 109.7, 108.4, 107.7, 99.4, 43.4 (q, 2

JCF = 30.0 Hz, CH), 23.6, 23.2, 22.7, 22.5.

F NMR (376.5 MHz, CDCl3): δ = -68.2 (d, 3JHF = 8.0 Hz).

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Anal. Calcd for C23H21F3N4 (410.44): C 67.31, H 5.16, F 13.89, N 13.65%. Found: C 67.52, H

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5.04, F 14.01, N 13.43%.

4.2.1.2. 4-{5-[2,2,2-Trifluoro-1-(4,5,6,7-tetrahydro-1H-indol-2-yl)ethyl]-1H-pyrrol-2-yl}aniline

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(3ab)

The dipyrromethane 3ab (0.334 g, 90%) was obtained in the presence of 0.20 mmol (0.026 g) of AlCl3 for 36 h as dark pink solid; mp 60–65 oC. IR (film): 3401, 3231, 3025, 2927, 2850, 1621, 1524, 1478, 1443, 1334, 1256, 1159, 105, 908, 831, 779, 730, 525 cm-1. 1

H NMR (400.1 MHz, CDCl3): δ = 8.23 (br. s, 1 H, NH), 7.67 (br. s, 1 H, NH), 7.27–7.24 (m, 2

H, Ph), 6.70–6.68 (m, 2 H, Ph), 6.33-6.32 (m, 1 H, H3’), 6.29–6.27 (m, 1 H, H4’), 6.02–6.01 (m, 1 H, H3), 4.80 (q, 1 H, 3JHF = 8.8 Hz, CHCF3), 3.69 (br. s, 2 H, NH2), 2.53–2.51 (m, 4 H, CH24,7), 1.81–1.77 (m, 4 H, CH25,6). 13С NMR (100.6 MHz, CDCl3): δ = 145.2, 133.5, 128.0, 125.4 (2C),

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125.3 (q, 1JCF = 280.1 Hz, CF3), 123.4, 123.1, 120.8, 117.5, 115.6 (2C), 110.4, 108.2, 104.6, 43.6 (q, 2JCF = 30.2 Hz, CH), 23.7, 23.3, 22.8, 22.7. 19

F NMR (376.5 MHz, CDCl3): δ = -68.6 (d, 3JHF = 8.8 Hz).

Anal. Calcd for C20H20F3N3 (359.40): C 66.84; H 5.61; F 15.86; N 11.69%. Found: C 66.96, H 5.49, F 15.93, N 11.62%.

4.2.1.3. 4-{5-[1-(4,5-Dihydro-1H-benzo[g]indol-2-yl)-2,2,2-trifluoroethyl]-1H-pyrrol-2yl}aniline (3bb) The dipyrromethane 3bb (0.334 g, 82%) was obtained in the presence of 0.50 mmol (0.067 g) of AlCl3 for 3.5 h as dark red solid; mp 95 oC. IR (film): 3428, 3325, 3230, 3054, 2934, 2895, 2841, 1

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1620, 1522, 1482, 1447, 1327, 1255, 1161, 1106, 908, 826, 769, 732, 527 cm-1.

H NMR (400.1 MHz, CDCl3): δ = 8.19 (br. s, 2 H, NH), 7.24-7.26 (m, 2 H, Ph), 7.21-7.15 (m, 2

H, Ar), 7.11-7.05 (m, 2 H, Ar), 6.70-6.68 (m, 2 H, Ph), 6.35-6.33 (m, 1 H, H3), 6.32-6.31 (m, 1 H, H4), 6.17 (d, 1 H, 3JNH = 1.7 Hz, H3’), 4.88 (q, 1 H, 3JHF = 8.8 Hz, CH), 3.68 (br. s, 2 H, NH2), 13

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2.97-2.93 (m, 2 H, CH24), 2.75-2.73 (m, 2 H, CH25).

С NMR (100.6 MHz, CDCl3): δ = 145.3, 134.9, 133.8, 128.8, 128.7, 128.4, 126.6, 125.5, 125.4

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(2C), 125.3 (q, 1JCF = 280.1 Hz, CF3), 123.4, 123.3, 122.7, 120.6, 118.5, 115.6 (2C), 110.8, 109.2, 104.8, 43.8 (q, 2JCF = 30.2 Hz, CH), 29.9, 21.7. 19

F NMR (376.5 MHz, CDCl3): δ = -68.1 (d, 3JHF = 8.8 Hz).

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4.77, F 14.20, N 10.01%.

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Anal. Calcd for C24H20F3N3 (407.44): C 70.75, H 4.95, F 13.99, N 10.31%. Found: C 71.02, H

4.2.1.4. 4,4,6,6-Tetramethyl-2-[2,2,2-trifluoro-1-(5-phenyl-1H-pyrrol-2-yl)ethyl]-4,5,6,7tetrahydro-1H-pyrrolo[3,2-c]pyridine (3cc)

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The dipyrromethane 3cc (0.289 g, 72%) was obtained in the presence of 1.00 mmol (0.133 g) of AlCl3 for 5 h as dark pink solid; mp 168-170 oC. IR (KBr): 3376, 3212, 3149, 2960, 2923, 2868,

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1604, 1509, 1467, 1376, 1329, 1243, 1163, 1106, 835, 799, 757 cm-1. 1

H NMR (400.1 MHz, CDCl3): δ = 8.33 (br. s, 1 H, NH), 7.61 (br. s, 1 H, NH), 7.45–7.43 (m, 2

H, Ph), 7.39–7.35 (m, 2 H, Ph), 7.25–7.21 (m, 1 H, Ph), 6.51-6.50 (m, 1 H, H3’), 6.32–6.31 (m, 1 H, H4’), 6.05 (d, 1 H, 4JNH = 1.4 Hz, H3), 4.83 (q, 1 H, 3JHF = 8.9 Hz, CH), 2.39 (s, 2 H, CH27), 1.39 (s, 6 H, 2 Me4), 1.22 (s, 6 H, 2 Me6). 13

С NMR (100.6 MHz, CDCl3): δ = 132.9, 132.3, 129.0 (2C), 126.6, 125.2 (q, 1JCF = 280.2 Hz,

CF3), 125.1, 124.3, 124.2, 123.9 (2C), 120.9, 110.8, 106.5, 105.6, 51.0, 50.9, 43.6 (q, 2JCF = 30.7 Hz, CH), 36.5, 33.2, 33.1, 30.6, 30.5. 19

F NMR (376.5 MHz, CDCl3): δ = -68.3 (d, 3JHF = 8.9 Hz).

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Anal. Calcd for C23H26F3N3 (401.48): C 68.81, H 6.53, F 14.20, N 10.47%. Found: C 68.97, H 6.31, F 14.38, N 10.33%.

4.2.1.5.

2-(4-Fluorophenyl)-5-[2,2,2-trifluoro-1-(5-phenyl-1H-pyrrol-2-yl)ethyl]-1H-pyrrole

(3dc) The dipyrromethane 3dc (0.346g, 90%) was obtained in the presence of 0.10 mmol (0.013 g) of AlCl3 for 1 h as red solid; mp 95-100 oC. IR (film): 3444, 3065, 1607, 1516, 1477, 1334, 1240, 1160, 1107, 1051, 908, 835, 762, 706 cm-1. 1

H NMR (400.1 MHz, CDCl3): δ = 8.35 (br. s, 1 H, NH), 8.27 (br. s, 1 H, NH), 7.46-7.44 (m, 2

H, H2,6, 4-F-Ph), 7.40-7.35 (m, 4 H, Ph), 7.25-7.22 (m, 1 H, Ph), 7.09-7.05 (m, 2 H, H3,5, 4-F-

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Ph), 6.52-6.51 (m, 1 H, H3’), 6.45-6.43 (m, 1 H, H3), 6.36-6.32 (m, 2 H, H4,4’), 4.96-4.89 (m, 1 H, CH). 13

C NMR (100.6 MHz, CDCl3): δ = 161.8 (d, J = 246.1 Hz, C4), 133.3, 132.4, 132.1, 129.0 (2C),

128.6, 128.5, 126.8, 125.7 (d, 3JCF = 8.0 Hz, С2,6), 125.3 (q, 1JCF = 280.0 Hz, CF3), 124.0 (2C), 19

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123.8, 123.7, 115.9 (d, 2JCF = 21.9 Hz, С3,5), 111.0, 106.6, 106.5, 43.6 (q, 2JCF = 30.4 Hz, CH). F NMR (376.5 MHz, CDCl3): δ = -67.9 (d, 3JHF = 8.8 Hz, CF3), -115.0 (m, CF).

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Anal. Calcd for C22H16F4N2 (384.38): C 68.75, H 4.20, F 19.77, N 7.29%. Found: C 68.92, H, 4.02, F 19.97, N 7.09%.

Yield of dipyrromethane 3dc prepared from trifluoro(pyrrolyl)ethanol 1d and pyrrole 2c in the

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presence of P2O5 (1.1 mol) at rt for 16 h is 82%.

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4.2.1.6. 3-Phenyl-5-(5-{2,2,2-trifluoro-1-[5-(4-fluorophenyl)-1H-pyrrol-2-yl]ethyl}-1H-pyrrol-2yl)-1,2-oxazole (3dd)

The dipyrromethane 3dd (0.406 g, 90%) was obtained in the presence of 0.10 mmol (0.013 g) of

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AlCl3 for 1 h as yellow solid; mp 147-149 oC. IR (film): 3438, 3270, 1627, 1558, 1518, 1480, 1452, 1400, 1253, 1163, 1108, 1048, 910, 935, 835, 772, 732, 694 cm-1. H NMR (400.1 MHz, CDCl3): δ = 8.77 (br. s, 1 H, NH), 8.28 (br. s, 1 H, NH), 7.83-7.82 (m, 2

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H, Ph), 7.48-7.47 (m, 3 H, Ph), 7.43-7.40 (m, 2 H, H2,6, 4-F-Ph), 7.07-7.05 (m, 2 H, H3,5, 4-FPh), 6.72-6.70 (m, 1 H, H4), 6.59 (s, 1 H, H4, oxazole), 6.45-6.44 (m, 1 H, H3), 6.41-6.40 (m, 1 H, H3’), 6.35-6.34 (m, 1 H, H4’), 4.94 (q, 1 H, 3JHF = 8.8 Hz, CH). 13

С NMR (100.6 MHz, CDCl3): δ = 163.4, 163.2, 161.8 (d, 1JCF 246.1 Hz, C4), 132.7, 130.3,

129.1 (2С), 128.8, 128.6 (d, 4JCF = 3.2 Hz, C1), 126.9 (2С), 126.7, 125.8 (d, 3JCF = 8.0 Hz, C2,6), 125.0 (q, 1JCF = 280.2 Hz, CF3), 123.1, 121.0, 115.8 (d, 2JCF = 21.8 Hz, C3,5), 111.3, 111.1, 110.7, 106.6, 95.4, 43.5 (q, 2JCF = 30.4 Hz, CH). 19

F NMR (376.5 MHz, CDCl3): δ = -68.0 (d, 3JHF = 8.8 Hz), -115.0 (m, CF).

9

Anal. Calcd for C25H17F4N3O (451.42): C 66.52, H 3.80, F 16.83, N 9.31, O 3.54%. Found: C 66.75, H 3.97, F 16.69, N 9.19%. Yield of dipyrromethane 3dd prepared from trifluoro(pyrrolyl)ethanol 1d and pyrrole 2d in the presence of P2O5 (1.1 mol) at rt for 16 h is 84%.

4.2.1.7. 3-Phenyl-5-(5-{2,2,2-trifluoro-1-[5-(1-naphthyl)-1H-pyrrol-2-yl]ethyl}-1H-pyrrol-2-yl)1,2-oxazole (3ed) The dipyrromethane 3ed (0.435 g, 90%) was obtained in the presence of 0.10 mmol (0.013 g) of AlCl3 for 2 h as dark pink solid; mp 105-107 oC. IR (KBr): 3423, 1627, 1558, 1453, 1397, 1256, 1162, 1108, 1045, 775, 693 cm-1. H NMR (400.1 MHz, DMSO-d6): δ = 12.09 (br. s, 1 H, NH), 11.53 (br. s, 1 H, NH), 8.26-8.24

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1

(m, 1 H, naphthyl), 7.98-7.96 (m, 1 H, naphthyl), 7.89-7.87 (m, 3 H, naphthyl), 7.56-7.53 (m, 7 H, naphthyl, Ph), 7.12 (s, 1 H, H4, oxazole), 6.75 (dd, 1 H, 3J = 3.3 Hz, 3JNH = 2.6 Hz, H4’), 6.46 (dd, 1 H, 3J = 3.3 Hz, 3J = 2.6 Hz, H4), 6.37-6.36 (m, 2 H, H3,3’), 5.22 (q, 1 H, 3JHF = 9.2 Hz, 13

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CHCF3).

С NMR (100.6 MHz, DMSO-d6): δ = 164.0, 162.1, 133.6, 130.9, 130.6, 130.1 (2C), 129.1

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(2C), 128.6, 128.3, 128.1, 127.1, 126.5 (2C), 126.5 (q, 1JCF = 280.1 Hz, CF3), 126.3, 126.2, 125.9, 125.4 (2C), 124.2, 119.7, 110.2, 110.1, 109.5, 109.1, 95.2, 42.1 (q, 2JCF = 29.5 Hz, CH). 19

F NMR (376.5 MHz, CDCl3): δ = -68.0 (d, 3JHF = 9.2 Hz).

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Anal. Calcd for C29H20F3N3O (483.49): C 72.04, H 4.17, F 11.79, N 8.69, O 3.31%. Found: C 72.26, H 3.98, F 11.85, N 8.54%.

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Yield of dipyrromethane 3ed prepared from trifluoro(pyrrolyl)ethanol 1e and pyrrole 2d in the presence of P2O5 (1.1 mol) at rt for 16 h is 80%.

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4.2.1.8. 3-Phenyl-5-(5-{2,2,2-trifluoro-1-[5-(2-naphthyl)-1H-pyrrol-2-yl]ethyl}-1H-pyrrol-2-yl)1,2-oxazole (3fd)

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The dipyrromethane 3fd (0.430 g, 89%) was obtained in the presence of 0.10 mmol (0.013 g) of AlCl3 for 2 h as purple solid; mp 104-106 oC. IR (KBr): 3445, 1554, 1488, 1402, 1232, 1282, 1145, 1083, 760, 732, 694 cm-1. 1

H NMR (400.1 MHz, DMSO-d6): δ = 12.10 (br. s, 1 H, NH), 11.60 (br. s, 1 H, NH), 8.12 (s, 1

H, naphthyl), 7.91-7.82 (m, 6 H, naphthyl, Ph), 7.54-7.48 (m, 4 H, naphthyl, Ph), 7.45-7.42 (m, 1 H, Ph), 7.12 (s, 1 H, H4, oxazole), 6.73-6.72 (m, 1 H, H4), 6.68-6.66 (m, 1 H, H3), 6.40-6.39 (m, 1 H, H4’), 6.31-6.30 (m, 1 H, H3’), 5.19 (q, 1 H, 3JCF = 9.4 Hz, CHCF3).

10 13

С NMR (100.6 MHz, DMSO-d6): δ = 164.0, 162.1, 133.4, 131.6, 131.5, 130.2, 129.9, 129.1

(2C), 128.6, 128.2, 128.0, 127.6, 127.4, 126.9 (q, 1JCF = 289.2 Hz, CF3), 126.5 (2C), 126.4, 125.2 (2C), 123.1, 120.5, 119.8, 110.1, 110.0, 109.7, 107.0, 95.2, 42.1 (q, 2JCF = 29.7 Hz, CH). 19

F NMR (376.5 MHz, CDCl3): δ = -67.9 (d, 3JHF = 9.4 Hz).

Anal. Calcd for C29H20F3N3O (483.49): C 72.04, H 4.17, F 11.79, N 8.69, O 3.31%. Found: C 72.29, H 3.89, F 11.91, N 8.50%. Yield of dipyrromethane 3fd prepared from trifluoro(pyrrolyl)ethanol 1f and pyrrole 2d in the presence of P2O5 (1.1 mol) at rt for 16 h is 83%.

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Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Acknowledgements

This work was supported by the Russian Science Foundation (Project 19-73-10063).

References [1]

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Authors acknowledge Baikal Analytical Center for collective use SB RAS for the equipment.

G. Simonneaux, P. Tagliatesta, Metalloporphyrin catalysts for organic synthesis, J. Porph.

[2]

na

Phthalocyan. 08 (2004) 1166-1171. https://doi.org/10.1142/S1088424604000507. T. E. Wood, A. Thompson, Advances in the chemistry of dipyrrins and their complexes, Chem. Rev. 107 (2007) 1831-1861. https://doi.org/10.1021/cr050052c. A. Ryan, A. Gehrold, R. Perusitti, M. Pintea, M. Fazekas, O. B. Locos, F. Blaikie, M. O.

ur

[3]

Senge, Porphyrin Dimers and Arrays, Eur. J. Org. Chem. (2011) 5817–5844.

Jo

https://doi.org/10.1002/ejoc.201100642. [4]

D. T. Gryko, D. Gryko, C.-H. Lee, 5-Substituted dipyrranes: synthesis and reactivity, Chem. Soc. Rev. 41 (2012) 3780-3789. https://doi.org/ 10.1039/c2cs00003b.

[5]

B. F. Hohlfeld, K. J. Flanagan, N. Kulak, M. O. Senge, M. Christmann, A. Wiehe, Synthesis of Porphyrinoids, BODIPYs, and (Dipyrrinato)-ruthenium(II) Complexes from Prefunctionalized Dipyrromethanes, Eur. J. Org. Chem. (2019) 4020-4033. https://doi.org/10.1002/ejoc.201900530.

11

[6]

R. Naik, P. Joshi, S. P. Kaiwar (nee Vakil), R. K. Deshpande, Facile synthesis of mesosubstituted dipyrromethanes and porphyrins using cation exchange resins, Tetrahedron 59 (2003) 2207-2213. https://doi.org/10.1016/s0040-4020(03)00245-x.

[7]

N. A. M. Pereira, T. M. V. D. Pinho e Melo, Recent Developments in the Synthesis of Dipyrromethanes. A Review, Org. Prepar. Proced. Intern. 46 (2014) 183-213. https://doi.org/10.1080/00304948.2014.903140.

[8]

S. M. M. Lopes, A. Lemos, T. M. V. D. Pinho e Melo, Reactivity of Dipyrromethanes towards Azoalkenes: Synthesis of Functionalized Dipyrromethanes, Calix[4]pyrroles, and Bilanes, Eur. J. Org. Chem. (2014) 7039-7048. https://doi.org/10.1002/ejoc.201402944.

[9]

R. Orłowski, D. Gryko, D. T. Gryko, Synthesis of Corroles and Their Heteroanalogs,

ro of

Chem. Rev. 117 (2017) 3102-3137. https://doi.org/10.1021/acs.chemrev.6b00434.

[10] B. Temelli, H. Kalkan, Synthesis and spectroscopic properties of β-meso directly linked porphyrin–corrole hybrid compounds, Beilstein J. Org. Chem. 14 (2018) 187-193. https://doi.org/10.3762/bjoc.14.13.

-p

[11] L. C. D. de Rezende, F. da Silva Emery, A Review of the synthetic Strategies for the Development of BODIPY Dyes for Conjugation with Proteins, Orbital Electr. J. Chem. 5

re

(2013) 62-83.

[12] L. Vellanki, R. Sharma, M. Ravikanth, Functionalized boron-dipyrromethenes and their applications, Reports in Org. Chem. 6 (2016) 1-24. https://doi.org/10.2147/ROC.S60504.

lP

[13] A. Bessette, T. Auvray, D. Désilets, G. S. Hanan, Non-symmetric benzo[b]-fused BODIPYs as a versatile fluorophore platform reaching the NIR: a systematic study of the

na

underlying structure–property relationship, Dalton Trans. 45 (2016) 7589-7604. https://doi.org/10.1039/c5dt04444h. [14] D. Hu, T. Zhang, S. Li, T. Yu, X. Zhang, R. Hu, J. Feng, S. Wang, T. Liang, J. Chen, L. N.

ur

Sobenina, B.A. Trofimov, Y. Li, J. Ma, G. Yang, Ultrasensitive reversible chromophore reaction of BODIPY functions as high ratio double turn on probe, Nature Commun. 9

Jo

(2018) 362. https://doi.org/10.1038/s41467-017-02270-0. [15] M. E. Pérez-Ojeda, C. Thivierge, V. Martín, Á. Costela, K. Burgess, I. García-Moreno, Highly efficient and photostable photonic materials from diiodinated BODIPY laser dyes, Opt. Mater. Express 1 (2011) 243-251. https://doi.org/10.1364/OME.1.000243.

[16] N. Boens, V. Leen, W. Dehaen, Fluorescent indicators based on BODIPY, Chem. Soc. Rev. 41 (2012) 1130-1172. https://doi.org/10.1039/c1cs15132k. [17] A. Kamkaew, S. H. Lim, H. B. Lee, L. V. Kiew, L. Y. Chung, K. Burgess, BODIPY dyes in photodynamic therapy, Chem. Soc. Rev. 42 (2013) 77-88. https://doi.org/10.1039/C2CS35216H.

12

[18] C. S. Kue, S. Y. Ng, S. H. Voon, A. Kamkaew, L. Y. Chung, L. V. Kiew, H. B. Lee, Recent strategies to improve boron dipyrromethene (BODIPY) for photodynamic cancer therapy: an updated review, Photochem. Photobiol. Sci. 17 (2018) 1691-1708. https://doi.org/10.1039/C8PP00113H. [19] P. Kaur, K Singh, Recent advances in the application of BODIPY in bioimaging and chemosensing, J. Mat. Chem. C 7 (2019) 11361-11405. https://doi.org/10.1039/C9TC03719E. [20] D. Ho, H. Kim, T.Earmme, H. Usta, C. Kim, BODIPY-Based Semiconducting Materials for Organic Bulk Heterojunction Photovoltaics and Thin-Film Transistors, ChemPlusChem 84 (2019) 18-37. https://doi.org/10.1002/cplu.201800543.

ro of

[21] M. K. Deliomeroglu, V. M. Lynch, J. L. Sessler, Non-cyclic formylated dipyrromethanes as phosphate anion receptors, Chem. Sci. 7 (2016) 3843-3850. https://doi.org/10.1039/c6sc00015k.

[22] J. Xu, Y. Guo and S. J. Shao, Colorimetric Detection of Aniline Based on

-p

Di(hydroxymethyl)-di-(2-pyrrolyl)methane-TCNQ System, Chin. Chem. Lett. 17 (2006) 377-379.

re

[23] Y. Guo, S. Shao, J. Xu, Y. Shi and S. Jiang, A specific colorimetric cysteine sensing probe based on dipyrromethane–TCNQ assembly, Tetrahedron Lett. 45 (2004) 6477-6480. https://doi.org/10.1016/j.tetlet.2004.06.109.

lP

[24] Y. Guo, S.-J. Shao, J. Xu, Y.-P. Shi, S.-X. Jiang, Selective colorimetric sensing of PO43and CO32- based on the assembly of dihydroxymethyl-di-(2-pyrrolyl)methane and TCNQ,

na

Inorg. Chem. Commun. 7 (2004) 333-336. https://doi.org/10.1016/j.inoche.2003.12.006. [25] P. Kaur, S. Kaur and K. Singh, A fluoride selective dipyrromethane-TCNQ colorimetric sensor based on charge-transfer, Talanta 84 (2011) 947-951.

ur

https://doi.org/10.1016/j.talanta.2011.02.034. [26] M. Yadav, A. K. Singh, R. Pandey, D. S. Pandey, Synthesis and characterization of

Jo

complexes imparting N-pyridyl bonded meso-pyridyl substituted dipyrromethanes, J. Organomet. Chem. 695 (2010) 841-849. https://doi.org/10.1016/j.jorganchem.2010.01.006.

[27] S. Majumder, A. L. Odom, Group-4 Dipyrrolylmethane Complexes in Intramolecular Olefin Hydroamination, Organometallics 27 (2008) 1174-1177. https://doi.org/10.1021/om700883a. [28] M. Wałęsa-Chorab, R. Banasz, M. Kubicki, V. Patroniak, Dipyrromethane functionalized monomers as precursors of electrochromic polymers, Electrochim. Acta 258 (2017) 571581. https://doi.org/10.1016/j.electacta.2017.11.100.

13

[29] L. Li, B. Nguyen, K. Burgess, Functionalization of the 4,4-difluoro-4-bora-3a,4a-diaza-sindacene (BODIPY) core, Bioorg. Med. Chem. Lett. 18 (2008), 3112-3116. https://doi.org/10.1016/j.bmcl.2007.10.103. [30] L. N. Sobenina, A. M. Vasil’tsov, O.V. Petrova, K.B. Petrushenko, I.A. Ushakov, G. Clavier, R. Meallet-Renault, A. I. Mikhaleva, B. A. Trofimov, General Route to Symmetric and Asymmetric meso-CF3-3(5)-Aryl(hetaryl)-and 3,5-Diaryl(dihetaryl)BODIPY Dyes, Org Lett., 13 (2011) 2524-2527. https://doi.org/10.1021/ol200360f. [31] S. Choi, J. Bouffard, Y. Kim, Aggregation-induced emission enhancement of a mesotrifluoromethyl BODIPY via J-aggregation, Chem Sci. 5 (2014) 751-755. https://doi.org/10.1039/c3sc52495g.

ro of

[32] C. Ray, J. Banuelos, T. Arbeloa, B. L. Maroto, F. Moreno, A. R. Agarrabeitia, M. J. Ortiz, I. López-Arbeloab, S. de la Moya, Push-pull flexibly-bridged bis(haloBODIPYs): solvent and spacer switchable red emission, Dalton Trans. 45 (2016) 11839-11848. https://doi.org/10.1039/c6dt01849a.

-p

[33] D. N. Tomilin, K. B. Petrushenko, L. N. Sobenina, M. D. Gotsko, I. A. Ushakov, A. D. Skitnevskaya, A. B. Trofimov, B. A.Trofimov, Synthesis and Optical Properties of meso-

re

CF3-BODIPY with Acylethynyl Substituents in the 3-Position of the Indacene Core, Asian J. Org.Chem. 5 (2016) 1288-1294. https://doi.org/10.1002/ajoc.201600303. [34] X-D. Jiang, T. Fang, X. Liu, D. Xi, Synthesis of meso-CF3-Substituted BODIPY

lP

Compounds with Redshifted Absorption, Eur. J. Org. Chem. (2017) 5074-5079. https://doi.org/10.1002/ejoc.201700800.

na

[35] K. B. Petrushenko, I. K. Petrushenko, O. V. Petrova, L. N. Sobenina, B. A. Trofimov, Novel environment-sensitive 8-CF3-BODIPY dye with 4-(dimethylamino)phenyl group at the 3-position: Synthesis and optical properties, Dyes and Pigments 136 (2017) 488-495.

ur

http://doi.org/10.1016/j.dyepig.2016.09.009. [36] D.N. Tomilin, L.N. Sobenina, K.B. Petrushenko, I.A. Ushakov, B.A. Trofimov, Design of

Jo

novel meso-CF3-BODIPY dyes with isoxazole substituents, Dyes and Pigments 152 (2018) 14-18. https://doi.org/10.1016/j.dyepig.2018.01.026.

[37] S. G. Awuah, J. Polreis, V. Biradar, Y. You, Singlet Oxygen Generation by Novel NIR BODIPY Dyes, Org Lett. 13 (2011) 3884-3887. https://doi.org/10.1021/ol2014076.

[38] S. G. Awuah, S. K. Das, F. D'Souza, Y. You, Thieno–Pyrrole-Fused BODIPY Intermediate as a Platform to Multifunctional NIR Agents, Chem Asian J. 8 (2013) 31233132. https://doi.org/10.1002/asia.201300855. [39] R. L. Watley, S. G. Awuah, M. Bio, R. Cantu, H. B. Gobeze, V. N. Nesterov, F. D'Souza, Y. You, Dual Functioning Thieno-Pyrrole Fused BODIPY Dyes for NIR Optical Imaging

14

and Photodynamic Therapy: Singlet Oxygen Generation without Heavy Halogen Atom Assistance, Chem Asian J. 10 (2015) 1335-1343. https://doi.org/10.1002/asia.201500140. [40] L. Liu, L. Fu, T. Jing, Z. Ruan, L. Yan, pH-Triggered Polypeptides Nanoparticles for Efficient BODIPY Imaging-Guided Near Infrared Photodynamic Therapy. ACS Appl Mater Interfaces 8 (2016) 8980-8990. https://doi.org/10.1021/acsami.6b01320. [41] J. Wang, J. Li, N. Chen, Y. Wu, E. Hao, Y. Wei, X. Mu, L. Jiao, Synthesis, structure and properties of thiophene-fused BODIPYs and azaBODIPYs as near-infrared agents, New J. Chem. 40 (2016) 5966-5975. https://doi.org/10.1039/c6nj01011c. [42] I. Kumadaki, A. Ando, M. Omote, Synthesis of fluorinated analogs of natural porphyrins potentially useful for the diagnosis and therapy of cancer, J. Fluorine Chem. 109 (2001)

ro of

67-81. https://doi.org/10.1016/S0022-1139(01)00381-5.

[43] Li-Mei Jin, Liang Chen, Juan-Juan Yin, Jin-Ming Zhou,| Can-Cheng Guo, Qing-Yun Chen, Rational Synthesis of meso- or β- Fluoroalkylporphyrin Derivatives via Halo-

fluoroalkylporphyrin Precursors: Electronic and Steric Effects on Regioselective

-p

Electrophilic Substitution in 5-Fluoroalkyl-10,20-diarylporphyrins, J. Org. Chem. 71 (2006) 527-536. https://doi.org/10.1021/jo051672g.

re

[44] M. Suzuki, S. Ishii, T. Hoshino, S. Neya, Syntheses of Highly Distorted mesoTrifluoromethyl-substituted β-Octaalkylporphyrins, Chem. Lett. 43 (2014) 1563–1565. https://doi.org/10.1246/cl.140561.

lP

[45] M. Suzuki, S. Neya, Y. Nishigaichi, Synthesis of 5,10-bis(Trifluoromethyl)Substituted Octamethylporphyrins and Central-Metal-Dependent Solvolysis of Their meso-

na

Trifluoromethyl Groups, Molecules 21 (2016) 252-259. https://doi.org/10.3390/molecules21030252. [46] T. P. Wijesekera, 5-Perfluoroalkyldipyrromethanes and porphyrins derived therefrom, Can.

ur

J. Chem. 74 (1996) 1868-1871. https://doi.org/10.1139/v96-209. [47] N. Nishino, R. W. Wagner, J. S. Lindsey, Synthesis of Linear Amphipathic Porphyrin

Jo

Dimers and Trimers: An Approach to Bilayer Lipid Membrane Spanning Porphyrin Arrays J. Org. Chem. 61 (1996) 7534-7544. https://doi.org/10.1021/jo9611576

[48] W. Dmowski, K. Piasecka-Maciejewska, Z. Urbaczyk-Lipkowska, Sodium DithioniteInitiated Coupling of 1-Bromo-1-chloro-2,2,2-trifluoroethane with Pyrroles: A New, Convenient and Economical Synthesis of 5-(Trifluoromethyl)dipyrromethanes, Synthesis (2003) 841-844. https://doi.org/10.1055/s-2003-38683. [49] Q.-C. Chen, M. Soll, A. Mizrahi, I. Saltsman, N. Fridman, M. Saphier, Z. Gross, One-pot synthesis of contracted and expanded porphyrins with meso-CF3 groups, from affordable

15

precursors, Angew. Chem. Int. Ed. 57 (2018) 1006-1010. http://dx.doi.org/10.1002/anie.201710106. [50] L. N. Sobenina, O. V. Petrova, K. B. Petrushenko, I. A. Ushakov, A. I. Mikhaleva, R. Meallet-Renault, B. A. Trofimov, Synthesis and Optical Properties of Difluorobora-sdiazaindacene Dyes with Trifluoromethyl meso-Substituents, Eur. J. Org. Chem. (2013)

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4107-4118. https://doi.org/10.1002/ejoc.201300212.

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Scheme captions

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Scheme 1. Synthetic route to the dipyrromethane 3aa.

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Scheme 2. Condensation of trifluoro(pyrrolyl)ethanol 1a with 2-(4-aminophenyl)pyrrole (2b) in the presence of

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AlCl3.

AlCl3.

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Scheme 3. Condensation of trifluoro(pyrrolyl)ethanol 1b with 2-(4-aminophenyl)pyrrole (2b) in the presence of

Scheme 4. Disproportionation of dipyrromethanes.

Scheme 5. Condensation of trifluoro(pyrrolyl)ethanol 1c with 2-phenylpyrrole (2c) in the presence of AlCl3.

17

Table

Table 1. The reaction of trifluoro(pyrrolyl)ethanols 1 with pyrroles 2 in the presence of AlCl3 (equimolar amount of 1 and 2, CH2Cl2, rt) AlCl3, %

Time, h

Yield, %a

1

10

16

70 (no reaction)

2

20

36

90 (no reaction)

Trifluoro(pyrrolyl) ethanol 1

Pyrrole 2

Dipyrromethane 3

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Entry

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3

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4

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5

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6

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8

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7

a

50

3.5

82 (no reaction)

100

5

72 (no reaction)

10

1

90 (82)

10

1

90 (84)

10

2

90 (80)

10

2

89 (83)

in brackets are given yields when P2O5 (1.1 eq) was used (CH2Cl2, rt, 16 h)