A high-efficiency and convenient preparation method of diaryl ketone

Abstract

The application belongs to the field of organic compound preparation chemistry, and specifically discloses a high-efficiency and convenient preparation method of diaryl ketone. The steps of the method are as follows: tartaric acid ester is reacted with aryl Grignard reagent to obtain 1,1,4,4-tetraaryl butanetetrol; then, the 1,1,4,4-tetraaryl butanetetrol is reacted with solid acid in a certain temperature and a certain organic solvent to obtain diaryl ketone with high yield. The method has the following remarkable characteristics: the raw material is cheap and easy to obtain, the synthesis process is simple, the operation is convenient, the method does not contain heavy metal, the reaction selectivity is excellent, the product yield is high, and the catalyst can be repeatedly used.

Description

Technical Field

[0001] This invention belongs to the field of organic compound preparation chemistry, specifically relating to an efficient and convenient method for preparing diaryl methyl ketone. Background Technology

[0002] Diaryl ketones, as a very important class of chemical products and pharmaceutical intermediates, are widely used in the synthesis of fine chemicals such as drugs, pesticides, and dyes ((a) Chemical & Pharmaceutical Bulletin, 2004, 52:818; (b) JM ed. Chem., 1997, 40:3937; (c) Invention Patent: Synthetic Process of Diaryl Ketone Derivatives, Publication No.: CN107032938A). Traditional synthetic methods include dihalogen hydrolysis, Friedel-Crafts acylation, oxidation or dehydrogenation of alcohols, and reaction of arylformyl chlorides with Grignard reagents or organolithium copper. The most commonly used method is Friedel-Crafts acylation, which often requires a large amount of Lewis acid catalyst, increasing the amount of metal residue to be processed. Furthermore, it causes serious equipment corrosion and environmental pollution (Organic Chemistry, 2011, 31, 1188). The preparation method involves arylformyl chlorides and organometallic reagents, but the resulting ketones readily react with Grignard reagents or organolithium copper reagents to form the corresponding tertiary alcohols (Synthesis, 1984, 9:734), and organometallic reagents are highly toxic (J. Am. Chem. Soc., 1983, 105:6129). The synthesis of diaryl ketones from aryl halides and arylboronic acids requires palladium as a catalyst (JA m. Chem. Soc., 2000, 122:11260), and these catalysts often contain heavy metal ions, which should be avoided as much as possible in drug synthesis.

[0003] In contrast, using inexpensive and readily available compounds to synthesize diaryl ketone compounds through efficient and practical synthetic methods undoubtedly has significant advantages. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing diaryl methyl ketones. This method uses inexpensive and readily available raw materials, has a simple synthesis process, is convenient to operate, is free of heavy metals, exhibits excellent reaction selectivity, and yields a high product.

[0005] The principle of this invention is as follows: 1,1,4,4-tetraarylbutanetetraol is prepared by reacting tartrate ester with aryl Grignard reagent, and then 1,1,4,4-tetraarylbutanetetraol reacts with solid acid in organic solvent to generate diaryl ketone.

[0006] The key technical point provided by this invention is that 1,1,4,4-tetraphenylbutanetetrol has a very rich chemical reaction due to the presence of its multiple hydroxyl groups. Our research group found (Tetrahedron:Asymmetry 20(2009)2474–2478) that when it reacts with liquid acid, different products are obtained under different conditions, as shown in formula (1): Under heterogeneous conditions, 1,1,4,4-tetraphenylbutanetetrol reacts with hydrohalic acid to undergo intramolecular dehydration reaction to generate tetrahydrofuran derivative; while under homogeneous conditions, 1,1,4,4-tetraphenylbutanetetrol reacts with hydrohalic acid to undergo C-C bond cleavage to generate 1,3-dioxocyclopentane derivative.

[0007]

[0008] Studies have shown that the reaction of diarylbenzyl alcohol with liquid acid HI can proceed to a diaryl ketone intermediate, but the reaction rarely stops at diaryl ketone; instead, it produces diarylmethane (Further studies on the reduction of benzylic alcohols by hypophosphorous acid / iodine, ARKIVOC 2005(vi)393-400, see Scheme 2). In this system, due to the presence of HI, the generated diaryl ketone will be further reduced to diarylmethane.

[0009] This invention provides a highly efficient method for preparing diaryl ketones by reacting 1,1,4,4-tetraarylbutyrate with a solid acid. Since the solid acid is insoluble in organic solvents, a heterogeneous reaction between a solution of 1,1,4,4-tetraarylbutyrate and the solid acid directly yields diaryl ketones, with the following structural formula:

[0010]

[0011] To achieve the above objectives, the present invention adopts the following technical solution:

[0012] A method for preparing diaryl methyl ketone comprises the following steps: reacting tartrate ester with an aryl Grignard reagent to obtain 1,1,4,4-tetraarylbutanetetraol; and then reacting it with a solid acid in a certain temperature and a certain organic solvent to obtain diaryl methyl ketone in high yield.

[0013] The reaction temperature for preparing diaryl methyl ketone is 20℃-120℃, preferably 30℃-80℃; within the reaction temperature range of 20℃-120℃, the higher the temperature, the faster the reaction rate and the shorter the reaction time.

[0014] The organic solvent used to prepare diaryl ketones is a common organic solvent that can dissolve 1,1,4,4-tetraarylbutanetetraethanolamine, and the solid acid is insoluble in this organic solvent. The organic solvent includes at least one of toluene, N,N-dimethylformamide, dioxane, and acetonitrile. The amount of the organic solvent has little effect on the reaction, so there are no special requirements for its amount, as long as it can dissolve 1,1,4,4-tetraarylbutanetetraethanolamine.

[0015] The solid acid used in the preparation of diaryl ketones is a heteropolyacid, wherein the coordinating atom in the heteropolyacid is Mo, W, V, etc., corresponding to heteropolymolybdic acid, heteropolytungstic acid, heteropolyvanadic acid, etc., preferably heteropolymolybdic acid, heteropolytungstic acid, or heteropolyvanadic acid of phosphoric acid. Further, the structure of the heteropolyacid is of type 1:12A, 1:12B, 1:6, 1:9, 2:18, etc.; the heteropolyacid is a heteropolyacid of phosphoric acid, taking heteropolymolybdic acid as an example, such as dodecamolybdic phosphomolybdic acid (also known as dodecamolybdic phosphate, phosphomolybdic acid), hexamolybdic phosphomolybdic acid, nonamolybdic phosphomolybdic acid, etc. Heteropolyacids represented by phosphomolybdic acid, phosphotungstic acid, and phosphovanadic acid can achieve efficient conversion of 1,1,4,4-tetraarylbutanetetrol to diaryl ketones.

[0016] The mass ratio of the solid acid used to prepare diaryl ketone to 1,1,4,4-tetraarylbutanetetraol is 1:(1-6); wherein, the more solid acid used, the shorter the reaction time, and the less solid acid used, the longer the reaction time.

[0017] The above-mentioned aryl Grignard reagent has the general formula RMgX, where R is aryl and X is Cl, Br or I; further, R is phenyl or substituted phenyl, the substituted phenyl is monosubstituted or disubstituted, the substitution position is meta and / or para of the benzene ring, and the substituted group is -CH3, -CF3, -F, tert-butyl; preferably, the aryl group is phenyl, 4-trifluoromethylphenyl, 3,5-di(trifluoromethyl)phenyl, 4-methylphenyl, 4-fluorophenyl, 4-tert-butylphenyl, etc.

[0018] The method for preparing diaryl methyl ketone of the present invention has significant advantages such as readily available raw materials, simple operation, high efficiency and convenience, high yield (all above 80%), and reusable catalyst. Detailed Implementation

[0019] The technical solution of the present invention will be further described below with reference to specific embodiments.

[0020] Example 1: Preparation of 1,1,4,4-Tetraphenylbutyritol

[0021]

[0022] 7.31–7.16(m,20H,Ar-H),4.66(d,J=7.3Hz,2H,OH),4.42(d,J=4.8Hz,2H,CH),3.78(d,J=5.4Hz,2H,OH). 13 C NMR (75MHz, Chloroform-d) δ144.1,143.9,128.7,128.5,127.4,127.3,126.1,125.0,81.8,71.2.

[0023] Example 2: Preparation of benzophenone

[0024]

[0025] g. The supernatant was collected and concentrated to obtain a viscous oily substance. 10 mL of methanol was added and heated to dissolve the substance. After cooling to room temperature (20°C), benzophenone crystals precipitated. Yield: 89%, mp: 49°C. 1 H NMR (600MHz, Chloroform-d) δ7.84–7.78(m,4H),7.62–7.56(m,2H),7.51–7.45(m,4H). 13 C NMR (151MHz, Chloroform-d) δ196.8,137.6,132.4,130.1,128.3.

[0026] In addition, the inventors also prepared the corresponding 1,1,4,4-tetraarylbutanetetraol by reacting Grignard reagents 4-trifluoromethylphenyl magnesium bromide, 3,5-bis(trifluoromethyl)phenyl magnesium bromide, 4-methylphenyl magnesium bromide, 4-fluorophenyl magnesium bromide, and 4-tert-butylphenyl magnesium bromide with diethyl tartrate according to the preparation method of Example 1; and prepared the corresponding diaryl ketones by reacting 1,1,4,4-tetraarylbutanetetraol with phosphomolybdic acid according to the preparation method of Example 2, with high yields of 85%, 87%, 90%, 84%, and 82%, respectively.

[0027] Example 3: Recycling of Heteropolyacid Catalysts

[0028] 2.13 g of 1,1,4,4-tetraphenylbutanetetrol prepared in Example 1 was dissolved in 15 mL of toluene, and then 1.86 g of phosphomolybdic acid recovered according to the method in Example 2 was added. The mixture was heated and stirred at 80 °C for 3 hours. After the reaction was completed, the solution was centrifuged, and the phosphomolybdic acid was recovered again. The supernatant was collected and concentrated to obtain a viscous oily substance. After dissolving in 10 mL of methanol by heating, the mixture was cooled to room temperature (20 °C) to precipitate benzophenone crystals. Yield: 86.0%.

[0029] The specific embodiments described in this specification are merely illustrative of the spirit of the invention. Those skilled in the art to which this invention pertains may make various modifications or additions to the described specific embodiments or use similar methods to substitute them, without departing from the spirit of the invention or exceeding the scope defined by the appended claims.

Claims

1. A method for preparing a diaryl methyl ketone, characterized in that, The steps are as follows: 1,1,4,4-tetraarylbutanetetraol is prepared by reacting tartrate ester with an aryl Grignard reagent; then, it is reacted with a solid acid in a certain temperature and a certain organic solvent to obtain diaryl methyl ketone in high yield; the aryl Grignard reagent has the general formula RMgX, where X is Cl, Br or I, R is phenyl or substituted phenyl, the substituted phenyl is monosubstituted or disubstituted, the substituted position is meta and / or para of the benzene ring, and the substituted group is -CH3, -CF3, -F, tert-butyl; The solid acid is at least one of heteropolymolybdic acid, heteropolytungstic acid, and heteropolyvanadic acid; The organic solvent is an organic solvent capable of dissolving 1,1,4,4-tetraarylbutanetetraethanol, and the solid acid is insoluble in this organic solvent.

2. The preparation method according to claim 1, characterized in that, The specified temperature is 20℃-120℃.

3. The preparation method according to claim 2, characterized in that, The specified temperature is 30℃-80℃.

4. The preparation method according to claim 2, characterized in that, The organic solvent is toluene. N,N - At least one of dimethylformamide, dioxane, and acetonitrile.

5. The preparation method according to any one of claims 1-4, characterized in that, The solid acid is at least one of the following: heteropolymolybdic acid, heteropolytungstic acid, and heteropolyvanadic acid, which are all forms of phosphoric acid.

6. The preparation method according to claim 5, characterized in that, The solid acid is any one of phosphomolybdic acid, phosphotungstic acid, and phosphovanadic acid.

7. The preparation method according to any one of claims 1-4, characterized in that, The mass ratio of the solid acid to 1,1,4,4-tetraarylbutanetetraol is 1:(1-6).

8. The preparation method according to claim 1, characterized in that, R is any one of phenyl, 4-trifluoromethylphenyl, 3,5-bis(trifluoromethyl)phenyl, 4-methylphenyl, 4-fluorophenyl, and 4-tert-butylphenyl.

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