Method of producing 1-acetyl-4- propionylbenzene

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 1-acetyl-4-propionylbenzene, which is starting material for making medicinal agents and dipyrrolylbenzenes, used in synthesis of conducting interlinked polymer systems, which can be used as electrode materials for energy accumulators, biosensors, photoluminescent materials, electroluminescent materials and electromagnetic shields. The method involves using propionyl chloride and ethylbenzene as starting material in an organic solvent medium, and carrying out the reaction in the presence of anhydrous aluminium chloride at temperature between 25 and 40°C for 20 to 60 minutes, with formation of an intermediate product 1-propionyl-4-ethylbenzene, which is separated and oxidised with potassium permanganate in an aqueous solution of magnesium nitrate at temperature between 65 and 80°C for 3 to 5 hours, forming the desired product which is extracted using toluene, with subsequent recrystallisation from n-hexane or petroleum ether. The method uses non-toxic and readily available components, which makes the proposed method suitable for industrial use.

EFFECT: design of a simple industrial method of producing 1-acetyl-4-propionylbenzene.

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The invention relates to the field of organic synthesis, in particular to methods for diketones of the benzene series, specifically concerns a method for obtaining 1-acetyl-4-propenylbenzene.

Among aromatic diketones 1,4-Vallandry, including 1-acetyl-4-propenylbenzene [synonyms; 4-acetylpyridine, para-acetylproline, 1-(4-acetylphenyl)-1-propanone], are the starting compounds for the synthesis of them (through the appropriate dioxime) dipirrolilmetanov under the reaction conditions Trofimova. On the basis of such dipyrroles get new conductive conjugated polymer systems, which are used as electrode materials for energy storage, biosensors, materials for photoluminescence, electroluminescence, electromagnetic screens. Polymers containing vysokomineralizovannye system of π-electrons, including poly(dipirrolilmetena)have nonlinear optical properties. Thus, 1-acetyl-4-propenylbenzene is the starting compound for the synthesis of poly(dipirrolilmetanov) - promising materials for advanced technologies.

In addition, 1-acetyl-4-propenylbenzene is the starting compound for the synthesis of a new medical drug "Propyfol" (link on the Internet http://w3.gre.ac.uk/schools/cls/PHAM0003_2003.doc), which has a powerful anesthetic effect and produced what about now the British company Abbey Pharmaceuticals (West Thamesmead, Kent, UK).

In the known methods to obtain 1-acetyl-4-propenylbenzene sophisticated catalysts based on complexes of palladium. Wakita and employees [Wakita y, Yasunaga T., Akita M, Kojima .J. were obtained. Chem., 1986, Vol. 301, No.2, P.17-C20] obtained 1-acetyl-4-propenylbenzene reaction Carboniferous cross-combination of triethylborane with 1-acetyl-4-yogansonom in the presence of palladium and zinc complexes with the release of 71.5%

Despite the relatively high yield of the target product, not given its physicochemical and spectral characteristics (melting point, IR spectra and NMR), and, apparently, he was not selected preparative. Significant disadvantages of the above method is the use of hard-to-reach and highly toxic reagents such as 1-acetyl-4-iadanza, triethylborane, carbon monoxide, expensive palladium catalyst, in addition, triethylborane is easy to vosplamenenii substances, all this makes this method unsuitable for industrial applications.

Sato and Narita (Sato N., Narita N. Synthesis, 2001, pp.1551-1555) was synthesized 1-acetyl-4-propenylbenzene by the reaction of the Steele interaction 1 tributylstannyl-1 ethoxy-1-propene with 1-acetyl-4-brombenzene in the presence of a palladium catalyst and copper iodide to yield 42%

The aim of the present invention is to develop a method to obtain 1-acetyl-4-propenylbenzene devoid of the disadvantages mentioned above and is suitable for industrial applications.

The objective is achieved by acylation industrially available ethylbenzene industrial available propionylcarnitine environment dichloromethane or benzene in the presence of anhydrous aluminium chloride with subsequent oxidation of the resulting 1-propionyl 4-ethylbenzene 1-acetyl-4-propenylbenzene potassium permanganate in aqueous solution of nitrates of magnesium

Acylation of benzene is carried out in an organic solvent (benzene, dichloromethane) at a temperature of 25-40°C (preferably 30-35°C) for 20 to 60 minutes (preferably 25-35 min), a molar ratio of reagents ethylbenzene:propionate:aluminium chloride anhydrous=(0.5-1.5):(0.5-1.5):(1-2 .5) (preferably 1: 1:1.5) and concentrations of reagents 0.5-1.5, 0.5-1.5, 1-2 .5 mol/l, respectively (preferably 1.1 and 1.5 mol/l), and it should be noted that the best the outputs are obtained, if you observe the following order of process: RA is Toru propionitrile and anhydrous aluminium chloride in dichloromethane add ethylbenzene, and not Vice versa (see example 3). Selection 1-propionyl 4-ethylbenzene is carried out by decomposition of the reaction mixture with a mixture of ice with concentrated hydrochloric acid in a mass ratio of 1.5:1, separation of the organic layer, washing the latter with water and drying with anhydrous potash, distillation of the solvent, followed by fractional distillation in vacuum.

Oxidation of the obtained 1-propionyl 4-ethylbenzene is carried out by the processing of his / her suspension in an aqueous solution of magnesium nitrate potassium permanganate at a temperature of 65-80°C (preferably 70-75°C) for 3-5 h (preferably 3-3 .5 h), a molar ratio of reagents 1-propionyl 4-ethylbenzene:permanganate of potassium nitrate magnesium=(0.5-1.5):(0.5-1.5):(0.5-1.5) (preferably 1:1.1:1) and concentration of 1-propionyl 4-ethylbenzene and nitrate magnesium 0.3-0.4, 0.3-0.5 mol/l, respectively (preferably 0.35 and 0.39 mol/l, respectively). The allocation of 1-acetyl-4-propenylbenzene is carried out by extraction with toluene, separation of the organic layer, washing the latter with water and drying with anhydrous potash, distillation of the solvent followed by crystallization of the desired product from n-hexane or petroleum ether (fraction with a boiling temperature of 70-100°C).

When carrying out the process under optimal conditions, the total yield of 1-acetyl-4-propenylbenzene (counting on taken ethylbenzene) is 5%. Thus, the advantage of the proposed method is the use of relatively cheap, accessible and safe handling of reagents, which can significantly reduce the cost of the target product and, if necessary, to synthesize it in an enlarged scale.

The following neogranichivatsya examples illustrate the invention.

Example 1.

Flask 0.5 l placed in a water bath mounted on a magnetic stirrer. Into the flask with dichloromethane (100 ml), include stirring, is added through a wide funnel aluminium chloride anhydrous (20 g, 0.15 mol) and portions propionate (9.25 g, 0.10 mol). The mixture darkens and the temperature rises. In bath for cooling portions add the cold water and the temperature of the mixture support in the range of 30-35°C. for About 15-20 minutes the formed complex of aluminium chloride with propionylcarnitine dissolved in dichloromethane. Ethylbenzene (10.6 g, 0.1 mol) from a dropping funnel at a temperature of 30-35°C for 10 minutes under vigorous stirring was added dropwise to the reaction mixture. After 1-2 min after the addition of ethylbenzene (HCl also ceases to stand out) the reaction solution with stirring, poured into a wide 0.5-litre glass with a mixture of 100 ml of concentrated hydrochloric acid and 150 g of crushed ice. After complete dissolution of the aluminum chloride and taniela the bottom layer is separated in a separating funnel, thrice washed with cold water portions of 15 ml, dried, calcined potash. After removal of the solvent by fractional distillation in vacuum to obtain 15.1 g of 1-propionyl 4-ethylbenzene (4-ethylpropylamine). (exit 93.0%, counting on taken ethylbenzene). 1-propionyl 4-ethylbenzene is a colorless liquid, BP. 93°C/3 mm Hg,

n_D²⁰1.525, d₄²⁰0.980. An NMR spectrum¹H (CDCl₃, δ, ppm): 7.88 (d, 2H, J=7.6 Hz, H_o), 7.26 (d, 2H, J=7.6 Hz, H_m), 2.96 (K, 2H, J=7.6 Hz,CH₂Me), 2.68 (K, 2H, J=7.6 Hz,CH₂Me), 1.24 (t, 3H, J=7.6 Hz, CH₂Me), 1.20 (t, 3H, J=7.6 Hz, CH₂Me). The data of elemental analysis: calculated, C, 81.44, H, 8.70; gross formula C₁₁H₁₄O; found, C 81.41, H 8.77. Physicochemical and spectral characteristics of the compounds obtained coincide with characteristics (n_D²⁰1.522-1.526, d₂₀²⁰0.977-0.981 g/ml, an NMR spectrum¹H) a commercial product of the firm "Labseeker" http://www.labseeker.corn/ChemicalBiotech/chem (moreinfo.asp?catalog_no=16927).

It heated up to 50°C a mixture of 1-propionyl 4-ethyl benzene (15 g, 0.09 mol), magnesium nitrate setevogo (23 g, 0.09 mol) and 250 ml of water for 40 minutes under stirring in small portions add the potassium permanganate (16 g, 0.1 mol). The reaction mixture was stirred further for 3 h at 70-75°C until complete disappearance of the purple color. After cooling, the product is extracted with toluene (5×30 ml), washed the t water (3×5 ml), dried with anhydrous sodium sulfate. After distillation of the toluene, the resulting mixture was dissolved in 150 ml of hot (60-65°C) n-hexane or petroleum ether (fraction with a boiling temperature of 70-100°C). The resulting solution was cooled to -10°C, the precipitation is filtered by the filter SCHOTT and washed with cold n-hexane or petroleum ether (15 ml). Obtain 8.0 g of the target 1-acetyl-4-propenylbenzene (yield 45%, counting on taken ethylbenzene), colorless needle crystals, TPL 78°C (from n-hexane or petroleum ether). IR (KBr), cm^-1: 1680 (C=O), 1401, 1354, 1222, 955, 856, 797. An NMR spectrum¹H (CDCl₃, δ, ppm): 8.03 (s, 4H, CH), 3.03 (q, 2H, J=7.2 Hz,CH₂Me), 2.64 (s, 3H, COMe, 124 (t, 3H, J=7.2 Hz, CH₂Me). An NMR spectrum¹³With (CDCl₃, δ, ppm): 200.08 (COMe), 197.42 (COEt), 140.06, 140.01, 128.52, 128.09, at 32.24 (COMe), 26.80 (CH₂Me), 8.05 (CH₂Me). The data of elemental analysis: calculated: C 74.98, H, 6.86; gross formula C₁₁H₁₂O₂; found: C 75.02, H 6.87. Physico-chemical (TPL 77-78°C) and spectral data (IR, NMR¹N) of the resulting product is completely consistent with literature data (Sato N., Narita N. Synthesis, 2001, pp.1551-1555).

Example 2.

In the conditions of example 1, in the same container, using the same load, except that the acylation of benzene is carried out in benzene, but not in dichloromethane. After all described in example 1 procedures obtain 4.3 g of C is left 1-acetyl-4-propenylbenzene (30%yield, counting on taken ethylbenzene).

Example 3.

In the conditions of example 1, in the same container, using the same load, except that a mixture of aluminium chloride and ethylbenzene in dichloromethane portions add propionate. After all described in example 1 procedures obtain 4.5 g of the target 1-acetyl-4-propenylbenzene (yield 32%, counting on taken ethylbenzene).

Example 4.

In the conditions of example 1, using the same load, except that the acylation of benzene is carried out at a temperature of 25-30°C for 1 h After all described in example 1 procedures obtain 7.1 g of the target 1-acetyl-4-propenylbenzene (yield 39%, counting on taken ethylbenzene).

Example 5.

In the conditions of example 1, using the same load, except that the acylation of benzene is carried out at a temperature of 35-40°C for 20 minutes After all described in example 1 procedures obtain 6.3 g of the target 1-acetyl-4-propenylbenzene (yield 35%, counting on taken ethylbenzene).

Example 6.

In the conditions of example 1, using the same load, except that the oxidation of 1-propionyl 4-ethylbenzene is carried out at a temperature of 75-80°C for 3 minutes After all described in example 1 procedures obtain 6.1 g of the target 1-acetyl-4-propenylbenzene (yield 33%, counting on taken ethylbenzene).

1. The way to obtain 1-acetyl-4-propenylbenzene 4-EtCOC₆H₄COMe from the causesa fact, as source use propionate and ethylbenzene in the environment of organic solvent, the reaction is carried out in the presence of anhydrous aluminum chloride at a temperature of 25-40°C for 20-60 min, with the formation of the intermediate product 1-propionyl 4-ethylbenzene, which is being allocated and then oxidized with potassium permanganate in aqueous solution magnesium nitrate at a temperature of 65-80°C for 3-5 h, forms a target product; selection last conducted by extraction with toluene, followed by recrystallization from n-hexane or petroleum ether.

2. The method according to claim 1, characterized in that the source components are taken in a molar ratio of ethylbenzene:propionate:aluminium chloride anhydrous, equal(0,5-1,5):(0,5-1,5):(1-2,5) (preferably 1:1:1.5) and concentrations of reagents of 0.5-1.5, 0.5 to 1.5, 1-2,5 mol/l, respectively (preferably 1.1 and 1.5 mol/l), and the oxidation of 1-propionyl 4-ethylbenzene is carried out at a molar ratio of reagents 1-propionyl 4-ethylbenzene:permanganate of potassium nitrate magnesium shestibalny=(0,5-1,5):(0,5-1,5):(0,5-1,5) (preferably 1:1.1:1) and concentration of 1-propionyl 4-ethylbenzene and nitrate magnesium setevogo 0.3 to 0.4, 0.3 to 0.5 mol/l, respectively (preferably of 0.35 and 0.39 mol/l).

3. The method according to claim 1, characterized in that the organic solvents used benzene and dichloromethane.

4. The method according to claim 1, ex is different, however, what is the maximum yield of 1-acetyl-4-propenylbenzene is achieved by observing the following order of process: to a solution of propionitrile and anhydrous aluminium chloride in dichloromethane add ethylbenzene.