Conversion of lactides into ethyl lactates and value-added products

Article abstract of DOI:10.1016/j.tetlet.2014.07.103

This Letter describes an attractive and efficient method for Mg(OR)₂-mediated lactide alcoholysis. The catalysts were generated in situ from di-n-butylmagnesium and ROH to prevent aggregation of Mg(OR)₂. The reaction of ROH [R = Me,

Full text of DOI:10.1016/j.tetlet.2014.07.103

Tetrahedron Letters 55 (2014) 5286–5289
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Conversion of lactides into ethyl lactates and value-added products
⇑
Dominik Bykowski, Agnieszka Grala, Piotr Sobota
Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
This Letter describes an attractive and efficient method for Mg(OR) -mediated lactide alcoholysis. The
2
Received 7 May 2014
Revised 1 July 2014
Accepted 24 July 2014
Available online 30 July 2014
catalysts were generated in situ from di-n-butylmagnesium and ROH to prevent aggregation of Mg(OR)
The reaction of ROH [R = Me, Et, RCO (Me)CH] with lactide initially yielded the ring-opened product
HO[CH(CH )CO] OR (n = 2 or 3). The complete consumption of lactide caused the reaction to proceed fur-
2
.
2
3
n
ther, giving environmentally friendly lactic acid esters in excellent yields under ambient conditions.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Alcoholysis
Ethyl lactate
Green solvent
Lactide
Mg(OR)
2
The production of chemical building blocks and polymer pre-
cursors from biorenewable and sustainable resources is an attrac-
tive method for bypassing traditional fossil-fuel-derived
tion of PLA into lactate esters through transesterification, using
triazabicyclodecene as an organocatalyst.
Our group has described the chemistry that enables the exclu-
sive preparation of alkyl lactyllactates by chemoselective alcoholy-
1
0
1
materials. Lactide (LA), which is a cyclic dimer of lactic acid and
is made by fermentation of carbohydrates such as corn, is not only
a valuable chemical feedstock for the production of bioplastics,
sis of
Mg(tbpca)
L
-LA mediated by a tetrahedral magnesium compound,
(tbpca = N-[methyl(2-hydroxy-3,5-di-tert-butyphe-
2
,3
2
1
1
but is also used to produce lactate esters, which are found in prod-
ucts such as cosmetics, perfumes, degreasers, food preservatives,
and environmentally friendly solvents.4 The concept of lactic acid
ester synthesis from LA is very well established. As early as 1945,
nyl)]-N-methyl-N-cyclohexylamine). Based on this concept, we
present an easy-to-use system, composed of a catalytic amount
of an alkoxo-magnesium compound and excess ROH with respect
to LA, for ring-opening alcoholysis, yielding valuable lactic acid
esters under ambient conditions in excellent yields.
Initially, the alcoholysis of L-LA with ROH (R = Me, Et) in the
presence of a catalytic amount of [Mg(OR)
model reaction (Scheme 1).
,5
5
6
Claborn, and later, in 1997, Wyffels, showed that alkyl lactyllac-
tates can be produced by heating a mixture of dry LA and the
appropriate anhydrous alcohol in the presence of an acid catalyst
at 70–90 °C for ca. 6–8 h. It is claimed that polylactide (PLA) under-
2
] was studied as a
goes depolymerization to methyl lactate at 150 °C in the presence
In the absence of a magnesium source, no ring-opening alcohol-
ysis product was detected (Table 1, entry 1). Magnesium alkoxides
4
2
of H SO
4
. Low molecular weight polylactates, HO[CH(CH
3
)CO]
n
OR
(
n = 3–7), can also be formed by self-alcoholysis of alkyl lactates or
Mg(OR)
showed low catalytic activity. Turova
Mg(OMe) is built from four types of units: neutral [Mg
OMe) (OMe)
2
are only slightly soluble in CH
2
Cl
2
and toluene, and
7
12
by condensation of lactic acid.
reported that solid
Currently, the simple and cheap alcoholysis of LA is attracting
significant interest because it provides an environmentally friendly
route to lactic acid esters. Phomphrai has shown that it is possible
to convert LAs into alkyl lactates (alacH), and lactyllactates (a(lac)2-
H), using a group 1 metal and a calcium alkoxide catalyst gener-
2
4
(
l
]
3
2
-
+
4
4
(MeOH)
8
] cubane, [Mg
4 3
(l
OMe)
4
(OMe)
2
(MeOH)10
À
cubane cations, [(MeO)
2
H] anions, and eight crystallographically
12
independent noncoordinated solvating methanol molecules. This
structure derives from the bridging ability of alkoxo oxygen atoms,
8
ated in situ. Recently, Jones has shown that group 4 salalen
complexes can be used to convert PLAs into lactate esters at room
9
temperature. Furthermore, Leibfarth reported the depolymeriza-
⇑
Corresponding author. Tel.: +48 71 375 7306.
E-mail address: piotr.sobota@chem.uni.wroc.pl (P. Sobota).
Scheme 1. Ring-opening alcoholysis of
presence of a catalytic amount of Mg(OR) .
L-LA with ROH[R = Me (1), Et (2)] in the
2
http://dx.doi.org/10.1016/j.tetlet.2014.07.103
040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
0

D. Bykowski et al. / Tetrahedron Letters 55 (2014) 5286–5289
5287
Table 1
Summary of the alcoholysis of L-LA using Mg(OMe)
2
(1) and Mg(OEt)
2
(2) as catalysts
Entry
Catalyst
Time (min)
%
L-LA
% a(lac) H % alacH
2
1
2
3
4
5
6
7
8
1
1
1
1
2
2
2
2
1
5
15
30
1
5
15
30
0
0
0
0
0
0
0
0
91
72
50
0
92
69
45
0
9
28
50
100
8
31
55
100
Scheme 2. Ring-opening alcoholysis of LA with alkyl lactate hydroxyl groups in the
presence of a catalytic amount of [(Mg(elac) ] (3).
2 2
L
-LA =
L
-lactide, a(lac)
2
H = alkyl lactyllactate, alacH = alkyl lactate, reaction condi-
-LA]/[ROH] = 1:50:200, ROH = MeOH (1), EtOH (2).
tions: rt, CH
2
Cl , 1 or 2/[L
2
which causes aggregation. In this study, to prevent aggregation of
Mg(OR) , the catalysts were generated in situ in CH Cl from
MgBu and ROH [R = Me (1), Et (2)] before use. In a typical exper-
iment, the monomer, that is, -LA, in CH Cl and previously dried
ethanol or methanol were placed in a Schlenk flask and stirred
under N . Next, commercially available MgBu was added in a
molar ratio of [MgBu ]/[ -LA]/[ROH] = 1:50:200. The solvent and
excess alcohol were removed to afford the desired lactate ester.
2
2
2
2
L
2
2
Scheme 3. Treatment of elacH with MgBu
3 and stoichiometric butane elimination.
2 2 2
in CH Cl at room temperature afforded
2
2
2
L
Data for
Table 1.
L-LA alcoholysis catalyzed by 1 and 2 are presented in
Results showed that in the first step ROH reacts rapidly with
-LA, giving the ring-opened alkyl lactyllactate, (a(lac) H), nearly
exclusively. When the -LA has been completely consumed, the
a(lac) H reacts further with the alcohol, giving alkyl lactate (alacH)
Table 1, entries 1–8).
Once we had found a suitable system for the alcoholysis of LA
into the corresponding lactate esters, we became interested in
exploring the influence of -LA on the final distribution of the reac-
tion products. We used the standard conditions, that is, [1]/[ -LA]/
MeOH] = 1:50:200, and monitored the course of the reaction using
L
2
L
2
(
L
L
[
1
H NMR spectroscopy. Addition to the reaction mixture containing
2% methyl lactyllactate (m(lac) H) and 28% methyl lactate
mlacH) (Table 1, entry 2) of a new portion of LA, 1/ -LA = 1:25
Fig. 1, spectrum A, signal a), resulted in total consumption (within
7
(
(
2
L
Figure 2. 1H NMR (benzene-d
6
, 293 K, 500 MHz) spectrum, showing proton signals,
2
-LA]/
⁄
2
3
min) of the added
min, shows the absence of signal b from the methine protons of
L
-LA (spectrum B). Spectrum C, recorded after
recorded after 1 min; CH Cl . Initial conditions: room temperature, [3]/[
L
2
[elacH] = 1:50:200.
mlacH as a result of self-alcoholysis; the signal reappeared after
5
min (spectrum D) (see Scheme 5).
When ethanol was used instead of methanol, the reaction
2
It is well known that alkyl lactate moieties, –OCH(Me)CO R
i
(
R = Me, Et, Pr), can be regarded as the propagating species in LA
course and reaction products were similar. However, the NMR
spectrum was more complex because the -LA and ethyl lactate
elacH) methine signals overlapped. It follows that the highly
active compounds 1 and 2 are able to catalyze not only the reaction
between -LA and ROH (Scheme 1), but also between -LA and
alacH. It can be assumed that during alcoholysis with the participa-
tion of alkyl lactate hydroxyl groups, a trimer, HO[CH(CH) CO] OEt
e(lac) H] can be formed, in accordance with Scheme 2.
1
3
14
15
16
polymerization with aluminum, zinc, gallium, and tin initi-
ators. For example, aluminum and gallium dimeric complexes of
L
(
formula [Me
insertions of
2
M(
l
-OCH(Me)CO
2
Et)]
2
(M = Al, Ga) mediated the
R bond to
L-LA monomers into the M–OCH(Me)CO
2
L
L
1
5
generate the PLA. This led us to investigate the possibility of LA
ring-opening by magnesium alkyl lactate [(Mg(elac) (3), and
2 2
]
3
3
we have used 3 generated in situ as a catalyst (Scheme 3).
[
3
Figure 1. 1H NMR (benzene-d
signals, recorded at various time intervals; residual solvent. Initial conditions:
, 293 K, 500 MHz) spectra, showing methine proton
6
⁄
Figure 3. ESI-MS spectrum recorded after 1 min. Initial conditions: room temper-
room temperature, CH
2
Cl
2
, [1]/[
L
-LA]/[MeOH] = 1:50:200.
ature, [3]/[L-LA]/[elacH] = 1:50:200.

5
288
D. Bykowski et al. / Tetrahedron Letters 55 (2014) 5286–5289
Table 2
Summary of the alcoholysis of L-LA using [Mg(elac)
2
]
2
(3) as catalyst
Entry
Time
%
L
-LA
% elacH
% e(lac)
2
H
3
% e(lac) H
1
2
3
4
1 min
5 min
2 h
0
0
0
0
77
73
68
51
4
19
13
13
12
14
19
37
22 h
L-LA =
L-lactide, elacH = ethyl lactate, e(lac)
2
H = ethyl lactyllactate, e(lac)
3
H = ethyl
lactolyllactoyllactate, reaction conditions: rt, CH
2
Cl , 3/[ -LA]/[elacH] = 1:50:200.
2
L
Figure 4. 1H NMR (benzene-d
signals recorded after 2 h. Initial conditions: room temperature, [MgBu
elacH] = 1:200.
, 293 K, 500 MHz) spectrum, showing the proton
]/
6
2
[
Scheme 4. Self-alcoholysis process of elacH.
Furthermore, when mlacH was used instead of elacH, the reac-
tion course and reaction products were similar. In a blank test per-
1
7
Attempts to isolate single crystals of 3 from toluene and CH
2
Cl
2
formed without catalyst 3, no reaction was observed.
Based on the reaction products and the 1H NMR and EIS-MS
results, it is proposed that the courses of the reactions with 1–3
are shown in Scheme 5. In the first step, LA reacts at the metal site
solutions were unsuccessful. We speculate that, by analogy with
the complexes of aluminum and gallium, 3 is also a dimer. With
suitable reaction parameters in hand, we used 3 generated
in situ in CH
2
Cl
The H NMR spectrum recorded after 1 min showed the disappear-
ance of all the -LA, e(lac) H, and e(lac) H signals, and traces of low
molecular weight oligomers, e(lac) H (Fig. 2). The formation of
e(lac) H was confirmed using ESI-MS (Fig. 3).
The appearance in the reaction product of e(lac)
2
at molar ratios of [3]/[
L
-LA]/[elacH] = 1:50:200.
with ROH and alacH, giving the ring-opened product a(lac) H (A)
2
1
or a(lac) H (B), exclusively. This product remains intact as long
3
L
3
2
as L-LA is present in the reaction mixture. After L-LA is completely
consumed, the dimer or trimer reacts with ROH, giving the final
product, alkyl (S)-lactate.
In summary, we have described an easily scalable system for
the efficient transformation of L-LA into valuable green chemicals
n
n
2
H besides
H was unexpected (Fig. 2 and Table 2). We assume that
H is formed during self-alcoholysis of elacH, according to
e(lac)
e(lac)
3
2
for use in cosmetics, food additives, solvents, and the production
of new materials. The reaction proceeds by ring-opening alcoholy-
sis, mediated by cheap and highly active magnesium alkoxides
formed in situ, without any bulky ligands. The mild reaction condi-
tions should make this methodology applicable in the production
of green solvents that could replace present examples, thereby
Scheme 4. Lactic esters are bifunctional, containing both hydroxyl
and ester groups within the same molecule. Alcoholysis results
from the interaction between these two functional groups. This
process is reversible and attains an equilibrium that is displaced
by the removal of alcohol from the reaction mixture.
7
1
To prove this, we used 3 generated in situ directly in the reac-
reducing industrial reliance on petrochemical feedstocks. Further-
tion of MgBu
2
with elacH at a molar ratio of 3/[elacH] = 1:200. As
more, the ability to produce higher order lactates simply from
L-LA
1
expected, the H NMR spectrum in benzene-d
tets (4.27, 5.04 ppm) and two doublets (1.21, 1.46 ppm), due to
the methane and methylene protons of e(lac) H (Fig. 4).
6
showed two quar-
and alkyl lactide esters is significant, as these molecules are tradi-
1
8
tionally difficult to synthesize.
2
Acknowledgments
We gratefully acknowledge the support by the Wroclaw
Research Centre EIT+ under the project ‘Biotechnologies and
advanced medical technologies’—BioMed (POIG.01.01.02-02-003/
0
8) financed from the European Regional Development Fund
(
Operational Programme Innovative Economy, 1.1.2).
Supplementary data
Supplementary data (general materials and experimental pro-
cedures, NMR and MS characterization data of important products)
associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.tetlet.2014.07.103.
References and notes
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