PL213609B1 - Process for the preparation of norbornene derivatives - Google Patents

Description

The subject of the invention is a process for the preparation of norbornene derivatives by the Diels-Alder reaction of cyclopentadiene with a dienophile at room temperature and atmospheric pressure in the presence of an ionic liquid as a solvent and catalyst.

The Diels-Alder reaction is very important in chemistry and organic technology, because it allows to obtain cyclic and / or bicyclic compounds from readily available substrates. The compounds obtained in the cycloaddition reaction are used in the pharmaceutical and petrochemical industries. For example, in the production of vitamins A, D2, E and K, and hormones - gibberellic acid, cortisone acetate. Some are used as monomers in polymerization reactions to synthesize plastics with specific properties. There is a huge number of publications on this subject in the literature. In the first place, a suitable reaction medium, i.e. a solvent, was sought. Most preferably, the Diels-Alder reaction is carried out in water [O. Diels, K. Alder, Ann. Chem. 1931, 390, 243]. Additionally, as proved by Rideout and Breslow, the formation of hydrogen bonds within the solvent has a positive effect on the increase of the reaction rate [D. C. Rideout, R. Breslow, J. Am. Chem. Soc. 1980, 102, 7816]. Unfortunately, a serious limitation is the poor solubility of organic compounds in water, and they are the reactants in this reaction. Thus, other solutions were used, including: solutions of LiCl, NaCl and LiClO4 salts in diethyl ether [Y. Pocker, D. L. Ellsworth, J. Am. Chem. Soc. 1977, 99, 2276] or supercritical carbon dioxide [R. D. Weinstein, A. R. Renslo, R. L. Danheiser, J. G. Harris, J. W. Tester, J. Phys. Chem. 1996, 100, 12337] as the reaction medium. Caring for the natural environment causes the abandonment of the use of conventional organic solvents, commonly considered harmful, and turns them into other. In traditional methods of obtaining norbornene derivatives in the Diels-Alder reaction, solvents such as methanol, acetonitrile, and toluene are used. The Diels-Alder reaction is used to prepare many simple and complex compounds. The wide use of this reaction in the production of norbornene is known. The type of solvent affects the selectivity and efficiency of the conversion to the desired product and its speed. Ionic liquids seem to be a very attractive reaction medium. These are new generation solvents, due to their specific properties, they are included in the group of so-called green solvents and are used as substitutes for volatile organic solvents. It is possible to use them together with Lewis acid catalysts, which additionally contribute to increasing the yield and selectivity of the reaction (G. Silvero, MJ Arevalo, JL Bravo, M. Avalos, JL Jimenez, I. Lopez, Tetrahedron, 2005, 61, 7105 - 7111; S. Kobayashi, I. Hachiya, M. Araki, H. Ishitani, Tetrahedron Letters, 1993, 34, 1755-3758; S. Otto, G. Boccaletti, JBFN Engberts, J. Am. Chem. Soc. 1998 , 120, 4238-4239). Ionic liquids dissolve these catalysts well. They provide an anhydrous reaction environment which is essential for the deactivation of catalysts by moisture. Due to the low vapor pressure of the ionic liquid, it is easy to isolate the reaction products from the ionic liquid by distillation or extraction, thanks to which the catalyst can be used multiple times. There are examples of the use of ionic liquids from the group of imidazolium and phosphonium salts as solvents in the Diels-Alder reaction (T. Fisher, A. Sethi, T. Welton, J. Woolf, Tetrahedron Lett. 1999, 40, 793-796; A. Aggarwal) , NL Lancaster, AR Sethi, T. Welton, Green Chem. 2002, 4, 517-520; E. Janus, W. Stefaniak, Catalysis Letters, 2008; 124 (1), 105-110.). It is known from US Patent No. 7,019,188, 2006 to use pyridinium ionic liquids in the process of selective isolation of alkenes from hydrocarbon fractions. The treatment of diesel engine fuel from sulfur-containing compounds is based on a similar phenomenon. In this case, the extractant is 3-methyl-N-propylpyridinium tetrafluoroborate [Hongshuai Gao, Yuguang Li, Yong Wu, Mingfang Luo, Qiang Li, Jianmin Xing, Huizhou Liu, Energy & Fuels 2009. 23. 2690]. Ionic liquids, also N-ethylpyridinium tetrafluoroborate and N-hexylpyridinium trifluoroacetate were used in the Diels-Alder reaction [Y. Xiao, S. V. Malhotra, Tetrahedron Letters, 2004. 45, 8339]. Reactions were carried out between isoprene and dienophiles: acrylonitrile, acrylic acid and methacrylic acid, the highest yield was obtained after 2 hours in N-hexylpyridinium trifluoroacetate.

The method of obtaining norbornene derivatives according to the invention consists in the Diels-Alder reaction of cyclopentadiene with a dienophile at room temperature, atmospheric pressure, in the presence of a catalyst and an ionic liquid as a solvent. The essence of the process is that the reaction is carried out in a catalytic system consisting of an ionic liquid - N-hexylpyridinium (bistrifluoromethylsulfonyl) imide of the formula 1 and a metal chloride catalyst of the formula

PL 213 609 B1

MClx or a metal trifluoromethanesulfonate of formula M (OTf) x, wherein M is a metal of groups 1 to 13 of the Periodic Table of the Elements, OTf - triflate group (CF3SO3 ^- ) x - metal valency. The metals of groups 1 to 13 are: Li, Na, K, Mg, Ca, Y, Yb, Zn, In, Al, Ag, Cu, La, Nd, Bi. The following are used as dienophiles: dimethyl maleate, methyl vinyl ketone, ethyl vinyl ketone, 4-hexen-3-one, methyl, ethyl, n-butyl acrylate and methacrolein. The concentration of dienophile in the ionic liquid is from 1 to 33 mol / dm ³ . of the diene from 1.5 to 12 mol / dm ³ , and the molar ratio of dienophile to diene is constant at 1: 1.5. The catalyst is used in such an amount that its molar ratio relative to the ionic liquid is equal to

0.0002: 0.05: 1. Preferably, after the reaction is completed, the mixture is distilled under reduced pressure to isolate the product and unchanged raw materials, and the ionic liquid with metal chloride or trifluoromethanesulfonate remaining in the distillation cavity is reused as the catalyst system.

The advantage of the process according to the invention is that a mixture of products is obtained in high yield with a predominance of the endo isomer, and the process is carried out under mild temperature conditions, under normal pressure, in simple apparatus, in a short time. The use of catalysts: MClx, M (OTf) x in the presence of an ionic liquid significantly increases the efficiency of the Diels-Alder reaction and its stereoselectivity. In these systems, after using the mentioned dienophiles and catalytic systems, the yield of the cycloaddition product is at the level of 90% by weight. after 10: 300 minutes, at room temperature and atmospheric pressure. Stereoselectivity, expressed by the endo to exo isomer ratio, ranges from 5-15. The catalyst system of the ionic liquid and the catalyst according to the invention can be used repeatedly in many cycles of the Diels-Alder reaction with consistent efficiency and stereo selectivity.

The method of obtaining norbornene derivatives is explained in more detail in the examples.

Example I ₃

The catalyst-ZnCl2 was introduced into the reactor in the form of a 4 cm ³ screw cap vial. 0.0014 g (0.01 mmol) and N-hexylpyridinium bis (trifluoromethylsulfonyl) imide in the amount of 0.3481 g (1 mmol). The contents of the vial were stirred with a magnetic stirrer in order to dissolve the zinc (II) chloride in the ionic liquid well. Then, methyl vinyl ketone was added in an amount of 0.0701 g (1 mmol) and cyclopentadiene in an amount of 0.099 g (1.5 mmol). The reaction vial was placed in a thermostated bath heated to 25 ° C. Samples of the reaction mixture were taken at 15-minute intervals until the yield was over 90% and analyzed by gas chromatography. Based on this analysis, the conversion of methyl vinyl ketone and the yield of two products were determined: endo-2-acetyl-5-norbornene and exo-2-acetyl-5-norbornene. The yield of the products was measured at 96% after 30 minutes. The selectivity, expressed as the molar ratio of endo to exo isomer, was 15.6.

Example II ₃

In a reactor with a capacity of 5 cm ³ was dissolved 0.0512 g of Mg (OTf) 2 2.780 g (8 mmoles) of bis (trifluoromethylsulfonyl) imidku N-heksylopirydyniowego. Dimethyl maleate was introduced successively in the amount of 1.154 g (8 mmol) and 0.792 g (12 mmol) of cyclopentadiene. The reaction was carried out at 25 ° C for 30 minutes. The yield of the products (as in Example 1) determined by gas chromatography was 98% and the molar ratio of endo to exo isomers was 7.0. The reaction products in the form of a mixture of endo, endo-2,3-di (methoxycarbonyl) -5-norbornene and exo, exo-2,3-di (methoxycarbonyl) -5-norbornene isomers were separated from the reaction medium by distillation under a pressure of 1 mm Hg in the temperature range of 95 ° C-105 ° C. New portions of the reactants, ie cyclopentadiene and methyl vinyl ketone, were added to the remaining ionic liquid containing the catalyst in the same amounts as before. The yield and selectivity of the reaction were controlled in the same manner and an equally high yield was obtained. The catalytic system was recirculated a total of 4 times without significantly changing the reaction yield and selectivity.

The obtained results of the yield and selectivity are summarized in Table 1.

T a b e l a 1

The recirculation rate of the ionic liquid with the catalyst 0 1 2 3 4 Endo / exo isomer yield / ratio 98 / 7.0 97 / 7.1 94 / 6.8 91 / 6.7 89 / 6.4

PL 213 609 B1

Example III ₃

The reactor in the form of a 4 cm ³ screw cap vial, equipped with a magnetic stirrer, was introduced in the following order: catalyst-Mg (OTf) 2 in the amount of 0.03 mmol (0.00967 g), bis (trifluoromethylsulfonyl) imide N-hexylpyridinium ( 1 mmol), 4-hexen-3-one in the amount of 0.0981 g (1 mmol). Finally, cyclopentadiene was added in an amount of 0.098 g (1.5 mmol). The vial with the mixture was placed in a thermostatic bath heated to 25 ° C. On the basis of the GC analysis, the conversion of the ketone and the yield of two products were determined: endo, exo-2-ethoxyl-3-methyl-5-norbornene and exo, endo-2-ethoxyl-3-methyl-5-norbornene and the stereoselectivity expressed by the molar ratio of these products, endo / exo for short. After 4 hours, a mixture of isomers was obtained with a yield of 90%, the ratio of endo and exo isomer was 14.8.

Example IV ₃

The reaction was carried out in a 4 cm ³ screw cap vial containing a rotor of a magnetic stirrer. The vial was loaded in the following order: catalyst-MgCl2 in the amount of 0.05 mmol (0.00476 g), which was dissolved in 0.3481 g of N-hexylpyridinium bis (trifluoromethylsulfonyl) imide (1 mmol), metacrolein in the amount of 0.0701 g ( 1 mmol). Then, cyclopentadiene was introduced in an amount of 0.099 g (1.5 mmol). The vial with the reaction mixture was placed in a thermostatic bath heated to 25 ° C continuously. On the basis of the GC analysis, the conversion of metacrolein and the yield of the following products were determined: endo-2-acetyl-2-methyl-5-norbornene and exo-2-acetyl-2-methyl-5-norbornene as well as the stereoselectivity expressed by the molar ratio of these products, abbreviated as endo / exo. After 30 minutes, the product was obtained in a quantitative yield of 72%, the quantitative ratio between the endo and exo isomer was 6.4.

Example V ₃

The reaction was carried out in a 4 cm ³ screw cap vial. The vial was charged in the following order: catalyst-ZnCl2, 0.05 mmol (0.0068 g), N-hexylpyridinium bis (trifluoromethylsulfonyl) imide 0.3484 g (1 mmol), ethyl acrylate 0.100 g ( 1 mmol), cyclopentadiene in the amount of 0.099 g (1.5 mmol). The reaction vial was placed in a thermostated bath heated to 25 ° C. During the synthesis, samples of the reaction mixture were tapped and subjected to GC analysis. On their basis, after three hours, the yield of the sum of endo and exo isomers was established at 93%. The selectivity of the conversion, expressed as the ratio between the isomers of endo-2-ethoxycarbonyl-5-norbornene and exo-2-ethoxycarbonyl-5-norbornene, was 13.2.

Example VI ₃

The reaction was carried out in a 5 cm ³ round bottom flask equipped with a rotor of a magnetic stirrer. The flask was charged in the following order: catalyst-YCl3 in the amount of 0.04 mmol (0.0078 g), ionic liquid N-hexylpyridinium bis (trifluoromethylsulfonyl) imide 0.3842 g (1 mmol), methyl acrylate 0.084 g (1 mmol), cyclopentadiene 0.0991 g (1.5 mmol). The reaction flask was placed in a thermostated bath heated to 25 ° C. After 15 minutes, a sample of the reaction mixture was taken. Based on GC analysis, the total conversion of methyl acrylate was calculated to be 94% and the stereoselectivity expressed as the molar ratio of the two products: endo-2-methoxycarbonyl-5-norbornene and exo-2-methoxycarbonyl-5-norbornene and these products was 11.7.

Example VII ₃

The reaction was carried out in a 4 cm ³ screw cap vial with a magnetic stirrer rotor. There was a magnetic stirrer in each of them. The vial was charged in the following order: catalyst-Nd (OTf) 3 in the amount of 0.01 mmol (0.0035 g), ionic liquid bis (trifluoromethylsulfonyl) N-hexylpyridinium imide in the amount of 0.347 g (1 mmol), n-butyl acrylate in the amount of 0.123 g (1 mmol), cyclopentadiene 0.099 g (1.5 mmol). The vial with the mixture was placed in a thermostatic bath heated to 25 ° C. After 4 hours from the moment of cyclopentadiene addition), a sample of the reaction mixture was taken and, based on GC analysis, this sample was calculated, the conversion of n-butyl acrylate was 91%. The selectivity, expressed as the ratio of the quantity between the endo-2-propoxycarbonyl-5-norbornene isomers and the exo-2-propoxycarbonyl-5-norbornene isomers was 9.1.

Example VIII ₃

The reaction was carried out in a 5 cm ³ spherical flask containing a PTFE-coated magnetic rotor. 0.01 mmol (0.0062 g) of catalyst Yb (OTf) ₃ -xH ₂ O was introduced into the flask and dissolved in N-hexylpyridinium bis (trifluoromethylsulfonyl) imide used in the amount of

PL 213 609 B1

0.385 g (1 mmol), then added ethyl vinyl ketone in an amount of 0.083 g (1 mmol) and cyclopentadiene in an amount of 0.099 g (1.5 mmol). The pot with the mixture was placed in a thermostatic bath heated to 25 ° C. After 30 minutes (counting from the moment of adding cyclopentadiene) a sample of the reaction mixture was taken. Based on GC analysis, it was determined that the conversion of ethyl vinyl ketone was 95%, the stereoselectivity expressed as the molar ratio of the products: endo-2-ethoxyl-5-norbornene and exo-2-ethoxyl-5-norbornene was 9.2.

Claims (5)

1. The method of obtaining norbornene derivatives by the Diels-Alder reaction of cyclopentadiene with a dienophile at room temperature, at atmospheric pressure, in the presence of a catalyst and an ionic liquid as a solvent, characterized in that the reaction is carried out in a catalytic system consisting of an ionic liquid - bis (trifluoromethylsulfonyl) N-hexylpyridinium imide of formula 1 and a metal chloride catalyst of formula MClx or a metal triflate of formula M (OTf) x, where M is a metal of groups 1 to 13 of the periodic table, OTf - triflate group (CF3SO3 ^- ), x - metal valence. 2. The method according to p. The process of claim 1, wherein the dienophiles are dimethyl maleate, methyl vinyl ketone, ethyl vinyl ketone, 4-hexen-3-one, methyl, ethyl, n-butyl acrylate and methacrolein. 3. The method according to p. 3. The method of claim 1 or 2, characterized in that the concentration of the dienophile in the ionic liquid is from 1 to 8 mol / dm ³ , the diene is from 1.5 to 12 mol / dm ³ , and the molar ratio of dienophile to diene is constant at 1: 1, 5. 4. The method according to p. The method of claim 1, wherein the catalyst is used in such an amount that its molar ratio with respect to the ionic liquid is 0.0002 * 0.05: 1. 5. The method according to p. A process as claimed in any of claims 1 to 5, characterized in that the mixture, after the reaction is completed, is subjected to distillation under reduced pressure to isolate the product and unchanged raw materials, and the ionic liquid with metal chloride or trifluoromethanesulfonate remaining in the distillation cavity is reused as a catalyst system.