Supporting information for

Improved Synthesis of N-Ethyl-3,7-Bis(Trifluoromethyl)Phenothiazine

Selin E. Ergun, Matthew D. Casselman, Aman Preet Kaur, N. Harsha Attanayake, Sean R. Parkin, and Susan A. Odom*

Department of Chemistry, University of Kentucky, Lexington, KY 40506 I. Cyclic Voltammetry Cyclic voltammetry (CV) experiments were performed using a 600D potentiostat (CH Instruments, Inc.) in a nitrogen-filled glovebox. CVs were recorded in 0.5 TEATFSI/ACN at 1 mM BCF3EPT with glassy carbon (CH Instruments, Inc.) as the working electrode, freshly anodized Ag/AgCl (CH Instruments, Inc.) as the reference electrode, and a Pt (CH Instruments, Inc.) wire as the counter electrode. Voltammograms were recorded at a scan rate of 100 mV s-1. Ferrocene was used as an internal reference and the oxidation potential was calibrated with respect to ferrocene/ferrocenium (Cp2Fe0/+) redox couple. 100% iR correction was applied to compensate the solution resistance before recording CVs. The solution resistance was determined using iR compensation technique (CH Instruments 600D potentiostat). The resistance measured was ca.70 Ω, which leads a to correction of less than 5 mV at the highest measured current. The diffusion coefficient of BCF3EPT at 1 mM concentration was calculated using Randles–Sevcik equation,

𝑖" = 0.4463𝑛𝐹𝐴𝑐 .𝑛𝐹𝐷𝑅𝑇

𝜈34.5

where ip is the peak current (A), n is the number of electrons transferred (-), F is the Faraday constant (96,485 C mol-1), A is the electrode area (cm2), c is the concentration (mol cm-3), D is the diffusion coefficient (cm2 s-1), R is the gas constant (8.314 J mol-1 K-1), T is the absolute temperature (K), and ν is the scan rate (V s-1). The following scan rates were used for diffusion coefficient calculations: 10, 25, 50, 75, 100, 200, 300, 400, and 500 mV s-1. Figure S1 shows a cyclic voltammogram of BCF3EPT that accessed the first oxidation, voltammograms of BCF3EPT at variable scan rates, and the Randels-Sevcik analysis.

Electronic Supplementary Material (ESI) for New Journal of Chemistry.This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2020

Figure S1. Cyclic voltammogram of 1 mM BCF3EPT in 0.5 M TEABF4 / ACN (a), analysis of the first oxidation at variable scan rates (b), and a Randles-Sevick analysis (c). This potential in (a) is 100 mV/s scan was calibrated to ferrocene/ferrocenium at 0 V. Figure S1 shows a cyclic voltammogram of BCF3EPT that includes ferrocene as an internal reference.

Figure S1. Cyclic voltammogram of X mM BCF3EPT in 0.5 M TEATFSI / ACN with ferrocene added as an internal reference, obtained at a scan rate of 100 mV/s. II. Synthesis of BCF3EPT-BF4 and Its Stability as Measured by UV-Vis Spectroscopy Materials Nitrosonium tertrafluoroborate (NOBF4, 98%) was purchased from Alfa Aesar and was stored and weighed in an argon atmosphere glovebox, and removed in a capped vial only immediately prior to use. Acetonitrile (ACN, anhydrous, 99.8%) and diethyl ether (extra dry, 99.5%) for radical cation synthesis were purchased from Sigma Aldrich and Acros Organics, respectively.

Synthesis of N-Ethyl-3,7-bis(trifluoromethyl)phenothiazinium tetrafluoroborate (BCF3EPT-BF4). BCF3EPT (0.200 g, 0.550 mmol) was added to an oven-dried and cooled (to RT with a stream of nitrogen) 50 mL round-bottomed flask containing a stir bar and was capped with a rubber septum. Anhydrous ACN (10 mL) was added into the flask and the resulting pale yellow solution was stirred under nitrogen for the subsequent steps. The reaction flask was then placed in an ice bath. NOBF4 (0.071 g, 0.606 mmol) was added to the solution, which immediately turned dark yellow. The reaction mixture was stirred for 15 minu, after which anhydrous diethyl ether (20 mL) was added gradually with continued stirring, producing a green precipitate. The precipitate was filtered, then washed with dry diethyl ether (10 mL). The precipitate was then dried under vacuum to yield BCF3EPT-BF4 as a green solid (0.127 g, 51%). UV-vis Spectroscopy UV-vis spectra were obtained using optical glass cuvettes (Starna) with 1 mm path length on an Agilent 8453 diode array spectrophotometer. The radical cation solution of BCF3EPT-BF4 was prepared at 10 mM in anhydrous ACN and in 0.1 M TEABF4/ACN, then pipetted into optical glass cuvettes inside an argon-filled glovebox. The capped cuvettes were taken out from the glove box for spectral analysis. UV-vis spectra were collected at 5, 30, 60, 120, and 180 min after preparing samples.

Figure S2. Absorption spectra of the BCF3EPT-BF4 at 10 mM in ACN (a) and in 0.1 M TEABF4/ACN (b) from 5 min to 3 h after dissolution. III. Synthesis of BCF3EPT Precursors N-Ethylphenothiazine (EPT). Sodium hydride (13.05 g, 326.2 mmol, 60% suspension in mineral oil) was added to a solution of phenothiazine (50.00 g, 250.1 mmol) in anhydrous DMF (600 mL) in an oven-dried 1 L round-bottomed flask under nitrogen atmosphere, which was immersed in an oil bath at 30 °C. The oil bath was then heated to 50 °C for 1 h. A reflux condenser was attached, and bromoethane (24.4 mL, 35.5 g, 326 mmol) was added to the reaction mixture dropwise through the condenser. The reaction mixture was then stirred for 10 h. Ice was added, and the organic product was extracted with ethyl acetate (3 × 400 mL). The combined organic layers were dried over MgSO4, filtered to remove solids, and the filtrate concentrated by rotary evaporation. The crude product was purified by column chromatography with hexanes as the eluent, yielding the product as a white solid (55.9 g, 98%). 1H NMR (400 MHz, DMSO-d6) d (ppm): 7.21–7.17 (m, 2H), 7.13

(dd, J =7.6, 1.6 Hz, 2H), 7.00 (dd, J = 8.2, 1.0 Hz, 2H), 6.92 (td, J = 7.5, 1.2 Hz, 2H), 3.9 (q, J = 6.9 Hz, 2H), 1.3 (t, J = 6.9 Hz, 3H). 13C NMR (100 MHz, DMSO-d6) d (ppm): 144.4, 127.6, 127.0, 123.0, 122.3, 115.4, 41.0, 12.7. GCMS: m/z 227 (50%), 212(10%), 198 (100%), 167 (13%). 3,7-Dibromo-N-ethylphenothiazine (DBrEPT). To a solution of EPT (14.9 g, 65.6 mmol) in DMF (300 mL) in a 1 L round-bottomed flask immersed in an ice-water bath, N-bromosuccinimide (23.9 g, 134 mmol, 2.05 eq.) was added in 3 portions, and the reaction mixture was stirred overnight. The reaction mixture was poured into saturated aqueous sodium thiosulfate. The organic products were extracted with ethyl acetate and dried over MgSO4, filtered to remove solids, and concentrated by rotary evaporation. The crude product was purified by column chromatography with hexanes/ethyl acetate (15:1) as the eluent, yielding the product as a yellow solid (21.3 g, 84%). 1H NMR (400 MHz, DMSO-d6) d (ppm): 7.36-7.34 (m, 4H), 6.94 (dd, J = 9.1, 0.8 Hz, 2H), 3.85 (q, J = 7 Hz, 2H), 1.25 (t, J = 7 Hz, 3H). 13C NMR (100 MHz, DMSO-d6) d (ppm): 143.8, 130.8, 129.4, 125.2, 117.7, 114.4, 41.8, 12.7. GCMS: m/z 387 (23%), 385 (45%), 383 (23%), 358 (54%), 356 (100%), 354 (54%). IV. NMR Spectroscopy 1H, 13C, and 19F NMR spectra of purified BCF3EPT are shown below.

Figure S3. 1H, 13C, and 19F nuclear magnetic resonance spectra of BCF3EPT in CDCl3.

V. X-Ray Crystallography Thermal ellipsoid Plots of BCF3EPT and BCF3EPT-SbCl6 obtained by single crystal X-ray diffraction are shown below.

Figure S4. X-ray crystal structure of BCF3EPT (a) and BCF3EPT-SbCl6 (b). Note: The unit cell for BCF3EPT contains two molecules; only one is displayed here.