Characterization of FOX-7, its Precursors and Possible Byproducts

Erik Holmgren*, Håkan Carlsson, Patrick Goede and Nikolaj Latypov

FOI, Swedish Defence Research Agency, Department of Energetic Materials,
S-147 25 Tumba, Sweden.

Carlo Crescenzi
Department of Analytical Chemistry, Stockholm University
S-106 91 Stockholm Sweden

Summary
Three different synthetic routes to FOX-7 are discussed and possible by-products are
identified. The route starting from 2-methyl-pyrimidine-4,6-dione is the method
currently used for production of FOX-7 on a pilot plant scale. Based on this route an
LC-MS method was developed for the analysis of FOX-7 its precursors and all major
by-products.

Keywords: FOX-7, HPLC, porous graphitic carbon, Hypercarb, Synthesis.

1. Introduction

1,1-diamino-2,2-dinitroethylene (FOX-7) (1) is a thermally stable impact insensitive

explosive with a performance very close to RDX1. The sensitivity of FOX-7 (1) to
physical constraints (impact, friction, heat, etc...) has been extensively studied2,3,
these studies support our belief that FOX-7 (1) is a prime candidate as a filler in
insensitive munitions.

FOX-7 (1) was first synthesized in 1998 by Latypov et al4. Since then different
synthetic methods have been developed and FOX-7 (1) is now synthesized in a pilot-
plant on a multi kilogram scale. Until now three different routes to prepare FOX-7
have been disclosed.
2. Synthesis

The first route is based upon the nitration of 2-methylimidazole (2) at a controlled
temperature (15-20°C) whereby 2-dinitromethylene-imidazolidine-4,5-dione (4) is
formed (15%). The reaction proceeds over the postulated intermediate 2-
dinitromethylene-5,5-dinitro-imidazolidin-4-one (3). This compound was isolated as a
white precipitate in low yield (max 15%) but upon standing at room temperature it
lost nitrogen oxides and produced 2-dinitromethylene-imidazolidine-4,5-dione (4)
(Scheme 1). When (4) was dissolved in aqueous ammonia a bright yellow solid
(FOX-7) precipitated in excellent yield (87%).

It was found to be very important to control the temperature of the nitration reaction.
If the reaction was run at room temperature or higher the only product of the reaction
was parabanic acid (5). Nitroform (6) was judged to be a further possible by-product
of the nitration of methyl imidazole (2) as a result of the possible trinitration of the
methyl group. During the ammonolysis of (4), ammonium oxalate is formed together
with FOX-7 (1). The oxalate was however not found in the product after washing.
There is however a possibility to get the product (1) contaminated by oxamide if the
ammonolysis is done at a too low temperature (<20° C)5.

NO2 NO2

H O2N H
O2N N N NO2
NO2
N HNO3/H2SO4 -N2O3 O2N
O
15-20oC +
HN HN
NO2 NO2
HN 4 6

2 HNO3/H2SO4 3 O O
NH3(aq)
45-50oC
O H
N
H2N NO2 O O O O
O
HN
+ +
5
H2N NO2 O O H2N NH2
O 1 7 8

Scheme 1: FOX-7 synthesis from methyl imidazole and possible by-products.

The second synthetic route to FOX-7 (1) proceeds via the nitration of 2-methoxy-2-
methyl-4,5-imidazolidinedione (9) and/or 2-methyl-4,5-imidazolidinedione (10). This
reaction produces the same 2-dinitromethylene-imidazolidine-4,5-dione (4) which
was obtained in route (1), but in much better yield (70%). FOX-7 is then obtained
from compound (4) in the same way as in route (1), by ammonolysis. The major
disadvantage of this route is the synthesis of the starting material which is
inconveniently prepared from acetamidine hydrochloride and diethyl oxalate whereby
a mixture of (9) and (10) is obtained. The product also has to be purified from
contaminating salts, which is only possible by cumbersome extractions. However, the
nitration works equally well with compound (9), (10) or a mixture of (9) and (10)4.

O
O H
N
NO2
O
HN
O2N H
N H2 N NO2 O O
9
O HNO3/H2SO4 NH3(aq)
O +
+ < 35oC HN
H H2 N NO2 O O
N 1 7
4
O + O
NO2
HN
O2N

10 O NO2
6

Scheme 2: FOX-7 synthesis from 2-methoxy-2-methyl-4,5-imidazolidinedione (9)

and/or 2-methyl-4,5-imidazolidinedione (10) and possible by-products.

The third synthetic route to FOX-7 (1) is based upon the nitration of 2-methyl-
pyrimidine-4,6-dione (11) in mixed acids at room temperature (Scheme 3). This
reaction leads to the precipitation of 2-Dinitromethylene-5,5-dinitro-dihydro-
pyrimidine-4,6-dione (12), which is easily hydrolysed in water to FOX-7 (1) and
dinitromethane. We were only able to isolate 2-methyl-5-nitro-1H-pyrimidine-4,6-
dione (13) as an intermediate. Even if less than 4 equivalents of the nitrating agent
were used only (12) and (13) could be isolated. The starting material (11) is prepared
from acetamidine hydrochloride and diethyl malonate. However, in contrast to
compound (9) it is easily purified. The overall yield of FOX-7 (1) from of 2-methyl-
pyrimidine-4,6-dione (11) is 80%. This route was first reported by Astrat’ev et al6 it
has since then been under investigation in Sweden7 and it has been adapted to pilot
plant synthesis at NEXPLO Bofors AB.
 O2N NO2

O O O O NO2
HNO3(exc) O2N

N NH H2SO4, RT HN NH + NO2
6

O2N NO2
11 HNO3(1eq) 12 OH-, -CO2
H2SO4, RT

HNO3(exc)
H2SO4, RT
H2N NO2 NO2
NO2
+
O O NO2
H2N 1 NO2
14
N NH

13

Scheme 3: FOX-7 synthesis from 2-methyl-pyrimidine-4,6-dione (11) and

possible by-products.

The synthetic path outlined in route 3 is the current commercial production method,
due to the formation of dinitromethane as a secondary product there is a continuous
interest in adapting route 1 and 2 as possible ways of production.

2. Experimental.

2.1 Chemicals and Reagents

The chemicals and reagents used were: water (HPLC Isocratic grade, J.T.Baker),
acetonitrile (HPLC Isocratic grade, J.T.Baker) and ammonia (water solution, 25%
analytical grade, Riedel-de Haen).

2.2 High Performance Liquid Chromatography

2.2.1 Analyte stock solutions:

The following compounds were dissolved in a 0.1 % NH3/water solution (v/v) to a

concentration of 0.2 µmole/ml and used as an analyte reference standard. FOX-7
(1,1-diamino-2,2-dinitroethylene, 1), 2-Methyl-1H-pyrimidine-4,6-dione (11),
dinitromethane (14), 2-methyl-5-nitro-1H-pyrimidine4,6-dione (13) and Nitroform
(6). 10 microliters of this solution were injected as a reference.

2.2.2 HPLC-UV-MS system:

A Waters 2695 Quartenary HPLC System (Waters, Milford , MA, USA) was used to
deliver the solvent mixture. HPLC separation was carried out on a HypercarbTM
porous graphitic carbon (PGC) 150x4,6 mm column (5 µm particles) (Thermo Quest,
Cheshire, UK) using a gradient mobile phase.
Gradient system , A 100 % Water, B 7 % Water, 3 % NH3 and 90 % acetonitrile (v/v).
Analysis starts with A/ B 95/5 for 2 min with a flow rate of 0.8 ml/min then during 10
min the mixture is changed to A/ B 0/100 and then held there for 3 min. The
temperature was kept at 55 °C. UV detection was conducted by a Waters UV Detector
Model 996 photodiode array detector at 250 nm. The masspectrometer used was a
Bruker Esquire 3000+ ion trap mass spectrometer (Bruker Daltonics, Bremen,
Germany) equipped with an electrospray ionization interface. Interface conditions
were set to the following values: Nebulizer Gas 60 psi, dry temp. 350°, dry gas
10l/min, HV 4000 volt, Trap Drive 74.4, Octopole RF Amplitude 114.6 Vpp.

3. Results and Discussions

3.1 Retention Behaviour of FOX-7 and its Possible By-products.

FOX-7 is very polar compound, which is virtually insoluble in many organic solvents
(except dimethylsulfoxide, dimethylformamide, γ-butyrolactone and N-methyl-2-
pyrrolidone). Compounds like these are usually very difficult to retain in conventional
reversed phase conditions without the addition of ion pair salts. As expected, when
using a C18 column under standard conditions FOX-7 eluted with the front8.

During the last years there has been a great interest in porous graphitic carbon (PGC)
as a column packing material9,10. The unique characteristic of this material is the
ability to interact, in reversed phase condition, with a polar molecule due to an
induced electrostatic dipole, (the so-called polar retention effect on graphite9). In this
way the retention time often increase with the polarity of the analyte. The advantage
of longer retention times for polar molecules suggested us to use this stationary phase
to separate and analyze the very polar explosive FOX-78. When studying the potential
by-products from the current synthesis method (route 3) special attention was needed
to address dinitromethane (14) and nitroform (6) two compounds which have pKa
values of 3.611 and 0.112 respectively, and in the solvent systems used they are thus
deprotonated. The intermediate (11) has a pKa of 6.3513 and (13) having an extra
electron withdrawing group should have an even lower pKa. Both (11) and (13) are
therefore deprotonated in the solvent system used and thus easily retained on the PGC
phase. This is in correspondence with earlier work which has shown that its possible
to retain salts on a PGC column14-16. Due to the high polarity of all of the analytes it
was possible to separate all of them using the developed analytical method.

3.2 HPLC-UV-MS Analysis of FOX-7, Intermediates and Possible

By-products.

As all the analytes were acidic they were all easily dissolved in slightly basic water
(0.1% NH3), which is optimal when running water based systems. The ammonia
stabilizes dinitromethane and nitroform in their ionic form which enhances their
retention behaviour and prevents them from decomposing. Ammonia is essential due
to the site competition effect of ammonia with the analytes. This leads to an improved
peak shape and shorter retention times. The use of ammonia in the gradient system
also improves the negative ionisation when using ESI-MS analysis on neutral species
with acidic protons. The system gradient is necessary to prevent co-elution of (11) and
(14), improve peak shape and obtain shorter retention times. The elution order when
using this system was found to be: 2-Methyl-1H-pyrimidine-4,6-dione (11),
dinitromethane (14), 2-methyl-5-nitro-1H-pyrimidine4,6-dione (13), FOX-7 (1,1-
diamino-2,2-dinitroethylene, (1)), and Nitroform (6) (Figure 1). The analysis and
equilibration step, when optimized, could be performed in 20 minutes. The limit of
detection for the analytes in negative ESI are 10-74 ng and in UV at 250 nm 3-13 ng
(Table 1).
 0.25 11

0.20

1
0.15
AU

13
0.10 6
14

0.05

0.00
5.00 10.00
Minute s

Figure 1. HPLC UV Chromatogram at 250 nm of FOX-7, Intermediates and

Possible By-products.

Intens. FOXdetection030214full scan.d: TIC-All

x106

13

3 6

1
11
14
0
50 51 52 53 54 55 56 57 58 59 Time[min]

Figure 2. MS-Chromatogram in negative ionization mode, monitoring full-scan

TIC.
 Intens. FOXdetection030214full scan.d: TIC+All
x107

1.0
11

0.8

1
0.6

0.4
13

0.2

0.0
50 51 52 53 54 55 56 57 58 59 Time[min]

Figure 3. MS-Chromatogram in positive ionization mode, monitoring full-scan

TIC.

It is possible to detect all analytes in the negative ionization mode due to the relative
ease to deprotonate them (Figure 2, Table 1). For some of the analytes it was also
possible to detect them in the positive ionization mode according to the M+H ions,
namely (11), (13) and (14) (Figure 3). All compounds showed a distinctive fragment
pattern in full scan mode. We have however not identified the structure of these
fragments (Table 1).
 LOD neg. Full Scan Full Scan
Compounds LOD pos. ESI LOD UV 250
ESI (ng) Fragments Fragments
(ng) nm (ng)
Neg ESI POS ESI
125 (100),81
11 10 18 127 (100) 3
(30)
14 74 NI 105 (100) NI 6
170
(100),153 172 (100),
13 15 27 13
(40),126 (1), 154 (26)
85 (4)
171 MNa+
147 (100), (100), 149
1 12 23 113 (13), 105 (66), 132 (4), 10
(34) 103 (16), 86
(8), 73 (9)
150 (100),
6 5 NI NI 12
104 (26)

Table 1. Detectionlimits and ESI-fragmentation for the analysis of FOX-7,

Intermediates and Possible By-products.

4. Conclusions

The method presented is suitable for purity analysis of FOX-7. Starting materials,
intermediates and proposed by-products from the present production method can all
be detected by LC-UV-ESI-MS in a single analysis. The detection levels are all in the
low nano-gram range which is sufficient for trace analysis of product impurities.

Acknowledgements

The authors would like to thank the Swedish Defence Forces and the Swedish
Defence Materiel Administration for giving financial support to this project.

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