Amide hydrazine compound as well as preparation method and application thereof

Abstract

The invention provides an amide hydrazine compound and a preparation method and application thereof.The structure of the amide hydrazine compound is shown in the formula I. The preparation method comprises the following steps that triaminoguanidine hydrochloride, water and acetylacetone are mixed to react, and the amide hydrazine compound is obtained. The amide hydrazine compound provided by the invention can be used in synthesis of 3, 6-bis (3, 5-dimethylpyrazol-1-yl)-1, 2-dihydro-1, 2, 4, 5-tetrazine, the preparation method is rapid, the yield is high, and an effective method is provided for preparation of DHBT and BT.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to an amide hydrazine compound and a preparation method and application thereof. Background Art

[0002] Tetrazines are currently one of the research hotspots of new high-nitrogen compounds. In recent years, the research on tetrazines at home and abroad has mainly focused on 1,2,4,5-tetrazine, and its synthesis mostly starts from 3,6-bis(3,5-dimethylpyrazol-1-yl)-1,2,4,5-tetrazine (BT), and 3,6-bis(3,5-dimethylpyrazol-1-yl)-1,2-dihydro-1,2,4,5-tetrazine (DHBT) is an important precursor for the production of BT. Therefore, the research on the synthesis of 3,6-bis(3,5-dimethylpyrazol-1-yl)-1,2-dihydro-1,2,4,5-tetrazine is particularly critical. However, the specific reaction process of 3,6-bis(3,5-dimethylpyrazol-1-yl)-1,2-dihydro-1,2,4,5-tetrazine has not been clearly analyzed, and there is no method for simply and quickly preparing 3,6-bis(3,5-dimethylpyrazol-1-yl)-1,2-dihydro-1,2,4,5-tetrazine. Therefore, it is urgent to provide a method for effectively and quickly preparing DHBT. Summary of the invention

[0003] In view of the deficiencies of the prior art, the object of the present invention is to provide an amide hydrazine compound and a preparation method and application thereof. The amide hydrazine compound provided by the present invention can be used in the synthesis of 3,6-bis(3,5-dimethylpyrazol-1-yl)-1,2-dihydro-1,2,4,5-tetrazine, the preparation method is fast and has a high yield, and provides an effective method for preparing DHBT and BT.

[0004] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0005] In a first aspect, the present invention provides an amide hydrazine compound, the structure of which is shown in Formula I:

[0007] Formula I.

[0008] The compound with the specific structure is used in the synthesis of 3,6-di(3,5-dimethylpyrazol-1-yl)-1,2-dihydro-1,2,4,5-tetrazine. The preparation method is fast and the yield is high, and an effective method is provided for the preparation of DHBT and BT.

[0009] In a second aspect, the present invention provides a method for preparing the amide hydrazine compound as described above, the preparation method comprising the following steps:

[0010] Triaminoguanidine hydrochloride, water and acetylacetone are mixed for reaction to obtain the amide hydrazine compound.

[0011] Preferably, the molar ratio of triaminoguanidine hydrochloride to acetylacetone is 1:(1-5), such as 1:1, 1:2, 1:3, 1:4 or 1:5, but is not limited to the above-listed values, and other unlisted values ​​within the above numerical range are also applicable.

[0012] Preferably, the molar ratio of triaminoguanidine hydrochloride to acetylacetone is 1:(1.9-2.1), such as 1:1.9, 1:1.95, 1:2, 1:2.05 or 1:2.1, etc., but is not limited to the above-listed values, and other unlisted values ​​within the above numerical range are also applicable.

[0013] The above specific molar ratio range can avoid the generation of by-products and effectively improve the purity and yield of the product.

[0014] Preferably, the mass ratio of triaminoguanidine hydrochloride to water is 1:(3-10), for example 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9 or 1:10, etc., but is not limited to the values ​​listed above, and other values ​​not listed within the above numerical range are also applicable.

[0015] Preferably, the reaction temperature is 0-40°C, for example 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C or 40°C, but is not limited to the above-listed values, and other unlisted values ​​within the above numerical range are also applicable.

[0016] Preferably, the reaction temperature is 15-20°C.

[0017] The above-mentioned specific temperature range can effectively control the reaction rate, prevent the generation of by-products, and effectively improve the purity and yield of the product.

[0018] Preferably, the reaction time is 15-30 min, for example, 15 min, 16 min, 17 min, 18 min, 19 min, 20 min, 21 min, 22 min, 23 min, 24 min, 25 min, 26 min, 27 min, 28 min, 29 min or 30 min, but is not limited to the above-listed values, and other values ​​not listed within the above numerical range are also applicable.

[0019] Preferably, the reaction is carried out under stirring, and the stirring rate is 200-500 rpm, for example, 200 rpm, 250 rpm, 300 rpm, 350 rpm, 400 rpm, 450 rpm or 500 rpm, but is not limited to the above-listed values, and other values ​​not listed within the above numerical range are also applicable.

[0020] In a third aspect, the present invention also provides the use of the amide hydrazide compounds described above in the research of DHBT synthesis.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] (1) The present invention provides an amide hydrazine compound, which is used in the synthesis of 3,6-di(3,5-dimethylpyrazol-1-yl)-1,2-dihydro-1,2,4,5-tetrazine. The preparation method is fast and has a high yield, and provides an effective method for preparing DHBT and BT.

[0023] (2) The present invention effectively prevents the generation of by-products by controlling specific reaction parameters, thereby improving the purity and yield of the amide hydrazine compound. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 is a liquid phase result diagram of the compound provided in Example 1;

[0025] Figure 2 is a mass spectrometry result diagram of the compound provided in Example 1;

[0026] Figure 3 is the result of H NMR spectrum of the compound provided in Example 1;

[0027] Figure 4 is the result of the carbon NMR spectrum of the compound provided in Example 1;

[0028] Figure 5 is the infrared spectrum result diagram of the compound provided in Example 1;

[0029] Figure 6 This is the result of the H-NMR spectrum of the compound provided in the application example. DETAILED DESCRIPTION

[0030] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0031] Example 1

[0032] This embodiment provides an amide hydrazine compound (1,1'-(3,5-dimethyl-pyrazol-1-yl)-enamine hydrazine hydrochloride), the structure of which is as follows:

[0033]

[0034] The preparation method is as follows:

[0035] Add triaminoguanidine hydrochloride (32 g) and deionized water (138 mL) into a 250 mL jacketed reactor, stir with an inclined blade paddle at 400 rpm, and use a thermostat to control the temperature of the entire reaction process between 15-20°C. When the internal temperature is 15°C, slowly add acetylacetone (46.6 mL) twice the molar amount of triaminoguanidine hydrochloride. Continue stirring and react for 25 min. After the reaction is completed, filter and wash the filter cake with petroleum ether. After natural drying, a pale yellow solid 1,1'-(3,5-dimethyl-pyrazole-1-yl)-enaminehydrazine hydrochloride crude product is obtained with a yield of 85.9%. The product was separated and purified by medium-pressure purification preparative chromatography (C-18 chromatographic column) with the mobile phase being 35% acetonitrile-pure water solution. The separated material was subjected to rotary evaporation to remove the solvent to obtain a high-purity 1,1'-(3,5-dimethyl-pyrazol-1-yl)-enaminehydrazine hydrochloride sample with a purity of 99.2%. The material composition was determined by HPLC-MS / MS and NMR analysis.

[0036] like Figure 1 As shown, there is no obvious impurity peak in the liquid phase diagram of the 1,1'-(3,5-dimethyl-pyrazol-1-yl)-enaminehydrazine hydrochloride, the mobile phase is 90% methanol-pure water solution, and the analysis is performed using the isocratic elution method; the flow rate is 0.7 mL / min; the detection wavelength is 246 nm; the column temperature is 35°C; the injection volume is 20 μL; and the retention time is 4.008 min.

[0037] like Figure 2 As shown, the mass spectrum of the 1,1'-(3,5-dimethyl-pyrazol-1-yl)-enamine hydrazine hydrochloride shows that it is a pure product with a molecular weight of 232 g / mol.

[0038] like Figure 3As shown, there is no obvious impurity peak in the NMR 1H spectrum of the 1,1'-(3,5-dimethyl-pyrazol-1-yl)-enamine hydrazine hydrochloride, and the peaks with chemical shift values ​​of 1.81, 2.07, 2.18, and 2.26 ppm correspond to methyl hydrogen, respectively, and the peaks with chemical shift values ​​of 5.99 and 6.03 ppm correspond to 1 H atom on the two pyrazole rings, and the peak with a chemical shift value of 6.83 ppm corresponds to 2 H atoms on the imine group. The peak with a chemical shift value of 2.51 ppm is the peak of the solvent DMSO, and the peak with a chemical shift value of 3.33 ppm is the water peak. The hydrogen on the four methyl groups shows an asymmetric structure, rather than two sets of symmetrical structures, indicating that one pyrazole ring of the intermediate structure is in the form of a salt. Its NMR data are as follows:

[0039] 1 H NMR (700 MHz, DMSO-d6): δ6.83(s,2H), 6.03(s,1H), 5.99(s,1H), 2.26(s,3H), 2.18(s,3H), 2.07(s,3H), 1.81(s,3H).

[0040] like Figure 4 As shown, there is no obvious impurity peak in the NMR 13C spectrum of the 1,1'-(3,5-dimethyl-pyrazol-1-yl)-enaminehydrazine hydrochloride, and the peaks with chemical shift values ​​of 10.51, 11.89, 13.76, and 13.89 ppm correspond to the C 5 Atoms, the peaks with chemical shift values ​​of 106.92 and 107.04 ppm correspond to the C 3 Atom, the peak with a chemical shift value of 126.26 ppm corresponds to the C1 atom, the peaks with chemical shift values ​​of 141.44 and 141.52 ppm correspond to the C2 atoms on the two pyrazole rings, the peaks with chemical shift values ​​of 148.90 and 150.34 ppm correspond to the C4 atoms on the two pyrazole rings, and the peak with a chemical shift value of 39.64-40.35 ppm is the peak of the solvent DMSO. The carbons on the two pyrazole rings all show an asymmetric structure, which again shows that one of the pyrazole rings in the intermediate structure is in the form of a salt. Its NMR data are as follows:

[0041] 13 C NMR (700 MHz, DMSO-d6): δ150.34, 148.90, 141.52, 141.44, 126.26, 107.04, 106.92, 13.89, 13.76, 11.89, 10.51.

[0042] like Figure 5As shown, the infrared spectrum of the 1,1'-(3,5-dimethyl-pyrazol-1-yl)-enaminehydrazine hydrochloride is 3382 cm -1 The absorption peak at 3220 cm -1 The corresponding groups of the absorption peaks at 2923 and 2967 cm -1 The absorption peak at 1656 cm -1 The absorption peak at 1567 cm -1 The absorption peak at 1470 cm -1 The absorption peak is the stretching vibration peak of the C—N bond in the quaternary ammonium salt.

[0043] Example 2

[0044] This embodiment provides an amide hydrazine compound (1,1'-(3,5-dimethyl-pyrazol-1-yl)-enamine hydrazine hydrochloride), the preparation method of which is as follows:

[0045] Add triaminoguanidine hydrochloride (24 g) and deionized water (72 mL) into a 250 mL jacketed reactor, stir with an inclined blade paddle at 300 rpm, and use a thermostat to control the temperature of the entire reaction process between 15-20°C. When the internal temperature is 15°C, slowly add 1.9 times the molar amount of triaminoguanidine hydrochloride acetylacetone. Continue stirring and react for 15 min. After the reaction is completed, filter and wash the filter cake with petroleum ether. After natural drying, a light yellow solid intermediate 1,1'-(3,5-dimethyl-pyrazol-1-yl)-enamine hydrazine hydrochloride is obtained with a yield of 81.4% and a purity of 98.1%.

[0046] Example 3

[0047] This embodiment provides an amide hydrazine compound (1,1'-(3,5-dimethyl-pyrazol-1-yl)-enamine hydrazine hydrochloride), the preparation method of which is as follows:

[0048] Add triaminoguanidine hydrochloride (12 g) and deionized water (120 mL) into a 250 mL jacketed reactor, stir with a pitch blade at 500 rpm, and use a thermostat to control the temperature of the entire reaction process between 15-20°C. When the internal temperature is 15°C, slowly add acetylacetone with a molar amount of 2.1 times that of triaminoguanidine hydrochloride. Continue stirring and react for 30 min. After the reaction is completed, filter, wash the filter cake with petroleum ether, and dry it naturally to obtain a light yellow solid intermediate 1,1'-(3,5-dimethyl-pyrazol-1-yl)-enaminehydrazine hydrochloride with a yield of 73.6% and a purity of 96.7%.

[0049] Example 4

[0050] This embodiment provides an amide hydrazine compound (1,1'-(3,5-dimethyl-pyrazol-1-yl)-enamine hydrazine hydrochloride), and the preparation method is consistent with that of Example 1 except that the reaction temperature is between 30-35°C.

[0051] The final product yield was 80.0% and the purity was 97.9%.

[0052] Example 5

[0053] This embodiment provides an amide hydrazine compound (1,1'-(3,5-dimethyl-pyrazol-1-yl)-enamine hydrazine hydrochloride), and the preparation method is consistent with that of Example 1 except that the reaction temperature is between 40-45°C.

[0054] The final product yield was 50.7% and the purity was 92.6%.

[0055] Example 6

[0056] This embodiment provides an amide hydrazine compound (1,1'-(3,5-dimethyl-pyrazol-1-yl)-enamine hydrazine hydrochloride). The preparation method is the same as that of Example 1 except that the amount of acetylacetone added is 2.3 times the molar amount of triaminoguanidine hydrochloride.

[0057] The final product yield was 62.5% and the purity was 96.4%.

[0058] Example 7

[0059] This embodiment provides an amide hydrazine compound (1,1'-(3,5-dimethyl-pyrazol-1-yl)-enamine hydrazine hydrochloride). The preparation method is the same as that in Example 1 except that the amount of acetylacetone added is 1.5 times the molar amount of triaminoguanidine hydrochloride.

[0060] The final product yield was 70.1% and the purity was 58.9%.

[0061] From the above data, it can be found that the present invention can effectively improve the yield and purity of the amide hydrazine compound 1,1'-(3,5-dimethyl-pyrazol-1-yl)-enamine hydrazine hydrochloride by selecting specific preparation parameters, facilitate the preparation of the product, and provide help for analyzing and understanding the synthesis process of 3,6-bis(3,5-dimethylpyrazol-1-yl)-1,2-dihydro-1,2,4,5-tetrazine.

[0062] Application Examples

[0063] This application example provides a method for preparing DHBT, characterized in that the preparation method comprises the following steps:

[0064] In a 250 mL glass jacketed reactor, 1,1'-(3,5-dimethyl-pyrazol-1-yl)-enaminehydrazine hydrochloride (24 g) and ethanol solvent (120 mL) provided in Example 1 were added, and stirred with a tetrafluoroethylene pitched blade stirring paddle at a stirring speed of 400 rpm, a reaction temperature of 70°C, and a reaction time of 2 h. The mixture was cooled to room temperature, filtered, and the filter cake was washed with water and petroleum ether, and dried to obtain a light yellow solid DHBT, with an actual yield of 78.1% and a purity of 96.3%.

[0065] The composition of the substance is determined by NMR spectroscopy, such as Figure 6 As shown, the NMR of the 3,6-bis(3,5-dimethylpyrazol-1-yl)-1,2-dihydro-1,2,4,5-tetrazine 1 There are no obvious impurity peaks in the H spectrum. The peaks with chemical shift values ​​of 2.18 ppm and 2.41 ppm correspond to the 6 H atoms on the 2 methyl groups on the two pyrazole rings on both sides, the peak with chemical shift value of 6.16 ppm corresponds to 1 H atom on the two pyrazole rings, and the peak with chemical shift value of 8.86 ppm corresponds to the 2 H atoms on the middle tetrazine ring. The peak with chemical shift value of 2.51 ppm is the peak of the solvent DMSO, and the peak with chemical shift value of 3.33 ppm is the water peak. Its NMR data are as follows:

[0066] 1 H NMR (700 MHz, DMSO-d6): δ8.86(s, 2H), 6.16(s, 2H), 2.41(s, 6H), 2.18(s, 6H).

[0067] From the above data, it can be found that the amide hydrazine compounds provided by the present invention can effectively and quickly prepare DHBT, and provide an effective method for the preparation of DHBT and BT.

[0068] The applicant declares that the present invention illustrates the amide hydrazine compounds and the preparation method and application thereof through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned embodiments, that is, it does not mean that the present invention must rely on the above-mentioned embodiments to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

[0069] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0070] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

Claims

1. An amide hydrazine compound, characterized in that The structure of the amide hydrazine compound is shown in Formula I: Formula I.

2. A method for preparing an amide hydrazine compound according to claim 1, characterized in that: The preparation method comprises the following steps: Triaminoguanidine hydrochloride, water and acetylacetone are mixed for reaction to obtain the amide hydrazine compound.

3. The method for preparing an amide hydrazine compound according to claim 2, wherein: The molar ratio of the triaminoguanidine hydrochloride to acetylacetone is 1:(1-5).

4. The method for preparing an amide hydrazine compound according to claim 2, wherein: The molar ratio of the triaminoguanidine hydrochloride to acetylacetone is 1:(1.9-2.1).

5. The method for preparing an amide hydrazine compound according to claim 2, characterized in that: The mass ratio of the triaminoguanidine hydrochloride to water is 1:(3-10).

6. The method for preparing an amide hydrazine compound according to claim 2, characterized in that: The reaction temperature is 0-40°C.

7. The method for preparing an amide hydrazine compound according to claim 2, characterized in that: The reaction temperature is 15-20°C.

8. The method for preparing an amide hydrazine compound according to claim 2, wherein: The reaction time is 15-30 min.

9. The method for preparing an amide hydrazine compound according to claim 2, characterized in that: The reaction is carried out under stirring at a rate of 200-500 rpm.

10. Use of the amide hydrazide compound according to claim 1 in the synthesis of DHBT.

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