CN104016915B - A kind of preparation method of boscalid amine - Google Patents
A kind of preparation method of boscalid amine Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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Abstract
The present invention relates to field of compound preparation, particularly a kind of preparation method of new type bactericide boscalid amine.The method is in polar aprotic solvent or high boiling solvent, and under alkali and quaternary ammonium salt exist, the Suzuki of palladium catalyst to chlorophenylboronic acid and adjacent kharophen bromobenzene is obtained by reacting intermediate product 4 '-chloro-2-kharophen biphenyl; Described intermediate product under concentrated hydrochloric acid exists after deprotection with the condensation of 2-chloronicotinoyl chloride, to obtain final product.The present invention uses Pd (OH)
2/ C is catalyzer, carries out Suzuki linked reaction, and repeatedly recovery is reused, and existing technology of comparing, saves catalyzer cost greatly, facilitates catalyst recovery to utilize, and avoids the adjacent Iodoaniline of use high cost raw material.
Description
Technical field
The present invention relates to field of compound preparation, particularly a kind of preparation method of new type bactericide boscalid amine.
Background technology
The full name of boscalid amine (popular name: Boscalid) is N-(4 '-chloro-2-xenyl)-2-chloro-3-pyridyl methane amide, the Novel tobacco amides systemic fungicide developed by BASF Aktiengesellschaft at first, obtain more than 50 countries such as Europe, the U.S. prevent and treat 80 kinds of diseases registration for 100 kinds of crops, be succsinic acid ubiquinone reductase inhibitor in mitochondrial respiratory chain, it mainly prevents and treats numerous diseases such as Powdery Mildew, gray mold, sclerotium disease, brown heart and root rot.Can be used for the control comprising the relevant diseases of crop such as rape, grape, fruit tree, tomato, vegetables and field crop.Its mechanism of action agent is unique, with other medicines without cross resistance, shows that boscalid amine is a kind of important new type bactericide to crop safety and favourable ecological effect and toxicity data.
At present, boscalid amine mainly with adjacent Iodoaniline and to chlorophenylboronic acid for starting raw material, four (triphenyl phosphorus) palladium (or, palladium charcoal) is catalyzer, mineral alkali and other solutions of complementary reagents back flow reaction, one step obtains 2-(4-chloro-phenyl-) aniline, then be dissolved in methylene dichloride, at room temperature drip the stirring of 2-chloronicotinoyl chloride and obtain target product.Although decrease single step reaction, there are 2 problems, the first uses homogeneous palladium catalysts as tetrakis triphenylphosphine palladium, not only reclaims difficulty, but also can increase residual heavy metal palladium in product; Its two, even if use callable palladium carbon, but adjacent Iodoaniline price is high, and the production cost of boscalid amine also all can be made to be unsuitable for industrialization higher than its market value.
Therefore, provide a kind of catalyzer to reuse, avoid the preparation method of the boscalid amine using the adjacent Iodoaniline of high cost raw material, there is realistic meaning.
Summary of the invention
In view of this, the invention provides a kind of preparation method of new type bactericide boscalid amine.The method uses Pd (OH)
2/ C is catalyzer, carries out Suzuki linked reaction, and repeatedly recovery is reused, and existing technology of comparing, saves catalyzer cost greatly, facilitates catalyst recovery to utilize, and avoids the adjacent Iodoaniline of use high cost raw material.
In order to realize foregoing invention object, the invention provides following technical scheme:
The invention provides a kind of preparation method of boscalid amine, in polar aprotic solvent or high boiling solvent, under alkali and quaternary ammonium salt exist, the Suzuki of palladium catalyst to chlorophenylboronic acid and adjacent kharophen bromobenzene is obtained by reacting intermediate product 4 '-chloro-2-kharophen biphenyl; Described intermediate product under concentrated hydrochloric acid exists after deprotection with the condensation of 2-chloronicotinoyl chloride, to obtain final product.
Described Suzuki reaction is with Pd (OH)
2/ C is catalyzer, under alkali and quaternary ammonium salt exist, carrying out in DMF.Reaction formula is as follows:
Under concentrated hydrochloric acid exists, the ethanoyl removed in 4 '-chloro-2-kharophen biphenyl obtains 4 '-chloro-2-phenylaniline hydrochloride, and its reaction formula is as follows:
Under diisopropyl ethyl amine (DIEA) exists, complete the condensation of 4 '-chloro-2-phenylaniline hydrochloride and 2-chloronicotinoyl chloride in dry methylene dichloride, its reaction formula is as follows:
In some embodiments of the invention, described palladium catalyst Pd (OH)
2/ C.
In some embodiments of the invention, described condensation is specially under diisopropyl ethyl amine (DIEA) exists, in dry methylene dichloride, and 4 '-chloro-2-phenylaniline hydrochloride and the condensation of 2-chloronicotinoyl chloride.
In some embodiments of the invention, the mol ratio of described palladium catalyst and adjacent kharophen bromobenzene is 0.5 ~ 1:100.
In some embodiments of the invention, described alkali is selected from salt of wormwood or seven water potassiumphosphates.
In some embodiments of the invention, described quaternary ammonium salt is selected from Tetrabutyl amonium bromide (TBAB) or cetyl trimethylammonium bromide (CTAB).
In some embodiments of the invention, described polar aprotic solvent is selected from DMF.
In some embodiments of the invention, described deprotection, for removing ethanoyl, is specially under the hydrochloric acid existence of 36%, in tetrahydrofuran solution, removes ethanoyl.
Present invention also offers the boscalid amine that above-mentioned preparation method obtains.
The invention provides a kind of preparation method of boscalid amine, in polar aprotic solvent or high boiling solvent, under alkali and quaternary ammonium salt exist, the Suzuki of palladium catalyst to chlorophenylboronic acid and adjacent kharophen bromobenzene is obtained by reacting intermediate product 4 '-chloro-2-kharophen biphenyl; Described intermediate product under concentrated hydrochloric acid exists after deprotection with the condensation of 2-chloronicotinoyl chloride, to obtain final product.
In the method, with Pd (OH)
2/ C is catalyzer, and in DMF, under alkali and quaternary ammonium salt exist, the Suzuki of catalysis to chlorophenylboronic acid and adjacent kharophen bromobenzene is obtained by reacting key intermediate species 4 '-chloro-2-kharophen biphenyl.Catalyst P d (OH)
2/ C reuses 6 times, still keeps catalytic activity.React with 2-chloronicotinoyl chloride after 4 '-chloro-2-kharophen biphenyl takes off ethanoyl under concentrated hydrochloric acid exists and obtain boscalid amine with the yield of 88%.The method, because recycled by noble metal catalyst, does not use containing iodine raw material again simultaneously, greatly reduces production cost, completely can industrialization.
The present invention uses Pd (OH)
2/ C is catalyzer, carries out Suzuki linked reaction, and repeatedly recovery is reused, and existing technology of comparing, saves catalyzer cost greatly, facilitates catalyst recovery to utilize, and avoids the adjacent Iodoaniline of use high cost raw material.
Accompanying drawing explanation
Fig. 1 shows the hydrogen spectrogram of 4 '-chloro-2-kharophen biphenyl in embodiment 1;
The hydrogen spectrum of product 4 '-chloro-2-kharophen biphenyl hydrochloride salt prepared by Fig. 2 embodiment 3;
Fig. 3 shows the hydrogen spectrum of product boscalid amine prepared by embodiment 4.
Embodiment
The invention discloses a kind of preparation method of new type bactericide boscalid amine, those skilled in the art can use for reference present disclosure, and suitable improving technique parameter realizes.Special needs to be pointed out is, all similar replacements and change apparent to those skilled in the art, they are all deemed to be included in the present invention.Method of the present invention and application are described by preferred embodiment, related personnel obviously can not depart from content of the present invention, spirit and scope methods and applications as herein described are changed or suitably change with combination, realize and apply the technology of the present invention.
In the preparation method of new type bactericide boscalid amine provided by the invention, raw materials used and reagent all can be buied by market.
Reaction process is monitored by thin-layer chromatography, spot ultraviolet lamp or containing Ce (NH
4)
2(NO
3)
6(0.5g) with (NH
4)
6mo
7o
244H
2o (24.0g) is at 6%H
2sO
4(500mL) yellow solution colour developing.The proton nmr spectra of reaction product is measured by Varianmercuryplus400MHz nuclear magnetic resonance analyser (TMS is interior mark), ESI mass spectrum is determined by the analysis of ESQUIREIonTrapLC/MS liquid chromatography/mass spectrometry combined instrument, and the purity of the mixture that reaction terminates and target product analyzes (KromasilC with Agilent1260 type high performance liquid chromatograph
18stainless steel column, 250mm × 4.6mm, methanol-watermixturesolvent, 65:35V/V are moving phase, flow velocity 1.0mL/min, photodiode array detector, wavelength 236nm, column temperature, 35 DEG C).
Below in conjunction with embodiment, set forth the present invention further:
The preparation of embodiment 14 '-chloro-2-kharophen biphenyl
2-kharophen bromobenzene (21.4g, 0.1mol), to chlorophenylboronic acid (18.7g, 0.12mol), 10% Pd (OH)
2/ C (the Pd (OH) of 0.14g, 1mmol
2), Tetrabutyl amonium bromide (6g) (or quaternary ammonium salt of other identical equivalents), 7 water potassiumphosphates (64g) (or mineral alkali of other identical equivalents) and DMF (or other solvents) (100mL) stir at the temperature set, after TLC monitoring reaction completes, stopped reaction, filter, filtrate is diluted by ethyl acetate (500mL), with the NaOH solution (300mL) of 1M wash, saturated aqueous common salt (3 × 500mL) washing, after anhydrous sodium sulfate drying, boil off solvent, obtain product 24.2g, yield 99%.
1HNMR(400MHz,CDCl
3)δ8.20(d,J＝6.4Hz,1H),7.46(d,J＝6.4Hz,2H),7.41-7.36(m,1H),7.31(d,J＝6.4Hz,2H),7.24-7.16(m,2H),6.90(s,br,1H,NH),2.04(s,3H)。ESI-MS,m/z,[M+H]
+：246.2。Filter cake recirculation after a small amount of water washing uses.
As stated above, with to chlorophenylboronic acid and adjacent kharophen bromobenzene for raw material, reaction result is at different conditions listed in table 1, wherein adjacent kharophen bromobenzene and Pd (OH)
2mol ratio be 100:1.
The yield of 4 '-chloro-2-kharophen biphenyl under table 1 different condition
The analytical results of note: a:HPLC, TBAB-Tetrabutyl amonium bromide; TBAI-tetrabutylammonium iodide; CTAB-cetyl trimethylammonium bromide; DMB-dimethylbenzene.
The result display of table 1, when temperature of reaction is 80 DEG C, when there is no quaternary ammonium salt, react 48 hours, all only detect that trace obtains product, be warming up to 120 DEG C, react 48 hours, also only detect that the adjacent kharophen bromobenzene of 5% is converted into product, this illustrates, quaternary ammonium salt also has considerable effect in the reaction.When temperature of reaction is 80 DEG C, use K
2cO
3for alkali, the speed of response that Tetrabutyl amonium bromide (TBAB) is auxiliary agent is comparatively slow, needs 48 hours, and reaction just completes substantially, but when temperature of reaction brings up to 125 DEG C, when other reaction conditionss are identical, within 13 hours, just reacts complete.We have also investigated the impact on reaction of other alkali and quaternary ammonium salt, find when other conditions are constant, with K
3pO
47H
2o is that the reaction of alkali is the fastest, within 11 hours, just can react complete, and with Na
2cO
3for the reaction of alkali is the slowest.Need just can complete reaction in 21 hours.When other conditions are constant, be that the reaction of auxiliary agent is best with tetrabutylammonium iodide, when making alkali with salt of wormwood, within 9 hours, complete reaction, use K
3pO
47H
2when O makes alkali, within 8 hours, just can react completely, this may be because I-can replace with the bromine generating portion in bromobenzene, thus the cause of accelerated reaction.Cetyl trimethylammonium bromide (CTAB), although better than Tetrabutyl amonium bromide (TBAB), does not have significant difference, but considers containing iodine reagent expensive, can increase cost during industrialization, and industrial generally as far as possible avoiding uses.
For the impact of solvent on reaction, except DMF, we have also investigated the Suzuki reaction in dimethylbenzene, toluene and ethylene glycol, and its effect is all not so good as the good of DMF.According to above experimental result, when selecting the reaction conditions of synthesis boscalid amine intermediate, we determine K
3pO
47H
2o is alkali, and Tetrabutyl amonium bromide (TBAB) is auxiliary agent, and in DMF, catalysis is to the reaction of chlorophenylboronic acid and adjacent kharophen bromobenzene.
Embodiment 2Pd (OH)
2the recycle of/C
2-kharophen bromobenzene (21.4g, 0.1mol), containing the Pd (OH) that filters out chlorophenylboronic acid (21.4g, 0.1mol), embodiment 1
2/ C, Tetrabutyl amonium bromide (6g), K
3pO
47H
2o (64g) and DMF (100mL), at 125 DEG C, be reacted to the some disappearance that TLC monitors 2-kharophen bromobenzene, aftertreatment is the same, the results are shown in Table 2.
Table 2Pd (OH)
2the result of the recycle of/C
The result of table 2 shows, in the circulation of first 2 times, the activity of catalyzer there is not change substantially, namely reacts 11 hours, and Suzuki just can be made to react and carry out completely, from the 3rd time, activity decreases, and needs the increase reaction times just can complete reaction.When being recycled to the 6th time, 14 hours ability is needed substantially to complete reaction.But all things considered, Pd (OH)
2/ C is when synthesis 4 '-chloro-2-kharophen biphenyl, and can repeatedly use, this will reduce the use cost of catalyzer greatly, is convenient to industrialization.
Embodiment 34 '-chloro-2-kharophen biphenyl deacetylation
The 4 '-chloro-2-kharophen biphenyl (9.2g that embodiment 1 is obtained, 3.7mmol), the mixture return stirring 24h that concentrated hydrochloric acid (20mL) and tetrahydrofuran (THF) (20mL) are formed, after TLC monitoring reaction completes, evaporates the water of tetrahydrofuran (THF) and half.Add isopropyl ether (10mL) after cooling, spend the night 4-6 DEG C of placement after stirring evenly.Filter, the cold isopropyl ether of filter cake washs once, the product 4 '-chloro-2-phenylaniline hydrochloride (6.4g of vacuum drying, 72%), after filtrate concentrates half, then at 4-6 DEG C of condition left overnight, there is crystallization again, filter to obtain product 1.5g (16.9%), add up to yield to be 88.9%.Nuclear-magnetism detected result:
1hNMR (400MHz, DMSO-d
6) δ 7.60-7.50 (dd, J=10.4Hz, J=12.4,8.8Hz), 7.51-7.42 (m, 2H), 7.39-7.31 (m, 2H).After testing, products obtained therefrom is 4 '-chloro-2-kharophen biphenyl hydrochloride salt.
The preparation of embodiment 4 boscalid amine
The 4 '-chloro-2-phenylaniline hydrochloride (24g that embodiment 3 is obtained, 0.1mol), under the mixture that dry methylene dichloride (200mL) and diisopropyl ethyl amine (30mL) are formed stirs at 0-5 DEG C, drip the solution that step 2-chloronicotinoyl chloride (18.5g, 0.105mol) is formed with methylene dichloride (50mL).3h is stirred again after being raised to room temperature.After TLC monitors the some disappearance of all 2-(4-chloro-phenyl-) anilinechlorides, stopped reaction.In reaction system, add methylene dichloride (200mL) again, wash 2 times with saturated sodium bicarbonate solution, then wash 1 time with water.After organic phase anhydrous sodium sulfate drying, evaporate methylene dichloride and obtain thick product (yield 100%).Head product recrystallizing methanol obtains product 25g, yield 72.9%.After filtrate reclaims evaporate to dryness, then recrystallization obtains product 6g (17.5%), amounts to yield 90.4%.Fusing point 141-143 DEG C.Purity (HPLC) 99%, nuclear-magnetism detected result:
1hNMR (400MHz, CDCl3), δ: 8.45 (dd, J=4.8,2.0Hz, 1H), 8.41 (d, J=8.4Hz), 8.20-8.10 (m, 2H, containing1NH), 7.50-7.42 (m, 3H), 7.36-7.31 (m, 3H), (7.28-7.26 m, 2H).ESI-MS,m/z,[M+H]
+:343.1。After testing, products obtained therefrom is boscalid amine.
The preparation of embodiment 5 boscalid amine
Adjacent kharophen bromobenzene (21.4g, 0.1mol), to chlorophenylboronic acid (18.7g, 0.12mol), 10% Pd (OH)
2/ C (the Pd (OH) of 0.14g, 0.5mmol
2), Tetrabutyl amonium bromide (6g) (or quaternary ammonium salt of other identical equivalents), 7 water potassiumphosphates (64g) (or mineral alkali of other identical equivalents) and DMF (or other solvents) (100mL) stir at the temperature set, after TLC monitoring reaction completes, stopped reaction, filter, filtrate is diluted by ethyl acetate (500mL), with the NaOH solution (300mL) of 1M wash, saturated aqueous common salt (3 × 500mL) washing, after anhydrous sodium sulfate drying, boil off solvent, obtain product 24.5g, yield ~ 100%.
1HNMR(400MHz,CDCl
3)δ8.20(d,J＝6.4Hz,1H),7.46(d,J＝6.4Hz,2H),7.41-7.36(m,1H),7.31(d,J＝6.4Hz,2H),7.24-7.16(m,2H),6.90(s,br,1H,NH),2.04(s,3H)。ESI-MS,m/z,[M+H]
+：246.2。Filter cake recirculation after a small amount of water washing uses.
4 '-chloro-2-kharophen biphenyl (9.2g, 3.7mmol), the mixture return stirring 24h that concentrated hydrochloric acid (20mL) and tetrahydrofuran (THF) (20mL) are formed, after TLC monitoring reaction completes, evaporates the water of tetrahydrofuran (THF) and half.Add isopropyl ether (10mL) after cooling, spend the night 4-6 DEG C of placement after stirring evenly.Filter, the cold isopropyl ether of filter cake washs once, the product 4 '-chloro-2-phenylaniline hydrochloride (6.5g of vacuum drying, 73.2%), after filtrate concentrates half, then at 4-6 DEG C of condition left overnight, there is crystallization again, filter to obtain product 1.45g (16.3%), add up to yield to be 89.5%.Nuclear-magnetism detected result:
1hNMR (400MHz, DMSO-d
6) δ 7.60-7.50 (dd, J=10.4Hz, J=12.4,8.8Hz), 7.51-7.42 (m, 2H), 7.39-7.31 (m, 2H).After testing, products obtained therefrom is 4 '-chloro-2-kharophen biphenyl hydrochloride salt.
4 '-chloro-2-phenylaniline hydrochloride (24g, 0.1mol), under the mixture that dry methylene dichloride (200mL) and diisopropyl ethyl amine (30mL) are formed stirs at 0-5 DEG C, drip the solution that step 2-chloronicotinoyl chloride (18.5g, 0.105mol) is formed with methylene dichloride (50mL).3h is stirred again after being raised to room temperature.After TLC monitors the some disappearance of all 2-(4-chloro-phenyl-) anilinechlorides, stopped reaction.In reaction system, add methylene dichloride (200mL) again, wash 2 times with saturated sodium bicarbonate solution, then wash 1 time with water.After organic phase anhydrous sodium sulfate drying, evaporate methylene dichloride and obtain thick product (yield 100%).Head product recrystallizing methanol obtains product 25.8g, yield 75.2%.After filtrate reclaims evaporate to dryness, then recrystallization obtains product 5.8g (16.9%), amounts to yield 92.1%.Fusing point 141-143 DEG C.Purity (HPLC) 98.4%, nuclear-magnetism detected result:
1hNMR (400MHz, CDCl3), δ: 8.45 (dd, J=4.8,2.0Hz, 1H), (8.41 d, J=8.4Hz), 8.20-8.10 (m, 2H, containing1NH), 7.50-7.42 (m, 3H), 7.36-7.31 (m, 3H), 7.28-7.26 (m, 2H).ESI-MS,m/z,[M+H]
+:343.1。After testing, products obtained therefrom is boscalid amine.
The preparation of embodiment 6 boscalid amine
Adjacent kharophen bromobenzene (21.4g, 0.1mol), to chlorophenylboronic acid (18.7g, 0.12mol), 10% Pd (OH)
2/ C (the Pd (OH) of 0.14g, 0.8mmol
2), Tetrabutyl amonium bromide (6g) (or quaternary ammonium salt of other identical equivalents), 7 water potassiumphosphates (64g) (or mineral alkali of other identical equivalents) and DMF (or other solvents) (100mL) stir at the temperature set, after TLC monitoring reaction completes, stopped reaction, filter, filtrate is diluted by ethyl acetate (500mL), with the NaOH solution (300mL) of 1M wash, saturated aqueous common salt (3 × 500mL) washing, after anhydrous sodium sulfate drying, boil off solvent, obtain product 24.4g, yield 99.4%.
1HNMR(400MHz,CDCl
3)δ8.20(d,J＝6.4Hz,1H),7.46(d,J＝6.4Hz,2H),7.41-7.36(m,1H),7.31(d,J＝6.4Hz,2H),7.24-7.16(m,2H),6.90(s,br,1H,NH),2.04(s,3H)。ESI-MS,m/z,[M+H]
+：246.2。Filter cake recirculation after a small amount of water washing uses.
4 '-chloro-2-kharophen biphenyl (9.2g, 3.7mmol), the mixture return stirring 24h that concentrated hydrochloric acid (20mL) and tetrahydrofuran (THF) (20mL) are formed, after TLC monitoring reaction completes, evaporates the water of tetrahydrofuran (THF) and half.Add isopropyl ether (10mL) after cooling, spend the night 4-6 DEG C of placement after stirring evenly.Filter, the cold isopropyl ether of filter cake washs once, the product 4 '-chloro-2-phenylaniline hydrochloride (6.42g of vacuum drying, 72.3%), after filtrate concentrates half, then at 4-6 DEG C of condition left overnight, there is crystallization again, filter to obtain product 1.5g (16.9%), add up to yield to be 89.2%.Nuclear-magnetism detected result:
1hNMR (400MHz, DMSO-d
6) δ 7.60-7.50 (dd, J=10.4Hz, J=12.4,8.8Hz), 7.51-7.42 (m, 2H), 7.39-7.31 (m, 2H).After testing, products obtained therefrom is 4 '-chloro-2-kharophen biphenyl hydrochloride salt.
4 '-chloro-2-phenylaniline hydrochloride (24g, 0.1mol), under the mixture that dry methylene dichloride (200mL) and diisopropyl ethyl amine (30mL) are formed stirs at 0-5 DEG C, drip the solution that step 2-chloronicotinoyl chloride (18.5g, 0.105mol) is formed with methylene dichloride (50mL).3h is stirred again after being raised to room temperature.After TLC monitors the some disappearance of all 2-(4-chloro-phenyl-) anilinechlorides, stopped reaction.In reaction system, add methylene dichloride (200mL) again, wash 2 times with saturated sodium bicarbonate solution, then wash 1 time with water.After organic phase anhydrous sodium sulfate drying, evaporate methylene dichloride and obtain thick product (yield 100%).Head product recrystallizing methanol obtains product 25.3g, yield 73.8%.After filtrate reclaims evaporate to dryness, then recrystallization obtains product 6.1g (17.7%), amounts to yield 91.5%.Fusing point 141-143 DEG C.Purity (HPLC) 98.7%, nuclear-magnetism detected result:
1hNMR (400MHz, CDCl3), δ: δ: δ: 8.45 (dd, J=4.8,2.0Hz, 1H), (8.41 d, J=8.4Hz), 8.20-8.10 (m, 2H, containing1NH), 7.50-7.42 (m, 3H), 7.36-7.31 (m, 3H), 7.28-7.26 (m, 2H).ESI-MS,m/z,[M+H]
+:343.1。After testing, products obtained therefrom is boscalid amine.
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (6)
1. a preparation method for boscalid amine, is characterized in that, in polar aprotic solvent, under alkali and quaternary ammonium salt exist, the Suzuki of palladium catalyst to chlorophenylboronic acid and adjacent kharophen bromobenzene is obtained by reacting intermediate product 4 '-chloro-2-kharophen biphenyl; Described intermediate product under concentrated hydrochloric acid exists after deprotection with the condensation of 2-chloronicotinoyl chloride, to obtain final product;
Described palladium catalyst is Pd (OH)
2/ C, described condensation is specially under diisopropyl ethyl amine exists, in dry methylene dichloride, 4 '-chloro-2-phenylaniline hydrochloride and the condensation of 2-chloronicotinoyl chloride.
2. preparation method according to claim 1, is characterized in that, the mol ratio of described palladium catalyst and adjacent kharophen bromobenzene is 0.5 ~ 1:100.
3. preparation method according to claim 1, is characterized in that, described alkali is selected from salt of wormwood or seven water potassiumphosphates.
4. preparation method according to claim 1, is characterized in that, described quaternary ammonium salt is selected from Tetrabutyl amonium bromide or cetyl trimethylammonium bromide.
5. preparation method according to claim 1, is characterized in that, described polar aprotic solvent is selected from DMF.
6. preparation method according to claim 1, is characterized in that, described deprotection, for removing ethanoyl, is specially under the hydrochloric acid existence of 36%, in tetrahydrofuran solution, removes ethanoyl.
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| CN114292681B (en) * | 2021-12-28 | 2024-03-19 | 安阳市锐普农化有限责任公司 | Novel smoke ignition method |
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| CN1751026A (en) * | 2003-02-14 | 2006-03-22 | 巴斯夫股份有限公司 | Novel crystalline forms of dehydrated boscalid |
| US20110054183A1 (en) * | 2008-05-08 | 2011-03-03 | Basf Se | Method For Manufacturing Aryl Carboxamides |
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