Supporting Information for

Catalyst-free synthesis of phenothiazines from N-(2-mercaptophenyl)acetamide and S-2-acetamidophenyl ethanethioate

Yue Zhou, Qingle Zeng,* Li Zhang

a State Key Laboratory of Geohazard Prevention and Geoenvironment Protection (Chengdu University of Technology), Chengdu University of Technology, College of Materials, Chemistry & Chemical Engineering, 1#, Dongsanlu, Erxianqiao, Chengdu 610059, Sichuan, P. R. China.

E-mail: ;

Table of Contents

General Information ------S2

General procedure ------S2-S3

Characterization Data of Compounds 3a-3j------S4-S7

References ------S8

Copies of 1H and 13C NMR Spectra for Compounds 3a-3j ------S9-S20


General Information

All chemicals including DMF and Cs2CO3 were purchased from Aldrich, Adamas, Alfa Aesar, Aladdin, and Kelong Chemical Co. and used as received, unless otherwise noted. Petroleum ether refers to the fraction boiling in the 60–90 °C range.

All reactions were carried out under an argon atmosphere. The glassware used was dried in an electric oven at 120 oC. 1H NMR spectra were determined on a Bruker Avance 300MHz instrument or on a Bruker Avance III 400 MHz instrument. 1H NMR data are reported in δ units (ppm), and were measured relative to the signals for residual chloroform (7.26 ppm), DMSO (2.50 ppm) or acetone (2.05 ppm) in the deuterated solvent, unless otherwise stated. 13C NMR spectra are reported in d (ppm) relative to deuterochloroform (77.2 ppm), DMSO (39.5 ppm) or acetone (206.7 ppm for C=O) unless otherwise stated, and all were obtained with 1H decoupling. IR spectra were taken on a Bruker Tensor-27 infrared spectrometer using an OPUS workstation. Electrospray ionization-mass spectra (ESI-MS) were obtained on a LC-MS spectrometer. High-resolution mass spectra are recorded on a Shimadzu LCMS-IT-TOF instrument in the ESI mode. High-resolution mass spectra are recorded on a Shimadzu LCMS-IT-TOF instrument. Melting points were determined using a Shanghai Jingke SGW X-4 microscope melting point apparatus.

Typical experimental procedure for transition metal free synthesis of phenothiazines from N-(2-mercaptophenyl)acetamide and S-2-acetamidophenyl ethanethioate

To an oven-dried 25 mL ground mouth test tube equipped with a stir bar was added S-2-acetamidophenyl ethanethioate (0.5 mmol), 1-bromo-2-iodobenzene (0.6 mmol), Cs2CO3 (2.0 mmol), DMF (3 mL). The test tube was sealed with a sleeve rubber stopper and evacuated and refilled with argon for three cycles. The mixture was stirred 130 oC for 10 hours. After cooling to room temperature, the reaction mixture was quenched with water (20 mL), and extracted with ethyl acetate (20 mL) for three times. The combined organic layer was dried with anhydrous MgSO4, and condensed in vacuum on a rotary evaporator. The residual was purified on a silica gel chromatograph column by means of gradient elution (eluent: petroleum ether / ethyl acetate) to give the desired product.

Characterization data of products 3a-3j


10H-phenothiazine (3a) [1]

Pale yellow solid. Mp. 179-182oC.

1H NMR (400 MHz, DMSO-d6) δ 8.66 (s, 1H), 7.04 (td, J = 7.8, 1.5 Hz, 2H), 6.97 (dd, J = 7.6, 1.3 Hz, 2H), 6.81 (td, J = 7.5, 1.2 Hz, 2H), 6.74 (dd, J = 7.9, 1.1 Hz, 2H).

13C NMR (101 MHz, DMSO-d6) δ 142.57 (s), 128.03 (s), 126.72 (s), 122.25 (s), 116.78 (s), 114.89 (s).

2-(trifluoromethyl)-10H-phenothiazine (3b) [1]

Yellow solid. Mp. 184-187 oC.

1H NMR (400 MHz, DMSO-d6) δ 8.96 (s, 1H), 7.17 (d, J = 8.0 Hz, 1H), 7.14 – 7.05 (m, 2H), 7.03 – 6.94 (m, 2H), 6.86 (td, J = 7.5, 1.3 Hz, 1H), 6.72 (dd, J = 7.9, 1.1 Hz, 1H).

13C NMR (101 MHz, DMSO-d6) δ 143.11 (s), 141.36 (s), 128.71 (s), 128.54 (s), 127.39 (s), 126.86 (s), 125.83 (s), 123.03 (s), 122.46 (s), 118.50 (s), 115.77 (s), 115.16 (s), 110.48 (s).

1-chloro-10H-phenothiazine (3c) [2]

Pale purple solid. Mp. 114-115 oC.

1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 1H), 6.98 (ddd, J = 22.7, 11.5, 4.9 Hz, 3H), 6.84 (d, J = 8.0 Hz, 1H), 6.75 (td, J = 7.6, 1.1 Hz, 1H), 6.69 – 6.61 (m, 1H), 6.57 (dd, J = 8.0, 0.9 Hz, 1H).

13C NMR 101 MHz, DMSO-d6) δ 143.61 (s), 141.40 (s), 130.02(s), 128.67(s), 128.53(s) 126.84 (s), 122.59 (s), 121.87 (s), 116.37 (s), 115.62 (s), 114.85 (s), 113.22 (s).


2-bromo-10H-phenothiazine (3d) [3]

White solid. Mp. 183-184 oC.

1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 1H), 7.13 (dt, J = 5.2, 2.2 Hz, 2H), 7.04 – 6.97 (m, 1H), 6.92 (dd, J = 7.7, 1.3 Hz, 1H), 6.77 (td, J = 7.5, 1.2 Hz, 1H), 6.67 (dd, J = 7.9, 1.1 Hz, 1H), 6.61 (d, J = 8.3 Hz, 1H).

13C NMR (101 MHz, DMSO-d6) δ 141.98 (s), 141.97(s), 130.54 (s), 128. 52(s), 128.29 (s), 126.78 (s), 122.58 (s), 119.45 (s), 116.32 (s), 116.05 (s), 115.05 (s), 112.84 (s).

2-Chloro-10H-phenothiazine (3e) [4]

Yellow solid. Mp. 188-192 oC.

1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 1H), 7.06 – 6.97 (m, 1H), 6.96 – 6.89 (m, 2H), 6.83 – 6.74 (m, 2H), 6.73 – 6.63 (m, 2H).

13C NMR (101 MHz, DMSO-d6) δ 143.98 (s), 141.55 (s), 132.25 (s), 128.26 (s), 127.92 (s), 126.81 (s), 122.82 (s), 121.67 (s), 116.48 (s), 115.96 (s), 115.14 (s), 114.18 (s).

4-Fluoro-10H-phenothiazine (3f) [5]

White solid. Mp. 178.8-181.2 oC.

1H NMR (400 MHz, DMSO-d6) δ 8.87 (s, 1H), 7.11 – 7.04 (m, 1H), 7.04 – 6.95 (m, 2H), 6.85 (td, J = 7.5, 1.3 Hz, 1H), 6.74 (dd, J = 7.9, 1.1 Hz, 1H), 6.66 (td, J = 8.5, 2.7 Hz, 1H), 6.56 (dd, J = 10.5, 2.7 Hz, 1H).

13C NMR (101 MHz, DMSO-d6) δ 163.65 (s), 144.39 (d, J = 11.0 Hz), 141.62 (s), 128.13 (s), 127.81 (d, J = 9.9 Hz), 126.76 (s), 122.78 (s), 116.85 (s), 115.07 (s), 112.25 (d, J = 2.5 Hz), 108.68 (s), 101.82 (s).

3-fluoro-10H-phenothiazine (3g) [6]

Pale purple solid. Mp. 186-187 oC.

1H NMR (400 MHz, DMSO-d6) δ 8.81 (s, 1H), 7.06 – 6.98 (m, 1H), 6.98 – 6.89 (m, 2H), 6.79 (td, J = 7.5, 1.2 Hz, 1H), 6.68 (dd, J = 7.9, 1.1 Hz, 1H), 6.60 (td, J = 8.5, 2.7 Hz, 1H), 6.51 (dd, J = 10.5, 2.7 Hz, 1H).

13C NMR (101 MHz, DMSO-d6) δ 163.64 (s), 144.38 (d, J = 11.0 Hz), 141.61 (s), 127.83 (d, J = 9.8 Hz), 126.77 (s), 122.79 (s), 116.83 (s), 115.07 (s), 112.23 (d, J = 2.7 Hz), 108.69 (s), 102.08 (s), 101.82 (s).

4-bromo-2-fluoro-10H-phenothiazine (3h)

Pale purple solid. Mp. 130-131 oC.

1H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 7.12 – 6.97 (m, 3H), 6.85 (td, J = 7.6, 1.1 Hz, 1H), 6.69 (dd, J = 7.9, 1.1 Hz, 1H), 6.51 (dd, J = 10.3, 2.6 Hz, 1H).

13C NMR (101 MHz, DMSO-d6) δ 162.97 (s), 160.54 (s), 144.77 (d, J = 11.8 Hz), 140.51 (s), 128.63 (s), 126.81 (s), 123.11 (s), 120.20 (d, J = 12.5 Hz), 116.16 (s), 114.89 (s), 111.74 (s), 101.25 (s).

ESI-MS (positive mode), m/z = 296 [M+H]+.

HR-MS (ESI-TOF) m/z [M+H+] calcd for C12H7BrFNS 295.9539; found 295.9552.

IR (KBr), ν (cm-1) 3297.73, 1581.37, 1510.01, 1444.45, 1417.45, 1382.73, 1305.59, 1268.95, 1122.39, 1029.89, 846.61, 742.47, 659.55, 592.05.

3-iodo-10H-phenothiazine-1-carboxylic acid (3i)

Brown solid. Mp. 234-235 oC.

1H NMR (400 MHz, DMSO-d6) δ 10.17 (s, 1H), 7.92 (d, J = 2.0 Hz, 1H), 7.55 (s, 1H), 7.10 (ddd, J = 17.9, 12.1, 4.5 Hz, 2H), 6.94 (t, J = 7.5 Hz, 1H), 6.83 (d, J = 7.9 Hz, 1H).

13C NMR (101 MHz, DMSO-d6) δ 168.71 (s), 144.76 (s), 139.55 (s), 138.18 (s), 137.83 (s), 128.54 (s), 126.82 (s), 124.01 (s), 121.60 (s), 116.61 (s), 116.57(s), 114.28 (s), 82.44 (s).

ESI-MS (positive mode), m/z = 370 [M+H]+.

HR-MS (ESI-TOF) m/z [M+H+] calcd for C13H9INO2S 369.9393; found 369.9374.

IR (KBr), ν (cm-1) 3309.30, 2852.97, 2616.97, 1662.37, 1488.80, 1484.94, 1434.94, 1251.60, 1216.88, 1130.10, 742.47, 838.70, 815.90, 570.84.

methyl 10H-phenothiazine-2-carboxylate (3j)

Yellow solid. Mp. 180-181 oC.

1H NMR (400 MHz, DMSO-d6) δ 9.11 (s, 1H), 7.57 (dd, J = 8.4, 2.0 Hz, 1H), 7.40 (d, J = 1.9 Hz, 1H), 7.05 – 6.97 (m, 1H), 6.92 (dd, J = 7.7, 1.3 Hz, 1H), 6.80 (td, J = 7.5, 1.2 Hz, 1H), 6.73 – 6.65 (m, 2H), 3.77 (s, 3H).

13C NMR (101 MHz, DMSO-d6) δ 165.79 (s), 146.62 (s), 140.67 (s), 129.99 (s), 128.32 (s), 127.49 (s), 126.76 (s), 123.28 (s), 122.97 (s), 116.69 (s), 116.27 (s), 115.38 (s), 114.26 (s), 52.26 (s).

ESI-MS (positive mode), m/z = 280 [M+Na]+.

HR-MS (ESI-TOF) m/z calcd for C14H11NNaO2S [M+Na+] 280.0403; found 280.0418.

IR (KBr), ν (cm-1) 3345.94, 2944.82, 2850.32, 1710.58, 1689.36, 1602.58, 1575.58, 1475.30, 1436.73, 1290.17, 1265.09, 1116.60, 833.11, 755.97, 626.76.


References

1.  Dai, C.; Sun, X. F.; Tu, X. Z.; Wu, L.; Zhan, D.; Zeng, Q. L. Chem. Commun. 2012, 48, 5367–5369.

2.  Hallberg, A.; Martin, A. R.Synth. Commun.1983,13,467-470.

3.  Bodea, C.; Terdic, M.; Silberg, L. Eur. J. Org. Chem. 1964, 673, 113-120.

4.  Ma, D. W.; Geng, Q.; Zhang, H.; Jiang, Y. W. Angew. Chem. Int. Ed. 2010, 49, 1291-1294.

5.  David, C.; Gilbert, B. C.; Hanson, P. J. Chem. Soc., Perkin Trans. 2 1977,517-525.

6.  Wu, S.; Hu, W. Y.; Zhang, S. L. RSC Adv. 2016, 6, 24257-24260.


Copies of 1H and 13C NMR Spectra for Compounds 3a-3j

3a 1H NMR

3a 1C NMR

3b 1H NMR

3b 1C NMR

3c 1H NMR

3c 1C NMR

3d 1H NMR

3d 1C NMR

3e 1H NMR

3e 1C NMR

3f 1H NMR

3f 1C NMR

3g 1H NMR

3g 1C NMR

3h 1H NMR

3h 1C NMR

3i 1H NMR

3i 1C NMR

3j 1H NMR

3j 1C NMR

S1