Sterically hindered malonamide monomers for the

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

Sterically hindered malonamide monomers for the step growth synthesis of polyesters and polyamides Simon N. G. Tylera and Ruth L Websterb* CatSci Ltd. Capital Business Park, Wentloog, Cardiff, UK, CF3 2PX Department of Chemistry, University of Bath, Claverton Down, Bath, UK, BA2 7AY [email protected]

General experimental procedures

2–3

Optimisation of pre-polymerisation process

3

Analysis data

3–8

1c 1H & 13C{1H} NMR spectra

9

Polymer spectra

NMR, GPC, MALDI-TOF, DSC

10 – 86

Cu(OTf)2 mediated polymerisation (MALDI-TOF data)

87 – 89

Reaction monitoring: PDI vs. time (1c + ethylene glycol)

90

Table S2 (extended table of results for Lewis acid assisted polymerisations)

90

GPC traces (Table S2)

91 – 108

References

108

General experimental conditions All chemicals were purchased from Sigma Aldrich or Alfa Aesar and used directly without further purification unless stated otherwise. Dry dichloromethane was used, taken from an xx SPS system. Measurements and instrumentation NMR spectroscopy was performed on Bruker 250/ 300/ 400/ 500 MHz instruments and referenced to residual solvent. Molecular weights and polydispersity were estimated by (GPC) using a Polymer Laboratories GPC 20 liquid chromatograph. A flow rate of 1.0 ml min-1 was used and samples were dissolved in THF (~ 4 mgml-1). The measurements were carried out at 35 °C with polystyrene standards. MALDI-TOF was run on a Voyager DE-STR with Linear and Reflectron analysers, 20,000 mass resolution and Nd:YAG laser (λ = 355nm) by Elforlight. Samples were dissolved in THF or HFIP and analysed by MALDI using dithranol matrix with NaOAc additive, in both positive-linear and reflectron modes to show as much of the polymer distribution as possible along with higher resolution allowing better mass accuracy and isotope pattern matching. A differential scanning calorimeter (DSC), TA instruments AQ20, calibrated with indium was employed to measure the glass transition temperature (Tg) of the polymers. Calorimetry was performed in a nitrogen atmosphere with approximately 2 to 5 mg of polymer. Samples were heated to 200 °C to remove the thermal history. Then the samples were cooled to -70 °C at a rate of 10 °C min-1 and subsequently were heated to 200 or 300 °C with the same rate as cooling. The glass transition temperature was traced from the second endothermic sequence. Synthesis of 1c. Malonic acid (312 mg, 3.0 mmol) was added to an RB flask with CH2Cl2 (60 ml). Mukaiyama’s reagent was added (1.7 g, 6.6 mmol, 2.2 eq) and the flask cooled to 0 °C. NEt3 (1 ml, 6.3 mmol, 2.1 eq) was added dropwise in 5 ml CH2Cl2 followed by HNiPrtBu (1 ml, 6.3 mmol, 2.1 eq) in 5 ml CH2Cl2. The flask was stirred at 0 °C for 1 hr, allowed to warm to room temperature then stirred for a further 2 h: stirring for extended periods of time leads to decomposition (homopolymerisation) of 1c. The solvent was removed in vacuo, the residue loaded onto silica and then purified by column chromatography (40% EtOAc/ pentane). The product was isolated as a colourless oil (380 mg, 42%) which is stored in a fridge. Storage at room temperature leads to decomposition within two weeks. Polymerisation procedure. 1c (200 mg, 0.67 mmol) was added to a reaction vessel equipped with stirrer bar and short path distillation apparatus (Figure S1). Dinucleophile was added (0.67 mmol, 1 eq) and the vessel placed in an oil bath at 110 °C. After the appropriate reaction time the reaction vessel was cooled, MeOH was added and the polymer was dried in vacuo. Polyamides formed insoluble solids, after the stated reaction time the solid was washed with MeOH and then dried in vacuo. Polyesters were analysed as the crude reaction mixture (precipitation of polymer was not possible), 1c was not detected by 1H NMR spectroscopy therefore quantitative yield of polymer is assumed. Instead of distillation of the amine (N-tert-butylisopropylamine), the reaction proceeds with identical results using a small vial, equipped with stirrer bar, open to air. The amine evaporates over the course of the reaction.

2

Reaction monitoring. Following the general polymerisation procedure, reactions were undertaken on a 200 mg scale (1c). Samples were removed at known time intervals, quenched by washing with MeOH/CH2Cl2, concentrated and then dissolved in THF prior to GPC analysis. Samples containing copper were filtered (x 2) prior to analysis. Figure S1. Short path distillation apparatus for amine isolation.

Table S1. Optimisation of aliphatic polyester synthesis Entry Diamide Conditionsa Mn (gmol-1)b PDIb c 1 1a 130 °C, 72 h n.r. n.r. d 2 1b 110 °C, 18 h 1000 1.12 3 1c 110 °C, 1 h 1900 1.37 4 1c 110 °C, 18 h 2100 1.52 e 5 1c 110 °C, 18 h, Decalin 1000 1.30 6e 1c 110 °C, 18 h, DMF 900 1.11 7 1c 80 °C, 64 h 2000 1.41 8 1c 50 °C, 64 h 800 1.40 a 1 (0.67 mmol), ethylene glycol (0.67 mmol). bDetermined by GPC, 35 °C, relative to polystyrene standards. cn.r. = no reaction (1H NMR). dTrimodal GPC trace. e3.35 mM.

1c

Colourless oil, 380 mg (42%). Rf 0.44 (40% EtOAc/pentane). 1H NMR (400 MHz; 298 K; CDCl3) δ 4.01 (br. s, 2H, CH(CH3)2), 3.52 (s, 2H, CH2), 1.48 (s, 18H, C(CH3)3), 1.41 (d, 12H, J 7.1 Hz, CH(CH3)2); 13C NMR (63 MHz; 298 K; CDCl3) δ 169.5 (C=O), 60.1 (C(CH3)3), 58.5 (CH(CH3)2), 49.0 (C(O)CH2C(O)), 29.6 (C(CH3)3), 23.3 (CH(CH3)2); IR (solid) ν 2967, 2928, 1629 cm-1; HRMS (LCMS) obs. for C17H34N2O2Na 321.2558, cald. 321.2518.

3

Pre-polymers Table 1, Entry 1

Colourless oil. 1H NMR (300 MHz; 298 K; CDCl3) δ 4.38 (s, poly-CH2CH2), 4.29 (br. s, end groupCH2CH2OH), 3.83 (t, J 4.7 Hz, end group-CH2CH2OH), 3.45 (s, C(O)CH2C(O)); 13C NMR (125 MHz; 298 K; CDCl3) δ 166.3 (C=O), 67.1 (end group-CH2CH2OH), 62.9 (poly-CH2CH2), 60.7 (end group-CH2CH2OH), 41.0 (C(O)CH2C(O)); IR (solid) ν 2960, 1725 cm-1.

Table 1, Entry 2

Colourless oil/gum. 1H NMR (300 MHz; 298 K; CDCl3) δ 4.30 (t, J 6.2 Hz, end group-CH2CH2CH2OH), 4.22 (t, J 6.2 Hz, poly-CH2CH2CH2), 3.71 (m, end group-CH2CH2CH2OH), 3.39 (s, C(O)CH2C(O)), 2.051.97 (m, poly-CH2CH2CH2 ), 1.93-1.82 (m, end group-CH2CH2CH2OH); 13C NMR (75 MHz; 298 K; CDCl3) δ 166.3 (C=O), 67.9 (end group-CH2CH2CH2OH), 61.8 (poly-CH2CH2CH2), 58.9 (end groupCH2CH2CH2OH), 41.2 (C(O)CH2C(O)), 27.6 (poly-CH2CH2CH2), 25.5 (end group-CH2CH2CH2OH); IR (solid) ν 2956, 1722 cm-1.

Table 1, Entry 3

Colourless oil/gum. 1H NMR (400 MHz; 298 K; CDCl3) δ 4.14 (s, poly-CH2CH2CH2CH2), 3.61 (m, end group-CH2CH2CH2CH2OH), 3.34 (s, C(O)CH2C(O)), 1.70 (s, poly-CH2CH2CH2CH2), 1.57 (m, end groupCH2CH2CH2CH2OH); 13C NMR (75 MHz; 298 K; CDCl3) δ 166.4 (C=O), 65.3 (end groupCH2CH2CH2CH2OH), 64.8 (poly-CH2CH2CH2CH2), 62.0 (end group-CH2CH2CH2CH2OH), 41.3 (C(O)CH2C(O)), 28.8 (end group-CH2CH2CH2CH2OH), 24.91 (poly-CH2CH2CH2CH2), 24.87 (end groupCH2CH2CH2CH2OH);ii IR (solid) ν 2960, 1724 cm-1.

Table 1, Entry 4

4

Colourless gum. 1H NMR (300 MHz; 298 K; CDCl3) δ 4.10 (t, J 6.6 Hz, poly & end group-OCH2)), 3.59 (t, J 6.6 Hz, end group-CH2OH), 3.34 (s, C(O)CH2C(O)), 1.63-1.49 (m, poly & end groupOCH2(CH2)2(CH2)2(CH2)2CH2OH), 1.29 (br. s, poly & end group-O(CH2)3(CH2)2(CH2)3OH); 13C NMR (75 MHz; 298 K; CDCl3) δ 166.7 (C=O), 65.6 (poly-OCH2), 58.7 (end group-OCH2), 47.8 (end group-CH2OH), 41.6 (C(O)CH2C(O)), 29.2 (end group-CH2CH2CH2CH2OH), 29.1 (end group-OCH2CH2CH2CH2), 29.0 (poly-O(CH2)3(CH2)2(CH2)3O), 28.6 (end group-OCH2CH2CH2CH2CH2CH2CH2CH2OH), 28.4 (polyOCH2CH2(CH2)4CH2CH2O), 26.2 (poly-O(CH2)2CH2(CH2)2CH2(CH2)2O); IR (solid) ν 2933, 1733 cm-1

Table 1, Entry 5

Colourless gum. 1H NMR (300 MHz; 298 K; CDCl3) δ 5.13 (br. s, poly-trans-H), 4.80 (br. s, poly-cis-H), 3.34 (m, C(O)CH2C(O)), 2.29-1.27 (br. m, poly- & end group-CH2); 13C NMR (125 MHz; 298 K; CDCl3) δ 165.8 (C=O), 71.6 (poly-cis-CH), 71.1 (poly-trans-CH), 47.8 (C(O)CH2C(O)), 35.2 (end groupCH(O)CH2CH(O)), 30.3 (poly-CH(O)CH2CH(O)), 26.4 (poly-CH2CH2CH2), 21.9 (poly-CH2CH2CH2);ii IR (solid) ν 2947, 1728 cm-1

Table 1, Entry 6

Colourless gum. 1H NMR (500 MHz; 298 K; CDCl3) δ 5.06 (br. s, poly-H2), 4.93 (m, end group-H2) 4.32-4.12 (m, poly-H1), 4.03 (m, end group-H1), 3.41 (m, C(O)CH2C(O)), 1.64 (app. quintet, J 7.6 Hz, poly-H3), 1.50 (m, end group-H3), 0.97 (t, J 7.6 Hz, end group-H4), 0.94 (t, J 7.6 Hz, poly-H4); 13C NMR (125 MHz; 298 K; CDCl3) δ 166.1 (C(O)OC2), 166.0 (C1OC(O)CH2C(O)OC1 or C1OC(O)CH2C(O)OC2), 165.9 (C1C(O)CH2C(O)C1 or C1C(O)CH2C(O)C2), 73.7 (poly-C2), 70.7 (end groupOCH2CH(CH2CH3)OH), 69.2 (end group-OCH(Et)CH2OH), 65.27 (end group-OCH2CH(CH2CH3)OH), 65.21 (poly-C1), 63.7 (end group-OCH(Et)CH2OH), 41.4 & 41.2 & 40.9 (C1C(O)CH2C(O)C1 and C1C(O)CH2C(O)C2 and C2C(O)CH2C(O)C2), 26.0 (end group-C3), 23.6 (poly-C3), 9.7 (end group-C4), 9.3 (poly-C4). Major environment believed to be 2°-OH end group i.e. end group-OCH2CH(Et)OH due to higher levels of 1° alcohol reactivity.i IR (solid) ν 2977, 2882, 1733 cm-1

Table 1, Entry 7

5

Colourless gum. 1H NMR (500 MHz; 298 K; CDCl3) δ 5.15 (m, end group-OCH(CH3)CH2CH2OH), 5.05 (m, poly-H3), 4.97 (m, end group-OCH2CH2CH(CH3)OH), 4.37 (m, end group-OCH2CH2CH(CH3)OH), 4.19 (m, poly-H1), 4.10 (t, 6.0 Hz, end group-CHOH), 3.90 (m, end group-OCH(CH3)CH2CH2OH), 3.65 (t, J 5.7 Hz, end group-CH2OH), 3.34 (m, C(O)CH2C(O), multiple environments: 3.37 C1OC(O)CH2C(O)OC1, 3.35 C1OC(O)CH2C(O)OC3, 3.33 C3OC(O)CH2C(O)OC3), 1.90 (m, poly-H2), 1.76 (m, end group-H2), 1.27 (d, J 6.3 Hz, poly-H4), 1.19 (d, J 6.3 Hz, end group-H4); 13C NMR (125 MHz; 298 K; CDCl3) δ 166.4 & 166.3 (C1OC(O)CH2C(O)OC1 and C1OC(O)CH2C(O)OC3), 165.94 & 165.86 (C3OC(O)CH2C(O)OC3 and C1OC(O)CH2C(O)OC3), 69.2 (poly-C3), 67.7 (end groupOCH(Me)CH2CH2OH), 64.7 (end group-OCH2CH2CH(Me)OH), 61.7 (poly-C1), 60.6 (end groupOCH2CH2CH(Me)OH), 58.7 (end group-OCH(Me)CH2CH2OH), 41.9 & 41.6 & 41.3 (C1C(O)CH2C(O)C1 and C1C(O)CH2C(O)C3 and C3C(O)CH2C(O)C3), 38.7 (end group-OCH(Me)CH2CH2OH), 37.7 (end group-OCH2CH2CH(Me)OH), 34.4 (poly-C2), 20.2 (end group-OCH2CH2CH(CH3)OH), 20.0 (end groupOCH(CH3)CH2CH2OH), 19.8 (poly-C4). Major environment believed to be 2°-OH end group i.e. end group-OCH2CH2CH(Me)OH due to higher levels of 1° alcohol reactivity.i IR (solid) ν 2982, 1733 cm-1.

Table 1, Entry 8

Colourless gum. 1H NMR (300 MHz; 298 K; CDCl3) δ 5.05 (d, J 5.7 Hz, poly-CH(CH3)), 3.37 (s, C(O)CH2C(O)), 1.25 (d, J 6.2 Hz, poly-CH3), 1.16 (d, J 6.6 Hz, end group-CH3); 13C NMR (125 MHz; 298 K; CDCl3) δ 165.7 (C=O), 72.4 (poly-CH(CH3)), 58.8 (end group-CH(CH3)), 41.6 (C(O)CH2C(O)), 15.0 (poly-CH3), 10.3 (end group-CH3).ii IR (solid) ν 3110, 2984, 1733 cm-1.

Table 1, Entry 9

Colourless gum. 1H NMR (300 MHz; 298 K; CDCl3) δ 7.26-7.15 (m, poly- & end group-ArH), 5.08-5.05 (m, ArCH2), 4.60-4.54 (m, end group-ArCH2OH ), 3.36 (s, C(O)CH2C(O)); 13C NMR (75 MHz; 298 K; CDCl3) δ 166.3 (C=O), 141.6 (end group-C1CH2OH), 135.7 (poly-C1), 135.4 (end group-OCH2C1), 128.9 (poly-C4), 128.8 (end group-C4), 128.2 (poly-C3), 127.9 (end group-C3), 127.3 (poly-C2), 127.0 (end group-C2), 67.2 (end group-CH2ArCH2OH), 66.9 (poly-ArCH2), 58.7 (end group-CH2ArCH2OH), 41.4 (C(O)CH2C(O)); IR (solid) ν 3104, 2981, 1732 cm-1.

Table 1, Entry 10

6

Off-white solid. 1H NMR (500 MHz; 298 K; D2O/(CF3)2CHOH, ~3:1) δ 3.53 (m, end group-CH2CH2NH2), 3.35 (s, C(O)CH2C(O)), 3.14 (m, end group-NH2), 1.33 (s, end group-C(CH3)3), 1.32 (d, J 7.6 Hz, CH(CH3)2). Poly-CH2CH2, end group-CH2CH2 and end group-CH(CH3)2 not obs. (obscured by HFIP); 13C NMR (125 MHz; 298 K; D2O/(CF3)2CHOH, ~3:1) δ 168.2 (C=O), 38.56 (C(O)CH2C(O)), 38.52 (end groupCH2CH2NH2), 37.8 (end group-CH2CH2OH), 37.1 (poly-CH2CH2). End group-CH(CH3)2 and end groupC(CH3)3 not obs. (weak and/or obscured by HFIP); IR (solid) ν 2929, 1628 cm-1 Table 1, Entry 11

Off-white solid. 1H NMR (500 MHz; 298 K; D2O/(CF3)2CHOH, ~4:1) δ 3.16 (s, poly-CH2CH2CH2CH2), 3.09 (s, C(O)CH2C(O)), 2.95 (m, end group-CH2CH2CH2CH2NH2), 1.65 (m, end group-CH2CH2NH2), 1.55 (m, end group-CH2CH2CH2CH2NH2), 1.47 (br. s, poly-CH2CH2CH2CH2), 1.35 (s, end group-NC(CH3)3), 1.28 (d, J 7.1 Hz, NCH(CH3)2). End group-CH2CH2CH2CH2NH2 obscured by signals at ~ 3 ppm, end groupNCH(CH3)2 not obs. 13C NMR (125 MHz; 298 K; D2O/(CF3)2CHOH, ~4:1) δ 168.6 (C=O), 54.7 (polyCH2CH2CH2CH2), 39.0 (end group-CH2CH2CH2CH2NH2), 38.9 (C(O)CH2C(O)), 38.3 (end groupCH2CH2CH2CH2NH2), 25.4 (end group-NC(CH3)3), 25.3 (poly-CH2CH2CH2CH2), 25.1 (end groupCH2CH2CH2CH2NH2), 23.9 (end group-CH2CH2CH2CH2NH2), 21.0 (end group-NCH(CH3)2). Other end groups not obs.ii IR (solid) ν 2927, 2858, 1627 cm-1

Table 1, Entry 12

White solid. 1H NMR (500 MHz; 298 K; DMSO-d6) δ 3.64 (br. s, poly-NCH2CH2N), 3.57 (m, NH), 3.49 (m, end group-NCH2CH2NH) 3.43 (br. s, C(O)CH2C(O)), 2.63 (dt, J 21.0, 4.7 Hz, end groupNCH2CH2NH), 1.07 (s, NC(CH3)3), 1.02 (d, J 6.3 Hz, NCH(CH3)2); 13C NMR (125 MHz; 298 K; DMSO-d6) δ 165.9 (C=O), 45.6 (poly-NCH2CH2N), 45.2 (end group-NCH2CH2NH), 41.3 (end group-NCH2CH2NH), 41.0 (C(O)CH2C(O)). End group-CH(CH3)2 and end group-C(CH3)3 not obs.ii IR (solid) ν 2928, 1611 cm-1

Table 1, Entry 13

7

Off-white solid. 1H NMR (500 MHz; 298 K; DMSO-d6) δ 8.47 (br. s, end group-Ar), 7.21 (m, poly-Ar), 4.25 (d, J 5.7 Hz, poly-ArCH2NH), 3.71 (br. s, end group-CH2NH2), 3.14 (s, C(O)CH2C(O)) , 1.07 (s, end group-C(CH3)3), 1.02 (d, J 6.0 Hz, end group-CH(CH3)2); 13C NMR (125 MHz; 298 K; DMSO-d6) δ 166.8 (C=O), 137.7 (C1), 127.22 (C2 & C3), 43.4 (C(O)CH2C(O)), 42.0 (ArCH2);ii IR (solid) ν 3295, 2910, 1623 cm-1.

Table 1, Entry 14

White solid. 1H NMR (300 MHz; 298 K; DMSO-d6) δ 7.83 (br. s, NH), 3.94-2.88 (m, end group & polyCH & CH(CH3)2 & C(O)CH2C(O)), 1.78-1.22 (m, end group & poly-CH2), 1.02 (s, end group-C(CH3)3), 1.02 (d, J 6.4 Hz, end group-CH(CH3)2); 13C NMR (75 MHz; 298 K; DMSO-d6) δ 166.8 (C=O), 54.9 (end group-CHNH2), 51.9 (end group-C(CH3)3), 50.8 (end group-CHNHC(O)), 48.6 (poly-CHNH), 47.9 (end group-CH(CH3)2), 42.7 (C(O)CH2C(O)), 29.6 (poly-CH2CHNH), 28.1 (end group-C(CH3)3), 26.2 (polyCH2CH2CHNH), 24.3 (end group-CH(CH3)2);ii IR (solid) ν 3273, 2930, 2857, 1636 cm-1.

8

2.00

1.48 1.42 1.40

1.91

O NiPrtBu

6.0

5.5

5.0

4.5 4.0 3.5 Chemical Shift (ppm)

180

2.5

60.13 58.54

3.0

160

140

120

100 80 Chemical Shift (ppm)

60

2.0

1.5

1.0

40

0.5

0

23.25

6.5

169.45

7.0

17.99 12.79

29.63

BuiPrN

48.98

t

7.5

3.52

O

4.01

Compound 1c

20

0

9

O O

O n

6.5

6.0

5.5

5.0


180

160

140

120


3.0

2.5

2.0

1.5

60

40

1.0

0.5

0

28.59

7.0

40.99

7.5

0.18 2.00

67.05 63.69 62.85 60.65

4.13

166.33

O

4.38 4.30 4.29 4.29 4.28 3.84 3.83 3.81 3.45

Table 1, Entry 1

20

0

10

GPC trace

11

MALDI-TOF

Zoom region

B

B

B C

D

A

C

A E

D

A

C

D

n=8

B

B B

A

C D A

C D

A

B C D

B

B

B

B

n = 11

12

Peak A (simulated): where n = 8 (C41H52NaO33)

Experimental data

13

Peak C (simulated): where n = 8 (C45H62NNaO33)

Experimental data

Peak C (simulated): where n = 8 (C45H63NNaO33)

Experimental data

14

Peak D (simulated): where n = 8 (C43H52NNaO36)

Experimental data

DSC thermogram

15

Table 2, Entry 1: Vacuum condensation

16

2.05 2.03 2.01 1.99 1.97 1.91 1.89 1.87

O

3.39

O

3.74 3.72 3.70 3.68

O

4.32 4.30 4.28 4.25 4.22 4.20

Table 1, Entry 2

2.00

2.14 0.36

O n

5.5

5.0

4.5 4.0 Chemical Shift (ppm)

3.5

3.0

168

67.85 160

152

144

136

128

120

112

104 96 88 Chemical Shift (ppm)

80

72

2.5

2.0

64

1.5

56

48

40

1.0

27.57 25.50

6.0

41.20

6.5

166.25

7.0

0.38

61.82 58.88

4.13

32

24

16

17

GPC trace

18

MALDI-TOF

19

Zoom region

A A

B

A B B

C

D

E

E C

C

D

D

E

n = 12

A A

B

A B

A B B

C

D

E

E C

D

E C

E

D C

D

n = 15

20

Peak D (simulated): where n = 15 (C96H128NaO65)

Experimental data

Peak E (simulated): where n = 15 (C97H131NaO65)

Experimental data

21

DSC thermogram

22


23

1.81 1.70 1.60 1.58 1.56

O O

O

n

6.5

6.0

5.5

5.0


180

3.0

2.5

160

140

120


60

2.0

1.5

40

1.0

0.5

0

28.82 24.91 24.87

7.0

6.29

65.31 64.78 61.96

7.5

1.00 2.55

41.32

5.28

166.43

O

4.14 3.70 3.63 3.61 3.60 3.34

Table 1, Entry 3

20

0

24

GPC trace

25

MALDI-TOF

Zoom region A A A A B

A

B

B

C

A

C

B

C

B

n = 14

A A A B

B

B

B

A

A B

A B

A

A

A

A

n = 19

26

Peak A (simulated): where n = 5 (C39H60NaO22)

27

DSC thermogram

Sample: RW260 Size: 4.2000 mg Method: Ruth polymer

File: F:\DSC\RW260.002 Operator: AK Run Date: 09-Sep-2013 14:38 Instrument: DSC Q20 V24.10 Build 122

DSC

0.4

0.2

-49.12°C

Heat Flow (W/g)

0.0

-47.52°C(I) -45.76°C

-0.2

-0.4

129.79°C -0.6109W/g

-0.6

-0.8 -100 Exo Up

-50

0

50

100

Temperature (°C)

150

200

250 Universal V4.5A TA Instruments

28


29

1.63 1.61 1.59 1.29

O O

O

n

6.0

5.5

5.0


180

3.0

2.5

160

140

120


2.0

60

1.5

1.0

0.5

0

41.58 29.22 29.02 28.58 28.39 26.24

6.5

47.77

7.0

18.5837.12

65.56

7.5

2.008.34

58.71

16.27

166.72

O

4.12 4.10 4.08 3.62 3.59 3.57 3.34

Table 1, Entry 4

40

20

0

30

GPC trace

31

MALDI-TOF

Zoom regioniii

B C

C

B

A

A

n=5

B

C

C

A

B

A

n=7

32

DSC thermogram

33

DSC thermogram: Zoom region

34


35

O

2.29 2.27 2.03 2.02 1.99 1.89 1.87 1.86 1.84 1.68 1.67 1.65 1.35 1.31 1.27

3.37 3.35 3.34 3.32

O

4.80

O

5.13

Table 1, Entry 5

O n

5.5

5.0

180

71.58 71.14


160

140

120


3.0

2.5

60

2.0

1.5

1.0

35.17 30.33 29.87 26.35 21.85

6.0

10.31

47.83

6.5

165.76

7.0

2.00

58.77

0.90 1.03

40

20

0

36

GPC trace

37

MALDI-TOF

Zoom regioniii A B A

C

B

A

C

D

D

B A

B A

C

D

C

D

38

39

DSC thermogram

40


41

190 7.5

180

2 1

0.88

7.0 6.5

170

160 6.0

150 5.5

140 5.0

130

120 1.92

110 100 90 Chemical Shift (ppm) 2.00


80

1.99

3.0 2.5

70

60

2.0

50

1.5

40

30 9.68 9.28

O

26.03 23.55

O

41.44 41.15 40.89

O

73.71 70.67 69.21 65.27 63.67

166.12 165.97 165.86

1.67 1.65 1.64 1.62 1.61 1.51 1.50 1.48 0.98 0.97 0.95 0.93 0.92

4.29 4.28 4.26 4.26 4.17 4.16 4.14 4.05 4.03 4.02 3.45 3.43 3.40 3.39

5.06 4.93

Table 1, Entry 6 3 4

O n

3.05

1.0 0.5

20

10

0

0

42

4 3

O O

O 2

1

n

8 16 24 32 40 48 56 64 72 80 88 96 104

F1 Chemical Shift (ppm)

O

112 120 128 136 144 152 160 168

5.0

4.5

4.0

3.5

3.0 F2 Chemical Shift (ppm)

2.5

2.0

1.5

1.0

43

GPC trace

44

MALDI-TOF

Zoom region D A

D D

A B C

B C

C

n=7

A

D A

D A

B B

B

45

46

DSC thermogram

47


48

O

7.5

160 3

7.0

150 2

0.95

6.5

140 6.0

130 5.5

120 5.0

110 2.090.10 0.092.00


100 90 80 Chemical Shift (ppm) 2.21

3.0

70

2.5

60

2.0

50

1.5

40

20.19 19.97 19.82

O

41.89 41.57 41.28 37.65 34.42

O

69.16 67.65 64.65 61.69 60.56 58.66

166.40 166.29 165.94 165.86

1.97 1.95 1.94 1.93 1.91 1.90 1.89 1.29 1.27 1.25 1.24 1.22 1.21

4.37 4.22 4.21 4.19 4.18 4.11 4.10 3.90 3.66 3.65 3.64 3.37 3.35 3.33

5.15 5.06 5.05 5.04 5.03

Table 1, Entry 7 4 1

O n

3.47 1.0

30

0.5 0

20

49

O

4 1

O

3

O 2

n

16 24 32 40 48 56 64 72 80 88 96 104

F1 Chemical Shift (ppm)

O

112 120 128 136 144 152 160 168

5.0

4.5

4.0

3.5

3.0 F2 Chemical Shift (ppm)

2.5

2.0

1.5

1.0

50

GPC trace

51

MALDI-TOF

Zoom region B B

A D

A D

C

C

n = 10

B

A

B B

D C

D C

A D C

52

53

54

DSC thermogram

55


56

1.26 1.24 1.17 1.15

3.37

O O

O

n

6.0

5.5

5.0

4.5


180

120


72.38

2.5

160

140

2.0

60

1.5

1.0

0.5

40

0

14.97 10.32

6.5

6.11

41.59

7.0

2.00

58.84

1.92

165.68

O

5.06 5.04

Table 1, Entry 8

20

0

57

GPC trace

58

MALDI-TOF

Zoom regioniii C C D

B

E

A

D E

B

n=7

C C

B A

D

C D

E

A

B

E A

B

D

E

59

60

Sample: RW326 Size: 3.2000 mg Method: Ruth polymer

File: G:\DSC\RW326.001 Operator: LH Run Date: 09-Oct-2013 11:52 Instrument: DSC Q20 V24.10 Build 122

DSC

DSC thermogram 0.6

0.4

Heat Flow (W/g)

0.2

-6.41°C

0.0

-4.18°C(I) -1.98°C

-0.2

-0.4

-0.6

-0.8 -100 Exo Up

-50

0

50

100

Temperature (°C)

150

200


61


62

O O

1

3.36

O

4.60 4.57 4.56 4.54

Table 1, Entry 9

2

O n

3 4

7

6

160

140

120

3.91


67.18 66.88 100 80 Chemical Shift (ppm)

3

60

2

1

41.40

8

141.58 135.67 135.42 128.94 128.75 128.22 127.92 127.25 126.98

166.26

9

5.05 1.00

58.69

6.13

40

20

0

63

GPC trace

64

MALDI-TOF

Zoom regioniii A B A

A B

B

n=7 A B A

B

A

A B

B

A

B

A

B

n = 10

65

66

DSC thermogram

67


68

O

H N

N H HFIP

1.40 1.33 1.32

n

3.53

H2O

3.15

O

3.35

Table 1, Entry 10

Solvent impurity

Solvent impurity

4.0

3.5

3.0 Chemical Shift (ppm)

120


2.5

2.0

1.5

170

38.56 38.52 37.82 37.09

169.18

4.5

160

150

140

130

80

70

60

50

40

69

Zoom regioniii

B C D A

E

F n=4

70

DSC thermogram

71

72

O

4.5

160 4.0

140

120

O N H


100 80 Chemical Shift (ppm) 2.5

60

39.03 38.90 38.34 25.44 25.33 25.08 23.93 20.98

54.74

168.58

1.87 1.67 1.65 1.63 1.61 1.56 1.54 1.47 1.35 1.28 1.27

3.16 3.09 2.97 2.95 2.93

4.34 4.32 4.30 4.29 4.27

Table 1, Entry 11 Solvent impurity

H N n

2.0 1.5

40

20

73

MALDI-TOF

Zoom region

D A

B

B C E

A

D C

E

n=4

B

A

B

C D

E

A

C

D E

n=6

74

75

DSC thermogram

76

Table 1, Entry 12

N

n

4.0

3.5

3.0

2.5 Chemical Shift (ppm)

2.0


80

1.5

1.0

168

0.5

0

45.58 45.18 41.28 40.98

165.89

4.5

1.07 1.03 1.01

N

2.66 2.65 2.64 2.62 2.61 2.60

H2O

O

3.64 3.57 3.56 3.49 3.48 3.43

O

160

152

144

136

128

120

112

72

64

56

48

40

32

24

77

MALDI-TOF

Zoom region

B

C B

E A

D

C E

F A

D

B F

C D

E

F

n=6

B

C E D

B

C E

F D

F

B

C E

B

C

n=9

78

Peak D (simulated): where n = 6 (C49H77ClN13O12). It is unlikely that the HCl salt has formed based on the isotope splitting pattern. Experimental data

79

O

1.07 1.02

3.14

3.71

4.26 4.25

7.27 7.26 7.21 7.20 7.14

8.47

Table 2, 1 Entry 13

O N H

H N

Sample: RW384 Size: 4.2000 mg Method: Heat/Cool/Heat

n

File: G:\RW259.015 Operator: CLJ Run Date: 01-Nov-2013 09:49 Instrument: DSC Q20 V24.10 Build 122

DSC

DSC thermogram 0.6

0.2 115.35°C 121.26°C(I) 127.17°C

0.0

6

-0.4 -100

0

291.20°C 2 -0.06498W/g

3

1

0

43.41 41.97

-0.2


127.22

7

137.73

8

166.79

Heat Flow (W/g)

0.4

100

200

300

Temperature (°C)

Exo Up


MALDI-TOFiii

180

160

140

120


60

40

20

0

80

A

B

A B

B A

B A

B

B

n=2

81

82

DSC thermogram

83

1.22 1.02 0.98 0.96

N H

N H

1.78

O

2.88

O

3.16

rw430.010.001.1r.esp

3.94

7.83

Table 1, Entry 14

n

180

160

140

6


3

2


60

40

1

0

29.57 28.11 26.19 24.26

7

51.88 50.80 48.63 47.94 42.65

rw430.011.001.1r.esp

8

166.84

9

20

0

84

Zoom region A

A A

n = 10

n=9

n = 11

A

A A A

A

85

Sample: RW430 Size: 3.1000 mg Method: Heat/Cool/Heat

File: E:\Ruth RW430.001 Operator: LH Run Date: 02-Dec-2013 09:41 Instrument: DSC Q20 V24.10 Build 122

DSC

DSC thermogram 1.0

Heat Flow (W/g)

0.5

52.17°C 60.20°C(I)

0.0

66.66°C

-0.5

-1.0 -100 Exo Up

-50

0

50

100

Temperature (°C)

150

200

250

300

Universal V4.5A TA Instruments

86

Table 2, Entry 1

A n = 2 + 2Cu

n = 2 + 3Cu

n = 2 + 4Cu

n = 4 + Na

+ Cu + Cu

+ Cu + Cu

n = 16 + Na

87

Species observed:

Peak A (simulated): where n = 2 + 2Cu (i.e. C12H18Cu2O10 and C12H19Cu2O10). Overlap of [M] and [M + H+] could account for splitting pattern.

88



89

Reaction monitoring: PDI vs. time 1.9 1.8 1.7 1.6

PDI

1.5 1.4 1.3 1.2 1.1

1 0

50

100

150

200

250 Time (min)

300

350

400

450

 Table 3, Entry 1 (Cu-free);  Table 3, Entry 5 (20 mol% Cu(OTf)2)

Table S2: Extended table of results for Lewis acid assisted polymerisation

1 2 3 4 5[b] 6[c] 7[d] 8 9 10 11 12 13 14

Lewis acid

Mn (gmol-1)[a]

PDI[a]

Bi(OTf)3 Sc(OTf)3 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OAc)2 CuCl2 Cu(NO3) Zn(OAc)2 ZnCl2 HfCl4 YbCl3

2100 1000 2100 3300 2400 2500 n.r. 1900 1900 1200 2200 1600 1300 1700

1.52 1.16 1.37 1.40 1.40 1.53 n.r. 1.60 2.96 2.02 1.52 1.41 1.42 1.44

Conditions: 1 (0.67 mmol, 200 mg), ethylene glycol (0.67 mmol, 37 μl), LA (0.134 mmol, 20 mol%), 110 °C, 18 h. [a] Determined by GPC. [b] 10 mol%. [c] 5 mol% [d] 0.67 mmol, 1 eq, n.r. = no reaction observed by GPC, see ESI pages 74 to 76 for MALDI-TOF spectra.

90

Table S1: GPC traces Entry 2

91

Entry 3

92

Entry 4

93

Entry 5

94

Entry 6

95

Entry 7

96

Entry 8

97

Entry 9

98

Entry 10

99

Entry 11

100

Entry 13

101

Entry 14

NMR and GPC data: Table 4

102

Table 4, Entry 1 (20 mol% Cu(OTf)2) 1,8-octanediol

O O

O

Amide

n

1.00 4.5

4.0

3.5

1.41 1.29

1.61

1,8-octanediol

3.34

Malonate

4.12 4.10 4.08

O

3.94 3.0


1.5

1.0

0.5

0

103

Table 4, Entry 2 (20 mol% Cu(OTf)2) Amide

4

O

1

O

1.31 5.0

Malonate

H4

2.94 4.5

2.99 4.0


2.81 2.5

2.0

1.45 1.44 1.43 1.30 1.29

1.98 1.97 1.95 1.94 1.93 1.90 1.86

n

3.37

2

3.75

3

4.21 4.20

O 5.06

O

15.005.41 1.5

1.0

104

Table 4, Entry 3 (20 mol% Cu(OTf) 2)

1.67 1.66 1.65 1.46 1.45 1.44

0.97 0.96 0.94

H4

3.43

Amide

4.31 4.28 4.18 4.16

5.09

Malonate

2.37

3.40

2.57 14.64

5.01

4

O

3

O O

5.5

O 2

5.0

1

n

4.5

4.0

3.5


2.0

1.5

1.0

0.5

0

105


O

Diol methyl

O O

O

Malonate

Amide

1.46 1.44 1.27 1.26 1.18 1.17

3.45 3.38

5.06 5.05

n

1.06 5.5

5.0

4.5

4.0

3.5


7.633.98 2.0

1.5

1.0

0.5

106


O

1

2

O n

Amide

1.40

Malonate

O

3.45

O

4.37

14.69

3 4

8

7

6

5

4 Chemical Shift (ppm)

3

2

1

0

107

i

M. B. Smith, March's advanced organic chemistry : reactions, mechanisms, and structure, Wiley, New York, 2001. ii 1 13 1 End groups signals believed to be obscured by polymer signals in H/ C{ H} NMR. iii All unassigned peaks show the characteristic [dinucleophile-malonate] repeat unit, novel end groups presumed to form during MALDI-TOF ionisation i.e. in situ functionalisation with solvent (1,1,1,3,3,3hexafluoro-2-propanol, HFIP) and matrix (dithranol/NaOAc) is possible.

108