CN105237330B

CN105237330B - A kind of synthetic method of 2,3,6 trichlorobenzoic acid and its intermediate

Info

Publication number: CN105237330B
Application number: CN201510800636.9A
Authority: CN
Inventors: 樊小彬; 林行军; 陈冬辉; 周述勇; 陈国彬
Original assignee: LIANHUA TECHNOLOGY (YANCHENG) Co Ltd; United Technology (taizhou) Co Ltd; JIANGSU LIANHUA TECHNOLOGY Co Ltd; Lianhe Chemical Technology Co Ltd
Current assignee: Jiangsu Lianhua Technology Co ltd; Lianhua Angjian Zhejiang Pharmaceutical Co ltd; Lianhe Chemical Technology Co Ltd
Priority date: 2015-11-18
Filing date: 2015-11-18
Publication date: 2017-11-21
Anticipated expiration: 2035-11-18
Also published as: CN105237330A

Abstract

The invention discloses the synthetic method of a kind of 2,3,6 trichlorobenzoic acids and its intermediate.The invention provides a kind of preparation method of 2,3,6 benzotrichlorides, it comprises the following steps：In the presence of catalyst, by the mixture of dichlorotoleune, carry out chlorination reaction with chlorination reagent and obtain 2,3,6 benzotrichlorides, described catalyst is metal and/or metal halide, and the mixture of described dichlorotoleune is 2,6 dichlorotoleune and 2, the mixture of 3 dichlorotoleune or 2,6 dichlorotoleune, 2,3 dichlorotoleune and 2, the mixture of 5 dichlorotoleune.Synthetic method reaction yield of the invention is high, selectivity is high, obtained product purity is high, production cost is low, simple to operate, reaction condition is gentle, is suitable for industrialized production.

Description

A kind of synthetic method of 2,3,6- trichlorobenzoic acids and its intermediate

Technical field

The present invention relates to the synthetic method of a kind of 2,3,6- trichlorobenzoic acids and its intermediate.

Background technology

2,3,6- trichlorobenzoic acids, trade name tribac, be benzoic acid herbicide, available for prevent and kill off it is some it is annual and Perennial deep root broad leaved weed and some shrubs.It can be as an important intermediate (US3444192) warp of synthesis Mediben Mediben (Dicamba) can be made with sodium methoxide single step reaction by crossing.Listed with the approval of anti-Mediben genetically modified crops, wheat The market prospects of grass fear are very good, and 2,3,6- trichlorobenzoic acids correspondingly will also have the increasing market demand.

The method of 2,3,6- trichlorobenzoic acids of synthesis mainly has following several at present：

Patent US3086991A, patent 20030216577A1 and document (Journal of the Chemical Society, 1951,1208-1212) report with 2,3,6- benzotrichlorides as raw material, with oxygen, the side of ozone or nitric acid oxidation Legal system obtains 2,3,6- trichlorobenzoic acids.These three methods are required for doing raw material with 2,3,6- benzotrichlorides, and price is all higher, city It is not easy to buy on a large scale on, raw material is relatively more limited, causes the economic feasibility of industrialized production poor.

Patent CN102947000A is reported with 1,2,4- trichloro-benzenes as raw material, in the complex catalysis of azepine Cabbeen and gold Lower and CO₂2,3,6- trichlorobenzoic acids are directly made in reaction.Shortcoming is to need the complex compound with azepine Cabbeen and gold to make catalyst, Catalyst is more expensive, and production cost is high, should not also be used in industrialized production.

Therefore searching raw material is simple and easy to get, preparation method is simple, production cost is low is suitable for the 2,3,6- of industrialized production The preparation method of trichlorobenzoic acid is the current technical problem for being badly in need of solving.

The content of the invention

The technical problems to be solved by the invention are to overcome the preparation side of 2,3,6- trichlorobenzoic acids in the prior art Method cost of material height is not easy to obtain, preparation method is complicated, reaction selectivity is poor, obtained product purity is poor, yield is low, is produced into This height, it is not suitable for the defects of industrialized production and provides a kind of synthesis side of 2,3,6- trichlorobenzoic acids and its intermediate Method.The synthetic method reaction yield of the present invention is high, selectivity is high, obtained product purity is high, production cost is low, it is simple to operate, Reaction condition is gentle, is suitable for industrialized production.

The invention provides a kind of preparation method of 2,3,6- benzotrichlorides, it comprises the following steps：In the presence of catalyst, By the mixture of dichlorotoleune, carry out chlorination reaction with chlorination reagent and obtain 2,3,6- benzotrichlorides, described catalyst For metal and/or metal halide, the mixture of described dichlorotoleune is mixed for 2,6-DCT and 2,3- dichlorotoleune The mixture of compound or 2,6-DCT, 2,3- dichlorotoleune and 2,5- dichlorotoleune；

In the preparation method of described 2,3,6- benzotrichlorides, described metal can have to be conventional in the art The element of the metal general character, the one or more in of the invention in particularly preferred iron powder, zinc powder, manganese powder, nickel powder and aluminium powder；Further It is preferred that iron powder.Described metal halide is the binary compound that the conventional metal in this area shows negative valency with the halogen that halogen is formed It is preferred that dichloride copper, zinc dichloride, cobaltous dichloride, Nickel Chloride, manganous chloride, lanthanum trichloride, indium trichloride, ferric trichloride, Alchlor, antimony trichloride, titanium tetrachloride, zirconium chloride, butter of tin, germanium tetrachloride, Antimony pentachloride, molybdenum pentachloride, chlordene Change tungsten, dibrominated copper, dibrominated zinc, cobalt dihromide, Nickel Bromide, manganese dibromide, tribromide lanthanum, indium bromide, ferric bromide, Alchlor, antimonous bromide, titanium tetrabromide, tetrabormated zirconium, tin tetrabromide, germanium tetrabromide, five bromination antimony, six tungsten bromides, diiodo- Change the one or more in copper, zinc diiodide, cobalt diiodide and diiodinating nickel；Further preferred alchlor, antimony trichloride, four One or more in titanium chloride and Nickel Chloride；Still further preferably antimony trichloride and/or titanium tetrachloride.

In the preparation method of described 2,3,6- benzotrichlorides, the mixing of described catalyst and described dichlorotoleune The mass values of thing preferably 0.001~0.05, further preferred 0.003~0.01, such as 0.005.

In the preparation method of described 2,3,6- benzotrichlorides, described chlorination reagent can be such chlorine in this area Conventional chlorinating agents such as chlorine or sulfonic acid chloride of change reaction etc., particularly preferred chlorine in the present invention.

In the preparation method of described 2,3,6- benzotrichlorides, described chlorination reagent is mixed with described dichlorotoleune The molar ratio of compound preferably 1~5, further preferred 1.1~2.0, such as 1.2,1.3,1.4 or 1.9.

In the preparation method of described 2,3,6- benzotrichlorides, in the mixture of described dichlorotoleune, described 2, Quality shared by 6- dichlorotoleune and described 2,3- dichlorotoleune is preferably greater than or equal to 65% than sum and is less than 100%, further Preferably greater than or equal to 80% is less than 100%；Described mass ratio refers to described 2,6-DCT and described 2,3- dichloros The gross mass of toluene accounts for the percentage of the mixture gross mass of described dichlorotoleune.

In the preparation method of described 2,3,6- benzotrichlorides, the temperature of described chlorination reaction can be in this area The ordinary temperature of such chlorination reaction, the present invention in particularly preferred 10 DEG C~50 DEG C, further preferred 25 DEG C~40 DEG C.

In the preparation method of described 2,3,6- benzotrichlorides, the process of described chlorination reaction can use this area In routine monitoring method (such as TLC, HPLC, GC or NMR) be monitored, typically disappeared with the mixture of described dichlorotoleune It is the terminal of reaction during mistake, preferably 5 hours~8 hours time of described chlorination reaction, such as 5.5 hours or 6 hours.

Described 2, the preparation method of 3,6- benzotrichlorides can be carried out in a solvent or under condition of no solvent, when described When the preparation method of 2,3,6- benzotrichlorides is carried out in a solvent, the selected preferred chlorinated hydrocarbon solvent of solvent；Described chlorohydrocarbon The preferred dichloromethane of class solvent, chloroform, 1,2- dichloroethanes and 1, the one or more in 2,3- trichloropropanes, further preferably 1,2- dichloroethanes.The mass values preferably 0.5~5 of described solvent and the mixture of described dichlorotoleune, it is further excellent Select 1~2.

In the preparation method of described 2,3,6- benzotrichlorides, when described chlorination reagent is chlorine, it is preferred to use Following steps：Chlorine is passed through in the system formed to the mixture of dichlorotoleune with catalyst, chlorination reaction is carried out, obtains 2,3, 6- benzotrichlorides.Preferred 1bar~the 1.5bar of pressure of described logical chlorine, the preferred 5g/h of speed of described logical chlorine ~15g/h, such as 10g/h.

Described 2, the preparation method of 3,6- benzotrichlorides preferably include following post-processing step：After reaction terminates, rectifying Obtain 2,3,6- benzotrichlorides.Described rectifying can use the conventional method of the generic operation in this area.

Described 2, the preparation method of 3,6- benzotrichlorides, preferably further comprise the following steps：Under condition of no solvent, urge In the presence of agent, 2- chlorotoluenes and chlorination reagent are subjected to chlorination reaction and obtain the mixture of described dichlorotoleune, institute The catalyst stated is M-ZSM-12, and the mixture of described dichlorotoleune is the mixing of 2,6-DCT and 2,3- dichlorotoleune The mixture of thing or 2,6-DCT, 2,3- dichlorotoleune and 2,5- dichlorotoleune；

Wherein, M-ZSM-12 represents the compound of molecular sieve and metal chloride, and M represents metal chloride, ZSM-12 tables Show molecular sieve of the particle diameter for the model ZSM-12 of the mesh of 400 mesh~500.

In the preparation method of the mixture of described dichlorotoleune, described metal chloride can be that this area is conventional The chlorine element that is formed of metal and chlorine element show the binary compound of negative valency, particularly preferably zinc dichloride, dichloride in the present invention In nickel, manganous chloride, ferric trichloride, alchlor, antimony trichloride, lanthanum trichloride, titanium tetrachloride, zirconium chloride and butter of tin One or more, the one or more in further preferred zinc dichloride, ferric trichloride, antimony trichloride and titanium tetrachloride.

In the preparation method of the mixture of described dichlorotoleune, described catalyst and the chloro- toluene of described 2- Mass values preferably 0.005~0.05, further preferred 0.01~0.02.

In the preparation method of the mixture of described dichlorotoleune, described chlorination reagent can be such in this area The conventional chlorinating agents of chlorination reaction such as chlorine or sulfonic acid chloride etc., the present invention in particularly preferred chlorine.

In the preparation method of the mixture of described dichlorotoleune, described chlorination reagent and described 2- chlorotoluenes Molar ratio preferably 0.7~1.5, further preferred 0.80~1.00, such as 0.89,0.86,1.23 or 0.94.

In the preparation method of the mixture of described dichlorotoleune, the temperature of described chlorination reaction can be this area In such chlorination reaction ordinary temperature, the present invention in particularly preferred 0 DEG C~60 DEG C, further preferred 25 DEG C~40 DEG C.

In the preparation method of the mixture of described dichlorotoleune, the process of described chlorination reaction can use ability Routine monitoring method (such as TLC, HPLC, GC or NMR) in domain is monitored, typically reach 80% with reaction conversion ratio~ It is the terminal of reaction when 90%, preferably 5 hours~10 hours time of described chlorination reaction, such as 5.5 hours or 7 hours.

In the preparation method of the mixture of described dichlorotoleune, when described chlorination reagent is chlorine, preferably adopt Use following steps：Chlorine is passed through in the mixture system formed to the chloro- toluene of 2- and catalyst, chlorination reaction is carried out, obtains institute (mixture of described dichlorotoleune is the mixing of 2,6-DCT and 2,3- dichlorotoleune to the mixture for the dichlorotoleune stated The mixture of thing or 2,6-DCT, 2,3- dichlorotoleune and 2,5- dichlorotoleune).The pressure of described logical chlorine is preferred 1bar~1.5bar, the preferred 5g/h~15g/h of speed of described logical chlorine, such as 10g/h.

The preparation method of the mixture of described dichlorotoleune preferably includes following post-processing step：After reaction terminates, essence Evaporating to obtain the mixture of described dichlorotoleune, (mixture of described dichlorotoleune is 2,6-DCT and 2,3- dichloromethane The mixture of benzene, or the mixture of 2,6-DCT, 2,3- dichlorotoleune and 2,5- dichlorotoleune).Described rectifying can With using the conventional method of the generic operation in this area.

The mixture that described dichlorotoleune is preferably made in the preparation method of the mixture of described dichlorotoleune is (described The mixture of dichlorotoleune is the mixture of 2,6-DCT and 2,3- dichlorotoleune, or 2,6-DCT, 2,3- bis- The mixture of chlorotoluene and 2,5- dichlorotoleune) after, without further isolating and purifying, it is directly used in the benzotrichloride of preparation 2,3,6- Reaction.

In the present invention, in the mixture of dichlorotoleune made from the preparation method of the mixture of described dichlorotoleune, institute Quality shared by the 2,6-DCT and described 2,3- dichlorotoleune stated is more than 65% than sum and is less than or equal to 100%, preferably Quality shared by described 2,6-DCT and described 2,3- dichlorotoleune is more than 80% than sum and is less than or equal to 100%, example Such as 81%, 93%, 95% or 99%.

In the preparation method of the mixture of described dichlorotoleune, described M-ZSM-12 can use following method systems It is standby：Under the action of an acid, ZSM-12 molecular sieves are reacted with metal chloride, obtains described M-ZSM-12.

In described M-ZSM-12 preparation method, described sour preferred inorganic acid, the preferred hydrochloric acid of described inorganic acid. Described hydrochloric acid can be commercially available hydrochloric acid reagent conventional in the art, the mass concentration preferably 5%~50% of described hydrochloric acid, Described mass concentration refers to that the quality of hydrogen chloride accounts for the percentage of hydrochloric acid gross mass.

In described M-ZSM-12 preparation method, described is sour excellent with the mass values of described ZSM-12 molecular sieves Select 5~10.

In described M-ZSM-12 preparation method, the matter of described metal chloride and described ZSM-12 molecular sieves Measure ratio preferably 0.1~1, such as 0.3.

In described M-ZSM-12 preparation method, preferably 80 DEG C~100 DEG C of the temperature of described reaction.

In described M-ZSM-12 preparation method, preferably 20 hours~30 hours time of described reaction.

Described M-ZSM-12 preparation method preferably includes following post-processing step：After reaction terminates, be washed to it is neutral, Dry, activation obtains described M-ZSM-12.It is described to wash, dry, activating and use the normal of the generic operation in this area The preferably 24 hours time of rule method, preferably 100 DEG C~150 DEG C of the temperature of described drying, such as drying described in 120 DEG C~ 30 hours.Preferably 400 DEG C~600 DEG C of the temperature of described activation, preferably 5 hours~10 hours time of described activation.

Described 2, the preparation method of 3,6- benzotrichlorides preferably use following synthetic routes：

Present invention also offers a kind of preparation method of 2,3,6- trichlorobenzoic acids, it comprises the following steps：According to above-mentioned Method is made 2,3,6- benzotrichlorides and then under the conditions of existing for catalyst, by 2,3,6- benzotrichlorides and oxidising agent Oxidation reaction is carried out, obtains 2,3,6- trichlorobenzoic acids；

Described 2, the synthetic method of 3,6- trichlorobenzoic acids can use the routine side of such oxidation reaction in this area Method, particularly preferred following reaction method and condition in of the invention：

In the synthetic method of described 2,3,6- trichlorobenzoic acids, the preferred oxygen of described oxidant, air, dioxygen Water, ozone, potassium permanganate, potassium bichromate, Peracetic acid, tert-Butanol peroxide, chromic acid, nitric acid, potassium peroxydisulfate, potassium hyperchlorate and chlorine One or more in sour potassium；One or more in further preferred potassium permanganate, nitric acid, oxygen.Described nitric acid can be with For conventional commercial nitron, the mass concentration preferably 10%~30% of described nitric acid, described mass concentration refers to nitric acid Quality account for the percentage of salpeter solution gross mass.When described oxidant is gas, such as when oxygen, air or ozone, institute The pressure preferred 0.7Mpa~2Mpa, further preferred 0.7Mpa~1Mpa for the reaction system stated.

In the synthetic method of described 2,3,6- trichlorobenzoic acids, described oxidant and described 2,3,6- tri- chloromethanes The molar ratio of benzene preferably 1~10, further preferred 2~5, such as 4.

In the synthetic method of described 2,3,6- trichlorobenzoic acids, the preferred vanadic anhydride of described catalyst, vanadic acid One or more in ammonium, tetrabutylammonium chloride, TBAB, tetrabutylammonium iodide, cobalt salt and manganese salt.Described cobalt salt Refer to the material that cobalt ions is formed with acid group, such as four acetate hydrate cobalts or cobalt acetate.Described manganese salt refers to manganese ion and acid The material that root is formed, such as manganese acetate.When oxidant is potassium permanganate, the preferred tetrabutylammonium chloride of described catalyst, four One or more in butylammonium bromide and tetrabutylammonium iodide；When oxidant is nitric acid, described catalyst preferably five oxygen Change two vanadium；When described oxidant is oxygen or air, described catalyst preferably four acetate hydrate cobalts, cobalt acetate and acetic acid One or more in manganese.When described catalyst is manganese salt (such as manganese acetate), described oxidation reaction is preferably urged helping Carried out under the conditions of agent is existing, the preferred KBr of described co-catalyst.Described co-catalyst and described catalyst Molar ratio preferably 1~3, further preferred 1~1.5.

In the synthetic method of described 2,3,6- trichlorobenzoic acids, described catalyst and described 2,3,6- tri- chloromethanes The molar ratio of benzene preferably 0.001~0.1, further preferred 0.005~0.05, still further preferably 0.007~0.01.

In the synthetic method of described 2,3,6- trichlorobenzoic acids, preferably 50 DEG C of the temperature of described oxidation reaction~ 200 DEG C, further preferred 50 DEG C~170 DEG C, such as 120 DEG C, 140 DEG C, 150 DEG C or 160 DEG C.

In the synthetic method of described 2,3,6- trichlorobenzoic acids, the process of described oxidation reaction can use ability Routine monitoring method (such as TLC, HPLC, NMR or GC) is monitored in domain, is anti-when typically being disappeared with 2,3,6- benzotrichlorides Answer terminal, preferably 1 hour~20 hours time of oxidation reaction, further preferred 2 hours~18 hours, still further preferably 2 Hour~7 hours, such as 4 hours~5 hours.

Described 2, the synthetic method of 3,6- trichlorobenzoic acids can be carried out in a solvent or under the conditions of solvent-free.When anti- When should carry out in a solvent, the one or more in the preferred water of described solvent, inorganic acid, organic acid and sulfone class solvent.It is described Inorganic acid preferably sulfuric acid.Described sulfuric acid can be conventional commercial sulphate reagent, and the mass concentration of described sulfuric acid is preferred 50%~90%, described mass concentration refers to that the quality of sulfuric acid accounts for the percentage of sulfuric acid solution gross mass.Described organic acid It is preferred that the one or more in acetic acid, propionic acid and butyric acid.The described preferred sulfolane of sulfone class solvent.Described solvent with it is described The mass values of 2,3,6- benzotrichlorides preferably 1~20, further preferred 1~10, such as 2~3.

Described 2, the synthetic method of 3,6- trichlorobenzoic acids, carried out preferably under the conditions of existing for co-catalyst, it is described The preferred KBr of co-catalyst.The molar ratio preferably 1~3 of described co-catalyst and described catalyst, it is further excellent Select 1~1.5.

When oxidant is potassium permanganate, it is preferred to use following post-processing step：Heat filter, filtrate regulation after reaction terminates PH3 or so, filtering, washing, drying obtain 2,3,6- trichlorobenzoic acids.Described washing preferably uses water.Described regulation pH It is preferred that hydrochloric acid is used, and the mass concentration preferably 1%~10% of described hydrochloric acid, further preferred 5%~10%.Described quality Concentration refers to that the quality of hydrogen chloride accounts for the percentage of hydrochloric acid gross mass.

When oxidant is nitric acid, it is preferred to use following post-processing step：After reaction terminates, filter, wash, recrystallize To 2,3,6- trichlorobenzoic acids.Described filtering, washing, recrystallization can use the conventional method of the generic operation in this area, The preferred water of recrystallization solvent.

When oxidant is oxygen or air, it is preferred to use following post-processing step：Reaction removes solvent, washed after terminating Wash, recrystallize, drying and obtain 2,3,6- trichlorobenzoic acids.Described washing preferably uses water.Described removing solvent, washing, Recrystallization, drying can use the conventional method of the generic operation in this area, the preferred water of recrystallization solvent.

In the present invention, described 2, the preparation method of 3,6- trichlorobenzoic acids preferably uses following synthetic route：

Without prejudice to the field on the basis of common sense, above-mentioned each optimum condition, can be combined, and it is each preferably to produce the present invention Example.

Agents useful for same and raw material of the present invention are commercially available.

In the present invention, described room temperature refers to that environment temperature is 20 DEG C~30 DEG C.

In the present invention, described normal pressure refers to 1 atmospheric pressure, is 101325Pa.

The positive effect of the present invention is：Synthetic method reaction yield of the invention is high, high, the obtained production of selectivity Product purity is high, production cost is low, simple to operate, reaction condition is gentle, is suitable for industrialized production.

Embodiment

The present invention is further illustrated below by the mode of embodiment, but does not therefore limit the present invention to described reality Apply among a scope.The experimental method of unreceipted actual conditions in the following example, conventionally and condition, or according to business Product specification selects.

Embodiment 1M-ZSM-12 preparation method

M-ZSM-12 preparation method is：Weigh a certain amount of ZSM-12 molecular sieves to be placed in round-bottomed flask, add 5 times of matter (described mass concentration refers to that the quality of hydrogen chloride accounts for the percentage of hydrochloric acid gross mass to the hydrochloric acid that the mass concentration for measuring equivalent is 5% Than) and 1/3rd mass equivalents metal chloride, 100 DEG C of return stirrings 20 hours, neutrality is washed with water to, then at 120 Activated 5 hours at a temperature of being dried at DEG C 24 hours, 400 DEG C.Metal chloride is zinc dichloride, ferric trichloride, trichlorine When changing antimony or titanium tetrachloride, gained compound is designated as Zn-ZSM-12, Fe-ZSM-12, Sb-ZSM-12, Ti-ZSM-12 respectively.

The preparation of the dichloro benzol mixture of embodiment 2

Add 100g ortho-chlorotolu'enes in four round flask, 1g Fe-ZSM-12, normal pressure leads to after 25 DEG C of stirrings 30 minutes Enter 49.8g chlorine, lead to chlorine speed 10g/h, after reacting about 5 hours, vapor detection conversion ratio 87%, stop logical chlorine.Obtain reaction solution 124.2g, form as ortho-chlorotolu'ene 13%, 2,6-DCT 42%, 2,3- dichlorotoleune 27%, 2,5- dichlorotoleune 16%, Benzotrichloride and other impurity 2.0%.Rectifying, ortho-chlorotolu'ene recovery is steamed, the dichloro benzol mixture 112.3g steamed, received Rate 88.3% (applies mechanically rear yield 95.7%), can be directly used for reacting in next step.

The preparation of the dichloro benzol mixture of embodiment 3

Add 100g ortho-chlorotolu'enes in four round flask, 1g Sb-ZSM-12, normal pressure leads to after 25 DEG C of stirrings 30 minutes Enter 48.2g chlorine, lead to chlorine speed 10g/h, after reacting about 5 hours, vapor detection conversion ratio 85%, stop logical chlorine.Obtain reaction solution 123.4g, form as ortho-chlorotolu'ene 15%, 2,6-DCT 55%, 2,3- dichlorotoleune 23%, 2,5- dichlorotoleune 6%, Benzotrichloride and other impurity 1.0%.Rectifying steams ortho-chlorotolu'ene recovery, the dichloro benzol mixture 109.5g steamed, receives Rate 86.1% (applies mechanically rear yield 96.8%), can be directly used for reacting in next step.

The preparation of the dichloro benzol mixture of embodiment 4

Add 100g ortho-chlorotolu'enes in four round flask, 1g Zn-ZSM-12, normal pressure leads to after 25 DEG C of stirrings 30 minutes Enter 68.9g chlorine, lead to chlorine speed 10g/h, after reacting about 7 hours, vapor detection conversion ratio 80%, stop logical chlorine.Obtain reaction solution 122.3g, form as ortho-chlorotolu'ene 20%, 2,6-DCT 36%, 2,3- dichlorotoleune 38%, 2,5- dichlorotoleune 4%, Benzotrichloride and other impurity 2.0%.Rectifying steams ortho-chlorotolu'ene recovery, the dichloro benzol mixture 103.3g steamed, receives Rate 81.2% (applies mechanically rear yield 95.6%), can be directly used for reacting in next step.

The preparation of the dichloro benzol mixture of embodiment 5

Add 100g ortho-chlorotolu'enes in four round flask, 1g Ti-ZSM-12, normal pressure leads to after 25 DEG C of stirrings 30 minutes Enter 52.9g chlorine, lead to chlorine speed 10g/h, after reacting about 5.5 hours, after vapor detection conversion ratio 85%, stop logical chlorine.Obtain instead Liquid 123.4g is answered, is formed as ortho-chlorotolu'ene 15%, 2,6-DCT 62%, 2,3- dichlorotoleune 21%, 2,5- dichlorotoleune 1%, benzotrichloride and other impurity 1%.Rectifying steams ortho-chlorotolu'ene recovery, the dichloro benzol mixture 109.5g steamed, Yield 86.1% (applies mechanically rear yield 96.8%), can be directly used for reacting in next step.

Embodiment 62,3, the preparation of 6- benzotrichlorides

Gained dichlorotoleune mixture 100g, the 1g iron powder of embodiment 5 is added in four round flask, 25 DEG C of normal pressures are passed through 53.9g chlorine, lead to chlorine speed 10g/h, after reacting about 5.5 hours, the reaction of vapor detection dichlorotoleune finishes, and stops logical chlorine. Reaction solution 120.9g, form as 2,3,6- benzotrichlorides 62%, 2,3,4- benzotrichlorides 6%, 2,4,6- benzotrichlorides 24%, 2, 4,5- benzotrichlorides 5%, other four chloro-products and impurity about 3%.Rectifying can obtain 2,3,6- benzotrichloride 80.5g, yield 66.3%, purity 93% (GC).

Embodiment 72,3, the preparation of 6- benzotrichlorides

Gained dichlorotoleune mixture 100g, the 1g alchlor of embodiment 5,25 DEG C of normal pressures are added in four round flask 59.5g chlorine is passed through, leads to chlorine speed 10g/h, after reacting about 6 hours, the reaction of vapor detection dichlorotoleune finishes, and stops logical chlorine. Reaction solution 121.3g, form as 2,3,6- benzotrichlorides 51%, 2,3,4- benzotrichlorides 6%, 2,4,6- benzotrichlorides 30%, 2,4,5- benzotrichlorides 8%, other four chloro-products and impurity about 5%.Rectifying can obtain 2,3,6- benzotrichloride 70.9g, yield 58.4%, purity 86% (GC).

Embodiment 82,3, the preparation of 6- benzotrichlorides

Gained dichlorotoleune mixture 100g, the 0.5g antimony trichloride of embodiment 5 is added in four round flask, 25 DEG C often Pressure is passed through 57.0g chlorine, leads to chlorine speed 10g/h, and after reacting about 6 hours, the reaction of vapor detection dichlorotoleune finishes, and stops logical Chlorine.Reaction solution 120.3g, form as 2,3,6- benzotrichlorides 91%, 2,3,4- benzotrichlorides 5%, 2,4,6- benzotrichlorides 0.5%, 2,4,5- benzotrichlorides 3%, other four chloro-products and impurity about 0.5%.Rectifying can obtain 2,3,6- benzotrichlorides 113.0g, yield 93.1%, purity 97% (GC).

Embodiment 92,3, the preparation of 6- benzotrichlorides

Gained dichlorotoleune mixture 100g, the 0.5g titanium tetrachloride of embodiment 5 is added in four round flask, 25 DEG C often Pressure is passed through 61.7g chlorine, leads to chlorine speed 10g/h, and after reacting about 6 hours, the reaction of vapor detection dichlorotoleune finishes, and stops logical Chlorine.Reaction solution 120.4g, form as 2,3,6- benzotrichlorides 86%, 2,3,4- benzotrichlorides 7%, 2,4,6- benzotrichlorides 2%, 2,4,5- benzotrichlorides 4%, other four chloro-products and impurity about 1%.Rectifying can obtain 2,3,6- benzotrichloride 108.2g, Yield 89.1%, purity 96% (GC).

Embodiment 102,3, the preparation of 6- benzotrichlorides

Gained dichlorotoleune mixture 100g, the 1g Nickel Chloride of embodiment 5,25 DEG C of normal pressures are added in four round flask 81.6g chlorine is passed through, leads to chlorine speed 10g/h, after reacting about 8 hours, the reaction of vapor detection dichlorotoleune finishes, and stops logical chlorine. Reaction solution 122.3g, form as 2,3,6- benzotrichlorides 47%, 2,3,4- benzotrichlorides 10%, 2,4,6- benzotrichlorides 25%, 2,4,5- benzotrichlorides 8%, other four chloro-products and impurity about 10%.Rectifying can obtain 2,3,6- benzotrichlorides 66.1g, yield 54.4%, purity 85% (GC).

Embodiment 112,3, the preparation of 6- benzotrichlorides

Gained dichlorotoleune mixture 100g, the 0.5g antimony trichloride of embodiment 2 is added in four round flask, 25 DEG C often Pressure is passed through 57.0g chlorine, leads to chlorine speed 10g/h, and after reacting about 6 hours, the reaction of vapor detection dichlorotoleune finishes, and stops logical Chlorine.Reaction solution 120.4g, form as 2,3,6- benzotrichlorides 75%, 2,3,4- benzotrichlorides 12%, 2,4,6- benzotrichlorides 1%, 2,4,5- benzotrichlorides 11%, other four chloro-products and impurity about 1%.Rectifying can obtain 2,3,6- benzotrichlorides 103.4g, yield 85.2%, purity 87% (GC).

Embodiment 122,3, the preparation of 6- benzotrichlorides

Gained dichlorotoleune mixture 100g, the 0.5g antimony trichloride of embodiment 3 is added in four round flask, 25 DEG C often Pressure is passed through 57.0g chlorine, leads to chlorine speed 10g/h, and after reacting about 6h, the reaction of vapor detection dichlorotoleune finishes, and stops logical chlorine. Reaction solution 120.5g, form as 2,3,6- benzotrichlorides 87%, 2,3,4- benzotrichlorides 6%, 2,4,6- benzotrichlorides 0.5%, 2,4,5- benzotrichlorides 5%, other four chloro-products and impurity about 1.5%.Rectifying can obtain 2,3,6- benzotrichloride 110.6g, receive Rate 91.1%, purity 95% (GC).

Embodiment 132,3, the preparation of 6- trichlorobenzoic acids

It is 98%H that 2,3,6- benzotrichloride 50g of the gained of embodiment 8 are added into 100g mass concentrations₂SO₄In it is (described Mass concentration refer to that the quality of sulfuric acid accounts for the percentage of sulfuric acid solution gross mass), add 0.5g vanadic anhydrides, be heated to 140 DEG C, it is that (described mass concentration refers to that the quality of nitric acid accounts for salpeter solution gross mass to 30% nitric acid that 215g mass concentrations, which are added dropwise, Percentage), reaction in 4 hours terminates rear near room temperature (25 DEG C), is diluted with water suction filtration, is washed with a small amount, produces 2,3,6- Trichlorobenzoic acid crude product.Reusable heat water recrystallizes afterwards, filters, and drying, that is, obtains 2,3,6- trichlorobenzoic acid sterling 52.9g, HPLC purity is 99%, yield 93.6%.

Embodiment 142,3, the preparation of 6- trichlorobenzoic acids

It is 98%H that 2,3,6- benzotrichloride 50g of the gained of embodiment 8 are added into 150g mass concentrations₂SO₄In it is (described Mass concentration refers to that the quality of sulfuric acid accounts for the percentage of sulfuric acid solution gross mass), 0.5g vanadic anhydrides are added, are heated to 160 DEG C, it is that (described mass concentration refers to that the quality of nitric acid accounts for salpeter solution gross mass to 30% nitric acid that 215g mass concentrations, which are added dropwise, Percentage), reaction in 4 hours terminates rear near room temperature (25 DEG C), is diluted with water suction filtration, is washed with a small amount, produces 2,3,6- tri- Chlorobenzoic acid crude product.Reusable heat water recrystallizes afterwards, filters, and drying, that is, obtains 2,3,6- trichlorobenzoic acid sterling 50.7g, HPLC Purity is 98%, yield 88.8%.

Embodiment 152,3, the preparation of 6- trichlorobenzoic acids

2 that embodiment 8 is obtained, 3,6- benzotrichloride 50g are added in reactor, add 150g acetic acid, the water of 0.5g tetra- Cobalt acetate is closed, 0.35g manganese acetates, 0.25g KBrs, oxygen is passed through, is warming up to 150 DEG C, pressurize >=0.7MPa in kettle, 5 hours Reaction is cooled to room temperature (25 DEG C) after terminating, be evaporated under reduced pressure recovery acetic acid, and the residual addition 20g mass concentrations of kettle are that 5% watery hydrochloric acid is taken out Filter, is washed with a small amount, 2 obtained, and 3,6- trichlorobenzoic acid crude products are recrystallized with hot water, is filtered, and drying, that is, obtains 2,3,6- Trichlorobenzoic acid sterling 51.9g, HPLC purity are 97%, yield 90%.

Embodiment 162,3, the preparation of 6- trichlorobenzoic acids

2 that embodiment 8 is obtained, 3,6- benzotrichloride 50g are added in 150g butyric acid, the acetate hydrate cobalts of 0.5g tetra-, 0.35g manganese acetates, 0.25g KBrs, 170 DEG C are warming up to, are passed through oxygen, pressurize >=0.7Mpa in kettle, reaction in 18 hours terminates After be cooled to room temperature (25 DEG C), be evaporated under reduced pressure recovery butyric acid, residual the additions 20g mass concentrations of kettle are 5% watery hydrochloric acid suction filtration, with a small amount of Water washing, drying, it is 98% to obtain 2,3,6- trichlorobenzoic acid 52g, HPLC purity, yield 91.1%.

Embodiment 172,3, the preparation of 6- trichlorobenzoic acids

2 that embodiment 8 is obtained, 3,6- benzotrichloride 39g are added in 100g water, are added 0.4g tetrabutylammonium chlorides and are made For phase transfer catalyst, 63g potassium permanganate is added, 50 DEG C is heated to, after 6h reactions terminate, filters while hot, filtrate is dense with quality Hydrochloric acid (described mass concentration refers to that the quality of hydrogen chloride accounts for the percentage of hydrochloric acid gross mass) the regulation pH to 3 of degree 5%, has big Measure white solid to separate out, filter the solid of precipitation, be washed with a small amount, dry, obtain 2,3,6- trichlorobenzoic acid 43.3g, HPLC purity 95%, yield 96%.

Embodiment 182,3, the preparation of 6- trichlorobenzoic acids

2 that embodiment 8 is obtained, it is 70%H that 3,6- benzotrichloride 39g, which are added to 100g mass concentrations,₂SO₄In it is (described Mass concentration refers to that the quality of sulfuric acid accounts for the percentage of sulfuric acid solution gross mass), 0.36g vanadic anhydrides are added, are heated to 120 DEG C, it is that (described mass concentration refers to that the quality of nitric acid accounts for salpeter solution gross mass to 30% nitric acid that 210g mass concentrations, which are added dropwise, Percentage), reaction in 4 hours terminates rear near room temperature (25 DEG C), filters the white crystals of precipitation, is washed with a small amount, and drying, obtains It is 95% to 2,3,6- trichlorobenzoic acid 41.0g, HPLC purity, yield 91%.

Embodiment 192,3, the preparation of 6- trichlorobenzoic acids

2 that embodiment 8 is obtained, it is 70%H that 3,6- benzotrichloride 39g, which are added to 100g mass concentrations,₂SO₄In it is (described Percentage refers to that the quality of sulfuric acid accounts for the percentage of sulfuric acid solution gross mass), 0.36g vanadic anhydrides are added, are heated to 140 DEG C, it is that (described percentage refers to that the quality of nitric acid accounts for the hundred of salpeter solution gross mass to 30% nitric acid that 210g mass concentrations, which are added dropwise, Divide ratio), reaction in 2 hours terminates rear near room temperature (25 DEG C), filters the white crystals of precipitation, is washed with a small amount, and drying, obtains 2,3,6- trichlorobenzoic acid 41.5g, HPLC purity are 95%, yield 92%.

Embodiment 202,3, the preparation of 6- trichlorobenzoic acids

2 that embodiment 8 is obtained, 3,6- benzotrichloride 39g are added in reactor, add 100g acetic acid, the water of 0.5g tetra- Cobalt acetate is closed, 0.35g manganese acetates, 0.24g KBrs, oxygen is passed through, is warming up to 150 DEG C, pressurize >=0.7MPa in kettle, 5 hours Reaction is cooled to room temperature (25 DEG C) after terminating, be evaporated under reduced pressure recovery acetic acid, be washed with a small amount, dry, obtain 2,3,6- trichlorines Benzoic acid 42.4g, HPLC purity are 95%, yield 94%.

Embodiment 212,3, the preparation of 6- trichlorobenzoic acids

2 that embodiment 8 is obtained, 3,6- benzotrichloride 39g are added in 100g butyric acid, the acetate hydrate cobalts of 0.5g tetra-, 0.35g manganese acetates, 0.24g KBrs, 150 DEG C are warming up to, are passed through oxygen, pressurize >=0.7Mpa in kettle, reaction in 18 hours terminates After be cooled to room temperature (25 DEG C), be evaporated under reduced pressure recovery butyric acid, be washed with a small amount, dry, obtain 2,3,6- trichlorobenzoic acids 42.8g, HPLC purity are 95%, yield 95%.

Embodiment 222,3, the preparation of 6- trichlorobenzoic acids

2,3,6- benzotrichloride 3.9kg are added in reactor, add 10kg acetic acid, the acetate hydrate cobalts of 50g tetra-, 35g Manganese acetate, 24g KBrs, is passed through oxygen, is warming up to 150 DEG C, pressurize >=0.7MPa in kettle, and reaction in 7 hours is cooled to after terminating Room temperature (25 DEG C), recovery acetic acid is evaporated under reduced pressure, is washed with a small amount, dries, obtains 2,3,6- trichlorobenzoic acid 4.3kg, HPLC Purity is 95%, yield 95%.

Claims

1. one kind 2,3, the preparation method of 6- benzotrichlorides, it is characterised in that it comprises the following steps：In the presence of catalyst, by two The mixture of chlorotoluene, carry out chlorination reaction with chlorination reagent and obtain 2,3,6- benzotrichlorides, described catalyst is gold Belong to halide, the mixture of described dichlorotoleune is 2,6-DCT and the mixture or 2,6- bis- of 2,3- dichlorotoleune The mixture of chlorotoluene, 2,3 dichloro toluene and 2,5- dichlorotoleune；Described metal halide is antimony trichloride and four chlorinations One or more in titanium；It is described in the mixture of described 2,6-DCT, 2,3- dichlorotoleune and 2,5- dichlorotoleune 2,6-DCT and described 2,3- dichlorotoleune shared by quality than sum be more than or equal to 65% be less than 100%, it is described Mass ratio refers to that the gross mass of described 2,6- dichlorotoleune and described 2,3 dichloro toluene accounts for the mixed of described dichlorotoleune The percentage of compound gross mass；

2. as claimed in claim 12, the preparation method of 3,6- benzotrichlorides, it is characterised in that：

In the preparation method of described 2,3,6- benzotrichlorides, described catalyst and the mixture of described dichlorotoleune Mass values are 0.001~0.05；

And/or

In the preparation method of described 2,3,6- benzotrichlorides, described chlorination reagent is chlorine or sulfonic acid chloride；

And/or

In the preparation method of described 2,3,6- benzotrichlorides, the mixture of described chlorination reagent and described dichlorotoleune Molar ratio be 1~5；

And/or

In the preparation method of described 2,3,6- benzotrichlorides, the temperature of described chlorination reaction is 10 DEG C~50 DEG C；

And/or

In the preparation method of described 2,3,6- benzotrichlorides, the time of described chlorination reaction is 5 hours~8 hours；

And/or

The preparation method of described 2,3,6- benzotrichlorides is carried out in a solvent or under condition of no solvent；

And/or

The preparation method of described 2,3,6- benzotrichlorides includes following post-processing step：After reaction terminates, rectifying obtains 2,3, 6- benzotrichlorides.

3. as claimed in claim 22, the preparation method of 3,6- benzotrichlorides, it is characterised in that：

In the preparation method of described 2,3,6- benzotrichlorides, described catalyst and the mixture of described dichlorotoleune Mass values are 0.003~0.01；

And/or

In the preparation method of described 2,3,6- benzotrichlorides, described chlorination reagent is chlorine；

And/or

In the preparation method of described 2,3,6- benzotrichlorides, the mixture of described chlorination reagent and described dichlorotoleune Molar ratio be 1.1~2.0；

And/or

In the preparation method of described 2,3,6- benzotrichlorides, in the mixture of described dichlorotoleune, described 2,6- bis- Quality shared by chlorotoluene and described 2,3- dichlorotoleune is more than or equal to 80% than sum and is less than 100%, and described mass ratio is The gross mass of 2,6- dichlorotoleune and described 2,3 dichloro toluene described in referring to accounts for the total matter of mixture of described dichlorotoleune The percentage of amount；

And/or

In the preparation method of described 2,3,6- benzotrichlorides, the temperature of described chlorination reaction is 25 DEG C~40 DEG C；

And/or

In the preparation method of described 2,3,6- benzotrichlorides, the time of described chlorination reaction is 5.5 hours or 6 hours；

And/or

When the preparation method of described 2,3,6- benzotrichlorides is carried out in a solvent, selected solvent is chlorinated hydrocarbon solvent；

And/or

When the preparation method of described 2,3,6- benzotrichlorides is carried out in a solvent, described solvent and described dichlorotoleune Mixture mass values be 0.5~5；

And/or

In the preparation method of described 2,3,6- benzotrichlorides, when described chlorination reagent is chlorine, using following steps： Chlorine is passed through in the system formed to the mixture of dichlorotoleune with catalyst, chlorination reaction is carried out, obtains 2,3,6- tri- chloromethanes Benzene.

4. as claimed in claim 32, the preparation method of 3,6- benzotrichlorides, it is characterised in that：

In the preparation method of described 2,3,6- benzotrichlorides, the mixture of described chlorination reagent and described dichlorotoleune Molar ratio be 1.2,1.3,1.4 or 1.9；

And/or

In the preparation method of described 2,3,6- benzotrichlorides, described catalyst and the mixture of described dichlorotoleune Mass values are 0.005；

And/or

When the preparation method of described 2,3,6- benzotrichlorides is carried out in a solvent, described solvent and described dichlorotoleune Mixture mass values be 1~2；

In the preparation method of described 2,3,6- benzotrichlorides, when described chlorination reagent is chlorine, the step of use in, The pressure of described logical chlorine is 1bar~1.5bar；

And/or

In the preparation method of described 2,3,6- benzotrichlorides, when described chlorination reagent is chlorine, the step of use in, The speed of described logical chlorine is 5g/h~15g/h.

5. as claimed in claim 12, the preparation method of 3,6- benzotrichlorides, it is characterised in that：The described chloromethanes of 2,3,6- tri- The preparation method of benzene, further comprises the steps：Under condition of no solvent, in the presence of catalyst, 2- chlorotoluenes and chlorination are tried Agent carries out chlorination reaction and obtains the mixture of described dichlorotoleune, and described catalyst is M-ZSM-12, and described two The mixture of chlorotoluene is mixture or 2,6- dichlorotoleune, the 2,3- dichloromethanes of 2,6- dichlorotoleune and 2,3 dichloro toluene The mixture of benzene and 2,5- dichlorotoleune；

Wherein, M-ZSM-12 represents the compound of molecular sieve and metal chloride, and M represents metal chloride, and ZSM-12 represents grain Footpath is the model ZSM-12 of the mesh of 400 mesh~500 molecular sieve；Described metal chloride is zinc dichloride, ferric trichloride, three One or more in antimony chloride and titanium tetrachloride.

6. as claimed in claim 52, the preparation method of 3,6- benzotrichlorides, it is characterised in that：

In the preparation method of the mixture of described dichlorotoleune, the quality of described catalyst and the chloro- toluene of described 2- Ratio is 0.005~0.05；

And/or

In the preparation method of the mixture of described dichlorotoleune, described chlorination reagent is chlorine or sulfonic acid chloride；

And/or

In the preparation method of the mixture of described dichlorotoleune, mole of described chlorination reagent and described 2- chlorotoluenes Ratio is 0.7~1.5；

And/or

In the preparation method of the mixture of described dichlorotoleune, the temperature of described chlorination reaction is 0 DEG C~60 DEG C；

And/or

In the preparation method of the mixture of described dichlorotoleune, the time of described chlorination reaction is 5 hours~10 hours；

And/or

In the preparation method of the mixture of described dichlorotoleune, when described chlorination reagent is chlorine, using following step Suddenly：Chlorine is passed through in the mixture system formed to the chloro- toluene of 2- and catalyst, chlorination reaction is carried out, obtains described dichloro The mixture of toluene；

And/or

The preparation method of the mixture of described dichlorotoleune includes following post-processing step：After reaction terminates, rectifying obtains institute The mixture for the dichlorotoleune stated；

And/or

After the mixture of described dichlorotoleune is made in the preparation method of the mixture of described dichlorotoleune, without further dividing From purifying, the reaction of the benzotrichloride of preparation 2,3,6- is directly used in.

7. as claimed in claim 62, the preparation method of 3,6- benzotrichlorides, it is characterised in that：

In the preparation method of the mixture of described dichlorotoleune, the quality of described catalyst and the chloro- toluene of described 2- Ratio is 0.01~0.02；

And/or

In the preparation method of the mixture of described dichlorotoleune, described chlorination reagent is chlorine；

And/or

In the preparation method of the mixture of described dichlorotoleune, mole of described chlorination reagent and described 2- chlorotoluenes Ratio is 0.80~1.00；

And/or

In the preparation method of the mixture of described dichlorotoleune, the time of described chlorination reaction is that 5.5 hours or 7 are small When；

And/or

In the preparation method of the mixture of described dichlorotoleune, the temperature of described chlorination reaction is 25 DEG C~40 DEG C；

And/or

In the preparation method of the mixture of described dichlorotoleune, when described chlorination reagent is chlorine, the step of use In, the pressure of described logical chlorine is 1bar~1.5bar；

And/or

In the preparation method of the mixture of described dichlorotoleune, when described chlorination reagent is chlorine, the step of use In, the speed of described logical chlorine is 5g/h~15g/h.

8. as claimed in claim 52, the preparation method of 3,6- benzotrichlorides, it is characterised in that：In described dichlorotoleune In the preparation method of mixture, described M-ZSM-12 is prepared using following methods：Under the action of an acid, by ZSM-12 molecular sieves Reacted with metal chloride, obtain described M-ZSM-12.

9. as claimed in claim 82, the preparation method of 3,6- benzotrichlorides, it is characterised in that：

In described M-ZSM-12 preparation method, described acid is inorganic acid；

And/or

In described M-ZSM-12 preparation method, it is described it is sour with the mass values of described ZSM-12 molecular sieves for 5~ 10；

And/or

In described M-ZSM-12 preparation method, the mass ratio of described metal chloride and described ZSM-12 molecular sieves It is worth for 0.1~1；

And/or

In described M-ZSM-12 preparation method, the temperature of described reaction is 80 DEG C~100 DEG C；

And/or

In described M-ZSM-12 preparation method, the time of described reaction is 20 hours~30 hours；

And/or

Described M-ZSM-12 preparation method preferably includes following post-processing step：After reaction terminates, it is washed to neutral, dry Dry, activation obtains described M-ZSM-12.

10. one kind 2,3, the preparation method of 6- trichlorobenzoic acids, it is characterised in that it comprises the following steps：According to claim 1 Preparation method described in~9 any one is made 2,3,6- benzotrichlorides and then under the conditions of existing for catalyst, by 2,3,6- Benzotrichloride carries out oxidation reaction with oxidising agent, obtains 2,3,6- trichlorobenzoic acids；