CN117402083A

CN117402083A - Preparation method of iminohydrazone intermediate

Info

Publication number: CN117402083A
Application number: CN202311260068.9A
Authority: CN
Inventors: 李志清; 宫风华; 吴伯洋; 仲建; 丁坤
Original assignee: Ningxia Gerui Fine Chemical Co ltd
Current assignee: Ningxia Gerui Fine Chemical Co ltd
Priority date: 2023-09-27
Filing date: 2023-09-27
Publication date: 2024-01-16

Abstract

The invention discloses a preparation method of an iminohydrazone intermediate, which comprises the step of carrying out reduction hydrogenation on a nitrohydrazone compound in the presence of a catalyst. The invention determines proper metal catalyst, relative proportion of catalyst, reaction temperature, hydrogen pressure and reaction time through screening; the method of the invention overcomes the pollution problem caused by large hazardous waste discharge in the prior art, and is a process for producing the intermediate I by reducing three waste discharge and being environment-friendly.

Description

Preparation method of iminohydrazone intermediate

Technical Field

The invention belongs to the field of fine organic chemical synthesis, and particularly relates to a preparation method of a mesotrione intermediate N '- (2, 4-dichlorophenyl) acetimzide and a triadimefon intermediate N' - (4-chloro-2-fluorophenyl) acetimzide.

Background

The sulfentrazone, also called sulfonylcarfentrazone, is a triazolinone herbicide developed by FMC company in 1985 and put on the market in 1996, and is a protoporphyrinogen oxidase inhibitor, and is mainly used for preventing and killing annual broadleaf weeds, grassy weeds, nutgrass flatsedge and the like in sugarcane, soybean and sunflower fields, and is applied before sowing and before emergence; the triadimefon is also called carfentrazone-ethyl, and is also a high-efficiency low-toxicity triazolinone herbicide developed by FMC company 1988, and has similar effect as sulfentrazone but higher efficacy.

In the synthetic route of the two, the mesotrione and the triadimefon are respectively obtained from the similar intermediate I through fluoromethylation, nitration, reduction and then methanesulfonylation or diazotization addition.

Intermediate I is generally prepared from hydrazine as a starting material. Current literature on the preparation of the mesotrione intermediate la from 2, 4-dichlorophenylhydrazine hydrochloride is directed to the synthesis of 4, 5-dihydro-3-methyl-1- (2, 4-dichlorophenyl) -1,2, 4-triazol-5 (1H) one, chemical industry, guangzhou, (2010), 38 (1), 79-80, 95:

in the method, a large amount of sodium sulfite is required for reducing diazonium salt in the production of raw material 2, 4-dichlorophenylhydrazine, a large amount of solid waste is generated, pollution is serious, a large amount of hydrochloric acid gas is required for the production of methyl acetimidate hydrochloride, triethylamine is required for synthesizing Ia as an acid binding agent, recycling is required, and a post-treatment process is increased.

The synthesis of carfentrazone-ethyl, a modern pesticide (2010), 9 (3), 28-30,33 reports the preparation method of triadimefon:

the synthesis of the intermediate acethydrazide takes hydrazine as a raw material, the production of the acethydrazide also generates a large amount of waste salt, and the use of phosphorus oxychloride generates a large amount of waste acid, so that the environmental protection pressure is high.

Whether the intermediate Ia of the sulfentrazone is prepared from 2, 4-dichloroaniline (hydrochloride) or the intermediate Ib of the triadimefon is prepared from 4-chloro-2-fluoroaniline (hydrochloride), the hydrazine is prepared from a large amount of inorganic reducing agents such as sodium sulfite and the synthesis of iminohydrazone generates a large amount of waste acid, so that the environmental protection pressure is high and the atom economy is low.

Disclosure of Invention

Aiming at the defects of the prior art, the invention provides a process for producing an intermediate I, which reduces three waste emission and is environment-friendly, in order to solve the pollution problem caused by large hazardous waste emission in the prior art.

In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:

there is provided a process for preparing a compound of the structure of formula I, comprising the step of subjecting a nitrohydrazone compound of formula a and/or formula B to hydrogenation reduction in the presence of a catalyst:

and/or +.>Wherein x=y=cl; or x=f, y=cl; or x=h, y=cl; or x=cl, y=h; or x=y=h.

Further, the invention provides a preparation method of the compound with the structure shown in the formula I, wherein the metal catalyst is selected from Ni, pt, ptO ₂ One or more of Rh.

Further, the invention provides a preparation method of the compound with the structure shown in the formula I, wherein the catalyst is one or more selected from Rh-C, raney nickel, raneCAT-8101, raneCAT-1000 and Pt-C, rh-C.

Further, the invention provides a preparation method of the compound with the structure shown in the formula I, wherein the catalyst is one or more selected from Raney nickel, raneCAT-8101 and RaneCAT-1000; preferably, the catalyst is selected from RaneCAT-8101.

Furthermore, the invention provides a preparation method of the compound with the structure shown in the formula I, wherein the addition amount of the catalyst is 5-20% of the mass of the nitrohydrazone compound, preferably 8-20%, and more preferably 8-15%.

Furthermore, the invention provides a preparation method of the compound with the structure shown in the formula I, wherein the pressure of the hydrogenation reduction reaction is 0.7-5 MPa, preferably 0.7-3 MPa or 1.5-2.5 MPa.

Furthermore, the invention provides a preparation method of the compound with the structure shown in the formula I, wherein the reaction temperature of the hydrogenation reduction reaction is 20-80 ℃, preferably 20-50 ℃.

Further, the present invention provides a process for preparing the compound of the structure of formula I above, wherein the hydrogenation reduction is carried out in the presence of a reaction solvent, which is well known and preferably selected from inert organic solvents.

Further, the present invention provides a process for preparing the compound of the structure of formula I, wherein the hydrogenation reduction reaction is carried out in the presence of a reaction solvent selected from benzene, toluene, xylene, chlorobenzene, halogenated hydrocarbon, C _1-4 One or more of alkyl alcohol, THF, dioxane, DMF, DMSO, ethyl acetate.

Further, the invention provides a preparation method of the compound with the structure shown in the formula I, wherein the hydrogenation reduction reaction is carried out in the presence of a reaction solvent, and the reaction solvent is selected from one or more of toluene, xylene, chlorobenzene, 1, 2-dichlorobenzene, dichloromethane, chloroform, 1, 2-dichloroethane, methanol, ethanol, n-propanol, isopropanol and n-butanol.

Further, the invention provides a preparation method of the compound with the structure shown in the formula I, which further comprises the step of monitoring the reaction and determining the reaction ending time.

Further, the present invention provides a method for preparing the compound of the structure shown in the formula I, wherein the reaction time of the method is not less than 6 hours, preferably not less than 2 days, or not less than 3 days.

Compared with the prior art, the invention has the following beneficial effects:

1. the method of the invention overcomes the pollution problem caused by large hazardous waste discharge in the prior art, and is a process for producing the intermediate I by reducing three waste discharge and being environment-friendly.

2. The method has simple post-treatment mode and less byproducts, and is particularly suitable for industrialized production of the intermediate I.

Drawings

FIG. 1 is a nuclear magnetic resonance spectrum of (Z) -N' - (2, 4-dichlorophenyl) -N "-hydroxyacetimidate hydrazide;

FIG. 2 shows nuclear magnetic resonance spectrum of (Z) -N' - (2, 4-dichlorophenyl) -N-hydroxy acethydrazide amide;

FIG. 3 is a partial enlargement of the nuclear magnetic hydrogen spectrum of (Z) -N' - (2, 4-dichlorophenyl) -N-hydroxyacetylhydrazinamide;

FIG. 4 is a nuclear magnetic resonance hydrogen spectrum of N' - (2, 4-dichlorophenyl) acetimide hydrazide;

FIG. 5 is a nuclear magnetic carbon spectrum for N' - (2, 4-dichlorophenyl) acetimide hydrazide;

FIG. 6 is a nuclear magnetic resonance hydrogen spectrum of N' - (4-chloro-2-fluorophenyl) acetylimide hydrazide;

FIG. 7 is a nuclear magnetic resonance spectrum of N' - (4-chlorophenyl) acetimide;

FIG. 8 is a nuclear magnetic resonance spectrum of N' - (2-chlorophenyl) acetimide;

FIG. 9 is a partial enlargement of the nuclear magnetic hydrogen spectrum of N' - (2-chlorophenyl) acetimide;

FIG. 10 is a nuclear magnetic hydrogen spectrum of N' -phenylacetylimine hydrazide;

Detailed Description

The invention is further described in connection with the following detailed description, in order to make the technical means, the creation characteristics, the achievement of the purpose and the effect of the invention easy to understand.

Throughout the specification and claims, unless explicitly stated otherwise, the term "comprise" or variations thereof such as "comprises" or "comprising", etc. will be understood to include the stated element or component without excluding other elements or other components.

The product content in the examples below was confirmed by liquid or gas chromatography, and tracking during the reaction was performed by calculating the yield by area normalization instead of external standard, with little deviation from the actual yield.

LC-MS: liquid chromatography mass spectrometry, liquid.

GC-MS, gas chromatography mass spectrometry, gas mass.

HPLC: high Performance Liquid Chromatography, high pressure liquid chromatography.

GC: gas chromatography, gas chromatography.

And (3) NMR: nuclear magnetic resonance spectrometry, nuclear magnetic resonance spectroscopy.

Aniline, 4-chloroaniline, 2, 4-dichloroaniline and 4-chloro-2-fluoroaniline in the following examples are commercially available; if not specified, the reaction process and the result are detected by high pressure liquid chromatography, the purity and the selectivity are normalized, and if not specified in the examples, raney nickel is prepared by adopting a nickel-aluminum alloy method, other modified Raney nickel catalysts RaneCAT-8101 and RaneCAT-1000 are all commercial products.

According to the method, byproducts or intermediate products can be generated along with different process conditions, isomers with different proportions can be generated in partial reaction, and by taking 2, 4-dichlorophenyl hydroxylamine hydrazone as an example, the hydrogen spectrum data of hydroxylamine hydrazone which is a first-step reduction product of nitrohydrazone can be seen to be mainly provided with two isomers A (containing A ') and B, wherein the A-isomer is mainly provided with the B-isomer, and the content of the A' -isomer is the lowest.

The obtained iminohydrazone is only one product IVa, delta 5.917 (s, 1H), delta 4.768 (brs, 2H) which indicates that NH moves to a high field and is a typical five-membered ring hydrogen bond structure, and the product is the most stable configuration due to the lowest energy; for a similar hydrogenation product ivb, δ9.36 (brs., 1H), it is demonstrated that the intermediate NH forms intramolecular hydrogen bonds of a six-membered ring with the F atom ortho to the benzene ring, with chemical shifts moving toward the lower field.

Examples 1 to 2 preparation of (Z) -N '- (2, 4-dichlorophenyl) -N "-hydroxyacetimidamide hydrazide and (Z) -N' - (2, 4-dichlorophenyl) -N-hydroxyacetylhydrazinamide

Example 1

1- (2, 4-dichlorophenyl) -2- (1-nitroethylene) hydrazine (1.30 g,96.0%,5.03 mmol), pt-C (0.13 g, 5%) and methanol (20 mL) were added to a 100mL autoclave, then hydrogen was exchanged three times, the hydrogen pressure was charged to 2MPa, and then stirring was carried out at room temperature for 6 hours until the hydrogen pressure was no longer reduced. Pt-C was removed by filtration, and after concentrating the filtrate, ethyl acetate was added: n-hexane (5 ml, V/v=1:3) was slurried and filtered to give 1.13g of a pale yellow solid with a purity of 97.7% and a yield of 93.8%. The product is (Z) -N ' - (2, 4-dichlorophenyl) -N ' -hydroxyacetyimide hydrazide and (Z) -N ' - (2, 4-dichlorophenyl) -N-hydroxyacetylhydrazine amide.

Analytical data for the structure of (Z) -N' - (2, 4-dichlorophenyl) -N "-hydroxyacetimidate hydrazide (a-isomer) (see fig. 1):

LCMS:[M+H] ⁺ ＝234；

¹ H NMR(DMSO-d6,500MHz),δ(ppm):9.271(s,1H),7.704(s,1H),7.667(s,1H),7.382(d,J＝2.0Hz,1H),7.258(dd,J1＝2.5Hz,J2＝9.0Hz,1H),6.821(d,J＝8.5Hz,1H),1.635(s,3H)

analytical data of (Z) -N' - (2, 4-dichlorophenyl) -N-hydroxyacetylhydrazinamide (B-isomer) structure (see fig. 2 and 3): LCMS [ M+H ]] ⁺ ＝234；

¹ H NMR(DMSO-d6,500MHz),δ(ppm):9.153(s,1H),7.552(s,1H),7.338(d,J＝2.5Hz,1H),7.202(dd,J1＝2.5Hz,J2＝9.0Hz,1H),6.997(s,1H),6.935(d,J＝9.0Hz，1H),1.792(s,3H)；

As can be seen from the accompanying figure 1, the product mainly comprises two isomers A and A ', wherein A and A ' are the same compound, the formation modes of hydrogen bonds are different, the A isomer of the hydrogen bond in the six-membered ring molecule is mainly used as the B isomer, the A ' -isomer is the minimum content of the intramolecular hydrogen bond configuration of the five-membered ring, the integration of the hydrogen spectrum is shown, and the molar ratio of the three isomers is about=1:0.1:0.03.

For the A-isomer, due to H _c Chemical shift of hydrogen bonds in the molecules forming six-membered rings shifts to delta 9.271 towards low fields (see figure 1); for the B-isomer, H _e Intramolecular hydrogen bond chemical shifts forming a six-membered ring with hydroxylamine hydrogen atoms shift to the low field to δ 9.153 (see fig. 2); for the A' -isomer, H _d The chemical shift of hydrogen bonds within the molecule forming a five-membered ring with the oxime hydrogen atom shifts to the high field to δ 7.919 (see fig. 1). Wherein the A-isomer is in a stable conformation with the lowest energy, followed by the B-isomer, and the A' -isomer has the highest energy content and the lowest energy content due to the intramolecular tension of the 5-membered ring.

Example 2

1- (2, 4-dichlorophenyl) -2- (1-nitroethylene) hydrazine (5.2 g,96.0%,20 mmol), ru-C (0.5 g, 5%) and methanol (50 mL) were added to a 100mL autoclave, followed by three hydrogen exchanges, charging the hydrogen pressure to 2MPa, heating to 50℃and stirring for 7 days, during which time hydrogen was replenished to 20kg/cm2. Ru-C was removed by filtration, and the filtrate was concentrated to give a mixture of (Z) -N '- (2, 4-dichlorophenyl) -N "-hydroxyacetimidamide hydrazide and (Z) -N' - (2, 4-dichlorophenyl) -N-hydroxyacetoamide as a pale yellow solid, 4.8g, 94.4% content, 4.3% chlorine removed product, 96.8% yield.

Example 3-example 9 preparation of N' - (2, 4-dichlorophenyl) acetimide hydrazide (Ia)

Example 3

1- (2, 4-dichlorophenyl) -2- (1-nitroethylene) hydrazine (51.7 g,96.0%,0.2 mmol), pt-C (5 g, 5%) and methanol (500 ml) were added to a 1L autoclave, then hydrogen was exchanged three times, the hydrogen pressure was charged to 2MPa, and then stirring was carried out at room temperature for 6 hours until the hydrogen pressure was no longer reduced. After detecting that the raw materials completely disappear, introducing hydrogen to an autoclave to 2MPa, heating to 50 ℃ for reaction for 6 days, filtering the reaction solution to recover platinum carbon, concentrating the filtrate in a rotating way and crystallizing to obtain N' - (2, 4-dichlorophenyl) acetylimide hydrazide which is 41.7g of pale hydrazone black solid, wherein the dechlorination byproduct accounts for about 3.7%, the purity of the product is 95.5%, and the yield is 91.3%.

Analytical data for N' - (2, 4-dichlorophenyl) acetyliminohydrazide structure:

LCMS:[M+H] ⁺ ＝218；

¹ H NMR(CDCl ₃ 500 MHz), δ (ppm): 7.258 (dd, j1=2.5 hz, j2=7.0 hz, 1H), 7.130 (dd, j1=2.0 hz, j2=9.0 hz, 1H), 7.070 (d, j=9.0 hz, 1H), 5.917 (s, 1H), 4.768 (brs, 2H), 2.043 (s, 3H) (see fig. 4) ¹³ C NMR(CDCl ₃ 126 MHz), δ:155.76,142.94,128.25,127.75,123.80,119.47,115.75,19.54 (see fig. 5);

from fig. 4, it can be seen that NH is in the high field, which indicates that the intramolecular hydrogen bond of the five-membered ring is formed, and the NH moves to δ 4.768 in the high field, which is a broad single peak; the presence of c=n bonds in the molecule can be seen from the carbon spectrum δ 155.76 of fig. 5. Thus, the intermediate Ia theoretically has two possible isomers, the C-imine isomer and the D-amide isomer. Wherein the C-form has two hydrogen bonding forms, the two hydrogen acids are more acidic (free hydrogen), thus forming a broader unimodal at delta 4.768; in the case of the D-amide isomer, two amide hydromagnets are not equivalent and are not acidic, so there are three different NH groups, and thus the structure of intermediate Ia should be of the formula C.

Example 4

A100 mL autoclave was charged with 1- (2, 4-dichlorophenyl) -2- (1-nitroethylene) hydrazine (5.2 g,96.0%,20 mmol), ptO ₂ (0.025 g) and ethanol (50 mL), then hydrogen was exchanged three times, the hydrogen pressure was increased to 2MPa, the temperature was increased to 50℃and stirring was carried out for 3 days, during which time hydrogen was supplied to 20kg/cm2. Filtering the reaction solution to remove the catalyst, concentrating the filtrate to obtain N' - (2, 4-dichlorophenyl) acetylimide hydrazide and crystallizing to obtain black color4.1g of solid, 95.7% and about 3.7% of dechlorinated product, 89.4% yield.

Example 5

1- (2, 4-dichlorophenyl) -2- (1-nitroethylene) hydrazine (5.2 g,96.0%,20 mmol), rh-C (10%, 0.025 g) and ethanol (50 mL) were charged into a 100mL autoclave, and then hydrogen was replaced three times, the hydrogen pressure was charged to 2MPa, and the temperature was raised to 35℃and stirred for 2 days, during which time hydrogen was replenished to 2MPa. The reaction solution was filtered, and the filtrate was concentrated to give N' - (2, 4-dichlorophenyl) acetylimide hydrazide which was crystallized to give 4.2g of a black solid with a content of 96.3%, a dechlorinated product of 2.2%, and a yield of 92.2%.

Example 6

1- (2, 4-dichlorophenyl) -2- (1-nitroethylene) hydrazine (1.04 g,96.0%,4.02mmol,1.0 eq.) RaneCAT-1000 (150 mg,15% wt.), toluene (10 mL) was added to the autoclave. The nitrogen is replaced for three times, the hydrogen is replaced for three times, the pressure is increased to 2MPa, and the mixture is stirred at room temperature for 48 hours until the raw materials disappear. Concentration and crystallization give 0.84g of black product with purity of 95.7%, and dechlorination byproduct accounting for 3.4% with yield of 91.7%.

Example 7

1- (2, 4-dichlorophenyl) -2- (1-nitroethylene) hydrazine (1.04 g,96.0%,4.02mmol,1.0 eq), naF (33.8 mg,0.81mmol,0.2 eq), raney-Ni (150 mg,15% wt), methanol (10 mL) were added to the autoclave. And (3) nitrogen replacement for three times, hydrogen replacement for three times, charging to the pressure of 0.7MPa, and stirring at room temperature. After 110 minutes LCMS detected 9% of the product, the hydrogen was repeatedly charged to a pressure of 0.7MPa during which time stirring was continued at room temperature until the starting material disappeared. LCMS detected product selectivity 95.45%, concentrated crystallization gave 0.83g of black product, 96.1% purity, 3.2% dechlorinated product, 90.9% yield.

Example 8

1- (2, 4-dichlorophenyl) -2- (1-nitroethylene) hydrazine (1.04 g,96.0%,4.02mmol,1.0 eq), raney-Ni (150 mg,15% Wt), 1, 2-dichlorobenzene (10 mL) was charged to the autoclave. And (3) nitrogen replacement for three times, hydrogen replacement for three times, filling to the pressure of 2.9MPa, stirring at room temperature for 40 hours, detecting that the raw materials of the product are completely reacted by LCMS, concentrating and crystallizing to obtain 820mg of black product, wherein the purity is 97.3%, the dechlorination byproduct accounts for 1.8%, and the yield is 91.0%.

Example 9

1- (2, 4-dichlorophenyl) -2- (1-nitroethylene) hydrazine (8.3 g,95.9%,32.1mmol,1.0 eq), raney-Ni (1.2 g,15% wt), methanol (60 mL) was added to the autoclave. Repeatedly replacing nitrogen for three times, replacing hydrogen for three times, filling to the pressure of 2.4MPa, stirring for two days at 20 ℃, sampling and detecting 70% of products, and 24% of raw materials are remained. Then hydrogen is filled to the pressure of 2.9MPa, stirring is continued for 18 hours at 20 ℃, the conversion rate of the product is 97.1%, and the raw materials are completely reacted. The Raney-Ni catalyst was recovered by centrifugation, the supernatant was filtered through celite, and concentrated to give 6.6g of a pale brown solid product with a purity of 96.1%, the dechlorinated by-product was 3.2%, and the yield was 90.6%.

Example 10

Dichloro nitrohydrazone (10.0 g,94.7%,38mmol,1.0 eq), raneCAT-8101 (1.4 g,14% wt), meOH (70 mL) was added to the autoclave. The hydrogen is replaced for three times, the pressurizing force is 2.6MPa, the stirring is carried out for 7 hours at 25 ℃, the pressure is reduced to 7kg/cm < 2 >, and the pressure is not changed any more for a long time. The sample was depressurized and checked by HPLC for 94% of product. Centrifuging and filtering to remove the catalyst. Concentrating until solvent is not distilled off, adding petroleum ether (20 mL), precipitating solid, mashing, stirring at room temperature for 0.5h, and standing for 0.5h. Filtration and concentration of the filter cake gave 7.6g of a pale brown solid product, 97.2% of which was 1.1% of dechlorinated by-product and 89.1% of yield.

Example 11

Dichloro nitrohydrazone (10.0 g,94.7%,38mmol,1.0 eq), raneCAT-8101 (1.1 g,11% Wt), meOH (70 mL) was added to the autoclave. The hydrogen is replaced for three times, the pressurizing force is 2.9MPa, the stirring is carried out for 8 hours at 25 ℃, the pressure is reduced to 1.1MPa, and the pressure is not changed any more for a long time. The sample was depressurized and checked by HPLC for 94% of product. Centrifuging and filtering to remove the catalyst. Concentrating until solvent is not distilled off, adding petroleum ether (30 mL), precipitating solid, mashing, stirring at room temperature for 0.5h, and standing for 0.5h. Filtration and filter cake concentration gave 7.7g of a pale brown solid product, which was 1.0% of dechlorinated by-product, 97.1% content and 90.2% yield.

Example 12

Dichloro nitrohydrazone (10.0 g,94.7%,38mmol,1.0 eq), raneCAT-8101 (1.0 g,10% wt), meOH (70 mL) was added to the autoclave. And replacing the hydrogen for three times, filling the mixture to the pressure of 2.8MPa, stirring the mixture for 6 hours at the temperature of 25 ℃, reducing the pressure to 1.2MPa, and keeping the pressure unchanged for a long time. The sample was depressurized and checked by HPLC to yield 97% of product. Centrifuging, recovering the catalyst, and filtering to remove residual catalyst. Concentrating until no solvent is distilled off, adding 20mL petroleum ether, precipitating solid, mashing, stirring at room temperature for 0.5h, and standing for 0.5h. Filtration and concentration of the filter cake gave 7.9g of a pale brown solid product, 97.8% in content, 0.8% by-product of dechlorination and 92.8% yield.

Example 13

Dichloro nitrohydrazone (10.0 g,94.7%,38mmol,1.0 eq), raneCAT-8101 (0.8 g,8% wt.), ethanol (70 mL) was added to the autoclave. The hydrogen is replaced for three times, the mixture is filled to the pressure of 2.9MPa, the mixture is stirred for 6.5 hours at the temperature of 25 ℃, the pressure is reduced to 1.1MPa, and the reaction time is continuously prolonged for 4 hours without changing the pressure. The sample was depressurized and checked by HPLC for 94% of product. Centrifuging, recovering the catalyst, and filtering to remove residual catalyst. When the mixture is concentrated to the residual 20mL of ethanol, 30mL of petroleum ether is added, solid is separated out, smashed, stirred for 0.5h at room temperature and kept stand for 0.5h. Filtration and concentration of the filter cake gave 7.6g of a pale brown solid product, which was 0.9% of dechlorinated by-product, 97.4% of the product and 89.3% of the yield.

Table 1: EXAMPLES 3-13 Effect of hydrogenation of Metal catalysts on the removal of products

Examples	Catalyst	Quantity (%)	Temperature (. Degree. C.)	Dechlorination product (%)	Purity (%)	Yield (%)
							3	Pt-C	5	50	3.7	95.5	91.3
4	PtO2	0.05	50	3.7	95.7	89.4
							5	Rh-C	10	35	2.2	96.3	92.2
6	RaneCAT-1000	15	rt	3.4	95.7	91.7
							7	Raney-Ni	15	rt	3.2	96.1	90.9
8	Raney-Ni	15	rt	1.8	97.3	91
							9	Raney-Ni	15	rt	3.2	96.1	90.6
10	RaneCAT-8101	14	rt	1.1	97.2	89.1
							11	RaneCAT-8101	11	rt	1	97.1	90.2
12	RaneCAT-8101	10	rt	0.8	97.8	92.8
							13	RaneCAT-8101	8	rt	0.9	97.7	89.3

The above experimental data indicate that: raney nickel also has larger difference in activity due to different processing forms and activation modes, generally has small particle size and higher activity, and more Raney nickel or RaneCAT-1000 is easy to generate dechlorinated byproducts, for example, dechlorinated byproducts of example 6-example 9 are generally higher than 3%, wherein the dechlorinated product of example 8 is less because 1, 2-dichlorobenzene is used as a solvent for the reaction; the RaneCAT-8101 with large particle size, poor activity and small amount is directly reduced into iminohydrazone through pressurized hydrogenation, dechlorination side reaction is reduced to about 1%, and generally, the more the catalyst is added, the more dechlorination byproducts are added, but the less RaneCAT-8101 is added, so that the reaction time is prolonged.

Example 14

1- (2, 4-dichlorophenyl) -2- (1-nitroethylene) hydrazine (1.04 g,96.0%,4.03mmol,1.0 eq.) palladium on carbon (100 mg,10% wt.), methanol (10 mL) was added to the autoclave. And (3) nitrogen is replaced three times, hydrogen is replaced three times, the pressure is increased to 0.7MPa, the mixture is stirred at room temperature for 2 days until the product disappears, and the pressure of the hydrogen is continuously increased to 0.7MPa. The LCMS detection product accounts for 9%, the removed mono-chlorine product accounts for 32% and 17%, and the removed dichloro product accounts for 38%. Experiments prove that only a small amount of products are obtained in the hydrogenation reaction of palladium-carbon, and the dechlorination products are mainly obtained.

EXAMPLE 15 preparation of N' - (4-chloro-2-fluorophenyl) acetimide hydrazide (Ib)

To a 250ml autoclave was added (E) -1- (4-chloro-2-fluorophenyl) -2- (1-nitroethylene) hydrazine and (Z) -1- (4-chloro-2-fluorophenyl) -2- (1-nitroethylene) hydrazine (3.0 g,99.6%,12.9 mmol), ethanol (30 ml), raneCAT-8101 (0.3 g,10% Wt) and the mixture was placed in the autoclave, and the mixture was subjected to hydrogen substitution for 3 times, and the mixture was then charged to a pressure of 3MPa, stirred at 30℃for 16 hours until the pressure was reduced to 2.4MPa, and the reaction of the starting materials was complete, and the product was 86.9%. Centrifugal filtration, mother liquor concentration crystallization to obtain 2.2g dark brown solid, purity 96.4%, yield 81.6%.

Analytical data for N' - (4-chloro-2-fluorophenyl) acetylimide hydrazide structure:

LCMS:[M+H] ⁺ ＝202；

¹ h NMR (DMSO-d 6,400 mhz), δ (ppm): 11.645 (s, 1H), 9.359 (brs, 1H), 8.680 (s, 1H), 7.404 (d, j=10.8 hz, 1H), 7.168 (d, j=7.6 hz, 1H), 6.971 (t, j=7.6 hz, 1H), 2.309 (s, 3H) (see fig. 6).

EXAMPLE 16 preparation of N' - (4-chlorophenyl) acetimide (ic)

To a 250ml autoclave was added (Z) -1- (4-chlorophenyl) -2- (1-nitroethylene) hydrazine (E) -1- (4-chlorophenyl) -2- (1-nitroethylene) hydrazine (3.0 g,98.4%,13.8 mmol), ethanol (70 ml), raneCAT-8101 (0.3 g,10% Wt) and the autoclave was purged with hydrogen 3 times and charged to a pressure of 1.5MPa and stirred at 20℃for 1 day. And (3) pressure relief detection, wherein the raw materials are completely reacted, the dechlorinated product accounts for 2.8%, and the product accounts for 95.5%. Centrifugal filtration, mother liquor concentration and residue column chromatography purification obtain 2.8g white solid with purity of 80.7% and yield of 89.5%.

Analytical data for N' - (4-chlorophenyl) acetimide hydrazide structure:

LCMS:[M+H] ⁺ ＝184；

¹ h NMR (DMSO-d 6,400 mhz), δ (ppm): 11.42 (brs., 1H), 9.13 (brs., 1H), 8.67 (s, 1H), 7.29 (d, j=8.0 hz, 2H), 6.86 (d, j=8.0 hz, 2H), 2.27 (s, 3H) (see fig. 7).

EXAMPLE 17 preparation of N' - (2-chlorophenyl) acetimide (Id)

A250 ml autoclave was charged with (E) -1- (2-chlorophenyl) -2- (1-nitroethylene) hydrazine and (Z) -1- (2-chlorophenyl) -2- (1-nitroethylene) hydrazine (3.0 g,97.1%,13.6 mmol), raneCAT-8101 (0.3 g,10% wt) and ethanol (70 ml), displacing the hydrogen, pressurizing to 2.1MPa, and reacting at 30℃for 16 hours, and the reaction was complete with about 3.9% of dechlorinated by-product, and the product was 93.7%. The catalyst was removed by filtration, and the filtrate was concentrated and purified by column to give 2.3g of a white solid with a purity of 98.2% and a yield of 90.8%.

Analytical data for N' - (2-chlorophenyl) acetimide hydrazide structure:

LCMS:[M+H] ⁺ ＝184；

¹ h NMR (DMSO-d 6,400 mhz), δ (ppm): 7.211 (dt, j1=0.8 hz, j2=7.2 hz, 2H), 7.124 (t, j=8.0 hz, 1H), 6.834 (s, 1H), 6.625 (dt, j1=1.6 hz, j2=7.6 hz, 1H), 6.043 (s, 2H), 1.845 (s, 3H) (see fig. 8 and 9).

EXAMPLE 18 preparation of N' -phenylacetimidate hydrazide (ie)

To a 250ml autoclave were added (Z) -1- (1-nitroethylene) -2-phenylhydrazine and (E) -1- (1-nitroethylene) -2-phenylhydrazine (6 g,90.1%,30.2 mmol), ethanol (80 ml) and RaneCAT-8101 (0.6 g), 3 times of hydrogen was replaced, the pressure of the hydrogen was increased to 2.9MPa, and the reaction was carried out at 30℃for 3 days while the pressure of the hydrogen was kept at about 30kg/cm 2. The decompression detection raw materials react completely, and the product accounts for 61%. The catalyst was removed by centrifugation and the filtrate was concentrated. The filtrate was stirred with 2N hydrochloric acid, then separated, extracted three times with dichloromethane, the pH of the aqueous phase was adjusted to 8-9 with sodium hydroxide solution, extracted three times with ethyl acetate, and excess impurities were removed. Then ph=14 was adjusted with sodium hydroxide solution, then extracted three times with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was removed to give 2.7g of a white solid with a purity of 87.0% and a yield of 52.2%

Analytical data for N' -phenylacetimidate hydrazide structure:

LCMS:[M+H] ⁺ ＝150；

¹ H NMR(DMSO-d6,400MHz),δ7.511 (s, 1H), 7.062 (t, J=7.2 Hz, 2H), 6.825 (d, J=8.0 Hz, 2H), 6.543 (t, J=7.2 Hz, 1H), 5.664 (s, 2H), 1.705 (s, 3H) (see FIG. 10).

The foregoing has shown and described the basic principles and main features of the present invention and the advantages of the present invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, and that the above embodiments and descriptions are merely illustrative of the principles of the present invention, and various changes and modifications may be made without departing from the spirit and scope of the invention, which is defined in the appended claims. The scope of the invention is defined by the appended claims and equivalents thereof.

Claims

1. A process for the preparation of a compound of the structure according to formula I, characterized in that it comprises the step of hydrodereducing a nitrohydrazone compound of formula a and/or formula B in the presence of a catalyst:

wherein x=y=cl; or x=f, y=cl; or x=h, y=cl; or x=cl, y=h; or x=y=h.

2. The process for the preparation of a compound of formula I according to claim 1, characterized in that the catalyst is selected from Ni, pt, ptO ₂ One or more of Rh.

3. A process for the preparation of a compound of formula I according to claim 1, characterized in that the catalyst is selected from one or more of Rh-C, raney nickel, raneCAT-8101, raneCAT-1000, pt-C, rh-C;

preferably, the catalyst is selected from one or more of Raney nickel, raneCAT-8101 and RaneCAT-1000; more preferably, the catalyst is selected from RaneCAT-8101.

4. The process for the preparation of a compound of formula I according to claim 1, characterized in that the catalyst is added in an amount of 5 to 20%, preferably 8 to 20%, more preferably 8 to 15% by mass of the nitrohydrazone compound.

5. The process for the preparation of a compound of formula I according to claim 1, characterized in that the hydrogenation reduction reaction is carried out at a pressure of 0.7 to 5MPa, preferably 0.7 to 3MPa or 1.5 to 2.5MPa.

6. The process for the preparation of the compounds of formula I according to claim 1, characterized in that the reaction temperature of the hydrogenation reduction reaction is 20-80 ℃, preferably 20-50 ℃.

7. The process for the preparation of the compounds of formula I according to claim 1, characterized in that the hydrogenation reduction is carried out in the presence of a reaction solvent, which is known and preferably is selected from inert organic solvents.

8. The process for the preparation of a compound of formula I according to claim 1, characterized in that the hydrogenation reduction is carried out in the presence of a reaction solvent selected from benzene, toluene, xylene, chlorobenzene, halogenated hydrocarbons, C _1-4 One or more of alkyl alcohol, THF, dioxane, DMF, DMSO, ethyl acetate.

Preferably, the hydrogenation reduction reaction is carried out in the presence of a reaction solvent selected from one or more of toluene, xylene, chlorobenzene, 1, 2-dichlorobenzene, dichloromethane, chloroform, 1, 2-dichloroethane, methanol, ethanol, n-propanol, isopropanol, n-butanol.

9. The method of preparing a compound of formula I according to claim 1, characterized in that the method further comprises the step of monitoring the reaction to determine the reaction end time.

10. The process for the preparation of a compound of formula I according to claim 1, characterized in that the reaction time of the process is not less than 6 hours, preferably not less than 2 days, or not less than 3 days.