1,2,3-Trimethoxypropane and glycerol ethers as bio-sourced solvents from glycerol: Synthesis by solvent-free phase-transfer catalysis and utilization as an alternative solvent in chemical transformations

Article abstract of DOI:10.1002/cctc.201300458

1,2,3-Trimethoxypropane (2), 1-alkoxy-2,3-dimethoxy-propanes, and 1-aryloxy-2,3-dimethoxypropanes were prepared in good yields and selectivity by solid-liquid phase-transfer catalysis in the presence of an inorganic base and an ammonium salt as the phase-transfer catalyst with no additional solvent. No heating was required, and the synthesis was easily performed under atmospheric pressure on a 150g scale. For the preparation of 2, the conversion of glycerol was complete and the selectivity for the expected glycerol trimethylether was above 95%. This product was utilized as a solvent in organic reactions such as transesterifications between glycerol and vegetable oil, organometallic reactions (Grignard- and Barbier-type reactions), carbon-carbon coupling reactions (Suzuki, Sonogashira, Heck), and in etherification reactions by dehydrogenative alkylation. The solvent showed interesting properties for the solubilization of polymers.

Full text of DOI:10.1002/cctc.201300458

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Bio-sourced sorcery: 1,2,3-Trimethoxy-
propane (1,2,3-TMP) was prepared in
one step from glycerol in good yield
and selectivity by phase-transfer cataly-
sis. No solvent or heating were required
and the process was adapted to a series
of glycerol monoethers to afford
a family of polar aprotic, glycerol-based
solvents. 1,2,3-TMP was evaluated as
a solvent in transesterifications, organo-
metallic, and carbon–carbon coupling
reactions.
M. Sutter, W. Dayoub, E. Mꢀtay, Y. Raoul,
M. Lemaire*
&& – &&
1,2,3-Trimethoxypropane and Glycerol
Ethers as Bio-Sourced Solvents from
Glycerol. Synthesis by Solvent-Free
Phase-Transfer Catalysis and
Utilization as an Alternative Solvent in
Chemical Transformations
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DOI: 10.1002/cctc.201300458
1,2,3-Trimethoxypropane and Glycerol Ethers as Bio-
Sourced Solvents from Glycerol. Synthesis by Solvent-Free
Phase-Transfer Catalysis and Utilization as an Alternative
Solvent in Chemical Transformations
Marc Sutter,[a] Wissam Dayoub,[a] Estelle Mꢁtay,[a] Yann Raoul,[b] and Marc Lemaire*[a]
1,2,3-Trimethoxypropane (2), 1-alkoxy-2,3-dimethoxy-propanes,
and 1-aryloxy-2,3-dimethoxypropanes were prepared in good
yields and selectivity by solid–liquid phase-transfer catalysis in
the presence of an inorganic base and an ammonium salt as
the phase-transfer catalyst with no additional solvent. No heat-
ing was required, and the synthesis was easily performed
under atmospheric pressure on a 150 g scale. For the prepara-
tion of 2, the conversion of glycerol was complete and the se-
lectivity for the expected glycerol trimethylether was above
95%. This product was utilized as a solvent in organic reac-
tions such as transesterifications between glycerol and vegeta-
ble oil, organometallic reactions (Grignard- and Barbier-type re-
actions), carbon–carbon coupling reactions (Suzuki, Sonoga-
shira, Heck), and in etherification reactions by dehydrogenative
alkylation. The solvent showed interesting properties for the
solubilization of polymers.
Introduction
Solvents are fundamental molecules used in numerous indus-
trial and academic processes as reaction media or as efficient
dissolving, diluting, and extracting agents. These chemical sub-
stances are employed in various applications that range from
coatings, inks, adhesives, paints, cleaning agent, pharmaceuti-
cal, and polymer synthesis because of their properties.[1] Their
increasing demand makes the world market grow by close to
20 million tons every year.[2] However, solvents have a negative
contribution to the environmental impact of chemical reac-
tions and manufacturing processes.[3]
ed in the last two decades. For example, solvent-free meth-
ods,[4e,5] ionic liquids,[6] supercritical fluids,[7] alternative ethers
such as cyclopentyl methyl ether,[8] and water[9] have been ex-
tensively studied, but several drawbacks and limitations were
found, which prevented their development on a larger scale in
many cases.
Based on green chemistry principles,[10] another way to
obtain “green” solvents is to synthesize organic molecules
from renewable resources that have a benign environmental
impact.[1–4,11] In this group, several compounds show interest-
ing physicochemical properties such as 2-methyltetrahydrofur-
an (2-MeTHF),[12] ethyl lactate,[13] lactic acid,[14] g-valerolac-
tone,[15] aqueous solutions of carbohydrates,[16] alcohols,[17] and
many others.[1–4,11,18]
Until now, the most commonly used solvents (aliphatic, aro-
matic, and halogenated hydrocarbons, alcohols, glycol ethers,
etc.) were obtained from nonrenewable feedstock. Despite
their positive effects in chemical transformations in terms of
conversion, yield, and selectivity, growing concerns over at-
mospheric pollution by volatile organic compounds, as well as
water and land pollution had led to the need for alternative
solvent systems.[1,4] Moreover, regulations that limit their use
have been adopted because of well-known health con-
cerns.[4c–e] Thus, more sustainable solutions have been evaluat-
In addition, these alternatives should be advantageous from
an economic point of view, with an easy access to the starting
material and reduced preparation, recycling, and disposal
costs. Thus, with its very attractive price and availability, glycer-
ol is an excellent candidate as substrate for the synthesis of
new solvents, and more than 2 million tons of this co-product
of the vegetable oil industry is produced every year.[19] To con-
sume the large surplus of glycerol, new large-scale applications
are reported in many research areas, which use glycerol itself
or as a building block for the preparation of high value-added
products.[20] Glycerol has been employed as a green solvent in
a variety of transformations and processes,[21] but for many ap-
plications, as well as chemical reactions, the use of polar aprot-
ic solvents with different physicochemical properties is very
useful and sometimes necessary.[4a,b]
[a] M. Sutter, Dr. W. Dayoub, Dr. E. Mꢀtay, Prof. M. Lemaire
Laboratoire de Catalyse, Synthꢁse et Environnement (CASYEN)
Groupe Lemaire, Institut de Chimie et Biochimie Molꢀculaires et
Supramolꢀculaires (ICBMS), CNRS. UMR5246
Universitꢀ Lyon 1, Bꢂtiment Curien-CPE, 38 ꢀtage
43 Bd du 11 Novembre 1918, 69622, Villeurbanne Cedex (France)
Fax: (+33)472431408
E-mail: marc.lemaire.chimie@univ-lyon1.fr
[b] Dr. Y. Raoul
Sofiprotꢀol
For these reasons, the preparation of glycerol ethers may
present a great interest. The etherification of glycerol to alkyl
glycerol ethers has been achieved by the Williamson ether syn-
11, rue de Monceau, CS 60003, 75378 Paris Cedex 08 (France)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201300458.
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thesis in basic media,[22] and also by catalytic telomerization
with butadiene derivatives.[23] An acid-catalyzed route with al-
cohols[24] and alkenes[25] was also reported, but limitations were
observed with these pathways.
glycerol or glycerol monoethers (GMEs) that could be adapted
on a larger scale with only small modifications of the proce-
dure. Then, the efficiency of 2 was evaluated in several chemi-
cal reactions as new bio-sourced solvent.
In search of new eco-efficient routes and inspired by pio-
neering work realized in our lab[26] and by others,[27] we recent-
ly developed the heterogeneously catalyzed reductive alkyla-
tion of glycerol with aldehydes and carboxylic acids and a two-
step procedure from methyl esters and vegetable oil.[28] We
have also reported a solvent-free preparation of aryl glycerol
ethers by the dehydrogenative arylation of glycerol with cyclo-
hexanone derivatives.[29] These two pathways give easy and
safe access to alkyl- and aryl glycerol ethers in good yields.
Based on our experience in the preparation of glycerol
ethers and taking into account the study of Garcꢂa and co-
workers,[22] which concerns the physicochemical properties of
these products, we thought that 1,2,3-trimethoxypropane (2)
and its derivatives may be good candidates as new aprotic
polar solvents in a broad range of applications. Thus, 2 can po-
tentially substitute traditional problematic solvents as glymes,
known for their serious health concerns.[4c] In fact, 2 presents
the same molecular formula as diglyme (C6H14O3), which is still
used for the preparation of active pharmaceutical ingredients.
Only a few reports describe the synthesis of 2,[22,30] but un-
fortunately low yields and selectivity for the trimethylated
product were observed.[30]
Results and Discussion
Synthesis of 1,2,3-trimethoxypropane (2)
Several strategies were presented for the preparation of 2. Our
priority was to develop synthetic conditions that were as
simple as possible and would ensure the highest yield of the
desired molecule.
Based on the conditions developed previously,[28] the reduc-
tive alkylation of glycerol (1) with formaldehyde (>35 wt% in
aqueous solution) and paraformaldehyde catalyzed by palladi-
um on carbon and Amberlyst 35 as acid cocatalyst (10 wt%)
under H2 pressure without additional solvent was performed.
Even after changing the molar ratio of the substrates, the
amount of heterogeneous Pd/C catalyst (1–5 mol%), and the
H2 pressure (10–30 bar) and temperature (100–1508C), no 2
was observed. In fact, a mixture of 1,3-dioxolane-4-methanol
and 1,3-dioxan-5-ol was obtained as major products, and only
traces of GME and glycerol dimethyl ethers were observed
(Scheme 2, path a).
Thus, the synthetic route for the preparation of 2 was modi-
fied by using a methylation agent. The main advantage of this
pathway is the possibility to perform the reaction in a conven-
tional tank reactor under normal atmospheric pressure, which
avoids the constraints of an autoclave. Dimethyl carbonate
(DMC) was first evaluated in several methylation experiments
because of its reported low toxicity,[31] despite its lower reactiv-
ity than dimethyl sulfate (DMS) and methyl iodide (MeI).[31c] If
the methylation of phenol derivatives with DMC was stud-
ied,[31c,32] the reaction with alcohols at high temperature (>
2008C) gave only a few positive results.[33] Indeed, transesterifi-
cation products were obtained in most of cases,[31,34] especially
if 1 was used as the starting material.[35] With basic (K2CO3,
KOH, 1,8-diazabicyclo[5.4.0]undec-7-ene) or acidic (camphorsul-
fonic acid, Amberlyst 35) catalysts, the best yield for 2 was
never more than 2%, regardless of the experimental conditions
tested (concentration, temperature, reaction time). The addi-
tion of a phase-transfer catalyst (tetrabutylammonium hydro-
gensulfate, nBu4NHSO4, TBAHS) did not improve the yield of
the desired product, and glycerol carbonates were observed as
major products of the reaction (Scheme 2, path b).
In this paper, we report the synthesis of 2 and 1-alkoxy- and
1-aryloxy-2,3-dimethoxypropanes 6 in one step without addi-
tional solvent by phase-transfer catalysis (Scheme 1). Our ob-
jective was to develop an efficient and direct etherification of
Scheme 1. Strategies for the synthesis of 1,2,3-TMP 2 in one step from
1 and 1-alkoxy- and 1-aryloxy-2,3-dimethoxypropanes 6 from GMEs 5
developed in this work.
Scheme 2. Methylation of 1 by a) reductive alkylation and b) with dimethyl carbonate as methylation agent.
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Synthesis of 2 by phase-transfer catalysis
1 is reduced. If water is replaced by toluene, the yield of 2 in-
creased to 66% (entry 2). With pentane, the expected product
was obtained in 67% yield, but the selectivity decreased slight-
ly to 68% (entry 3). With 2-MeTHF and tetrahydrofuran (THF),
the yield for 2 increased to 71 and 79%, respectively (entries 4
and 5, GC analysis of the reaction in THF is shown in the Sup-
porting Information). This can be explained by a better solubili-
ty of both the substrates and products in these more polar sol-
vents, which reduces mass-transfer problems. Finally, the best
result was obtained in the solvent-free etherification of 1 with
DMS (entry 6). After 24 h, the conversion of 1 was complete
and 2 was obtained in 95% yield and 96% selectivity. As
shown in the GC chromatogram of the crude product
(Figure 1), the only detected byproducts were the dimethylat-
ed products 3a and 3b. An explanation of this good result
could be the reaction under
In view of these results, and despite its toxicity, DMS was em-
ployed as the methylation agent in the presence of a base
(KOH) because of its better availability in industry than MeI, as
well as its better atom economy if both methyl groups are in-
corporated on 1.[31c] As the use of DMS was necessary, our goal
was to perform the reaction under mild conditions to limit its
negative impact. In addition, we thought that a synthesis by
phase-transfer catalysis,[36] which is widespread in industrial ap-
plications and organic reactions,[36,37] can be used in the trime-
thylation reaction of 1. Thus, it can be an effective method to
obtain 2 in good yield and selectivity in a multiphasic system.
In our study, the quaternary ammonium salt TBAHS was used
as cheap phase-transfer catalyst (Scheme 3).
phase-transfer
catalysis
in
a liquid–solid system: the sub-
strates were not diluted in a sol-
vent, which improved the reac-
tion rate, as well as the contact
between the phase-transfer cata-
lyst (TBAHS), the solid phase
Scheme 3. Synthesis of 2 from 1 by solid–liquid phase-transfer catalysis with all detected byproducts performed
under nonoptimized conditions.
Effect of an additional solvent
To obtain a liquid–liquid system (1–organic phase), our first at-
tempts were performed in the presence of solvents. Several
solvents were tested in the reaction of 1 with KOH (3.3 equiva-
lents) and DMS (2.5 equivalents) at room temperature cata-
lyzed by nBu4NHSO4 (10 mol%). All experiments were per-
formed with a concentration of 1 in the solvent of 1.5m.
If the reaction was performed with water to dissolve the
KOH in the medium, the selectivity for 2 after 24 h was only
25% (Table 1, entry 1). Under these conditions, the methylation
reaction also gave three glycerol ether intermediates as by-
products: 1,3-dimethoxypropan-2-ol (3a) was obtained in 18%
yield, 2,3-dimethoxypropan-1-ol (3b) in 21% yield, and 3-me-
thoxypropan-1,2-diol (4) was detected in 36% yield. As already
observed in the literature,[30] this result is explained by the side
reaction of water with DMS to form methanol as a byproduct.
Figure 1. GC chromatogram of the solvent-free methylation reaction of 1 by
phase-transfer catalysis (table 1, entry 6). Conditions: 1 (1 equiv.), KOH
(3.3 equiv.), TBAHS (10 mol%), DMS (2.5 equiv), room temperature, 24 h.
Consequently, the availability of DMS for the methylation of
Table 1. Influence of the solvent on the methylation reaction of 1 by
(KOH), and the liquid phase (1 and DMS). In addition, it is also
possible that traces of water in the phase that contained 1 and
that formed during the reaction facilitate the dissolution of the
KOH pellets without impacting the selectivity for 2.
phase-transfer catalysis.[a]
Entry
Solvent
Conversion
of 1 [%][b]
Yield [%][b]
Selectivity
2
3a
3b
4
to 2 [%]
1
2
3
4
5
6
water
toluene
pentane
2-MeTHF
THF
99
95
99
95
99
99
25
66
67
71
79
95
18
9
12
8
6
3
21
8
10
10
6
36
25
70
68
75
80
96
12
10
6
8
<1
Influence of the experimental parameters
Once the solvent-free phase-transfer catalysis was found to be
efficient for the synthesis of 2, the influence of the other ex-
perimental parameters was studied (Table 2). By changing the
methylation agent to MeI in the same liquid–solid conditions,
the conversion of 1 was complete after 24 h, but the yield for
2 decreased to 72% (entry 1).
–
2
[a] Experimental conditions:
1 (1 equiv.), KOH (3.3 equiv.), TBAHS
(10 mol%), solvent (1.5m), DMS (2.5 equiv.), room temperature, 24 h.
[b] Conversions and yields were determined by GC, GC–MS, and 1H NMR
spectroscopy.
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the product from the salts. Thus
by using a Soxhlet apparatus to
extract the remaining 2 from the
Table 2. Influence of the nature, the amount of reagents, and the phase-transfer catalyst on the reaction.[a]
Entry
KOH
Methyl source
[equiv.]
(nBu)4NHSO4
Conversion
of 1 [%][b]
Yield [%][b]
Selectivity
[equiv.]
[mol%]
2
3a
3b
4
to 2 [%]
salts, the isolated yield of
2
could be improved to 79% after
distillation. In addition, induc-
tively coupled plasma mass
spectrometry (ICP-MS) showed
that no traces of DMS were pres-
ent in the pure product.
1
2
3
4
5
6
7
3.3
3.5
3.3
3.3
3.3
3.3
3.3
3.3
3
MeI (4)
10
20
10
5
99
99
99
92
65
99
99
99
89
72
94
95
53
33
96
91
95
69
16
3
3
15
9
2
4
2
10
11
2
2
12
9
2
4
2
8
1
73
96
96
58
50
96
92
DMS (2.7)
DMS (2.5)
DMS (2.5)
DMS (2.5)
DMS (2.2)
DMS (1.7)
DMS (1.7)
DMS (1.5)
<1
<1
14
14
<1
1
–
10
10
10
10
8[c]
9
1
2
96 (79)[d]
78
Mechanistic considerations
[a] Experimental conditions: 1 (1 equiv.), KOH (3.3 equiv.), TBAHS, methylation agent, room temperature, 24 h.
[b] Conversions and yields were determined by GC, GC–MS, and H NMR spectroscopy. [c] Reaction time=36 h.
1
Mechanisms that occur in phase-
transfer catalysis have been
studied extensively over the last
few decades in liquid–liquid sys-
[d] Isolated yield in parentheses.
Then, to study the influence of the amount of TBAHS on the
methylation reaction of 1, experiments were performed with
20, 10, and 5 mol% and without phase-transfer catalysis. Com-
pound 1 was completely converted if TBAHS was added in
amounts above 10 mol% with an excellent selectivity for 2 (en-
tries 2 and 3). With a further decrease of the quantity of TBAHS
to 5 mol%, the conversion dropped to 92% and the yield of 2
fell to 53% (entry 4). If the reaction was performed without
phase-transfer catalysis, a moderate conversion of 1 was ob-
served (65%), and the yield for 2 decreased to 33% (entry 5).
In this last experiment, the reaction occurred because of the
traces of water present in 1, which could dissolve a small
amount of KOH. On the basis of these results, 10 mol% of
TBAHS was chosen as the optimized amount of phase-transfer
catalyst.
tems but few reports describe the mechanisms possible in
a solid–liquid system.[36] Based on our observations, a two-
phase solid–liquid system was considered: an anhydrous KOH
solid phase and a liquid phase that includes 1 and DMS
(Scheme 4). The key step of this transformation is the genera-
tion of quaternary ammonium hydroxide II by ion exchange at
the solid surface between TBAHS Ia and the solid nucleophilic
KOH. This reaction generates a new solid phase KHSO4. Next,
ion pair II, which becomes soluble in the liquid phase and
makes the hydroxide anion highly nucleophilic, reacts with
1 to form a reactive quaternary ammonium alkoxide III, which
undergoes a reaction with DMS to form 4 and ion pair Ib. In
a new cycle, K2SO4 is formed by reaction of Ib with KOH and
a second hydroxyl is methylated to form 3a or 3b. Finally, in
a last catalytic cycle, 2 is obtained. Water is generated during
the reaction and as already mentioned, DMS can react with
H2O to afford sulfuric acid and methanol. As reported,[36d] other
mechanisms can be retained for this reaction, such as a homo-
geneous solubilization in the liquid phase of a very low
amount of KOH, followed by the ion exchange of TBAHS with
the dissolved solid. In this case, the catalyst does not interact
with the solid surface but with the hydroxide anion dissolved
in the liquid phase, and the presence of traces of water can
help the dissolution of KOH. Inspired by an interfacial mecha-
nism in a liquid–liquid system, the adsorption of 1 on the solid
surface can also be considered, as reported by Makosza.[36f]
Compound 1 can be deprotonated on the KOH surface to
form an alkoxide ion that reacts with TBAHS to form species III
soluble in the liquid phase, in which the methylation of 4
occurs.
Theoretically, if one molar equivalent of 1 is added into the
reactor, only three molar equivalents of KOH and 1.5 molar
equivalents of DMS are necessary to convert all the substrate
to 2. Therefore, the effect of the amounts of KOH and DMS
was evaluated. By decreasing the molar equivalent of DMS
from 2.5 to 2.2, the conversion of 1 and the yield for 2 re-
mained unchanged (entry 6). With 1.7 equivalents of DMS,
a slight decrease of the 2 yield to 91% was observed at a reac-
tion time of 24 h (entry 7). Nevertheless, with a longer reaction
time of 36 h under the same conditions, the yield of the de-
sired trimethylated glycerol ether reached 95% (entry 8). Final-
ly, with three molar equivalents of KOH and 1.5 molar equiva-
lents of DMS, the conversion of 1 decreased to 89%, and the
yield for 2 dropped to 69% (entry 9). Thus, a slight excess of
KOH and DMS was necessary, which is because of the con-
sumption of DMS by the water present in 1 and/or that
formed during the methylation reaction. Based on these con-
siderations, 3.3 molar equivalents of KOH and 1.7 molar equiva-
lents of DMS were chosen to start the reaction. To produce
larger quantities of 2, the reaction was scaled-up in a 2 L
double-walled glass reactor equipped with a mechanical stirrer.
No decrease of product yield was noticed at 1.5–1.6 mol scale.
Finally, the isolated yield for 2 after filtration of the salts with
pentane, concentration, and distillation was reduced to 57%
because of the volatility of 2 and the difficulty to extract all
Dimethylation of glycerol ethers
With the optimized conditions for the preparation of 2 by
phase-transfer catalysis in hand and based on our experience
in the synthesis of GMEs,[28,29] we were interested to prepare
a variety a glycerol triethers. Therefore, we envisaged two
simple procedures to give a new, easy, and eco-efficient access
to polar aprotic solvents from 1 (Scheme 5). First, by reductive
alkylation of carboxylic acids 7 with 1 without solvent and cat-
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simplicity of these proposed syn-
thetic routes should be feasible
at larger scales with relatively
small modifications.
Thus, using these synthetic
strategies, various glycerol trieth-
ers were prepared in good yields
by solvent-free phase-transfer
catalysis (Table 3). The amounts
of KOH (2.3 molar equivalents)
and DMS (1.3 molar equivalents)
were adapted, and for solid sub-
strates such as aryl ethers 5h
and 5i additional solvent (THF)
was necessary. From 1-O-buty-
loxyglycerol ether 5a, the de-
sired 1-(2,3-dimethoxypropoxy)-
butane 6a was isolated in 72%
yield with an overall yield of
54% for the two steps (reductive
alkylation and methylation reac-
tion, entry 1). If the methylation
reaction was performed with
GMEs that bear longer alkyl
chains such as pentyl, hexyl, and
octyl moieties, the correspond-
ing glycerol triethers 6b, 6c, and
6d were isolated in 75, 78, and
72% yield, respectively (en-
tries 2–4). The overall yield of
the two steps was above 55%
for 6b and 6c but decreased to
43% for 6d as the reductive al-
kylation afforded GME 5d in
a lower isolated yield of 60%,
presumably because of an in-
crease of the octanoic acid hy-
drophobicity, which made its re-
ductive alkylation with 1 more
difficult, as explained in our pre-
vious report.[28c] If the reaction
was performed with branched
GMEs 5e and 5 f, the isolated
yields of triethers 6e and 6 f
were 77 and 74%, respectively
(entries 5 and 6). With a cyclic
substrate 5g, the phase-transfer
Scheme 4. Postulated mechanism for the preparation of 2 by phase-transfer catalysis in a solid–liquid system
(KOH pellets–1).
Scheme 5. Envisaged strategies for the synthesis of 1-alkoxy- and 1-aryloxy-2,3-dimethoxypropanes. Conditions:
i) carboxylic acid/1 1:40, 1 mol% Pd/C, 10 wt% Amberlyst 35, 50 bar H2, 1208C, 16 h. ii) Monoglycerol ether 5
(1 equiv.), KOH (2.3 equiv.), (nBu)4NHSO4 (10 mol%), DMS (1.3 equiv.), room temperature, 24 h. iii) Cyclohexanone
8h/1 1:20, Pd/C (5%, 2 mol%), 1308C, open reactor (air), 60 h or a-tetralone 8i/1 1:5, Pd/C (5%, 1 mol%), 1508C,
sealed tube (argon), 16 h.
alyzed by a recyclable heterogeneous catalytic system (Pd/C
and Amberlyst 35), 1-O-alkylglycerol monoethers can be ob-
tained in good yields and selectivity without the formation of
unwanted inorganic salts. Alternatively, starting from cyclohex-
anone derivatives 8, 1-O-arylglycerol monoethers can be pre-
pared by the solvent-free, heterogeneous Pd/C-catalyzed dehy-
drogenative alkylation of 1. The Pd/C catalyst can also be recy-
cled in these methodologies.
catalysis gave the expected triether 6g in 79% isolated yield
(entry 7). Finally, two reactions were conducted with aryl glyc-
erol ethers 5h and 5i obtained by the dehydrogenative alkyla-
tion of 1 with cyclohexanone 8h and b-tetralone 8i. The dime-
thylation afforded products 6h and 6i in very good isolated
yields of 88 and 93% with good overall yields for the two
steps of 59 and 67%, respectively (entries 8 and 9). To the best
of our knowledge, no experimental data on the physicochemi-
cal properties of these new glycerol triethers is available, thus
the evaluation of these properties is underway.
Once the GMEs were prepared by these two procedures, the
dimethylation was performed by phase-transfer catalysis. The
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which would allow reactions to be performed at
higher temperatures, another main advantage of 2
was the possibility to remove it from the medium by
evaporation under reduced pressure, thus simplifying
the purification of the products and the recovery of
the solvent.
Table 3. Methylation of various glycerol ethers by phase-transfer catalysis.[a]
Entry Substrate (5)
Product (6)
Yield [%][b]
72 (54)
1
2
3
5a
5b
5c
5d
6a
6b
6c
6d
Transesterification of 1 with methyl stearate and
vegetable oil
75 (56)
Monoglycerides find applications in several fields as
surfactants. However, one major issue in their prepa-
ration by transesterification is the poor solubility of
1 in the methyl stearate (9) or triolein (10) phase.
Thus, the selectivity of the transesterification reaction
for the desired monoglyceride is often low, and sev-
eral reports propose new basic catalysts that improve
both the yield and selectivity of the reaction.[20d,38]
We thought that 2 could be a good solvent for this
transformation by mixing both substrates efficiently
in a homogeneous medium. The transesterification
reactions were catalyzed by a supported BaO/Al2O3
catalyst (10 wt%), which we found to be efficient in
a previous study (Scheme 6).[28d]
78 (57)
4
5
72 (43)
77 (58)
5e
6e
6
7
5 f
6 f
74 (45)
79 (60)
5g
6g
8[c]
5h
5i
6h
6i
88 (59)
93 (67)
Experiments were performed with a concentration
of 9 or 10 in 2 of 0.5m by using 1 or diglycerol as
substrates. To evaluate the solvent effect, experi-
ments with 2 were compared with solvent-free reac-
9[c]
[a] Experimental conditions: Monoglycerol ether
5 (1 equiv.), KOH (2.3 equiv.),
(nBu)4NHSO4 (10 mol%), DMS (1.3 equiv.), room temperature, 24 h. [b] Isolated yield;
overall yield of the two steps in parentheses. [c] Reaction performed in THF (2m).
tions (Table 4). The transesterification of
9 with
1 under solvent-free conditions at 2008C in a sealed
Valorization of 1,2,3-TMP in chemical transforma-
tions
In organic synthesis, especially for the production of
fine chemicals, in the pharmaceutical industry, or on
a laboratory scale, among classic petroleum-based
solvents such as THF and toluene, polar aprotic sol-
vents are often necessary to perform syntheses. Such
solvents show excellent properties for many chemical
transformations by solubilizing organic compounds
and salts but they also present environmental prob-
lems (difficulty to remove from the medium, toxicity).
N,N-Dimethylformamide (DMF), dimethylacetamide
(DMA), dimethylsulfoxide (DMSO), N-methyl-2-pyrroli-
Scheme 6. Transesterification of a) methyl stearate 9 with (di)glycerol and b) of high oleic
sunflower refined oil 10 with 1 in 2.
done (NMP), hexamethylphosphoramide (HMPA), and
glymes are relevant examples.[4a,b,c] To date, good al-
ternatives have not been found for this group of sol-
vents.[4d]
Thus, we were interested to test 2 in several chemical trans-
formations as a new and alternative bio-sourced solvent. Most
of the following examples were not optimized as far as possi-
ble: reactions were mostly performed based on conditions re-
ported previously. Our priority was to demonstrate that 2 can
be a good and suitable alternative to classic organic solvents.
In addition to its high boiling point (1438C at 760 mmHg),[30]
reactor afforded the corresponding glyceryl stearate 11 a in
54% isolated yield after 16 h (entry 1). Under these conditions,
the conversion of the starting methyl ester was 94% and 40%
of unwanted diglyceride was also obtained. If the reaction was
performed in 2, the conversion was complete after 16 h and
monoglyceride 11 a could be isolated in an improved yield of
78% (entry 2). If the reaction was performed with diglycerol,
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Carbon–carbon coupling reactions: Suzuki,
Sonogashira, and Heck reactions
Table 4. Transesterification tests of (di)glycerol with 9 and 10 in 2.[a]
Entry Polyol
Substrate Co-solvent Conversion
Yields [%][b]
(0.5m)
[%]
a-Mono-ester 11 Diesters
Coupling reactions such as Heck, Stille, Suzuki, and
Sonogashira reactions are a subject of intensive work
because of their efficiency and the versatility of prod-
ucts that can be prepared.[40] These transformations
were also studied in different media such as water,
ionic liquids, supercritical fluids, and alternative sol-
vents.[41] Three metal-catalyzed cross-coupling reac-
tions were performed in 2. First, the Suzuki coupling
was tested: the reaction of 4-bromoanisole (15) with
phenylboronic acid was performed with tetrakis(tri-
1
2
3
4
5
6
7
8
1
1
9
9
9
9
10
10
–
2
–
2
–
2
–
2
94
>99
96
>99
>99
>99
>99
>99
54
78
53
67
51
88
41
63
40
22
47
33
49
12
50
22
diglycerol
diglycerol
1
1
diglycerol 10
diglycerol 10
[a] Experimental conditions: molar ratio substrate/(di)glycerol of 1:20, BaO/Al2O3
(10 wt%), 2008C, 16 h. [b] Isolated yield.
53% of diglycerol stearate 11 b was isolated (entry 3),
whereas the reaction in glycerol trimethyl ether gave
11 b in 67% yield (entry 4). Then, we examined the
reactivity of oleic sunflower refined oil (ꢀ90% of trio-
lin 10) with 1. Under solvent-free conditions, the cor-
responding glyceryl oleate 11 c could be isolated in
51% yield (entry 5), and in the presence of 2 the
yield for product 11 c was improved to 88% (entry 6).
Finally, the reaction of oleic oil with diglycerol gave
the desired diglyceryl oleate 11 d in only 41% yield
without solvent (entry 7), whereas the yield reached
63% in 2 (entry 8). These results demonstrate that 2
can be advantageously employed for this type of re-
Scheme 7. a) Grignard-type reaction of 12 and isopropylmagnesium chloride in 2. Condi-
tions: 12 (2 mmol, 1.0m in 2), iPrMgCl (3 mmol, 2.0m in THF), at room temperature
under argon for 16 h. b) Barbier-type reaction of 12 and allyl bromide with magnesium
in 2. Conditions: 12 (4 mmol, 2.0m in 2), C3H6Br (8 mmol), Mg (8 mmol), at 608C under
argon for 3 h.
action. Indeed, the solvent solubilized both sub-
strates efficiently during the reaction.
Organometallic reactions: Grignard- and Barbier-
type
phenylphosphine)palladium as a robust catalyst and K2CO3 as
Since the discovery of the Barbier and Grignard reac-
the base at 1408C for 16 h (Scheme 8). Without optimization
of the experimental conditions, the conversion of the starting
material was approximately 80%, and the desired biaryl prod-
tions at the beginning of the 20th century,[39] organometallic
reactions have been extensively studied in organic chemistry
as a powerful tool for the formation of carbon–carbon bonds.
Grignard cross-couplings are typically performed in
THF or ethereal anhydrous solvents to ensure a good
solubility and stability of the Grignard reagent in the
reaction mixture. Thus, we tested 2 as an alternative
solvent in these reactions (Scheme 7).
The reaction of benzaldehyde (12) with isopropyl-
magnesium chloride (2m in THF) generally gives very
good results in anhydrous THF. Thus, we tested this
reaction in 2 at room temperature. After a reaction
time of 16 h, the desired product 13 was isolated in
75% yield (Scheme 7a). The Barbier-type reaction can
be performed either in organic solvents or in aque-
ous medium, depending on the nature of the sub-
Scheme 8. Suzuki coupling reaction of 15 with phenylboronic acid in 2. Conditions: 15
(1 mmol, 0.5m in 2), phenylboronic acid (1.5 mmol), [Pd(PPh3)4] (0.1 mmol), K2CO3
(1.5 mmol), at 1408C under argon for 16 h.
uct 16 was isolated in 63% yield. The Sonogashira coupling
strates and the metal. Therefore, this reaction was also evaluat-
ed in 2 using 12 and allyl bromide as substrates and magnesi-
um as the metal. After 3 h at 608C, the corresponding alcohol
14 was isolated in 70% yield (Scheme 7b). Unfortunately, we
were not able to prepare a Grignard reagent in 2.
was also performed in 2 by reacting 15 with phenylacetylene
using a combination of CuI and [Pd(PPh3)4] as catalysts. N,N-Dii-
sopropylethylamine (DIPEA) was used as a base for this reac-
tion. After 16 h at 708C, the desired product 17 was isolated in
76% yield (Scheme 9).
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the optimized conditions, but with 2 as the solvent,
the reaction of cyclohexanone with hexanol gave the
desired aryl ether 19 in a good 87% isolated yield
with the complete conversion of the starting material
(Scheme 11, GC analysis of the crude mixture is
shown in the Supporting Information). Even if the re-
action time is longer than under solvent-free condi-
tions (48 versus 24 h), performing a reaction in 2 can
be a good alternative if both substrates (alcohol and
cyclohexanone derivatives) are solid and/or expen-
sive.
Scheme 9. Sonogashira coupling reaction of 15 with phenylacetylene in 2. Conditions:
15 (1 mmol, 1m in 2), phenylacetylene (1.6 mmol), DIPEA (2 mmol), CuI (0.1 mmol),
[Pd(PPh3)4] (0.1 mmol), at 708C under argon for 16 h.
Finally, 2 was also used as solvent in a Heck coupling reac-
tion between 15 and styrene. DIPEA, palladium acetate, and
The use of 2 as a solvent for polymer solubilization
the cyclohexyl JohnPhos ligand were added to the medium,
and the reaction was performed at 1008C for 16 h. Under
these conditions, the expected product 18 was isolated in
75% yield (Scheme 10). In these three examples, 2 was suc-
cessfully used as a solvent in cross-coupling reactions. Even if
the experimental parameters can be further optimized, this
preliminary study gives encouraging results.
As pointed out by Jessop,[4a] solvents used as reaction media
in organic synthesis represent only a small portion of the total
volume consumed. In fact, solvents are extensively used in
other applications and industrial activities at larger scale.
Therefore, to decrease the environmental impact of solvents,
other applications have to be considered. For example, in the
field of synthetic polymers, produced at over 30 million tons
every year, solvents represent the largest amount of
waste.[6f] Polymer dissolution in solvents is very im-
portant for many industrial fields such as reaction
media, plastic recycling, and the production of mate-
rials and fine chemicals.[44] In this area, the utilization
of “green” solvents such as water, supercritical fluids,
and ionic liquids is a topic of great interest.[6f] There-
fore, 2 may be a bio-sourced alternative for the prep-
aration or recycling of polymers. More interestingly,
its particular properties may be useful for the synthe-
sis of new polymers.
Polymer dissolution tests in 2 were performed. For
this study, we used the following procedure: in
a sealed tube under an argon atmosphere, a defined
mass of polymer was added to 2 mL of glycerol tri-
methyl ether. The solution was heated for 16–48 h
Scheme 10. Heck coupling reaction of 15 with styrene in 2. Conditions: 15 (1 mmol,
0.5m in 2), styrene (2 mmol), DIPEA (2 mmol), Pd(OAc)2 (0.08 mmol), L (0.1 mmol) at
1008C under argon for 16 h.
Aryl ether synthesis by dehydrogenative alkylation
reaction
The formation of CÀO bonds is also a topic of great
interest in organic chemistry, especially for the prepa-
ration of arylethers. Highly efficient transition-metal-
catalyzed CÀO cross-coupling reactions have been re-
Scheme 11. Dehydrogenative alkylation reaction of cyclohexanone 8h with hexanol in 2.
Conditions: 8h (3 mmol, 2m in 2), hexanol (3.3 mmol), 1-octene (6 mmol), Pd/C
(0.03 mmol) at 1508C under argon for 48 h.
ported, such as the Ullmann synthesis or the Buch-
wald–Hartwig reaction.[40d,42] Recently, other routes
from nonaromatic substrates have been described.[43]
In this topic, we reported of the solvent-free dehy-
drogenative alkylation of readily available cyclohexanones with
various alcohols by heterogeneous catalysis.[29] The reaction is
catalyzed by a recyclable Pd/C catalyst, and an alkene is added
to the medium under anaerobic conditions. Moreover, no addi-
tional oxidant is required. As an excess of alcohol was necessa-
ry to perform the reaction under solvent-free conditions
(5 molar equivalents), we envisaged an experiment in 2 with
amounts of reagents very close to the stoichiometry. Under
with vigorous stirring. Next, 1 mL of the supernatant liquid was
taken at high temperature before evaporation. This procedure
gave us the saturation concentration of the polymer dissolved
in 2 at a defined temperature (Table 5).
Polyamides such as nylon 6, nylon 6,6, and nylon 11 showed
a poor solubility in 2 with saturation concentrations between
1 and 4 gLÀ1 (entries 1–3). These results are not surprising as
polyamides are known for their difficulty to be solubilized in
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However, to definitely describe 2 as good alterna-
tive solvent, two main aspects have to be resolved.
First, its toxicity should be very low. Unfortunately,
there is no experimental data on the toxicity of 2 at
the moment, even if the reported toxicities of other
glycerol ethers are generally low.[46] Therefore, we are
currently evaluating the toxicity of 2 according to the
http://www.oecd.org/ (OECD) guidelines, and indeed
the first results showed a very low toxicity for this
compound. For example, preliminary results for acute
oral toxicity gave a LD50 >2000 mgkgÀ1, which classi-
fies 2 as nontoxic for this test (OECD 423). Complete
results will be published as soon as possible. Second-
ly, despite our attempts to use bio-based or less
harmful methylation agents (dimethyl carbonate and
formaldehyde), the best results were obtained with
toxic DMS. Even if no solvent and a very low amount
of energy are necessary to prepare 2 by this pathway,
Table 5. Dissolution tests of polymers in 2.[a]
[b]
Entry Polymer
Mn Mw
T
t
Conc.[c]
[8C] [h] [gLÀ1
]
1
2
3
4
Nylon 6
Nylon 6,6
Nylon 11
cellulose
–
–
–
–
120 48
120 48
120 48
80 48
120 16
150 48
120 48
120 48
1.5
<1
4
2
57
40
27
<1
5
6
7
8
9[d]
10[d]
11
12
cellulose acetate
polyvinyl chloride
polyethylene
poly(acrylamide)
polystyrene
polycaprolactone
poly(ethylene terephtalate)
poly(bisphenol-A-carbonate) Mw ꢁ45000
Mn ꢁ30000
–
Mn ꢁ1700; Mw ꢁ4000
Mw ꢁ5000000
Mw ꢁ250000
120 16 >410
Mn ꢁ10000; Mw ꢁ14000 120 16
406
13
37
–
120 48
120 16
[a] 0.5 g of polymer in 2 mL of 2, 800 rpm. [b] Supplier specifications in styrene equiv-
alents. [c] Concentration of dissolved polymer. [d] 1 g of polymer in 2 mL of 2.
common solvents.[45] Cellulose was heated at a lower tempera-
ture (808C) to prevent any degradation of the polymer, and
2 gLÀ1 could be dissolved in 2 (entry 4). Cellulose acetate
could be dissolved at 57 gLÀ1 (entry 5). For polyolefins such as
polyvinylchloride (PVC) and polyethylene (PE), the dissolution
tests afforded positive results: 40 and 27 gLÀ1 of polymer was
dissolved, respectively (entries 6 and 7). Polyacrylamide was
not soluble in 2 (entry 8), but polystyrene was highly soluble
with a saturation concentration of above 410 gLÀ1 (entry 9). An
experiment with polycaprolactone also gave a good result
(406 gLÀ1, entry 10). Finally, the solubilities of poly(ethylene
terephtalate) and poly(bisphenol-A-carbonate) were 13 and
37 gLÀ1, respectively (entries 11 and 12).
we aim to find an alternative process for its preparation. Final-
ly, other chemical reactions are underway in 2 in the laboratory
to valorize this solvent as powerful substitute for existing
petrol-based conventional solvents, as well as to find particular
properties that can make it a solvent of choice in the future.
Experimental Section
General
All reagents, reactants, and catalysts were supplied by Acros,
Sigma–Aldrich, Alfa Aesar, and Strem and used as received without
further purification. Oleic sunflower refined oil (ꢀ90%) was provid-
ed by our industrial partner, and glycerol, 99%, Reagentplus was
purchased from Sigma–Aldrich. The BaO/Al2O3 catalyst was pre-
pared by an incipient-wetness impregnation method.[28d]
Conclusions
1H and 13C NMR spectra were recorded by using a Bruker DRX 300
or Bruker ALS 300 (1H 300 MHz, 13C 75 MHz) in CDCl3 (except when
mentioned) and chemical shifts are given in ppm. J values are
given in Hz. Abbreviations are defined as follows: br=broad sin-
glet, s=singlet, d=doublet, dd=doublet of doublets, t=triplet,
m=multiplet.
1,2,3-Trimethoxypropane (2) was prepared in good yield and
selectivity in one step from glycerol (1) by a solid–liquid
phase-transfer catalysis, with dimethyl sulfate (DMS) as the
methylation agent, potassium hydroxide (KOH) as the base,
and tetrabutylammonium hydrogensulfate (TBAHS) as the
phase-transfer catalyst. These conditions were also employed
for the synthesis of a family of 1-alkoxy- and 1-aryloxy-2,3-di-
methoxypropanes from 1. After the first reductive alkylation of
1 with a carboxylic acid or a dehydrogenative alkylation of
1 with cyclohexanone, a wide variety of polar aprotic, glycerol-
derived solvents can be obtained in only two steps.
IR spectra were recorded by using a Spectro Nicolet IS10 Smart ITR
with an Attenuated total reflectance (ATR) diamond.
The ESI HRMS mass spectra were recorded in positive-ion mode by
using a hybrid quadrupole time-of-flight mass spectrometer (Micro-
TOFQ-II, Bruker Daltonics, Bremen) with an electrospray ionization
(ESI) ion source. The flow of spray gas was at 0.6 bar and the capil-
lary voltage was 4.5 kV. The solutions were infused at 180 mLhÀ1 in
a mixture of solvents (methanol/dichloromethane/water 45:40:15).
The mass range of the analysis was m/z 50–1000 and the calibra-
tion was performed with sodium formate.
For the first time, 2 was evaluated as an alternative and bio-
sourced solvent for chemical transformations as transesterifica-
tions between 1 and methyl stearate or oleic oil, organometal-
lic reactions (Grignard- and Barbier-type), carbon–carbon cou-
pling reactions (Suzuki, Sonogashira, Heck) and etherification
by dehydrogenative alkylation. This preliminary study showed
encouraging results in this field, but one should bear in mind
that solvents are employed in many other applications. Thus, 2
also showed interesting properties in polymer dissolution
tests, and, essentially, this solvent may present particular prop-
erties that can be useful in other chemical transformations, ex-
isting processes or new applications.
GC–MS analyses were performed by using a Focus GC (Thermo
Electron Corporation, Bremen, Germany) equipped with a DB-5 MS
capillary column (30 m, 0.25 mm i.d., 0.25 mm film thickness) and
a DSQ mass spectrometer as a detector (Thermo Electron Corpora-
tion, Bremen, Germany). The carrier gas was helium at a flow rate
of 1 mLminÀ1. The column temperature was initially 708C for
2 min, then gradually increased to 3108C at 158CminÀ1, and finally
kept at 3108C for 10 min. The injector temperature was 2208C and
the transfer-line temperature was 2808C. For GC–MS detection, an
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electron ionization system was used with an electron energy of
70 eV, and the mass analyzer was a simple quadrupole.
1,3-Dimethoxypropan-2-ol [CAS 623-69-8] (3a)
Colorless liquid; 1H NMR: d=2.31 (br, 1H, OH), 3.38 (s, 6H, CH3),
3.39–3.52 (m, 4H, CH2), 3.92–3.98 ppm (m, 1H, CH); 13C NMR: d=
59.2 (CH3), 69.3 (CH), 73.9 ppm (CH2); IR (ATR): n˜max =3422, 2892,
2821, 1452, 1195, 1102 cmÀ1; GC–MS: RT=3.88 min, m/z (%)=102
(8) [MÀH2O]+, 88 (10), 75 (50), 71 (16), 59 (6), 45 (100); HRMS (ESI):
m/z calcd for C5H12NaO3: 143.0679 [M+Na]+; found: 143.0673.
GC analyses were performed by using a GC-2025 gas chromato-
graph (Shimadzu) equipped with a ZB-5-MS column (30.0 m,
0.25 mm i.d., 025 mm film thickness). The carrier gas was N2 at
a flow rate of 1.27 mLminÀ1. The column temperature was initially
408C for 4 min, then gradually increased to 2008C at 158CminÀ1
,
and finally kept at 2008C for 15 min. The injector temperature was
2508C, and for detection a flame ionization detector (FID) was
used (2808C).
2,3-Dimethoxypropan-1-ol [CAS 40453-77-8] (3b)
Colorless liquid; 1H NMR: d=2.09 (br, 1H, OH), 3.37 (s, 3H, CH3),
3.38–3.45 (m, 1H, CH), 3.46 (s, 3H, CH3), 3.48–3.53 (m, 2H, CH2),
3.59–3.78 ppm (m, 2H, CH2); 13C NMR: d=57.7 (CH3), 59.3 (CH3),
62.0 (CH2), 72.2 (CH2), 80.1 ppm (CH); IR (ATR): n˜max =3424, 2930,
2883, 2828, 1459, 1191, 1085, 1052 cmÀ1; GC–MS: RT=4.22 min, m/
z (%)=89 (60), 75 (72), 58 (96), 45 (100); HRMS (ESI): m/z calcd for
C5H12NaO3: 143.0679 [M+Na]+; found: 143.0672.
Preparation of 1,2,3-TMP by phase-transfer catalysis
In a 2 L double-walled glass reactor equipped with a cooling
system (water stream) and a mechanical anchor Teflon stirrer, glyc-
erol (139 g, 111 mL, 1.51 mol, 1 equiv.), KOH pellets 85% (142 g,
2.53 mol, 1.65 equiv.), and (nBu)4NHSO4 (5.28 g, 15.6 mmol,
10 mol%) were successively introduced in small portions with stir-
ring. The mixture was then stirred at RT for 30 min until the
medium became more homogeneous. After cooling the reactor to
158C by using a cold water stream, DMS (166 g, 125 mL, 1.30 mol,
0.85 equiv.) was slowly added dropwise to the reaction medium.
Next, the rest of the KOH was added slowly (142 g, 2.53 mol,
1.65 equiv.) before the remaining DMS was added dropwise (166 g,
125 mL, 1.30 mol, 0.85 equiv.). The basicity of the mixture was then
checked by pH measurement, and the medium was vigorously
stirred at RT for 24–36 h. Pentane was then added to the crude
mixture, and the salts (K2SO4) were removed by filtration and
washed several times with pentane. Next, the salts were extracted
in a Soxhlet extractor overnight with pentane as extraction solvent.
The solutions obtained after filtration and Soxhlet extraction were
concentrated and finally distilled under reduced pressure over
CaH2 to remove pentane at 358C/950 mbar, and to separate traces
of 3-methoxy-1,2-propanediol (4), 3a, and 3b. Finally, 2 was ob-
tained at 66–698C/90 mbar in 79% yield (161 g) as a colorless
liquid. Without Soxhlet extraction of the salts, 2 was isolated in
57% yield.
3-Methoxypropan-1,2-diol [CAS 623-39-2] (4)
Colorless liquid; 1H NMR: d=2.80 (br, 2H, OH), 3.38 (s, 3H, CH3),
3.44–3.47 (m, 2H, CH2), 3.57–3.72 (m, 2H, CH2), 3.82–3.88 ppm (m,
1H, CH); 13C NMR: d=59.2 (CH3), 64.0 (CH2), 70.8 (CH), 74.1 ppm
(CH2); IR (ATR): n˜max =3357, 2927, 2883, 1453, 1194, 1090,
1037 cmÀ1; GC–MS: RT=4.17 min, m/z (%)=88 (6) [MÀH2O]+·, 75
(40), 61 (26), 45 (100); HRMS (ESI): m/z calcd for C4H10NaO3:
129.0522 [M+Na]+; found: 129.0522.
1-(2,3-Dimethoxypropoxy)butane [CAS 1242082-85-4] (6a)
1
Colorless liquid; H NMR: d=0.91 (t, J=6.9 Hz, 3H, CH3), 1.31–1.41
(m, 2H, CH2), 1.53–1.59 (m, 2H, CH2), 3.37 (s, 3H, CH3), 3.42–
3.50 ppm (m, 10H, CH2, CH, CH3); 13C NMR: d=13.9 (CH3), 19.3
(CH2), 31.7 (CH2), 57.9 (CH3), 59.2 (CH3), 70.2 (CH2), 71.4 (CH2), 72.5
(CH2), 79.3 ppm (CH); IR (ATR): n˜max =2930, 2871, 1459, 1194,
1110 cmÀ1; HRMS (ESI): m/z calcd for C9H20NaO3: 199.1305 [M+Na]+;
found: 199.1306.
General procedure for the dimethylation of glycerol ethers
To a Schlenk tube equipped with a septum under an argon flow
was added a magnetic stirring bar followed by glycerol ether 5a–
i (3 mmol) and KOH 85% (0.46 g, 6.9 mmol, 2.3 equiv.). Next,
(nBu)4NHSO4 (102 mg, 0.3 mmol, 10 mol%) was added to the mix-
ture. The medium was stirred for 20 min at RT until it became ho-
mogeneous. Then, DMS (0.42 g, 0.31 mL, 3.3 mmol, 1.3 equiv.) was
carefully added dropwise. The reaction mixture was vigorously
stirred for 16 h at RT. The crude was dissolved in CH2Cl2, and the
salts (K2SO4) were removed by filtration and washed several times
with CH2Cl2. The solvent was then evaporated under reduced pres-
sure, and the residue was finally purified by silica flash column
chromatography to afford products 6a–i as colorless oils (eluent:
cyclohexane/ethyl acetate 7:1).
1-(2,3-Dimethoxypropoxy)pentane [CAS 1428897-03-3] (6b)
1
Colorless liquid; H NMR (400 MHz): d=0.89 (t, J=6.8 Hz, 3H, CH3),
1.29–1.35 (m, 4H, CH2), 1.53–1.59 (m, 2H, CH2), 3.37 (s, 3H, CH3),
3.42–3.52 ppm (m, 10H, CH2, CH, CH3); 13C NMR (100 MHz): d=14.2
(CH3), 22.6 (CH2), 28.4 (CH2), 29.4 (CH2), 58.1 (CH3), 59.4 (CH3), 70.3
(CH2), 71.8 (CH2), 72.6 (CH2), 79.4 ppm (CH); IR (ATR): n˜max =2929,
2861, 1460, 1194, 1111 cmÀ1; HRMS (ESI): m/z calcd for C10H22NaO3:
213.1461 [M+Na]+; found: 213.1457.
1-(2,3-Dimethoxypropoxy)hexane [CAS 1428897-04-4] (6c)
1,2,3-Trimethoxypropane [CAS 20637-49-4] (2)
1
Colorless liquid; H NMR: d=0.88 (t, J=6.8 Hz, 3H, CH3), 1.25–1.35
1
Colorless liquid; H NMR: d=3.37 (s, 6H, CH3), 3.42–3.52 ppm (m,
(m, 6H, CH2), 1.53–1.60 (m, 2H, CH2), 3.37 (s, 3H, CH3), 3.41–
3.52 ppm (m, 10H, CH2, CH, CH3); 13C NMR: d=14.1 (CH3), 22.7
(CH2), 25.8 (CH2), 29.6 (CH2), 31.7 (CH2), 58.0 (CH3), 59.3 (CH3), 70.2
(CH2), 71.7 (CH2), 72.5 (CH2), 79.3 ppm (CH); IR (ATR): n˜max =2928,
2859, 1459, 1194, 1111 cmÀ1; HRMS (ESI): m/z calcd for C11H24NaO3:
227.1618 [M+Na]+; found: 227.1623.
8H, CH3, CH, CH2); 13C NMR: d=57.6 (CH3), 59.0 (CH3), 72.0 (CH2),
78.9 ppm (CH); IR (ATR): n˜max =2981, 2888, 2815, 1452, 1192, 1107,
961, 834 cmÀ1
;
GC–MS: RT=4.12 min, m/z (%)=102 (48)
[MÀCH3OH]+·, 89 (100), 71 (16), 59 (92), 45 (46); HRMS (ESI): m/z
calcd for C6H14NaO3: 157.0835 [M+Na]+; found: 157.0831.
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 13
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CHEMCATCHEM
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118.9 (CHarom), 123.7 (CHarom), 126.4 (CHarom), 126.8 (CHarom), 127.6
(CHarom), 129.1 (Cq), 129.4 (CHarom), 134.5 (Cq), 156.7 ppm (Cq); IR
(ATR): n˜max =2927, 2880, 2825, 1628, 1600, 1510, 1465, 1257, 1217,
1181, 1117, 1094, 836, 810, 746 cmÀ1; HRMS (ESI): m/z calcd for
C15H18NaO3: 269.1148 [M+Na]+; found: 269.1148.
1-(2,3-Dimethoxypropoxy)octane [CAS 1428897-05-5] (6d)
1
Colorless liquid; H NMR: d=0.87 (t, J=6.7 Hz, 3H, CH3), 1.25–1.35
(m, 10H, CH2), 1.51–1.60 (m, 2H, CH2), 3.37 (s, 3H, CH3), 3.41–
3.51 ppm (m, 10H, CH2, CH, CH3); 13C NMR: d=14.1 (CH3), 22.7
(CH2), 26.2 (CH2), 29.3 (CH2), 29.5 (CH2), 29.7 (CH2), 31.9 (CH2), 58.0
(CH3), 59.3 (CH3), 70.2 (CH2), 71.8 (CH2), 72.5 (CH2), 79.3 ppm (CH);
IR (ATR): n˜max =2924, 2856, 1459, 1194, 1112 cmÀ1; HRMS (ESI): m/z
calcd for C13H28NaO3: 255.1931 [M+Na]+; found: 255.1933.
GC chromatograms of pure 2, 3a, 3b, 4, and 1 are given in the
Supporting Information. All experimental procedures and all prod-
uct characterizations (1H NMR, 13C NMR, IR, GC–MS, GC, and HRMS),
including the products obtained if using 2 as the solvent in chemi-
cal transformations are also given in the Supporting Information.
1-(2,3-Dimethoxypropoxy)-3-methylbutane [no CAS number]
(6e)
Acknowledgements
1
Colorless liquid; H NMR: d=0.89 (d, J=6.6 Hz, 6H, CH3), 1.43–1.50
(m, 2H, CH2), 1.60–1.75 (m, 1H, CH), 3.36 (s, 3H, CH3), 3.43–
3.52 ppm (m, 10H, CH2, CH, CH3); 13C NMR: d=22.7 (CH3), 25.1
(CH), 38.5 (CH2), 58.0 (CH3), 59.3 (CH3), 70.1 (CH2), 70.3 (CH2), 72.5
(CH2), 79.3 ppm (CH); IR (ATR): n˜max =2955, 2926, 2870, 1466, 1194,
; HRMS (ESI): m/z calcd for C11H24NaO3: 227.1618
[M+Na]+; found: 227.1623.
The authors thank Sofiprotꢀol for their financial support and F.
Albrieux, C. Duchamp, and N. Henriques (Centre Commun de
Spectromꢀtrie de Masse, ICBMS UMR-5246) for assistance and
access to the Mass Spectrometry facilities.
1111 cmÀ1
Keywords: alkylation
chemistry · phase-transfer catalysis · transesterification
·
CÀC coupling
· glycerol · green
3-[(2,3-Dimethoxypropoxy)methyl]heptane [no CAS number]
(6 f)
[1] a) C. Reichardt, T. Welton, Solvents and Solvent Effects in Organic Chemis-
try, 4th ed., Wiley-VCH, Weinheim, 2011; b) L. Moity, M. Durant, A. Be-
nazzouz, C. Pierlot, V. Molinier, J.-M. Aubry, Green Chem. 2012, 14,
1132–1145.
[2] R. Hçfer, J. Bigorra, Green Chem. 2007, 9, 203–212.
[3] J. M. DeSimone, Science 2002, 297, 799–803.
[4] a) P. G. Jessop, Green Chem. 2011, 13, 1391–1398; b) R. A. Sheldon,
Green Chem. 2005, 7, 267–278; c) R. K. Henderson, C. Jimꢁnez-Gonzꢃlez,
D. J. C. Constable, S. R. Alston, G. G. A. Inglis, G. Fisher, J. Sherwood, S. P.
Binks, A. D. Curzons, Green Chem. 2011, 13, 854–862; d) K. Alfonsi, J.
Colberg, P. J. Dunn, T. Fevig, S. Jennings, T. A. Johnson, H. P. Kleine, C.
Knight, M. A. Nagy, D. A. Perry, M. Stefaniak, Green Chem. 2008, 10, 31–
36; e) J. H. Clark, S. J. Taverner, Org. Process Res. Dev. 2007, 11, 149–155;
f) C. Capello, U. Fischer, K. Hungerbꢄhler, Green Chem. 2007, 9, 927–
934.
1
Colorless liquid (mixture of diastereoisomers); H NMR: d=0.87 (m,
6H, CH3), 1.23–1.38 (m, 8H, CH2), 1.47–1.54 (m, 1H, CH), 3.32 (d, J=
6.0 Hz, 2H, CH2), 3.37 (s, 3H, CH3), 3.43–3.52 ppm (m, 8H, CH2, CH,
CH3); 13C NMR: d=11.1 (CH3), 14.2 (CH3), 23.2 (CH2), 23.9 (CH2), 29.1
(CH2), 30.6 (CH2), 39.6 (CH), 58.1 (CH3), 59.3 (CH3), 70.5 (CH2), 72.7
(CH2), 74.5 (CH2), 79.3 ppm (CH); IR (ATR): n˜max =2958, 2926, 2873,
1460, 1194, 1109 cmÀ1; HRMS (ESI): m/z calcd for C13H28NaO3:
255.1931 [M+Na]+; found: 255.1919.
[(2,3-Dimethoxypropoxy)methyl]cyclohexane [CAS 811804-21-4]
(6g)
1
Colorless liquid; H NMR: d=0.88–0.97 (m, 2H, CH2), 1.12–1.28 (m,
[5] K. Tanaka, F. Toda, Chem. Rev. 2000, 100, 1025–1074.
3H, CH2, CH), 1.54–1.76 (m, 6H, CH2), 3.24 (d, J=6.5 Hz, 2H, CH2),
3.37 (s, 3H, CH3), 3.43–3.52 ppm (m, 8H, CH2, CH, CH3); 13C NMR:
d=25.9 (CH2), 26.7 (CH2), 30.1 (CH2), 30.1 (CH2), 38.0 (CH), 58.0
(CH3), 59.3 (CH3), 70.4 (CH2), 72.6 (CH2), 77.6 (CH2), 79.3 ppm (CH);
IR (ATR): n˜max =2921, 2851, 1449, 1193, 1112 cmÀ1; HRMS (ESI): m/z
[M+Na]+ calcd for C12H24NaO3: 239.1618 found: 227.1611.
[6] a) M. Petkovic, K. R. Seddon, L. P. N. Rebelo, C. S. Pereira, Chem. Soc. Rev.
2011, 40, 1383–1403; b) J. Ranke, S. Stolte, R. Stçrmann, J. Aming, B.
Jastorff, Chem. Rev. 2007, 107, 2183–2206; c) J. P. Hallett, T. Welton,
Chem. Rev. 2011, 111, 3508–3576; d) L. ꢅlvarez de Cienfuegos, R. Robles,
D. Miguel, J. Justicia, J. M. Cuerva, ChemSusChem 2011, 4, 1035–1048;
e) H. Zhao, G. A. Baker, J. Chem. Technol. Biotechnol. 2013, 88, 3–12; f) T.
Erdmenger, C. Guerrero-Sanchez, J. Vitz, R. Hoogenboom, U. S. Schu-
bert, Chem. Soc. Rev. 2010, 39, 3317–3333.
[7] a) M. J. Hernꢃiz, A. R. Alcꢃntara, J. I. Garcꢂa, J. V. Sinisterra, Chem. Eur. J.
2010, 16, 9422–9437; b) T. Adschiri, Y.-W. Lee, M. Goto, S. Takami, Green
Chem. 2011, 13, 1380–1390; c) P. Licence, J. Ke, M. Sokolova, S. K. Ross,
M. Poliakoff, Green Chem. 2003, 5, 99–104; d) A. Loppinet-Serani, C.
Aymonier, F. Cansell, ChemSusChem 2008, 1, 486–503.
[8] a) K. Watanabe, N. Yamagiwa, Y. Torisawa, Org. Process Res. Dev. 2007,
11, 251–258; b) K. Beydoun, H. Doucet, ChemSusChem 2011, 4, 526–
534; c) K. Watanabe, Molecules 2013, 18, 3183–3194.
(2,3-dimethoxypropoxy)benzene [CAS 256444-82-3] (6h)
Colorless liquid; 1H NMR: d=3.40 (s, 3H, CH3), 3.52 (s, 3H, CH3),
3.53–3.65 (m, 2H, CH2), 3.68–3.75 (m, 1H, CH), 4.01–4.12 (m, 2H,
CH2), 6.91–6.98 (m, 3H, CHarom), 7.24–7.31 ppm (m, 2H, CHarom);
13C NMR: d=58.2 (CH3), 59.4 (CH3), 67.3 (CH2), 72.0 (CH2), 78.7 (CH),
114.6 (CHarom), 121.0 (CHarom), 129.5 (CHarom), 158.8 ppm (Cq); IR
(ATR): n˜max =2927, 2880, 2826, 1599, 1587, 1496, 1456, 1243, 1194,
1095, 1037, 752, 691 cmÀ1; HRMS-ESI: m/z [M+Na]+ calcd for
C11H16NaO3: 219.0992 found: 219.0987.
[9] a) M.-O. Simon, C.-J. Li, Chem. Soc. Rev. 2012, 41, 1415–1427; b) C.-J. Li,
L. Chen, Chem. Soc. Rev. 2006, 35, 68–82; c) A. Chanda, V. V. Fokin,
Chem. Rev. 2009, 109, 725–748.
[10] P. Anastas, N. Eghbali, Chem. Soc. Rev. 2010, 39, 301–312.
[11] a) S. M. Payne, F. M. Kerton, Green Chem. 2010, 12, 1648–1653; b) L.
Lomba, I. Bandrꢁs, C. Lafuente, M. R. Pino, B. Giner, Green Chem. 2011,
13, 2062–2070.
[12] V. Pace, P. Hoyos, L. Castoldi, P. Domꢂnguez de Maria, A. R. Alcꢃntara,
ChemSusChem 2012, 5, 1369–1379.
[13] a) S. Aparicio, R. Alcalde, Green Chem. 2009, 11, 65–78; b) C. S. M. Pereir-
an, V. M. T. M. Silva, A. E. Rodrigues, Green Chem. 2011, 13, 2658–2671.
[14] J. Yang, J.-N. Tan, Y. Gu, Green Chem. 2012, 14, 3304–3317.
2-(2,3-Dimethoxypropoxy)naphthalene [no CAS number] (6i)
Colorless liquid; 1H NMR: d=3.43 (s, 3H, CH3), 3.57 (s, 3H, CH3),
3.59–3.70 (m, 2H, CH2), 3.76–3.83 (m, 1H, CH), 4.15–4.25 (m, 2H,
CH2), 7.17–7.21 (m, 2H, CHarom), 7.31–7.37 (m, 1H, CHarom), 7.41–7.47
(m, 1H, CHarom), 7.71–7.76 ppm (m, 3H, CHarom); 13C NMR: d=58.2
(CH3), 59.4 (CH3), 67.4 (CH2), 72.0 (CH2), 78.6 (CH), 106.8 (CHarom),
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 13
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&
ÞÞ
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CHEMCATCHEM
FULL PAPERS
www.chemcatchem.org
[15] a) I. T. Horvꢃth, H. Mehdi, V. Fꢃbos, L. Boda, L. T. Mika, Green Chem.
2008, 10, 238–242; b) D. M. Alonson, S. G. Wettstein, J. A. Dumesic,
Green Chem. 2013, 15, 584–595.
[31] a) A.-A. G. Shaikh, S. Sivaram, Chem. Rev. 1996, 96, 951–976; b) P.
Tundo, M. Selva, Acc. Chem. Res. 2002, 35, 706–716; c) M. Selva, A.
Perosa, Green Chem. 2008, 10, 457–464.
[16] A. Bellomo, R. Daniellou, D. Plusquellec, Green Chem. 2012, 14, 281–
284.
[17] M. Schlaf, Dalton Trans. 2006, 4645–4653.
[32] a) U. Tilstam, Org. Process Res. Dev. 2012, 16, 1150–1153; b) G. Wu, X.
Wang, B. Chen, J. Li, N. Zhao, W. Wei, Y. Sun, Appl. Catal. A 2007, 329,
106–111; c) Z. L. Shen, X. Z. Jiang, W. M. Mo, B. X. Hu, N. Sun, Green
Chem. 2005, 7, 97–99; d) S. Ouk, S. Thiebaud, E. Borredon, P. Legars, L.
Lecomte, Tetrahedron Lett. 2002, 43, 2661–2663; e) T. M. Jyothi, T. Raja,
M. B. Talawar, B. S. Rao, Appl. Catal. A 2001, 211, 41–46.
[33] a) M. Selva, E. Millitello, M. Fabris, Green Chem. 2008, 10, 73–79; b) P.
Tundo, S. Memoli, D. Hꢁrault, K. Hill, Green Chem. 2004, 6, 609–612.
[34] a) B. Veldurthy, J.-M. Clacens, F. Figueras, J. Catal. 2005, 229, 237–242;
b) P. Tundo, F. Trotta, G. Moraglio, Ind. Eng. Chem. Res. 1988, 27, 1565–
1571.
[18] a) J. H. Clark, D. J. Macquarrie, J. Sherwood, Green Chem. 2012, 14, 90–
93; b) S. Salehpour, M. A. Dubꢁ, Green Chem. 2008, 10, 321–326.
[19] “Introduction on Glycerol as co-product from biodiesel plants” http://
www.supermethanol.eu.
[20] a) C.-H. Zhou, J. N. Beltramini, Y.-X. Fan, G. Q. Lu, Chem. Soc. Rev. 2008,
37, 527–549; b) A. Behr, J. Eilting, K. Irawadi, J. Leschinski, F. Linder,
Green Chem. 2008, 10, 13–30; c) M. Pagliaro, R. Cirimina, H. Kimura, M.
Rossi, C. Della Pina, Angew. Chem. 2007, 119, 4516–4522; Angew. Chem.
Int. Ed. 2007, 46, 4434–4440; d) F. Jꢁrꢆme, Y. Pouilloux, J. Barrault,
ChemSusChem 2008, 1, 586–613.
[35] M. O. Sonnati, S. Amigoni, E. P. Taffin de Givenchy, T. Darmanin, O. Chou-
let, F. Guittard, Green Chem. 2013, 15, 283–306.
[21] a) A. E. Dꢂaz-ꢅlvarez, V. Cadierno, Appl. Sci. 2013, 3, 55–69; b) A. E. Dꢂaz-
ꢅlvarez, J. Francos, B. Lastra-Barreira, P. Crochet, V. Cadierno, Chem.
Commun. 2011, 47, 6208–6227; c) Y. Gu, F. Jꢁrꢆme, Green Chem. 2010,
12, 1127–1138; d) M. Delample, N. Villandier, J.-P. Douliez, S. Camy, J.-S.
Condoret, Y. Pouilloux, J. Barrault, F. Jꢁrꢆme, Green Chem. 2010, 12,
804–808; e) A. Wolfson, C. Dluggy, Y. Shotland, D. Tavor, Tetrahedron
Lett. 2009, 50, 5951–5953; f) A. Wolfson, C. Dluggy, Y. Shotland, Environ.
Chem. Lett. 2007, 5, 67–71; g) G. Cravotto, L. Orio, E. Calcio Gaudino, K.
Martina, D. Tavor, A. Wolfson, ChemSusChem 2011, 4, 1130–1134.
[22] J. I. Garcꢂa, H. Garcꢂa-Marꢂn, J. A. Mayoral, P. Pꢁrez, Green Chem. 2010,
12, 426–434.
[23] a) R. Palkovits, I. Nieddu, C. A. Kruithof, R. J. M. Klein Gebbink, B. M.
Weckhuysen, Chem. Eur. J. 2008, 14, 8995–9005; b) R. Palkovits, I.
Nieddu, R. J. M. Klein Gebbink, B. Weckhuysen, ChemSusChem 2008, 1,
193–196; c) A. Behr, J. Leschinski, C. Awungacha, S. Simic, T. Knoth,
ChemSusChem 2009, 2, 71–76; d) L. Conceicao, R. Bogel-Lukasik, E.
Bogel-Lukasik, Green Chem. 2012, 14, 673–681; e) S. Bigot, J. Lai, I.
Suisse, M. Sauthier, A. Mortreux, Y. Castanet, Appl. Catal. A 2010, 382,
181–189.
[24] a) K. Klepacova, D. Mravec, M. Bajus, Appl. Catal. A 2005, 294, 141–147;
b) Y. Gu, A. Azzouzi, Y. Pouilloux, F. Jꢁrꢆme, J. Barrault, Green Chem.
2008, 10, 164–167; c) S. Pariente, N. Tanchoux, F. Fajula, Green Chem.
2009, 11, 1256–1261; d) P. Gaudin, R. Jacquot, P. Marion, Y. Pouilloux, F.
Jꢁrꢆme, ChemSusChem 2011, 4, 719–722; e) F. Liu, K. De Oliveira Vigier,
M. Pera-Titus, Y. Pouilloux, J.-M. Clacens, F. Decampo, F. Jꢁrꢆme, Green
Chem. 2013, 15, 901–909.
[25] a) J. A. Melero, G. Vicente, G. Morales, M. Paniagua, J. M. Moreno, R.
Roldꢃn, A. Ezquerro, C. Pꢁrez, Appl. Catal. A 2008, 346, 44–51; b) A. M.
Ruppert, A. N. Parvulescu, M. Arias, P. J. C. Hausoul, P. C. A. Bruijnincx,
R. J. M. Klein Gebbink, B. M. Weckhuysen, J. Catal. 2009, 268, 251–259.
[26] V. Bethmont, F. Fache, M. Lemaire, Tetrahedron Lett. 1995, 36, 4235–
4236.
[36] Selected articles and reviews: a) M. Makosza, W. Wawrzyniewicz, Tetra-
hedron Lett. 1969, 10, 4659–4662; b) C. M. Starks, J. Am. Chem. Soc.
1971, 93, 195–199; c) H. H. Freedman, R. A. Dubois, Tetrahedron Lett.
1975, 16, 3251–3254; d) M. Makosza, Pure Appl. Chem. 2000, 72, 1399–
1403; e) S. D. Naik, L. K. Doraiswamy, AIChE J. 1998, 44, 612–646; f) M.
´
Makosza, M. Fedorynski, Catal. Rev. Sci. Eng. 2003, 45, 321–367; g) A.
McKillop, J.-C. Fiaud, R. R. Hug, Tetrahedron Lett. 1974, 15, 1379–1382;
h) H.-M. Yang, P.-I. Wu, C.-M. Li, Appl. Catal. A 2000, 193, 129–137; i) B.
Lygo, B. I. Andrews, Acc. Chem. Res. 2004, 37, 518–535; j) T. Ooi, K. Mar-
uoka, Angew. Chem. 2007, 119, 4300–4345; Angew. Chem. Int. Ed. 2007,
46, 4222–4266; k) G. Keglevich, T. Novꢃk, L. Vida, I. Greiner, Green Chem.
2006, 8, 1073–1075.
[37] H. H. Freedman, Pure Appl. Chem. 1986, 58, 857–868.
[38] A. Corma, S. Iborra, S. Miquel, J. Primo, J. Catal. 1998, 173, 315–321.
[39] a) P. Barbier, Compt. Rend. 1899, 128, 110; b) V. Grignard, Compt. Rend.
1900, 130, 1322; c) V. Grignard, Ann. Chim. 1901, 24, 433.
[40] Some representative reports: a) T. Mizoroki, K. Mori, A. Ozaki, Bull. Chem.
Soc. Jpn. 1971, 44, 581; b) R. F. Heck, J. P. Nolley, J. Org. Chem. 1972, 37,
2320–2322; c) I. P. Beletskaya, A. V. Cheprakov, Chem. Rev. 2000, 100,
3009–3066; d) J. Hassan, M. Sꢁvignon, C. Gozzi, E. Schulz, M. Lemaire,
Chem. Rev. 2002, 102, 1359–1469; e) N. Miyaura, T. Yanagi, A. Suzuki,
Synth. Commun. 1981, 11, 513–519; f) A. Suzuki, J. Organomet. Chem.
1999, 576, 147–168; g) K. Sonogashira, Y. Tohda, Y. Hagihara, Tetrahe-
dron Lett. 1975, 16, 4467–4470; h) R. Chinchilla, C. Nꢃjera, Chem. Rev.
2007, 107, 874–922.
[41] a) C.-J. Li, Chem. Rev. 2005, 105, 3095–3165; b) J. Dupont, R. F. de Souza,
P. A. Z. Suarez, Chem. Rev. 2002, 102, 3667–3692; c) R. S. Oakes, A. A.
Clifford, C. M. Rayner, J. Chem. Soc. Perkin Trans. 1 2001, 917–941.
[42] a) F. Ullmann, Ber. Dtsch. Chem. Ges. 1903, 36, 2382–2384; b) F. Ullmann,
Ber. Dtsch. Chem. Ges. 1904, 37, 853–854; c) J. F. Marcoux, S. Doye, S. L.
Buchwald, J. Am. Chem. Soc. 1997, 119, 10539–10540; d) G. Mann, J. F.
Hartwig, Tetrahedron Lett. 1997, 38, 8005–8008.
[27] a) Y. Fujii, H. Furugaki, S. Yano, K. Kita, Chem. Lett. 2000, 926–927; b) C.
Linder, L. J. Gooben, Synlett 2006, 3489–3491.
[43] a) Y. Izawa, D. Pun, S. S. Stahl, Science 2011, 333, 209–213; b) M. O.
Simon, S. A. Girard, C. J. Li, Angew. Chem. 2012, 124, 7655–7658;
Angew. Chem. Int. Ed. 2012, 51, 7537–7540.
[44] B. A. Miller-Chou, J. L. Koenig, Prog. Polym. Sci. 2003, 28, 1223–1270.
[45] R. Mendichi, S. Russo, L. Ricco, A. Giacometti Schieroni, J. Sep. Sci. 2004,
27, 637–644.
[28] a) Y. Shi, W. Dayoub, G. R. Chen, M. Lemaire, Tetrahedron Lett. 2009, 50,
6891–6893; b) Y. Shi, W. Dayoub, G. R. Chen, M. Lemaire, Green Chem.
2010, 12, 2189–2195; c) M. Sutter, W. Dayoub, E. Mꢁtay, Y. Raoul, M.
Lemaire, ChemSusChem 2012, 5, 2397–2409; d) M. Sutter, W. Dayoub, E.
Mꢁtay, Y. Raoul, M. Lemaire, Green Chem. 2013, 15, 786–797.
[29] M. Sutter, N. Sotto, Y. Raoul, E. Mꢁtay, M. Lemaire, Green Chem. 2013,
15, 347–352.
[46] J. Wagner, H. Grill, US 3888994, 1975.
Received: June 13, 2013
[30] J.-S. Chang, Y.-D. Lee, L. Chao-Shan Chou, T.-R. Ling, T.-C. Chou, Ind. Eng.
Chem. Res. 2012, 51, 660–666.
Published online on && &&, 0000
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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