CN109293491B - Method for removing acyl from diazo salt of aryl - Google Patents

Method for removing acyl from diazo salt of aryl Download PDF

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CN109293491B
CN109293491B CN201811165630.9A CN201811165630A CN109293491B CN 109293491 B CN109293491 B CN 109293491B CN 201811165630 A CN201811165630 A CN 201811165630A CN 109293491 B CN109293491 B CN 109293491B
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唐真宇
杨宇明
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Central South University
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Abstract

The invention provides a method for removing diazo acyl from aryl diazonium salt and derivatives thereof, which comprises the step of carrying out illumination reaction on the aryl diazonium salt and the derivatives thereof and an o-dicarbonyl compound to obtain corresponding aryl acyl products, wherein the yield of the obtained products is high, metal participation is not required, and the process is simple.

Description

Method for removing acyl from diazo salt of aryl
Technical Field
The invention relates to a method for removing acyl from diazo of aryl diazonium salt; belongs to the field of organic chemical synthesis.
Background
Amine compounds widely exist in nature, a plurality of natural products contain amino compounds, aromatic amine compounds also exist in nature and in industry in large quantity, and due to the characteristics of low price, high activity and the like, the aromatic amine compounds are used as substrates in the field of organic synthesis in large quantity, aryl diazonium salts are simply synthesized from aromatic amines, and the diazo deacetylation reaction of the aryl diazonium salts has important significance.
Since acylation is a very common group, it is widely found in natural and synthetic compounds, and is also a common group in the structure of many drugs and dyes. The introduction of an acyl group into a compound is therefore an essential step in some synthetic processes. However, the aryl acylation has been mainly carried out by Friedel-Crafts acylation, in which an aromatic hydrocarbon is reacted with an acid chloride or acid anhydride under the action of a Lewis acid such as anhydrous AlCl3, and a hydrogen atom on the ring can be substituted with an acyl group. The Attilio Citterio team reported 1982 that arylacetylation was carried out with aryldiazonium salts and butanedione as raw materials in dimethyl sulfoxide as a solvent in the presence of copper (Attilio Citterio, Marco Servalle, Elena Viscara Tetrahedron Letters, 23(17), 1831-18-34). The Carlos Roque d.cordia team reported in 2009 the use of n-butyl vinyl ether and aryl diazonium salts as starting materials, acetonitrile as solvent, sodium acetate as base, followed by palladium catalyzed reaction by acidification with hydrochloric acid to achieve aryl acetylation (Angelo h.l. machado, marico a.de Sousa, Carlos Roque d.cordia Tetrahedron Letters, 50(11), 1222-.
So far, the reaction of using arylamine as a substrate to realize acyl functionalization by illumination has not been reported, and needs to be completed in the field of organic reaction.
Disclosure of Invention
Aiming at the technical defects of the prior art that aryl diazonium salt compounds are subjected to diazotization to generate acylated aryl compounds, the invention aims to provide an aryl diazonium salt diazotization and acylation method, which aims to carry out acylation on aryl groups mildly by using aryl diazonium salts and ortho-dicarbonyl compounds as substrates through illumination.
A method for removing diazo and acyl from aryl diazonium salt comprises the steps of reacting aryl diazonium salt with a structural formula 1 or 2 with an o-dicarbonyl compound with a structural formula 3 under light irradiation to obtain an aromatic acylation product with a structural formula 4;
Figure BDA0001819634030000021
a-is an anion;
R2～R8is alone H, C1～C6Alkyl of (C)1～C6Alkoxy, phenoxy, benzyloxy, nitro, halogen, cyano, ester, trifluoromethyl, C1～C4Alkylthio or allyloxy of (a); and R is7、R8Wherein at least one substituent is H; r1Is H or F;
r9 is alkyl, cycloalkyl, heterocycloalkyl, phenyl or heterocycloaryl; said alkyl, cycloalkyl, heterocycloalkyl, phenyl or heterocycloaryl optionally containing C1～C4Alkyl of (C)1～C4One or more of alkoxy, phenyl, halogen and ester group.
In the invention, the diazo group can be removed by using the aromatic diazonium salt with the structure of the formula 1 or the formula 2 and the o-dicarbonyl compound under the irradiation of light, and the acyl group is connected at the position of the removed diazo group. The method has simple operation, short flow and high product yield; furthermore, the process of the present invention has an incomparable position selectivity compared to existing processes (e.g.Friedel-Crafts acylation).
The aryl diazonium salts with the structures of formula 1 and formula 2 according to the present invention have been found to be the key to ensure successful preparation. When the aryl diazonium salt is a compound of formula 1, at least one group ortho to the diazonium is H, which facilitates successful acylation. As another example, when the aryl diazonium salt is a compound of formula 2, the acylation may be unexpectedly achieved with the diazonium group meta to the pyridine ring; diazo groups are either ortho or para to the pyridine ring and are difficult to acylate successfully.
Through further research, the invention discovers that the yield of the target product is further improved by controlling the substituent groups and the substituent positions of the aryl diazo salt.
Preferably, R1Is H. Found that R1Being hydrogen, the yield of the product can be improved.
Preferably, R2Hydrogen, methyl, methoxy, methylthio, nitro, trifluoromethyl, benzyloxy, allyloxy, fluorine, bromine, chlorine atom or cyano.
Preferably, R3Is hydrogen, methyl, methoxy, nitro, trifluoromethyl, fluorine, bromine, chlorine or cyano;
preferably, R4Is bromine, chlorine or nitreAnd (4) a base.
Further preferably, R1、R2、R4Is H, R3When the electron donating group is preferably an alkoxy group, particularly a methoxy group, for the electron donating group, the yield of the product is higher.
The method has good diazo removal and acylation effects on the benzene diazonium salt with the structure of the formula 1; the research shows that the method can also be applied to the pyridine ring which is difficult to be acylated in the prior art.
The present inventors have found that, in addition to controlling the diazo group to be in the meta position on the pyridine ring, the absence of a substituent in at least one ortho position of the diazo group is also one of the keys to ensure the production, that is, R in the formula 2 is required7、R8At least one substituent in (a) is H; preferably R7、R8Are all H.
Studies have also found that control of other substituents on the pyridine ring also contributes to further increases in yield.
Preferably, R5Is hydrogen, methyl, methoxy, nitro, fluorine, bromine, chlorine or cyano; preferably H.
Preferably, R6Is hydrogen, methyl, methoxy, methylthio, nitro, trifluoromethyl, benzyloxy, allyloxy, fluoro, bromo, chloro or cyano.
A-is tetrafluoroborate radical and sulfate radical (HSO)4-), triflate, Cl-, CF3COO-or bromate.
The aryl diazonium salt can be obtained by diazotization reaction of corresponding aromatic amine.
In the invention, R is9Is C1～C6Alkyl, cyclopentyl, cyclohexyl, oxygen or sulfur hybridized cyclopentyl or cyclohexyl, phenyl, five-membered or six-membered heterocyclic aryl. The alkyl, cyclopentyl, cyclohexyl, heterocyclic cyclopentyl or cyclohexyl and phenyl groups can contain C1～C4Alkyl of (C)1～C4One or more of alkoxy, phenyl, halogen and ester group.
Further preferred isSaid R is9Is C1～C3Alkyl groups of (a); for example methyl, ethyl or propyl.
R9The photocatalytic intensity of the group (b) is different from that of the group (c), and light having an appropriate wavelength can be adjusted according to the difference. For example, when R is9When the methyl is adopted, the diazotization and acetylation of the diazonium salt can be well promoted under visible light or blue light.
Preferably, the reaction is further added with an auxiliary agent, and the auxiliary agent is at least one of sodium trifluoromethanesulfonate, sodium acetate and sodium carbonate. It was found that the addition of certain auxiliaries helps to further increase the product yield and, in addition, helps to avoid the by-products which are only de-diazotized and not acylated.
Preferably, the molar ratio of the aryl diazonium salt to the auxiliary agent is 1: 0.5-2. At this preferred molar ratio, it contributes to further facilitating the use of light, thereby contributing to further increasing the yield of the acylation product and reducing the by-product of de-diazotization. The addition of the auxiliary agent at an equivalent of more than 2 is not favorable for light utilization.
The research of the invention finds that the control of parameters such as the adding proportion of the aryl diazonium salt and the ortho-dicarbonyl compound, the reaction solvent and the like is helpful for further improving the yield of the prepared product.
Preferably, the molar ratio of the aryl diazonium salt to the ortho-dicarbonyl compound is 1: 10-50. The research finds that the control in the preferable range is beneficial to the utilization of light and is helpful for further improving the yield of the product. Yields of less than 10 equivalents of product are low.
More preferably, the molar ratio of the aryl diazonium salt to the ortho-dicarbonyl compound is 1: 10-20.
The solvent used in the reaction is at least one of water, ethyl acetate, acetonitrile, dichloromethane, diethyl ether and N, N-dimethylformamide; further preferred is acetonitrile. The research of the invention finds that the adoption of the preferred solvent is helpful for further improving the yield of the product.
In the reaction starting solution, the concentration of the aryl diazonium salt is 0.05-0.5 mol/L.
The reaction temperature is 0-50 ℃; further preferably room temperature (for example, 15 to 35 ℃).
The light is preferably blue light, for example 36w blue light.
The illumination reaction time is preferably 2 to 20 hours.
After the reaction is finished, extracting by a hydrophobic solvent, concentrating and extracting to obtain an organic phase, and purifying by chromatography to obtain the compound.
According to the technical scheme, after the reaction is finished, extracting reaction mixed liquid by dichloromethane, and carrying out reduced pressure rotary evaporation to obtain a crude product; and separating and purifying the crude product by a chromatographic column to obtain the final product. The eluent used by the chromatographic column is petroleum ether, the product with larger polarity is mixed eluent of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 50: 1-1: 1.
The beneficial technology is as follows:
1. the technical scheme of the invention firstly carries out the diazotization and the acetyl-adding of the aryl diazonium salt, thus filling the defects of the prior art;
2. the technical scheme of the invention adopts a one-pot reaction, has mild process conditions, short flow, simple steps and wide substrate applicability, and meets the requirements of industrial production;
3. the technical scheme of the invention produces the corresponding acetylated substrate from the aryl diazonium salt and the derivative substrate thereof, and has high yield. (ii) a The research shows that the yield of the product can reach 72%.
Drawings
FIG. 1 shows the product obtained in example 11H NMR spectrum.
FIG. 2 shows the product obtained in example 113CNMR spectrogram.
FIG. 3 shows the product obtained in example 41H NMR spectrum.
FIG. 4 shows the product obtained in example 413C NMR spectrum.
FIG. 5 shows the product obtained in example 61H NMR spectrum.
FIG. 6 shows the product obtained in example 613C NMR spectrum.
Detailed Description
The following examples are intended to illustrate the present invention, but not to further limit the scope of the claims.
The following examples and comparative examples, unless otherwise stated, all of the illumination is referred to as blue light; for example, there is a 36W blue light irradiation reaction.
Example 1
Synthesizing, separating and purifying 1-bromo-4-acetylbenzene: 4-bromophenyl diazotetrafluoroborate (formula shown in Table 1; 1mmol, 1.0eq) and sodium trifluoromethanesulfonate (310mg, 2 mmol, 2.0eq) were charged in a 20mL glass bottle with 4mL acetonitrile. Dimethyl diketone (1mL, 20mmol, 20.0eq) was then added to the reaction flask with a syringe and the reaction was left to light for 12 hours at room temperature. After the reaction is finished, quenching the reaction solution by water, extracting the reaction solution twice by using 20mL of dichloromethane, drying the obtained organic phase by using anhydrous sodium sulfate, filtering, and carrying out reduced pressure rotary evaporation to obtain a crude product with a small amount of solvent. The crude product is then separated on a silica gel column, and the eluent is petroleum ether: ethyl acetate 20: 1 to obtain the final product: 1-bromo-4-acetylbenzene was a yellow oily liquid in 68% yield.
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.
Example 2
Synthesizing, separating and purifying 1-methoxy-4-acetylbenzene: 4-Methoxyphenyldiazotetrafluoroborate (1mmol, 1.0eq) and sodium trifluoromethanesulfonate (310mg, 2mml, 2.0eq) were added to a 20mL glass bottle with 4mL acetonitrile. Dimethyl diketone (1mL, 20mmol, 20.0eq) was then added to the reaction flask with a syringe and the reaction was left to light for 12 hours at room temperature. After the reaction is finished, quenching the reaction solution by water, extracting the reaction solution twice by using 20mL of dichloromethane, drying the obtained organic phase by using anhydrous sodium sulfate, filtering, and carrying out reduced pressure rotary evaporation to obtain a crude product with a small amount of solvent. Then separating the crude product by a silica gel chromatographic column, and eluting by a mixed solution of petroleum ether and ethyl acetate of 20: 1 to obtain a final product: the 1-methoxy-4-acetylbenzene was a yellow oily liquid in 72% yield.
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.
Example 3
Synthesizing, separating and purifying 1-phenoxy-4-acetylbenzene: 4-Phenoxyphenyldiazotetrafluoroborate (1mmol, 1.0eq) and sodium trifluoromethanesulfonate (310mg, 2mml, 2.0eq) were added to a 20mL glass bottle with 4mL acetonitrile. Dimethyl diketone (1mL, 20mmol, 20.0eq) was then added to the reaction flask with a syringe and the reaction was left to light for 12 hours at room temperature. After the reaction is finished, the reaction solution is extracted twice by 20mL dichloromethane, and then the obtained organic phase is dried by anhydrous sodium sulfate, filtered and decompressed and evaporated to obtain a crude product with a small amount of solvent. The crude product is then separated on a silica gel column, and the eluent is petroleum ether: ethyl acetate 20: 1 to obtain the final product: 1-phenoxy-4-acetylbenzene was a yellow oily liquid with a yield of 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.
Example 4
Synthesis, separation and purification of 1-benzyloxy-3-acetylbenzene: 3-Benzyloxyphenyldiazotetrafluoroborate (1mmol, 1.0eq) and sodium trifluoromethanesulfonate (310mg, 2mml, 2.0eq) were added to a 20mL glass bottle with 4mL acetonitrile. Dimethyl diketone (1mL, 20mmol, 20.0eq) was then added to the reaction flask with a syringe and the reaction was left to light for 12 hours at room temperature. After the reaction is finished, quenching the reaction solution by water, extracting the reaction solution twice by using 20mL of dichloromethane, drying the obtained organic phase by using anhydrous sodium sulfate, filtering, and carrying out reduced pressure rotary evaporation to obtain a crude product with a small amount of solvent. The crude product is then separated on a silica gel column, and the eluent is petroleum ether: ethyl acetate ═ 20: 1 to obtain a final product: 1-benzyloxy-3-acetylbenzene was a yellow oily liquid in 51% yield.
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.
Example 5
Synthesis, separation and purification of 1-chloro-4-acetylbenzene: 4-chlorophenyl diazotetrafluoroborate (1mmol, 1.0eq) and sodium trifluoromethanesulfonate (310mg, 2mml, 2.0eq) were added to a 20mL glass bottle with 4mL acetonitrile. Dimethyl diketone (1mL, 20mmol, 20.0eq) was then added to the reaction flask with a syringe and the reaction was left to light for 12 hours at room temperature. After the reaction is finished, quenching the reaction solution by water, extracting the reaction solution twice by using 20mL of dichloromethane, drying the obtained organic phase by using anhydrous sodium sulfate, filtering, and carrying out reduced pressure rotary evaporation to obtain a crude product with a small amount of solvent. Then separating the crude product by a silica gel chromatographic column, and eluting by a mixed solution of petroleum ether and ethyl acetate of 20: 1 to obtain a final product: 1-chloro-4-acetylbenzene was a yellow oily liquid with a yield of 65%.
1H NMR(400MHz，CDCl3)δ＝7.93-7.85(m，1H)，7.48-7.40(m，1H)，2.59(s，2H).13CNMR(101 MHz，CDCl3)δ＝196.8，139.6，135.4，129.7，128.9，77.3，76.7，26.5.
Example 6
Synthesis, separation and purification of 1-methyl-4-acetylbenzene: 4-Methylphenyldiazotetrafluoroborate (1mmol, 1.0eq) and sodium trifluoromethanesulfonate (310mg, 2mml, 2.0eq) were added to a 20mL glass bottle with 4mL acetonitrile. Dimethyl diketone (1mL, 20mmol, 20.0eq) was then added to the reaction flask with a syringe and the reaction was left to light for 12 hours at room temperature. After the reaction is finished, quenching the reaction solution by water, extracting the reaction solution twice by using 20mL of dichloromethane, drying the obtained organic phase by using anhydrous sodium sulfate, filtering, and carrying out reduced pressure rotary evaporation to obtain a crude product with a small amount of solvent. Then separating the crude product by a silica gel chromatographic column, and eluting by a mixed solution of petroleum ether and ethyl acetate of 20: 1 to obtain a final product: 1-methyl-4-acetylbenzene was a yellow oily liquid in 67% yield.
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.
Example 7
Synthesizing, separating and purifying 1-ethyl formate-4-acetylbenzene: 4-Methoxycarboxylated phenyldiazotetrafluoroborate (1mmol, 1.0eq) and sodium trifluoromethanesulfonate (310mg, 2mml, 2.0eq) were added to a 20mL glass bottle with 4mL acetonitrile. Dimethyl diketone (1mL, 20mmol, 20.0eq) was then added to the reaction flask with a syringe and the reaction was left to light for 12 hours at room temperature. After the reaction is finished, quenching the reaction solution by water, extracting the reaction solution twice by using 20mL of dichloromethane, drying the obtained organic phase by using anhydrous sodium sulfate, filtering, and carrying out reduced pressure rotary evaporation to obtain a crude product with a small amount of solvent. Then separating the crude product by a silica gel chromatographic column, and eluting by a mixed solution of petroleum ether and ethyl acetate of 20: 1 to obtain a final product: methyl 1-carboxylate-4-acetylbenzene was a yellow oily liquid in 43% yield.
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.
Example 8
Synthesis, separation and purification of 1, 3-di-acetylbenzene: 3-Acetylphenyl diazotetrafluoroborate (1mmol, 1.0eq) and sodium trifluoromethanesulfonate (310mg, 2mml, 2.0eq) were added to a 20mL glass bottle with 4mL acetonitrile. Dimethyl diketone (1mL, 20mmol, 20.0eq) was then added to the reaction flask with a syringe and the reaction was left to light for 12 hours at room temperature. After the reaction is finished, quenching the reaction solution by water, extracting the reaction solution twice by using 20mL of dichloromethane, drying the obtained organic phase by using anhydrous sodium sulfate, filtering, and carrying out reduced pressure rotary evaporation to obtain a crude product with a small amount of solvent. Then separating the crude product by a silica gel chromatographic column, and eluting by a mixed solution of petroleum ether and ethyl acetate of 20: 1 to obtain a final product: the 1, 3-acetylbenzene was a yellow oily liquid with a yield of 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.
Example 9
Synthesis, separation and purification of 1-chloro-2-methoxy-5-acetylbenzene: 3-chloro-4-methoxyphenyl diazotetrafluoroborate (1mmol, 1.0eq) and sodium trifluoromethanesulfonate (310mg, 2mml, 2.0eq) were added to a 20mL glass bottle with 4mL acetonitrile. Dimethyl diketone (1mL, 20mmol, 20.0eq) was then added to the reaction flask with a syringe and the reaction was left to light for 12 hours at room temperature. After the reaction is finished, quenching the reaction solution by water, extracting the reaction solution twice by using 20mL of dichloromethane, drying the obtained organic phase by using anhydrous sodium sulfate, filtering, and carrying out reduced pressure rotary evaporation to obtain a crude product with a small amount of solvent. Then separating the crude product by a silica gel chromatographic column, and eluting by a mixed solution of petroleum ether and ethyl acetate of 20: 1 to obtain a final product: 1-chloro-2-methoxy-4-acetylbenzene was a yellow oily liquid in 53% yield.
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.
Example 10
2-chloro-5 acetylpyridine synthesis, separation and purification:
2-chloropyridine-5-basic diazotetrafluoroborate (formula shown in Table 1; 1mmol, 1.0eq) and sodium trifluoromethanesulfonate (155mg, 1mmol, 1.0eq) were charged in a 20mL glass bottle with 4mL acetonitrile. Butanedione dimethyldione (1mL, 20mmol, 20.0eq) was then added to the reaction flask by syringe and the reaction was left to light for 12h at room temperature. After the reaction is finished, quenching the reaction solution by water, extracting the reaction solution twice by using 20mL of dichloromethane, drying the obtained organic phase by using anhydrous sodium sulfate, filtering, and carrying out reduced pressure rotary evaporation to obtain a crude product with a small amount of solvent. Then separating the crude product by a silica gel chromatographic column, and eluting by a mixed solution of petroleum ether and ethyl acetate of 20: 1 to obtain a final product: 2-chloro-5 acetylpyridine as a white solid in 45% yield.
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.
The substrates, products and yields of examples 1-10 are shown in Table 1;
TABLE 1
Figure BDA0001819634030000091
Figure BDA0001819634030000101
As can be seen from the data in Table 1, the yield of the diazo having a substituent at the para-position is superior to that at the meta-position; further, it was found that when the electron donating group is at the para position, for example, an alkyl group or an alkoxy group, the yield of the product is higher. In addition, the invention also realizes the acylation of pyridine.
Example 11
Compared with the example 2, the difference is that the auxiliary agent is not added, and the specific operation is as follows:
4-Methoxyphenyldiazotetrafluoroborate (1mmol, 1.0eq) was added to a 20mL glass vial with 4mL acetonitrile. Dimethyldione (1mL, 20mmol, 20.0eq) was then added to the reaction flask via syringe and the reaction was allowed to light for 12h at room temperature. Working up according to the working-up method of the invention gives a product yield of 56% and a de-diazotised by-product content of 37% is produced. The product of this case is less than 72% of example 2; this comparative example illustrates that higher yields can be achieved when acetyl groups are added to the aryldiazonium salt to effect the deamidation, and in addition, helps to avoid the production of by-products that are only diazotized.
Example 12
Compared with the example 2, the difference is mainly that the adopted solvent is water or DCM, which is specifically as follows:
synthesizing, separating and purifying 1-methoxy-4-acetylbenzene: 4-Methoxyphenyldiazotetrafluoroborate (1mmol, 1.0eq) and sodium trifluoromethanesulfonate (310mg, 2mml, 2.0eq) were added to a 20mL glass bottle, water or DCM4 mL. Dimethyl diketone (1mL, 20mmol, 20.0eq) was then added to the reaction flask with a syringe and the reaction was left to light for 12 hours at room temperature.
The research shows that when water is used as a solvent, the yield of the product is 64 percent; when DCM is used as the solvent, the yield of the product is less than 10%. The product yield was higher with acetonitrile as solvent, as compared to example 2.
Comparative example 1
Compared with the example 2, the difference is mainly that the reaction is not carried out under the illumination, and the specific difference is as follows:
synthesizing, separating and purifying 1-methoxy-4-acetylbenzene: 4-Methoxyphenyldiazotetrafluoroborate (1mmol, 1.0eq) and sodium trifluoromethanesulfonate (310mg, 2mml, 2.0eq) were added to a 20mL glass bottle with 4mL acetonitrile. Dimethyl diketone (1mL, 20mmol, 20.0eq) was then added to the reaction flask with a syringe and reacted for 12 hours at room temperature with the exclusion of light. Work-up according to the working-up method of the invention gives a product yield of 8%. Compared with the example 2, the yield of the product is obviously reduced without the light treatment.
Comparative example 2
Compared with example 10, the difference is that 2-pyridine diazo tetrafluoroborate is adopted
Figure BDA0001819634030000111
Replacing said 2-chloropyridine-5-basic diazotetrafluoroborate. The results showed that the formation of the desired product was not detected.
Comparative example 3
Compared with example 10, with the difference that 4-pyridine-nitrogen tetrafluoroborate is used
Figure BDA0001819634030000112
Replacing said 2-chloropyridine-5-basic diazotetrafluoroborate. The results showed that the formation of the desired product was not detected.
It was found by example 10, comparative example 2 and comparative example 3 that it is necessary for the diazo group to be in the meta position to the pyridine nitrogen.
Comparative example 4
Compared with the example 2, the difference is that the addition equivalent of the dimethyl diketone (the molar ratio of the dimethyl diketone to the 4-methoxyphenyl diazo tetrafluoroborate) is as follows:
4-Methoxyphenyldiazotetrafluoroborate (1mmol, 1.0eq) and sodium trifluoromethanesulfonate (310mg, 2mml, 2.0eq) were added to a 20mL glass bottle with 4mL acetonitrile. Dimethyl diketone (1.0 eq, 2eq, 4eq, respectively) was then added to the reaction flask with a syringe and reacted for 12 hours under light. The yield of the product is less than 10%.
Comparative example 5
Compared with example 2, the difference is that 4-methoxyphenyl diazotetrafluoroborate is replaced by an ortho methoxy-substituted substrate (2-methoxyphenyl diazotetrafluoroborate). The product yield was found to be less than 10%. The research shows that the yield of the diazo group containing group at the ortho position is obviously reduced.
In summary, aryl de-diazotization and acylation can be accomplished by the diazonium salts and diketone compounds of the structures shown in formulas 1 and 2 in the presence of light. Research also finds that in formula 1 and formula 2, the yield of the substituent at the para position of the diazo group is better than that at the meta position; the meta position of the diazo group has a substituent with a better yield than the ortho position. When the para position of the diazo group is an electron donating substituent, particularly an alkoxy group, the yield is more excellent.
In addition, studies have found that the ortho position of the diazonium group contains, in addition to the H or F group, a significant effect on the yield of the product.
It has been found that the addition of said auxiliary agents contributes to an increase in the product yield and, in addition, reduces or even avoids the elimination of diazo groups without acylation of the by-products.

Claims (9)

1. The method for removing acyl from diazo aryl diazonium salt is characterized in that aryl diazonium salt with a structural formula 1 or 2 and an o-dicarbonyl compound with a structural formula 3 react under the irradiation of light to obtain an aromatic acylation product with a structural formula 4; the reaction is also added with an auxiliary agent, and the auxiliary agent is at least one of sodium trifluoromethanesulfonate, sodium acetate and sodium carbonate; the solvent used in the reaction is at least one of water and acetonitrile; the molar ratio of the aryl diazonium salt to the ortho-dicarbonyl compound is 1: 10-50;
Figure FDA0002412029830000011
A-is an anion;
R1is H or F;
R2～R8is alone H, C1～C6Alkyl of (C)1～C6Alkoxy, phenoxy, benzyloxy, nitro, halogen, cyano, ester, trifluoromethyl, C1～C4Alkylthio or allyloxy of (a); and R is7、R8Wherein at least one substituent is H;
said R9Is alkyl, cycloalkyl, heterocycloalkyl, phenyl or heterocycloaryl; said alkyl, cycloalkyl, heterocycloalkyl, phenyl or heterocycloaryl optionally containing C1～C4Alkyl of (C)1～C4One or more of alkoxy, phenyl, halogen and ester group.
2. The method of claim 1, wherein R is1Is H;
R2is hydrogen, methyl, methoxy, methylthio, nitro, trifluoromethyl, benzyloxy, allyloxy, fluorine, bromine, chlorine atom or cyano;
R3is hydrogen, methyl, methoxy, nitro, trifluoromethyl, fluorine, bromine, chlorine or cyano;
R4is bromine, chlorine or nitro.
3. The method of claim 1, wherein R is5Is hydrogen, methyl, methoxy, nitro, fluorine, bromine, chlorine or cyano;
R6is hydrogen, methyl, methoxy, methylthio, nitro, trifluoromethyl, benzyloxy, allyloxy, fluoro, bromo, chloro or cyano;
R7、R8are all H.
4. The method of claim 1, wherein R is9Is C1～C3Alkyl group of (1).
5. The method of claim 1 wherein a-is tetrafluoroborate, sulfate, triflate, Cl ", CF3COO-, bromate.
6. The process of claim 1 wherein the molar ratio of aryl diazonium salt to adjuvant is 1: 0.5-2.
7. The method of claim 1, wherein the concentration of the aryl diazonium salt in the reaction starting solution is 0.05 to 0.5 mol/L.
8. The method of claim 1, wherein the reaction temperature is 0-50 °;
the light is blue light.
9. The method of claim 8, wherein the light reaction time is 2 to 20 hours.
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