Organoselenium compounds based on substituted acetanilides:...

1

Electronic Supplementary Data

Organoselenium compounds based on substituted acetanilides: Synthesis,

characterization and antioxidant activity

Prasad P Phadnisa, Ananda S Hodage

a, K I Priyadarsini

b & Vimal K Jain

a, *

aChemistry Division, Bhabha Atomic Research Centre, Mumbai 400 085, India bRadiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400 085, India

Email: [email protected]

No. Contents Pg No.

1 Synthesis of Se{(CH2)nCOOH}2 (n = 1-2) and (SeCH2CH2COOH)2 2

2 Synthesis and characterization of paracetamol 3

3 Figs S1-S48 – 1H,

13C{

1H} and

77Se{

1H} NMR and mass spectra of compounds 1-12 4

4 Tables S1-S14 – Experimental data for DPPH radical scavenging activity of 28

organoselenium compounds

2

Synthesis of Se{(CH2)nCOOH}2 (n = 1-2) and (SeCH2CH2COOH)2

Synthesis of Se(CH2COOH)223

To a suspension of selenium powder (4.0 g, 0.051 mol) in water (150 ml) was added

carefully a sodium borohydride (NaBH4) (4.23 g, 0.111 mol) at 5-10 oC temperature with

magnetic stirring. Selenium got consumed after vigorous reaction and the colourless solution of

NaHSe was achieved. To which 2-bromoacetic acid (14.77 g, 0.106 mol) was added and stirred

further for 2 h. Later the aqueous work up was followed by extraction with diethyl ether (3×50 ml)

which on evaporation in vacuo gave a white product. The crude product was recrystallized with

diethyl ether-hexane mixture which afforded white crystalline compound (3.25 g, 33%), m.p. 103 ºC.

Anal. Calcd. for C4H6O4Se (MW 197.05): C, 24.4; H = 3.1 %. Found: C, 24.3; H, 2.8%.

IR (nujol, υ cm-1

): 1687 (CO), 458 (Se-C). NMR spectral data: (DMSO-d6) δ: 1H NMR: 3.29 (s,

JSe-H = 6.6 Hz, SeCH2); 13

C NMR: 24.2 (SeCH2, JSe-C = 33.0 Hz), 172.5 (O=C); 77

Se NMR:

215.3 ppm.

Synthesis of Se(CH2CH2COOH)224

To a suspension of selenium powder (2.0 g, 0.025 mol) in water (75 ml) sodium

borohydride (NaBH4) (3.35 g, 0.088 mol) was added carefully at room temperature with

magnetic stirring. Selenium reacted and the colourless solution of Na2Se was achieved. To this

3-brompropionic acid (7.74 g, 0.051 mol) was added and stirred further for 2 h. Later the

aqueous work up was followed by extraction with diethyl ether (3 x 50 ml) which on evaporation

in vacuo gave a white product. The crude product was recrystallized with diethyl ether-hexane

mixture which afforded white crystalline compound (1.65 g, 29 %), m.p. 143 ºC. Anal. Calcd. for

C6H10O4Se (MW 225.1): C, 32.0; H, 4.5 %. Found: C, 32.2; H, 4.2 %. IR (nujol, υ cm-1

): 1708

(CO), 482 (Se-C). NMR spectral data: (DMSO-d6) δ: 1H NMR: 2.62 (t, J = 5.4 Hz, 2 H, SeCH2),

2.67 (t, J = 5.4 Hz, 2 H, SeCH2CH2); 13

C NMR: 18.2 (SeCH2, JSe-C = 31.0 Hz), 35.8

(SeCH2CH2), 173.9 (O=C); 77

Se NMR: 194.5 ppm.

3

(SeCH2CH2COOH)225

To a suspension of selenium powder (3.0 g, 37.9 mmol) in water (100 ml) was added

sodium borohydride (NaBH4) (1.44 g, 39.9 mmol) at 5-10 oC with constant stirring. A brown

solution of Na2Se2 was formed. To this solution, 3-bromopropionic acid (5.79 g, 37.9 mmol)

was added with stirring whereupon a pale yellow precipitate formed. Stirring continued for 2 h.

The aqueous work up was followed by extraction with diethyl ether (3 x 50 ml) which

on evaporation in vacuo gave a pale yellow product. The latter was dissolved in hot water which

after cooling at room temperature afforded pale yellow crystalline compound (4.8 g, 83 %),

mp 140 ºC. Anal. Calcd. for C6H10O4Se2: C, 23.7; H, 3.3 %. Found: C, 23.3; H, 3.2 %.

1H NMR (dmso-d6): δ 2.74 (t, J = 6.9 Hz, 2 H, SeCH2), 3.04 (t, J = 6.9 Hz, 2 H, SeCH2CH2);

13C{

1H} NMR (dmso-d6): δ 24.2 (JSe-C = 75 Hz, SeCH2), 35.7 (SeCH2CH2), 173.4 (O=C);

77Se{

1H} NMR (dmso-d6): δ 316 ppm

Synthesis and characterization of paracetamol26

The mixture of p-hydroxy aniline (2.0 g, 18.35 mmol), acetic anhydride (1.9 ml,

20.18 mmol) and acetic acid (25 ml) was refluxed for 2 hrs. The reaction mixture was diluted

with excess of water, extracted with ethyl acetate (3 x 25 ml) and organic layer was dried to yield

a white crystalline solid (2.2 g, 80 %). 1H NMR (dmso-d6) δ: 1.98 (s, 3H, -CH3), 6.68 (d, J = 8.7,

2H, C6H4), 7.34 (d, J = 8.7, 2H,C6H4), 9.16 (s, 1H, -CONH), 9.67 (s, 1H, -OH).

4

1H,

13C{

1H} and

77Se{

1H} NMR and mass spectra of compounds 1-12

Compound 1:

Fig. S1

Fig. S2

5

Fig. S3

Fig. S4

6

Compound 2:

Fig. S5

Fig. S6

7

Fig. S7

Fig. S8

8

Compound 3:

Fig. S9

Fig. S10

9

Fig. S11

Fig. S12

10

Compound 4:

Fig. S13

Fig. S14

11

Fig. S15

Fig. S16

12

Compound 5:

Fig. S17

Fig. S18

13

Fig. S19

Fig. S20

14

Compound 6:

Fig. S21

Fig. S22

15

Fig. S23

Fig. S24

16

Compound7:

Fig. S25

Fig. S26

17

Fig. S27

Fig. S28

18

Compound 8:

Fig. S29

Fig. S30

19

Fig. S31

Fig. S32

20

Compound9:

Fig. S33

Fig. S34

21

Fig. S35

Fig. S36

22

Compound10:

Fig. S37

Fig. 38

23

Fig. S39

Fig. 40

24

Compound11:

Fig. S41

Fig. 42

25

Fig. S43

Fig. S44

26

Compound12:

Fig. S45

Fig. S46

27

Fig. S47

Fig. S48

28

Experimental data for DPPH radical scavenging activity of organoselenium compounds

Table S1

Compound 1

Ao = 0.360 Ao= 0.365

Conc (µM) As IC1 As IC2 Mean S.D Mean+S.D.

50 0.265 26.38888889 0.263 27.94520548 27.16704718 1.100482015 27.16 + 1.1

20 0.318 11.66666667 0.315 13.69863014 12.6826484 1.436815149 12.68 + 1.4

10 0.33 8.333333333 0.335 8.219178082 8.276255708 0.080719952 8.27 + 0.1

5 0.337 6.388888889 0.339 7.123287671 6.75608828 0.519298359 6.75 + 0.5

2 0.34 5.555555556 0.342 6.301369863 5.928462709 0.527370354 5.92 + 0.5

Table S2

Compound 2

Ao = 0.360 Ao= 0.362


50 0.13 63.88888889 0.133 63.25966851 63.5742787 0.444925998 63.57 + 0.4

20 0.189 47.5 0.175 51.65745856 49.57872928 2.939767143 49.57 + 2.9

10 0.238 33.88888889 0.235 35.08287293 34.48588091 0.844274211 34.48 + 0.8

5 0.285 20.83333333 0.282 22.09944751 21.46639042 0.895277923 21.46 + 0.9

2 0.31 13.88888889 0.298 17.67955801 15.78422345 2.680407842 15.78 + 2.6

Table S3

Compound 3

Ao = 0.360 Ao= 0.365


50 0.11 69.44444444 0.1 72.60273973 71.02359209 2.233252011 71.02 + 2.2

20 0.165 54.16666667 0.159 56.43835616 55.30251142 1.606327049 55.30 + 1.6

10 0.215 40.27777778 0.219 40 40.13888889 0.19641855 40.13 + 0.2

5 0.268 25.55555556 0.272 25.47945205 25.51750381 0.053813301 25.51 + 0.1

2 0.305 15.27777778 0.311 14.79452055 15.03614916 0.341714464 15.03 + 0.3

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Table S4

Compound 4

Ao = 0.360 Ao= 0.362


50 0.156 56.66666667 0.158 56.35359116 56.51012891 0.221377814 56.51 + 0.2

20 0.199 44.72222222 0.201 44.47513812 44.59868017 0.174714843 44.59 + 0.2

10 0.25 30.55555556 0.246 32.0441989 31.29987723 1.0526298 31.29 + 1.1

5 0.28 22.22222222 0.283 21.82320442 22.02271332 0.282148194 22.02 + 0.3

2 0.31 13.88888889 0.312 13.8121547 13.85052179 0.054259268 13.85 + 0.1

Table S5

Compound 5

Ao= 0.350 Ao= 0.365


50 0.315 10 0.325 10.95890411 10.47945205 0.678047598 10.47 + 0.7

20 0.328 6.285714286 0.335 8.219178082 7.252446184 1.367165362 7.15 + 1.3

10 0.335 4.285714286 0.343 6.02739726 5.156555773 1.231555842 5.15 + 1.2

5 0.341 2.571428571 0.348 4.657534247 3.614481409 1.475099469 3.61 + 1.4

2 0.346 1.142857143 0.351 3.835616438 2.489236791 1.904068358 2.48 + 1.9

Table S6

Compound 6

Ao = 0.360 Ao= 0.350


50 0.293 18.61111111 0.286 18.28571429 18.4484127 0.230090302 18.44 + 0.2

20 0.332 7.777777778 0.325 7.142857143 7.46031746 0.448956686 7.46 + 0.4

10 0.346 3.888888889 0.338 3.428571429 3.658730159 0.325493598 3.65 + 0.3

5 0.351 2.5 0.342 2.285714286 2.392857143 0.151522882 2.39 + 0.1

2 0.354 1.666666667 0.346 1.142857143 1.404761905 0.370389266 1.40 + 0.4

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Table S7

Compound 7

Ao= 0.374 Ao= 0.362


50 0.215 42.51336898 0.216 40.33149171 41.42243035 1.542820214 41.42 + 1.5

20 0.269 28.07486631 0.262 27.62430939 27.84958785 0.318591852 27.84 + 0.3

10 0.293 21.65775401 0.28 22.6519337 22.15484386 0.702991201 22.15 + 0.7

5 0.312 16.57754011 0.301 16.85082873 16.71418442 0.193244238 16.71 + 0.2

2 0.339 9.35828877 0.312 13.8121547 11.58522173 3.149358799 11.58 + 3.1

Table S8

Compound 8

Ao= 0.364

Ao= 0.365


50 0.165 54.67032967 0.166 54.52054795 54.59543881 0.105911674 54.59 + 0.1

20 0.205 43.68131868 0.203 44.38356164 44.03244016 0.496560761 44.03 + 0.5

10 0.246 32.41758242 0.24 34.24657534 33.33207888 1.2932933 33.33 + 1.3

5 0.28 23.07692308 0.273 25.20547945 24.14120126 1.505116647 24.14 + 1.5

2 0.302 17.03296703 0.305 16.43835616 16.7356616 0.420453377 16.73 + 0.4

Table S9

Compound 9

Ao= 0.362 Ao= 0.358


50 0.161 55.52486188 0.156 56.42458101 55.97472144 0.636197496 55.97 + 0.6

20 0.21 41.98895028 0.205 42.73743017 42.36319022 0.529255207 42.36 + 0.5

10 0.265 26.79558011 0.255 28.77094972 27.78326492 1.396797247 27.78 + 1.4

5 0.309 14.64088398 0.3 16.20111732 15.42100065 1.103251575 15.42 + 1.1

2 0.331 8.563535912 0.325 9.217877095 8.890706503 0.462689088 8.89 + 0.5

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Table S10

Compound 10

Ao = 0.355 Ao= 0.358


50 0.16 54.92957746 0.151 57.82122905 56.37540326 2.044706445 56.37 + 2.0

20 0.216 39.15492958 0.221 38.26815642 38.711543 0.62704331 38.71 + 0.6

10 0.256 27.88732394 0.252 29.60893855 28.74813125 1.217365361 28.74 + 1.2

5 0.286 19.43661972 0.29 18.99441341 19.21551656 0.312687081 19.21 + 0.3

2 0.31 12.67605634 0.315 12.01117318 12.34361476 0.470143387 12.34 + 0.5

Table S11

Compound 11

Ao = 0.348 Ao= 0.358


50 0.2 42.52873563 0.211 41.06145251 41.79509407 1.037525843 41.79 + 1.0

20 0.257 26.14942529 0.255 28.77094972 27.4601875 1.853697704 27.46 + 1.8

10 0.289 16.95402299 0.294 17.87709497 17.41555898 0.652710459 17.41 + 0.6

5 0.317 8.908045977 0.325 9.217877095 9.062961536 0.219083685 9.06 + 0.2

2 0.333 4.310344828 0.34 5.027932961 4.669138894 0.507411435 4.66 + 0.5

Table S12

Compound 12

Ao= 0.358 Ao= 0.365


50 0.228 36.31284916 0.23 36.98630137 36.64957527 0.476202623 36.64 + 0.5

20 0.277 22.62569832 0.28 23.28767123 22.95668478 0.468085533 22.95 + 0.5

10 0.315 12.01117318 0.318 12.87671233 12.44394276 0.612028598 12.44 + 0.6

5 0.325 9.217877095 0.33 9.589041096 9.403459095 0.262452582 9.40 + 0.3

2 0.345 3.631284916 0.343 6.02739726 4.829341088 1.694307287 4.82 + 1.6

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Table S13

BHT

Ao = 0.355 Ao= 0.350


50 0.198 44.22535211 0.201 42.57142857 43.39839034 1.169500552 43.39 + 1.1

20 0.26 26.76056338 0.26 25.71428571 26.23742455 0.739830033 26.23 + 0.7

10 0.288 18.87323944 0.291 16.85714286 17.86519115 1.425595563 17.86 + 1.4

5 0.309 12.95774648 0.31 11.42857143 12.19315895 1.081290048 12.19 + 1.1

2 0.323 9.014084507 0.325 7.142857143 8.078470825 1.323157558 8.07 + 1.3

Table S14

Paracetamol

Ao = 0.348 Ao= 0.365


50 0.2 42.52873563 0.219 40 41.26436782 1.788086113 41.26 + 1.8

20 0.26 25.28735632 0.275 24.65753425 24.97244528 0.44535146 24.97 + 0.4

10 0.291 16.37931034 0.31 15.06849315 15.72390175 0.926887727 15.72 + 0.9

5 0.31 10.91954023 0.322 11.78082192 11.35018107 0.609018122 11.35 + 0.6

2 0.325 6.609195402 0.335 8.219178082 7.414186742 1.138429671 7.41 + 1.1

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