A safe two-step process for manufacturing glycidyl nitrate from glycidol involving solid-liquid phase-transfer catalysis

Article abstract of DOI:10.1021/op200066e

A new and safer two-step process for manufacturing glycidyl nitrate from glycidol is reported. In the first step glycidyl tosylate is obtained by reacting glycidol with p-tosyl chloride in the presence of triethylamine according to any one of the well-known procedures for obtaining tosyl esters described in the literature. In the second step, glycidyl tosylate is reacted with NaNO₃ in refluxing acetonitrile under solid-liquid phase-transfer catalysis conditions using tetrabutylammonium nitrate as catalyst. Acetonitrile and the phase-transfer catalyst were recycled 12 times without deactivation, yielding 99% pure glycidyl nitrate in a cumulative isolated yield of 81.5% with a catalyst turnover number of 85.7 mol substrate per mol phase-transfer catalyst. This procedure avoids the use of the dangerous reactants used in the current manufacturing processes of glycidyl nitrate and could be useful as a safe and general method for obtaining nitrate esters.

Full text of DOI:10.1021/op200066e

TECHNICAL NOTE
pubs.acs.org/OPRD
A Safe Two-Step Process for Manufacturing Glycidyl Nitrate from
Glycidol Involving SolidÀLiquid Phase-Transfer Catalysis
Josꢀe R. Ochoa-Gꢀomez†,* and Juan J. Blanco-Gꢀomez‡
†Universidad Alfonso X el Sabio, Department of Industrial Technology, Avda de la Universidad 1, 28696 Villanueva de la Ca~nada,
ꢀ
Madrid, Spain, and Tecnalia Research and Innovation, Tecnalia-Energy, Department of Bioenergy, Parque Tecnolꢀogico de Alava,
ꢀ
Leonardo Da Vinci, 11, 01510 Mi~nano, Alava, Spain
‡Reuser S.L., C/Chile 10, Edificio Madrid 92, Oficina 43, 28290 Las Rozas, Madrid, Spain
ABSTRACT: A new and safer two-step process for manufacturing glycidyl nitrate from glycidol is reported. In the first step glycidyl
tosylate is obtained by reacting glycidol with p-tosyl chloride in the presence of triethylamine according to any one of the well-known
procedures for obtaining tosyl esters described in the literature. In the second step, glycidyl tosylate is reacted with NaNO3 in
refluxing acetonitrile under solidÀliquid phase-transfer catalysis conditions using tetrabutylammonium nitrate as catalyst.
Acetonitrile and the phase-transfer catalyst were recycled 12 times without deactivation, yielding 99% pure glycidyl nitrate in a
cumulative isolated yield of 81.5% with a catalyst turnover number of 85.7 mol substrate per mol phase-transfer catalyst. This
procedure avoids the use of the dangerous reactants used in the current manufacturing processes of glycidyl nitrate and could be
useful as a safe and general method for obtaining nitrate esters.
’ INTRODUCTION
’ RESULTS AND DISCUSSION
Glycidyl nitrate (GN) is a valuable chemical used for manu-
facturing energetic polymers such as hydroxy-terminated poly-
(glycidyl nitrate) which in turn is used as a component of high-
energy binder matrices in propellant compositions.1 GN has
been synthesized from glycidol by a two-step procedure in which
glycidyl tosylate (GT) is obtained from glycidol and tosyl
chloride (TsCl) in a first step, and GT is converted into GN in
a second step by reacting with concentrated (70 wt %) HNO3 at
10 °C or less under N2 atmosphere,2,3 from glycidol in a single
step by reaction with N2O5 in an inert solvent such as dichlor-
omethane at temperatures between À10 °C and À20 °C,4 and
from glycerol in a two-step synthesis in which dinitroglycerol is
first obtained by reacting glycerol with concentrated (90 wt %)
HNO3 in CH2Cl2 at temperatures below 15 °C, and subse-
quently it is reacted with 50 wt % NaOH in CH2Cl2 at
temperatures below 25 °C to yield GN.5 All of these synthetic
methods have in common the use of hazardous chemicals (N2O5
and concentrated HNO3) and/or the formation of dangerous
intermediates and/or byproduct such as dinitroglycerol and
nitroglycerin. However, green and safer synthetic pathways of
energetic materials for defense and space applications are cur-
rently desired.6
In this contribution, a safe and easy process for manufacturing
GN from glycidol avoiding the above-mentioned drawbacks is
described (Scheme 1). The procedure consists of two steps: (a)
step 1: synthesis of GT by reacting glycidol with TsCl in the
presence of triethylamine (TEA) to scavenge the HCl formed
and (b) step 2: synthesis of GN by reacting GT with solid
NaNO3 in refluxing acetonitrile (ACN) using tetrabutylammo-
nium nitrate (TBAN) as a solidÀliquid phase-transfer catalyst
(PTC). This synthetic pathway could be used as a safe and
general method for obtaining nitrate esters useful as explosives
and pharmaceuticals.
Manufacturing of Glycidyl Tosylate (GT) (Step 1). The
preparation of tosyl esters is a well-known reaction which often
proceeds in yields higher than 90% in the presence of a base such
as triethylamine.7,8 Consequently, we have not studied this step
at this process development stage but instead we have used
commercially available GT.
Manufacturing of Glycidyl Nitrate from Glycidyl Tosylate
(Step 2). No GN formation was detected in a series of pre-
liminary experiments carried out using solid NaNO3 as nucleo-
phile and molten GT as both solvent and reactant at temperatures
between 50 and 100 °C. However, reaction was observed in
aprotic organic solvents such as dimethylacetamide (DMA) and
dimethylformamide (DMF). For instance, a 95% yield (HPLC,
not isolated) was obtained in DMA after 5 h, but temperatures
close to 100 °C were needed, and glycidol was formed as a
byproduct probably by base-catalyzed hydrolysis of GT due to
the presence of water, always present in trace amounts in such
hygroscopic solvents. Likewise, glycerol 1-mononitrate was de-
tected in very low amounts together with acetic acid resulting from
GN and solvent hydrolysis, respectively. On the other hand, the
proximity between the boiling points of GN (179.7 °C) and
DMA (165 °C) was a drawback for a straightforward isolation of
GN in high purity. ACN is a solvent that could facilitate the
isolation of GN because it is easily removed from a reaction
mixture by evaporation at mild temperatures, but no reaction was
observed in said solvent after 7 h under reflux, very probablÀy due
to the insolubility of NaNO3 in ACN which makes NO3 not
available for reaction with GT.
Special Issue: Safety of Chemical Processes 11
Received: March 17, 2011
Published: April 19, 2011
r
2011 American Chemical Society
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|

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TECHNICAL NOTE
Scheme 1. Proposed two-step synthesis of glycidyl nitrate from glycidol (PTC = phase-transfer catalyst)
Scheme 2. Schematic representation of step 2
Phase-transfer catalysis is a well-known methodology for
facilitating interphase transfer of species, making reactions
between reagents in two immiscible phases possible.9,10 Conse-
quently, we thought that the reaction could proceed in ACN if
NO3À could be transferred from the solid phase to the liquid one
by means of a PTC soluble in ACN. Quaternary ammonium salts
are typical PTC, but we decided to reject quaternary ammonium
halides as PTCs because their halide anions could act as nucleo-
philes yielding the corresponding epihalohydrins. Finally, we
decided that the best choice was to use a quaternary ammonium
nitrate becausenitrate was thedesired nucleophile for the intended
reaction. Tetrabutylammonium nitrate (TBAN) was ultimately
chosen as PTC to be tested in this reaction. According to our
hypothesis, the reaction should proceed as depicted in Scheme 2.
TBAN 2 would be solubilized in ACN and could react with GT 1
through a SN2 mechanism to give the desired product 3 and
tetrabutylammonium p-tolylsulfonate 4. The latter would react at
the solidÀliquid interface with NaNO3 5 in the solid phase,
yielding sodium p-tolylsulfonate 6, which would precipitate from
the reaction medium, and TBAN 2, thereby achieving the
transference of the nitrate ion from the solid to the liquid phase
and allowing the reaction to proceed to completion.
Our hypothesis was confirmed by reacting GT (0.25 mol),
NaNO3, and TBAN in a 1:1.5:0.14 molar ratio, respectively, in
refluxing ACN (60 g, 82 °C) for 6 h under vigorous stirring. GN
yield was 58% by HPLC, and 99% pure GN was isolated in a 34%
yield after workup. A much higher isolated yield of 76% was
obtained by carrying out the reaction under the same conditions
but in a 1:3.2:0.14 GT/NaNO3/TBAN molar ratio, indicating
that GT/NaNO3 molar ratio is a key parameter although its
influence on conversions and yields has not been deeply studied.
The residue obtained after workup consisted of quaternary
ammonium salt, unreacted GT (in low amounts as detected by
TLC with CHCl3 as eluent, UV detection at 254 nm), and
undistilled GN. Then, the possibility of recycling this residue was
studied by adding fresh GT (0.25 mol) and NaNO3 in a 1:3.2
molar ratio and recycling the ACN previously recovered by
evaporation. No amount of TBAN was added. Reaction was then
repeated under the same conditions, and the residue obtained
after workup was successively recycled by adding into it fresh GT
and NaNO3 at the above-mentioned molar ratio, and using the
recovered acetonitrile from the former reaction as solvent.
Results are depicted in Figure 1. As it can be seen, the isolated
cumulative yield increases slightly with the number of recycles
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Organic Process Research & Development
TECHNICAL NOTE
observations, the acquisition of reaction safety data by
reaction calorimetry and DSC is strongly recommended
prior to any further scale-up.
’ CONCLUSIONS
By taking into account the high yields (often >90%) usually
obtained in the synthesis of tosyl esters (step 1), the overall
isolated yield of the process herein outlined may be about 75%,
a good yield, taking into account that the process has not been
optimized. The process is safer than those currently used for
manufacturing GN, and the catalyst turnover number was
85.7 mol substrate/mol PTC (69.8 mol of isolated GN per mol
of PTC) equivalent to a specific consumption of the phase-
transfer catalyst as low as 0.036 kg/kg isolated GN, an amount
which can even be further reduced because no catalyst deactiva-
tion was observed after 12 recycles. The solvent, ACN, is easily
recovered by distillation and recycled. At first, the characteristics
of the waste streams generated in step 1 (TEA hydrochloride) and
in step 2 (a mixture of NaNO3 and sodium-p-toluenesulfonate)
should enable, after a relatively easy treatment, a recovery of
NaNO3 and the regeneration of TEA and p-toluenesulfonyl
chloride, all of them to be recycled into the process. Considering
that the process has not been optimized, the results obtained are
very promising for industrial application.
Figure 1. Cumulative isolated glycidyl nitrate yield (Y) versus the
number of recycles of phase-transfer catalyst (PTC) and solvent.
from 76% at run 1 to 81.5% at run 8 and then remains constant.
Catalyst turnover number (TON) was 85.7 mol substrate/mol
PTC (69.8 mol of isolated GN per mol of PTC) and probably
may be significantly increased according to the results shown in
Figure 1 in which no loss in catalyst activity is observed.
The reaction was also carried out on a 2-L scale with the same
results.
’ EXPERIMENTAL SECTION
Ideas for Process Optimization. In our opinion, any project
for process optimization should address at least the following items:
(a) Reduction of Solvent Inventory. In a further develop-
ment of step 1 the same solvent, ACN, used in step 2
should be the first choice.
(b) Process Intensification. If items (a) works successfully,
a process intensification of the overall process could be
easily carried out; after completion of step 1, the reaction
mixture is filtered to remove the precipitate of TEA
hydrochloride, and the filtrate consisting of a solution of
GT in ACN is directly used in step 2 without further
purification.
(c) TEA Recovery in Step 1. TEA hydrochloride obtained as
byproduct can be treated with aqueous NaOH to release
TEA which can be easily separated by distillation and
recycled to the TsCl synthesis, or alternatively, TEA
can be recovered by treating an aqueous solution of
TEA hydrochloride by electrohydrolysis with bipolar
membranes,11,12 generating a useful aqueous HCl stream
at the same time.
(d) Recovery of Excess NaNO3 and Sodium p-Tolylsulfo-
nate in Step 2. A solid mixture consisting of unreacted
NaNO3 and sodium p-tolylsulfonate is obtained as waste
in step 2, but taking into account the different character-
istics of both salts, their separation by solidÀliquid
extraction or fractional crystallization must not be a
difficult task, bearing in mind that NaNO3 can be recycled
to this step even with a relatively large amount of sodium
p-tolylsulfonate as impurity. After a suitable treatment
(for instance, acidification to give the free acid) isolated
sodium p-tolylsulfonate could be reused for manufactur-
ing the raw material, TsCl, to be used in step 1.
Materials. All chemicals were chemically pure reagents. TBAN
was synthesized by neutralizing a 40 wt % aqueous solution
of tetrabutylammonium hydroxide with 20 wt % aqueous nitric
acid. After water evaporation at vacuum in a rotatory evaporator,
cooling of the concentrated solution, filtering off the precipitated
product, and drying at 100 °C overnight, TBAN was obtained as
a white solid (mp ranged from 110 to 120 °C, depending on the
batch).
Analytical Methods. GN was quantified (wt %) by HPLC
using a Perkin-Elmer chromatograph model 3B and a UV detector
Perkin-Elmer LC-75 at 195 nm, according to the procedure
described by Kaplan et al.13 1H NMR spectra were measured with
a Varian VXR-200 spectrometer (200 MHz) at 25 °C in CDCl3
using tetramethylsilane as internal reference standard. IR spectra
were recorded in a Perkin-Elmer FTIR spectrometer model
Spectrum 2000. GN purity was also calculated as the percentage
of nitrogen relative to the theoretical one as determined by
elemental analysis using a LECO CHN-800 analyzer.
Synthesis of Glycidyl Nitrate (GN). GT (0.25 mol), NaNO3
(0.83 mol), TBAN (0.034 mol), and ACN (60 g) are charged
into the reactor described above, and the reaction mixture
was refluxed (85 °C) for 6 h under vigorous stirring. Sodium
p-tolylsulfonate precipitated off with time as a pearly looking
solid, causing a significant amount of foam. Consequently, it is
advisible to keep the volume of the reaction mixture equal to or
below 60% of that of the reactor. Then, the solid obtained
consisting of a mixture of unreacted sodium nitrate and sodium
p-tolylsulfonate was filtered off and washed with ACN. ACN in
the combined filtrates was recovered by distillation at 100 mmHg
and 50 °C and can be reused in further reactions. The residue
was distilled at 1À3 mmHg at a boiler temperature e100 °C for
avoiding GN degradation. Glycidyl nitrate distillates were ob-
tained as a clear liquid, yielding 22.6 g (0.19 mol, 76% yield) with
a purity of 99% as determined by elemental analysis and HPLC.
(e) Safety Data. Even though step 2 does not seem to be
a problematic reaction according to the laboratory
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TECHNICAL NOTE
Elemental analysis. Calculated: C (30.26%), H (4.23%), N
(11.76%), O (53.75%); Found: C (30.09%), H (4.17%), N
(11.65%), O (54.09%).
1H NMR: δ (CDCl3) 2.72 (1H, dd); 2.92 (1H, t); 3.29 (1H, m);
4.77 (1H, dd); 4.34 (1H, dd) ppm.
IR: ν max (film): 1632, 1424, 1343, 1280, 1133, 997, 968, 908,
858, 756, 663 cmÀ1
.
’ AUTHOR INFORMATION
Corresponding Author
*jrochoag@telefonica.net.
’ ACKNOWLEDGMENT
The contribution of Mr. Josꢀe Ma Garrido to the experimental
work is gratefully acknowledged.
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