CN111606791B - Synthetic method of aromatic benzyl ketone - Google Patents
Synthetic method of aromatic benzyl ketone Download PDFInfo
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- C07C45/32—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen
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Abstract
The invention discloses a synthetic method of aromatic benzyl ketone, which comprises the following steps: oxidizing an aromatic benzyl compound shown in a formula (I) under the action of a catalytic system by taking oxygen and/or air as an oxidant to prepare aromatic benzyl ketone shown in a formula (II); the catalytic system is a combination of ferric ions, nitrate radicals and N-hydroxyimide derivativesThe iron nitrate fertilizer is used and does not contain heavy metal ions harmful to human bodies, wherein the molar ratio of ferric ions to nitrate radicals is 1:0.5-5, the molar ratio of ferric ions to the N-hydroxyimide derivative is 0.01-0.1. The method has the advantages of wide substrate applicability, high atom utilization rate, avoidance of the use of harmful heavy metals such as copper, cobalt and the like, and high efficiency, economy and environmental protection. Ar-CH 2 ‑R (I) Ar‑CO‑R (II)。
Description
The technical field is as follows:
the invention relates to a method for generating aromatic benzyl ketone by oxidizing benzylic methylene of aromatic benzyl compound.
(II) background technology:
the reaction of oxidizing the benzyl position of methylene compound to ketone is an important organic reaction and has important application in pharmaceutical, cosmetic, dye synthesis and other related industries. Among the many oxidants available for this oxidation reaction, oxygen is certainly the most inexpensive and readily available oxidant.
The oxidation of methylene or methyl compounds in oxygen or air is known as autoxidation. CN101759542B and CN101759540B use iron, manganese or cobalt and ligand, ethylbenzene or propyl benzene autoxidation gets corresponding ketone, the metal catalyst used in the reaction is mainly manganese or cobalt, it is apt to cause pollution, and need to use the bionical ligand of large molecular weight and can't be reclaimed and applied mechanically, the reaction system is complicated, the atom economy is low. The autoxidation reaction of the p-nitrotoluene disclosed in CN108238946A does not use a heavy metal catalyst, but the reaction needs to be carried out under a higher pressure, and more than 5 equivalents of alkali are used, so that waste is caused and a certain potential safety hazard is caused. CN102656143B uses oxygen to directly and selectively oxidize alkane, the reaction temperature is higher, special equipment (bubble column type reactor) is needed, and the substrate is mainly saturated aliphatic hydrocarbon such as cyclohexane. CN107176899A uses ferric nitrate as catalyst and TEMPO as photoinitiator, and oxidizes alcohol or aldehyde under the catalysis of inorganic halide to obtain acid, the substrate is mostly aliphatic alcohol or aldehyde, and alcohol or aldehyde itself is hydrocarbon oxidation product, which is not easy to obtain as hydrocarbon. Furthermore, the use of TEMPO/halides also increases the complexity of the post-treatment and the polluting nature of the waste water.
N-hydroxyimide derivatives (NHIs) are a class of efficient free radical initiators which, in combination with metal catalysts, catalyze benzylic autoxidation. CN1814615A discloses CrO 3 The allylic methylene autoxidation reaction of a carrier/N-hydroxyphthalimide (NHPI)/dichloromethane system uses a heavy metal cadmium which is easy to cause pollution as a cocatalyst. CN104109083B discloses a method for preparing adipic acid by cyclohexane autoxidation under the catalysis of NHIs, which uses cobalt salt and manganese salt which are easy to cause pollution to react to obtain adipic acid which is a thorough oxidation product. CN106423170A uses cobalt/graphene composite and NHPI to co-catalyze ethylbenzene autoxidation to acetophenone, although the amount of cobalt used in the reaction is small and the oxygen pressure is mild, the preparation process of the catalyst cobalt/graphene composite is complicated. CN107628947A uses NHPI/cobalt acetate/oxygen catalytic system in the synthesis of pemetrexed disodium key intermediate, and directly oxidizes benzyl methyl into carboxyl.
In summary, in the autoxidation reaction of the aromatic benzyl compound, metals such as cobalt, cadmium, manganese and the like are usually used as catalysts, and after the reaction is finished, the color of the solution is dark, and heavy metal ions harmful to human bodies are easily complexed with aromatic rings in the product, so that the application of the aromatic benzyl compound in the pharmaceutical and food industries is limited. Therefore, the development of an environment-friendly, high-selectivity and high-efficiency reaction from the perspective of green chemistry has great significance for reducing the cost and expanding the application range of the reaction.
(III) the invention content:
the technical problem to be solved by the invention is to provide a method for synthesizing aromatic benzyl ketone by oxidizing aromatic benzyl compound, which has the characteristics of wide applicability of substrate, high atom utilization rate, avoidance of use of harmful heavy metals such as copper, cobalt and the like, high efficiency, economy and environmental protection.
In order to solve the technical problems, the invention adopts the following technical scheme:
a method of synthesizing an aromatic benzyl ketone, the method comprising: oxidizing an aromatic benzyl compound shown in a formula (I) under the action of a catalytic system by taking oxygen and/or air as an oxidant to prepare aromatic benzyl ketone shown in a formula (II); the catalyst system is formed by combining ferric ions, nitrate radicals and N-hydroxyimide derivatives (NHIs) and does not contain heavy metal ions harmful to human bodies, wherein the molar ratio of the ferric ions to the nitrate radicals is 1:0.5-5, the molar ratio of ferric ions to the N-hydroxyimide derivative is 0.01-0.1;
Ar-CH 2 -R(I) Ar-CO-R(II)
wherein Ar is an aromatic ring or a substituted aromatic ring containing no heteroatom, the substituent on the substituted aromatic ring is one or more, and each substituent is independently selected from methyl, C5-C12 aryl, amino, alkyl substituted amino, carboxyl, alkoxy, halogen, cyano, acyloxy, amido or nitro;
r is selected from C1-C12 alkyl or C5-C12 aryl;
or-CH 2 -R forms with the adjacent group on the Ar ring a 5-7 membered ring a containing no or no heteroatoms, said 5-7 membered ring a being unsubstituted or substituted by at least one of the following groups: methyl, C5-C12 aryl, amino, alkyl substituted amino, carboxyl, alkoxy, halogen, cyano, acyloxy, amido and nitro; optionally, the substituent on the 5-7 membered ring a may further form a 5-7 membered aromatic ring B with the adjacent group on the 5-7 membered ring a, the aromatic ring B being unsubstituted or substituted with at least one of the following groups: methyl, C5-C12 aryl, amino, alkyl substituted amino, carboxyl, alkoxy, halogen, cyano, acyloxy, acylamino and nitro; and, when the 5-7 membered ring A is contained in the formula (I), whether or not the 5-7 membered aromatic ring B is contained, at least one of the alpha positions of the 5-7 membered ring A is-CH 2 -for reaction to form a carbonyl group;
the C5-C12 aryl is unsubstituted or substituted by substituent groups, and the substituent groups are selected from amino, substituted amino, carboxyl, alkoxy, halogen, cyano, acyloxy, acylamino or nitro.
Preferably, ar is a benzene ring, a naphthalene ring, an anthracene ring or a phenanthrene ring.
Preferably, the C5-C12 aryl group may be an unsubstituted or substituted phenyl group.
Preferably, the 5-to 7-membered aromatic ring B is a benzene ring.
Preferably, the heteroatom in ring a is O, N or S.
In the present invention, the alkoxy group may be a C1-C4 alkoxy group such as methoxy, ethoxy, propoxy, butoxy, etc., or a phenoxy group. The acyloxy group may be a C1-C4 acyloxy group such as formyloxy, acetyloxy, propionyloxy, butyryloxy, benzoyloxy, etc. The amide group may be a C1-C4 amide group, such as a carboxamide group, an acetamido group, or the like. The alkyl-substituted amino group may be an N, N- (C1-C4 alkyl) amino group, such as an N, N-dimethylamino group, or the like.
In a specific embodiment of the present invention, the aromatic benzyl compound having a 5-to 7-membered ring A includes fluorene, tetrahydronaphthalene, indane, xanthene and isochroman.
In the invention, the catalyst system is the combination of ferric ions, nitrate and N-hydroxyimide derivatives (NHIs), wherein the nitrate is used as a cocatalyst to promote the NHIs to generate free radicals, thereby promoting the autooxidation of benzyl (methylene) and reducing the dosage of a metal catalyst. The "ferric ion, nitrate radical and N-hydroxyimide derivative (NHIs) are used together", which means that the invention can add ferric nitrate and NHIs directly into the reaction system, can also add soluble salt containing ferric ion, salt containing nitrate radical ion and NHIs, and can also add substances which can generate the above catalytic components simultaneously in the reaction process, which belongs to the protection scope of the invention.
Preferably, the catalyst added to the reaction system is ferric nitrate and N-hydroxyimide derivatives (NHIs). Further preferably, in the reaction system, the feeding molar ratio of the ferric nitrate, the NHIs and the aromatic benzyl compound is 0.01-0.1. Still more preferably: the feeding molar ratio of the aromatic benzyl compound with an electron-donating group connected to an aromatic ring is 0.01-0.05.
Preferably, the N-hydroxyimide derivative used in the present invention is selected from one of the following: n-hydroxyphthalimide (NHPI), N '-dihydroxypyromellitimide (NDHPI), N' -trihydroxyimine cyanuric acid (THICA), N-hydroxysuccinimide (NHSI), N-hydroxy-1, 8-naphthalimide (NHNI), the formula of which is shown below, and NHSI, NHPI or NHNI is more preferable.
The oxidation reaction of the present invention uses oxygen and/or air as an oxidant, i.e. the oxidation reaction is performed in oxygen or air or oxygen and air atmosphere, and preferably the oxidation reaction is performed under normal pressure by controlling the pressure of oxygen and/or air.
In the oxidation reaction of the present invention, an organic solvent with relatively high polarity is preferably used as a reaction solvent, such as acetic acid, benzonitrile, acetonitrile, ethyl acetate, and the like, and further preferably, the organic solvent is acetic acid or benzonitrile.
The oxidation reaction according to the present invention is preferably carried out at a temperature of 60 ℃ to 150 ℃, most preferably 100 ℃. The end point of the oxidation reaction can be monitored by gas chromatography.
After the oxidation reaction is finished, the target product can be obtained by simply post-treating the obtained reaction mixture, for example, after the solvent in the reaction system is evaporated out under reduced pressure, the target product is obtained by column chromatography separation or recrystallization, and the specific post-treatment method can be automatically adjusted according to the property of the target product. In addition, the reaction of the inventive NHSI as a catalyst, which can be recycled (see example 9 for details.
Compared with the prior art, the invention is characterized in that:
(1) The catalyst system used in the invention is the combination of ferric ions, nitrate radicals and N-hydroxyimide derivatives (NHIs), and the harmless metal ferric ions and NHIs of human body are used as catalysts, so that the use of metal ions harmful to human body such as copper, cobalt, manganese and the like and the residue in the product are avoided, and the application of the catalyst system in drug synthesis is facilitated; nitrate ions are used as a cocatalyst to promote the formation of free radicals from NHIs, thereby promoting the autooxidation of benzyl (methylene) groups and reducing the dosage of the metal catalyst.
(2) The method uses oxygen or air as an oxidant, is relatively cheap and green, most substrates can be oxidized only at a mild temperature, and a small part of substrates only need to increase the reaction temperature to promote the increase of the conversion rate.
(IV) specific embodiment:
the following examples are given by way of illustration and are not intended to limit the present invention.
Example 1
A round bottom flask equipped with a mechanical stir bar and reflux condenser was charged with 42.5g of ethylbenzene, 4.8g of ferric nitrate nonahydrate, 3.2g of NHPI,200mL of acetic acid. After the addition, the temperature of the oil bath is raised to 100 ℃, the reaction is stopped after 12 hours of reaction under open stirring, the conversion rate of the ethylbenzene is 98 percent by gas chromatography detection. Acetic acid in the reaction system is evaporated under reduced pressure, and then the product acetophenone 45.2g (colorless liquid) is obtained by reduced pressure distillation, with the yield of 94%.
Nuclear magnetic identification data of the product:
1 H NMR(500MHz,Chloroform-d)δ7.93-7.91(m,2H),7.52(tt,J＝7.5,1.5Hz,1H),7.43–7.40(m,2H),2.55(s,3H).
13 C NMR(125MHz,Chloroform-d)δ198.06,137.09,133.09,128.55,128.28,26.54.
example 2
A round bottom flask equipped with a magnetic stir bar and reflux condenser was charged with 5.3g of butylbenzene, 0.4g of iron nitrate nonahydrate, 0.3g of NHPI,30mL of acetonitrile. After the addition, sleeving a three-way valve to connect an oxygen balloon, carrying out three times of ventilation under the action of an air pump to replace the air in the reaction system with oxygen, raising the temperature of the oil bath to 100 ℃, reacting for 15 hours under stirring reflux, detecting by gas chromatography, and stopping the reaction, wherein the conversion rate of the butylbenzene is 91%. The solvent in the reaction system was evaporated under reduced pressure, and the product, phenylbutanone, was separated by column chromatography (petroleum ether/ethyl acetate = 100.
Nuclear magnetic identification data of the product:
1 H NMR(500MHz,Chloroform-d)δ7.95-7.93(m,2H),7.51(tt,J＝7.5Hz,1.5Hz,1H),7.42(t,J＝7.5Hz,2H),2.91(t,J＝7.5Hz,2H),1.75(qt,J＝7.5Hz,2H),0.98(t,J＝7.5Hz,3H).
13 C NMR(125MHz,Chloroform-d)δ200.02,136.92,132.61,129.31,40.23,17.53,13.64.
example 3
A round bottom flask equipped with a mechanical stir bar and reflux condenser was charged with 6.6g of diphenylmethane, 0.4g of ferric nitrate nonahydrate, 0.3g of NHPI,20mL of benzonitrile. After the addition, sleeving a three-way valve to connect an oxygen balloon, carrying out three times of ventilation under the action of an air pump to replace the air in the reaction system with oxygen, raising the temperature of the oil bath to 90 ℃, reacting for 12 hours, detecting by gas chromatography, and stopping the reaction, wherein the conversion rate of the diphenylmethane is 100%. After benzonitrile in the reaction system was distilled off under reduced pressure, and separated by column chromatography (petroleum ether/ethyl acetate = 100.
Nuclear magnetic identification data of the product:
1 H NMR(500MHz,Chloroform-d)δ7.88–7.78(m,4H),7.60(tt,2H,J＝7.5,2Hz),7.55–7.46(m,4H).
13 C NMR(125MHz,Chloroform-d)δ196.8,137.6,132.4,130.1,128.3.
example 4
A round bottom flask equipped with a mechanical stir bar and reflux condenser was charged with 5.24g of tetralin, 0.4g of ferric nitrate nonahydrate, 0.32g of NHPI,30mL of benzonitrile. After the addition, a three-way valve is sleeved on the reaction kettle, an oxygen balloon is connected, air exchange is carried out for three times under the action of an air pump, so that the air in the reaction system is replaced by oxygen, the reaction oil bath is heated to 120 ℃, after 12 hours of reaction, gas chromatography detection is carried out, the conversion rate of tetrahydronaphthalene is 91%, and the reaction is stopped. After the benzonitrile remaining in the reaction system was distilled out under reduced pressure, column chromatography was performed (petroleum ether, ethyl acetate = 80.
Nuclear magnetic identification data of the product:
1 H NMR(500MHz,Chloroform-d)δ7.98(dd,J＝8.0Hz,1.5Hz,1H),7.40(td,J＝7.5Hz,1.5Hz,1H),7.24(td,J＝7.5Hz,1H),7.19(d,J＝7.5Hz,1H),2.90(t,J＝6.5Hz,1H),2.59(t,J＝6.5Hz,1H),2.10-2.03(m,1H).
13 C NMR(125MHz,Chloroform-d)δ197.9,144.2,133.1,132.4,128.6,126.8,126.3,38.9,29.4,23.1.
example 5
A round bottom flask equipped with a mechanical stir bar and reflux condenser was charged with 5.29g of 3-ethylbenzonitrile, 0.6g of iron nitrate nonahydrate, 0.23g of NHSI, and 20mL of benzonitrile. And performing three times of ventilation under the action of an air pump to ensure that all the air in the reaction system is replaced by oxygen. The reaction oil bath was raised to 110 ℃ and after 18 hours of reaction, the conversion of 3-cyanoethylbenzene was 88% by gas chromatography and the reaction was stopped. Most of benzonitrile in the reaction system was distilled off under reduced pressure, and then separated by column chromatography (petroleum ether, ethyl acetate = 80.
Nuclear magnetic identification data of the product:
13 C NMR(125MHz,Chloroform-d)δ196.5,139.9,132.5,128.7,117.9,116.4,28.7.
1 H NMR(500MHz,Chloroform-d)δ8.05(d,J＝8Hz,2H),7.79(d,J＝8.5Hz,2H),2.65(s,3H).
example 6
A round bottom flask equipped with a mechanical stirring rod and a reflux condenser was charged with 66.5g of fluorene, 3.8g of ferric nitrate nonahydrate, 3.2g of NHPI, and 200mL of acetic acid, the reaction oil bath was raised to 100 ℃, and after an open reaction for 10 hours, the reaction was stopped with a fluorene conversion of 99% by gas chromatography. Distilling off residual acetic acid in the reaction system under reduced pressure, washing the residual residue with water, filtering, dissolving the filter cake in ethanol, decolorizing with active carbon, adding water into the filtrate to crystallize and separate out the product, and filtering to obtain 6.6g (white solid, melting point 83-84 ℃) of the product 9-fluorenone with yield of 92%.
Nuclear magnetic identification data of the product:
1 H NMR(500MHz,Chloroform-d)δ7.66(dt,J＝7.5Hz,1Hz,2H),7.51(dt,J＝7.5Hz,1Hz,2H),7.49(d,J＝1.5Hz,2H),7.29(td,J＝7.5Hz,1.5Hz,2H).
13 C NMR(125MHz,Chloroform-d)δ193.9,144.4,134.7,134.1,129.0,124.3,120.3.
example 7
A round bottom flask equipped with a mechanical stir bar and reflux condenser was charged with 4.25g of p-diethylbenzene, 0.40g of iron nitrate nonahydrate, 0.32g of NHPI, and 30mL of acetic acid, the reaction oil bath was raised to 100 deg.C, and after 10 hours of open reaction, the reaction was stopped at 98% conversion of p-diethylbenzene as determined by gas chromatography. After distilling off the acetic acid remaining in the reaction system under reduced pressure, the product p-ethylacetophenone was separated by column chromatography (petroleum ether, ethyl acetate = 100.
Nuclear magnetic identification data of the product:
1 H NMR(500MHz,Chloroform-d)δ7.89(d,J＝8.0Hz,2H),7.28(d,J＝8.0Hz,2H),2.71(q,J＝7.5Hz,2H),2.58(s,3H),1.26(t,J＝7.5Hz,3H).
13 C NMR(125MHz,Chloroform-d)δ197.8,150.0,134.9,128.5,128.0,28.9,26.5,15.1.
example 8
Adding 1.2g of indan, 0.1g of ferric nitrate nonahydrate, 0.10g of NHNI and 10mL of benzonitrile into a round-bottomed flask provided with a magnetic stirrer and a reflux condenser, sleeving a three-way valve with an oxygen balloon, carrying out three-time ventilation under the action of an air pump to ensure that the air in a reaction system is replaced by oxygen, raising the reaction oil bath to 125 ℃, carrying out open reflux reaction for 20 hours, detecting by gas chromatography, ensuring that the conversion rate of the indan is 91 percent, and stopping the reaction. After distilling off the acetic acid remaining in the reaction system under reduced pressure, the product 1-indanone 1.2g with a yield of 90% was obtained by column chromatography (petroleum ether, ethyl acetate = 120.
Nuclear magnetic identification data of the product:
1 H NMR(500MHz,Chloroform-d)δ7.76(d,J＝7.5Hz,1H),7.59(td,J＝7.5Hz,1.0Hz,1H),7.50-7.48(m,1H),7.39-7.36(m,1H),3.15(t,J＝6Hz,2H),2.70(t,J＝6Hz,3H)
13 C NMR(125MHz,Chloroform-d)δ207.1,155.1,137.0,134.6,127.2,126.7,123.7,36.2,25.8.
example 9
A round bottom flask equipped with a mechanical stir bar was charged with 6.1g of 4-nitroethylbenzene, 0.6g of ferric nitrate nonahydrate, 0.46g of NHSI,25mL of benzonitrile. And (3) carrying out air exchange for three times under the action of an air pump to ensure that the air in the reaction system is replaced by oxygen, raising the reaction oil bath to 110 ℃, reacting for 18 hours, detecting by using a gas chromatography, wherein the conversion rate of the 4-nitroethylbenzene is 98%, and stopping the reaction. After most of benzonitrile in the reaction system is evaporated and recovered under reduced pressure, the solid is left after washing with water, filtrate and filter cake are obtained after filtration, and the product 4-nitroacetophenone 5.95g (yellow solid, melting point 80-81 ℃) is obtained after the filter cake is recrystallized by ethyl acetate/petroleum ether, the yield is 90%. After the filtrate was depressurized and distilled to remove water, 6.05g of 4-nitroethylbenzene, 0.6g of ferric nitrate nonahydrate, and recovered and reused benzonitrile (new benzonitrile was added to a total volume of 25 ml) were directly added to perform the next reaction. The catalyst is continuously used for three times, and the yield can still be kept above 80% (see table 2)
TABLE 2 Recycling of NHSI
| Number of NHSI uses | Reaction time (h) | Isolation yield (%) |
| 1 | 18 | 90 |
| 2 | 20 | 88 |
| 3 | 24 | 83 |
| 4 | 30 | 81 |
Nuclear magnetic identification data of the product:
1 H NMR(500MHz,Chloroform-d)δ8.31-8.29(m,2H),8.12-8.01(m,2H),2.68(s,3H).
13 C NMR(125MHz,Chloroform-d)δ196.27,150.33,141.39,129.27,123.80,26.90.
example 10
A round bottom flask equipped with a mechanical stir bar was charged with 3.6g of xanthene, 0.2g of iron nitrate nonahydrate, 0.1g of NHSI,20mL of benzonitrile. Carrying out air exchange for three times under the action of an air pump to ensure that the air in the reaction system is replaced by oxygen, raising the reaction oil bath to 100 ℃, reacting for 11 hours, detecting by gas chromatography, and stopping the reaction when the conversion rate of the raw materials is 99%. After most of benzonitrile in the reaction system was distilled off and recovered under reduced pressure, column chromatography separation (petroleum ether, ethyl acetate =80, 1-50.
Nuclear magnetic identification data of the product:
1H NMR(500MHz,Chloroform-d)δ8.33(dd,J＝8.0Hz,1.5Hz,2H),7.72–7.69(m,2H),7.47(d,J＝8.5Hz,2H),7.38–7.35(m,2H).
13C NMR(125MHz,Chloroform-d)δ177.1,156.1,134.7,126.7,123.9,121.8,117.9.
example 11
Adding 1.2g of isochroman, 0.1g of ferric nitrate nonahydrate, 0.10g of NHPI and 10mL of acetic acid into a round-bottomed flask provided with a magnetic stirrer and a reflux condenser, sleeving a three-way valve and connecting an oxygen balloon, carrying out three-time ventilation under the action of an air pump, replacing air in a reaction system with oxygen, raising the reaction oil bath to 100 ℃, carrying out open reaction for 12 hours, detecting by gas chromatography, and stopping the reaction, wherein the conversion rate of the raw materials is 98%. After distilling off the acetic acid remaining in the reaction system under reduced pressure, the product 1-isochromanone 1.4g with a yield of 93% was obtained by column chromatography (petroleum ether, ethyl acetate = 100.
Nuclear magnetic identification data of the product:
1 H NMR(500MHz,Chloroform-d)δ8.04(d,J＝7.5Hz,1H),7.51(tt,J＝7.5Hz,1.25Hz,1H),7.35(t,J＝7.5Hz,1H),7.24(d,J＝7.5Hz,1H),4.50(t,J＝5.5Hz,2H),3.03(t,J＝6.0Hz,2H)
13 C NMR(125MHz,Chloroform-d)δ165.0,139.5,133.5,130.1,127.5,127.2,125.1,67.2,27.6.
comparative example:
a round bottom flask equipped with a mechanical stir bar and reflux condenser was charged with 2mmol of ethylbenzene, 0.1mmol of iron salt, 0.2mmol of NHPI,2mL of acetic acid. After the addition was complete, the oil bath temperature was raised to 100 ℃ and after the reaction was complete with open stirring, the conversion of ethylbenzene was determined by gas chromatography (using chlorobenzene as the internal standard) and the results are shown in table 2.
TABLE 2 oxygen oxidation of ethylbenzene under the catalysis of various iron salts
| Iron salts | Conversion (%) |
| Fe(acac) 2 | 83 |
| Fe(NO 3 ) 2 | 98 |
| FeCl 3 | 66 |
| Iron stearate | 87 |
| Fe 2 (SO 4 ) 3 | 19 |
Example 12
A round bottom flask equipped with a mechanical stir bar was charged with 4.8g of p-methyl ethylbenzene, 0.32g of ferric nitrate nonahydrate, 0.23g of NHSI,20mL of benzonitrile. Carrying out air exchange for three times under the action of an air pump to ensure that the air in the reaction system is replaced by oxygen, raising the reaction oil bath to 100 ℃, reacting for 8 hours, detecting by using a gas chromatography, ensuring that the conversion rate of the raw materials is 92 percent, and stopping the reaction. After most of benzonitrile in the reaction system was distilled off and recovered under reduced pressure, the product was obtained in 4.7g (white solid, melting point 28 ℃) by column chromatography (petroleum ether: ethyl acetate = 100.
Nuclear magnetic identification data of the product:
13 C NMR(125MHz,Chloroform-d)δ197.6,143.7,134.6,129.1,128.3,26.3,21.5.
1 H NMR(500MHz,Chloroform-d)δ7.84(d,J＝8.5Hz,2H),7.24(d,J＝8Hz,2H),2.55,(s,3H),2.39(s,3H).
example 13
A round bottom flask equipped with a mechanical stir bar was charged with 7.4g of para-bromoethylbenzene, 0.8g of ferric nitrate nonahydrate, 0.32g of NHPI,20mL of benzonitrile. Performing three times of ventilation under the action of an air pump to ensure that all air in the reaction system is replaced by oxygen, raising the reaction oil bath to 100 ℃, reacting for 24 hours, detecting by using gas chromatography, and stopping the reaction, wherein the conversion rate of the raw materials is 95%. After most of benzonitrile in the reaction system was distilled off and recovered under reduced pressure, column chromatography separation (petroleum ether/ethyl acetate =80, 1-50).
Nuclear magnetic identification data of the product:
1H NMR(500MHz,Chloroform-d)δ7.83(J＝8.5Hz,1H),7.61(d,J＝8.5Hz,1H),2.59(s,3H).
13C NMR(125MHz,Chloroform-d)δ197.0,135.9,131.9,129.8,128.3,26.5.
example 14
A round bottom flask equipped with a mechanical stir bar was charged with 7.4g of o-bromoethylbenzene, 0.4g of ferric nitrate nonahydrate, 0.3g of NHPI,20mL of benzonitrile. Performing air exchange for three times under the action of an air pump to ensure that the air in the reaction system is replaced by oxygen, raising the reaction oil bath to 100 ℃, reacting for 20 hours, detecting by using a gas chromatography, ensuring that the conversion rate of the raw materials is 97 percent, and stopping the reaction. After most of benzonitrile in the reaction system was distilled off and recovered under reduced pressure, column chromatography separation (petroleum ether/ethyl acetate =80: 1-40) was performed to obtain 7.5g (white solid, melting point 48-51 ℃) of the product, yield 95%.
Nuclear magnetic identification data of the product:
1 H NMR(500MHz,Chloroform-d)δ7.57(dd,J＝8Hz,1Hz,1H),7.43(dd,J＝7.5Hz,2Hz,1H),7.33(td,J＝7.5Hz,1Hz,1H),7.26(td,J＝8Hz,1.5Hz,1H),2.59(s,3H).
13 C NMR(125MHz,Chloroform-d)δ201.1,141.3,133.7,131.7,128.8,127.3,118.7,30.1.
example 15
A round bottom flask equipped with a mechanical stir bar was charged with 6.56g of p-ethylphenyl ester, 0.65g of iron nitrate nonahydrate, 0.65g of NHPI,20mL of benzonitrile. Carrying out air exchange for three times under the action of an air pump to ensure that the air in the reaction system is replaced by oxygen, raising the reaction oil bath to 100 ℃, reacting for 20 hours, detecting by using a gas chromatography, and stopping the reaction when the conversion rate of the raw materials is 94%. After most of benzonitrile in the reaction system was distilled off and recovered under reduced pressure, column chromatography separation (petroleum ether/ethyl acetate =80, 1-50).
Nuclear magnetic identification data of the product:
1 H NMR(500MHz,Chloroform-d)δ7.89–7.83(m,2H),7.10–7.05(m,2H),2.45(d,1H),2.18(d,1H).
13 C NMR(125MHz,Chloroform-d)δ196.4,168.5,154.1,134.4,129.6,121.5,26.6,20.7.
example 16
Nuclear magnetic identification data of the product:
1H NMR(500MHz,Chloroform-d)δ7.80-7.76(m,4H),7.62(tt,J＝7.5Hz,1.5Hz,1H),7.53-7.47(m,4H).
13C NMR(125MHz,Chloroform-d)δ195.5,138.9,137.3,135.9,132.7,131.5,129.9,128.7,128.4.
while typical embodiments have been set forth for the purpose of illustration, the foregoing descriptions and examples should not be deemed to be a limitation on the scope hereof. Accordingly, various changes, modifications, and alterations may be made by those skilled in the art without departing from the spirit and scope of the invention.
Claims (7)
1. A method of synthesizing an aromatic benzyl ketone, the method comprising: oxidizing an aromatic benzyl compound shown in a formula (I) under the action of a catalytic system by taking oxygen and/or air as an oxidant, wherein the oxidation reaction is carried out at the temperature of 90-125 ℃ for 8-24h to prepare aromatic benzyl ketone shown in a formula (II); the catalytic system is formed by combining ferric nitrate and N-hydroxyimide derivatives, wherein the molar ratio of the ferric nitrate to the N-hydroxyimide derivatives is 0.01-0.1; the oxidation reaction uses one of the following organic solvents as a reaction solvent: acetic acid, benzonitrile;
Ar-CH 2 -R（I） Ar-CO-R（II）
wherein Ar is an aromatic ring or a substituted aromatic ring without heteroatoms, the substituent on the substituted aromatic ring is one or more, and each substituent is independently selected from methyl, halogen, cyano, acyloxy or nitro;
r is selected from C1-C3 alkyl or a benzene ring, wherein the benzene ring is unsubstituted or substituted by a substituent selected from halogen;
or-CH 2 -R forms with the adjacent groups on the Ar ring a 5-6 membered ring A containing no or no heteroatoms, said 5-6 membered ring A being notSubstituted; optionally, the substituent on the 5-6 membered ring A may further form a 6-membered aromatic ring B with the adjacent group on the 5-6 membered ring A, the aromatic ring B being unsubstituted; and, when the 5-6 membered ring A is contained in the formula (I), at least one of the alpha positions of the 5-6 membered ring A is-CH irrespective of whether or not the 6-membered aromatic ring B is contained 2 -for reaction to form a carbonyl group; the heteroatom in the ring A is O, and the 6-membered aromatic ring B is a benzene ring.
2. The method of synthesis of claim 1, wherein: and Ar is a benzene ring or a naphthalene ring.
3. The method of synthesis of claim 1, wherein: the acyloxy is C1-C4 alkanoyloxy or benzoyloxy.
4. The method of synthesis of claim 2, wherein: the acyloxy is C1-C4 alkanoyloxy or benzoyloxy.
5. The method of synthesis according to any one of claims 1 to 4, characterized in that: in the reaction system, the feeding molar ratio of the ferric nitrate to the NHIs to the aromatic benzyl compound is 0.01-0.1.
6. The method of synthesis according to one of claims 1 to 4, characterized in that: the N-hydroxyimide derivative is selected from one of the following: n-hydroxyphthalimide, N ' -dihydroxypyromellitimide, N ' ' -trihydroxyimine cyanuric acid, N-hydroxysuccinimide, N-hydroxy-1, 8-naphthalimide.
7. The method of synthesis according to one of claims 1 to 4, characterized in that: the oxidation reaction takes oxygen and/or air as an oxidant, namely the oxidation reaction is carried out in oxygen or air or oxygen and air atmosphere, and the pressure of the oxygen and/or air is controlled to carry out the oxidation reaction under normal pressure.
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| CN106748688A (en) * | 2016-11-29 | 2017-05-31 | 中国科学院兰州化学物理研究所苏州研究院 | A kind of preparation method of benzaldehyde and its derivative |
| CN107011133A (en) * | 2017-05-25 | 2017-08-04 | 中国科学技术大学 | The method that a kind of benzyl position C H keys are direct oxidation into ketone |
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| CN107011133A (en) * | 2017-05-25 | 2017-08-04 | 中国科学技术大学 | The method that a kind of benzyl position C H keys are direct oxidation into ketone |
Non-Patent Citations (2)
| Title |
|---|
| Aerobic oxidation of secondary alcohols using NHPI and iron saltas catalysts at roomtemperature;Hanqing Zhao等;《Journal of Molecular CatalysisA:Chemical》;20140613;第393卷;全文 * |
| NHPI and ferric nitrate: a mild and selective system for aerobic oxidation of benzylic methylenes;Chengxia Miao等;《Catalysis Science & Technology》;20151008;第6卷(第5期);第1379页第1栏第1段-第1382页第2栏第2段，方案1，表3 * |
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