Selective Ethenolysis and Oestrogenicity of Compounds from Cashew Nut Shell Liquid

Jennifer Julis,a Stuart A. Bartlett a, Sabrina Baader,b Nicola Beresford, c Edwin J. Routledge,c Catherine S. J. Cazina and David J. Cole-Hamiltona*

Supplementary Information

1. Products from metathesis of cardanol

OH

OH

OH

OH

OH

+

OH

+

OH

+OH

+

+OH

+ OH

2a

2b

2c

4

4

42d

5

5

6

7

BMolecular Weight: 246.39

Figure S1. Routes to observed products from ethenolysis of cardanol (2).

Electronic Supplementary Material (ESI) for Green Chemistry.This journal is © The Royal Society of Chemistry 2014

2. NMR SpectraAnacardic acid (1)1H NMR

13C NMR

Cardanol (2)1H NMR

13C NMR

Monounsaturated Cardanol (2b)1H NMR

13C NMR

Cardanol methylether (8)1H NMR

Monounsatured cardanol methylether (8b)

1H NMR

3-Hydroxyphenyl oleate (11)1H NMR

3-Hydroxyphenyl linoleate (13)

1H NMR

3-Non-8-enylphenol (4)1H NMR

13C NMR

3-Nonylphenol from hydrogenation of 3-non-8-enylphenol catalysed by Pd/C1H NMR

3-nonylphenol from hydrogenation of 3-non-8-enylphenol catalysed by [RhCl(PPh3)3]1H NMR

13C NMR

Dimethylprotected anacardic acid (14)1H NMR

BAA1850-DEST-H.ESP

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)

1.812.52.63.22.12.13.02.90.83.20.42.01.5

CHLOROFORM-d

M07(s)

M06(s)

M10(m)

M05(m)

M03(s)

M04(m)M09(m)

M01(m)

M02(m)

M08(d)

0.06

0.870.870.89

1.231.241.251.251.26

1.281.281.29

1.291.311.321.32

1.552.002.012.022.03

2.502.522.522.54

3.76

3.80

3.89

5.335.346.73

6.756.796.81

7.23

7.24

7.25

1H NMR (400 MHz, CHLOROFORM-d) ppm 7.20 - 7.30 (m, 1 H) 6.68 - 6.85 (m, 2 H) 5.34 (d, J=5.5 Hz, 3 H) 3.89 (s, 3 H) 3.80 (s, 3 H) 2.46 - 2.58 (m, 2 H) 1.93 - 2.08 (m, 3 H) 1.55 (s, 2 H) 1.20 - 1.43 (m, 11 H) 0.78 - 0.94 (m, 2 H)

12

34

5

6

1213

1415

1617

1819 20

2122 23

2425

CH226

O7

9

O10

O27

CH38

CH311

13C NMR

BAA1850-dest-c.esp

200 180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)

M35(s) M32(s)

M29(s)

M27(s)

M24(s)

M23(s)

M21(s)

M20(s)

M19(s) M04(s)

M03(s)

M02(s)

M37(s) M36(s)

M34(s)

M33(s)

M31(s)

M30(s)

M28(s)

M26(s)

M25(s)

M22(s)

M18(s)

M17(s)

M16(s)

M14(s)

M13(s)

M11(s)

M10(s)

M07(s)

M06(s)

M05(s)

M01(s)

13.83

14.1322.6822.82

25.5827.24

29.0129.2229.3329.4829.63

29.6729.76

31.1531.5431.80

33.4952.16

55.87

76.72

77.03

77.35

108.36

121.49126.83

129.31129.84129.96130.25130.40

136.84141.35156.25168.98

13C NMR (101 MHz, CHLOROFORM-d) ppm 169.0 (s) 156.2 (s) 141.3 (s) 136.8 (s) 130.4 (s) 130.3 (s) 130.0 (s) 129.8 (s) 129.3 (s) 126.8 (s) 121.5 (s) 114.7 (s) 108.4 (s) 77.4 (s) 77.0 (s) 76.7 (s) 55.9 (s) 52.2 (s) 33.5 (s) 31.8 (s) 31.5 (s) 31.1 (s) 29.8 (s) 29.7 (s) 29.6 (s) 29.5 (s) 29.3 (s) 29.3 (s) 29.2 (s) 29.0 (s) 27.2 (s) 27.2 (s) 25.6 (s) 22.8 (s) 22.7 (s) 14.1 (s) 13.8 (s)

1

2

3

4

5

6

12

13

14

15

16

17

18

19 20

21

22 23

24

25 CH226

O7

9

O10

O27

CH38

CH311

3. GC analyses

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JJ15-2.D\FID1A

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JJ13-2.D\FID1A

OH

and isomers

cardanolsaturated

B5

N N

RuCl

Cl

PCy3

PCy3

RuCl

Cl

PCy3

Figure S2. Comparison of the GC FID of the crude products from the ethenolysis of cardanol (2).catalysed by M2 and M1.

M2

M1

OH B

OH 5

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TIC: SAB018#.D

Figure S3. GC-MS of monounsaturated cardanol (2b) showing a variety of positional isomers for the double bond. The peak from saturated cardanol (3-pentadecylphenol/ 2a) has a retention time of 36.5 min and is obscured by the main peak.

34.60 34.80 35.00 35.20 35.40 35.60 35.80 36.00 36.20

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TIC: SAB20-4#-ME-MONO.D

35.80 36.00 36.20 36.40 36.60 36.80 37.00 37.20 37.40 37.60 37.80 38.00

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TIC: SAB018#.D

Figure S4. GC-MS of monounsaturated cardanol methylether (8b) showing a variety of positional isomers for the double bond. The peak with a retention time of 35.3 min is from saturated cardanol methyl ether (methyl(3-pentadecylphenyl)ether, 8a).

Figure S5. GC-MS of the crude product obtained from ethenolysis of monounsaturated cardanol (8); using Caz-1 and cyclohexadiene (Table 4, Entry 2). Numbers indicate alkene chain length, UP indicates 3-substiuted phenols with monounsaturated chains of the given length.

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Response_

JJ-103-1.D\FID1A

View Mode: Integration

Figure S6. GC of the crude product obtained from ethenolysis of methyl oleate in the (MS RT 30.6 min, methyl oleate, 18.3 min, methyl 9-decenoate 11.3 min, 1-decene, Table 6, Entry 1).

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JJ-111-3.D\FID1A

Figure S7. GC of the crude product obtained from ethenolysis of methyl oleate (10) in the presence of 1,4-cyclohexadiene (Table 6, Entry 2.)

39.00 39.20 39.40 39.60 39.80 40.00 40.20 40.40 40.60 40.80

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TIC: JJ110-1#.D

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Scan 6694 (39.775 min): JJ110-1#.D110

55

26581

135 247165183 37420730 356 446

Figure S8. GC-MS of 3-hydroxyphenyl oleate (11) (MS RT = 39.8 – 3-hydroxyphenyl oleate [MW 374]).

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TIC: JJ118-2#.D

Figure S9. GC-MS of the crude product from the ethenolysis of 3-hydroxyphenyl oleate (11) (RT 40 min, 3-hydroxyphenyl oleate, 31 min, 4-hydroxyphenyl dec-9-enoate - 17.5 min, 1,3-dihydroxybenzene Table 6, Entry 3). The peak at 28.5 min is from an impurity in the starting material.

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JJ-120-1.D\FID1A

Figure S10. GC-MS of the crude product from the ethenolysis of 3-hydroxyphenyl oleate (11) in the presence of 1,4-cyclohexadiene (RT 41 min, 3-hydroxyphenyl oleate, 32.3 min, 4-hydroxyphenyl dec-9-enoate, 18 min, 1,3-dihydroxybenzene, 11.3 min decene, Table 6, Entry 4).

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JJ-124-3.D\FID1A

Figure S11. GC of the crude sample obtained from ethenolysis of methyl linolenate (12) in the presence of 1,4-cyclohexadiene (RT 30.7min, methyl linolenate, Table 6, Entry 6).

39.20 39.40 39.60 39.80 40.00 40.20 40.40 40.60

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TIC: JJ110-2#.D

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Scan 6702 (39.822 min): JJ110-2#.D110

79

55

135 370

191173 314261 341232154 21336 281 446

Figure S12. GC-MS of 3-hydroxyphenyl linoleate (13) (MS RT [MW 370]).

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TIC: JJ118-3#.D

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Scan 5208 (30.965 min): JJ118-3#.D110

55

6941

1358315397 26212330 165179 276220198 234

Figure S13. GC-MS of the crude sample obtained from the ethenolysis of 3-hydroxyphenyl linolenate (13) (RT:40.5 min, 3-hydroxyphenyl linoleate; 30.9 min, 3-hydroxyphenyl dec-9-enoate-1- [MW 262]; 7.5 min, 1,3-dihydroxybenzene; 10.2 min, 1-decene;* 10 min, 1,4-octadiene; Table 6, Entry 7). The peak at 38.5 min is from an impurity in the starting material.*1, 4, 7-dodecatriene would be expected but, on the basis of the cardanol reactions, it is anticipated that this will cyclise to 1,4-cyclohexadiene and 1-butene. The 1-decene probably arise from a small amount of oleate present in the starting material. GC-MS analysis shows that the methyl linolenate is significantly contaminated with methyl linoleate and contains traces of methyl oleate.

.

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JJ-120-2.D\FID1A

Figure S 14. GC-MS of the crude sample obtained from the ethenolysis of 3-hydroxyphenyl linolenate (13) acid in the presence of 1,4-cyclohexadiene (Table 6, Entry 8). The peak at 38.5 min is from an impurity in the starting material.

Figure S15. GC of dimethylprotected anacardic acid (14).

Figure S16 GC of the crude product from ethenolysis of 14 catalysed by HG1 at 25 oC (Table 7, Entry 1)

n-dodecane

15

14