KR102392169B1 - Method for manufacturing substituted cyclopentadiene - Google Patents

Abstract

The present invention relates to a method for preparing a substituted cyclopentadiene using a strong base and an etheric solvent having a high boiling point. Using this production method, economical mass production of high-purity alkyl-substituted cyclopentadiene is possible.

Description

Method for manufacturing substituted cyclopentadiene

The present invention relates to a method for preparing a substituted cyclopentadiene using a strong base and an etheric solvent having a high boiling point.

When the substituted cyclopentadiene derivative is reacted with a metal such as zirconium in the presence of a base, a metallocene complex is formed.

The synthesized metallocene catalyst is a compound that is usefully used as a catalyst in organic chemical reactions, and this metallocene complex is known to play an excellent catalyst role in the polymerization of olefins. A metallocene catalyst made using a cyclopentadiene derivative with an alkyl group is widely used in the polymerization of alkene because the properties of the polymer can be controlled in the polymer synthesis step.

Therefore, in order to synthesize an industrially important metallocene complex, methods for synthesizing cyclopentadiene substituted with various kinds of alkyl groups are known. As a method of synthesizing a cyclopentadiene compound with an alkyl group, there is a method of synthesizing a cyclopentadiene having a double bond, such as fulvene, by reducing it with LiAlH ₄ . However, this method has many problems in the separation of the synthesized product.

Another method is to obtain an anion by dissolving cyclopentadiene in a monoether solvent such as THF and reacting it with a strong base, and then reacting the anion with a halogenated alkane compound. As a strong base, sodium metal and Grignard reagents can be used. However, since these methods use a solvent such as THF, there is a problem in separating the solvent and the product when the boiling point of the product is low.

US Registered Patent No. 6884901

Accordingly, the present inventors have diligently researched a method for preparing a substituted cyclopentadiene that can be mass-produced economically, and as a result, a cyclopentadienyl anion is generated using a strong base instead of an expensive reagent to produce an alkyl-substituted cyclopentadiene derivative while preparing an alkyl-substituted cyclopentadiene derivative in an ether solvent. The present invention was completed by discovering that high-purity cyclopentadiene substituted in large quantities can be produced by easy distillation under reduced pressure by using a stable reaction solvent having a high boiling point.

An aspect of the present invention is a first step (S100) of preparing a base solution by adding a base having a pKa of 17 or higher to an ether solvent having a boiling point of 150°C or higher with reference to FIG. 1 ; a second step (S200) of adding cyclopentadiene to the base solution and stirring to produce a cyclopentadienyl anion mixed solution; a third step (S300) of preparing an alkyl-substituted cyclopentadiene solution by adding an alkyl halide to the cyclopentadienyl anion mixture solution and stirring; and a fourth step (S400) of separating the alkyl-substituted cyclopentadiene by distilling the solution prepared in the third step under reduced pressure.

The present invention relates to a cyclopentadienyl anion using a strong base, among others, an alkali metal amide or alkali metal hydride, alkali metal silylamide, alkali metal, alkali metal alkoxide or lithium alkyl having a pKa of 17 or higher in an ether solvent having a high molecular weight. It relates to a method for preparing substituted cyclopentadiene by reacting with an alkyl halide, wherein cyclopentadiene is an economical mass of substituted cyclopentadiene that can be usefully used in metallocene complex synthesis and manufacturing fields such as pharmaceuticals/polymers, etc. It is characterized by a production manufacturing method.

As used herein, the term “substituted” means that the group after the term has one or more moieties in place of one or more hydrogens at any position, and the moiety may be a C1 to C10 alkyl group.

The first step (S100) of the present invention may refer to a step of using a strong base having a pKa of 17 or more instead of a conventional expensive source of cyclopentadienyl anion.

The strong base having a pKa of 17 or more in the first step (S100) may be an alkali metal amide, an alkali metal hydride, an alkali metal silylamide, an alkali metal, an alkali metal alkoxide, or lithium alkyl.

Specifically, the alkali metal amides (alkali metal amides) may be any one base selected from the group consisting of sodium amide (NaNH ₂ ), potassium amide (KNH ₂ ), and lithium amide (LiNH ₂ ). For alkali metal amides, it is a strong base with a pKa of about 38.

Specifically, the alkali metal hydride may be any one base selected from the group consisting of sodium hydride (NaH), lithium hydride (LiH), and potassium hydride (KH). For alkali metal halides, it is a strong base with a pKa of about 35.

The alkali metal silylamides are specifically sodium hexamethylsilylamide (NaHMDS), potassium hexamethylsilylamide (KHMDS) and lithium hexamethylsilylamide (LiHMDS). can For alkali metal silylamides, it is a strong base with a pKa of about 25.

Specifically, the alkali metal may be any one base selected from the group consisting of sodium (Na), lithium (Li), and potassium (K). For alkali metals, it is a strong base with a pKa of about 35 or higher.

Specifically, the alkali metal alkoxide may be any one base selected from the group consisting of sodium t-butoxide (NaOtBu), lithium t-butoxide (LiOtBu), and potassium t-butoxide (KOtBu). For alkali metal alkoxides, it is a strong base with a pKa of about 19.

In addition, the lithium alkyl may be more specifically the alkyl having 1 to 10 carbon atoms, and is a strong base having a pKa of about 50.

The ether solvent in the first step (S100) may have a boiling point of 150° C. or higher.

The ether solvent in the first step (S100) is typically a glyme solvent, and the glyme is also called glycol diether and is a saturated acyclic polyether that does not contain other functional groups. It is a polar aprotic solvent and is chemically stable, even under basic conditions. In addition, the longer the chain of glyme, the better the reaction rate. This may be because polyglyme and the like have improved cation dissolving ability compared to monoglyme.

Specifically, the glyme solvent may be any one selected from the group consisting of diglyme, triglyme, tetraglyme, pentaglyme, hexaglyme, heptaglyme, octaglyme, and polyglyme. . The solvent used in one embodiment of the present invention is triglyme and has a boiling point of about 220°C.

In the first step (S100), the ether solvent is a compound having a high boiling point R-(-OCH ₂ CH ₂ -) _n -OR' (R=alkyl, R'=alkyl) structure ([Formula 1]) The phosphorus may be polyethylene glycol dialkyl ether. The polyethylene glycol dialkyl ether may mean a liquid at room temperature and pressure. More specifically, R and R' may be any one selected from the group consisting of linear, pulverized, and cyclic alkyl having 2 to 6 carbon atoms, and n may mean an integer of 1 to 8. It has a high boiling point similar to glyme, and may be a suitable solvent for the vacuum distillation of the present invention.

In the first step (S100), the ether solvent is a compound having a high boiling point R-(-OCH ₂ CHMe-) _n -OR' (R=alkyl, R'=alkyl) structure ([Formula 2]) It may be polypropylene glycol dialkyl ether. The polypropylene glycol dialkyl ether may mean that it is liquid at room temperature and pressure. More specifically, R and R' are any one selected from the group consisting of linear, pulverized, and cyclic alkyl having 1 to 6 carbon atoms, and n may mean an integer of 1 to 8, similar to glyme. It may be a solvent suitable for the vacuum distillation of the present invention because of its high boiling point.

In the first step (S100), the ether solvent may be a dialkyl ether, a compound having a high boiling point R-O-R' (R=alkyl, R'=alkyl) structure ([Formula 3]). The dialkyl ether may mean a liquid at room temperature and pressure. More specifically, R and R' may be any one selected from the group consisting of straight-chain, pulverized, and cyclic alkyl having 4 to 10 carbon atoms. It has a high boiling point similar to glyme, and may be a suitable solvent for the vacuum distillation of the present invention.

The second step (S200) may refer to a step of allowing the base to generate a cyclopentadienyl anion intermediate from cyclopentadiene.

In the second step (S200), the stirring may be performed using a magnetic bar at 60 rpm to 300 rpm or less for about 1 hour to about 2 hours. The temperature conditions during stirring may be different depending on the reactants, but may be made at about 0°C to 30°C.

The third step (S300) is a step of preparing an alkyl-substituted cyclopentadiene solution by adding an alkyl halide to the cyclopentadienyl anion mixed solution and then stirring. Specifically, the cyclopentadienyl anion is mixed with an alkyl halide A nucleophilic substitution reaction may be performed to obtain a solution containing alkyl-substituted cyclopentadiene.

In the third step (S300), in the alkyl halide, the alkyl may have 1 to 10 carbon atoms, and the halide may be F, Cl, Br, or I. The alkyl is any one alkyl selected from the group consisting of linear, pulverized, and cyclic alkyl having 1 to 10 carbon atoms, and non-limiting examples of the alkyl substituent include methyl, ethyl, n-propyl, isopropyl, n-butyl , t-butyl, s-butyl, iso-butyl, n-pentyl, t-pentyl, iso-pentyl, s-pentyl, neo-pentyl, straight and branched hexyl, cyclopentyl, or cyclohexyl.

In the third step (S300), the alkyl halide may be added slowly over about 1 to 2 hours. This is to minimize unreacted alkyl halides and to minimize by-products.

In the third step (S300), the stirring may be performed sufficiently at a temperature of about 24° C. to about 34° C. using a magnetic bar for about 10 to 20 hours. The stirring speed may be about 60 rpm to 300 rpm, but is not limited thereto.

The fourth step (S400) is a step of separating the alkyl-substituted cyclopentadiene from the solution prepared in the third step (S300). Specifically, the solvent is removed by distillation under reduced pressure, and the final product is an alkyl-substituted cyclo It may refer to the step of separating pentadiene.

As used herein, the term 'reduced distillation' may refer to a method of increasing the distillation rate by reducing the pressure applied to the liquid in order to separate a liquid mixture having a relatively high boiling point. Such distillation under reduced pressure has the advantage of increasing the distillation amount per hour and separating the product at a low temperature.

The boiling point of the alkyl-substituted cyclopentadiene finally produced in the fourth step (S400) is about 100° C. or less, so for example, conventional THF (when dissolved in a solvent with a boiling point of about 66° C., even if separated by vacuum distillation, no solvent is included. However, in the present invention, it can be easily separated by vacuum distillation by using a solvent having a large boiling point difference from the alkyl-substituted cyclopentadiene.

The vacuum degree of the vacuum distillation in the fourth step (S400) may be adjusted using a vacuum pump, and the vacuum degree may be 3 torr to 50 torr. If the pressure is maintained as low as in the above range, the boiling point is lowered, so that the final product, the alkyl-substituted cyclopentadiene, can be separated in the temperature range of 10°C to 100°C.

The present invention is theoretically to completely react an equimolar amount of a base with a pKa of about 17 or higher, cyclopentadiene, and an alkyl halide as a source of an alkyl group, but within a certain mole range, in order to reduce the production of undesirable impurities in the reaction mixture, The reactants can be mixed in equal mole ratios.

Specifically, according to an embodiment of the present invention, in order to obtain cyclopentadiene of high purity,

In the second step (S200), the cyclopentadiene may be added to the base having a pKa of about 17 or more in a molar ratio of 1:0.9 to 1:1.1, and more preferably in a molar ratio of 1:0.9 to 1:1. there is.

In the third step (S300), the alkyl halide may be added to the cyclopentadiene in a molar ratio of 1: 0.5 to 1:1.

The present inventors have completed an economical method for mass production of high-purity alkyl-substituted cyclopentadiene using a strong base and an ether solvent having a high boiling point. The alkyl-substituted cyclopentadiene produced by the above preparation method can contribute economically to the synthesis of a metallocene complex, and will be usefully used in the manufacture of pharmaceuticals and polymers.

1 is a flowchart of a method for preparing an alkyl-substituted cyclopentadiene.

Hereinafter, the present invention will be described in more detail through examples. These Examples are for explaining the present invention in more detail, and the scope of the present invention is not limited by these Examples.

Example 1. Preparation of ethylcyclopenta-1,3-diene

[Scheme 1]

The reaction was carried out as shown in Scheme 1 above. The reactants were mixed to proceed with the reaction. NaNH ₂ (about 101 g, about 2.59 mol) was added to triglyme (about 1 L) and the solution was stirred at about 0°C. Cyclopenta-1,3-diene (about 180 g, about 2.73 mol) was slowly added to this solution for about 1.5 hours. In this process, it was confirmed that the reaction proceeded through the release of ammonia gas. The reaction mixture was then stirred at about 0° C. for about 1 hour further. Bromoethane (about 267 g, about 2,45 mol) was added to the reaction mixture over about 1.5 hours. (The internal temperature is kept below about 15°C). The reaction mixture was brought to room temperature and stirred for about 15 hours. The progress of the reaction was confirmed by NMR by taking a portion of the solution. After the reaction was terminated, the solution was distilled in a vacuum of about 12 torr. At first, because ammonia gas came out, the temperature was raised slowly. It was confirmed that a product was formed through NMR analysis by collecting the products at a gas temperature of about 30°C to 32°C. ¹ H NMR (300 MHz, CDCl ₃ ): δ 6.53-5.95 (m, 3H), 2.98-2.79 (m, 2H), 2.47-2.26 (m, 2H), 1.14 (t, J = 6 Hz, 3H) .

Finally, about 158 g, about 1.68 mol of ethylcyclopenta-1,3-diene was obtained, which was calculated in a yield of about 69%.

Example 2. Isopropylcyclopenta-1,3-diene

[Scheme 2]

The reaction was carried out as shown in Scheme 2 above. NaNH ₂ (about 81.4 g, about 2.09 mol) was added to triglyme (about 870 mL) and the solution was stirred at 0°C. Cyclopenta-1,3-diene (about 243 g, about 1.98 mol) was slowly added to this solution for about 1 hour. In this process, it was confirmed that the reaction proceeded through the release of ammonia gas. The reaction mixture was then stirred at about 0° C. for about 1 hour further. 2-Bromopropane (ca. 243 g, ca. 1.98 mol) was added to the reaction mixture over 1 h (the internal temperature was maintained below about 15° C.). The reaction mixture was brought to room temperature and stirred for about 15 hours. The progress of the reaction was confirmed by NMR by taking a portion of the solution. After the reaction was terminated, the solution was distilled in a vacuum of about 12 torr. At first, because ammonia gas came out, the temperature was raised slowly. It was confirmed that a product was formed through NMR analysis by collecting the gases from about 28°C to 30°C. ¹ H NMR (300 MHz, CDCl ₃ ): δ6.59-5.96 (m, 3H), 3.01-2.88 (m, 2H), 2.77-2.59 (m, 1H), 1.15 (d, J = 9 Hz, 6H) ).

Finally, about 131 g of isopropylcyclopenta-1,3-diene was obtained, and about 1.21 mol was obtained, which was calculated in a yield of about 61%.

Example 3. sec -Preparation of butylcyclopenta-1,3-diene

[Scheme 3]

The reaction was carried out as shown in Scheme 3 above. NaNH ₂ (about 84.2 g, about 2.09 mol) was added to triglyme (about 1 L) and the solution was stirred at about 23°C. Cyclopenta-1,3-diene (about 150 g, about 2.20 mol) was slowly added to this solution for 1 hour. In this process, it was confirmed that the reaction proceeded through the release of ammonia gas. The reaction mixture was then stirred at 23° C. for a further 1 h. 2-Bromobutane (about 280 g, about 1.98 mol) was added to the reaction mixture over 1 hour (the internal temperature was maintained below about 28°C). The temperature of the reaction mixture was lowered to room temperature and stirred for about 15 hours. The progress of the reaction was confirmed by NMR by taking a portion of the solution. After the reaction was terminated, the solution was distilled in a vacuum of about 9 torr. At first, because ammonia gas came out, the temperature was raised slowly. It was confirmed that the product was produced through NMR analysis by collecting the gas at a gas temperature of about 20 ° C to 22 ° C. ¹ H NMR (300 MHz, CDCl ₃ ): δ6.53-5.96 (m, 3H), 2.98-2.84 (m, 2H), 2.56-2.37 (m, 1H), 1.63-1.36 (m, 2H), 1.12 (d, J = 9 Hz, 3H), 0.85 (t, J = 9 Hz, 3H)

Finally, about 110 g, about 0.90 mol of sec -butylcyclopenta-1,3-diene was obtained, which was calculated in a yield of about 45%.

As described above, it was confirmed that the production of substituted cyclopentadiene is possible even by economical use of a base and easy distillation under reduced pressure through the production method according to an embodiment of the present invention. It can be usefully used in the manufacture of catalysts, pharmaceuticals, polymers, etc. using pentadiene.

Although the above has been described with reference to a preferred embodiment of the present invention, those skilled in the art or those having ordinary skill in the art will not depart from the spirit and scope of the present invention described in the claims to be described later. It will be understood that various modifications and variations of the present invention can be made without departing from the scope of the present invention.

Accordingly, the technical scope of the present invention should not be limited to the content described in the detailed description of the specification, but should be defined by the claims.

S100: base solution preparation step
S200: cyclopentadienyl anion generation step
S300: Alkyl-substituted cyclopentadiene production step
S400: Separation of alkyl-substituted cyclopentadiene

Claims (10)

A first step of preparing a base solution by adding a base having a pKa of 17 or higher to a glyme solvent having a boiling point of 150°C or higher;
a second step of adding cyclopentadiene to the base solution and stirring to produce a cyclopentadienyl anion mixed solution;
a third step of preparing an alkyl-substituted cyclopentadiene solution by adding an alkyl halide to the cyclopentadienyl anion mixture solution and stirring; and
A fourth step of separating the alkyl-substituted cyclopentadiene by distilling the solution prepared in the third step under reduced pressure,
The vacuum distillation is carried out at 3 torr to 50 torr and 10 to 100 °C,
The base pKa of 17 or more is sodium amide (NaNH ₂ ), potassium amide (KNH ₂ ), sodium hydride (NaH), potassium hydride (KH), sodium hexamethylsilylamide (NaHMDS), potassium hexamethylsilylamide (KHMDS) ), sodium (Na), potassium (K), sodium t-butoxide (NaOtBu) and potassium t-butoxide (KOtBu) any one base selected from the group consisting of, a method for producing a substituted cyclopentadiene.
delete delete According to claim 1,
The glyme solvent is any one selected from the group consisting of diglyme, triglyme, tetraglyme, pentaglyme, hexaglyme, heptaglyme, octaglyme and polyglyme, a substituted cyclopenta Diene manufacturing method.
delete delete delete According to claim 1,
In the alkyl halide, the alkyl is any one selected from the group consisting of linear, pulverized, and cyclic alkyl having 1 to 10 carbon atoms,
The halide is one selected from the group consisting of F, Cl, Br, I, a method for producing a substituted cyclopentadiene.
According to claim 1,
The method for producing a substituted cyclopentadiene, wherein the cyclopentadiene is added to the base with a pKa of 17 or more in a molar ratio of 1: 0.9 to 1: 1.1.
According to claim 1,
A method for producing a substituted cyclopentadiene, wherein the alkyl halide is added to the cyclopentadiene in a molar ratio of 1:0.5 to 1:1.

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