Supporting Information

2-(Phenylseleno)ethanesulfon-amide as a Novel Protecting Group for Aniline that

can be Deprotected by a Radical Reaction

Nobuhiro Kihara, Yuji Mitsuhashi, Makoto Sato, Shun-ichi Hirose, Erika Goudo,

Yoshinori Uzawa, Natsumi Shirai, Sari Hamamoto, Ryo Iwasaki, Akane Fujioka

Department of Chemistry, Faculty of Science, Kanagawa University

2946 Tsuchiya, Hiratsuka 259-1293, Japan

Experimental

Materials

Toluene was used after distillation over P2O5. 2-Allylaniline 1d1 and tert-butyl N-(4-

aminophenyl)carbazate 1i2,3 were prepared according to the literatures with some

modifications. All other chemicals and solvents were reagent-grade, and were used

without further purification.

Instruments

NMR spectra were recorded on JEOL JNM-ECP300, JNM-EX400, and JNM-ECP500

spectrometers using tetramethylsilane as an internal standard. IR spectra were recorded

on a JASCO FT/IR 4100 spectrometer. Melting points were observed on a Yanaco MP-

500D instrument. Gas chromatography analysis was carried out using Shimadzu GC-

8A instrument with SE30 stationary phase.

2-(3-Phenylprop-2-enyl)aniline 1e

A solution of palladium(II) acetate (12.4 mg, 0.0552 mmol), tris(o-tolyl)phosphane

(65.7 mg, 0.216 mmol), iodobenzene (225 mg, 1.10 mmol), triethylamine (0.16 mL,

1.15 mmol), and 2-allylaniline 1d (117 mg, 0.792 mmol) in acetonitrile (7 mL) was

refluxed under nitrogen atmosphere for 4 h. After evaporation, the residue was

dissolved in ethyl acetate, and washed with sodium bicarbonate solution. The aqueous

layer was extracted with ethyl acetate twice. The combined organic layer was dried

over anhydrous magnesium sulfate, and evaporated. The residue was chromatographed

(eluent; ethyl acetate-hexane, 1/9, v/v) to obtain 2-(3-phenylprop-2-enyl)aniline 1e (136

1

mg, 82 %) as a pale brown solid. The 1H NMR spectrum of the product was identical to

that reported by Motokura et al.4

1H-NMR (CDCl3, 400 MHz): 7.37-7.18 (m, 5H), 7.13-7.02 (m, 2H), 6.80-6.64 (m,

2H), 6.47 (d, J = 16.0 Hz, 1H), 6.34 (dt, J = 16.0 and 6.4 Hz, 1H), 3.69 (br, 2H), 3.47 (d,

J = 6.4 Hz, 2H)

Vinylsulfonamide: Typical procedure

To a solution of 2-chloroethanesulfonyl chloride (1.56 g, 9.57 mmol) in THF (10 mL)

was added dropwise N-methylaniline (989 mg, 9.23 mmol) followed by triethylamine (5

mL, 36 mmol) at 0 °C. After stirring for 3 h, ethyl acetate was added, and the reaction

mixture was washed with 3 M hydrochloric acid then brine, dried over magnesium

sulfate, evaporated in vacuo to obtain 1.76 g (97 %) of vinylsulfonamide 3a as a pale

brown solid. The product was spectroscopically pure, and was used without further

purification.

Figure S1. 1H NMR spectrum of 3a (CDCl3, 300 MHz)

3a: １ H-NMR (CDCl3, 300 MHz): 7.41-7.25 (m, 5H), 6.46 (dd, J = 16.6 and 9.9 Hz,

1H), 6.20 (d, J = 16.6 Hz, 1H), 6.01 (d, J = 9.9 Hz, 1H), 3.25 (s, 3H) ppm.

2

Figure S2. 1H NMR spectrum of 3b (CDCl3, 500 MHz)

3b: １ H-NMR (CDCl3, 300 MHz): 7.36-7.14 (m, 5H), 6.56 (dd, J = 16.5 and 9.9 Hz,

1H), 6.45 (br, 1H), 6.29 (d, J = 16.5 Hz, 1H), 5.96 (d, J = 9.9 Hz, 1H) ppm.

3

Figure S3. 1H NMR spectrum of 3c (CDCl3, 400 MHz)

3c: １ H-NMR (CDCl3, 400 MHz): 7.41-7.26 (m, 5H), 6.52 (dd, J = 16.6 and 9.9 Hz,

1H), 6.14 (d, J = 16.6 Hz, 1H), 5.94 (d, J = 9.9 Hz, 1H), 3.57 (t, J = 7.1 Hz, 2H), 1.49-

1.28 (m, 4H), 0.87 (t, J = 7.3 Hz, 3H) ppm.

Figure S4. 1H NMR spectrum of 3d (CDCl3, 300 MHz)

3d: １ H-NMR (CDCl3, 300 MHz): 7.48-7.73 (m, 1H), 7.29-7.14 (m, 3H), 6.58 (dd, J

= 16.5 and 9.8 Hz, 1H), 6.39 (br, 1H), 6.27 (d, J = 16.5 Hz, 1H), 6.02-5.88 (m, 2H),

5.20 (dq, J = 10.1 and 1.6 Hz, 1H) 5.07 (dq, J = 17.2 and 1.6 Hz, 1H), 3.42 (dt, J = 5.9

and 1.6 Hz, 2H) ppm.

4

Figure S5. 1H NMR spectrum of 3e (CDCl3, 300 MHz)

3e: １ H-NMR (CDCl3, 300 MHz): 7.48-7.15 (m, 9H), 6-59-5.86 (m, 6H), 3.60-3.55

(m, 2H) ppm.

5

Figure S6. 1H NMR spectrum of 3f (CDCl3, 400 MHz)

3f: １ H-NMR (CDCl3 , 400 MHz):7.17-7.12 (m, 2H), 6.88-6.83 (m, 2H), 54 (dd,

J = 16.6 and 10.0 Hz, 1H), 6.38 (br, 1H), 6.19 (d, J = 16.6 Hz, 1H), 5.93 (d, J = 10.0

Hz, 1H), 3.79 (s, 3H) ppm.

Figure S7. 1H NMR spectrum of 3g (CDCl3, 400 MHz)

3g: １ H-NMR (CDCl3 , 400 MHz): 8.04-7.99 (m, 2H), 7.21-7.16 (m, 2H), 6.78 (br,

1H), 6.58 (dd, J = 16.5 and 9.8 Hz, 1H), 6.39 (d, J = 16.5 Hz, 1H), 6.04 (d, J = 9.8 Hz,

1H), 4.37 (q, J = 7.1 Hz, 2H), 1.39 (t, J = 7.1 Hz, 3H) ppm.

6

Figure S8. 1H NMR spectrum of 3h (CDCl3, 500 MHz)

3h: １ H-NMR (CDCl3, 500 MHz): 7.46-7.42 (m, 2H), 7.07-7.04 (m, 2H), 6.54 (dd, J

= 16.5 and 9.8 Hz, 1H), 6.52 (br, 1H), 6.29 (d, J = 16.5 Hz, 1H), 5.99 (d, J = 9.8 Hz,

1H) ppm.

7

Figure S9. 1H NMR spectrum of 3i (CDCl3, 400 MHz)

3i: １ H-NMR (CDCl3, 400 MHz): 7.35-7.30 (m, 2H), 7.14-7.09 (m, 2H), 6.51 (dd, J

= 16.8 and 10.0 Hz, 1H), 6.45 (br, 1H), 6.21 (d, J = 16.8 Hz, 1H), 6.15 (br, 1H), 5.92 (d,

J = 10.0 Hz, 1H), 1.51 (s, 9H) ppm.

8

Figure S10. 1H NMR spectrum of 3j (CDCl3, 500 MHz)

3j: １ H-NMR (CDCl3 , 500 MHz): 7.32-7.27 (m, 2H), 7.23-7.15 (m, 3H), 6.49 (dd, J =

16.5 and 9.9 Hz, 1H), 6.24 (d, J = 16.5 Hz, 1H), 5.93 (d, J = 9.9 Hz, 1H), 4.21 (br, 1H),

3.08-3.03 (m, 2H), 2.68 (t, J = 7.6 Hz, 2H), 1.93-1.86 (m, 2H) ppm.

9

Figure S11. 1H NMR spectrum of 3k (CDCl3, 300 MHz)

3k: １ H-NMR (CDCl3, 300 MHz): 7.36-7.17 (m, 5H), 6.47 (dd, J = 16.6 and 9.8 Hz,

1H), 6.26 (d, J = 16.6 Hz, 1H), 6.05 (d, J = 9.8 Hz, 1H), 3.92-3.84 (m, 2H), 2.77-2.52

(m, 3H), 1.99-1.76 (m, 4H) ppm.

2-(Phenylseleno)ethanesulfonamide (SeES amide): Typical procedure

To a suspension of diphenyl diselenide (0.90 g, 2.9 mmol) in ethanol (100 mL) was

added sodium tetrahydrideborate until the yellow color of diselenide was disappeared.

Vinylsulfonamide 3a (1.13 g, 5.38 mmol) was added. After stirring for 1 h, acetic acid

(1 mL) was added, and the reaction mixture was stirred overnight. After the solvent was

evaporated, dichloromethane was added, and the organic layer was washed with 3 M

hydrochloric acid then saturated sodium hydrogencarbonate solution, dried over

magnesium sulfate, and evaporated in vacuo. The residue was chromatographed

(eluent: ethyl acetate/hexane = 1/3, v/v) to obtain 1.75 g (88 %) of SeES amide 4a as a

white solid.

10

Figure S12. 1H NMR spectrum of 4a (CDCl3, 400 MHz)

4a: mp 80.6-81.0 °C (cyclohexane-hexane). １ H-NMR (CDCl3 , 400 MHz): 7.51-7.45

(m, 2H), 7.37-7.25 (m, 8H), 3.32-3.25 (m, 5H), 3.16-3.10 (m, 2H) ppm. MS (EI): m/z

355 (M+). Anal: Calcd for C15H17NO2SSe, C, 50.85; H, 4.84; N, 3.95, Found, C, 51.18;

H, 4.90; N, 4.00.

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Figure S13. 1H NMR spectrum of 4b (CDCl3, 300 MHz)

4b: １ H-NMR (CDCl3 , 300 MHz): 7.43-7.09 (m, 10H), 6.39 (br, 1H), 3.42-3.34 (m,

2H), 3.20-3.12 (m, 2H) ppm.

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Figure S14. 1H NMR spectrum of 4c (CDCl3, 400 MHz)

4c: １ H-NMR (CDCl3 , 400 MHz): 7.55-7.48 (m, 2H), 7.38-7.19 (m, 8H), 3.63 (t, J =

7.2 Hz, 2H), 3.31-3.24 (m, 2H), 3.19-3.13 (m, 2H), 1.45-1.24 (m, 4H), 0.85 (t, J = 7.3

Hz, 3H) ppm.

13

Figure S15. 1H NMR spectrum of 4d (CDCl3, 400 MHz)

4d: １ H-NMR (CDCl3 , 400 MHz): 7.46-7.41 (m, 2H), 7.33-7.12 (m, 7H), 6.29 (br,

1H), 5.96-5.85 (m, 1H), 5.16-5.13 (m, 1H), 5.07-5.00 (m, 1H), 3.42-3.35 (m, 4H), 3.17-

3.12 (m, 2H) ppm.

14

Figure S16. 1H NMR spectrum of 4e (CDCl3, 300 MHz)

4e: １ H-NMR (CDCl3 , 300 MHz): 7.43-7.12 (m, 14H), 6.55-6.07 (m, 3H), 3.59-3.53

(m, 2H), 3.43-3.31 (m, 2H), 3.16-3.07 (m, 2H) ppm.

15

Figure S17. 1H NMR spectrum of 4f (CDCl3, 300 MHz)

4f: １ H-NMR (CDCl3 , 400 MHz): 7.447-7.42 (m, 2H), 7.32-7.23 (m, 3H), 7.09-7.03

(m, 2H), 6.85-6.79 (m, 2H), 6.25 (br, 1H), 3.80 (s, 3H), 3.35-3.27 (m, 2H), 3.18-3.11

(m, 2H) ppm.

Figure S18. 1H NMR spectrum of 4g (CDCl3, 300 MHz)

4g: １ H-NMR (CDCl3 , 500 MHz): 8.00-7.95 (m, 2H), 7.40-7.36 (m, 2H), 7.29-7.18

(m, 3H), 7.15-7.11 (m, 2H), 6.68 (br, 1H), 4.39 (q, J = 7.1 Hz, 2H), 3.46-3.38 (m, 2H),

3.17-3.09 (m, 2H), 1.41 (t, J = 7.1 Hz, 3H) ppm.

16

Figure S19. 1H NMR spectrum of 4h (CDCl3, 500 MHz)

4h: １ H-NMR (CDCl3 , 500 MHz): 7.42-7.39 (m, 4H), 7.33-7.22 (m, 3H), 7.01-6.97

(m, 2H), 6.38 (br, 1H), 3.38-3.33 (m, 2H), 3.15-3.10 (m, 2H) ppm.

17

Figure S20. 1H NMR spectrum of 4i (CDCl3, 400 MHz)

4i: １ H-NMR (CDCl3 , 400 MHz): 7.45-7.41 (m, 2H), 7.33-7.23 (m, 5H), 7.08-7.03

(m, 2H), 6.47 (br, 1H), 6.24 (br, 1H), 3.35-3.28 (m, 2H), 3.17-3.11 (m, 2H), 1.53 (s, 9H)

ppm.

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Figure S21. 1H NMR spectrum of 4j (CDCl3, 300 MHz)

4j: １ H-NMR (CDCl3 , 400 MHz): 7.53-7.49 (m, 2H), 7.33-7.25 (m, 5H), 7.24-7.13

(m, 3H), 4.12 (t, J = 6.0 Hz, 1H), 3.29-3.24 (m, 2H), 3.18-3.12 (m, 2H), 3.09-3.03 (m,

2H), 2.65 (t, J = 7.6 Hz, 2H), 1.88-1.81 (m, 2H) ppm.

19

Figure S22. 1H NMR spectrum of 4k (CDCl3, 500 MHz)

4k: １ H-NMR (CDCl3 , 500 MHz): 7.56-7.51 (m, 2H), 7.34-7.16 (m, 8H), 3.90-3.85

(m, 2H), 3.26-3.17 (m, 4H), 2.86-2.79 (m, 2H), 2.62-2.55 (m, 1H), 1.93-1.88 (m, 2H),

1.80-1.71 (m, 2H) ppm.

Radical deprotection of SeES amide 4a: Typical procedure

To a solution of SeES amide 4a (175 mg, 0.494 mmol) in freshly distilled toluene (10

mL) were simultaneously added 1.00 mL of AIBN solution (325 mg, 1.98 mmol, of

AIBN in 2.00 mL of acetonitrile) and 1.00 mL of tributyltin hydride solution (1150 mg,

3.95 mmol, of tin hydride in 2.00 mL of hexane) over the period of 20 h using syringe

pump under nitrogen atmosphere at 80 °C. The resulting mixture was stirred for

additional 1 h at 80 °C. The yield of N-methylaniline 1a (92 %) was determined by gas

chromatography using dodecane as the internal standard.

Radical deprotection of SeES amide 4b: Typical procedure

To a solution of SeES amide 4b (170 mg, 0.500 mmol) in freshly distilled toluene (10

mL) were simultaneously added 1.00 mL of AIBN solution (330 mg, 2.00 mmol, of

20

AIBN in 2.00 mL of acetonitrile) and 1.00 mL of tributyltin hydride solution (1161 mg,

3.99 mmol, of tin hydride in 2.00 mL of hexane) over the period of 20 h using syringe

pump under nitrogen atmosphere at 80 °C. After the resulting mixture was stirred for

additional 1 h at 80 °C, acetic anhydride (1 mL, 10.6 mmol) was added before stirring

overnight at room temperature. The volatiles were evaporated out, and the residue was

chromatographed (eluent: ethyl acetate/hexane = 1/1, v/v) to obtain 53 mg (79 %) of

acetanilide as the colorless crystal.

References

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8319.

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Nagano, T. Org. Lett. 2010, 12, 1704-1707.

3 Xi, L.; Zhang, J.-O.; Liu, Z.-C.; Zhang, J.-H.; Yan, J.-F.; Jin, Y.; Lin, J. Org. Bioorg.

Chem. 2013, 11, 4367-4378.

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