A Mannich-Type Reaction at the meso-Methyl Position of the BODIPY Fluorophore

Abstract

Treatment of 2,6-diethyl-4,4-difluoro-1,3,5,7,8-penta­methyl-4-bora-3a,4a-diaza-s-indacene (BODIPY) with secondary amines in dihalomethane resulted in carbon–carbon bond formation at the meso-methyl position of BODIPY via Mannich-type reactions. The resulting modified BODIPY fluorophores possess high fluorescent quantum yields.

Key words

BODIPY - Mannich reaction - fluorophore - dihalomethane - secondary amine

• References

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• 7 Synthesis of 2,6-Diethyl-4,4-difluoro-1,3,5,7-tetramethyl-8-(N,N-diethylaminoethyl)-4-bora-3a,4a-diaza-s-indacene (2a) Diethylamine (0.65 mL, 6.28 mmol) was added to a solution of 4,4-difluoro-2,6-diethyl-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (1, 100 mg, 0.314 mmol) in dry CH₂Cl₂ (4.0 mL) in a reaction vial. After the sealed reaction mixture was heated to 40 °C for 3 d, the resulting products were diluted with CH₂Cl₂ (10 mL) and washed successively with sat. NH₄Cl solution (2 × 10 mL) and brine (10 mL). The organic layer was dried (MgSO₄) and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel. The appropriate fractions, which were eluted with CH₂Cl₂–MeOH (99:1 v/v) were combined and evaporated under reduced pressure to give the title compound as an orange solid (78 mg, 62%). R_f = 0.4 (CH₂Cl₂–MeOH = 95:5 v/v). HRMS (EI): m/z calcd for ¹²C₂₃ ¹H₃₆ ¹¹B¹⁹F₂ ¹⁴N₃: 403.29703; found: 403.29742. ¹H NMR (300.1 MHz, CDCl₃): δ = 1.06 (12 H, t, J = 7.3), 2.38–2.47 (10 H, m), 2.51 (6 H, s), 2.65 (6 H, m), 3.25 (2 H, m). ¹³C NMR (75.5 MHz, CDCl₃): δ = 11.6, 12.4, 13.5, 14.8, 17.2, 27.8, 46.6, 55.1, 131.2, 132.6, 135.9, 142.3, 152.3. ¹¹B NMR (CDCl₃): δ = 0.60 (t, J = 33.2)
• 8 2,6-Diethyl-4,4-difluoro-1,3,5,7-tetramethyl-8-(N,N-diethylaminoethyl)-4-bora-3a,4a-diaza-s-indacene (2a) was also prepared independently according to the following procedure. N,N,N′,N′-Tetraethylmethylene diamine (3, 0.89 mL, 4.56 mmol) was added to a solution of 2,6-diethyl-4,4-difluorine-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (1, 75 mg, 0.24 mmol) in dry THF (4.0 mL). After the reaction mixture was heated at 40 °C overnight, the products were diluted with CH₂Cl₂ (10 mL) and washed successively with sat. NH₄Cl solution (2 × 10 mL) and brine (10 mL). The organic layer was dried (MgSO₄) and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel. The appropriate fractions, which were eluted with CH₂Cl₂–MeOH (99:1 v/v) were combined and evaporated under reduced pressure to give 2,6-diethyl-4,4-difluoro-1,3,5,7-tetramethyl-8-(N,N-diethylamino ethyl)-4-bora-3a,4a-diaza-s-indacene (2a) as an orange solid (78 mg, 82%)
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