Supporting Information for

Transcription

1 Page of Submitted to The Journal of Organic Chemistry S Supporting Information for Syntheses and Spectral Properties of Functionalized, Water-soluble BODIPY Derivatives Lingling Li, Junyan Han, Binh Nguyen and Kevin Burgess * Texas A & M University, Chemistry Department, P.O. Box 00, College Station Texas, USA. burgess@tamu.edu Page General Experimental Conditions S Procedures for the preparation of Compounds, F, a, b, a, b S-S Copies of H NMR and C NMR Spectra of Compounds - S-S

2 Submitted to The Journal of Organic Chemistry Page 0 of S General Experimental Procedures. All chemicals were obtained from commercial suppliers and used without further purification. Chlorosulfonic acid was purchased from Aldrich and can be used within two to three months before it decomposed in to sulfuric acid. Dichloromethane was dried with MBRAUN MB-SPS solvent purification system. Chromatography on silica gel was performed using a forced flow of the indicated solvent on EM reagents silica gel 0 (0-0 mesh). H NMR spectra were recorded at room temperature and chemical shifts are reports in ppm from the solvent resonance (CDCl. ppm, DMSO-d.0 ppm, CD OD. ppm, D O. ppm). Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, br = broad, m = multiplet), number of protons, and coupling of constants. Proton decoupled C NMR spectra were also reported at room temperature. Chemical shifts are reported in ppm from tetramethylsiliane resonance (CDCl. ppm, DMSO-d. ppm, CD OD. ppm). Mass spectra were measured under ESI condition.

3 Page of Submitted to The Journal of Organic Chemistry S Procedures for the preparation of Compounds, F, a, b, a, b -(-Bromophenyl)dipyrromethane () Pyrrole ( ml,. mol) and -bromobenzaldehyde (. g, mmol) were added to a 00 ml dry round-bottomed flask and degassed with a stream of N for min. trifluoroacetic acid (TFA, 0. ml) was then added. The solution was stirred under N at room temperature for h, then the excess pyrrole was removed under reduced pressure. The residue was recrystallized from a hexane/dichloromethane mixture to give a white solid (. g, %). H NMR (00 MHz, CDCl ) δ. (br, H),. (d, H, J =. Hz),. (d, H, J =. Hz),. (s, H),. (m, H),. (s, H),. (s, H); C NMR ( MHz, CDCl ) δ.,.0,., 0.,.0,.,.,.,.. MS (ESI) calcd for C H BrN + (M+H) found (-Nitrophenyl)dipyrromethane (F) Pyrrole ( ml, 0 mmol) and -nitrobenzaldehyde (. g,. mmol) were added to a dry round-bottomed flask and degassed with a stream of N for min. TFA (0. ml) was then added, and the solution was stirred under N at room temperature for h and then quenched with 0. M NaOH. Ethyl acetate (0 ml) was then added. The organic phase was washed with water ( x 0 ml), dried over anhydrous Na SO, filtered, and dried in vacuo. The crude (ca % pure by H NMR as compared with the literature ) product was solidified from EtOAc/hexane as a green powder (. g, % crude yield). It was used to synthesize b directly without any further purification., -Dichloro--(-bromophenyl)dipyrromethene (a)

4 Submitted to The Journal of Organic Chemistry Page of S A solution of (. g, mmol) in 00 ml dry tetrahydrofuran (THF) was purged with N and cooled to - o C. A suspension of N-chlorosuccinimide (NCS,. g,. mmol) in 0 ml THF was added to the cooled solution. The reaction mixture was stirred at - o C for. h, warmed to room temperature, then stirred for an additional h. Water (0 ml) was added to the mixture. After extraction with CH Cl ( x 0 ml), the combined organic layers were dried over anhydrous Na SO, filtered, and the solution was evaporated to dryness. The residue was used for oxidation immediately without further purification. Dichloro dicyano quinone (DDQ,. g,. mmol) was added to the solution of the intermediate dichloro-dipyrromethane generated above in 0 ml CH Cl. The mixture was stirred at room temperature for h. After evaporation the solvent, the residue was loaded onto a silica gel flash column, and eluted using hexane to afford an orange powder (.0 g, % for steps). R f = 0. (0% EtOAc/hexane). H NMR (00 MHz, CDCl ) δ. (d, H, J =. Hz),. (d, H, J =. Hz),. (d, H, J =. Hz),.0 (d, H, J =. Hz); C NMR ( MHz, CDCl ) δ.,.,.,.,.,., +.,.,.; ΜS (ESI) calcd for C H BrCl N (M+H) +. found.., -Dichloro--(-nitrophenyl)dipyrromethene (b) A solution of F (. g,. mmol) in 0 ml dry THF was purged with N and cooled to - o C. A suspension of N-chlorosuccinimide (. g,. mmol) in ml THF was added to the cooled solution. The reaction mixture was stirred at - o C for. h, warmed to room temperature then stirred for an additional h. Water (0 ml) was added to the mixture. After extraction with CH Cl ( x 0 ml), the combined organic layers

5 Page of Submitted to The Journal of Organic Chemistry S were dried over anhydrous Na SO, filtered, and the solution was evaporated to dryness. The residue was used for oxidation immediately without further purification. The oxidant DDQ (. g,. mmol) was added to the solution of dichlorodipyrromethane generated above in ml CH Cl. The mixture was stirred at room temperature for h. After evaporation of the solvent, the residue was loaded onto a silica gel flash column, and eluted using 0% EtOAc/Hexane to afford an orange powder (. g, % for steps). R f = 0. (0% EtOAc/hexane). H NMR (00 MHz, CDCl ) δ. (d, H, J =. Hz),. (d, H, J =. Hz),. (d, H, J =. Hz),.0 (d, H, J =. Hz),. (br, H); C NMR ( MHz, CDCl ) δ.,.,.,.,.,.,.,.,.0.,-dichloro--( -bromophenyl)-,-difluoro--bora-a, a-diaza-s-indacence (a) A solution of a (. g, mmol) and triethylamine (.0 ml,. mmol) in 0 ml dry CH Cl was stirred under N at room temperature for min. Then boron trifluoride etherate (.0 ml,. mmol) was added slowly within min. The resulting solution was stirred for h, then washed with water ( x 0 ml), dried over anhydrous Na SO, filtered, and evaporated to dryness. The residue was loaded onto a silica gel flash column, and eluted using EtOAc. After removing EtOAc under vacuum, the product a was recrystallized from a hexane/dichloromethane mixture as a red crystal (. g, %). H NMR (00 MHz, CDCl ) δ. (d, H, J =. Hz),. (d, H, J =. Hz),. (d, H, J =. Hz),. (d, H, J =. Hz); C NMR ( MHz, CDCl ) δ.,.,.,.,.,.,.,.; MS (ESI) calcd for C H BBrCl F N + (M+H) +. found.. IR (thin film),,,,,,,, cm -.

6 Submitted to The Journal of Organic Chemistry Page of S,-Dichloro--( -nitrophenyl)-,-difluoro--bora-a, a-diaza-s-indacence (b) A solution of b (. g,. mmol) and triethylamine (. ml, mmol) in 0 ml dry CH Cl was stirred under N at room temperature for min. Then boron trifluoride etherate (. ml, mmol) was added slowly within min. The resulting solution was stirred for h, then washed with water ( x 0 ml), dried over anhydrous Na SO, filtered, and evaporated to dryness. The residue was loaded onto a silica gel flash column, and eluted using EtOAc. After removing the solvent under vacuum, the product b was recrystallized from EtOAc as a green crystal (. g, %). H NMR (00 MHz, CDCl ) δ. (d, H, J =. Hz),.0 (d, H, J =. Hz),. (d, H, J =. Hz),.0 (d, H, J =. Hz); C NMR ( MHz, CDCl ) δ.,.,.,.,.,.,.,., 0.0; MS (ESI) calcd for C H BCl FN O + (M-F) +.00 found.00; IR (thin film),,,,,,,,, cm -.

7 Page of Submitted to The Journal of Organic Chemistry H NMR (CDCl ) C NMR (CDCl ) Br NH HN S

8 Submitted to The Journal of Organic Chemistry Page of H NMR (CDCl ) C NMR (CDCl ) Cl Br N HN a Cl S

9 Page of Submitted to The Journal of Organic Chemistry H NMR (CDCl ) C NMR (CDCl ) Cl NO N HN b Cl S

10 Submitted to The Journal of Organic Chemistry Page of H NMR (CDCl ) C NMR (CDCl ) Cl Br N BF N a Cl S

11 Page of Submitted to The Journal of Organic Chemistry H NMR (CDCl ) C NMR (CDCl ) Cl NO N BF N b Cl S

12 Submitted to The Journal of Organic Chemistry Page of Mass spectrum S

13 Page of Submitted to The Journal of Organic Chemistry H NMR (CD OD) C NMR (CD OD) I N BF N a SO Na S

14 Submitted to The Journal of Organic Chemistry Page of Mass spectrum S

15 Page of Submitted to The Journal of Organic Chemistry H NMR (D O) C NMR (D O) NaO S I N BF N b SO Na S

16 Submitted to The Journal of Organic Chemistry Page of Mass spectrum S

17 Page of Submitted to The Journal of Organic Chemistry H NMR (CD OD) C NMR (CD OD) Cl Br N BF N a Cl S SO Na

18 Submitted to The Journal of Organic Chemistry Page of Mass spectrum S

19 Page of Submitted to The Journal of Organic Chemistry H NMR (D O) C NMR (D O) NaO S Cl Br N BF N b Cl SO Na S

20 Submitted to The Journal of Organic Chemistry Page of Mass spectrum S0

21 Page of Submitted to The Journal of Organic Chemistry H NMR (CD OD) C NMR (CD OD) NH N BF N a S SO Na

22 Submitted to The Journal of Organic Chemistry Page 0 of Mass spectrum S

23 Page of Submitted to The Journal of Organic Chemistry H NMR (D O) C NMR (D O) NaO S NH N BF N b SO Na S

24 Submitted to The Journal of Organic Chemistry Page of Mass spectrum S

25 Page of Submitted to The Journal of Organic Chemistry H NMR (D O) C NMR (D O) N N BF N a S SO Na

26 Submitted to The Journal of Organic Chemistry Page of Mass spectrum S

27 Page of Submitted to The Journal of Organic Chemistry H NMR (D O) C NMR (D O) NaO S N N BF N b SO Na S

28 Submitted to The Journal of Organic Chemistry Page of Mass spectrum S

29 Page of Submitted to The Journal of Organic Chemistry H NMR (D O) C NMR (D O) NaO S HOOC N N N N N BF S SO Na

30 Submitted to The Journal of Organic Chemistry Page of Mass spectrum S0

31 Page of Submitted to The Journal of Organic Chemistry H NMR (CD OD) NO N BF N a S SO Na

32 Submitted to The Journal of Organic Chemistry Page 0 of C NMR (CD OD) Mass spectrum S

33 Page of Submitted to The Journal of Organic Chemistry H NMR (D O) C NMR (D O) NaO S NO N BF N b SO Na S

34 Submitted to The Journal of Organic Chemistry Page of Mass spectrum S

35 Page of Submitted to The Journal of Organic Chemistry HO S N N BF H NMR (D O) SO H S

36 Submitted to The Journal of Organic Chemistry Page of Mass spectrum S

37 Page of Submitted to The Journal of Organic Chemistry H NMR (DMSO-d ) C NMR (DMSO-d ) Cl NO N BF N a Cl SO Na S

38 Submitted to The Journal of Organic Chemistry Page of Mass spectrum S

39 Page of Submitted to The Journal of Organic Chemistry H NMR (D O) C NMR (D O) NaO S Cl NO N BF N b Cl S SO Na

40 Submitted to The Journal of Organic Chemistry Page of Mass spectrum S