CN115703728A - Trifluoromethyl phenyl thiocyanate compound - Google Patents

Trifluoromethyl phenyl thiocyanate compound Download PDF

Info

Publication number
CN115703728A
CN115703728A CN202110905031.1A CN202110905031A CN115703728A CN 115703728 A CN115703728 A CN 115703728A CN 202110905031 A CN202110905031 A CN 202110905031A CN 115703728 A CN115703728 A CN 115703728A
Authority
CN
China
Prior art keywords
reaction
thiocyanate
chloro
trifluoromethylphenyl
formula
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202110905031.1A
Other languages
Chinese (zh)
Inventor
谭昊明
付其璋
陈和粲
刘雨阳
请求不公布姓名
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shanghai Taichu Chemical Technology Co ltd
Original Assignee
Shanghai Taichu Chemical Technology Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shanghai Taichu Chemical Technology Co ltd filed Critical Shanghai Taichu Chemical Technology Co ltd
Priority to CN202110905031.1A priority Critical patent/CN115703728A/en
Publication of CN115703728A publication Critical patent/CN115703728A/en
Pending legal-status Critical Current

Links

Landscapes

  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses a trifluoromethyl phenyl thiocyanate (general formula (I)) compound and a preparation method of the compound, and discloses a method for synthesizing penoxsulam and a key intermediate 2-halogeno-6 trifluoromethyl benzene sulfonyl chloride by using the compound as a starting material.

Description

Trifluoromethyl phenyl thiocyanate compound
Technical Field
The invention belongs to the field of organic synthesis, discloses a preparation method of a trifluoromethyl phenyl thiocyanate compound, and discloses a new route and a new method for preparing an agricultural herbicide and an intermediate thereof by taking the compound as a starting raw material, in particular to a preparation method of the trifluoromethyl phenyl thiocyanate, and a synthesis method for synthesizing the herbicide penoxsulam and the intermediate 2-halo-6-trifluoromethyl benzene sulfonyl chloride thereof by taking the intermediate as the starting raw material.
Background
Penoxsulam is a pesticide herbicide, and 2-halogeno-6-trifluoromethylbenzenesulfonyl chloride is a main intermediate for synthesizing the herbicide. Of these intermediates, only 2-fluoro-6-trifluoromethylbenzenesulfonyl chloride was used in the synthesis of penoxsulam. The main raw materials for synthesizing the intermediate comprise 2-chloro-6-fluoro-trifluoromethylaniline, 2-fluoro-6-trifluoromethylaniline and 2,3-dichlorotrifluorotoluene.
CN201610769458.2 discloses a method for preparing 2-fluoro-6-trifluoromethylbenzenesulfonyl chloride by diazotization-sulfonyl chlorination-fluorination with 2-chloro-6-trifluoromethylaniline (see reaction formula (i)).
Figure 100002_DEST_PATH_IMAGE001
Reaction type 1
The preparation of the 2-chloro-6-trifluoromethyl aniline is difficult and not easy to obtain, and even if the synthesis and preparation cost is high, the reaction route is only in a laboratory stage at the present stage.
In 2002, U.S. Pat. No. 5, 6433169 reports the preparation of 2-fluoro-6-trifluoromethylbenzenesulfonyl chloride from 2-fluoro-6-trifluoromethylaniline as a raw material by amino diazotization under the action of cuprous chloride and sulfur dioxide (see reaction formula (II)).
Figure 100002_DEST_PATH_IMAGE002
Reaction type 2
Although the method has short synthetic route, the cost of raw materials is high.
Chinese patent CN104693080A reports that 2,3-dichlorobenzotrifluoride is used as a raw material, and the raw material is subjected to fluorine displacement and hydrocarbon sulfydryl substitution to generate 6-fluorine-2-trifluoromethylphenyl sulfide (the synthetic process is shown as a reaction formula (III)), and then the product is prepared by chlorine oxidation.
Figure 100002_DEST_PATH_IMAGE003
Reaction type III
The method has more synthesis steps, products need to be separated by distillation after fluorine replacement, and the energy consumption is increased, and particularly, the 2,3-dichlorobenzotrifluoride is difficult to prepare.
Chinese patent CN201510993472.6 uses o-trifluoromethylaniline as raw material, and synthesizes intermediate 2-fluoro-6-trifluoromethylbenzenesulfonyl chloride through acylation, alkylation, nitration, dealkylation, reduction, diazotization fluorination, hydrolysis and sulfonylation reactions. The method has more synthesis steps, and is not beneficial to industrial production through 10 steps of reaction (the synthesis process is shown in a reaction formula (IV)).
Figure 100002_DEST_PATH_IMAGE004
Reaction type (IV)
The core intermediate 2-fluoro-6-trifluoromethylbenzene sulfonyl chloride for preparing penoxsulam is expensive in raw material source and long in preparation route, so that the finding of a raw material which is cheap and easy to prepare 2-halo-6-trifluoromethylbenzene sulfonyl chloride is particularly important.
Disclosure of Invention
In order to reduce the production cost of penoxsulam, the invention discloses a new raw material 2-halogeno-4-nitro-6-trifluoromethylphenyl thiocyanate for synthesizing 2-halogeno-6-trifluoromethylbenzenesulfonyl chloride.
The technical scheme is as follows:
a trifluoromethyl phenyl thiocyanate compound (the structure is shown in a general formula (I)) is applied to the preparation of penoxsulam and an intermediate compound 2-halogeno-6-trifluoromethyl benzene sulfonyl chloride.
Figure 100002_DEST_PATH_IMAGE005
General formula (I)
In the general formula (I), X is halogen and is selected from fluorine, chlorine and bromine.
In the compound (I) in the general formula, 1) when X is Br or Cl, the synthetic route is 2-chloro-3-bromo-5-nitro-benzotrifluoride or 2,3-dichloro-5-nitro-benzotrifluoride and alkali metal and/or alkaline earth metal salt of thiocyanic acid (the reaction process is shown in the reaction formula (V)): 2) When X is fluorine, the synthetic route is 2,3-difluoro-5-nitro-benzotrifluoride and the alkali metal and/or alkaline earth metal salt of thiocyanic acid (the reaction process is shown in the formula (VI)).
Figure 100002_DEST_PATH_IMAGE006
In the reaction formula (V), X is Cl or Br;
Figure 100002_DEST_PATH_IMAGE007
reaction type (six)
For a further improvement of the synthetic preparation of 2-halo-4-nitro-6-trifluoromethylphenyl thiocyanate, 1) when X is Cl, 2,3-dichloro-5-nitrobenzotrifluoride was prepared according to the following synthetic route: nitrating 2-chloro-benzotrifluoride with nitric acid to prepare 2-chloro-5-nitrobenzotrifluoride, and then chlorinating 2-chloro-5-nitrobenzotrifluoride to prepare 2,3-dichloro-5-nitrotoluene (the reaction process is shown as a reaction formula (VII)); 2) When X is Br, 2-chloro-3-bromo-5-nitro-trifluorotoluene is prepared according to the following synthetic route: the 2-chloro-trifluorotoluene is first nitrated with nitric acid to prepare 2-chloro-5-nitrotrifluorotoluene, and then the 2-chloro-5-nitrotrifluorotoluene is brominated to prepare 2-chloro-3-bromo-5-nitrotrifluorotoluene (see the reaction formula (eight) for the reaction process). 3) When X is F, 2,3-difluoro-5-nitrobenzotrifluoride is prepared by the following synthetic route: firstly, dinitration is carried out on 2-chloro-benzotrifluoride by nitric acid to prepare 2-chloro-3,5-dinitro-benzotrifluoride, and then potassium fluoride is used for replacing 2-chlorine and 3-nitro to prepare 2,3-difluoro-5-nitrobenzotrifluoride (the reaction process is shown in a reaction formula (nine)).
Figure DEST_PATH_IMAGE008
Reaction type (seven)
Figure DEST_PATH_IMAGE009
Reaction type (eight)
Figure DEST_PATH_IMAGE010
Reaction type (nine)
For further improvement of the chlorination reaction of the 2-chloro-5-nitrobenzotrifluoride, the following technical scheme is selected: 1) Chlorine and 2-chloro-5-nitrobenzotrifluoride are selected to be directly subjected to chlorination reaction under the catalysis of a catalyst, the reaction temperature of the reaction is 20-140 ℃, the reaction time of the reaction is 2-48 hours, and the catalyst comprises one or more than two of aluminum trichloride, ferric trichloride, boron trifluoride and antimony pentachloride; 2) Chlorinating with N-chlorosuccinimide or 1,3-dichloro-5,5-dimethylhydantoin (dichlorodimethylhydantoin) in a solvent comprising one or more of sulfuric acid, phosphoric acid, pentane, hexane, octane, cyclohexane, cyclopentane, acetonitrile or benzonitrile;
for further improvement of the bromination reaction of the 2-chloro-5-nitrobenzotrifluoride, the following technical scheme is adopted: 1) Bromine and 2-chlorine-5-nitryl benzotrifluoride are used for direct bromination reaction under the catalysis of a catalyst, wherein the catalyst comprises one or more than two of aluminum trichloride, ferric trichloride, antimony pentachloride, aluminum tribromide, ferric tribromide and antimony pentabromide; 2) Bromination of N-chlorosuccinimide and/or 1,3-dibromo-5,5-dimethylhydantoin (dibromodimethylhydantoin) with 2-chloro-5-nitrobenzotrifluoride in a solvent comprising one or more of sulfuric acid, phosphoric acid, pentane, hexane, N-heptane, octane, 60-90 petroleum ether, cyclohexane, cyclopentane, acetonitrile, butyronitrile and benzonitrile.
For further improvement of the preparation method of 2,3-difluoro-5-nitro-benzotrifluoride, the following technical scheme is adopted: the preparation method is characterized in that 2-chloro-3,5-dinitro-benzotrifluoride and SDKF (spray-dried potassium fluoride) are subjected to catalytic reaction in a solvent by using a catalyst and/or a nitrite quenching agent (the reaction process is shown in a reaction formula (nine)). The catalyst comprises one or more than two of tetramethyl ammonium fluoride, tetramethyl phosphine fluoride, tetrabutyl ammonium chloride and tetrabutyl ammonium bromide; the nitrite quenching agent comprises one or more than two of phthaloyl chloride, phthaloyl fluoride and tetrafluoro 4,4' diphenyl tetracarboxyl fluoride.
As a further optimization for preparing the trifluoromethyl phenyl thiocyanate compound of the general formula (I) by 2-halo-4-nitro-6-trifluoromethyl sulfocyanation reaction, the sulfocyanation reaction is catalyzed by using a catalyst, the catalyst is a phase transfer catalyst, and the phase transfer catalyst comprises one or more than two of tetrabutylammonium bromide, benzyltrimethylammonium chloride and benzyltriethylammonium chloride; the reaction temperature of the reaction is 20-120 ℃, preferably 40-80 ℃, and the reaction time of the reaction is 2-48 hours; the solvent comprises one or more than two of N, N-Dimethylformamide (DMF), N-methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO) and sulfolane.
As a further optimization for the preparation of the trifluoromethyl phenyl thiocyanate compound of the general formula (I) by the 2-halo-4-nitro-6-trifluoromethyl sulfocyanation reaction, the alkali metal comprises one or more than two of sodium, potassium, lithium and cesium, and the alkaline earth metal comprises one or more than two of calcium, magnesium, beryllium and barium.
The invention also discloses a synthesis method for synthesizing an intermediate 2-halogeno-6-trifluoromethylbenzenesulfonyl chloride of penoxsulam by using the trifluoromethyl phenyl thiocyanate compound with the general formula (I) as a starting raw material, wherein the synthesis process is as follows (the synthesis process is shown as a reaction formula (ten)):
Figure DEST_PATH_IMAGE011
reaction type (ten)
1) Reducing the nitro group of the compound to an amino group;
2) Diazotizing an amino compound to remove amino to prepare 2-halogenated-6-trifluoromethyl phenyl thiocyanate;
3) Oxidizing and chlorinating 2-halogeno-6-trifluoromethylphenyl thiocyanate by introducing chlorine to obtain 2-halogeno-6-trifluoromethylbenzenesulfonyl chloride.
In a further improvement of the synthesis method of 2-halo-6-trifluoromethylbenzenesulfonyl chloride, which is an intermediate for synthesizing penoxsulam by using a trifluoromethylphenyl thiocyanate compound of the general formula (I) as a starting material, in the above reaction process 1), reduction of nitro group to amino group is carried out by the following method: a) Reducing the reduced iron powder and hydrochloric acid; b) Reducing stannous chloride; c) Reducing a sulfur-containing compound, wherein the sulfur-containing compound comprises one or more of sodium sulfide, sodium polysulfide, sodium hydrosulfide and sodium hydrosulfite; d) Reducing a phosphorus-containing compound, wherein the phosphorus-containing compound comprises one or more than two of hypophosphorous acid, phosphorous acid, sodium phosphite and sodium hypophosphite; in addition, e) ferric trichloride/active carbon is used as a catalyst to catalyze hydrazine hydrate for reduction; f) Carrying out catalytic hydrogenation reduction by using a catalyst, wherein the catalyst comprises a Raney nickel catalyst containing thiourea as a secondary catalyst and sodium phosphite, and a supported noble metal catalyst, and the supported noble metal catalyst comprises Pt/C, pd/C, pt/Al 2 O 3 , Pd/ Al 2 O 3 One or two or more of (1).
In a further improvement of the synthesis method of 2-halogeno-6-trifluoromethylbenzenesulfonyl chloride, which is an intermediate for synthesizing penoxsulam from a trifluoromethyl phenyl thiocyanate compound of the general formula (I) as a starting material, in the above reaction process 2), amino groups are removed by using the following reaction system: a) Diazotizing a sodium nitrite/sulfuric acid system and deaminating alcohol, wherein the alcohol comprises one or more than two of isopropanol, isobutanol, methanol and ethanol; b) Removing amino from nitrite, wherein the nitrite comprises one or more than two of isopropyl nitrite, n-propyl nitrite, n-butyl nitrite, sec-butyl nitrite, tert-butyl nitrite, isobutyl nitrite and isoamyl nitrite; c) The removal of the amino groups is carried out with gas nitric oxide/alcohol, nitric oxide, oxygen and alcohol.
The invention also discloses a synthesis method for synthesizing penoxsulam from 2-halogeno-6-trifluoromethylbenzenesulfonyl chloride prepared from the trifluoromethyl phenyl thiocyanate compound with the general formula (I), which comprises the following steps: 1) Condensing 2-halogeno-6-trifluoromethylbenzene sulfonyl chloride and 5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidine-2-amine in a solvent under the action of an acid-binding agent to prepare N- (5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidine-2) yl-2-halogeno-6-trifluoromethylbenzene sulfonamide; 2) N- (5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2) yl-2-fluoro-6-trifluoromethylbenzenesulfonamide is reacted with (2,2) -difluoroethanol to prepare the penoxsulam.
The invention has the beneficial effects that:
1. the invention discloses a novel compound which is easy to prepare;
2. the reaction steps for preparing the 2-halogenated-6-trifluoromethyl benzene sulfonyl chloride by using the compound and further preparing the penoxsulam are less.
Detailed Description
The present invention will now be described with reference to specific embodiments, but the present invention should not be construed as being limited to the scope of the specific embodiments.
A first part: synthesis of phenyl thiocyanate compounds
Example 1 synthesis of 2, 3-dichloro-5-nitro-trifluorotoluene
Step 1 Synthesis of 2-chloro-5-nitrobenzotrifluoride
The reaction formula is as follows:
Figure DEST_PATH_IMAGE012
reaction type (eleven)
The operation process is as follows: 54.2g 2-chloro-benzotrifluoride (0.3 mol) and 75ml93% concentrated sulfuric acid are added into a 250ml three-neck flask containing a mechanical stirring thermometer, 45ml (0.45 mol) of 65% concentrated nitric acid is dripped in 2 hours at 5-10 ℃, after the dripping is finished, the temperature is raised to 25 ℃ in 1 hour, the reaction is continued for 1 hour, then the reaction is continued for 2 hours at 40-50 ℃, the reaction is stopped by gas chromatography tracking, and when the content of the 2-chloro-benzotrifluoride is less than 1%, the reaction liquid is added into a 250ml conical separating funnel for separating. The upper organic phase was separated and washed twice with aqueous solution. 43.0g of 2-chloro-5-nitrotrichlorotoluene (94.2% in content) was produced;
step 2: synthesis of 2,3-dichloro-5-nitrobenzotrifluoride
The reaction formula is as follows:
Figure DEST_PATH_IMAGE013
reaction type (twelve)
The operation process is as follows: 34.0g of 2-chloro-5-nitrobenzotrifluoride prepared above was charged into a 100ml three-necked flask equipped with a thermometer, a reflux condenser and a stirring device. Adding 5g of antimony pentachloride into a reaction system, heating to 100 ℃, introducing 10g of chlorine gas within 48 hours, tracing by a reaction gas chromatography, blowing out the residual chlorine gas by using nitrogen gas after the content of a 2-chloro 5-nitrobenzotrifluoride raw material in the reaction system is less than 1%, and distilling under reduced pressure at the temperature of 10mmHg116-118 ℃ to evaporate 30.0g of 2, 3-dichloro-5-nitrobenzotrifluoride (the purity is 95%).
Example 2:2,3-dichloro-5-nitrobenzotrifluoride synthesis
Step 1: procedure example 1 step 1
Step 2:2,3-dichloro-5-nitrobenzotrifluoride
The reaction formula is as follows:
Figure 128597DEST_PATH_IMAGE013
reaction formula (thirteen)
The operation process is as follows: a500 mL four-necked flask with stirring was charged with 200mL of concentrated sulfuric acid, 45.0g (0.2 mol) of 2-chloro-5-nitrobenzotrifluoride, incubated at 30 ℃ and at this temperature, 1,3-dichloro-5,5-dimethylhydantoin 28.0g (0.14 mol) (dichlorohydantoin) was added in portions and incubated. After GC detection of complete conversion of the starting material, the temperature was reduced to 25 ℃ and poured into 300g of crushed ice, extracted three times with 100ml of dichloromethane, and the dichloromethane was removed to give 2,3-dichloro-5-nitrobenzotrifluoride in 96% yield.
Example 3: 2-chloro-3-trifluoromethyl-5-nitrobromobenzene
Step 1
Procedure example 1 step 1
Step 2:
the reaction formula is as follows:
Figure DEST_PATH_IMAGE014
reaction type (fourteen)
The operation process is as follows: 34.0g of 2-chloro-5-nitrobenzotrifluoride prepared above was charged into a 100ml three-necked flask equipped with a thermometer, a reflux condenser and a stirring device. Adding 5g of antimony pentachloride into a reaction system, heating to 60 ℃, dripping 20.0g of liquid bromine within 48 hours, tracing by a reaction gas chromatography, blowing out residual bromine by using nitrogen after the content of a 2-chloro-5-nitrotrifluorotoluene raw material in the reaction system is less than 1%, and distilling under reduced pressure at the temperature of 5mmHg126-128 ℃ to evaporate 30g of 2-chloro-3-trifluoromethyl-5-nitrobromobenzene (the purity is 95%).
Example 4: 2-chloro-3-trifluoromethyl-5-nitrobromobenzene
Step 1 procedure as in step 1 of example 1
Step 2: 2-chloro-3-trifluoromethyl-5-nitrobromobenzene
The reaction formula is as follows:
Figure 829094DEST_PATH_IMAGE014
reaction type (fifteen)
The operation process is as follows: a500 mL four-necked flask with stirring was charged with 200mL of concentrated sulfuric acid, 44g (0.2 mol) of 2-chloro-5-nitrobenzotrifluoride, incubated at 30 ℃ and 28g (0.10 mol) of 1,3-dibromo-5,5-dimethylhydantoin dibromohydantoin was added in portions at this temperature and incubated. When GC detects that the raw material is completely converted, the temperature is reduced to 25 ℃, the raw material is poured into 300g of crushed ice, 100ml of dichloromethane is used for extraction three times, and the dichloromethane is removed to obtain the 2-chloro-3-trifluoromethyl-5-nitrobromobenzene with the yield of 96%.
Example 5:2,3-difluoro-5-nitrobenzotrifluoride
Step 1: nitration of 2-chlorotrifluorotoluene to produce 2-chloro-3,5-dinitrobenzotrifluoride
The reaction formula is as follows:
Figure DEST_PATH_IMAGE015
reaction type (sixteen)
The operation process is as follows: a250 mol four-necked flask equipped with a mechanical stirrer and a thermometer was charged with 50g of 98% sulfuric acid and 25g of 96% fuming nitric acid, and 36.2g of 2-chloro-trifluorotoluene was added dropwise over 2 hours. Separating out lower layer mixed acid after the dropwise adding is finished; the upper organic phase was added dropwise to a 250ml four-necked flask containing a mechanical thermometer, 20% fuming sulfuric acid 50g,96% nitric acid 25g, reacted at 90-100 ℃ for 8 hours, GC followed by phase separation at about 80 ℃ after the mononitrated product was <1%, the organic phase was washed once with 5%100ml sodium bicarbonate and twice with 100ml water, and the organic phase was separated to obtain 46.2g of 2-chloro-3,5-dinitrobenzotrifluoride with a content of 95% and a yield of 85.3% after pH of the organic phase was around 6-7.
Step two: 2,3-difluoro-5-nitro-benzotrifluoride
The reaction formula is as follows:
Figure DEST_PATH_IMAGE016
reaction type (seventeen)
The operation process is as follows: in a 1000ml four-necked flask equipped with a mechanical stirrer, a thermometer and a reflux condenser, 5g of tetrabutylammonium fluoride, 450g of sulfolane and 94g of spray-dried potassium fluoride (SDKF) were heated to 160g, and 50g of sulfolane was distilled off under reduced pressure; 2-chloro-3,5-dinitrobenzotrifluoride (109g, 0.4mol); o-benzoyl chloride (165.6 g, 0.82mol) was added dropwise to the reaction system, and reacted at 130 ℃ for 6 hours. The reaction mixture was filtered, and the filtrate was subjected to reduced pressure of 15 to 20mmHg, a fraction of 65.1g2, 3-difluoro-5-nitro-benzotrifluoride g (GC purity 95%, yield 68.0%)
Example 6: 2-chloro-4-nitro-6-nitrophenyl thiocyanate
The reaction formula is as follows:
Figure DEST_PATH_IMAGE017
reaction type (eighteen)
The operation process is as follows: in a 250ml four-necked flask with a mechanical stirrer, a thermometer and a reflux condenser, 25.9g2, 3-dichloro-5-nitrobenzotrifluoride (0.10 mol), 15.7g potassium thiocyanate (98%, 0.162 mol), 100mol dimethyl sulfoxide and 0.1g tetrabutylammonium bromide are added, the mixture reacts for 8 hours at the temperature of 80 ℃, GC is used for tracing until the content of 2,3-dichloro-5-nitrobenzotrifluoride is less than 1%, the mixture is filtered, 200ml water is added into the filtrate, 100ml 3 dichloromethane is used for extraction, and after an organic phase is evaporated to dryness, 25.2g 2-chloro-4-nitro-6-trifluoromethylphenyl thiocyanate (95%, the yield is 84%) is obtained. 1 HNMR（DCCl 3 ）：δ8.02（s，1H），δ，8.11（s，1H）。
Example 7: 2-chloro-4-nitro-6-trifluoromethylphenyl thiocyanate
The reaction formula is as follows:
Figure DEST_PATH_IMAGE018
reaction type (nineteen)
The operation process is as follows: 25.9g2, 3-dichloro-5-nitrotrifluorotoluene (0.10 mol), 12.4g calcium thiocyanate (98%, 0.080 mol), 100mol dimethyl sulfoxide and 0.1g tetrabutylammonium bromide are added into a 250ml four-mouth bottle with a mechanical stirrer, a thermometer and a reflux condenser, the mixture reacts for 8 hours at the temperature of 80 ℃, the GC is used for tracking until the content of 2,3-dichloro-5-nitrotrifluorotoluene is less than 1%, the mixture is filtered, 200ml water is added into the filtrate, 100ml 3 dichloromethane is used for extraction, and 26.2g 2-chloro-4-nitro-6-trifluoromethylphenyl thiocyanate (95%, yield 88%) is obtained after the organic phase is evaporated to dryness.
Example 8: 2-bromo-4-nitro-6-trifluoromethylphenyl thiocyanate
The reaction formula is as follows:
Figure DEST_PATH_IMAGE019
reaction type (twenty)
The operation process is as follows: 30.3g of 2-chloro-3-bromo-5-nitrobenzotrifluoride (0.10 mol), 12.4g of potassium thiocyanate (98%, 0.080 mol), 100mol of dimethyl sulfoxide and 0.1g of tetrabutylammonium bromide are added into a 250ml four-neck flask with a mechanical stirrer, a thermometer and a reflux condenser, the mixture is reacted at 80 ℃ for 8 hours, the reaction is followed by GC until the content of the 2-chloro-3-bromo-5-nitrobenzotrifluoride is less than 1%, the reaction solution is filtered, 200ml of water is added into the filtrate, 100ml of dichloromethane is used for extraction, and after the organic phase is evaporated to dryness, 30.6g of 2-bromo-4-nitro-6-trifluoromethylphenyl thiocyanate (95%, yield 89.4%) is obtained. 1 HNMR（DCCl 3 ）：δ8.22（s，1H），δ，8.31（s，1H）。
Example 9: 2-fluoro-4-nitro-6-trifluoromethylphenyl thiocyanate
The reaction formula is as follows:
Figure DEST_PATH_IMAGE020
reaction type (twenty one)
The operation process is as follows: 22.7g of 2, 3-difluoro-5-nitrobenzotrifluoride (0.10 mol), 15.7g of potassium thiocyanate (98%, 0.162 mol), 100mol of dimethyl sulfoxide and 0.1g of tetrabutylammonium bromide were placed in a 250ml four-necked flask equipped with a mechanical stirrer, a thermometer and a reflux condenser, reacted at 80 ℃ for 8 hours, followed by GC until the 2,3-difluorotrifluoro-5-nitrotoluene content became less than 1%, filtered, the filtrate was added to 200ml of water and extracted with 100ml of 3 dichloromethane, and the organic phase was evaporated to dryness to obtain 21.2g of 2-fluoro-4-nitro-6 trifluoromethylphenyl thiocyanate (95%, yield 86.7%). 1 HNMR（DCCl 3 ）：δ7.65（d，1H），δ，8.05（s，1H）。
A second part: preparation of 2-halo-6-trifluoromethylphenyl thiocyanate from trifluoromethylphenyl thiocyanate of general formula Compound (I)
Step 1:
example 10: 2-bromo-4-amino-6-trifluoromethylphenyl thiocyanate
Reaction type
Figure DEST_PATH_IMAGE021
Reaction type (twenty two)
The operation process is as follows: 65.2g (0.20 mol) of 2-bromo-4-nitro-6-trifluoromethylphenyl thiocyanate were dissolved in 130mL of ethanol and 130mL of water, 5g of ammonium chloride was added, the mixture was heated to reflux, and 53.2 (0.95 mol) of iron powder was added in portions. Keeping the temperature at 60 ℃ for 3 hours, detecting by GC, cooling after the raw materials are completely converted, carrying out suction filtration, and recovering iron powder. After the aqueous layer was extracted with 3X 100mL of toluene, the combined organic phases were washed with water to neutrality and desolventized to give 54.0g of (95) 2-bromo-4-amino-6-trifluoromethylphenyl thiocyanate in 87% yield.
Example 11: 2-bromo-4-amino-6-trifluoromethylphenyl thiocyanate
Figure 516820DEST_PATH_IMAGE021
Reaction type (twenty three)
The operation process is as follows: adding 65.2g (0.20 mol) of 2-bromo-4-nitro-6-trifluoromethylphenyl thiocyanate into 200g of hydrochloric acid with the mass fraction of 10%, heating to 65 ℃, then adding 36g (0.558 mol) of zinc powder in batches, preserving heat for 5 hours, detecting by GC, cooling after the raw materials are completely converted, and adjusting the pH value to 8-9 by using 30% sodium hydroxide. The filtered solid is filtered to obtain 52.4g of 2-bromo-4-amino-6-trifluoromethyl phenyl thiocyanate, the purity is 95 percent, and the yield is 84.3 percent.
Example 12: 2-bromo-4-amino-6-trifluoromethylphenyl thiocyanate
The reaction formula is as follows:
Figure 39593DEST_PATH_IMAGE021
reaction type (twenty four)
The operation process is as follows: 65.2g (0.20 mol) of 2-bromo-4-nitro-6-trifluoromethylphenyl thiocyanate were dissolved in 130mL of ethanol and 130mL of water, 5g of ammonium chloride were added, the mixture was heated to reflux, and 39 (0.6 mol) of zinc dust was added in portions. Keeping the temperature for 3 hours, detecting by GC, cooling after the raw materials are completely converted, carrying out suction filtration, and recovering zinc powder. After the aqueous layer was extracted with 3X 100mL of toluene, the combined organic phases were washed with water to neutrality and desolventized to obtain 52.4g of 2-bromo-4-amino-6-trifluoromethylphenyl thiocyanate with a yield of 86.9%.
Example 13: 2-bromo-4-amino-6-trifluoromethylphenyl thiocyanate
The reaction formula is as follows:
Figure 509757DEST_PATH_IMAGE021
reaction type (twenty five)
The operation process is as follows: dissolving 65.2g (0.20 mol) of 2-bromo-4-nitro-6-trifluoromethylphenyl thiocyanate in 130mL of isopropanol, 0.5g of activated carbon and 0.1g of anhydrous ferric chloride, dropwise adding 45.0g of hydrazine hydrate (80%, 0.72 mol) at 80-85 ℃ within 2 hours, then preserving heat for 3 hours, detecting by GC, adding 200mol of water after the raw materials are completely converted, extracting a water layer by using 3X 100mL of toluene, combining organic phases, washing to be neutral by water, and desolventizing to obtain 52.5g of 2-bromo-4-amino-6-trifluoromethylphenyl thiocyanate, wherein the yield is 89.2% and the purity is 95%.
Example (c); 14: 2-bromo-4-amino-6-trifluoromethylphenyl thiocyanate
Reaction type
Figure 456854DEST_PATH_IMAGE021
Reaction type (twenty six)
The operation process is as follows: 65.2g (0.20 mol) of 2-bromo-6-4-nitro-trifluoromethylphenyl thiocyanate was dissolved in 130mL of methanol, 44.8g of sodium hydrosulfide (0.80 mol) was added at 60-65 ℃ and the mixture was incubated for 3 hours, GC was used for detection, after complete conversion of the starting material, 200mol of water was added, 3X 100mL of toluene was used for extraction of the aqueous layer, the combined organic phases were washed with water to neutrality and desolventized to obtain 51.4g of 2-bromo-4-amino-6-trifluoromethylphenyl thiocyanate with a purity of 95% (GC) and a yield of 82.4%.
Example 15: 2-chloro-4-amino-6-trifluoromethylphenyl thiocyanate
The reaction formula is as follows:
Figure DEST_PATH_IMAGE022
reaction type (twenty seven)
The operation process comprises the following steps: dissolving 56.4g (0.20 mol) of 2-chloro-4-nitro-6-trifluoromethylphenyl thiocyanate in 130mL of isopropanol, 0.5g of activated carbon and 0.1g of anhydrous ferric chloride, dropwise adding 45.0g of hydrazine hydrate (80%, 0.72 mol) at 80-85 ℃ within 2 hours, then preserving the temperature for 3 hours, detecting by GC, adding 200mol of water after the raw materials are completely converted, extracting a water layer by using 3 x 100mL of toluene, combining organic phases, washing the organic phases to be neutral, and desolventizing to obtain 48.5g of 2-chloro-4-amino-6-trifluoromethylphenyl thiocyanate, wherein the yield is 91.2%, and the purity is 95%.
Example 16: 2-fluoro-4-amino-6-trifluoromethylphenyl thiocyanate
The reaction formula is as follows:
Figure DEST_PATH_IMAGE023
reaction type (twenty eight)
The operation process is as follows: the operation process is as follows: dissolving 53.2g (0.20 mol) of 2-fluoro-4-nitro-6-trifluoromethylphenyl thiocyanate in 130mL of isopropanol, 0.5g of activated carbon and 0.1g of anhydrous ferric chloride, dropwise adding 45.0g of hydrazine hydrate (80 percent, 0.72 mol) at 80-85 ℃ within 2 hours, then preserving the temperature for 3 hours, detecting by GC, adding 200mol of water after the raw materials are completely converted, extracting a water layer by using 3 x 100mL of toluene, combining organic phases, washing the organic phases to be neutral, and desolventizing to obtain 43.5g of 2-fluoro-4-amino-6-trifluoromethylphenyl thiocyanate, wherein the yield is 89.4 percent and the purity is 95 percent.
Step 2:
example 17: 2-bromo-6-trifluoromethylphenyl thiocyanate
The reaction formula is as follows:
Figure DEST_PATH_IMAGE024
reaction type (twenty nine)
Has been operatedThe process: 59.2g (0.20 mol) of 2-bromo-4-amino-6-trifluoromethylphenyl thiocyanate is dissolved in 168g of 80% sulfuric acid, the temperature is reduced to-5 ℃, 75g of 20% sodium nitrite aqueous solution is added dropwise at the temperature, and the temperature is kept for 2h after the dripping is finished. Slowly adding 150g of isopropanol, stirring for 10h at the temperature, detecting by GC, heating to 25 ℃ after the raw materials are completely converted, extracting by using 3X 100mL of ethyl acetate, combining and desolventizing 39.1g to obtain the 2-bromo-6-trifluoromethylphenyl thiocyanate with the purity of 95 percent and the yield of 65.8 percent. 1 HNMR（DCCl 3 ）：δ7.15（m，1H），7.35-7.55，（m，2H）。
Example 18: 2-bromo-6-trifluoromethylphenyl thiocyanate
Reaction type
Figure 983210DEST_PATH_IMAGE024
Reaction type (thirty)
The operation process is as follows: 59.2g (0.20 mol) of 2-bromo-4-amino-6-trifluoromethylphenyl thiocyanate is dissolved in 50g of tetrahydrofuran, 15.7g (0.23 mol) of sodium nitrite is dissolved in 30g of water, the sodium nitrite and the water are respectively slowly dripped into 100g of 60 percent sulfuric acid with the temperature of minus 5 ℃, the temperature is kept for 1 hour after dripping, 59.4g of hypophosphorous acid is then slowly added, stirring is carried out for 8 hours at the temperature until the raw material in GC is completely converted, and desolventization is carried out after extraction by 3X 100mL of ethyl acetate to obtain 45.6g of 2-bromo-6-trifluoromethylphenyl thiocyanate with the yield of 76.5 percent.
Example 19: 2-bromo-6-trifluoromethylphenyl thiocyanate
The reaction formula is as follows:
Figure 306744DEST_PATH_IMAGE024
reaction type (thirty one)
The operation process is as follows: 59.2g (0.20 mol) of 2-bromo-4-amino-6-trifluoromethylphenyl thiocyanate was dissolved in 200g of tetrahydrofuran, 26.2g of isobutyl nitrite (0.254 mol) was added dropwise to the solution, and the reaction was carried out at 60 to 65 ℃ for 8 hours, and the solvent was distilled off to obtain 48.6g of 2-bromo-6-trifluoromethylphenyl thiocyanate with a purity of 95% and a yield of 82.1%.
Example 20: 2-bromo-6-trifluoromethylphenyl thiocyanate
The reaction formula is as follows:
Figure 103186DEST_PATH_IMAGE024
reaction (thirty-two) procedure: 59.2g (0.20 mol) of 2-bromo-4-amino-6-trifluoromethylphenyl thiocyanate was dissolved in 200g of tetrahydrofuran, air was replaced by bubbling nitrogen gas, 120g of nitrogen monoxide gas (0.254 mol) was bubbled through the solution, and the reaction was carried out at 60 to 65 ℃ for 8 hours, followed by distilling off the solvent to obtain 52.6g of 2-bromo-6-trifluoromethylphenyl thiocyanate with a purity of 95% and a yield of 88.9%.
Example 21: 2-chloro-6-trifluoromethylphenyl thiocyanate
The reaction formula is as follows:
Figure DEST_PATH_IMAGE025
reaction type (thirty three)
The operation process is as follows: 50.4g (0.20 mol) of 2-chloro-4-amino-6-trifluoromethylphenyl thiocyanate was dissolved in 200g of tetrahydrofuran, 26.2g of isobutyl nitrite (0.254 mol) was added dropwise to the solution, and the reaction was carried out at 60 to 65 ℃ for 8 hours, and the solvent was distilled off to obtain 42.6g of 2-chloro-6-trifluoromethylphenyl thiocyanate with a purity of 95% and a yield of 85.7%. 1 HNMR（DCCl 3 ）：δ7.10（m，1H），7.25（dd，1H），7.85，（dd，1H）。
Example 22: 2-fluoro-6-trifluoromethylphenyl thiocyanate
The reaction formula is as follows:
Figure DEST_PATH_IMAGE026
reaction type (thirty-four)
The operation process comprises the following steps: 47.2g (0.20 mol) of 2-fluoro-4-amino-6-trifluoromethylphenyl thiocyanate were dissolved in 200g of tetrahydrofuran and added to this solution26.2 isobutyl nitrite (0.254 mol) is added dropwise, reaction is carried out for 8 hours at the temperature of 60-65 ℃, and the solvent is distilled off, so that 39.2g of 2-fluoro-6-trifluoromethylphenyl thiocyanate is obtained, the purity is 95 percent, and the yield is 84.2 percent. 1 HNMR（DCCl 3 ）：δ7.02（m，1H），7.25（m，1H），7.35，（dd，1H）。
Step three:
example 23: 2-bromo-6-trifluoromethylbenzenesulfonyl chloride
The reaction formula is as follows:
Figure DEST_PATH_IMAGE027
reaction type (thirty-five)
The operation process is as follows: 28.3g (0.1 mol) of 2-bromo-6-trifluoromethylphenyl thiocyanate were dissolved in 100mL of acetic acid and 10mL of water and the temperature was raised to 45 ℃. After chlorine gas (49.7g, 0.7mol) was introduced, the temperature was raised to 55 ℃ and the temperature was maintained for 2 hours. The reaction system is poured into 200mL water, and after extraction with 3X 50mL ethyl acetate, the white solid 2-bromo-6-trifluoromethylbenzenesulfonyl chloride 31.2g with purity of 95% and yield of 91.2% are obtained by combination and desolvation. 1 HNMR（DCCl 3 ）：δ7.55（m，1H），7.85（dd，1H），8.05，（dd，1H）。
Example 24: 2-chloro-6-trifluoromethylbenzenesulfonyl chloride
The reaction formula is as follows:
Figure DEST_PATH_IMAGE028
reaction type (thirty six)
The operation process is as follows: 23.6g (0.1 mol) of 2-bromo-6-trifluoromethylphenyl thiocyanate were dissolved in 100mL of acetic acid and 10mL of water and the temperature was raised to 45 ℃. After chlorine gas (49.7g, 0.7mol) was introduced, the temperature was raised to 55 ℃ and the temperature was maintained for 2 hours. The reaction system was poured into 200mL of water, extracted with 3X 50mL of ethyl acetate, combined and desolventized to give 26.8g of 2-chloro-6-trifluoromethylbenzenesulfonyl chloride as a white solid with a purity of 95% and a yield of 91.9%. 1 HNMR（DCCl 3 ）：δ7.66-7.90（m，3H）。
Example 24: 2-fluoro-6-trifluoromethylbenzenesulfonyl chloride
The reaction formula is as follows:
Figure DEST_PATH_IMAGE029
reaction type (thirty seven)
The operation process is as follows: 22.1g (0.1 mol) of 2-fluoro-6-trifluoromethylphenyl thiocyanate were dissolved in 100mL of acetic acid and 10mL of water and the temperature was raised to 45 ℃. After chlorine gas (49.7g, 0.7mol) was introduced, the temperature was raised to 55 ℃ and the temperature was maintained for 2 hours. The reaction system is poured into 200mL of water, extracted by 3X 50mL of ethyl acetate, and then combined and desolventized to obtain 25.2g of white solid 2-bromofluoro-6-trifluoromethylbenzenesulfonyl chloride with the purity of 95 percent and the yield of 91.2 percent. 1 HNMR（DCCl 3 ）：δ7.55（m，1H），7.65（m，1H），7.85，（dd，1H）
And a third part: synthesis of penoxsulam
The 2-halogeno-6-trifluoromethylbenzene sulfonyl chloride prepared by the intermediate disclosed by the invention is condensed with 5,8-dimethoxy- (1,2,4) triazole- (1,5-c) pyrimidine-2-amine to obtain the compoundN- (5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2) yl-2-fluoro-6-trifluoromethylbenzenesulfonamideN- (5,8-dimethoxy- (1,2,4) triazole and- (1,5 c) pyrimidine-2) base-2-fluorine-6-trifluoromethyl benzene sulfonamide reacts with (2,2) -difluoroethanol to prepare the compoundN- (5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2) yl-2- (2,2-difluoroethoxy) -6-trifluoromethylbenzenesulfonamide (penoxsulam) (see reaction formula (thirty eight) for the reaction process).
The reaction formula is as follows:
Figure DEST_PATH_IMAGE030
reaction type (thirty eight)
Example 25: preparation of penoxsulam from 2-fluoro-6-trifluoromethylbenzenesulfonyl chloride
Step 1:
the reaction formula is as follows:
Figure DEST_PATH_IMAGE031
reaction type (thirty-nine)
The operation process is as follows: in a 550ml four-necked flask equipped with mechanical stirring, thermometer, reflux condenser, 26.2g (0.10 mol) of 2-fluoro-6-trifluoromethylbenzenesulfonyl chloride, 3,5-lutidine 214g (2 mol, solvent), 5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2-amine 19.5g (0.1 mol) were added, heated to 80 ℃ and reacted at 80 ℃ for 8 hours. HPLC analysis until the 2-fluoro-6-trifluoromethylbenzenesulfonyl chloride content<1%, cooling to 25 ℃, adding the reaction solution into a 1000ml beaker, adding 300ml of water into the reaction solution, and stirring for 30 minutes. Filtering, extracting the filtrate with 100ml × 3 of ethyl acetate, evaporating the extract to dryness, combining the filter cake and the residue, and drying to obtain 39.8gN- (5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2) yl-2-fluoro-6-trifluoromethylbenzenesulfonamide.
Step two:
the reaction formula is as follows:
Figure DEST_PATH_IMAGE032
reaction type (forty)
The operation process is as follows: in a 1000ml four-necked flask equipped with a mechanical stirrer and a thermometer, 2.5g (0.12 mol) of sodium hydride and 100ml of tetrahydrofuran were added, and the mixture was cooled to 0 to 5 ℃ and then added dropwise to the solutionN46.2g (content 90%,0.98 mol) of crude product of- (5,8-dimethoxy- (1,2,4) triazole- (1,5-c) pyrimidine-2) yl-2-fluoro-6-trifluoromethyl benzene sulfonamide, 2,2-difluoroethanol 9.84g (1.2 mol) 300ml tetrahydrofuran solution, continuously reacting at 0-5 ℃ for 6 hours after the dropwise addition, heating to 25 ℃, preserving the temperature for 16 hours, tracking by HPLC (high performance liquid chromatography), and continuously reacting for 6 hours after the dropwise addition is finishedN- (5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2) yl-2-fluoro-6-trifluoromethylbenzenesulfonamide<1 percent, dripping hydrochloric acid into the reaction solution, filtering and drying when the pH value of the solution is 6-8 to obtainN- (5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidine-2)46g (purity 85%, yield 81%) of 2- (2,2-difluoroethoxy) -6-trifluoromethylbenzenesulfonamide (penoxsulam).
Example 26: preparation of penoxsulam from 2-chloro-6-trifluoromethylbenzenesulfonyl chloride
The method comprises the following steps:
the reaction formula is as follows:
Figure DEST_PATH_IMAGE033
reaction type (forty one)
The operation process comprises the following steps: 27.8g (0.10 mol) of 2-chloro-6-trifluoromethylbenzenesulfonyl chloride, 3,5-lutidine, 214g (2 mol, solvent), 5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2-amine, 19.5g (0.1 mol) were added to a 550ml four-necked flask equipped with mechanical stirring, thermometer, reflux condenser, and the mixture was heated to 80 ℃ and reacted at 80 ℃ for 8 hours. HPLC analysis until the 2-chloro-6-trifluoromethylbenzenesulfonyl chloride content<1%, cooling to 25 ℃, adding the reaction solution into a 1000ml beaker, adding 300ml of water into the reaction solution, and stirring for 30 minutes. Filtering, extracting the filtrate with 100ml × 3 of ethyl acetate, evaporating the extractive solution to dryness, combining the filter cake and the residue, and drying to obtain 41.8gN- (5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2) yl-2-chloro-6-trifluoromethylbenzenesulfonamide.
Step two
The reaction formula is as follows:
Figure DEST_PATH_IMAGE034
reaction type (forty two)
The operation process comprises the following steps: in a 1000ml four-necked flask equipped with a mechanical stirrer and a thermometer, 2.5g (0.12 mol) of sodium hydride and 100ml of tetrahydrofuran were added, and the mixture was cooled to 0 to 5 ℃ and then added dropwise to the solutionN- (5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2) yl-2-chloro-6-trifluoromethylbenzenesulfonamide crude 48.5g (content 90%,0.98 mol), 2,2-difluoroethanol 9.84g (1.2 mol) 300ml tetrahydrofuran solution, and after the dropwise addition, the reverse reaction at 0-5 ℃ is continuedHeating to 25 deg.C for 6 hr, holding the temperature for 32 hr, and tracking by HPLCN- (5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2) yl-2-fluoro-6-trifluoromethylbenzenesulfonamide<1 percent, dripping hydrochloric acid into the reaction solution, filtering and drying when the pH value of the solution is 6-8 to obtainN45.2g (85% purity, 80% yield) of (5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2) yl-2- (2,2-difluoroethoxy) -6-trifluoromethylbenzenesulfonamide (penoxsulam).
Example 27: preparation of penoxsulam from 2-bromo-6-trifluoromethylbenzenesulfonyl chloride
The method comprises the following steps:
the reaction formula is as follows:
Figure DEST_PATH_IMAGE035
reaction type (forty three)
The operation process is as follows: in a 550ml four-necked flask equipped with mechanical stirring, thermometer, reflux condenser, 32.2g (0.10 mol) of 2-bromo-6-trifluoromethylbenzenesulfonyl chloride, 3,5-lutidine 214g (2 mol, solvent), 5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2-amine 19.5g (0.1 mol) were added, heated to 80 ℃ and reacted at 80 ℃ for 8 hours. HPLC analysis until the content of 2-bromo-6-trifluoromethylbenzenesulfonyl chloride<1%, cooling to 25 ℃, adding the reaction solution into a 1000ml beaker, adding 300ml of water into the reaction solution, and stirring for 30 minutes. Filtering, extracting the filtrate with 100ml × 3 of ethyl acetate, evaporating the extractive solution to dryness, combining the filter cake and the residue, and drying to obtain 44.8gN- (5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2) yl-2-bromo-6-trifluoromethylbenzenesulfonamide (crude content 90%).
Step two:
the reaction formula is as follows:
Figure DEST_PATH_IMAGE036
reaction type (forty four)
The operation process is as follows: in the presence of mechanical stirring and temperatureIn a 1000ml four-necked flask, 2.5g (0.12 mol) of sodium hydride and 100ml of tetrahydrofuran are added, the temperature is reduced to 0-5 ℃, and the solution is added dropwiseN- (5,8-dimethoxy- (1,2,4) triazole and- (1,5 c) pyrimidine-2) base-2-bromine-6-trifluoromethyl benzene sulfonamide crude product 51.2.2g (content 90%,0.10 mol), 2,2-difluoroethanol 9.84g (1.2 mol) 300ml tetrahydrofuran solution, when the dropwise adding is finished, the reaction is continued for 6 hours at 0-5 ℃, the temperature is raised to 25 ℃, the temperature is kept for 48 hours, the HPLC tracking is carried out, when the HPLC is carried out, the reaction is carried outN- (5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2) yl-2-bromo-6-trifluoromethylbenzenesulfonamide<1 percent, dripping hydrochloric acid into the reaction solution, filtering and drying when the pH value of the solution is 6-8 to obtainN46.1g (85% purity, 81.1%) of- (5,8-dimethoxy- (1,2,4) triazolo- (1,5-c) pyrimidin-2) yl-2- (2,2-difluoroethoxy) -6-trifluoromethylbenzenesulfonamide (penoxsulam).

Claims (10)

1. A trifluoromethyl phenyl thiocyanate compound is applied to synthesizing penoxsulam and an intermediate 2-halogeno-6-trifluoromethyl benzene sulfonyl chloride thereof, and the structure of the compound is shown in a general formula (I):
Figure DEST_PATH_IMAGE001
(general formula (I))
X is a halogen selected from: f, cl and Br.
2. A process for the preparation of trifluoromethylphenyl thiocyanate compounds according to claim 1, when X in formula (I) is Br or Cl, said compounds being prepared by reacting 2-chloro-3-bromo-5-nitro-benzotrifluoride or 2,3-dichloro-5-nitro-benzotrifluoride with an alkali metal and/or alkaline earth metal salt of thiocyanic acid, of the formula:
Figure DEST_PATH_IMAGE002
in the formula: and X is Cl or Br.
3. A process for the preparation of trifluoromethylphenyl thiocyanate compounds as claimed in claim 1 when X of formula (I) is F, which is prepared by reacting 2,3-difluoro-5-nitrobenzotrifluoride with an alkali metal and/or alkaline earth metal salt of thiocyanic acid of the formula:
Figure DEST_PATH_IMAGE003
。
4. the method for preparing trifluoromethylphenyl thiocyanate compound according to claim 1 according to claim 2 or 3, wherein said alkali metal includes one or two or more of sodium, potassium, lithium and cesium.
5. The method for preparing trifluoromethylphenyl thiocyanate compound according to claim 1 according to claim 2 or 3, wherein the alkaline earth metal includes one or more of calcium, magnesium, beryllium and barium.
6. The method of claim 2, wherein 2,3-dichloro-5-nitrobenzotrifluoride is prepared by chlorination of 2-chloro-5-nitrobenzotrifluoride, the reaction formula is as follows:
Figure DEST_PATH_IMAGE004
。
7. the process for preparing trifluoromethylphenyl thiocyanate compound according to claim 1 according to claim 2, wherein 2-chloro-3-bromo-5-nitro-benzotrifluoride is prepared by bromination of 2-chloro-5-nitro-benzotrifluoride, the reaction formula is:
Figure DEST_PATH_IMAGE005
。
8. the method of claim 3, wherein 2,3 difluoro-5-nitrobenzotrifluoride is prepared by the reaction of 2-chloro-3,5-dinitro-benzotrifluoride with SDKF (spray dried potassium fluoride) in a solvent catalyzed by a catalyst and/or a nitrite quencher, according to the formula:
Figure DEST_PATH_IMAGE006
。
9. a method for synthesizing penoxsulam intermediate 2-halo-6-trifluoromethylbenzenesulfonyl chloride by using the trifluoromethyl phenyl thiocyanate compound of the general formula (I) as shown in claim 1 as a starting material comprises the following synthetic process:
1) The compound reduces the nitro group into amino group by a reduction method;
2) Removing amino from amino compound by diazotization deamino method;
3) Introducing chlorine into the 2-halogenated-6-trifluoromethyl phenyl thiocyanate to obtain 2-halogenated-6-trifluoromethyl benzenesulfonyl chloride;
the reaction formula is as follows:
Figure DEST_PATH_IMAGE007
。
10. a method for synthesizing penoxsulam by using 2-halogeno-6-trifluoromethylbenzenesulfonyl chloride prepared by using the trifluoromethyl phenyl thiocyanate compound shown in the general formula (I) in claim 1 as a starting material.
CN202110905031.1A 2021-08-08 2021-08-08 Trifluoromethyl phenyl thiocyanate compound Pending CN115703728A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110905031.1A CN115703728A (en) 2021-08-08 2021-08-08 Trifluoromethyl phenyl thiocyanate compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110905031.1A CN115703728A (en) 2021-08-08 2021-08-08 Trifluoromethyl phenyl thiocyanate compound

Publications (1)

Publication Number Publication Date
CN115703728A true CN115703728A (en) 2023-02-17

Family

ID=85179388

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110905031.1A Pending CN115703728A (en) 2021-08-08 2021-08-08 Trifluoromethyl phenyl thiocyanate compound

Country Status (1)

Country Link
CN (1) CN115703728A (en)

Similar Documents

Publication Publication Date Title
CN106866553B (en) Synthesis method of Favipiravir
AU2018383864B2 (en) Method for synthesis of Roxadustat and intermediate compounds thereof
CN113045505A (en) Favipiravir intermediate and synthesis method of favipiravir
CN109879817B (en) Preparation method of mesosulfuron-methyl
WO2022052683A1 (en) Method for preparing water-soluble magnolol derivative and honokiol derivative, methods for preparing intermediates of water-soluble magnolol derivative and honokiol derivative, and related monohydroxy protected intermediate
CN111269175B (en) Nicorandil preparation method
JP4412449B2 (en) Method for producing diaminoresorcinol compound
EP4313954A1 (en) Preparation of 2-chloro-4-fluoro-5-nitrobenzoic acid
US20050059692A1 (en) Process for the preparation of 17beta-N-[2,5-bis(trifluoromethyl)phenyl] carbamoyl-4-aza-5-alpha-androst-1-en-3-one
CN115703728A (en) Trifluoromethyl phenyl thiocyanate compound
CN112939818B (en) Synthetic method of 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride
CN115490622A (en) Trifluoromethyl thiophenol compound
CN115703726B (en) Trifluoromethyl phenyl sulfide compound
JP2794861B2 (en) Method for producing isocyanate compound
JP2780786B2 (en) Method for producing propenoic acid derivative
JPH0354930B2 (en)
EP1295864B1 (en) Process for preparation of 1,5-diaminonaphthalenes
JP4636761B2 (en) Process for producing 2-methoxy-4- (Nt-butylaminocarbonyl) benzenesulfonyl chloride
KR880000203B1 (en) Process for the preparation of 3.3&#39;-dinitrodi-phenyleter
CN113527191B (en) Preparation method of 2,3-dichloro-5-trifluoromethylpyridine
CN114478326B (en) Synthesis method of saflufenacil key intermediate
JP3193421B2 (en) Method for producing 2-amino-4-fluorobenzoic acid
CN117946013A (en) Method for synthesizing 5, 6-dihalogen-3-aminopyrazine-2-methyl formate by one-pot method
JPS61221157A (en) Production of diaminodiphenyl ether
CN117820176A (en) Sulfoxide-based benzotrifluoride compound

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination