Electronic Supplementary Material (ESI) for New Journal of Chemistry.

This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2023

Electronic supplementary information (ESI)

for

Rapid alcoholysis of cyclic esters using metal alkoxides:

access to linear lactyllactate-grafted polyglycidol

Supajittra Yimthachote and Khamphee Phomphrai*

Department of Materials Science and Engineering, School of Molecular Science and

Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC)
555 Payupnai, Wang Chan, Rayong 21210, Thailand.
*Email: [email protected]

S1
Experimental section

Materials
All syntheses and manipulations were carried out under nitrogen atmosphere using standard
Schlenk techniques, or in a nitrogen-filled glovebox (MBRAUN, MB 200G, equipped with a
purification system). Dichloromethane and toluene were dried using a solvent purification system
(PURE SOLV MD-5, Innovative Technology). Al(OiPr)3 was purchased from Acros Organics and
used as received. L-Lactide was recrystallized in dry toluene, followed by sublimation three times
prior to use. ɛ-Caprolactone (ɛ-CL), δ-valerolactone (δ-VL), β-butyrolactone (β-BL), γ-
butyrolactone (γ-BL), methanol, ethanol, benzyl alcohol, isopropanol, propargyl alcohol, and
glycidol were distilled twice over calcium hydride. 2-Hydroxyethyl methacrylate (HEMA) was
dried over activated 4-Å-molecular sieves and stored in the glovebox at -30°C.

Measurements
1
H, 13C, and 2D-DOSY NMR spectra were recorded on a Bruker AVANCE III HD-600
MHz spectrometer at 30°C in chloroform-d (CDCl3) and deuterium oxide (D2O) referenced to a
protic residual solvent peak at 7.26 and 4.79 ppm, respectively as an internal standard. High-
resolution mass spectra were obtained by compact QTOF Bruker mass spectrometer, using
QtofControl analysis, atmospheric pressure compressed interface (APCI) mode. GPC analysis for
poly(glycidyl lactyllactate) was performed on a Malvern Viscotek TDAmax double detector
device with a refractive index detector and a viscometer with two 300 mm x 8.0 mm ID columns
packed with a porous styrene divinylbenzene copolymer. GPC columns were eluted using
tetrahydrofuran with a flow rate of 1.0 mL/min at 35°C. The universal calibration curve was
calibrated with polystyrene standards ranging from 1,200 to 4,200,000 amu. Molecular weight and
polydispersity were calculated by the conventional method using refractive index.1, 2 GPC analysis
of polyglycidol was carried out on Shimadzu HPLC 10Avp equipped with a refractive index
detector. GPC column, Shodex SB-804 HQ, was eluted by DI water with a flow rate of 0.5 mL/min
at 30°C. The water solution of polymer was filtered and injected into the GPC column (20 μL)
with a run time of 30 min. Molecular weight and polydispersity were determined by the
conventional method using refractive index calibrated with Pullulan standards ranging from 500-
800,000 Da.
Thermogravimetric Analysis (TGA) was determined by Rigaku STA8122
Thermogravimetric Analyzer over a temperature range from 40°C to 500°C at a heating rate of
10°C/min under a nitrogen atmosphere with a gas flow rate of 200 mL/min. Differential Scanning
Calorimetry (DSC) measurement was performed on a PerkinElmer DSC-8500 to analyze the glass-
transition temperature (Tg) of polymers over a temperature range from -60°C to 100°C at a heating
rate of 10°C/min and a gas flow rate of 20 mL/min under nitrogen atmosphere.

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General procedure for the alcoholysis of cyclic esters using metal alkoxides

A solution of Al(OiPr)3 (35.5 mg, 174 μmol, 5 mol%) and dry alcohol (17.4 mmol, 5 equiv.)
in 2 mL of toluene was prepared and added to a solution of cyclic esters (3.5 mmol, 1 equiv.) in 2
mL of toluene. The reaction mixture was then heated at 70°C with stirring. After completion or at
the desire time, the reaction was quenched with a few drops of acetic acid. All volatile components
were subsequently removed under reduced pressure and further purified by vacuum distillation
and/or silica gel column chromatography with stepwise gradient polarity using ethyl
acetate:hexane (10:90, 20:80, 30:70, 40:60, and 50:50), giving colorless liquid as a product. The
products were then analysed by 1H- and 13C-NMR spectroscopy and APCI mass spectrometry. The
amounts of other catalysts, alcohols, and cyclic esters in other alcoholysis were modified
accordingly. Alcoholysis was performed in triplicate.

Methyl (S,S)-lactyllactate

Colorless liquid, 90% isolated yield, 1H NMR (600 MHz, Chloroform-d) δ 5.20 (q, J = 7.1
Hz, 1H), 4.36 (p, J = 6.6 Hz, 1H), 3.76 (s, 3H), 2.68 (d, J = 5.9 Hz, 1H), 1.54 (d, J = 7.1 Hz, 3H),
1.50 (d, J = 6.9 Hz, 3H). 13C NMR (151 MHz, Chloroform-d) δ 175.29, 170.76, 69.49, 66.89,
52.64, 20.64, 17.02. APCI MS (m/z) calc. for C7H12O5 [M-H]+ = 177.0757, found 177.0772.

Methyl 3-hydroxybutyrate

Colorless liquid, 90% isolated yield, 1H NMR (600 MHz, Chloroform-d) δ 4.19 (ddt, J =
12.5, 9.5, 4.8 Hz, 1H), 3.71 (s, 3H), 2.95 (s, 1H), 2.49 (dd, J = 16.5, 3.4 Hz, 1H), 2.43 (dd, J =
16.5, 8.8 Hz, 1H), 1.23 (d, J = 6.3 Hz, 3H). 13C NMR (151 MHz, Chloroform-d) δ 173.46, 64.39,
51.86, 42.69, 22.58. APCI MS (m/z) calc. for C5H10O3 [M-H]+ = 119.0703, found 119.0719.

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Methyl 4-hydroxybutanoate

Colorless liquid, 35% isolated yield, 1H NMR (600 MHz, Chloroform-d) δ 3.71-3.69 (m,
5H), 2.45 (t, J = 7.1 Hz, 2H), 1.89 (t, J = 6.6 Hz, 2H). 13C NMR (151 MHz, Chloroform-d) δ
174.53, 62.28, 51.85, 30.95, 27.82. APCI MS (m/z) calc. for C5H10O3 [M-H]+ = 119.0703, found
119.0580.

Methyl 5-hydroxypentanoate

Colorless liquid, 82% isolated yield, 1H NMR (600 MHz, Chloroform-d) δ 3.66 (s, 3H),
3.64 (t, J = 6.4 Hz, 2H), 2.35 (t, J = 7.3 Hz, 2H), 1.71 (p, J = 7.4 Hz, 2H), 1.59 (p, J = 6.5 Hz, 2H).
13
C NMR (151 MHz, Chloroform-d) δ 174.32, 62.37, 51.68, 33.78, 32.17, 21.21. APCI MS (m/z)
calc. for C6H12O3 [M-H]+ = 133.0859, found 133.0931.

Methyl 6-hydroxyhexanoate

Colorless liquid, 90% isolated yield, 1H NMR (600 MHz, Chloroform-d) δ 3.66 (s, 3H),
3.64 (t, J = 6.5 Hz, 2H), 2.32 (t, J = 7.5 Hz, 2H), 1.74 (s, 1H), 1.65 (p, J = 7.5 Hz, 2H), 1.57 (p, J
= 6.7 Hz, 2H), 1.39 (p, J = 7.7 Hz, 2H). 13C NMR (151 MHz, Chloroform-d) δ 174.32, 62.77,
51.63, 34.12, 32.44, 25.42, 24.76. APCI MS (m/z) calc. for C7H14O3 [M-H]+ = 147.1016, found
147.1074.

Ethyl (S,S)-lactyllactate

Colorless liquid, 5% isolated yield, 1H NMR (600 MHz, Chloroform-d) δ 5.17 (q, J = 7.1
Hz, 1H), 4.35 (p, J = 6.9 Hz, 1H), 4.21 (qd, J = 7.2, 2.6 Hz, 2H), 2.70 (d, J = 5.9 Hz, 1H), 1.53 (d,

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J = 7.1 Hz, 3H), 1.50 (d, J = 7.0 Hz, 3H), 1.28 (t, J = 7.2 Hz, 3H). 13C NMR (151 MHz,
Chloroform-d) δ 175.32, 170.30, 69.62, 66.87, 61.74, 20.68, 17.00, 14.21. APCI MS (m/z) calc.
for C8H14O5 [M-H]+ = 191.0914, found 191.0784.

Benzyl (S,S)-lactyllactate

Colorless liquid, 17% isolated yield, 1H NMR (600 MHz, Chloroform-d) δ 7.35 (dt, J =
21.7, 7.1 Hz, 5H), 5.26–5.13 (m, 3H), 4.34 (p, J = 6.6 Hz, 1H), 2.67 (d, J = 5.9 Hz, 1H), 1.54 (d,
J = 7.2 Hz, 3H), 1.44 (d, J = 7.0 Hz, 3H). 13C NMR (151 MHz, Chloroform-d) δ 175.29, 170.13,
135.22, 128.80, 128.71, 128.41, 69.57, 67.42, 66.86, 20.60, 16.98. APCI MS (m/z) calc. for
C13H16O5 [M-H]+ = 253.1071, found 253.1074.

Isopropyl (S,S)-lactyllactate

Colorless liquid, 13% isolated yield, 1H NMR (600 MHz, Chloroform-d) δ 5.13 (q, J = 7.1
Hz, 1H), 5.06 (p, J = 6.3 Hz, 1H), 4.35 (p, J = 6.9 Hz, 1H), 2.69 (d, J = 5.6 Hz, 1H), 1.51 (dd, J =
9.2, 7.0 Hz, 6H), 1.26 (dd, J = 15.3, 6.2 Hz, 6H). 13C NMR (151 MHz, Chloroform-d) δ 175.30,
169.83, 69.75 (d, J = 2.7 Hz), 69.47 (d, J = 2.3 Hz), 66.83, 21.79 (d, J = 4.6 Hz), 20.69, 16.93.
APCI MS (m/z) calc. for C9H16O5 [M-H]+ = 205.1071, found 205.1103.

2-(methacryloyl)ethyl-(S,S)-lactyllactate

Colorless liquid, 55% isolated yield, 1H NMR (600 MHz, Chloroform-d) δ 6.12 (s, 1H),
5.60 (s, 1H), 5.20 (q, J = 7.1 Hz, 1H), 4.50 – 4.41 (m, 1H), 4.39-4.33 (m, 4H), 1.94 (s, 3H), 1.53
(d, J = 7.1 Hz, 3H), 1.48 (d, J = 6.9 Hz, 3H). 13C NMR (151 MHz, Chloroform-d) δ 175.17, 170.10,

S5
167.17, 135.95, 126.38, 69.37, 66.87, 63.27, 62.16, 20.56, 18.34, 16.96. APCI MS (m/z) calc. for
C12H18O7 [M-H]+ = 275.1125, found 275.1173.

Propargyl-(S,S)-lactyllactate

Colorless liquid, 34% isolated yield, 1H NMR (600 MHz, Chloroform-d) δ 5.22 (q, J = 7.0
Hz, 1H), 4.74 (qd, J = 15.5, 2.5 Hz, 2H), 4.36 (p, J = 6.8 Hz, 1H), 2.67 (d, J = 5.9 Hz, 1H), 2.50
(t, J = 2.5 Hz, 1H), 1.56 (d, J = 7.1 Hz, 3H), 1.51 (d, J = 6.9 Hz, 3H). 13C NMR (151 MHz,
Chloroform-d) δ 175.25, 169.54, 76.87, 75.75, 69.29, 66.88, 53.09, 20.67, 16.86. APCI MS (m/z)
calc. for C9H12O5 [M-H]+ = 201.0757, found 201.0883.

Glycidyl-(S,S)-lactyllactate

Colorless liquid, 85% isolated yield. Product existed as a pair of diastereomers. 1H NMR
(600 MHz, Chloroform-d) δ 5.20 (p, J = 6.9 Hz, 1H), 4.48 (td, J = 12.2, 2.8 Hz, 1H), 4.35 (p, J =
6.3 Hz, 1H), 4.00 (ddd, J = 17.9, 12.2, 6.3 Hz, 1H), 3.19 (ddd, J = 13.2, 5.9, 3.0 Hz, 1H), 2.84 (q,
J = 4.3 Hz, 1H), 2.77 (d, J = 4.6 Hz, 1H), 2.64 (ddd, J = 15.5, 4.4, 2.5 Hz, 1H), 1.55 (d, J = 7.1
Hz, 3H), 1.50 (d, J = 6.9 Hz, 3H). 13C NMR (151 MHz, Chloroform-d) δ 175.26 (d, J = 2.3 Hz),
170.06, 69.42 (d, J = 1.1 Hz), 66.88 (d, J = 1.2 Hz), 66.16, 65.72, 49.14 (d, J = 1.2 Hz), 44.66,
44.61, 20.61 (d, J = 2.1 Hz), 16.98 (d, J = 1.9 Hz). APCI MS (m/z) calc. for C9H14O6 [M-H]+ =
219.0863, found 219.0931.

S6
Figure S1 1H-NMR spectrum (CDCl3, 600 MHz, 30°C) of the purified methyl (S,S)-lactyllactate.

Figure S2 13C-NMR spectrum (CDCl3, 151 MHz, 30°C) of the purified methyl (S,S)-lactyllactate.

S7
Figure S3 1H-NMR spectrum (CDCl3, 600 MHz, 30°C) of the purified methyl 3-hydroxybutyrate.

Figure S4 13C-NMR spectrum (CDCl3, 151 MHz, 30°C) of the purified methyl 3-hydroxybutyrate.

S8
Figure S5 1H-NMR spectrum (CDCl3, 600 MHz, 30°C) of the purified methyl 4-
hydroxybutanoate.

Figure S6 13C-NMR spectrum (CDCl3, 151 MHz, 30°C) of the purified methyl 4-
hydroxybutanoate.

S9
Figure S7 1H-NMR spectrum (CDCl3, 600 MHz, 30°C) of the purified methyl 5-
hydroxypentanoate.

Figure S8 13C-NMR spectrum (CDCl3, 151 MHz, 30°C) of the purified methyl 5-
hydroxypentanoate.
S10
Figure S9 1H-NMR spectrum (CDCl3, 600 MHz, 30°C) of the purified methyl 6-
hydroxyhexanoate.

Figure S10 13C-NMR spectrum (CDCl3, 151 MHz, 30°C) of the purified methyl 6-
hydroxyhexanoate.

S11
Figure S11 1H-NMR spectrum (CDCl3, 600 MHz, 30°C) of the purified ethyl (S,S)-lactyllactate.

Figure S12 13C-NMR spectrum (CDCl3, 151 MHz, 30°C) of the purified ethyl (S,S)-lactyllactate.

S12
Figure S13 1H-NMR spectrum (CDCl3, 600 MHz, 30°C) of the purified benzyl (S,S)-lactyllactate.

13
Figure S14 C-NMR spectrum (CDCl3, 151 MHz, 30°C) of the purified benzyl (S,S)-
lactyllactate.

S13
Figure S15 1H-NMR spectrum (CDCl3, 600 MHz, 30°C) of the purified isopropyl (S,S)-
lactyllactate.

13
Figure S16 C-NMR spectrum (CDCl3, 151 MHz, 30°C) of the purified isopropyl (S,S)-
lactyllactate.
S14
Figure S17 1H-NMR spectrum (CDCl3, 600 MHz, 30°C) of the purified 2-(methacryloyl)ethyl
(S,S)-lactyllactate.

Figure S18 13C-NMR spectrum (CDCl3, 151 MHz, 30°C) of the purified 2-(methacryloyl)ethyl
(S,S)-lactyllactate.

S15
Figure S19 1H-NMR spectrum (CDCl3, 600 MHz, 30°C) of the purified propargyl (S,S)-
lactyllactate.

13
Figure S20 C-NMR spectrum (CDCl3, 151 MHz, 30°C) of the purified propargyl (S,S)-
lactyllactate.
S16
Figure S21 1H-NMR spectrum (CDCl3, 600 MHz, 30°C) of the purified glycidyl (S,S)-
lactyllactate (mixtures of diastereomers).

Figure S22 13C-NMR spectrum (CDCl3, 151 MHz, 30°C) of the purified glycidyl (S,S)-
lactyllactate (mixtures of diastereomers).

S17
Scheme S1 Proposed mechanism of the methanolysis of L-lactide.

Figure S23 1H-NMR spectrum (CDCl3, 600 MHz, 30°C) of the free isopropanol generated
instantaneously from the fast proton exchange between Al(OiPr)3 and excess methanol.

S18
Table S1 Alcoholysis of L-lactide with different alcohols

[ROH]/ Time Product Distribution

Entry ROH T (°C) %Conva
[LA] (min) %ALLa %ALa
1 EtOH 5 70 10 98 18 82
2 BnOH 5 70 15 99 34 66
i
3 PrOH 5 70 2h 94 30 70
4 HEMA 1.5 90 30 94 75 25
5 PrGOH 1.5 90 10 97 35 65
Reaction conditions: L-lactide (3.47 mmol), alcohol, catalyst (5 mol%, 174 μmol), toluene
(4 mL), performed at least in duplicate. aDetermined by 1H-NMR analysis.

Table S2 Methanolysis of lactones catalyzed by Al(OiPr)3 catalyst

Entry Monomer Time (h) %Conva

1 β-BL 8 94
2 γ-BL 2 92
3 δ-VL 1.5 94
4 ɛ-CL 4 93
Reaction conditions: lactone (3.47 mmol), methanol (0.7 mL, 17.4 mmol), Al(OiPr)3 (5
mol%, 174 μmol), DCM (4 mL), RT. aDetermined by 1H-NMR analysis.

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General procedure for the synthesis of poly(glycidyl lactyllactate) (PGDLA)

The reaction mixture of GDLA (1.83 mmol, 0.4 g) in the presence of Al(OiPr)3 catalyst
(3.74 mg, 18.3 μmol, 1 mol%) was prepared and then heated at 130°C with stirring for 72 h
yielding viscous PGDLA polymer (93% conversion of GDLA). The crude polymer was dissolved
in dichloromethane and then filtered to remove all solid components. The resulting polymers were
subsequently purified by precipitating in cold hexane and dry under vacuum. The product was
analysed by 1H- and 13C-NMR spectroscopy, GPC, TGA, and DSC measurements.

Figure S24 1H-DOSY-NMR spectrum (CDCl3, 600 MHz, 30°C) of the resulting poly(glycidyl
lactyllactate).

S20
Figure S25 1H-NMR spectrum (CDCl3, 600 MHz, 30°C) of the resulting poly(glycidyl
lactyllactate).

Figure S26 13C-NMR spectrum (CDCl3, 151 MHz, 30°C) of the resulting poly(glycidyl
lactyllactate).

S21
Figure S27 13C-NMR spectra (CDCl3, 30°C) at carbonyl, methine, and methyl carbon regions of
(a) glycidyl (S,S)-lactyllactate (GDLA), (b) poly(glycidyl lactyllactate) (PGDLA), and (c) PGDLA
reacted with excess HDI.

Figure S28 1H-NMR spectrum (D2O, 600 MHz, 30°C) of the obtained polyglycidol (PGD) from
the ring-opening polymerization of glycidol at 130°C under neat condition using 5 mol% Al(OiPr)3
as a catalyst.

S22
Figure S29 DEPT-135 13C-NMR spectrum (D2O, 151 MHz, 30°C) of the obtained polyglycidol
(PGD) from the ring-opening polymerization of glycidol at 130°C under neat condition using 5
mol% Al(OiPr)3 as a catalyst.3, 4 D: Dendritic units; L1,3: Linear 1,3 units; L1,4: Linear 1,4 units;
T1,2: Terminal 1,2 units; T1,3: Terminal 1,3 units.

Figure S30 GPC profile of the resultant poly(glycidyl lactyllactate) (PGDLA) obtained using 1
mol% Al(OiPr)3 as a catalyst.

S23
Figure S31 DSC curves of the polymers obtained by using Al(OiPr)3 as a catalyst. PGD:
Polyglycidol. PGDLA: Poly(glycidyl lactyllactate).

Figure S32 Derivative mass curves for the polymers heated at a heating rate of 10°C/min. The
numbers represent the temperatures of maximum mass loss rate (Tmax). PGD: Polyglycidol.
PGDLA: Poly(glycidyl lactyllactate).

S24
Figure S33 The solubility of PGD and PGDLA in (a) water and (b) DCM.

References
1. Z. Grubisic, P. Rempp and H. Benoit, J. Polym. Sci., Part B Polym. Phys., 1996, 34, 1707-1713.
2. H. Coll, Sep. Sci., 1970, 5, 273-282.
3. G. Rokicki, P. Rakoczy, P. Parzuchowski and M. Sobiecki, Green Chem., 2005, 7, 529-539.
4. L.-c. Cao, M. Mou and Y. Wang, J. Mater. Chem., 2009, 19, 3412-3418.

S25