One-Pot Synthesis of Cross-Linked Sub-Micron Microgels from Pure Cellulose Via the Ugi

One-pot synthesis of cross-linked sub-micron microgels from pure cellulose via the Ugi reaction and their application as emulsifiers

Iliya D. Shulepov, Ksenia V. Kozhikhova, Yulia S. Panfilova, Maria N. Ivatsova, Maxim A. Mironov

Supporting information

Characterization of synthesized compounds 10, 14a,b, 15a-d and 16a-d using NMR, IR, MS, DLS and elemental analysis data

Compound 10can be synthesized according to the well-known protocol described by I. Ugi, POCl3/NEt3 method (Ugi I, Fetzer U, Eholzer U, Knupfer H, Offermann K (1965)IsonitrileSynthesen.Angew. Chem. 77:492-504).

Mp= 71°С. 1H NMR (400 MHz, DMSO-d6) δ: 1.78(2Н, br. s., СН2), 2.25-2.48 (6H, m, NCH2), 3.47 (2Н, br. s., СН2). MS (m/z, %):220 [M+] (28), 219(7), 190 (14), 180 (13), 176 (6), 166 (36), 165 (11), 164 (49), 152 (19), 139 (24), 123 (72), 97 (74), 84 (64), 70(100), 56 (83). IR (cm-1):1310(-C-N), 1448(-C-C-), 2150 (-N≡C), 2801(-C-H)), 2932 (-CH-).

Compounds 14

A mixture of 0.5 mmol of each of the starting reagents: isocyanide10, 4-picolyl amine (a) or benzylamine (b)11a,b, acetic acid 12and formaldehyde 13in methanol or water (1mL) were mixed together and stirred at the temperature in range 25-30 C for 5 h. The product 14 was extracted from reaction mixture by hexane (10 mL), which was treated with CuBr to remove isocyanide and after that was evaporated to dryness.

Compound 14a

Mp= 123-124°С. 1H NMR (400 MHz, D2O) δ: 1.55-1.66 (2H, m, CH2), 2.24 (3H, s, CH3), 2.29-2.25 (2H, m, NCH2), 2.43-2.57(4H, m, Piperazine ring), 3.17 (2H, t, J = 6.8 Hz, CH2NH), 4.01 (2H, s, CH2), 4.43 (2H, s, 2CH2), 7.31-7.42 (2H, m, Pyr), 8.45-8.52 (2H, m, Pyr).

13C NMR (100MHz, DMSO-d6) : 21.9 (Me), 29.5 (CH2), 41.2 (CH2), 46.2 (CH2), 53.8 (CH2), 55.2 (CH2N), 58.5 (2CH2N), 123.2 (2C-Ar), 145.7 (C-Ar), 149.3 (2C-Ar), 168.2 (C=O), 170.9 (C=O).

Elemental analysis: calcd for C30H44N8O4: C, 62.05; H, 7.64 N, 19.30. Found: C, 62.32; H, 7.55; N, 19.36.

IR (cm-1): 1260 (C-N), 1555 (NH), 1658 (C=O), 2930 (СН).

Compound 14b

Oil. 1H NMR (400 MHz, D2O) δ: 1.54-1.68 (2H, m, CH2), 2.26 (3H, s, CH3), 2.31-2.36 (2H, m, NCH2), 2.42-2.56(4H, m, Piperazine ring), 3.15 (2H, t, J = 6.8 Hz, CH2NH), 4.07 (2H, s, CH2), 4.59 (2H, s, CH2),7.29-7.51 (5H, m, Ph).

13C NMR (100MHz, DMSO-d6) : 22.6 (Me), 28.3 (CH2), 40.7 (CH2), 46.8 (CH2), 51.6 (CH2), 55.4 (CH2N), 58.1 (2CH2N), 127.1 – 129.5 (5C-Ar), 134.2 (C-Ar), 168.0 (C=O), 171.3 (C=O).

Elemental analysis: calcd for C32H46N6O4: C, 66.41; H, 8.01; N, 14.52. Found: C, 66.33; H, 7.98; N, 14.39.

IR (cm-1): 1265 (C-N), 1557 (NH), 1659 (C=O), 2930 (СН).

Compound 15a

1H NMR (400 MHz,D2O) δ: 1.52-1.65 (2H, m, CH2), 2.20-2.28 (2H, m, NCH2), 2.35-2.52(4H, m, Piperazine ring), 3.15-3.32 (2H, m, CH2NH), 3.38 (1H, br.s., H-2 of CMC), 3.65-4.35 (9H, m, H-3, H-4, H-5, H-6a,b of CMC + 3CH2), 4.57 (1H, br.s, H-1 of CMC), 7.28-7.45 (2H, m, Pyr), 8.45-8.52 (2H, m, Pyr).

Calculated degree of substitution 9.0% (82% yield).

Elemental analysis: N, 2.58. Found: N, 2.65.

IR (cm-1)Na salt: 1074 (C-O), 1540 (NH), 1665 (C=O), 2923 (СН).

DLS: Average diameter 209 nm, polydispersity index 0.12

Compound 15b

1H NMR (400 MHz,D2O) δ: 1.54-1.65 (2H, m, CH2), 2.19-2.26 (2H, m, NCH2), 2.36-2.54(4H, m, Piperazine ring), 3.13-3.31 (2H, m, CH2NH), 3.38 (1H, br.s., H-2 of CMC), 3.64-4.34 (9H, m, H-3, H-4, H-5, H-6a,b of CMC + 3CH2), 4.58 (1H, br.s, H-1 of CMC),7.22-7.30 (5H, m, Ph).

Calculated degree of substitution 8.5% (77% yield).

Elemental analysis: N, 1.65. Found: N, 1.63.

IR (cm-1) Na salt: 1063 (C-O), 1544 (NH), 1663 (C=O), 2932 (СН).Free acid: 1060 (C-O), 1597 (NH), 1660 (C=O), 1731 (C=O), 2909 (СН).

DLS: Average diameter 267 nm, polydispersity index 0.17

Compound 15c

1H NMR (400 MHz,D2O) δ: 1.51-1.63 (2H, m, CH2), 2.22-2.30 (2H, m, NCH2), 2.36-2.49(4H, m, Piperazine ring), 3.15-3.30 (2H, m, CH2NH), 3.39 (1H, br.s., H-2 of CMC), 3.64-4.33 (9H, m, H-3, H-4, H-5, H-6a,b of CMC + 3CH2), 4.59 (1H, br.s, H-1 of CMC) 6.32-6.53 (2H, m, Furan), 7.50-7.61 (1H, m, Furan).

Calculated degree of substitution 10.0% (91% yield).

Elemental analysis: N, 2.10. Found: N, 2.16.

IR (cm-1)Na salt: 1053 (C-O), 1542 (NH), 1666 (C=O), 2919 (СН).

DLS: Average diameter 248nm, polydispersity index 0.23

Compound 15d

1H NMR (400 MHz,D2O) δ: 1.22 (6H, d, J = 6.9 Hz, CH3), 1.52-1.65 (2H, m, CH2), 2.20-2.28 (2H, m, NCH2), 2.35-2.52(4H, m, Piperazine ring), 3.15-3.32 (2H, m, CH2NH), 3.38 (1H, br.s., H-2 of CMC), 3.65-4.35 (9H, m, H-3, H-4, H-5, H-6a,b of CMC + CH + 2CH2), 4.57 (1H, br.s, H-1 of CMC).

Calculated degree of substitution 7.5% (68% yield).

Elemental analysis: N, 1.62. Found: N, 1.57.

IR (cm-1)Na salt: 1062 (C-O), 1540 (NH), 1667 (C=O), 2925 (СН).

DLS: Average diameter 312 nm, polydispersity index 0.28

Compound 16a

1H NMR (400 MHz,D2O) δ: 1.53-1.67 (2H, m, CH2), 2.22-2.29 (2H, m, NCH2), 2.34-2.50(4H, m, Piperazine ring), 3.13-3.31 (2H, m, CH2NH), 3.38 (1H, br.s., H-2 of CMC), 3.62-4.37 (9H, m, H-3, H-4, H-5, H-6a,b of CMC + 2CH2), 4.58 (1H, br.s, H-1 of CMC), 7.29-7.47 (2H, m, Pyr), 8.44-8.51 (2H, m, Pyr).

Calculated degree of substitution 6% (54% yield).

IR (cm-1)Na salt: 1065 (C-O), 1541 (NH), 1665 (C=O), 2930 (СН).

DLS: Average diameter 235 nm, polydispersity index 0.15

Compound 16b

1H NMR (400 MHz,D2O) δ: 1.54-1.66 (2H, m, CH2), 2.19-2.27 (2H, m, NCH2), 2.36-2.53(4H, m, Piperazine ring), 3.14-3.32 (2H, m, CH2NH), 3.37 (1H, br.s., H-2 of CMC), 3.64-4.35 (9H, m, H-3, H-4, H-5, H-6a,b of CMC + 2CH2), 4.57 (1H, br.s, H-1 of CMC),7.21-7.33 (5H, m, Ph).

Calculated degree of substitution 5.0% (45% yield).

Elemental analysis: N, 1.04. Found: N, 1.07.

IR (cm-1)Na salt: 1062 (C-O), 1543 (NH), 1664 (C=O), 2927 (СН).

DLS: Average diameter 358 nm, polydispersity index 0.25

Compound 16c

1H NMR (400 MHz,D2O) δ: 1.50-1.64 (2H, m, CH2), 2.21-2.26 (2H, m, NCH2), 2.36-2.52(4H, m, Piperazine ring), 3.15-3.31 (2H, m, CH2NH), 3.36 (1H, br.s., H-2 of CMC), 3.66-4.38 (9H, m, H-3, H-4, H-5, H-6a,b of CMC + 2CH2), 4.59 (1H, br.s, H-1 of CMC),6.31-6.52 (2H, m, Furan), 7.52-7.62 (1H, m, Furan).

Calculated degree of substitution 6.0% (55% yield).

Elemental analysis: N, 1.28. Found: N, 1.24.

IR (cm-1) Na salt: 1065 (C-O), 1543 (NH), 1665 (C=O), 2927 (СН).

DLS: Average diameter 310 nm, polydispersity index 0.23

Compound 16d

1H NMR (400 MHz,D2O) δ: 1.51-1.66 (2H, m, CH2), 2.22-2.27 (2H, m, NCH2), 2.34-2.50(4H, m, Piperazine ring), 3.14-3.30 (2H, m, CH2NH), 3.37 (1H, br.s., H-2 of CMC), 3.64-4.36 (9H, m, H-3, H-4, H-5, H-6a,b of CMC + 2CH2), 4.58 (1H, br.s, H-1 of CMC).

Calculated degree of substitution 4.0% (38% yield).

Elemental analysis: N, 0.91. Found: N, 0.97.

IR (cm-1)Na salt: 1060 (C-O), 1542 (NH), 1666 (C=O), 2931 (СН).Free acid: 1056 (C-O), 1623 (C=O), 1731 (C=O), 2925 (СН)

DLS: Average diameter 420 nm, polydispersity index 0.4

Analysisofspectraldata

AsaresultoftheUgireactionisocyanogroupistransformedintoamidegroup. Thecharacteristicshiftofα-methylenegroupfrom 3.47 ppm to 3.15 ppm is observed that is one of indicators of the isocyanide conversion.

NMR data for compounds 10(signal of water is deleted).

Comparison with model compounds 14a

NMR data for compounds 14a

The similar shift is observed for cellulose derivatives:

NMRdataforcompounds15a

Inmodelcompounds14thesignalsofacylgroup are presented,in target CMC derivatives we can observe the signals of glucose residue. Othersignalsareremainedwithoutanychanges.

Comparison the compounds 14a and 15a:

NMR data of 14a

NMR data of 15a

Comparison the compounds 14b and 15b:

NMR data of 14b

NMR data of 15b

Conversion of isocyano group during the cross-linkage.

At the final step of our method, the resulting mixture is stepwise neutralized with 1 wt% solution of HCl until pH is reached 4. Atthisstageisocynogroupistransformed into formamide group, which has the distinctive signal in NMR spectra. Low intensity of this signal reflects high conversion of isocyano group via the Ugi reaction.

NMR data for formamide, which is product of full hydrolysis of compounds 10

Signals of aliphatic part of this compound

Signals of formamide group

In spectra of the model compounds 14 we can see these signals:

InNMRspectraofCMCderivatives 15and16these signals are close to the resolution limit of our instrument. This is a good evidence of high effectiveness of the cross-linkage methodology.

NMRdataforcompounds15a-daresimilarandcan be distinguished by distribution of side functional groups:

NMR data of 15a

NMR data of 15b

NMR data of 15c

NMR data of 15d

ThemainfeaturesofNMRdataforcompounds16a-darelowintensityofsidegroupsignalsandwideningofallsignalsowingto the lower solubility in D2O.

NMR data for compounds 16b

NMR data for compounds 16d

IR spectrum of the starting isocyanide10 contents very intensive band at 2150 cm-1, which is indicative of the existence of isocyano groups.

IR of compound 10.

Hydrolysis of isocyano group results in the appearance of distinctive bands in the region 1550 – 1700 cm-1which can be assigned to the carbonyl stretching vibration mode of secondary amide (amide band I) and the bending vibration mode of the amide band II, respectively.

IR of hydrolysis product.

The similar pictures are available for model compounds 14.

IR of model compound 14a.

IR spectra of target compounds 15, 16 also contain amide band I and amide band II. However, the character of IR spectra for compounds 15 depends on pH, because all samples contain carboxyl groups, which remain in the structure of CMC after the Ugi reaction.

IR of 15a in the form of Na salt (COONa in the region nearby 1650 cm-1).

IR of 15b in the form of free acid (COOH band at 1731 cm-1).

IR spectra of compounds 16are similar to 15.

IR of 16d in the form of free acid (COOH band at 1731 cm-1).