Continuous flow microfluidic process for synthesis of 3,4-dinitropyrazole
Disclosed herein is a synthetic method, apparatus, and system for the continuous-flow synthesis of 3,4-dinitropyrazole from pyrazole in a microfluidic environment. This synthetic strategy consist of three (3) synthetic steps, including (1) N-nitration of pyrazole, (2) thermal rearrangement into 3-nitropyrazole, and (3) 4-nitration of 3-nitropyrazole. The current technique produces 3,4-dinitropyrazole in yields up to 85% in particular embodiments, in comparison to 40-50% yields demonstrated by the current state of-the-art batch process for large scale synthesis from pyrazole.
1. A continuous flow microfluidic process comprising
in a first microreactor, reacting a mixture of pyrazole:
and acetic anhydride with nitric acid to yield a first reaction solution comprising 1-nitropyrazole:
2. The continuous flow microfluidic process of claim 1 , further comprising
in a second microreactor, thermally rearranging the 1-nitropyrazole to yield a second reaction solution comprising 3-nitropyrazole:
3. The continuous flow microfluidic process of claim 2 , further comprising
in a third microreactor, reacting the 3-nitropyrazole with a mixture of nitric acid and sulfuric acid to yield a third reaction solution comprising 3,4-dinitropyrazole.
4. The continuous flow microfluidic process of claim 1 , wherein the acetic anhydride solution further comprises acetic acid.
5. The continuous flow microfluidic process of claim 1 , wherein the molar ratios of pyrazole:acetic anhydride are 1.0:1.0 to 2.0:1.0.
6. The continuous flow microfluidic process of claim 1 , wherein the reaction is performed between 20-50° C.
7. The continuous flow microfluidic process of claim 1 , further comprising collecting and isolating the 1-nitropyrazole.
8. The continuous flow microfluidic process of claim 1 , wherein the molar ratio of nitric acid:pyrazole is 1.0:0.3 to 1.0:1.0.
9. The continuous flow microfluidic process of claim 2 , wherein the thermal rearrangement is performed between 110-180° C.
10. The continuous flow microfluidic process of claim 2 , further comprising collecting and isolating the 3-nitropyrazole.
11. The continuous flow microfluidic process of claim 3 , further comprising collecting and isolating the 3,4-dinitropyrazole.
12. The continuous flow microfluidic process of claim 3 , wherein the sulfuric acid is 98 wt % and the nitric acid is 100 wt %.
13. The continuous flow microfluidic process of claim 3 , further comprising performing the reaction of the 3-nitropyrazole with the mixture of nitric acid and sulfuric acid to yield 3,4-dinitropyrazole at 25-80° C.
14. The continuous flow microfluidic process of claim 3 , wherein the first, second, and third microreactors each have an inside diameter of between 0.2-1.0 mm.
15. The continuous flow microfluidic process of claim 3 , wherein the first, second, and third microreactors are made from any of FEP (fluorinated ethylene propylene) tubing, FEP tubing with static helical mixers, and glass.
16. The continuous flow microfluidic process of claim 3 , further comprising diluting the third reaction mixture containing 3,4-dinitropyrazole with deionized water and extracting the 3,4-dinitropyrazole with an immiscible organic solvent selected from the group consisting of chloroform, ethyl acetate, hexanes, and diethyl ether.
17. The continuous flow microfluidic process of claim 16 , further comprising diluting and extracting the 3,4-dinitropyrazole in-flow.
18. The continuous flow microfluidic process of claim 6 , wherein the reaction is performed between 20-30° C.
19. The continuous flow microfluidic process of claim 6 , wherein the reaction is performed with a residence time of 0.17-10 minutes.
20. The continuous flow microfluidic process of claim 9 , wherein the thermal rearrangement is performed between 110-180° C. for at least 15 minutes.
21. The continuous flow microfluidic process of claim 12 , wherein the molar ratio of nitric acid:sulfuric acid is 1.0:1.0 to 1:10.
22. The continuous flow microfluidic process of claim 12 , wherein the molar ratio of nitric acid:sulfuric acid is 1:5.
23. The continuous flow microfluidic process of claim 12 , wherein the reaction of the 3-nitropyrazole with a mixture of nitric acid and sulfuric acid in the third microreactor includes a residence time of 1-10 minutes.
24. A continuous flow microfluidic process, comprising
in a microreactor, thermally rearranging 1-nitropyrazole to yield a reaction solution comprising 3-nitropyrazole.
25. A continuous flow microfluidic process, comprising
in a microreactor, reacting 3-nitropyrazole with a mixture of nitric acid and sulfuric acid to yield a reaction solution comprising 3,4-dinitropyrazole.