Synthesis of dioxolanes and oxazolidines by silica gel catalysis

Article abstract of DOI:10.1007/s00706-018-2198-7

Abstract: Ethylene glycol condensed with carbonyl compounds in the presence of silica gel or alumina, without solvent and under pressure, affords 1,3-dioxolanes. 2-Amino-2-methylpropanol also condensed with carbonyl compounds in the presence of silica gel or an acid-activated clay, without solvent and under pressure, produces oxazolidines. To explain these results, we propose that the glycol and the aminopropanol react with Br?nsted (H⁺) and Lewis acid sites (Si and Al) located on the surface of the catalysts, leading to the products via various ionic intermediates.

Full text of DOI:10.1007/s00706-018-2198-7

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ORIGINAL PAPER
Synthesis of dioxolanes and oxazolidines by silica gel catalysis
2
2
Taoufik Rohand1
Jerome Savary Istvan E. Marko
•
•
´ ˆ
´
´
Received: 15 January 2018 / Accepted: 3 April 2018
Ó Springer-Verlag GmbH Austria, part of Springer Nature 2018
Abstract
Ethylene glycol condensed with carbonyl compounds in the presence of silica gel or alumina, without solvent and under
pressure, affords 1,3-dioxolanes. 2-Amino-2-methylpropanol also condensed with carbonyl compounds in the presence of
silica gel or an acid-activated clay, without solvent and under pressure, produces oxazolidines. To explain these results, we
propose that the glycol and the aminopropanol react with Brønsted (H?) and Lewis acid sites (Si and Al) located on the
surface of the catalysts, leading to the products via various ionic intermediates.
Graphical abstract
Keywords 2-Amino-2-methylpropanol Á Carbonyl compounds Á Dioxolanes Á Ethylene glycol Á Oxazolidines
Introduction
For example, the condensation of epoxystyrene with
benzylmethylamine, the cyclization of enones, the vinylo-
gous Michael double additions, the rearrangement of
1-amino-2-ketoesters and of 4-amino-3,4-dihydro-2H-1,4-
thiazines have all been carried out in the presence of silica gel
[6–8]. Alumina also catalyzes the oxidation of alcohols to
ketones by trichloroacetic acid, the dehydration of alcohols
to alkenes, the synthesis of isoxazolines and of 1,2-
aminoalcohols [9–13]. Other studies have used natural alu-
minosilicates, such as clays, for the iodo-functionalization of
alkenes by water and alcohols, the esterification of phenyl-
acetic acid, the dehydration of glucose and the rearrange-
ment of epoxy chalcones [14–17]. Ethylene glycol is
frequently used in organic synthesis to protect aldehydes and
ketones, enabling other functional groups in the molecule to
undergo chemoselective transformations. These acetaliza-
tion and ketalization reactions are typically carried out in
ecologically harmful organic solvents, in the presence of
noxious protic acids, at various temperatures and, typically,
at atmospheric pressure [18–20] (Figs. 1, 2, 3).
Protic acids are well-known to suffer from a number of
shortcomings, including their corrosive and noxious nature
[1, 2]. The recent move towards green chemistry has seen
silica gel, alumina, and clays gradually replacing mineral
acids in the synthesis of organic compounds. Indeed, these
non-polluting heterogeneous catalysts possess numerous
advantages such as ready availability, efficient recycling,
low cost, and ease of separation from crude reaction mix-
tures by simple filtration [3–5].
´ ´
Istvan E. Marko prematurely passed away on July 31, 2017.
& Taoufik Rohand
taoufik.rohand@ucam.ac.ma
1
´
Laboratoire de Chimie Analytique et Moleculaire,
Departement de Chimie, Faculte Polydisciplinaire de Safi,
´
´
´
Universite Cadi Ayyad, 46000 Safi, Morocco
To better understand the catalytic role played by these
heterogeneous catalysts, we have decided to study their
activity in the preparation of oxygen-containing five-
2
Department of Chemistry, Laboratoire de Chimie Organique
´
et Medicinale, Universite Catholique de Louvain, Place Louis
Pasteur 1, L4.01.02, 1348 Louvain-la-Neuve, Belgium
´
123

T. Rohand et al.
Table 1 Reaction of pure ethylene glycol (1) in the presence of sul-
furic acid or silica gel under different experimental conditions
Run
Catalyst
T/°C
t/h
2/%
3/%
5a/%
Fig. 1 Reaction of pure ethylene glycol (1) in the presence of sulfuric
acid or silica gel under various experimental conditions
1
2
3
4
5
6
H2SO4 (4% wt)
H2SO4 (4% wt)
H2SO4 (4% wt)
Silica gel
196a
150b
150b
196
3
4
1
9
9
–
–
–
–
3
24
120
3
16
65
1
–
–
–
Silica gel
150
–
–
Silica gel
150
7
–
19
aP. atm: atmospheric pressure = 101 kPa. Reactor: 50 cm3 flask
bP auto: autogenic pressure. P150° = 153 kPa
Fig. 2 Synthesis of dioxolanes 5b–5o catalyzed by silica gel and
alumina
With the desire to convert this reaction into a more
selective transformation, it was initially decided to repro-
duce this process under the previously described condi-
tions. Hence, ethylene glycol was heated in the presence of
H2SO4 (4% by mass) at 196 °C and under atmospheric
pressure for 3 h. In contrast to the results reported in the
literature [21–23], only diethylene glycol and 1,4-dioxane
were obtained, in 4 and 1% yields (Table 1). It is inter-
esting to note that the yield of compounds 2 and 3
increased after treatment of 1 with H2SO4 (4% by mass) in
an autoclave, under pressure, at a temperature of 150 °C.
Moreover, prolonged heating of this reaction mixture from
3 to 24 h considerably increased the amount of 2 (65%),
while the quantity of 3 (9%) remained constant.
Fig. 3 Synthesis of oxazolidines 7g–7o catalyzed by silica gel and
activated clay
membered ring heterocycles, such as dioxolanes and oxa-
zolidines, in the absence of solvent and under pressure, by
the condensation of the corresponding carbonyl compounds
with ethylene glycol and 2-amino-2-methylpropanol,
respectively.
Results and discussion
Replacing sulfuric acid by silica gel led to almost no
dimerization of glycol 1 to diethylene glycol (1%), and no
products 3 and 5a were obtained even after refluxing for
5 days (Table 1, run 4). However, heating compound 1 at
150 °C, under pressure, resulted in a mixture of diethylene
glycol and 2-methyl-1,3-dioxolane in yields depending
upon the reaction time (Table 1, runs 5 and 6). In all cases,
compound 2 remained a minor component of this mixture
(1–3%), while the yield of dioxolane 5a reached a value of
Previous publications from various authors reported that
the distillation of ethylene glycol (1) in the presence of
sulfuric acid (4% by mass) leads to a mixture of four
products [21–23]. According to these reports, 1,4-dioxane
(3) is the major component of this reaction, while diethy-
lene glycol (2), acetaldehyde, and 2-methyl-1,3-dioxolane
(5a) are obtained in low yields.
Scheme 1
123

Synthesis of dioxolanes and oxazolidines by silica gel catalysis
22% after 24 h of heating. It then decreased slowly with
time. It is interesting to note that diethylene glycol is
stable on silica gel even after heating at 150 °C for 24 h,
without solvent, and under pressure. This result demon-
strates that the acidity of the catalyst plays an important
role in the various pathways leading to the different
products obtained in this transformation. Indeed, the linear
dimer 2 is dehydrated to the cyclic dimer 3 in the presence
of strong Brønsted acids such as sulfuric acid, while it is
inert with respect to the Lewis acidic sites present in the
silica gel.
activate the dimerization reaction of glycol 1, delivering a
mixture of diethylene glycol and 1,4-dioxane, whilst Lewis
acids mainly convert compound 1 into 2-methyl-1,3-diox-
olane via acetaldehyde.
Following these promising results, we decided to gen-
eralize this heterogeneous ketalization reaction to a variety
of carbonyl compounds 4b–4o by treating them with
ethylene glycol, in the presence of catalytic amounts of
silica gel, under solventless conditions, and at various
temperatures. All these experiments were conducted in an
autogenous pressure autoclave; the correlation between the
temperature and the inner pressure is given in Table 2.
The results collected in Table 3 reveal that the aliphatic
aldehydes 4b and 4c are almost inert under these condi-
tions. However, unsaturated and aromatic aldehydes 4d–
4g, bearing inductive and mesomeric donor groups react
with glycol 1 to afford the corresponding dioxolanes 5d–5g
with yields ranging from 9 to 24%. On the other hand, the
presence of the strongly electron-withdrawing para-nitro
substituent activates the carbonyl group of the aldehyde 4h
and dramatically increases the yield of dioxolane 5h (86%).
In addition, we have studied the reaction of ethylene
glycol with ketones 4i–4o in the presence of silica gel. We
noticed that ketones 4i–4l are transformed into dioxolanes
5i–5l in modest yields (5–8%). On the other hand, the
presence of a phenyl substituent alpha to the carbonyl
group of 4m and 4n greatly raised the yield of dioxolane
5m and 5n (24–26%). Even more advantageous is the use
of chloroacetone (4o), which is more reactive than other
ketones by virtue of the electron-withdrawing inductive
effect of the chlorine atom, providing dioxolane 5o in
excellent yield (78%).
Next, we tested the stability of the dioxolane 5a by
heating it in the presence of wet silica gel at 150 °C for
24 h. The recovery of a small amount of ethylene glycol
(10%) from 2-methyl-1,3-dioxolane (5a) confirmed our
assumption that 5a is hydrolysed under these conditions,
affording compounds 1 and absence of acetaldehyde. The
absence of acetaldehyde can be explained by its release,
either during the heating process or during the treatment of
the crude reaction mixture at ambient temperature (bp
24 °C). It is noteworthy that other studies have also shown
that 1,3-dioxolanes are unstable in the presence of protic
acids (AcOH, TsOH, and HCl) and Lewis acid (BF3)
[4, 24–27].
At this stage, we can conclude that the selectivity of the
reaction pathways when ethylene glycol is treated with
various acids depends upon the nature of the catalyst used
and the pressure exerted on the system. Brønsted acids
Table 2 Variation of the autogenous pressure as a function of
temperature
T/°C
Auto. P./kPa
40
70
90
110
132
140
146
150
153
Furthermore, the results in Table 4 show that the
ketalization of benzaldehyde (4g) and of phenylacetone
(4m) by ethylene glycol, in the presence of a large amount
108
119
122
Table 3 Synthesis of
dioxolanes 5b–5o catalyzed by
silica gel and alumina
Run
4
R
R0
T/°C
5
SiO2
Al2O3
References
1
4b
4c
4d
4e
4f
H
CH3CH2
(CH3)2CH
4-MeOC6H4
PhCH = CH
4-MeC6H4
C6H5
40
40
5b
5c
5d
5e
5f
Traces
Traces
[31, 32]
[32, 33]
[34, 35]
[36]
2
H
Traces
9
Traces
8
3
H
140
140
140
150
140
90
4
H
14
23
24
86
5
18
23
22
76
4
5
H
[37, 38]
[39, 40]
[41, 42]
[43, 44]
[45, 46]
[30–47]
[48, 49]
[50, 51]
[45–52]
[53, 54]
6
4g
4h
4i
H
5g
5h
5i
7
H
4-O2NC6H4
CH3CH2
C6H5
8
CH3CH2
CH3
CH3
CH3
CH3
PhCH2
CH3
9
4j
140
40
5j
7
8
10
11
12
13
14
4k
4l
CH3
5k
5l
8
9
CH3CH2
PhCH2
70
6
8
4m
4n
4o
140
140
110
5m
5n
5o
24
26
78
20
23
56
PhCH2
ClCH2
123

T. Rohand et al.
reagent 1 with 4b–4o in the presence of silica gel or alu-
mina (Tables 4, 5). The absence of 5a indicates that the
ketalisation reaction of 4b–4o is much faster than the
competitive dehydration of 1 into acetaldehyde.
Table 4 Synthesis of dioxolanes 5g and 5m catalyzed by silica gel
(10 eq)
Carbonyl compound
Run
T/°C
t/h
Dioxolanes 5/%
This observation suggests that the sp2 oxygen of the
carbonyl compounds 4 could react more readily with the
Lewis sites of the silica gel and the alumina than the
hydroxyl groups of the excess ethylene glycol, leading to a
single dioxolane 5. It is also possible that hydrogen
bonding between the remaining ethylene glycol and ketal 5
could prevent its subsequent rearrangement into dioxolane
5a. It should be noted that silica gel and alumina (Lewis
acids) catalyze the preparation of dioxolanes with yields
close to those reported in the literature. Indeed, the
microwave irradiation of a mixture of ethylene glycol and
para-nitrobenzaldehyde (4h) or acetophenone (4j), in the
presence of the para-toluene sulfonic acid (Brønsted acid)
and under solventless conditions, leads to the dioxolanes
5h and 5j in 93 and 13% yields, respectively [28].
4g
R = H; R0 = C6H5
1
2
3
4
5
6
40
150
150
150
140
140
7
7
3
15
29
24
13
29
24
48
7
4m
R = CH3; R0 = PhCH2
24
of silica gel (10 eq), depends upon the temperature and the
duration of the reaction. It is also noteworthy that lowering
the amount of silica gel (1 eq) slightly decreases the yield
of dioxolanes 5g and 5m (compare Tables 3, 4).
The results obtained thus far, using silica gel, prompted
us to test another solid catalyst known for its Lewis acidity,
i.e., alumina [9–13]. The experimental results reported in
Table 3 clearly show that alumina catalyzes the synthesis
of dioxolanes substituted with electron-donating groups in
yields close to those obtained with silica gel. However,
condensation of ethylene glycol with para-nitrobenzalde-
hyde (4h) and chloroacetone (4o), in the presence of alu-
mina, results in dioxolanes 5h and 5o in yields much lower
than those obtained using silica gel.
To extend the scope of this method to other five-mem-
bered ring oxygen-containing heterocycles, 2-amino-2-
methylpropanol (6) was selected and used instead of
ethylene glycol. As expected, silica gel promoted the for-
mation of oxazolidines 7 in yields usually higher than for
their dioxolane counterparts (Table 5). Under these con-
ditions, oxazolidines 7g and 7o are obtained in a satisfac-
tory yield of 42%.
It appears that the reaction of the carbonyl compounds
4h and 4o, carrying electron-withdrawing groups is easier
with the catalyst possessing the largest specific surface area
(SBET: silica gel 415 m2/g, alumina 20 m2/g). Curiously,
in all these ketalization reactions, we did not obtain a
mixture of 2-methyl-1,3-dioxolane and either monosubsti-
tuted or disubstituted dioxolanes 5b after treatment of
However, the ketones 4j–4o with a methyl group are
converted into oxazolidines 7j–7o in yields ranging from
15 to 28%. Moreover, we have also studied the conden-
sation between reagents 4 and 6 in the presence of a third,
natural catalyst based upon silica and alumina. For that
purpose, we employed H2-activated clay possessing
Table 5 Synthesis of
oxazolidines 7 catalyzed by
silica gel and activated clay
Run
Catalyst
4
R
R0
T/°C
7/%
References
[55]
1
Silica gel
4g
4g
4j
H
C6H5
150
140
90
42
47
11
14
15
22
23
17
22
25
21
24
21
28
16
42
2
Activated clay
Silica gel
H
C6H5
3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
PhCH2
PhCH2
CH3
CH3
C6H5
[56]
4
Silica gel
4j
C6H5
140
140
40
5
Activated clay
Silica gel
4j
C6H5
6
4k
4k
4l
CH3
[57]
[58]
[59]
7
Activated clay
Silica gel
CH3
40
8
CH3CH2
CH3CH2
PhCH2
PhCH2
PhCH2
PhCH2
PhCH2
ClCH2
ClCH2
70
9
Activated clay
Silica gel
4l
70
10
11
12
13
14
15
16
4m
4m
4m
4n
4n
4o
4o
90
Silica gel
140
140
140
140
140
140
Activated clay
Silica gel
[59]
[59]
Activated clay
Silica gel
Activated clay
123

Synthesis of dioxolanes and oxazolidines by silica gel catalysis
Brønsted and Lewis sites on its active surface [21–23].
From the results collected in Table 4, we can conclude that
this natural heterogeneous catalyst is much more efficient
than silica gel in the synthesis of oxazolidines 7.
Chloroacetone (4o) and 2-amino-2-methylpropanol (6)
condense even better in the presence of H2-activated clay
than with silica gel (SBET: silica gel 415 m2/g;
clay 169 m2/g). These results reveal that the specific sur-
face area of the catalyst is not the only criterion, but that
the number of Brønsted and Lewis sites located on the
active surface of the H2-clay is also important in the for-
mation of oxazolidine 7o.
Scheme 2
From these observations, we can conclude that the yield
of oxazolidine 7 depends upon the temperature of the
reaction and the autogenous pressure exerted on the sys-
tem. It is also interesting to note that, whatever the catalyst
used, we have not isolated ketal by addition of
2-aminoalcohol 6.
Scheme 3
To explain the dimerization of ethylene glycol by sul-
furic acid to a mixture of diethylene glycol and 1,4-diox-
ane, we suggest that protonation of one of the hydroxyl
functions of glycol 1 by the Brønsted acid leads either to a
primary carbocation (high energy pathway, disfavored) or
to the protonated epoxide 9 by direct intramolecular
cyclization of 8 (favored pathway). The addition of a
second molecule of ethylene glycol to the epoxonium ion 9
generates diethylene glycol via hydronium cation 10.
Protonation of dimer 2 provides cation 11 that cyclizes to
dioxane 3.
Studies have shown that the silicon atom in heteroge-
neous catalysts possesses vacant electron-accepting orbi-
tals, akin to those of aluminum and boron and capable of
acting as Lewis acids. Indeed, Sakuri [28] reported that
lithium 2,20-biphenolate reacts with alkenyltrichlorosilanes
to form b-allylic alcohols via lithium silicate intermediates
(Scheme 1).
On the other hand, loss of proton from 12 can afford
directly acetaldehyde (18) and wet silica 17. The oxygen of
the carbonyl group of acetaldehyde can then be attached to
the silicon atom located on the active surface of the catalyst
to give oxonium silicate 19. The addition of ethylene
glycol to 19 forms hydronium silicate 20. Cyclization of 20
to 2-methyl-1,3-dioxolane most probably proceeds via the
oxonium cation 21, ultimately releasing water and regen-
erating the silica catalyst (Scheme 3).
To explain the formation of 1,3-dioxolane 5a from
ethylene glycol and silica gel, we suggest the mechanistic
pathways depicted in Schemes 2 and 3. It is well-known
that the active surface of the silica gel has siloxy (SiO)
groups and silanol (SiOH) functions [29]. These Lewis
sites form coordinating bonds with electron donors, namely
the hydroxyl groups of ethylene glycol. The heterolytic
cleavage of the C–O bond of the oxonium silicate 12 leads
to the ionic intermediates 13 and 9. The epoxonium cation
9 can lose a proton and react with silica gel to form the
epoxonium silicate 14, which immediately condenses with
excess ethylene glycol to yield coordinated diethylene
glycol 15. Proton exchange and release of silica liberates
the dimer 2 (Scheme 2). It is important to note that dioxane
3 was not isolated, probably owing to the stability of die-
thylene glycol again this Lewis acid.
We can also propose a similar ionic mechanism, passing
through oxonium silicates 22 or oxonium aluminates 25, to
explain the formation of dioxolanes 5b–5o from ethylene
glycol and carbonyl compounds 4b–4o in the presence of
silica gel or alumina. Thus, the Lewis (Si and Al) sites
located on the active surface of these two catalysts form
coordination complexes with the sp2 oxygen of the car-
bonyl compound 4 (Scheme 4). The nucleophilic attack of
ethylene glycol on the tetra coordinated aluminates 25
(route b) and the pentacoordinated silicates 22 (route a)
leads to zwitterions 26 and 23. Finally, cyclization of these
intermediates, probably through oxonium cation 24, gives
123

T. Rohand et al.
pressure, without solvent, and generate the desired adducts
in satisfactory yields. The extension of these reactions to
the synthesis of other heterocycles, in the presence of these
solid catalysts and under optimum experimental conditions
responding to the demands of green chemistry, is currently
being pursued in our laboratory.
Scheme 4
Experimental
NMR spectra were recorded on a Bruker AC spectrometer
1
(300 MHz H and 75 MHz 13C) in CDCl3 solution. The
chemical shift (d) of the signals described is expressed in
ppm relative to TMS taken as internal reference. The fol-
lowing abbreviations are used: s: singlet, d: doublet, t:
triplet, m: multiplet, l: large. The coupling constants (J) are
expressed in Hz. The reagents are from Aldrich. The silica
gel is commercial type Merck 60 (70–230 mesh) and alu-
mina is an Aldrich commercial product. The clay H2 is
prepared by acid activation, for 2 h, from the original Hb-
clay from Morocco.
dioxolanes 5, releases water and regenerates the corre-
sponding catalysts.
The formation of oxazolidines 7 from 2-amino-2-
methylpropanol and carbonyl compounds 4 can also be
rationalized by similar ionic mechanisms (Scheme 5).
Under acidic conditions, such as acid-activated clay, pro-
tonation of ketones 4 generates oxonium species 27 that
reacts with 6 to form the protonated hemiaminal 28. Proton
shift, followed by loss of water, leads to iminium ion 30
that cyclizes to O,N-acetal 7 (Scheme 5).
In all the experiments, ethylene glycol (1) or 2-amino-2-
methylpropanol (6) present in the crude reaction product is
removed by adding water to the crude reaction mixture.
After treatment, a mixture of carbonyl compounds 4 and
dioxolane 5 or oxazolidine 7 is recovered. The yields of
In the catalytic process using silica or alumina,
adsorption of the carbonyl compound 4 onto the active
surface of the catalysts takes place, leading to the oxonium
silicate 22 and the oxonium aluminate 25. Subsequent
nucleophilic attack of the nitrogen of aminoalcohol 6 on
the zwiterions 22 and 25 generates the ammonium alumi-
nate 32 and ammonium silicate 31 that cyclize to oxazo-
lidine 7, via iminium ion 30, release water and regenerate
the clay (Scheme 6, routes a and b).
1
products 5 and 7 are estimated from the H NMR and 13C
NMR spectra of the crude reaction mixtures to avoid their
decomposition during chromatographic purifications, as
reported in other work [15]. Compounds 2, 3, 5a, 5k, and 5l
1
are identified by comparing their H and 13C NMR spectra
with authentic samples marketed by Aldrich.
Synthesis of 1,3-dioxolanes
Conclusions
Synthesis of 2-methyl-1,3-dioxolane (5a) using sulfuric
acid Procedure at atmospheric pressure: 7.67 g of ethy-
lene glycol (1, 124 mmol) and H2SO4 (4% by mass) are
placed in a flask (50 cm3) equipped with a reflux condenser
We have developed a novel method for the synthesis of
dioxolanes and oxazolidines in the presence of catalysts
based on silica and alumina. The reactions proceed under
Scheme 5
123

Synthesis of dioxolanes and oxazolidines by silica gel catalysis
Scheme 6
and then heated at 196 °C for 3 h. After cooling, 20 cm3 of
water is added to the crude mixture to remove residual
ethylene glycol. The aqueous solution is extracted with
ether (3 9 50 cm3). The organic phases are combined and
then dried over MgSO4. After filtration and evaporation of
the ether in vacuo, a mixture of 2 and 3 is recovered. The
yields of products 2 and 3 are displayed in Table 1.
Procedure under pressure: 7.67 g of ethylene glycol (1,
124 mmol) and H2SO4 (4% by mass) are placed in an
autoclave (100 cm3). The sealed reactor is heated at 150 °C
for 3 h or for 24 h. After cooling, the residue is treated in
the same manner as described above. The yields of
products 2 and 3 are listed in Table 1.
cooling and separating the silica gel by filtration, the
residue is treated in the same manner as described above.
The yields of dioxolanes are given in Tables 3 and 4.
Synthesis of 1,3-dioxolanes 5b–5o using alu-
mina Ethylene glycol (1, 3.41 g, 55 mmol), carbonyl
compound 4 (1.50 mmol), and 50 mg of alumina were
placed in an autoclave (100 cm3). The sealed reactor was
heated for 24 h at various temperatures. After cooling and
separation of the alumina by filtration, the residue was
treated in the same manner described above. The isolated
yields of dioxolanes are given in Table 3.
Trace amounts of the dioxolanes 5b and 5c can be
detected in the 13C NMR spectra of the crude reaction
mixture by the presence of the low intensity signals
corresponding to the C2–H carbons at 102.51 and
102.45 ppm, respectively.
Synthesis of 2-methyl-1,3-dioxolane (5a) Procedure at
atmospheric pressure: 7.67 g of ethylene glycol (1,
124 mmol) and 0.1 g of silica gel are placed in a flask
(50 cm3) equipped with a reflux condenser and the whole is
heated at 196 °C for 120 h. After cooling and separating
the silica gel by filtration, the residue is treated in the same
manner as described above. Diethylene glycol (2) was
obtained in a yield of 1% (Table 1).
Synthesis of oxazolidines 7
Synthesis of oxazolidines by silica gel
Procedure under pressure: 7.67 g of ethylene glycol (1,
124 mmol) and 0.1 g of silica gel are placed in an
autoclave (100 cm3). The sealed reactor is heated to
150 °C for various amounts of time. After cooling and
separating the silica gel by filtration, the residue is treated
in the same manner as described above. The yields of
products 2 and 5a are listed in Table 1.
2-Amino-2-methylpropanol (6, 4.89 g, 55 mmol, 8.5 eq),
6.50 mmol of carbonyl compound 4 (1 eq), and 50 mg of
silica gel are placed in an autoclave (100 cm3). The sealed
reactor is heated for 24 h at various temperatures. After
cooling and separating the silica gel by filtration, the
residue is treated in the same manner as described above.
The yields of isolated oxazolidines 7 are given in Table 5.
Synthesis of 1,3-dioxolanes 5b–5o Ethylene glycol (1,
3.41 g, 55 mmol, 36 eq), 1.50 mmol of carbonyl com-
pound 4 (1 eq), and 50 mg (1 eq) or 500 mg (10 eq) of
silica are placed in an autoclave (100 cm3). The sealed
reactor is heated for 24 h at various temperatures. After
Synthesis of oxazolidines by acid-activated clay
2-Amino-2-methylpropanol (6, 4.89 g, 55 mmol, 8.5 eq),
6.50 mmol of carbonyl compound 4 (1 eq), and 50 mg of
123

T. Rohand et al.
24. Crimmins MT, Guise LE (1994) Tetrahedron Lett 35:1657
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RC (1973) J Org Chem 38:1974
H2-activated clay are placed in an autoclave (100 cm3).
The sealed reactor is heated for 24 h at various tempera-
tures. After cooling and separation of the H2-clay by fil-
tration, the residue is treated in the same manner as
described above. The yields of oxazolidines 7 are given in
Table 5.
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Acknowledgements Prof. Dr. Taoufik Rohand thanks the University
Cadi Ayyad and specially the Faculty Polydisciplinaire of Safi for a
´ ˆ
professorship and financial support for the LACM laboratory. Jerome
Savary thanks the Catholic University of Louvain-La-Neuve for a
scholarship.
33. Tugarova A, Kazakova A, Kamnev A, Zlotskii S (2014) Russ J
Gen Chem 84:1930
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JS, Wagner A (2016) Org Biomol Chem 14:4794
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