Preparation method for 3,5-dinitropyrazole

Abstract

The present invention relates to a process for preparing 3,5-dinitropyrazole which includes a step of obtaining N-acetyl-3-nitropyrazole from pyrazole, and a step of sigmatropic rearrangement of the compound obtained.

Description

Title of the invention: Process for preparing 3,5-dinitropyrazole Technical field of the invention

[0001] The invention relates to the field of energetic molecules that can be used in the manufacture of pyrotechnic charges. More particularly, the invention relates to a process for preparing precursors of 3,4,5-trinitropyrazole. State of the art

[0002] Energetic molecules such as 3,4,5-trinitropyrazole (hereinafter, "3,4,5-TNP") or derivatives of this compound (such as those described in EP-A-2 130 821) are suitable for the manufacture of pyrotechnic charges due to their interesting properties in terms of performance and sensitivity, while maintaining a high level of thermal stability, compatible with their use in the fields of propulsion and explosives.

[0003] A synthetic route for 3,4,5-TNP from 3,5-dinitropyrazole (hereinafter, "3,5-DNP") is described in application FR-A-2 917 409. Another process for preparing 3,4,5-TNP from 3,5-DNP is described in application CN105669557. Operating conditions for the sigmatropic rearrangement of N-nitropyrazole are described, for example, in J. Org. Chem. 1973, 38(10), 1777-1782. These operating conditions (6 h at 160°C) are considered limiting for industrial-scale development. This results in poor efficiency and yield for the reaction to obtain 3,4,5-TNP from N-nitropyrazole. Application FR-A-3 085 377 describes a process for the synthesis of 3,5-DNP from pyrazole; this process involves two sigmatropic rearrangement steps by microwave heating. However, the use of microwaves is a limiting factor for considering industrial-scale development.

[0004] This observation led the inventors to seek solutions to improve the operating conditions for the synthesis of 3,5-DNP on an industrial scale. Summary of the invention

[0005] The inventors have highlighted the fact that it is possible to simplify the synthesis of 3,5-DNP by using a specific intermediate, namely N-acetyl-3-nitropyrazole.

[0006] Thus, according to a first aspect, the invention relates to a process for preparing 3,5-dinitropyrazole of formula (I):

[0007] which includes:

[0008] a) the nitration of pyrazole in the presence of acetic anhydride;

[0009] b) the heat treatment of the mixture obtained in step a) to obtain a mixture containing the compound of formula (II): .... CW;

[0010] c) hydrolysis of the mixture obtained in step b) to obtain a mixture containing the compound of formula (III): (in);

[0011] d) nitration of the mixture obtained in step c) in the presence of acetic anhydride to obtain a mixture containing the compound of formula (IV): (IV); and

[0012] e) the heat treatment of the mixture obtained in step d).

[0013] According to a second aspect, the invention relates to the intermediate of formula (II). Brief description of the drawings

[0014] Figures 1 and 2 illustrate the use of a continuous flow setup to perform certain steps of the process according to the invention. Description of the invention

[0015] According to a first aspect, the invention relates to a method for preparing the 3,5-Dinitropyrazole of formula (I):

[0016] which includes:

[0017] a) the nitration of pyrazole in the presence of acetic anhydride;

[0018] b) the heat treatment of the mixture obtained in step a) to obtain a mixture containing the compound of formula (II):

[0019] c) hydrolysis of the mixture obtained in step b) to obtain a mixture containing the compound of formula (III):

[0020] d) nitration of the mixture obtained in step c) in the presence of acetic anhydride to obtain a mixture containing the compound of formula (IV): (IV); and

[0021] e) the heat treatment of the mixture obtained in step d).

[0022] Step a) of the process includes the nitration of pyrazole in the presence of acetic anhydride.

[0023] The nitration step of pyrazole is carried out by reacting pyrazole with nitric acid in the presence of acetic anhydride.

[0024] In some embodiments, the nitration is carried out at a temperature of about 0 to about 40°C, for example from about 10 to about 30°C. Advantageously, the nitration is carried out at a temperature in the range of 20 to 30°C.

[0025] In some embodiments, the duration of the nitration step is from about 5 minutes to about 1 hour, for example from about 5 minutes to about 50 minutes, or from about 10 minutes to about 40 minutes, in particular about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes or about 30 minutes.

[0026] In some embodiments the nitration is carried out using nitric acid, and with an excess of acetic anhydride relative to the nitric acid, for example with about 2 to about 5 equivalents, in particular about 3 equivalents of acetic anhydride, for 1 equivalent of nitric acid.

[0027] Step b) of the process includes heat-treating the mixture obtained in step a) to obtain a mixture containing the compound of formula (II). This mixture contains predominantly N-acetyl-3-nitropyrazole (compound of formula (II)) as well as N-acetylpyrazole. It is used as is for carrying out the next step of the process.

[0028] In some embodiments, the heat treatment is carried out at a temperature of about 160 to about 240°C, for example about 180 to about 220°C, in particular about 200°C.

[0029] In some embodiments, the duration of the heat treatment is from about 5 minutes to about 1 hour, for example from about 5 minutes to about 45 minutes, in particular about 10 minutes, about 20 minutes, about 30 minutes or about 40 minutes.

[0030] In some embodiments, steps a) and b) are carried out in mode discontinuous ("batch").

[0031] In some embodiments, steps a) and b) are carried out in continuous flow. Continuous flow chemistry consists of carrying out syntheses in devices through which the reaction medium flows, in which all reactions and physicochemical transformations are performed without isolating the intermediates. [Fig. 1] illustrates a continuous flow chemistry setup used in the examples below to couple steps a) and b).

[0032] Step c) of the process includes hydrolysis of the mixture obtained in step b) to obtain a mixture containing the compound of formula (III).

[0033] In some embodiments, the hydrolysis of the mixture is carried out at a temperature of about 60 to about 120°C, for example about 70 to about 110°C, in particular about 80°C.

[0034] In some embodiments, the duration of the hydrolysis step is from about 30 minutes to about 2 hours, for example from about 45 minutes to about 90 minutes, in particular about 1 hour.

[0035] In some embodiments, hydrolysis is carried out with an excess of water relative to the pyrazole species present in the mixture, for example about 2 to about 5 equivalents, in particular about 3 equivalents of water, for 1 equivalent of pyrazole species.

[0036] Step d) involves nitrating the mixture obtained in step c) in the presence of acetic anhydride to obtain a mixture containing the compound of formula (IV). This mixture contains predominantly 1,3-dinitropyrazole (compound of formula (IV)), as well as V-nitropyrazole, 3-nitropyrazole (III), and N-acetyl-3-nitropyrazole (II). It is used as is for the implementation of the next step of the process.

[0037] As in step a), the nitration step of the mixture obtained in step c) is carried out by reacting said mixture with nitric acid in the presence of acetic anhydride.

[0038] In some embodiments, the nitration is carried out at a temperature of approximately 20 to approximately 40°C, for example from approximately 20 to approximately 30°C. Advantageously, the nitration is carried out at ambient temperature, which, within the scope of the present invention, will be in the range of approximately 20 to approximately 25°C.

[0039] In some embodiments, the duration of this second nitration step is from about 2 hours to about 24 hours, for example from about 5 hours to about 20 hours, or from about 10 hours to about 20 hours, in particular about 18 hours.

[0040] In some embodiments the nitration is carried out using nitric acid, and with an excess of acetic anhydride relative to the nitric acid, for example about 2 to about 5 equivalents, in particular about 3 or about 4 equivalents of acetic anhydride, for 1 equivalent of nitric acid.

[0041] In some embodiments, steps c) and d) are carried out in continuous flow. In some embodiments, steps c) and d) are carried out in discontinuous mode and, advantageously, consecutively.

[0042] Step e) includes heat treatment of the mixture containing the compound of formula (IV) to obtain 3,5-DNP.

[0043] In some embodiments, this second heat treatment step is carried out at a temperature of about 160 to about 240°C, for example about 180 to about 220°C, in particular about 200°C.

[0044] In some embodiments, the duration of this second heat treatment step is from about 5 minutes to about 1 hour, for example from about 5 minutes to about 50 minutes, in particular about 10 minutes, about 20 minutes, about 30 minutes or about 40 minutes.

[0045] In some embodiments, step e) is carried out in continuous flow.

[0046] According to another aspect, the invention relates to the intermediate of formula (II): (H),

[0047] commonly referred to as N-acetyl-3-nitropyrazole (IUP name AC = l-(3-nitropyrazol-l-yl)ethanone).

[0048] According to another aspect, the invention relates to a process for preparing 3,4,5-trinitropyrazole which comprises:

[0049] a) the preparation of 3,5-dinitropyrazole by the process as defined above, and

[0050] b) the nitration of the 3,5-dinitropyrazole thus obtained.

[0051] The nitration step of 3,5-DNP is carried out in a manner known to those skilled in the art, typically by reacting 3,5-DNP with fuming nitric acid in the presence of pure sulfuric acid and sulfuric oleum.

[0052] The 3,5-DNP preparation process according to the invention has the following advantages:

[0053] - reduction of the number of synthesis steps;

[0054] - reduction of synthesis time and effluents;

[0055] - elimination of solvents, in particular toxic solvents, such as bro- mobenzene, from synthesis;

[0056] - use of a conventional heater for ease of implementation;

[0057] - increased safety (resulting from the use of flow chemistry) and scalability facilitated.

[0058] The invention will be better understood with the aid of the following examples, given purely for illustrative purposes. Examples

[0059] Material 1

[0060] The setup used for steps a) and b) of the 3,5-DNP preparation process is shown in [Fig. 1]. The equipment used is as follows:

[0061] 2 piston pumps (FLOM Intelligent Pump UI-22);

[0062] 3 Corning microreactors (Ix LFSHH + 2x LFR*H);

[0063] 1 hot plate;

[0064] 1 back pressure regulator (BPR) (Zaiput BPR- 10);

[0065] 3 manual two-way valves;

[0066] 1 manual three-way valve;

[0067] 1 cryostat (Huber ministat 240);

[0068] 3 thermocouples (1 in line and two for the double jacket);

[0069] 1 pressure sensor;

[0070] PFA tubes resistant to 200°C / 10 bar;

[0071] Plastic connector resistant to 18 bar;

[0072] 2 scales;

[0073] 1 nitrogen gas inlet.

[0074] The nitrogen gas supply maintains the BPR setpoint at 10 bar, which is necessary to contain the gases formed during thermal rearrangement. It also allows the assembly to be purged in case of emergency.

[0075] The solutions were prepared at room temperature (0°C) and then adjusted using volumetric flasks to obtain a precise concentration. The pyrazole solutions were injected at room temperature. In contrast, the acetonitrile solutions (nitric acid + acetic anhydride (Ac2O)) were kept at 0°C, even during injection, to prevent their degradation. The mass flow rates of the solutions were monitored using two balances, and the density of the solutions allowed for the calculation of the volumetric flow rates.

[0076] Operating conditions 1 (for steps a) and b))

[0077] Assembly pressure: 10 bars;

[0078] Concentration of nitric acid in acetic anhydride (nitric acid 99%): 317 g / L;

[0079] Concentration of pyrazole in acetic anhydride: 342 g / L;

[0080] Flow rates of the solutions (equal for both solutions): 1 to 6 mL / min;

[0081] Temperature of the double jacket of the Corning microreactors: 28 °C;

[0082] Temperature of the reaction loop (nitration): TA;

[0083] Temperature of the reaction loop (thermal rearrangement): 200 °C;

[0084] Residence time (nitration): 15 minutes;

[0085] Residence time (thermal rearrangement): 10 minutes;

[0086] Time out before collection: 1 hour.

[0087] Material 2

[0088] The setup used for step e) of the 3,5-DNP preparation process is shown in [Fig. 2]. The equipment used is as follows:

[0089] 1 piston pump (FLOM Intelligent Pump UI-22);

[0090] 1 thermocouple (T);

[0091] 1 pressure sensor (P);

[0092] 3 manual two-way valves;

[0093] 1 manual three-way valve;

[0094] 1 back pressure regulator (Zaiput BPR-10);

[0095] PFA tubes resistant to 200°C / 10 bar;

[0096] Plastic connector resistant to 18 bar;

[0097] 1 hot plate;

[0098] 1 arrival of nitrogen gas;

[0099] 1 balance.

[0100] Operating conditions 2 (for step e))

[0101] Assembly pressure: 10 bars;

[0102] Solution flow rates: 1 to 6 mL / min;

[0103] Temperature of the reaction loop (thermal rearrangement): 200 °C;

[0104] Dwell time: 10 minutes;

[0105] Time out before collection: 30 minutes. Example 1: N-acetyl-3-nitropyrazole

[0106] With reference to [Fig. 1] and the equipment and operating conditions 1, 2.15 mL / min of pyrazole solution in acetic anhydride (342 g of pyrazole per liter) and 2.15 mL / min of acetonitrile solution (317 g of fuming nitric acid per liter) were introduced in parallel into a first mixing microreactor. The reaction mixture was then reacted in a second microreactor for 15 min at 28 °C. The reaction mixture was then transferred to a third microreactor for heat treatment (200 °C for 10 min). Following this heat treatment, a clear orange liquid containing the compound of titration (508 g of reaction mixture) was obtained and used as is. ¹H NMR analysis of this medium revealed the presence of the compound (II) at a level of 67% and V-Acetylpyrazole at a level of 33%.

[0107] RMN XH (N-acetyl-3-nitropyrazole, CD3NO2, 400 MHz, 21°C): ô (ppm) = 8.39 (d, 1H, NC(NO2)CHCHN(Ac), 3Jhh = 3.0 Hz), 7.11 (d, 1H, NC(NO2)CÆCHN(Ac), 3JHH = 2.9 Hz), 2.76 (s, 3H,

[0108] RPN 1H, N(Ac)CHCHCHN, 3JHH = 2.8 Hz, 3JHH = 1.6 Hz), 2.65 (s, 3H, CH^. Example 2: 3-nitropyrazole

[0109] In a 2 L flask, the entire reaction mixture containing the N-acetyl-3-nitropyrazole obtained in Example 1, i.e., 508 g of solution, was placed. Sixty-five mL of water (3.15 equivalents with respect to the pyrazole species present in the mixture) were added in portions, and the mixture was heated for 1 h at 80°C. A reaction mixture was obtained in the form of a yellow liquid containing the compound of titration, which was used as is. Analysis of this mixture by ¹H NMR revealed complete conversion of N-acetyl-3-nitropyrazole to 3-nitropyrazole.

[0110] Example 3: 1,3-dinitropyrazole

[0111] To the entire reaction mixture obtained in Example 2, acetic anhydride (430 mL) and then fuming nitric acid (47.6 mL, 1 equivalent with respect to the pyrazole species present in the mixture) were added, and the reaction mixture was left at room temperature for 18 hours. A new reaction mixture was obtained in the form of a clear yellow liquid containing the compound of titration, which was used as is. Proton NMR analysis revealed the presence of several pyrazole species and their relative proportions:

[0112] 1,3-Dinitropyrazole (IV): 52%

[0113] V-Nitropyrazole: 32%

[0114] 3-Nitropyrazole (III): 9%

[0115] N-acetyl-3-nitropyrazole (II): 7%

[0116] 3.1Hz).

[0117] 6.61 (dd, 1H, N(NO2)CHŒCHN, 3Jhh = 3.0 Hz, 3JHH = 1.7 Hz). Example 4: 3,5-dinitropyrazole

[0118] With reference to [Fig.2] and to the equipment and operating conditions 2, 4.3 mL / min of the reaction mixture obtained in Example 3, containing 1,3-dinitropyrazole, was added to a microreactor for heat treatment (200°C for 10 min). Following this heat treatment, a clear, dark orange liquid containing the compound was obtained and evaporated to dryness. The recovered solid was ground in 130 mL of dichloromethane. Filtration followed by two 50 mL washes with dichloromethane isolated the pure compound as a white solid (35.9 g, yielding 27% of the starting pyrazole). Characterization of the final product:

[0119] XH NMR (3,5-Dinitropyrazole, Acetone d6, 400 MHz, 21°C): (ppm) = 7.82 (s, 1H, CH)

[0120] 13C NMR (3,5-Dinitropyrazole, Acetone d6, 100 MHz, 21°C): (ppm) = 152.4 (C NO2), 100.3 (CH).

[0121] DSC (40 pL aluminium crucible with perforated lid, 35 to 400°C, 5°C.min'): 170.4°C (endo, -149.7 Jg', melting), 240.3°C (endo, -315.5 Jg*, evaporation).

Claims

Claims

1. Process for the preparation of 3,5-dinitropyrazole of formula (I): which includes: (a) nitration of pyrazole using nitric acid and an excess of acetic anhydride relative to nitric acid; b) heat treatment, at a temperature of 160 to 240°C, of ​​the mixture obtained in step a) to obtain a mixture containing the compound of formula (II): c) hydrolysis of the mixture obtained in step b) to obtain a mixture containing the compound of formula (III): (in); d) nitration of the mixture obtained in step c) in the presence of acetic anhydride to obtain a mixture containing the compound of formula (IV): (IV); and e) heat treatment of the mixture obtained in step d).

2. Method according to claim 1, wherein step a) is carried out at a temperature of 0 to 40°C, advantageously of 20 to 30°C, preferably for a duration of 5 min to 1 h, advantageously of 10 min to 40 min.

3. Method according to any one of the preceding claims, in which step b) is carried out for a period of 5 min to 1 h.

4. Process according to any one of the preceding claims, in which step c) is carried out at a temperature of 60 to 120°C, preferably for a period of 30 min to 2 h, and preferably with an excess of water relative to the pyrazole species present in the mixture obtained in step b).

5. A method according to any one of the preceding claims, wherein step d) is carried out at a temperature of 20 to 40°C, preferably for a period of 2h to 24h, and preferably using nitric acid, with an excess of acetic anhydride relative to the nitric acid.

6. A method according to any one of the preceding claims, wherein step e) is carried out at a temperature of 160 to 240°C, preferably for a period of 5 min to 1 h.

7. A method according to any one of the preceding claims, wherein steps a), b) and e), and optionally steps c) and d), are carried out in a continuous flow.

8. A process for the preparation of 3,4,5-trinitropyrazole which comprises: a) preparing 3,5-dinitropyrazole by the process as defined in any one of claims 1 to 8, and b) nitrating the 3,5-dinitropyrazole thus obtained.

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