CN105085275B - O-nitrophenol and its derivative synthesis method - Google Patents
O-nitrophenol and its derivative synthesis method Download PDFInfo
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Abstract
The invention relates to an organic compound synthesis method. The organic compound synthesis method solves the problem that the existing o-nitrophenol synthesis method utilizes strong acid, produces environmental pollution and has long and complex steps. The invention provides an o-nitrophenol and its derivative synthesis method. The synthesis method comprises that a phenol compound is synthesized into 2-(phenoxy)pyridine, the product 2-(phenoxy)pyridine, a catalyst, tert-butyl nitrite and an organic solvent are orderly added into a sealed pressure-resistant container, the mixed materials are heated in an oil bath at a temperature of 50-100 DEG C and undergo a reaction for 10-30h to produce 2-(2-nitrophenyl)oxypyridine, and the 2-(2-nitrophenyl)oxypyridine is treated to form o-nitrophenol and its derivative. The synthesis method has simple processes and high efficiency.
Description
Technical field
The present invention relates to a kind of synthetic method of organic compound, relates in particular to and a kind of ortho-nitrophenyl phenols chemical combination
The preparation method of thing.
Background technology
Onitrophenol can be used for the intermediate of medicine, dyestuff, rubber chemicals and sensitive material, it is also possible to make monochromatic pH value
Indicator, therefore the preparation of onitrophenol is extremely important with regard to what is shown.At present the production technology of onitrophenol is more ripe, passes
The method of system is that, with nitric acid as nitrating agent, by phenol nitration, but the method by substituent effect due to being restricted, onitrophenol
Poor selectivity, product is the mixture of onitrophenol and paranitrophenol, it is difficult to separated, at the same the method because concentrated nitric acid have
It is oxidizing, it is quinoness by oxidation of phenol, cause onitrophenol yield relatively low, such as Chinese patent
CN201210463229.X, which discloses a kind of method that phenol nitration selectivity prepares onitrophenol, in addition China
Patent CN102344372A discloses the synthetic method of a kind of onitrophenol and ortho-nitroanisole, with o-nitrochlorobenzene as original
Material, is hydrolyzed reaction with sodium hydroxide solution, then the acidifying of Jing sulphuric acid, cooling, crystallizes, and separation can prepare ortho-nitrophenyl
Phenol, but the method uses alkali liquor and acid treatment, causes environmental pollution.
At present the ortho-nitrophenyl phenols compound containing various substituent groups is limited to the locating rule of benzene ring substituents, causes
The more difficult regiospecificity ground synthesis of such compound, needs longer reactions steps to synthesize corresponding onitrophenol, and
The reactions steps that different substituent groups is related to are different, the general method synthesis of neither one.
In view of with present on problem, design one it is general, simple ortho-nitrophenyl phenols compound synthesis route shows
Obtain and be extremely necessary.
The content of the invention
The serious problem of environmental pollution that strong acid is caused used in onitrophenol building-up process in solve prior art
And the longer more complicated problem of synthesis step, the synthesis side for proposing a kind of ortho-nitrophenyl phenols and its derivant of the invention
Method, the method is easy, efficiently.
The present invention is achieved by the following technical solutions：A kind of method of synthesis ortho-nitrophenyl phenols compound, it is described
Method be following steps：
(1) with phenol compound as raw material, the structural formula of raw material is as shown in (I)：
Wherein, R1, R2, R3 and R4 are respectively and independently selected from hydrogen, alkyl, halogen, aromatic group a kind of；
(2) by phenol compound, 2- (phenoxy group) pyridine is synthesized.
Preferably, synthesis step is specially：By phenol compound, tripotassium phosphate, Hydro-Giene (Water Science)., 2- pyridine carboxylic acids,
2- bromopyridines, add in reaction dissolvent under inert gas shielding, and mixture is heated to back flow reaction 10～30 hours, is cooled to
Room temperature, reactant liquor extraction gained mixed liquor, organic faciess are sloughed after drying solvent, obtain solid 2- phenoxypyridines.
Phenol compound is 1.2～2: 1 with the mol ratio of 2- bromopyridines；
Reaction dissolvent is selected from high boiling solvent, and reaction dissolvent has preferable dissolubility to raw material and reaction reagent.As excellent
Choosing, reaction dissolvent elects DMSO (dimethyl sulfoxide) as, and concentration of the phenol compound in reaction dissolvent is 0.1N～5.0N；
The mol ratio of tripotassium phosphate and phenol compound is 1.5～3: 1, Hydro-Giene (Water Science). and phenol compound mole
Than for 0.01～0.05: 1, phenol compound is 1: 0.08～0.5 with the mol ratio of 2- pyridine carboxylic acids.
Preferably, mixture is heated to back flow reaction 24 hours, and after being subsequently adding 5～10 times of diluted ethyl acetate, extraction
The mixed solution of gained is taken, after organic faciess anhydrous sodium sulfate drying, filtered, sloughed solvent, obtain solid 2- phenoxypyridines.
(3) product, catalyst, nitrite tert-butyl and organic solvent that step (2) is obtained are sequentially added into sealing resistance to
In pressure vessel, 50～100 DEG C are heated in oil bath, reacted 10～30 hours, obtain 2- (2- Nitrobenzol) epoxide pyridine；
The catalyst is selected from bivalence palladium salt, preferably Palladous chloride., palladium, the one kind in trifluoracetic acid palladium, more preferably
For palladium, feature is that yield is high, price is relatively inexpensive and is easy to preserve and takes.The 2- benzene oxygen obtained with step (2)
The mol ratio of yl pyridines is 1: 5～10, preferably 1: 10.
The nitrite tert-butyl as nitrating agent, the mol ratio of the 2- phenoxypyridines obtained with step (2) is 1～
3: 1, preferably 2: 1.
Organic solvent is selected from low polar organic solvent；Preferably 1,2- dichloroethanes (DCE), 1,2- dichloroethanes are dielectric
The low solvent of constant, its boiling point is of a relatively high, not volatile, easily storage.The 2- phenoxypyridines that step (2) is obtained is organic
Concentration in solvent is 0.1N～0.5N, preferably 0.1N.
Preferably, temperature is 80 DEG C in oil bath, react 24 hours.
(4) product for obtaining step (3) is processed and obtains ortho-nitrophenyl phenols and its derivant；
Preferably, process step is specially：Trifluoromethanesulfonic acid is added after the product toluene dissolving that step (3) is obtained
Methyl ester, 90～120 DEG C are reacted 2～3 hours under inert gas shielding, add the mixed solution of active metal and methanol,
70～100 DEG C are stirred 10～60 minutes, and reactant liquor extraction gained mixed liquor, organic faciess are sloughed after drying solvent, obtain adjacent nitre
Base phenol and its derivant.
Preferably, active metal is selected from alkali metal.
Preferably, 2- (2- Nitrobenzol) epoxide pyridines are 3～7mmol with the molal volume ratio of Methyl triflate:
1ml,
The active metal is selected from alkali metal, preferably metallic sodium.Active metal and 2- (2- Nitrobenzol) epoxide pyridine
Mol ratio is 10～25: 1, and active metal concentration in methyl alcohol is 0.1～0.25N.
Above-mentioned noble gases are preferably in nitrogen, argon a kind of.
The present invention directly with phenol (various substituent groups can be contained) as raw material, by the way that phenolic hydroxyl group is converted into into 2- oxy picolinates
Base, then with palladium as catalyst, in the presence of nitrite tert-butyl, realize that the carbon-hydrogen link on 2- oxy picolinate bases ortho position is lived
Change mono-nitration reaction, again 2- oxy picolinate bases are converted to into corresponding phenol finally by chemical method, so as in phenol chemical combination
Realize that nitrification obtains a series of ortho-nitrophenyl phenols compound in the ortho position of thing hydroxyl.
Compared with prior art, the invention has the beneficial effects as follows：
(1) safety and environmental protection, it is easy to operate, do not produce waste gas waste water
(2) without the need for oxidant；
(3) substrate adaptability is good, and various substituent groups can realize ortho-nitration；
(4) nitration reaction regioselectivity is good；
Specific embodiment
The present invention is described in further detail below by embodiment.
Embodiment 1：
(1) with phenol as raw material.
(2) by phenol 1.2mmol, tripotassium phosphate 2mmol, 2- pyridine carboxylic acid 0.1mmol, 2- bromopyridine 1mmol, iodate is sub-
Copper 0.05mmol, 2ml DMSO, in adding 25ml there-necked flasks.Mixture under argon protection, at 90 DEG C after backflow 24 hours
TLC detection reactions terminate, and gained mixed solution is extracted with ethyl acetate, and solvent is sloughed in decompression after anhydrous sodium sulfate drying, is obtained
Faint yellow solid 2- (phenoxy group) pyridine (95% yield).
(3) by 2- (phenoxy group) pyridine 0.5mmol, Palladium Diacetate 0.05mmol, nitrite tert-butyl 1.0mmol and 1,
2- dichloroethanes 5ml are sequentially added in the sealed pressure vessel of 25ml.By mixture in 80 DEG C of oil baths reacting by heating 24 hours.
After TLC detection reactions terminate, reactant liquor dchloromethane is filtrated to get clear liquid, with column chromatography chromatogram method (leacheate proportioning：
Petroleum ether is to ethyl acetate volume ratio 6: 1) isolated weak yellow liquid 2- (2- nitros) phenoxypyridines (90% yield).
(4) by 2- (2- nitros) phenoxypyridines 0.5mmol, Methyl triflate 0.1ml, it is dissolved in 20ml toluene
In, under argon protection 90 DEG C in the there-necked flask at react 2 hours.Add 12.5mmol metallic sodiums, 20ml methanol, under argon protection
30min is reacted at 80 DEG C.After TLC detection reactions terminate, ethyl acetate extraction, extract reduces pressure Jing after anhydrous sodium sulfate drying
Solvent is sloughed, with column chromatography chromatogram method (leacheate proportioning: petroleum ether is to ethyl acetate volume ratio 6: 1) isolated 2- Nitrobenzol
Phenol (88% yield).
Yellow solid；mp45℃；IR(KBr)：V=1530 (NO2), 3510 (OH) cm-1；1H NMR (500MHz, CDCl3)：
δ 10.60 (s, 1H), 8.12 (dd, J1=8.5Hz, J2=1.5Hz, 1H), 7.62-7.60 (m, 1H), 7.17 (dd, J1=
8.5Hz, J2=1.5Hz, 1H), 7.02-6.99 (m, 1H)；13C NMR (125MHz, CDCl3)：δ 155.1,137.5,133.7,
125.1,120.2,120.0.
Embodiment 2：
(1) with phenol as raw material.
(2) by phenol 1.2mmol, tripotassium phosphate 1.8mmol, 2- pyridine carboxylic acid 0.1mmol, 2- bromopyridine 0.6mmol, iodine
Change cuprous 0.05mmol, 4ml DMSO, in adding 50ml there-necked flasks.Mixture flows back 24 hours under nitrogen protection at 90 DEG C
TLC detections reaction afterwards terminates, and gained mixed solution is extracted with ethyl acetate, and solvent is sloughed in decompression after anhydrous sodium sulfate drying, is obtained
To faint yellow solid 2- (phenoxy group) pyridine (95% yield).
(3) by 2- (phenoxy group) pyridine 0.5mmol, Palladium Diacetate 0.05mmol, nitrite tert-butyl 0.5mmol and 1,
2- dichloroethanes 5ml are sequentially added in the sealed pressure vessel of 25ml.By mixture in 80 DEG C of oil baths reacting by heating 24 hours.
After TLC detection reactions terminate, reactant liquor dchloromethane is filtrated to get clear liquid, with column chromatography chromatogram method (leacheate proportioning：
Petroleum ether is to ethyl acetate volume ratio 6: 1) isolated weak yellow liquid 2- (2- nitros) phenoxypyridines (60% yield).
(4) by 2- (2- nitros) phenoxypyridines 0.5mmol, Methyl triflate 0.16ml, it is dissolved in 20ml toluene
In, under nitrogen protection 90 DEG C in the there-necked flask at react 3 hours.Solvent is sloughed, 7mmol metallic sodiums, 50ml methanol, nitrogen is added
60min is reacted under protection at 70 DEG C.After TLC detection reactions terminate, ethyl acetate extraction, extract Jing anhydrous sodium sulfate dryings
Solvent is sloughed in decompression afterwards, with column chromatography chromatogram method (leacheate proportioning：Petroleum ether is to ethyl acetate volume ratio 6: 1) isolated 2-
Nitrophenol (88% yield).
Yellow solid；mp45℃；IR(KBr)：V=1530 (NO2), 3510 (OH) cm-1；1H NMR (500MHz, CDCl3)：
δ 10.60 (s, 1H), 8.12 (dd, J1=8.5Hz, J2=1.5Hz, 1H), 7.62-7.60 (m, 1H), 7.17 (dd, J1=
8.5Hz, J2=1.5Hz, 1H), 7.02-6.99 (m, 1H)；13C NMR (125MHz, CDCl3)：δ 155.1,137.5,133.7,
125.1,120.2,120.0.
Embodiment 3：
(1) with phenol as raw material.
(2) by phenol 1.2mmol, tripotassium phosphate 3mmol, 2- pyridine carboxylic acid 0.3mmol, 2- bromopyridine 0.6mmol, iodate
Cuprous 0.012mmol, 5ml DMSO, in adding 50ml there-necked flasks.Mixture flows back 30 hours under argon protection at 90 DEG C
TLC detections reaction afterwards terminates, and gained mixed solution is extracted with ethyl acetate, and solvent is sloughed in decompression after anhydrous sodium sulfate drying, is obtained
To faint yellow solid 2- phenoxypyridines (95% yield).
(3) by 2- phenoxypyridines 0.5mmol, trifluoracetic acid palladium 0.08mmol, nitrite tert-butyl 1.5mmol and 1,
2- dichloroethanes 5ml are sequentially added in the sealed pressure vessel of 25ml.By mixture in 80 DEG C of oil baths reacting by heating 24 hours.
After TLC detection reactions terminate, reactant liquor dchloromethane is filtrated to get clear liquid, with column chromatography chromatogram method (leacheate proportioning：
Petroleum ether is to ethyl acetate volume ratio 6: 1) isolated weak yellow liquid 2- (2- nitros) phenoxypyridines (78% yield).
(4) by 2- (2- nitros) phenoxypyridines 0.5mmol, Methyl triflate 0.07ml, it is dissolved in 20ml toluene
In, under argon protection 120 DEG C in the there-necked flask at react 2 hours.Solvent is sloughed, 5mmol metallic sodiums, 20ml methanol, argon is added
10min is reacted under gas shielded at 100 DEG C.After TLC detection reactions terminate, ethyl acetate extraction, extract Jing anhydrous sodium sulfates
Solvent is sloughed in decompression after drying, with column chromatography chromatogram method (leacheate proportioning：Petroleum ether is to ethyl acetate volume ratio 6: 1) separates
To 2- nitrophenols (88% yield).
Yellow solid；mp45℃；IR(KBr)：V=1530 (NO2), 3510 (OH) cm-1；1H NMR (500MHz, CDCl3)：
δ 10.60 (s, 1H), 8.12 (dd, J1=8.5Hz, J2=1.5Hz, 1H), 7.62-7.60 (m, 1H), 7.17 (dd, J1=
8.5Hz, J2=1.5Hz, 1H), 7.02-6.99 (m, 1H)；13C NMR (125MHz, CDCl3)：δ 155.1,137.5,133.7,
125.1,120.2,120.0.
Embodiment 4：
(1) with o-chlorphenol as raw material.
(2) by o-chlorphenol 1.2mmol, tripotassium phosphate 2.5mmol, 2- pyridine carboxylic acid 0.5mmol, 2- bromopyridine 1mmol,
Hydro-Giene (Water Science). 0.012mmol, 7ml DMSO, in adding 50ml there-necked flasks.Mixture flows back under nitrogen protection 20 at 90 DEG C
TLC detections reaction after hour terminates, and gained mixed solution is extracted with ethyl acetate, and decompression after anhydrous sodium sulfate drying is sloughed molten
Agent, obtains 2- (2- chlorophenoxies) pyridine (93% yield).
(3) by 2- (2- chlorophenoxies) pyridine 0.5mmol, palladium 0.05mmol, nitrite tert-butyl 1.5mmol, with
And 1,2- dichloroethanes 5ml is sequentially added in the sealed pressure vessel of 25ml.By mixture in 90 DEG C of oil baths reacting by heating 18
Hour.After TLC detection reactions terminate, reactant liquor dchloromethane is filtrated to get clear liquid, with column chromatography chromatogram method (leacheate
Proportioning：Petroleum ether is to ethyl acetate volume ratio 6: 1) isolated weak yellow liquid 2- (the chloro- 6- nitro-phenoxies of 2-) pyridine
(56% yield).
(4) by 2- (the chloro- 6- nitro-phenoxies of 2-) pyridine 0.5mmol, Methyl triflate 0.08ml, it is dissolved in 20ml
In toluene, under nitrogen protection 100 DEG C in the there-necked flask at react 2 hours.Solvent is sloughed, 10mmol metallic sodiums, 20ml first is added
Alcohol, 30min is reacted under nitrogen protection at 80 DEG C.After TLC detection reactions terminate, ethyl acetate extraction, the anhydrous sulfur of extract Jing
Solvent is sloughed in decompression after sour sodium is dried, with column chromatography chromatogram method (leacheate proportioning：Petroleum ether is to ethyl acetate volume ratio 6: 1) divides
From obtaining 2 chloro- 6- nitrophenols (89% yield).
Yellow oil；IR(KBr)：V=1521 (NO2), 3294 (OH) cm-1；1H NMR (500MHz, CDCl3)：δ
11.06 (s, 1H), 8.08 (dd, J1=9.0Hz, J2=1.5Hz, 1H), 7.72 (dd, J1=7.5Hz, J2=2.5Hz, 1H),
6.98 (t, J=8.0Hz, 1H)；13C NMR (125MHz, CDCl3)：δ 151.5,137.6,134.6,124.7,123.6,
119.7.
Embodiment 5：
(1) with 5- bromophenols as raw material.
(2) by 5- bromophenol 1.2mmol, tripotassium phosphate 2mmol, 2- pyridine carboxylic acid 0.1mmol, 2- bromopyridine 1mmol, iodine
Change cuprous 0.05mmol, 12ml DMSO, in adding 50ml there-necked flasks.Mixture backflow 24 at 90 DEG C under argon protection is little
When after TLC detection reaction terminate, gained mixed solution is extracted with ethyl acetate, after anhydrous sodium sulfate drying decompression slough solvent,
Obtain faint yellow solid 2- (5- bromobenzene epoxides) pyridine (95% yield).
(3) by 2- (5- bromobenzene epoxides) pyridine 0.5mmol, palladium 0.1mmol, nitrite tert-butyl 1.0mmol and
1,2- dichloroethanes 5ml is sequentially added in the sealed pressure vessel of 25ml.By mixture, reacting by heating 24 is little in 80 DEG C of oil baths
When.After TLC detection reactions terminate, reactant liquor dchloromethane is filtrated to get clear liquid, and with column chromatography chromatogram method, (leacheate is matched somebody with somebody
Than：Petroleum ether is to ethyl acetate volume ratio 6: 1) isolated weak yellow liquid 2- (the bromo- 2- nitro-phenoxies of 5-) pyridine (78%
Yield).
(4) by 2- (the bromo- 2- nitro-phenoxies of 5-) pyridine 0.5mmol, Methyl triflate 0.1ml, it is dissolved in 20ml
In toluene, under argon protection 90 DEG C in the there-necked flask at react 2 hours.Solvent is sloughed, 12.5mmol metallic sodiums, 20ml first is added
Alcohol, 30min is reacted under argon protection at 80 DEG C.After TLC detection reactions terminate, ethyl acetate extraction, the anhydrous sulfur of extract Jing
Solvent is sloughed in decompression after sour sodium is dried, with column chromatography chromatogram method (leacheate proportioning：Petroleum ether is to ethyl acetate volume ratio 6: 1) divides
From obtaining 5 bromo- 2- nitrophenols (90% yield).
Yellow solid；mp89℃；V=1528 (NO2), 3436 (OH) cm-1；1H NMR (500MHz, CDCl3)：δ
10.63 (s, 1H), 7.99 (d, J=9.0Hz, 1H), 7.39 (d, J=2.0Hz, 1H), 7.15 (dd, J1=9.0Hz, J2=
2.0Hz, 1H)；13C NMR (125MHz, CDCl3)：δ 155.4,143.8,132.4,126.1,123.9,123.1.
Embodiment 6：
(1) with 5- chlorophenols as raw material.
(2) by 5- chlorophenol 1.2mmol, tripotassium phosphate 3.6mmol, 2- pyridine carboxylic acid 0.1mmol, 2- bromopyridine 1mmol,
Hydro-Giene (Water Science). 0.05mmol, 2ml DMSO, in adding 50ml there-necked flasks.Under nitrogen protection backflow 24 is little at 90 DEG C for mixture
When after TLC detection reaction terminate, gained mixed solution is extracted with ethyl acetate, after anhydrous sodium sulfate drying decompression slough solvent,
Obtain faint yellow solid 2- (5- chlorophenoxies) pyridine (95% yield).
(3) by 2- (5- chlorophenoxies) pyridine 0.5mmol, palladium 0.1mmol, nitrite tert-butyl 1.0mmol,
1.0mmol and 1,2- dichloroethanes 8ml are sequentially added in the sealed pressure vessel of 25ml.Mixture is added in 90 DEG C of oil baths
Thermal response 30 hours.After TLC detection reactions terminate, reactant liquor dchloromethane is filtrated to get clear liquid, uses column chromatography chromatogram
Method (leacheate proportioning：Petroleum ether is to ethyl acetate volume ratio 6: 1) isolated weak yellow liquid 2- (the chloro- 2- Nitrobenzol oxygen of 5-
Base) pyridine (72% yield).
(4) by 2- (the chloro- 2- nitro-phenoxies of 5-) pyridine 0.5mmol, Methyl triflate 0.1ml, it is dissolved in 20ml
In toluene, under nitrogen protection 90 DEG C in the there-necked flask at react 2 hours.Solvent is sloughed, 12.5mmol metallic sodiums, 20ml first is added
Alcohol, 30min is reacted under nitrogen protection at 80 DEG C.After TLC detection reactions terminate, ethyl acetate extraction, the anhydrous sulfur of extract Jing
Solvent is sloughed in decompression after sour sodium is dried, with column chromatography chromatogram method (leacheate proportioning：Petroleum ether is to ethyl acetate volume ratio 6：1) divide
From obtaining the chloro- 2- nitrophenols of 5- (95% yield).
White solid；mp92℃；IR(KBr)：V=1529 (NO2), 3436 (OH) cm-1；1H NMR (500MHz,
CDCl3)：δ 10.67 (s, 1H), 8.08 (d, J=9.0Hz, 1H), 7.20 (d, J=2.2Hz, 1H), 6.99 (dd, J1=9.0Hz,
J2=2.0Hz, 1H)；13C NMR (125MHz, CDCl3)：δ 155.5,143.8,132.4,126.2,121.0,119.9.
Embodiment 7：
(1) with 4- bromophenols as raw material.
(2) by 4- bromophenol 1.2mmol, tripotassium phosphate 2mmol, 2- pyridine carboxylic acid 0.1mmol, 2- bromopyridine 1mmol, iodine
Change cuprous 0.05mmol, 2ml DMSO, in adding 50ml there-necked flasks.Mixture flows back 24 hours under nitrogen protection at 90 DEG C
TLC detections reaction afterwards terminates, and gained mixed solution is extracted with ethyl acetate, and solvent is sloughed in decompression after anhydrous sodium sulfate drying, is obtained
To faint yellow solid 2- (4- bromobenzene epoxides) pyridine (95% yield).
(3) by 2- (4- bromobenzene epoxides) pyridine 0.5mmol, palladium 0.05mmol, nitrite tert-butyl 1.5mmol, with
And 1,2- dichloroethanes 4ml is sequentially added in the sealed pressure vessel of 25ml.By mixture in 90 DEG C of oil baths reacting by heating 24
Hour.After TLC detection reactions terminate, reactant liquor dchloromethane is filtrated to get clear liquid, with column chromatography chromatogram method (drip washing
Liquid proportioning：Petroleum ether is to ethyl acetate volume ratio 6: 1) isolated weak yellow liquid 2- (the bromo- 2- nitro-phenoxies of 4-) pyridine
(65% yield).
(4) by 2- (the bromo- 2- nitro-phenoxies of 4-) pyridine 0.5mmol, Methyl triflate 0.1ml, it is dissolved in 20ml
In toluene, under nitrogen protection 90 DEG C in the there-necked flask at react 2 hours.Solvent is sloughed, 12.5mmol metallic sodiums, 20ml first is added
Alcohol, 30min is reacted under nitrogen protection at 80 DEG C.After TLC detection reactions terminate, ethyl acetate extraction, the anhydrous sulfur of extract Jing
Solvent is sloughed in decompression after sour sodium is dried, with column chromatography chromatogram method (leacheate proportioning：Petroleum ether is to ethyl acetate volume ratio 6: 1) divides
From obtaining the bromo- 2- nitrophenols of 4- (89% yield).
Yellow oil；IR(KBr)：V=1526 (NO2), 3435 (OH) cm-1；1H NMR (500MHz, CDCl3)：δ
10.51 (s, 1H), 8.26 (d, J=2.5Hz, 1H), 7.68 (dd, J1=9.0Hz, J2=2.5Hz, 1H), 7.09 (d, J=
9.0Hz, 1H)；13C NMR (125MHz, CDCl3)：δ 154.1,140.4,132.4,127.3,121.7,111.7.
Embodiment 8
(1) with 4- phenylphenols as raw material.
(2) by 4- phenylphenol 1.2mmol, tripotassium phosphate 2mmol, 2- pyridine carboxylic acid 0.1mmol, 2- bromopyridine 1mmol,
Hydro-Giene (Water Science). 0.05mmol, 2ml DMSO, in adding 50ml there-necked flasks.Mixture backflow 10 at 90 DEG C under argon protection is little
When after TLC detection reaction terminate, gained mixed solution is extracted with ethyl acetate, after anhydrous sodium sulfate drying decompression slough solvent,
Obtain faint yellow solid 2- (4- phenylphenoxies) pyridine (95% yield).
(3) by 2- (4- phenylphenoxies) pyridine 0.5mmol, palladium 0.1mmol, nitrite tert-butyl 1.5mmol, with
And 1,2- dichloroethanes 5ml is sequentially added in the sealed pressure vessel of 25ml.By mixture in 80 DEG C of oil baths reacting by heating 30
Hour.After TLC detection reactions terminate, reactant liquor dchloromethane is filtrated to get clear liquid, with column chromatography chromatogram method (leacheate
Proportioning：Petroleum ether is to ethyl acetate volume ratio 6: 1) isolated weak yellow liquid 2- (4- phenyl -2- nitro-phenoxies) pyridine
(55% yield).
(4) by 2- (4- phenyl -2- nitro-phenoxies) pyridine 0.5mmol, Methyl triflate 0.1ml, it is dissolved in
In 20ml toluene, under argon protection 90 DEG C in the there-necked flask at react 2 hours.Solvent is sloughed, 12.5mmol metallic sodiums are added,
20ml methanol, 30min is reacted under argon protection at 80 DEG C.After TLC detection reactions terminate, ethyl acetate extraction, extract Jing
Solvent is sloughed in decompression after anhydrous sodium sulfate drying, with column chromatography chromatogram method (leacheate proportioning：Petroleum ether is to ethyl acetate volume ratio
6: 1) isolated 4- phenyl -2- nitrophenols (93% yield).
White solid；mp73.8℃；IR(KBr)：V=1536 (NO2), 3437 (OH) cm-1；1H NMR (500MHz,
CDCl3)：δ 10.60 (s, 1H), 8.32 (d, J=2.0Hz, 1H), 7.84 (dd, J1=8.5Hz, J2=2.0Hz, 1H), 7.56
(d, J=7.5Hz, 2H), 7.48 (t, J=7.5Hz, 2H), 7.41 (t, J=7.5Hz, 1H), 7.25 (d, J=9.0Hz, 1H)；13C NMR (125MHz, CDCl3)：δ 154.3,138.2,136.3,133.8,133.8,129.1,127.9,126.7,122.8,
120.4.
Embodiment 9
(1) with 2- methylphenols as raw material.
(2) by 2- methylphenol 1.2mmol, tripotassium phosphate 2mmol, 2- pyridine carboxylic acid 0.1mmol, 2- bromopyridine 1mmol,
Hydro-Giene (Water Science). 0.05mmol, 2ml DMSO, in adding 50ml there-necked flasks.Under nitrogen protection backflow 24 is little at 90 DEG C for mixture
When after TLC detection reaction terminate, gained mixed solution is extracted with ethyl acetate, after anhydrous sodium sulfate drying decompression slough solvent,
Obtain faint yellow solid 2- (2- methylphenoxy) pyridine (95% yield).
(3) by 2- (2- methylphenoxy) pyridine 0.5mmol, palladium 0.05mmol, nitrite tert-butyl 1.0mmol,
And 1,2- dichloroethanes 3ml is sequentially added in the sealed pressure vessel of 25ml.By mixture in 100 DEG C of oil baths reacting by heating
10 hours.After TLC detection reactions terminate, reactant liquor dchloromethane is filtrated to get clear liquid, with column chromatography chromatogram method (drip washing
Liquid proportioning：Petroleum ether is to ethyl acetate volume ratio 6: 1) (79% receives isolated 2- (2- methyl -6- nitro-phenoxies) pyridine
Rate).
(4) by 2- (2- methyl -6- nitro-phenoxies) pyridine 0.5mmol, Methyl triflate 0.1ml, it is dissolved in
In 20ml toluene, under nitrogen protection 90 DEG C in the there-necked flask at react 2 hours.Solvent is sloughed, 12.5mmol metallic sodiums are added,
20ml methanol, 30min is reacted under nitrogen protection with 80 DEG C.After TLC detection reactions terminate, ethyl acetate extraction, extract Jing
Solvent is sloughed in decompression after anhydrous sodium sulfate drying, with column chromatography chromatogram method (leacheate proportioning：Petroleum ether is to ethyl acetate volume ratio
6: 1) isolated 2- (2- methyl -6- nitro-phenoxies) pyridine (97% yield).
Yellow oil；IR(KBr)：V=1521 (NO2), 3294 (OH) cm-1；1H NMR (500MHz, CDCl3)δ10.93
(s, 1H), 7.97 (d, J=8.5Hz, 1H), 7.46 (d, J=7.0Hz, 1H), 6.89 (dd, J1=8.5Hz, J2=7.5Hz,
1H), 2.35 (s, 3H)；13C NMR (125MHz, CDCl3)：δ 153.7,138.1,133.5,129.5,122.6,119.3,
15.8.
Embodiment 10
(1) with 4- iodophenols as raw material.
(2) by 4- iodophenol 1.2mmol, tripotassium phosphate 2mmol, 2- pyridine carboxylic acid 0.1mmol, 2- bromopyridine 1mmol, iodine
Change cuprous 0.05mmol, 2ml DMSO, in adding 50ml there-necked flasks.Mixture flows back 24 hours under nitrogen protection at 90 DEG C
TLC detections reaction afterwards terminates, and gained mixed solution is extracted with ethyl acetate, and solvent is sloughed in decompression after anhydrous sodium sulfate drying, is obtained
To faint yellow solid 2- (4- iodobenzene epoxides) pyridine (95% yield).
(3) by 2- (4- iodobenzene epoxides) pyridine 0.5mmol, palladium 0.1mmol, nitrite tert-butyl 1.2mmol, and
1,2- dichloroethanes 5ml is sequentially added in the sealed pressure vessel of 25ml.By mixture, reacting by heating 20 is little in 100 DEG C of oil baths
When.After TLC detection reactions terminate, reactant liquor dchloromethane is filtrated to get clear liquid, and with column chromatography chromatogram method, (leacheate is matched somebody with somebody
Than：Petroleum ether is to ethyl acetate volume ratio 6: 1) isolated 2- (the iodo- 2- nitro-phenoxies of 4-) pyridine (66% yield).
(4) by 2- (the iodo- 2- nitro-phenoxies of 4-) pyridine 0.5mmol, Methyl triflate 0.1ml, it is dissolved in 20ml
In toluene, under nitrogen protection 90 DEG C in the there-necked flask at react 2 hours.Solvent is sloughed, 12.5mmol metallic sodiums, 20ml first is added
Alcohol, 30min is reacted under nitrogen protection at 80 DEG C.After TLC detection reactions terminate, ethyl acetate extraction, the anhydrous sulfur of extract Jing
Solvent is sloughed in decompression after sour sodium is dried, with column chromatography chromatogram method (leacheate proportioning：Petroleum ether is to ethyl acetate volume ratio 6: 1) divides
From obtaining the iodo- 2- nitrophenols of 4- (91% yield).
White solid；mp80℃；IR(KBr)：V=1521 (NO2), 3294 (OH) cm-1；1H NMR (500MHz,
CDCl3)：δ 10.53 (s, 1H), 8.43 (d, J=2.5Hz, 1H), 7.84 (dd, J1=8.5Hz, J2=2.0 Hz, 1H), 6.96
(d, J=9.0Hz, 1H)；13C NMR (125MHz, CDCl3)：δ 154.8,145.9,134.5,133.3,122.0,80.4.
Embodiment 11
(1) with MX as raw material.
(2) by MX 1.2mmol, tripotassium phosphate 2mmol, 2- pyridine carboxylic acid 0.1mmol, 2- bromopyridines
1mmol, Hydro-Giene (Water Science). 0.05mmol, 2ml DMSO, in adding 50ml there-necked flasks.Mixture argon protection under in 90 DEG C next time
TLC detections reaction after flowing 24 hours terminates, and gained mixed solution is extracted with ethyl acetate, and decompression after anhydrous sodium sulfate drying is sloughed
Solvent, obtains faint yellow solid 2- (3,5- dimethyl phenoxy) pyridine (95% yield).
(3) by 2- (3,5- dimethyl phenoxy) pyridine 0.5mmol, palladium 0.08mmol, nitrite tert-butyl
1.0mmol, and 1,2- dichloroethanes 4ml sequentially added in the sealed pressure vessel of 25ml.By mixture in 95 DEG C of oil baths
Reacting by heating 16 hours.After TLC detection reactions terminate, reactant liquor dchloromethane is filtrated to get clear liquid, uses column chromatography color
Spectrometry (leacheate proportioning：Petroleum ether is to ethyl acetate volume ratio 6: 1) isolated 2- (3,5- dimethyl -2- nitro-phenoxies)
Pyridine (51% yield).
(4) by 2- (3,5- dimethyl -2- nitro-phenoxies) pyridine 0.5mmol, Methyl triflate 0.1ml, dissolving
In 20ml toluene, under argon protection 90 DEG C in the there-necked flask at react 2 hours.Solvent is sloughed, 12.5mmol metallic sodiums are added,
20ml methanol, 30min is reacted under argon protection at 80 DEG C.After TLC detection reactions terminate, ethyl acetate extraction, extract Jing
Solvent is sloughed in decompression after anhydrous sodium sulfate drying, with column chromatography chromatogram method (leacheate proportioning：Petroleum ether is to ethyl acetate volume ratio
6: 1) isolated 3,5- dimethyl -2- nitrophenols (90% yield).
White solid；mp110-111℃；IR(KBr)：V=1537 (NO2), 3436 (OH) cm-1；1H NMR
(500MHz, CDCl3)：δ 10.63 (s, 1H), 6.82 (s, 1H), 6.65 (s, 1H), 2.61 (s, 3H), 2.33 (s, 3H)；13C
NMR (125MHz, CDCl3)：δ 155.8,147.2,136.8,133.2,125.3,117.6,22.9,21.6.
Embodiment 12
(1) with 4-TBP as raw material.
(2) by 4-TBP 1.2mmol, tripotassium phosphate 2mmol, 2- pyridine carboxylic acid 0.1mmol, 2- bromopyridines
1mmol, Hydro-Giene (Water Science). 0.05mmol, 2ml DMSO, in adding 50ml there-necked flasks.Mixture under nitrogen protection in 90 DEG C next time
TLC detections reaction after flowing 24 hours terminates, and gained mixed solution is extracted with ethyl acetate, and decompression after anhydrous sodium sulfate drying is sloughed
Solvent, obtains faint yellow solid 2- (4- tert-butyl benzene epoxides) pyridine (95% yield).
(3) by 2- (4- tert-butyl benzene epoxides) pyridine 0.5mmol, palladium 0.08mmol, nitrite tert-butyl
1.0mmol, 1,2- dichloroethanes 5ml is sequentially added in the sealed pressure vessel of 25ml.Mixture is heated in 50 DEG C of oil baths
Reaction 30 hours.After TLC detection reactions terminate, reactant liquor dchloromethane is filtrated to get clear liquid, uses column chromatography chromatogram method
(leacheate proportioning：Petroleum ether is to ethyl acetate volume ratio 6: 1) isolated 2- (the 4- tert-butyl group -2- nitro-phenoxies) pyridine
(59% yield).
(4) by 2- (the 4- tert-butyl group -2- nitro-phenoxies) pyridine 0.5mmol, Methyl triflate 0.1ml, it is dissolved in
In 20ml toluene, under nitrogen protection 90 DEG C in the there-necked flask at react 2 hours.Solvent is sloughed, 12.5mmol metallic sodiums are added,
20ml methanol, 30min is reacted under nitrogen protection at 80 DEG C.After TLC detection reactions terminate, ethyl acetate extraction, extract Jing
Solvent is sloughed in decompression after anhydrous sodium sulfate drying, with column chromatography chromatogram method (leacheate proportioning：Petroleum ether is to ethyl acetate volume ratio
6: 1) the isolated 4- tert-butyl groups -2- nitrophenols (94% yield).
White solid；mp89-91℃；IR(KBr)：V=1536 (NO2), 3249 (OH) cm-1；1H NMR (500MHz,
CDCl3)：δ 10.48 (s, 1H), 8.08 (d, J=2.5Hz, 1H), 7.65 (dd, J1=9.0Hz, J2=2.5Hz, 1H), 7.11
(d, J=9.0Hz, 1H), 1.34 (s, 9H)；13C NMR (125MHz, CDCl3)：δ 153.1,143.7,135.5,133.0,1..
Claims (7)
1. the synthetic method of a kind of ortho-nitrophenyl phenols and its derivant, it is characterised in that：Described synthetic method is following step
Suddenly：
（1）With phenol compound as raw material, the structural formula of raw material is such as（I）It is shown：
Wherein, R1, R2, R3 and R4 are respectively and independently selected from hydrogen, alkyl, halogen, aromatic group a kind of；
（2）By phenol compound, tripotassium phosphate, Hydro-Giene (Water Science)., 2- pyridine carboxylic acids, 2- bromopyridines, under inert gas shielding
In adding reaction dissolvent, mixture is heated to back flow reaction 10 ~ 30 hours, is cooled to room temperature, and reactant liquor extracts gained mixed liquor,
Organic faciess slough after drying solvent, obtain solid 2- phenoxypyridines；
（3）By step（2）In the product, catalyst, nitrite tert-butyl, the organic solvent addition sealed pressure vessel that obtain,
50 ~ 100 DEG C are heated in oil bath, is reacted 10 ~ 30 hours, obtain 2-（2- Nitrobenzol）Epoxide pyridine, catalyst is selected from Palladous chloride., vinegar
Sour palladium, the one kind in trifluoracetic acid palladium；
（4）By step（3）Methyl triflate is added after the product toluene dissolving for obtaining, 90 under inert gas shielding ~
120 DEG C are reacted 2 ~ 3 hours, add the mixed solution of active metal and methanol, are stirred 10 ~ 60 minutes at 70 ~ 100 DEG C, reaction
Liquid extraction gained mixed liquor, organic faciess are sloughed after drying solvent, obtain ortho-nitrophenyl phenols and its derivant.
2. the synthetic method of a kind of ortho-nitrophenyl phenols according to claim 1 and its derivant, it is characterised in that：Phenol
Class compound is 1.2 ~ 2 with the mol ratio of 2- bromopyridines：1；Reaction dissolvent is selected from dimethyl sulfoxide, and phenol compound is in reaction
Concentration in solvent is 0.1 N～5.0 N；Tripotassium phosphate is 1.5 ~ 3 with the mol ratio of phenol compound：1, Hydro-Giene (Water Science). with
The mol ratio of phenol compound is 0.01 ~ 0.05：1, phenol compound is 1 with the mol ratio of 2- pyridine carboxylic acids：0.08~
0.5。
3. the synthetic method of a kind of ortho-nitrophenyl phenols according to claim 1 and its derivant, it is characterised in that：It is described
Step（3）Middle catalyst and step（2）The mol ratio of the 2- phenoxypyridines for obtaining is 1：5~10.
4. the synthetic method of a kind of ortho-nitrophenyl phenols according to claim 1 and its derivant, it is characterised in that：Nitrous
Tert-butyl acrylate and step（2）The mol ratio of the 2- phenoxypyridines for obtaining is 1～3：1.
5. the synthetic method of a kind of ortho-nitrophenyl phenols according to claim 1 and its derivant, it is characterised in that：Step
（3）Middle organic solvent is selected from 1,2- dichloroethanes；Step（2）The 2- phenoxypyridines for obtaining concentration in organic solvent is
0.1 N～0.5 N.
6. the synthetic method of a kind of ortho-nitrophenyl phenols according to claim 1 and its derivant, it is characterised in that：2-
（2- Nitrobenzol）Epoxide pyridine is 3 ~ 7mmol with the molal volume ratio of Methyl triflate：1ml, active metal and 2-（2- nitre
Base benzene）The mol ratio of epoxide pyridine is 10 ~ 25：1, active metal concentration in methyl alcohol is 0.1 ~ 0.25 N.
7. a kind of ortho-nitrophenyl phenols according to claim 1 or 6 and its synthetic method of derivant, it is characterised in that：
Active metal is selected from metallic sodium.
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