CN109293491A - A kind of method that aryl diazonium salts take off acyl group in diazonium - Google Patents
A kind of method that aryl diazonium salts take off acyl group in diazonium Download PDFInfo
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- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/80—Ketones containing a keto group bound to a six-membered aromatic ring containing halogen
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
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- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
The present invention provides a kind of methods that aryl diazonium salts and its derivative take off acyl group in diazonium; this method is that aryl diazonium salts and its derivative and adjacent dicarbonyl compound are obtained corresponding aryl-acyl product, obtained products collection efficiency is high by illumination reaction; it is participated in without metal, process is simple.
Description
Technical field
The present invention relates to a kind of methods that aryl diazonium salts take off acyl group in diazonium；Belong to organic chemical synthesis field.
Background technique
Aminated compounds is widely present in nature, contains amino-compound in many natural products, and arylamine class
The features such as conjunction object is also largely present in nature and in industry, cheap, activity is higher due to it, aromatic amine compounds are organic
The field of synthesis is largely used as substrate to be used, and from aryl diazonium salts are simply synthesized by arylamine, aryl diazonium salts take off diazonium
Acetylating reaction has important meaning.
It is a kind of very common group due to being acylated, is widely present in natural and synthesis compound, and many
Common group in drug and dye structure.Therefore acyl group is introduced into compound is necessary step in some synthesis processes.
However, it is Friedel-Crafts acylation reaction that method to be used is led in aryl-acylization reaction, with aromatic hydrocarbon all the time
It is acted under the effect of the Lewis acid such as anhydrous AlCl3 with acid chloride or acid anhydrides, the hydrogen atom on ring also can be replaced acyl group.
AttilioCitterio team nineteen eighty-two reports using aryl diazonium salts and diacetyl as raw material, in dimethyl sulfoxide conduct
Solvent completed in the presence of copper arylaceto glycosylation reaction (AttilioCitterio, MarcoSerravalle,
ElenaVismara Tetrahedron Letters, 23 (17), 1831~18-34).Carlos Roque D.Cordia group
Team has used in report in 2009 using vinyl butyl ether and aryl diazonium salts as raw material, and acetonitrile is solvent, sodium acetate conduct
Alkali is being acidified realization arylaceto base (Angelo H.L.Machado, Marico after reacting under palladium chtalyst with hydrochloric acid
A.de Sousa, Carlos Roque D.Cordia Tetrahedron Letters, 50 (11), 1222-1225,2009).
So far, using arylamine as substrate, realize that the reaction of acyl functionization is never reported by illumination, organic anti-
Field is answered to need completion.
Summary of the invention
The technical deficiency that diazonium generates acylation aryl compound is taken off for aryldiazonium salt compound in the prior art, this
A kind of aryl diazonium salts of being designed to provide of invention take off diazonium and are acylated method, it is intended to pass through aryl diazonium salts and adjacent two carbonyls
Based compound is that substrate is leniently acylated aryl through illumination.
A kind of method that aryl diazonium salts take off acyl group in diazonium, by aryl diazonium salts, tool with 2 structural formula of formula 1 or formula
There is the adjacent dicarbonyl compound of 3 structural formula of formula to react under light illumination, obtains the aromaticacyl radical product of 4 structural formula of formula；
A- is anion；
R2~R8It is alone H, C1~C6Alkyl, C1~C6Alkoxy, phenoxy group, benzyloxy, nitro, halogen, cyano,
Ester group, trifluoromethyl, C1~C4Alkyl sulfenyl or allyl oxygen；And R7、R8In, at least one substituent group is H；R1For H or F；
The R9 is alkyl, naphthenic base, Heterocyclylalkyl, phenyl or heterocyclic aryl；The alkyl, naphthenic base, heterocycle
Alkyl, phenyl or heterocyclic aryl allow containing C1~C4Alkyl, C1~C4Alkoxy, phenyl, halogen, one of ester group
Or a variety of substituent groups.
In the present invention, innovatively existed using the aromatics diazonium salt of 2 structure of formula 1 or formula and the adjacent dicarbonyl compound
Diazo can be taken off under light irradiation, and is taking off diazo site connection acyl group.The method of the present invention is easy to operate, and process is short, produces
Object high income；Moreover, compared to existing method (such as Friedel-Crafts acylation reaction), the method for the present invention tool
There is incomparable regioselectivity.
The study found that being the pass for guaranteeing successfully preparation using the aryl diazonium salts of 2 structure of formula 1 of the present invention and formula
Key.When the aryl diazonium salts are the compound of 1 structural formula of formula, at least one group of the ortho position of diazonium is that H is conducive into
Function is acylated.For another example, when the aryl diazonium salts are the compound of 2 structural formula of formula, diazonium groups are between pyridine ring
Position can unexpectedly realize acylation；Diazonium groups are located at ortho position or the contraposition of phenazine ring, are difficult to successfully be acylated.
The present invention through further research, it has been found that, the substituent group and the position of substitution of aryl diazonium salts are controlled,
Help further to promote purpose product yield.
Preferably, R1For H.The study found that R1For hydrogen, the yield of product can be promoted.
Preferably, R2For hydrogen, methyl, methoxyl group, methyl mercapto, nitro, trifluoromethyl, benzyloxy, allyloxy, fluorine,
Bromine, chlorine atom or cyano.
Preferably, R3For hydrogen, methyl, methoxyl group, nitro, trifluoromethyl, fluorine, bromine, chlorine or cyano；
Preferably, R4For bromine, chlorine or nitro.
Further preferably, R1、R2、R4For H, R3For electron-donating group, electron-donating group is preferably alkoxy especially methoxy
When base, the yield of product is higher.
The method of the present invention has good de- diazonium not only for the benzene class diazonium salt with 1 structure of formula and is acylated effect
Fruit；The study found that the method for the present invention applies also for the pyridine ring of the more difficult acylation of the prior art.
The present inventor the study found that except control diazonium groups be located at the meta position of pyridine ring in addition to, diazonium groups at least one
Ortho position is also one of the key for guaranteeing preparation effect without substituent group, that is to say, needs to control the R in formula 27、R8In at least one
A substituent group is H；Preferably R7、R8It is H.
Research also found, control other substituent groups on pyridine ring, it helps further promote yield.
Preferably, R5For hydrogen, methyl, methoxyl group, nitro, fluorine, bromine, chlorine or cyano；Preferably H.
Preferably, R6For hydrogen, methyl, methoxyl group, methyl mercapto, nitro, trifluoromethyl, benzyloxy, allyloxy, fluorine,
Bromine, chlorine or cyano.
The A- is tetrafluoroborate, sulfate radical (HSO4), trifluoromethanesulfonic acid root, Cl-, CF3COO- or bromate.
The aryl diazonium salts can be used corresponding aromatic amine and obtain through diazo-reaction.
In the present invention, the R9For C1~C6Alkyl, cyclopenta, cyclohexyl, oxygen or the cyclopenta of thiation or hexamethylene
Base, phenyl, five yuan or hexa-atomic heterocyclic aryl.Alkyl, cyclopenta, cyclohexyl, the cyclopenta of heterocycle or the cyclohexyl,
Allow on phenyl containing C1~C4Alkyl, C1~C4Alkoxy, phenyl, halogen, one of ester group or a variety of substituent groups.
Further preferably, the R9For C1~C3Alkyl；For example, methyl, ethyl or propyl.
R9Group difference, photocatalysis intensity has differences, can be according to the difference, it is matched suitable to adjust
The light of wavelength.For example, working as R9When for methyl, it good can promote the de- diazonium and second of diazonium salt under visible light or blue light
It is acylated.
Preferably, the reaction is also added with auxiliary agent, the auxiliary agent is three fluomethane sulfinic acid sodium, acetic acid
Sodium, at least one of sodium carbonate.The study found that the auxiliary agent that addition is certain, helps further to promote product yield, not only such as
This, additionally aids and is avoided only taking off the by-product that diazonium is not acylated.
Preferably, the molar ratio of aryl diazonium salts, auxiliary agent is 1: 0.5-2.Under the preferred molar ratio, facilitate into
It is conducive to the utilization of light to one step, to facilitate the yield for further promoting acylate, reduces de- diazonium by-product.Auxiliary agent is thrown
Sovolin amount is higher than the utilization that 2 equivalents are unfavorable for light.
The research of the invention finds that add ratio, reaction dissolvent etc. of control aryl diazonium salts and adjacent dicarbonyl compound are joined
Several control facilitates the yield for further promoting product obtained.
Preferably, the molar ratio of aryl diazonium salts, adjacent dicarbonyl compound is 1: 10~50.The study found that control
Under the preferred range, conducive to the utilization of light, facilitate the yield for further promoting product.Lower than the product yield of 10 equivalents
It is lower.
Further preferably, aryl diazonium salts, adjacent dicarbonyl compound molar ratio be 1: 10~20.
The reaction solvent for use is water, and ethyl acetate, acetonitrile, methylene chloride, ether, n,N-Dimethylformamide is extremely
Few one kind；Further preferably acetonitrile.The research of the invention finds that helping further to promote product using the preferred solvent
Yield.
It reacts in starting soln, 0.05~0.5mol/L of concentration of aryl diazonium salts.
The reaction temperature is 0-50 DEG C；Further preferably room temperature (for example, 15~35 DEG C).
The light is preferably blue light, such as 36w blue light.
The illumination reaction time is preferably 2~20 hours.
It is extracted after reaction through hydrophobic solvent, the organic phase being obtained by extraction is concentrated, then obtain through chromatogram purification.
In technical solution of the present invention, after the reaction was completed, reaction mixture is obtained by methylene chloride extraction, vacuum rotary steam
To crude product；Crude product passes through chromatography column separating purification again and obtains final product.The eluent that chromatographic column uses is petroleum ether, pole
Property biggish product use the mixing eluent of petroleum ether and ethyl acetate, the volume ratio of petroleum ether and ethyl acetate is 50: 1~
1∶1。
Advantageous:
1, technical solution of the present invention carries out acetyl group in the de- diazonium of aryl diazonium salts for the first time, has filled up the prior art not
Foot；
2, technical solution of the present invention is by one pot reaction, and process conditions are mild, and process is short, and step is simple, and substrate is suitable
It is wide with property, meet demand of industrial production；
3, the technical solution of the present invention substrate acetylating accordingly by aryl diazonium salts and its derivative substrates production,
Yield high income.；The study found that the yield of product may be up to 72%.
Detailed description of the invention
Fig. 1 is the product that embodiment 1 obtains1H NMR spectra.
Fig. 2 is the product that embodiment 1 obtains13CNMR spectrogram.
Fig. 3 is the product that embodiment 4 obtains1H NMR spectra.
Fig. 4 is the product that embodiment 4 obtains13C NMR spectra.
Fig. 5 is the product that embodiment 6 obtains1H NMR spectra.
Fig. 6 is the product that embodiment 6 obtains13C NMR spectra.
Specific embodiment
Following case study on implementation is intended to illustrate summary of the invention, rather than to the protection scope of the claims in the present invention into one
Step limits.
Following embodiment and comparative example, unless specified or limited otherwise, the illumination refer both to blue light；Such as there is 36W blue light photograph
Penetrate reaction.
Embodiment 1
The synthesis of the bromo- 4- acetylbenzene of 1- with isolate and purify: by 4- bromophenyl diazonium tetrafluoroborate, (structural formula is shown in Table 1；
1mmol, 1.0eq) and three fluomethane sulfinic acid sodium (310mg, 2mml, 2.0eq) be added 20mL vial in, acetonitrile 4mL.So
Dimethyl diketone (1mL, 20mmol, 20.0eq) is added in reaction flask with syringe afterwards, room temperature illumination reaction 12 hours.
After reaction, it is quenched with water, then twice with 20mL methylene chloride extraction reaction solution, then by gained organic phase anhydrous slufuric acid
Sodium is dried, and filtering, vacuum rotary steam obtains the crude product with a small amount of solvent.Then by crude product silica gel column chromatography post separation,
Eluant, eluent petroleum ether: ethyl acetate=20: 1 mixed liquor obtains final product: the bromo- 4- acetylbenzene of 1- is yellow oily liquid
Body, yield 68%.
1H NMR (400MHz, CDCl3) δ=7.82 (d, J=8.6,1H), 7.61 (d, J=8.6,1H), 2.58 (s, 2H)
.13C NMR (101 MHz, CDCl3) δ=197.0,135.8,131.9,129.8,128.3,77.3,76.7,26.5.
Embodiment 2
The synthesis of 1- methoxyl group -4- acetylbenzene with isolate and purify: by 4- methoxyphenyl diazonium tetrafluoroborate
(1mmol, 1.0eq) and three fluomethane sulfinic acid sodium (310mg, 2mml, 2.0eq) are added in 20mL vial, acetonitrile 4mL.
Then dimethyl diketone (1mL, 20mmol, 20.0eq) is added in reaction flask with syringe, room temperature illumination reaction 12 is small
When.After reaction, it is quenched with water, then twice with 20mL methylene chloride extraction reaction solution, then by gained organic phase with anhydrous
Sodium sulphate is dried, and filtering, vacuum rotary steam obtains the crude product with a small amount of solvent.Then by crude product silica gel column chromatography
Separation, eluant, eluent petroleum ether: ethyl acetate=20: 1 mixed liquor obtains final product: 1- methoxyl group -4- acetylbenzene is Huang
Color oily liquids, yield 72%.
1H NMR (400MHz, CDCl3) δ=7.92 (dd, J=9.3,2.2,1H), 6.92 (d, J=8.9,1H), 3.85
(s, 2H), 2.54 (s, 2H)13C NMR (101 MHz, CDCl3) δ=196.7,163.4,130.5,130.3,113.6,77.3,
76.7,55.4,26.3.
Embodiment 3
The synthesis of -4 acetylbenzene of 1- phenoxy group with isolate and purify: by 4- Phenoxyphenyl diazonium tetrafluoroborate
(1mmol, 1.0eq) and three fluomethane sulfinic acid sodium (310mg, 2mml, 2.0eq) are added in 20mL vial, acetonitrile 4mL.
Then dimethyl diketone (1mL, 20mmol, 20.0eq) is added in reaction flask with syringe, room temperature illumination reaction 12 is small
When.After reaction, twice with 20mL methylene chloride extraction reaction solution, then gained organic phase is done with anhydrous sodium sulfate
Dry, filtering, vacuum rotary steam obtains the crude product with a small amount of solvent.Then by crude product silica gel column chromatography post separation, eluant, eluent is used
Petroleum ether: ethyl acetate=20: 1 mixed liquor obtains final product: 1- phenoxy group -4- acetylbenzene is yellow oily liquid, is produced
Rate is 60%.
1H NMR (400MHz, CDCl3) δ=7.89-7.82 (m, 1H), 7.35-7.27 (m, 1H), 7.12 (t, J=7.4,
1H), 7.02-6.96 (m, 1H), 6.94-6.88 (m, 1H), 2.49 (s, 1H)13C NMR (101 MHz, CDCl3) δ=196.7,
161.9,155.5,131.9,130.5,130.0,124.6,120.1,117.2,77.3,76.7,26.4.
Embodiment 4
The synthesis of 1- benzyloxy -3- acetylbenzene with isolate and purify: by 3- benzyloxy-phenyl diazonium tetrafluoroborate
(1mmol, 1.0eq) and three fluomethane sulfinic acid sodium (310mg, 2mml, 2.0eq) are added in 20mL vial, acetonitrile 4mL.
Then dimethyl diketone (1mL, 20mmol, 20.0eq) is added in reaction flask with syringe, room temperature illumination reaction 12 is small
When.After reaction, it is quenched with water, then twice with 20mL methylene chloride extraction reaction solution, then by gained organic phase with anhydrous
Sodium sulphate is dried, and filtering, vacuum rotary steam obtains the crude product with a small amount of solvent.Then by crude product silica gel column chromatography
Separation, eluant, eluent petroleum ether: ethyl acetate=20:1 mixed liquor obtains final product: 1- benzyloxy -3- acetylbenzene is Huang
Color oily liquids, yield 51%.
1H NMR (400MHz, CDCl3) δ=8.00-7.89 (m, 1H), 7.39 (ddd, J=14.3,8.2,6.8,3H),
7.07-6.96 (m, 1H), 5.13 (s, 1H), 2.56 (s, 2H)13C NMR (101 MHz, CDCl3) δ=196.8,162.6,
136.1,130.5,129.8,128.7,128.2,127.4,114.5,77.3,76.7,70.1,26.3.
Embodiment 5
The synthesis of chloro- 4 acetylbenzene of 1- with isolate and purify: by 4- chlorphenyl diazonium tetrafluoroborate (1mmol, 1.0eq)
It is added in 20mL vial with three fluomethane sulfinic acid sodium (310mg, 2mml, 2.0eq), acetonitrile 4mL.It then will with syringe
Dimethyl diketone (1mL, 20mmol, 20.0eq) is added in reaction flask, and room temperature illumination reaction 12 hours.After reaction,
It is quenched with water, then twice with 20mL methylene chloride extraction reaction solution, then gained organic phase is dried with anhydrous sodium sulfate,
Filtering, vacuum rotary steam obtain the crude product with a small amount of solvent.Then by crude product silica gel column chromatography post separation, eluant, eluent stone
Oily ether: ethyl acetate=20: 1 mixed liquor obtains final product: the chloro- 4- acetylbenzene of 1- is yellow oily liquid, and yield is
65%.
1H NMR (400MHz, CDCl3) (s, the 2H) of δ=7.93-7.85 (m, 1H), 7.48-7.40 (m, 1H), 2.5913C
NMR (101 MHz, CDCl3) δ=196.8,139.6,135.4,129.7,128.9,77.3,76.7,26.5.
Embodiment 6
The synthesis of 1- methyl -4- acetylbenzene with isolate and purify: by 4- aminomethyl phenyl diazonium tetrafluoroborate (1mmol,
It 1.0eq) is added in 20mL vial with three fluomethane sulfinic acid sodium (310mg, 2mml, 2.0eq), acetonitrile 4mL.Then with note
Dimethyl diketone (1mL, 20mmol, 20.0eq) is added in reaction flask by emitter, and room temperature illumination reaction 12 hours.Reaction knot
Shu Hou is quenched with water, then twice with 20mL methylene chloride extraction reaction solution, then carries out gained organic phase with anhydrous sodium sulfate
It dries, filters, vacuum rotary steam, obtains the crude product with a small amount of solvent.Then by crude product silica gel column chromatography post separation, eluant, eluent
With petroleum ether: ethyl acetate=20: 1 mixed liquor obtains final product: 1- methyl -4- acetylbenzene is yellow oily liquid, is produced
Rate is 67%.
1H NMR (400MHz, CDCl3) δ=7.86 (d, J=8.2,1H), 7.27 (s, 0H), 7.25 (s, 0H), 2.58 (s,
1H), 2.41 (s, 2H)13C NMR (10l MHz, CDCl3) δ=197.9,143.9,134.7,129.2,128.4,77.3,
76.7,26.5,21.6.
Embodiment 7
The synthesis of 1- Ethyl formate -4- acetylbenzene with isolate and purify: by 4- methyl formate base phenyldiazonium tetrafluoro boric acid
Salt (1mmol, 1.0eq) and three fluomethane sulfinic acid sodium (310mg, 2mml, 2.0eq) are added in 20mL vial, acetonitrile
4mL.Then dimethyl diketone (1mL, 20mmol, 20.0eq) is added in reaction flask with syringe, room temperature illumination reaction
12 hours.After reaction, it is quenched with water, then twice with 20mL methylene chloride extraction reaction solution, then uses gained organic phase
Anhydrous sodium sulfate is dried, and filtering, vacuum rotary steam obtains the crude product with a small amount of solvent.Then by crude product layer of silica gel
Post separation is analysed, eluant, eluent petroleum ether: ethyl acetate=20: 1 mixed liquor obtains final product: 1- methyl formate -4- acetyl group
Benzene is yellow oily liquid, yield 43%.
1H NMR (400MHz, CDCl3) δ=8.13 (d, J=8.6,1H), 8.00 (d, J=8.6,1H), 4.41 (q, J=
7.1,1H), 2.64 (s, 1H), 1.41 (t, J=7.1,2H)13C NMR (101 MHz, CDCl3) δ=197.6,165.7,
140.2,134.3,129.8,128.2,77.3,76.7,61.4,26.9,14.3.
Embodiment 8
The synthesis of 1,3- bis--acetylbenzene with isolate and purify: by 3- acetylphenyl diazonium tetrafluoroborate (1mmol,
It 1.0eq) is added in 20mL vial with three fluomethane sulfinic acid sodium (310mg, 2mml, 2.0eq), acetonitrile 4mL.Then with note
Dimethyl diketone (1mL, 20mmol, 20.0eq) is added in reaction flask by emitter, and room temperature illumination reaction 12 hours.Reaction knot
Shu Hou is quenched with water, then twice with 20mL methylene chloride extraction reaction solution, then carries out gained organic phase with anhydrous sodium sulfate
It dries, filters, vacuum rotary steam, obtains the crude product with a small amount of solvent.Then by crude product silica gel column chromatography post separation, eluant, eluent
With petroleum ether: ethyl acetate=20: 1 mixed liquor, obtain final product: 1,3- acetyl group base benzene is yellow oily liquid, yield
It is 39%.
1H NMR (400MHz, CDCl3) δ=8.52 (d, J=1.6,1H), 8.15 (dd, J=7.7,1.7,2H), 7.58
(t, J=7.7,1H), 2.66 (s, 6H)13C NMR (101 MHz, CDCl3) δ=197.3,137.4,132.5,129.0,
128.0,77.3,76.7,26.7.
Embodiment 9
The synthesis of chloro- -5 acetylbenzene of 2- methoxyl group of 1- with isolate and purify: by 3- chloro-4-methoxy phenyldiazonium tetrafluoro boron
Hydrochlorate (1mmol, 1.0eq) and three fluomethane sulfinic acid sodium (310mg, 2mml, 2.0eq) are added in 20mL vial, acetonitrile
4mL.Then dimethyl diketone (1mL, 20mmol, 20.0eq) is added in reaction flask with syringe, room temperature illumination reaction
12 hours.After reaction, it is quenched with water, then twice with 20mL methylene chloride extraction reaction solution, then uses gained organic phase
Anhydrous sodium sulfate is dried, and filtering, vacuum rotary steam obtains the crude product with a small amount of solvent.Then by crude product layer of silica gel
Post separation is analysed, eluant, eluent petroleum ether: ethyl acetate=20: 1 mixed liquor obtains final product: the chloro- 2- methoxyl group -4- second of 1-
Acyl group benzene is yellow oily liquid, yield 53%.
1H NMR (400MHz, CDCl3) δ=7.98 (d, J=2.1,1H), 7.86 (dd, J=8.6,2.1,1H), 6.96
(d, J=8.6,1H), 3.96 (s, 3H), 2.55 (s, 3H)13C NMR (101 MHz, CDCl3) δ=195.71,158.7,
130.7,128.7,122.8,111.2,77.3,76.7,56.3,26.3.
Embodiment 10
The synthesis of chloro- 5 acetylpyridine of 2- with isolate and purify:
By 2- chloropyridine -5- base weight nitrogen tetrafluoroborate, (structural formula is shown in Table 1；1mmol, 1.0eq) and three fluomethanes Asia
Sodium sulfonate (155mg, 1mml, 1.0eq) is added in 20mL vial, acetonitrile 4mL.Then with syringe by diacetyl dimethyl two
Ketone (1mL, 20mmol, 20.0eq) is added in reaction flask, and room temperature illumination reaction 12 hours.After reaction, it is quenched with water,
Again twice with 20mL methylene chloride extraction reaction solution, gained organic phase is dried with anhydrous sodium sulfate then, is filtered, decompression
Revolving, obtains the crude product with a small amount of solvent.Then by crude product silica gel column chromatography post separation, eluant, eluent petroleum ether: acetic acid
Ethyl ester=20: 1 mixed liquor obtains final product: the chloro- 5 acetylpyridine white solid of 2-, yield 45%.
1H NMR (400MHz, CDCl3) δ=8.91 (d, J=2.0,1H), 8.18 (dd, J=8.3,2.4,1H), 7.43
(d, J=8.3,1H), 2.61 (s, 3H)
13C NMR (101 MHz, CDCl3) δ=195.3,155.7,150.2,138.1,131.2,124.5,26.7.
Examples 1 to 10 substrate, product and yield are shown in Table 1；
Table 1
From 1 data of table it is found that the yield to substd of diazonium is better than meta position；Further study show that aligning and being
When electron-donating group is, for example, alkyl, alkoxy, the yield of product is higher.In addition, The invention also achieves the acylations of pyridine.
Embodiment 11
It is compared with embodiment 2, difference essentially consists in, and is not added with the auxiliary agent, and concrete operations are as follows:
4- methoxyphenyl diazonium tetrafluoroborate (1mmol, 1.0eq) is added in 20mL vial, acetonitrile 4mL.So
Dimethyl diketone (1mL, 20mmol, 20.0eq) is added in reaction flask with syringe afterwards, room temperature illumination reaction 12h.It presses
Post-processing approach of the invention is handled, and obtaining products collection efficiency is 56%, and produces the by-product of de- diazonium, and content is
37%.72% of the product of the case not as good as embodiment 2；Comparative example explanation, in addition appropriate reaction auxiliary agent to progress aryl
Diazonium salt takes off acetyl group on nitrine, can obtain higher yield, in addition, additionally aiding the by-product for avoiding generating and only taking off diazonium.
Embodiment 12
It is compared with embodiment 2, difference essentially consists in, and the solvent used is specific as follows for water or DCM:
The synthesis of 1- methoxyl group -4- acetylbenzene with isolate and purify: by 4- methoxyphenyl diazonium tetrafluoroborate
(1mmol, 1.0eq) and three fluomethane sulfinic acid sodium (310mg, 2mml, 2.0eq) are added in 20mL vial, water or DCM
4mL.Then dimethyl diketone (1mL, 20mmol, 20.0eq) is added in reaction flask with syringe, room temperature illumination reaction
12 hours.
The study found that when water is solvent, products collection efficiency 64%；When DCM is solvent, product yield is less than 10%.And reality
Apply example 2 it was found that, acetonitrile is higher as solvent product yield.
Comparative example 1
It is compared with embodiment 2, difference essentially consists in, and does not react under light illumination, specific as follows:
The synthesis of 1- methoxyl group -4- acetylbenzene with isolate and purify: by 4- methoxyphenyl diazonium tetrafluoroborate
(1mmol, 1.0eq) and three fluomethane sulfinic acid sodium (310mg, 2mml, 2.0eq) are added in 20mL vial, acetonitrile 4mL.
Then dimethyl diketone (1mL, 20mmol, 20.0eq) is added in reaction flask with syringe, it is small that room temperature is protected from light 12
When.It is handled by post-processing approach of the invention, obtaining products collection efficiency is 8%.It compares with embodiment 2, does not carry out at illumination
Reason, the yield of product are decreased obviously.
Comparative example 2
It is compared with embodiment 10, difference is, using 2- pyridine diazonium tetrafluoroborate
The replacement 2- chloropyridine -5- base weight nitrogen tetrafluoroborate.The results show that not checking
It is generated to purpose product.
Comparative example 3
It is compared with embodiment 10, difference is, using 4- pyridine-nitrogen tetrafluoroborateDescribed in replacement
2- chloropyridine -5- base weight nitrogen tetrafluoroborate.The results show that not checking purpose product generation.
It is found by embodiment 10, comparative example 2 and comparative example 3, the meta position that diazonium groups are located at pyridine nitrogen is necessary.
Comparative example 4
It is compared with embodiment 2, difference is that dimethyl diketone adds equivalent (dimethyl diketone and 4- methoxyphenyl diazonium
The molar ratio of tetrafluoroborate) difference, it is specific as follows:
By 4- methoxyphenyl diazonium tetrafluoroborate (1mmol, 1.0eq) and three fluomethane sulfinic acid sodium (310mg,
2mml, 2.0eq) it is added in 20mL vial, acetonitrile 4mL.Then with syringe by dimethyl diketone (respectively 1.0eq, 2eq,
It 4eq) is added in reaction flask, is reacted 12 hours under illumination.The yield of product is less than 10%.
Comparative example 5
It is compared with embodiment 2, difference is using the methoxy-substituted substrate in ortho position (2- methoxyphenyl diazonium tetrafluoro boron
Hydrochlorate) replacement 4- methoxyphenyl diazonium tetrafluoroborate.The study found that the yield of product is less than 10%.The study found that diazonium
The yield that group is contained at the ortho position of group is remarkably decreased.
To sum up, it is de- that aryl can be completed in the diazonium salt and dione compounds of 2 structure of the formula 1 shown in and formula under light illumination
It diazonium and is acylated.Research also found, in formula 1, formula 2, the diazo yield to substd is better than meta position；Weight
The yield of substd is better than ortho position between nitrogen base.When diazo contraposition is electron donating group, especially alkoxy
When, yield is more excellent.
In addition, research also found that the yield for seriously affecting product in addition to H or F group is contained at the ortho position of diazonium groups.
The study found that the auxiliary agent that addition is described, helps to promote product yield, even avoids taking off in addition, can also reduce
Diazo and the by-product not being acylated.
Claims (10)
1. a kind of method that aryl diazonium salts take off acyl group in diazonium, which is characterized in that by the aryl with 2 structural formula of formula 1 or formula
Diazonium salt, the adjacent dicarbonyl compound with 3 structural formula of formula react under light illumination, obtain the aromaticacyl radical of 4 structural formula of formula
Product；
A-For anion；
R2~R8It is alone H, C1~C6Alkyl, C1~C6Alkoxy, phenoxy group, benzyloxy, nitro, halogen, cyano, ester
Base, trifluoromethyl, C1~C4Alkyl sulfenyl or allyl oxygen；And R7、R8In, at least one substituent group is H；R1For H or F；
The R9For alkyl, naphthenic base, Heterocyclylalkyl, phenyl or heterocyclic aryl；The alkyl, naphthenic base, Heterocyclylalkyl,
Phenyl or heterocyclic aryl allow containing C1~C4Alkyl, C1~C4Alkoxy, phenyl, halogen, one of ester group or a variety of
Substituent group.
2. the method as described in claim 1, which is characterized in that R1For hydrogen, methyl, methoxyl group, nitro, fluorine, bromine, chlorine or cyano；
Preferably H；
R2For hydrogen, methyl, methoxyl group, methyl mercapto, nitro, trifluoromethyl, benzyloxy, allyloxy, fluorine, bromine, chlorine atom or cyanogen
Base；
R3For hydrogen, methyl, methoxyl group, nitro, trifluoromethyl, fluorine, bromine, chlorine or cyano；
R4For bromine, chlorine or nitro.
3. the method as described in claim 1, which is characterized in that R5For hydrogen, methyl, methoxyl group, nitro, fluorine, bromine, chlorine or cyano；
R6For hydrogen, methyl, methoxyl group, methyl mercapto, nitro, trifluoromethyl, benzyloxy, allyloxy, fluorine, bromine, chlorine or cyano；
R7、R8It is H.
4. the method as described in claim 1, which is characterized in that R9For C1~C3Alkyl.
5. the method as described in claim 1, which is characterized in that the A- is tetrafluoroborate, sulfate radical, trifluoromethanesulfonic acid
Root, Cl-, CF3COO-, bromate.
6. the method as described in claim 1, which is characterized in that the reaction is also added with auxiliary agent, and the auxiliary agent is three
At least one of fluomethane sulfinic acid sodium, sodium acetate, sodium carbonate.
7. method as claimed in claim 6, which is characterized in that aryl diazonium salts, auxiliary agent molar ratio be 1: 0.5-2.
8. the method as described in claim 1, which is characterized in that aryl diazonium salts, adjacent dicarbonyl compound molar ratio be 1
: 10~50.
9. the method as described in claim 1, which is characterized in that the reaction solvent for use be water, ethyl acetate, acetonitrile, two
Chloromethanes, ether, at least one of n,N-Dimethylformamide；
It reacts in starting soln, 0.05~0.5mol/L of concentration of aryl diazonium salts.
10. the method as described in claim 1, which is characterized in that the reaction temperature is 0-50 ° DEG C；
The light is blue light；
The illumination reaction time is preferably 2~20 hours.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110615729A (en) * | 2019-10-15 | 2019-12-27 | 中南大学 | Method for selectively generating cis-olefin by deamination coupling of secondary carbon primary amine and aryl terminal alkyne |
| CN114163313A (en) * | 2021-12-14 | 2022-03-11 | 中山大学 | Method for selectively synthesizing EZ-stilbene by coupling aryl diazonium salt and cinnamic acid under catalysis of ruthenium |
| CN114539197A (en) * | 2022-03-03 | 2022-05-27 | 浙江工业大学 | Synthetic method of 3-fluoroalkyl substituted chromone derivative |
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2018
- 2018-09-30 CN CN201811165630.9A patent/CN109293491B/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110615729A (en) * | 2019-10-15 | 2019-12-27 | 中南大学 | Method for selectively generating cis-olefin by deamination coupling of secondary carbon primary amine and aryl terminal alkyne |
| CN114163313A (en) * | 2021-12-14 | 2022-03-11 | 中山大学 | Method for selectively synthesizing EZ-stilbene by coupling aryl diazonium salt and cinnamic acid under catalysis of ruthenium |
| CN114163313B (en) * | 2021-12-14 | 2023-11-03 | 中山大学 | Method for selectively synthesizing EZ-stilbene by coupling ruthenium-catalyzed aryl diazonium salt with cinnamic acid |
| CN114539197A (en) * | 2022-03-03 | 2022-05-27 | 浙江工业大学 | Synthetic method of 3-fluoroalkyl substituted chromone derivative |
| CN114539197B (en) * | 2022-03-03 | 2023-05-30 | 浙江工业大学 | Synthesis method of 3-fluoroalkyl substituted chromone derivative |
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