CN109553535A - A kind of method that one kettle way prepares the chloro- 2`- nitrobiphenyl of 4- - Google Patents
A kind of method that one kettle way prepares the chloro- 2`- nitrobiphenyl of 4- Download PDFInfo
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- CN109553535A CN109553535A CN201910013585.3A CN201910013585A CN109553535A CN 109553535 A CN109553535 A CN 109553535A CN 201910013585 A CN201910013585 A CN 201910013585A CN 109553535 A CN109553535 A CN 109553535A
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
Abstract
The invention discloses a kind of methods that one kettle way prepares the chloro- 2'- nitrobiphenyl of 4-; using para chlorobromobenzene, connection pinacol borate as starting material; palladium catalyst, Phosphine ligands, alkali A is added; under inert gas protection; para chlorobromobenzene is heated to react completely; 2- chloronitrobenzene is directly added into reaction system, alkali B continues heating reaction and obtains target product.The present invention is directly realized by the preparation of target compound using one kettle way, and easy to operate, the catalyst and ligand equivalent used is low, avoids using dangerous Grignard Reagent and expensive to chlorophenylboronic acid, and yield is high, at low cost and be easy to industrialize.
Description
Technical field
The present invention relates to field of compound preparation, the in particular to chloro- 2 '-nitro of efficient germicide Boscalid intermediate 4-
The preparation method of biphenyl.
Background technique
Boscalid (common name: Boscalid) is the novel nicotinamide absorbability sterilization of BASF Aktiengesellschaft's exploitation
Agent, mechanism of action be inhibit mitochondrial respiratory chain in succinic acid ubiquinone reductase, can be used for include rape, grape, fruit tree,
The prevention and treatment of the related disease of the crops such as tomato, vegetables and field crop, such as prevents and treats powdery mildew, gray mold, sclerotiniose, brown rot and root
Numerous diseases such as maize ear rot have its distinctive mechanism of action agent of broad spectrum antibacterial, with other medicines no interactions resistance, pacify to crop
It is a kind of important new type bactericide entirely with advantageous ecological effect and toxicity data.
The chloro- 2 '-nitrobiphenyl of 4- is the important intermediate in Boscalid commercial synthesis.The chloro- 2 '-nitrobiphenyl of 4- is through iron
It after powder or other modes reduction, then reacts up to Boscalid with 2- chloronicotinoyl chloride, such as shown in (I).
The preparation method about the chloro- 2 '-nitrobiphenyl of 4- reported in existing method include using to chlorophenylboronic acid or
Two (4- chlorphenyl) boric acid and o-chloronitrobenzene are raw material, and suzuki coupling system occurs under the catalytic action of Metal Palladium or nickel
The standby chloro- 2 '-nitrobiphenyl of 4-, used in above-mentioned system it is expensive and unstable to chlorophenylboronic acid reagent, and in reaction process
It is easy to generate the by-product A being excessively coupled, such as shown in (II).
Another kind report is occurred under palladium catalyst and polar solvent high temperature even using o-nitrobenzoic acid and para chlorobromobenzene
Connection, which reacts, is made target compound.The reaction temperature is higher, and has used the mantoquita and multiple additives of equivalent, higher cost,
Reaction condition is unfavorable for industrial production.
There are also document disclose using to chlorophenylboronic acid and adjacent nitro phenylhydrazine as starting material, in palladium catalyst and organic
Realize that coupling reaction prepares target compound under the co-catalysis of acid.The system equally uses expensive and unstable to chlorine
Phenyl boric acid, and adjacent nitro phenylhydrazine has high toxicity, is unfavorable for the production of actual industrial metaplasia.
In addition, it is raw material that Chinese patent, which is disclosed using rubigan Grignard Reagent and o-chloronitrobenzene, in Raney nickel
In the presence of realize that the coupling reaction method for preparing the chloro- 2 '-nitrobiphenyl of 4-, which need to carry out under low temperature, and use and have
And flammable Grignard Reagent, it is unfavorable for industrial amplification.
Other than above-mentioned coupling mode, Yuan Yan company disclose using o-nitrobenzaldehyde be raw material, through aldol condensation,
Target compound is made in the multistep reactions such as Diels-Alder reaction, oxidation aromatization.This method processing step complexity is tediously long, aromatization
It is inflammable and explosive to change extremely low yield, reagent nitromethane and 1,3 butadiene.
Summary of the invention
For expensive starting materials, the high, reaction condition using reagent risk in the chloro- existing preparation method of 2 '-nitrobiphenyl of 4-
It is harsh, be unfavorable for industrialized disadvantage, use is cheap and easy to get, safety and stability raw material, passes through mild reaction condition and realizes
One kettle way prepares the chloro- 2 '-nitrobiphenyl of 4-.This method is easy to operate, catalyst uses low equivalent, reaction selectivity and yield
Height, process safety are easily operated, are conducive to industrial amplification production.
In order to achieve the above object, the present invention provides a kind of methods that one kettle way prepares the chloro- 2 '-nitrobiphenyl of 4-, should
Method includes:
1. para chlorobromobenzene, connection pinacol borate are starting material, palladium catalyst, Phosphine ligands, alkali A, inert gas is added
Under in a solvent heating reaction reacted completely to raw material para chlorobromobenzene；
2. 2- chloronitrobenzene is added directly into reaction system, alkali B continues under inert gas to be heated to reaction to terminate, and obtains
To the chloro- 2 '-nitrobiphenyl of product 4-.
Wherein, para chlorobromobenzene described in the reaction: connection pinacol borate: the molar ratio of o-chloronitrobenzene is 1.0:
1.0~1.5:0.9~1.1, further preferably 1.0:1.0~1.1:0.9~1.0.
Palladium catalyst is acid chloride or tris(dibenzylideneacetone) dipalladium, preferably acid chloride in the reaction.Palladium used
The equivalent of catalyst is the 0.1%-2%, preferably 0.1%-0.5% of para chlorobromobenzene.
The ligand of the reaction is 3- (tert-butyl) -4- (2,6- Dimethoxyphenyl) -2,3- dihydrobenzo [d] [1,3]
Oxygen, penta yoke of phosphine (BIDIME) and 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine
(AntPhos), preferably 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine (AntPhos)；
The molar ratio of used Phosphine ligands and palladium catalyst is 1.0~1.5:1.0, preferably 1.0~1.1:1.0.
Phosphine ligands structural formula is as follows:
Wherein, alkali A is sodium acetate or potassium acetate, preferably potassium acetate in the reaction.The dosage of alkali A is para chlorobromobenzene
100%~200%, preferably 100%~150%.
Alkali B is selected from potassium carbonate, potassium phosphate, sodium carbonate, sodium hydroxide, sodium bicarbonate, potassium fluoride in the reaction, preferably
Potassium carbonate.The dosage of alkali B is the 100%~200% of para chlorobromobenzene mole, preferably 100%~150%.
Solvent in the reaction is organic solvent or organic solvent/water mixed solvent system, preferably organic solvent/water
Mixed system.The organic solvent is tetrahydrofuran and/or toluene, the organic solvent/water mixed solvent system ratio
Example is 2~10:1, preferably 2~5:1.Solvent usage is 2~10L/1mol para chlorobromobenzene, and preferably 4~8L/1mol is to chlorine bromine
Benzene.
1. and 2. middle heating reaction temperature is 60~80 DEG C, preferably 60~70 DEG C to the step.
Reaction mechanism be with para chlorobromobenzene and connection pinacol borate starting material, by palladium catalyst, Phosphine ligands, alkali A,
Miyaura coupling reaction obtained 4- chlorophenylboronic acid pinacol ester in situ is realized in heating reaction under inert gas；Then to reactant
It is directly added into 2- chloronitrobenzene and alkali B in system, carries out subsequent suzuki coupling reaction, one kettle way realizes the chloro- 2- nitro connection of 4-
The efficient preparation of benzene.
Foregoing invention has following advantage:
(1) using in raw material para chlorobromobenzene that is cheap and easy to get, stablizing safety, connection pinacol borate substitution existing method
The expensive reagent rubigan Grignard Reagent high to chlorophenylboronic acid or risk, it is more safe and efficient；
(2) one kettle way realizes the conversion of two steps, avoids separation, the purification process of intermediate, and process route is brief, saves
Labour cost；
(3) reaction condition is mild, avoids the generation of the excessively by-products such as coupling, and reaction yield and selectivity are high.
Detailed description of the invention
Fig. 1 is compound 4-chloro -2 '-nitrobiphenyl prepared by the present invention1H NMR spectra.
Fig. 2 is compound 4-chloro -2 '-nitrobiphenyl prepared by the present invention13C NMR spectra.
Specific embodiment
The technical scheme in the embodiments of the invention will be clearly and completely described below, it is clear that described implementation
Example is only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, this field is common
Technical staff's every other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses.
Embodiment 1
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (381mg, 1.5mmol) in reaction tube,
Sodium acetate (123mg, 1.5mmol), substitutes nitrogen three times, is added tetrahydrofuran (5mL).It is added under stirring into above-mentioned reaction tube
Palladium acetate (2.2mg, 0.01mmol), 3- (tert-butyl) -4- (2,6- Dimethoxyphenyl) -2,3- dihydrobenzo [d] [1,3]
Oxygen, penta yoke of phosphine (BIDIME, 3.6mg, 0.011mmol).Above-mentioned reaction system is heated to 75 DEG C, TLC detection para chlorobromobenzene disappears
After mistake, addition 2- chloronitrobenzene (157mg, 1mmol), potassium carbonate in reaction system are stated directly up under nitrogen atmosphere
(207mg, 1.5mmol), airtight reactor tube simultaneously continue to heat reaction at 75 DEG C, after reacting 12h, stop heating, be filtered to remove
Inorganic salts are grease after concentration, and the direct column chromatography purifying (eluant, eluent: petrol ether/ethyl acetate=5/1) of grease is obtained
The chloro- 2 '-nitrobiphenyl of product 4- is light yellow solid 151mg, 65% yield, purity > 98%.As shown in Figure 1, implementing for invention
The preparation of example 1 is the chloro- 2 '-nitrobiphenyl of 4-1H NMR data spectrogram, as shown in Fig. 2, the 4- prepared for the embodiment of the present invention 1
Chloro- 2 '-nitrobiphenyl13C NMR data spectrogram.
Embodiment 2
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (381mg, 1.5mmol) in reaction tube,
Potassium acetate (147mg, 1.5mmol), substitutes nitrogen three times, is added tetrahydrofuran (5mL).It is added under stirring into above-mentioned reaction tube
Palladium acetate (2.2mg, 0.01mmol), ligand 3- (tert-butyl) -4- (2,6- Dimethoxyphenyl) -2,3- dihydrobenzo [d] [1,
3] oxygen, penta yoke of phosphine (BIDIME, 3.6mg, 0.011mmol).Above-mentioned reaction system is heated to 75 DEG C, TLC detects para chlorobromobenzene
After disappearance, addition o-chloronitrobenzene (157mg, 1mmol), potassium carbonate in reaction system are stated directly up under nitrogen atmosphere
(207mg, 1.5mmol), airtight reactor tube simultaneously continue to heat reaction at 75 DEG C, after reacting 12h, stop heating, be filtered to remove
Inorganic salts are grease after concentration, and the direct column chromatography purifying (eluant, eluent: petrol ether/ethyl acetate=5/1) of grease is obtained
The chloro- 2 '-nitrobiphenyl of product 4- is light yellow solid 172mg, and 74% yield, purity > 98%, nuclear magnetic data is the same as embodiment 1.
Embodiment 3
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (280mg, 1.1mmol) in reaction tube,
Potassium acetate (147mg, 1.5mmol), substitutes nitrogen three times, is added tetrahydrofuran (5mL).It is added under stirring into above-mentioned reaction tube
Palladium acetate (2.2mg, 0.01mmol), ligand 3- (tert-butyl) -4- (2,6- Dimethoxyphenyl) -2,3- dihydrobenzo [d] [1,
3] oxygen, penta yoke of phosphine (BIDIME, 3.6mg, 0.011mmol).Above-mentioned reaction system is heated to 75 DEG C, TLC detects para chlorobromobenzene
After disappearance, addition o-chloronitrobenzene (157mg, 1mmol), potassium carbonate in reaction system are stated directly up under nitrogen atmosphere
(207mg, 1.5mmol), airtight reactor tube simultaneously continue to heat reaction at 75 DEG C, after reacting 12h, stop heating, be filtered to remove
Inorganic salts are grease after concentration, and the direct column chromatography purifying (eluant, eluent: petrol ether/ethyl acetate=5/1) of grease is obtained
The chloro- 2 '-nitrobiphenyl of product 4- is light yellow solid 184mg, and 79% yield, purity > 98%, nuclear magnetic data is the same as embodiment 1.
Embodiment 4
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (280mg, 1.1mmol) in reaction tube,
Potassium acetate (147mg, 1.5mmol), substitutes nitrogen three times, is added tetrahydrofuran (5mL).It is added under stirring into above-mentioned reaction tube
Palladium acetate (2.2mg, 0.01mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, phosphine penta
Yoke (AntPhos, 4.1mg, 0.011mmol).Above-mentioned reaction system is heated to 75 DEG C, after TLC detects para chlorobromobenzene disappearance,
It is stated directly up under nitrogen atmosphere in reaction system and o-chloronitrobenzene (157mg, 1mmol) is added, potassium carbonate (207mg,
1.5mmol), airtight reactor tube and continuation are heated at 75 DEG C reacts, and after reacting 12h, stops heating, is filtered to remove inorganic salts,
Solid crude product is obtained after concentration, is directly added into petroleum ether 10mL mashing, filtering, dry light yellow solid, it is chloro- to be identified as 4-
2 '-nitrobiphenyl 198mg, 85% yield, purity > 98%, nuclear magnetic data is the same as embodiment 1.
Embodiment 5
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (280mg, 1.1mmol) in reaction tube,
Potassium acetate (147mg, 1.5mmol), substitutes nitrogen three times, is added tetrahydrofuran (5mL).It is added under stirring into above-mentioned reaction tube
Palladium acetate (2.2mg, 0.01mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, phosphine penta
Yoke (AntPhos, 4.1mg, 0.011mmol).Above-mentioned reaction system is heated to 75 DEG C, after TLC detects para chlorobromobenzene disappearance,
It is stated directly up under nitrogen atmosphere in reaction system and o-chloronitrobenzene (157mg, 1mmol) is added, potassium phosphate (318mg,
1.5mmol), airtight reactor tube and continuation are heated at 75 DEG C reacts, and after reacting 12h, stops heating, is filtered to remove inorganic salts,
Solid crude product is obtained after concentration, is directly added into petroleum ether 10mL mashing, filtering, dry light yellow solid, it is chloro- to be identified as 4-
2 '-nitrobiphenyl 191mg, 82% yield, purity > 98%, nuclear magnetic data is the same as embodiment 1.
Embodiment 6
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (280mg, 1.1mmol) in reaction tube,
Potassium acetate (147mg, 1.5mmol), substitutes nitrogen three times, is added toluene (5mL).Acetic acid is added into above-mentioned reaction tube under stirring
Palladium (2.2mg, 0.01mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine
(AntPhos, 4.1mg, 0.011mmol).Above-mentioned reaction system is heated to 75 DEG C, after TLC detects para chlorobromobenzene disappearance, in nitrogen
Atmosphere is stated in reaction system directly up under enclosing and o-chloronitrobenzene (157mg, 1mmol) is added, potassium carbonate (207mg,
1.5mmol), airtight reactor tube and continuation are heated at 75 DEG C reacts, and after reacting 12h, stops heating, is filtered to remove inorganic salts,
Solid crude product is obtained after concentration, is directly added into petroleum ether 10mL mashing, filtering, dry light yellow solid, it is chloro- to be identified as 4-
2 '-nitrobiphenyls, 200mg, 86% yield, purity > 98%, nuclear magnetic data is the same as embodiment 1.
Embodiment 7
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (280mg, 1.1mmol) in reaction tube,
Potassium acetate (147mg, 1.5mmol), substitutes nitrogen three times, is added toluene (5mL).Acetic acid is added into above-mentioned reaction tube under stirring
Palladium (2.2mg, 0.01mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine
(AntPhos, 4.1mg, 0.011mmol).Above-mentioned reaction system is heated to 75 DEG C, after TLC detects para chlorobromobenzene disappearance, in nitrogen
Atmosphere is stated in reaction system directly up under enclosing and o-chloronitrobenzene (157mg, 1mmol) is added, potassium carbonate (207mg,
1.5mmol), water (1mL), airtight reactor tube simultaneously continue to heat reaction at 75 DEG C, after reacting 12h, stop heating, be filtered to remove
Inorganic salts obtain solid crude product after concentration, are directly added into petroleum ether 10mL mashing, filtering, dry light yellow solid, identified
For the chloro- 2 '-nitrobiphenyl 208mg of 4-, 90% yield, purity > 98%, nuclear magnetic data is the same as embodiment 1.
Embodiment 8
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (280mg, 1.1mmol) in reaction tube,
Potassium acetate (147mg, 1.5mmol), substitutes nitrogen three times, is added toluene (5mL).Acetic acid is added into above-mentioned reaction tube under stirring
Palladium (2.2mg, 0.01mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine
(AntPhos, 4.1mg, 0.011mmol).Above-mentioned reaction system is heated to 65 DEG C, after TLC detects para chlorobromobenzene disappearance, in nitrogen
Atmosphere is stated in reaction system directly up under enclosing and o-chloronitrobenzene (157mg, 1mmol) is added, potassium carbonate (207mg,
1.5mmol), water (1mL), airtight reactor tube simultaneously continue to heat reaction at 65 DEG C, after reacting 12h, stop heating, be filtered to remove
Inorganic salts obtain solid crude product after concentration, are directly added into petroleum ether 10mL mashing, filtering, dry light yellow solid, identified
For the chloro- 2 '-nitrobiphenyl 214mg of 4-, 92% yield, purity > 98%, nuclear magnetic data is the same as embodiment 1.
Embodiment 9
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (280mg, 1.1mmol) in reaction tube,
Potassium acetate (147mg, 1.5mmol), substitutes nitrogen three times, is added toluene (5mL).Three are added into above-mentioned reaction tube under stirring
(dibenzalacetone) two palladium (4.5mg, 0.005mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d]
[1,3] oxygen, penta yoke of phosphine (AntPhos, 4.1mg, 0.011mmol).Above-mentioned reaction system is heated to 65 DEG C, TLC is detected to chlorine
After bromobenzene disappears, addition o-chloronitrobenzene (157mg, 1mmol), potassium carbonate in reaction system are stated directly up under nitrogen atmosphere
(207mg, 1.5mmol), water (1mL), airtight reactor tube simultaneously continue to heat reaction at 65 DEG C, after reacting 12h, stop heating,
Inorganic salts are filtered to remove, obtain solid crude product after concentration, petroleum ether 10mL mashing is directly added into, filters, is light yellow admittedly dry
Body is identified as the chloro- 2 '-nitrobiphenyl 198mg of 4-, and 85% yield, purity > 98%, nuclear magnetic data is the same as embodiment 1.
Embodiment 10
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (280mg, 1.1mmol) in reaction tube,
Potassium acetate (147mg, 1.5mmol), substitutes nitrogen three times, is added toluene (5mL).Acetic acid is added into above-mentioned reaction tube under stirring
Palladium (2.2mg, 0.01mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine
(AntPhos, 4.1mg, 0.011mmol).Above-mentioned reaction system is heated to 65 DEG C, after TLC detects para chlorobromobenzene disappearance, in nitrogen
Atmosphere is stated in reaction system directly up under enclosing and o-chloronitrobenzene (157mg, 1mmol) is added, potassium carbonate (207mg,
1.5mmol), water (1mL), airtight reactor tube simultaneously continue to heat reaction at 60 DEG C, after reacting 12h, stop heating, be filtered to remove
Inorganic salts obtain solid crude product after concentration, are directly added into petroleum ether 10mL mashing, filtering, dry light yellow solid, identified
For the chloro- 2 '-nitrobiphenyl 205mg of 4-, 88% yield, purity > 98%, nuclear magnetic data is the same as embodiment 1.
Embodiment 11
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (280mg, 1.1mmol) in reaction tube,
Potassium acetate (147mg, 1.5mmol), substitutes nitrogen three times, is added toluene (5mL).Acetic acid is added into above-mentioned reaction tube under stirring
Palladium (2.2mg, 0.01mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine
(AntPhos, 4.1mg, 0.011mmol).Above-mentioned reaction system is heated to 65 DEG C, after TLC detects para chlorobromobenzene disappearance, in nitrogen
Atmosphere is stated in reaction system directly up under enclosing and o-chloronitrobenzene (157mg, 1mmol) is added, sodium carbonate (159mg,
1.5mmol), water (1mL), airtight reactor tube simultaneously continue to heat reaction at 65 DEG C, after reacting 12h, stop heating, be filtered to remove
Inorganic salts obtain solid crude product after concentration, are directly added into petroleum ether 12mL mashing, filtering, dry light yellow solid, identified
For the chloro- 2 '-nitrobiphenyl 168mg of 4-, 72% yield, purity > 95%, nuclear magnetic data is the same as embodiment 1.
Embodiment 12
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (280mg, 1.1mmol) in reaction tube,
Potassium acetate (147mg, 1.5mmol), substitutes nitrogen three times, is added toluene (5mL).Acetic acid is added into above-mentioned reaction tube under stirring
Palladium (2.2mg, 0.01mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine
(AntPhos, 4.1mg, 0.011mmol).Above-mentioned reaction system is heated to 65 DEG C, after TLC detects para chlorobromobenzene disappearance, in nitrogen
Atmosphere is stated in reaction system directly up under enclosing and o-chloronitrobenzene (157mg, 1mmol) is added, sodium bicarbonate (159mg,
2.0mmol), water (1mL), airtight reactor tube simultaneously continue to heat reaction at 65 DEG C, after reacting 12h, stop heating, be filtered to remove
Inorganic salts are grease after concentration, and the direct column chromatography purifying (eluant, eluent: petrol ether/ethyl acetate=5/1) of grease is obtained
The chloro- 2 '-nitrobiphenyl of product 4- is light yellow solid 47mg, and 20% yield, purity > 98%, nuclear magnetic data is the same as embodiment 1.
Embodiment 13
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (280mg, 1.1mmol) in reaction tube,
Potassium acetate (147mg, 1.5mmol), substitutes nitrogen three times, is added toluene (5mL).Acetic acid is added into above-mentioned reaction tube under stirring
Palladium (2.2mg, 0.01mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine
(AntPhos, 4.1mg, 0.011mmol).Above-mentioned reaction system is heated to 65 DEG C, after TLC detects para chlorobromobenzene disappearance, in nitrogen
Atmosphere is stated in reaction system directly up under enclosing and o-chloronitrobenzene (157mg, 1mmol) is added, sodium hydroxide (60mg,
1.5mmol), water (1mL), airtight reactor tube simultaneously continue to heat reaction at 65 DEG C, after reacting 12h, stop heating, be filtered to remove
Inorganic salts obtain solid crude product after concentration, are directly added into petroleum ether 15mL mashing, filtering, dry light yellow solid, identified
For the chloro- 2 '-nitrobiphenyl 149mg of 4-, 64% yield, purity > 96%, nuclear magnetic data is the same as embodiment 1.
Embodiment 14
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (280mg, 1.1mmol) in reaction tube,
Potassium acetate (147mg, 1.5mmol), substitutes nitrogen three times, is added toluene (5mL).Acetic acid is added into above-mentioned reaction tube under stirring
Palladium (2.2mg, 0.01mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine
(AntPhos, 4.1mg, 0.011mmol).Above-mentioned reaction system is heated to 65 DEG C, after TLC detects para chlorobromobenzene disappearance, in nitrogen
Atmosphere is stated in reaction system directly up under enclosing and o-chloronitrobenzene (157mg, 1mmol) is added, potassium fluoride (87mg, 1.5mmol),
Water (1mL), airtight reactor tube simultaneously continues to heat reaction at 65 DEG C, after reacting 12h, stops heating, be filtered to remove inorganic salts, dense
It is grease after contracting, the direct column chromatography purifying (eluant, eluent: petrol ether/ethyl acetate=5/1) of grease is obtained light yellow solid
Body is identified as the chloro- 2 '-nitrobiphenyl 135mg of 4-, and 58% yield, purity > 98%, nuclear magnetic data is the same as embodiment 1.
Embodiment 15
It sequentially adds para chlorobromobenzene (191mg, 1mmol), joins pinacol borate (280mg, 1.1mmol) in reaction tube,
Potassium acetate (147mg, 1.5mmol), substitutes nitrogen three times, is added toluene (5mL).Acetic acid is added into above-mentioned reaction tube under stirring
Palladium (2.2mg, 0.01mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine
(AntPhos, 4.1mg, 0.011mmol).Above-mentioned reaction system is heated to 65 DEG C, after TLC detects para chlorobromobenzene disappearance, in nitrogen
Atmosphere is stated in reaction system directly up under enclosing and o-chloronitrobenzene (157mg, 1mmol) is added, potassium carbonate (138mg,
1.0mmol), water (1mL), airtight reactor tube simultaneously continue to heat reaction at 65 DEG C, after reacting 12h, stop heating, be filtered to remove
Inorganic salts obtain solid crude product after concentration, are directly added into petroleum ether 12mL mashing, filtering, dry light yellow solid, identified
For the chloro- 2 '-nitrobiphenyl 175mg of 4-, 75% yield, purity > 95%, nuclear magnetic data is the same as embodiment 1.
Table 1
Note: (a) molar ratio of the following reagent of general conditions are as follows: para chlorobromobenzene/o-chloronitrobenzene/alkali A/ alkali B=1/1/
1.5/1.5.Palladium catalyst/ligand=1/1.1, palladium catalyst equivalent are the 1mol% of para chlorobromobenzene；(b) para chlorobromobenzene/neighbour's chlorine
Nitrobenzene/alkali A/ alkali B=1/1/1.5/1.0.
Embodiment 16
It sequentially adds para chlorobromobenzene (1.91g, 10mmol), joins pinacol borate (2.80g, 1.1mmol) in reaction tube,
Potassium acetate (1.47g, 1.5mmol), substitutes nitrogen three times, is added toluene (50mL).Vinegar is added into above-mentioned reaction tube under stirring
Sour palladium (22mg, 0.10mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine
(AntPhos, 41mg, 0.11mmol).Above-mentioned reaction system is heated to 65 DEG C, after TLC detects para chlorobromobenzene disappearance, in nitrogen
It is stated directly up under atmosphere in reaction system and o-chloronitrobenzene (1.57g, 10mmol) is added, potassium carbonate (2.07g, 15mmol),
Water (10mL), airtight reactor tube simultaneously continue to heat reaction at 65 DEG C, after reacting 12h, stop heating, be filtered to remove inorganic salts,
Solid crude product is obtained after concentration, is directly added into petroleum ether 100mL mashing, filtering, dry the chloro- 2 '-nitro of light yellow solid 4-
Biphenyl 2.14g, 92% yield, purity > 97%, nuclear magnetic data is the same as embodiment 1.
Embodiment 17
It sequentially adds para chlorobromobenzene (1.91g, 10mmol), joins pinacol borate (2.80g, 1.1mmol) in reaction tube,
Potassium acetate (1.47g, 1.5mmol), substitutes nitrogen three times, is added toluene (50mL).Vinegar is added into above-mentioned reaction tube under stirring
Sour palladium (11mg, 0.05mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine
(AntPhos, 20mg, 0.055mmol).Above-mentioned reaction system is heated to 65 DEG C, after TLC detects para chlorobromobenzene disappearance, in nitrogen
Atmosphere is stated in reaction system directly up under enclosing and o-chloronitrobenzene (1.57g, 10mmol) is added, potassium carbonate (2.07g,
10mmol), water (10mL), airtight reactor tube simultaneously continue to heat reaction at 65 DEG C, after reacting 12h, stop heating, be filtered to remove
Inorganic salts obtain solid crude product after concentration, are directly added into petroleum ether 100mL mashing, filter, is dry that light yellow solid 4- is chloro-
2 '-nitrobiphenyl 2.09g, 90% yield, purity > 97%, nuclear magnetic data is the same as embodiment 1.
Embodiment 18
It sequentially adds para chlorobromobenzene (1.91g, 10mmol), joins pinacol borate (2.80g, 1.1mmol) in reaction tube,
Potassium acetate (1.47g, 1.5mmol), substitutes nitrogen three times, is added toluene (50mL).Vinegar is added into above-mentioned reaction tube under stirring
Sour palladium (4.5mg, 0.02mmol), ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine
(AntPhos, 8.1mg, 0.022mmol).Above-mentioned reaction system is heated to 65 DEG C, after TLC detects para chlorobromobenzene disappearance, in nitrogen
Atmosphere is stated in reaction system directly up under enclosing and o-chloronitrobenzene (1.57g, 10mmol) is added, potassium carbonate (2.07g,
15mmol), water (10mL), airtight reactor tube simultaneously continue to heat reaction at 65 DEG C, after reacting 12h, stop heating, be filtered to remove
Inorganic salts obtain solid crude product after concentration, are directly added into petroleum ether 100mL mashing, filter, is dry that light yellow solid 4- is chloro-
2 '-nitrobiphenyl 1.98g, 85% yield, purity > 97%, nuclear magnetic data is the same as embodiment 1.
Embodiment 19
It is sequentially added in reaction tube para chlorobromobenzene (10.0g, 52.3mmol), connection pinacol borate (14.0g,
55mmol), potassium acetate (7.68g, 78.5mmol) substitutes nitrogen three times, is added toluene (210mL).To above-mentioned reaction under stirring
Palladium acetate (23.4mg, 0.10mmol) is added in pipe, ligand 4- (9- anthryl) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,
3] oxygen, penta yoke of phosphine (AntPhos, 42mg, 0.11mmol).Above-mentioned reaction system is heated to 65 DEG C, TLC detection para chlorobromobenzene disappears
After mistake, addition o-chloronitrobenzene (8.2g, 52.3mmol), potassium carbonate in reaction system are stated directly up under nitrogen atmosphere
(10.8g, 78.5mol), water (50mL), airtight reactor tube simultaneously continue to heat reaction at 65 DEG C, after reacting 12h, stop heating,
Inorganic salts are filtered to remove, obtain solid crude product after concentration, petroleum ether 400mL mashing is directly added into, filters, is light yellow admittedly dry
The chloro- 2 '-nitrobiphenyl 10.7g of body 4-, 88% yield, purity > 97%, nuclear magnetic data is the same as embodiment 1.
The characterization of the chloro- 2 '-nitrobiphenyl of 4- prepared by embodiment 1~19:
1H NMR(400MHz,CDCl3, 298K) and δ (ppm) 7.25 (d, 2H, J=7.64Hz), 7.40 (d, 2H, J=
8.36Hz), 7.50 (m, 1H), 7.62 (m, 1H), 7.88 (d, 1H, J=8.36Hz).
13C NMR(100MHz,CDCl3,298K)δ(ppm)124.,128.4,128.8,129.1,131.7,132.3,
134.3,135.0,135.7,148.9。
It is discussed in detail although the contents of the present invention have passed through above preferred embodiment, but it should be appreciated that above-mentioned
Description is not considered as limitation of the present invention.After those skilled in the art have read above content, for of the invention
A variety of modifications and substitutions all will be apparent.Therefore, protection scope of the present invention should be limited to the appended claims.
Claims (8)
1. a kind of method that one kettle way prepares the chloro- 2'- nitrobiphenyl of 4-, which is characterized in that this method includes:
1. palladium catalyst, Phosphine ligands, alkali A, inert gas ring is added using para chlorobromobenzene, connection pinacol borate as starting material
Heating reaction to raw material para chlorobromobenzene reacts completely in a solvent under border；
2. 2- chloronitrobenzene is added directly into reaction system, alkali B continues under inert gas environment to be heated to reaction to terminate, and obtains
To the chloro- 2'- nitrobiphenyl of product 4-；
2. the method that one kettle way according to claim 1 prepares the chloro- 2'- nitrobiphenyl of 4-, which is characterized in that pair
Chloro-bromobenzene: connection pinacol borate: the molar ratio of 2- chloronitrobenzene is 1.0:1.0~1.5:0.9~1.1.
3. the method that one kettle way according to claim 1 prepares the chloro- 2'- nitrobiphenyl of 4-, which is characterized in that the palladium
Catalyst is selected from acid chloride or tris(dibenzylideneacetone) dipalladium, and the dosage of the catalyst is the 0.1%- of para chlorobromobenzene equivalent
2%.
4. the method that one kettle way according to claim 1 prepares the chloro- 2'- nitrobiphenyl of 4-, which is characterized in that the phosphine
Ligand is 3- (tert-butyl) -4- (2,6- Dimethoxyphenyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine or 4- (9- anthracene
Base) -3- (tert-butyl) -2,3- dihydrobenzo [d] [1,3] oxygen, penta yoke of phosphine, the molar ratio of the Phosphine ligands and palladium catalyst is 1
~1.5:1.
5. the method that one kettle way according to claim 1 prepares the chloro- 2'- nitrobiphenyl of 4-, which is characterized in that the alkali
A is sodium acetate or potassium acetate, and the dosage of the alkali A is the 100%~200% of para chlorobromobenzene.
6. the method that one kettle way according to claim 1 prepares the chloro- 2'- nitrobiphenyl of 4-, which is characterized in that the alkali
B is selected from potassium carbonate, potassium phosphate, sodium carbonate, sodium hydroxide, sodium bicarbonate, potassium fluoride, and the dosage of the alkali B is para chlorobromobenzene
100%~200%.
7. the method that one kettle way described according to claim 1~any one of 6 prepares the chloro- 2'- nitrobiphenyl of 4-, feature
Be, the solvent be organic solvent or organic solvent/water mixed solvent system, the organic solvent be tetrahydrofuran and/
Or toluene, the organic solvent/water mixed solvent system ratio are 2~10/1.
8. the method that one kettle way described according to claim 1~any one of 6 prepares the chloro- 2'- nitrobiphenyl of 4-, feature
It is, the reaction temperature of the step 1. and 2. is 60~80 DEG C.
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