Monoalkylation of cyclopentadiene
The method addresses the dimerization and alkylation challenges of cyclopentadienes by using a modifier in the reaction with dicyclopentadiene magnesium or cyclopentadiene magnesium halide to produce monoalkylated cyclopentadiene with high selectivity and yield, enhancing the efficiency and purity of the synthesis.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- ENTEGRIS INC
- Filing Date
- 2023-07-11
- Publication Date
- 2026-06-26
AI Technical Summary
Cyclopentadienes tend to dimerize via the Diels-Alder reaction, complicating synthetic processes and reducing yields, and alkylation reactions often result in the formation of di- and tri-alkyl species, necessitating further separation and purification.
A method involving the reaction of dicyclopentadiene magnesium or cyclopentadiene magnesium halide with an alkylating agent in the presence of a modifier, such as dimethyl sulfoxide, to produce monoalkylated cyclopentadiene with high selectivity and yield, avoiding the formation of dialkylated species.
The method achieves high conversion rates of monoalkylation, with minimal dialkylated products detected, improving the efficiency and purity of cyclopentadiene derivatives production.
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Abstract
Description
[Technical Field]
[0001] This disclosure generally relates to methods for preparing monoalkylated cyclopentadiene compounds. [Background technology]
[0002] Cyclopentadienes are useful as intermediates to many other useful organic compounds. Certain alkyl-substituted cyclopentadienes are useful as synthetic lubricants. (See, for example, U.S. Patents 5,144,095 and 5,012,022.) In addition, the cyclopentadiene structure can also be found in many so-called single-site metallocene catalysts used to produce polyolefins such as polyethylene and polypropylene. (See, for example, U.S. Patent 7,579,415.)
[0003] One inherent problem in handling cyclopentadienes is their tendency to dimerize via the Diels-Alder reaction. This dimerization proceeds over several hours at room temperature but can be reversed by heating, requiring cracking in some cases. In addition, alkylation reactions using cyclopentadiene anion species can result in the formation of di- and tri-alkyl species, further complicating the synthetic regime by reducing yields and requiring further separation and purification.
[0004] Therefore, an improved methodology is needed for the monoalkylation of cyclopentadiene structures. [Overview of the Initiative]
[0005] In summary, this disclosure provides an improved method for preparing monoalkylated cyclopentadiene species in high yield and with high selectivity. The method involves reacting a solution of either dicyclopentadiene magnesium or cyclopentadiene magnesium halide with an alkylating agent in the presence of a modifier to provide a monoalkylated product. In this method, only the monoalkylated species is produced, and no detectable amounts of dialkylated product are observed by gas chromatography. [Modes for carrying out the invention]
[0006] As used in this specification and the attached claims, the singular “a,” “an,” and “the” refer to multiple subjects unless the context clearly indicates otherwise. As used in this specification and the attached claims, the term “or” generally means to include “and / or” unless the context clearly indicates otherwise.
[0007] The term "approximately" generally refers to a range of numbers that are considered equivalent to the value being described (for example, having the same function or result). In many cases, the term "approximately" may include numbers that are rounded to the nearest significant figure.
[0008] A numerical range expressed using endpoints includes all numbers contained within that range (for example, 1-5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5).
[0009] In the first aspect, this disclosure relates to formula (I): TIFF0007881043000001.tif23170[where, R 1 [These are linear or branched C1-C8 alkyl groups.] A method for preparing the compound, Formula (A) or (B): TIFF0007881043000002.tif43170[In the formula, X is a halo] The solution of the compound is brought into contact with the modifier, and then the formula R 1 -X 1 [In the formula, X 1 The present invention provides a method comprising treating with a compound [which is a halo, alkyl, or aromatic sulfonate].
[0010] In the method of this disclosure, preferably, first, the compound of formula (A) or (B) is dissolved or suspended in a solvent effective to at least partially dissolve the cyclopentadiene magnesium species or cyclopentadiene magnesium halide species, either alone or in combination with other solvents described below. In one embodiment, tetrahydrofuran (THF) is used. In particular, attempting to dissolve (A) in dimethyl sulfoxide (DMSO) at room temperature results in an exothermic reaction, producing a black / brown residue at room temperature. In the method of this disclosure, the exothermic nature of this reaction can be controlled at low temperatures to lead to the formation of the desired product (e.g., monoalkylated cyclopentadiene). In the method of this disclosure, after dissolving the starting material (A) or (B), a modifier is added, which is selected to produce a cyclopentadiene anionic ring associated with a magnesium cation, followed by the formation of formula R 1 -X 1The desired product (i.e., the compound of formula I) is obtained in high yield without observing a detectable amount of dialkylated (or trialkylated) species by gas chromatography upon addition of the compound of . In certain embodiments, the modifier is selected from solvents such as dimethyl sulfoxide; dimethylacetamide; N-methyl-2-pyrrolidone; hexamethylphosphoramide; pyridine, and its alkylated and alkylamino derivatives (an example of the latter is dimethylaminopyridine (DMAP)); crown ethers; and combinations thereof. In one embodiment, the modifier is dimethyl sulfoxide. In some embodiments, the method can produce a dialkylated (or trialkylated) product that is 1.0% or less, 0.75% or less, 0.50% or less, 0.25% or less, 0.10% or less, 0.05% or less, or 0.01% or less as measured by gas chromatography. In some embodiments, the conversion rate to the compound of formula I can be 80% or more, 82% or more, 85% or more, 87% or more, 90% or more, 92% or more, or 95% or more as measured by gas chromatography.
[0011] Formula -X 1 The group of is a suitable leaving group, such as halo, mesylate, tosylate, etc. Formula R 1 -X 1 Exemplary compounds of include methyl bromide, methyl iodide, ethyl bromide, ethyl iodide, isopropyl bromide, isopropyl iodide, ethyl tosylate, isopropyl tosylate, ethyl mesylate, isopropyl mesylate, etc.
[0012] Exemplary solvents useful for the purpose of dissolving / suspending the compound of formula (A) or (B) include solvents such as tetrahydrofuran, diethyl ether, toluene, etc., the only consideration being that the compound of formula (A) or (B) is desirably at least partially soluble in the solvent.
[0013] As used herein, the term "crown ether" refers to a cyclic compound containing several ether groups. Exemplary crown ethers include cyclic oligomers of ethylene oxide, including nitrogen-containing macrocyclic molecules. Examples include 12-crown-4, 15-crown-5, 18-crown-6, dibenzo-18-crown-6, and aza-crown. Numerous crown ethers are commercially available from Sigma Aldrich.
[0014] In certain embodiments, the modifier is present in an amount of at least about 3 molar equivalents, based on the amount of compound of formula (A) or (B) present. In other embodiments, the modifier is present in an amount of 3 to about 50 molar equivalents, based on the amount of compound of formula (A) or (B) present, and in other embodiments, the modifier is present in an amount of about 6 to about 15 molar equivalents, based on the amount of compound of formula (A) or (B) present.
[0015] As mentioned above, alkylating agents are of formula R 1 -X[wherein, R 1 [ is a compound of a linear or branched C1-C8 alkyl group, where X is a halo, e.g., bromo or iodine]. In certain embodiments, R 1 R is selected from methyl, ethyl, n-propyl, n-butyl, sec-butyl, etc. In a particular embodiment, R 1 The group is a branched chain group, such as isopropyl. Surprisingly, the result of the reaction is monoalkylation of the cyclopentadiene ring, and the dialkylated species is not detected by gas chromatography.
[0016] In various embodiments, R 1 The compound is selected from methyl, ethyl, and isopropyl. [Examples]
[0017] Example 1 - Bis(η) 5 Synthesis of cyclopentadienyl magnesium(II)-Cp2Mg Newly cracked cyclopentadiene (50 g, 0.76 mol) was dissolved in 0.7 M di-hexane in a 1 L Schlenk flask under nitrogen. n Butylmagnesium [350 mL, in hexanes or heptanes, di- n Butyl magnesium, or di- sec Butyl magnesium, or n Butyl sec Butylmagnesium can be used. It was slowly added at room temperature with stirring. The temperature during addition was maintained at 22±3°C using an isopropane / dry ice bath. After the addition was complete, the reaction mixture was stirred at room temperature for 6 hours, then cooled to 10°C, and the product formed and precipitated in the flask. The mother liquor was removed using a cannula. All volatile substances were removed under reduced pressure to produce 44.2 g of Cp2Mg in 82% yield. 1 H NMR(C6D6):6.00ppm(s, 12H, Cp-H); 13 C NMR(C6D6):107.6~107.8ppm(bm, Cp-CH)
[0018] Examples 2-5 Synthesis of Isopropyl-CpH (iPrCpH) As shown in Table 1 below, under four conditions i PrCpH was synthesized. In Examples 2 and 3, at room temperature under nitrogen, a 250 mL Schlenk flask was filled with the amounts of Cp2Mg shown in Table 1, followed by THF (46.7 g), while stirring. The Cp2Mg was completely dissolved. The amounts shown in Table 1 i PrBr (isopropyl bromide) was slowly added to the Cp2Mg solution while stirring. The resulting mixture was stirred at the time and temperature shown in Table 1, and then quenched with 5% HCl solution (50 mL). The organic phase was separated and analyzed by gas chromatography (GC). i The percentage conversion to PrCpH is shown.
[0019] In Examples 4 and 5, at room temperature under nitrogen, a 250 mL Schlenk flask was filled with the amounts of Cp2Mg shown in Table 1, followed by THF (46.7 g), while stirring. After completely dissolving the Cp2Mg, the amounts of anhydrous DMSO shown in Table 1 were slowly added to the Cp2Mg solution while stirring. The resulting mixture / slurry was stirred for 30 minutes, or until a uniform, freely flowing liquid was formed. i PrBr (isopropyl bromide) was slowly added to the Cp2Mg / DMSO slurry while stirring. The resulting mixture was stirred at the time and temperature shown in Table 1, and then quenched with 5% HCl solution (50 mL). The organic phase was separated and analyzed by GC. i The percentage conversion to PrCpH is shown. No detectable amounts of dialkylated (or trialkylated) species were observed by gas chromatography.
[0020] The results in Table 1 show that the addition of DMSO as a modifier in Examples 4 and 5 resulted in higher levels of performance than in Examples 2 and 3, where no modifier such as DMSO was added. i This indicates that it resulted in a PrCpH conversion rate of over 90%. TIFF0007881043000003.tif101170
[0021] Examples 6-7 Synthesis of ethyl-Cp(EtCpH) EtCpH was synthesized under two conditions, as shown in Table 2 below. In Example 6, Cp2Mg, followed by THF, was packed into a 250 mL Schlenk flask with stirring under nitrogen at room temperature. After completely dissolving the Cp2Mg, anhydrous DMSO was slowly added to the Cp2Mg solution with stirring. The resulting mixture / slurry was stirred for 30 minutes, or until a uniform, freely flowing liquid was formed. Ethyl bromide (EtBr) was slowly added to the Cp2Mg / DMSO slurry with stirring. The resulting mixture was stirred at room temperature for 1 hour, and then quenched with 50 mL of 5% HCl solution. The organic phase was separated, and the percentage conversion to EtCpH was shown by gas chromatography (GC) analysis. No detectable amounts of dialkylated (or trialkylated) species were observed by gas chromatography (GC) analysis.
[0022] In Example 7, Cp2Mg, followed by THF, was packed into a 250 mL Schlenk flask at room temperature under nitrogen while stirring. The Cp2Mg was completely dissolved. Ethyl bromide (EtBr) was slowly added to the Cp2Mg solution while stirring. The resulting mixture was stirred at room temperature for 1 hour, and then quenched with a 5% HCl solution (50 mL). The organic phase was separated, and the percentage conversion to EtCpH was shown by gas chromatography (GC) analysis.
[0023] The results in Table 1 show that the addition of DMSO as a modifier in Example 6 resulted in a higher EtCpH conversion rate (over 90%) than in Example 7, where no modifier such as DMSO was added. TIFF0007881043000004.tif58170
[0024] manner In the first aspect, this disclosure relates to formula (I): TIFF0007881043000005.tif23170[where, R 1 [These are linear or branched C1-C8 alkyl groups.] A method for preparing the compound, Formula (A) or (B): TIFF0007881043000006.tif41170[In the formula, X is a halo] The solution of the compound is brought into contact with the modifier, and then the formula R 1 -X 1 [In the formula, X 1 The present invention provides a method comprising treating with a compound [which is a halo, alkyl, or aromatic sulfonate].
[0025] In a second aspect, the disclosure provides a method of the first aspect, wherein the modifier is selected from the group consisting of dimethyl sulfoxide; dimethylacetamide; N-methyl-2-pyrrolidone; hexamethylphosphoramide; pyridine, and their alkylated and alkylamino derivatives, such as dimethylaminopyridine (DMAP); crown ethers; and combinations thereof.
[0026] In a third aspect, this disclosure is R 1 The present invention provides a method according to a first or second embodiment, wherein isopropyl.
[0027] In a fourth aspect, the disclosure provides the method of claim 1, wherein the alkyl or aryl sulfonate is a mesylate or tosylate.
[0028] In a fifth aspect, the disclosure provides one of the first to fourth aspects, wherein the modifier is present in an amount of at least about 3 molar equivalents, based on the amount of compound of formula (A) or (B) present.
[0029] In a sixth aspect, the disclosure provides one of the first to fourth aspects of the method wherein the modifier is present in an amount of 3 molar equivalents to about 50 molar equivalents, based on the amount of compound of formula (A) or (B) present.
[0030] In a seventh aspect, the disclosure provides one of the first to fourth aspects, wherein the modifier is present in an amount of about 6 to about 15 molar equivalents, based on the amount of compound of formula (A) or (B) present.
[0031] In the eighth aspect, the disclosure provides one of the first to seventh aspects of the method, wherein the modifier is dimethyl sulfoxide.
[0032] In the ninth aspect, the present disclosure relates to formula (I): TIFF0007881043000007.tif23170[where, R 1 [These are linear or branched C1-C8 alkyl groups.] A method for preparing the compound, Formula (A): A solution of the compound TIFF0007881043000008.tif40170 is brought into contact with a modifier, and then the formula R 1 -X 1 [In the formula, X 1 The present invention provides a method comprising treating with a compound [which is a halo, alkyl, or aromatic sulfonate].
[0033] In a tenth aspect, the disclosure provides a method according to the ninth aspect, wherein the modifier is dimethyl sulfoxide.
[0034] In the eleventh aspect, this disclosure is R 1 The present invention provides a ninth or tenth embodiment of the method, which is selected from methyl, ethyl, isopropyl, n-butyl, or sec-butyl.
[0035] In the twelfth aspect, this disclosure is R 1 The present invention provides a method according to the 9th, 10th, or 11th embodiment, wherein isopropyl.
[0036] In the 13th aspect, this disclosure is R 1 The present invention provides a method according to the 9th, 10th, or 11th embodiment, wherein is ethyl.
[0037] In a fourteenth aspect, the Disclosure relates to formula (I): TIFF0007881043000009.tif23170[where, R 1[These are linear or branched C1-C8 alkyl groups.] A method for preparing the compound, Formula (B): TIFF0007881043000010.tif23170[In the formula, X is a halo] The solution of the compound is brought into contact with the modifier, and then the formula R 1 -X 1 [In the formula, X 1 The present invention provides a method comprising treating with a compound [which is a halo, alkyl, or aromatic sulfonate].
[0038] In a 15th aspect, the disclosure provides a method of the 14th aspect, wherein the modifier is dimethyl sulfoxide.
[0039] In the sixteenth aspect, this disclosure is R 1 The present invention provides a 14th or 15th embodiment of the method, selected from methyl, ethyl, and isopropyl.
[0040] In the 17th aspect, this disclosure is R 1 The present invention provides a method according to the 14th, 15th, or 16th embodiment, wherein isopropyl.
[0041] In the 18th aspect, the disclosure provides a method according to any of the preceding aspects, wherein a dialkylated compound is formed in an amount of 1.0% or less, 0.75% or less, 0.50% or less, 0.25% or less, 0.10% or less, 0.05% or less, or 0.01% or less, as measured by gas chromatography.
[0042] In a 19th aspect, the disclosure provides a method according to any of the preceding embodiments, wherein the conversion rate of the compound of formula (I) can be measured by gas chromatography to be 80% or more, 82% or more, 85% or more, 87% or more, 90% or more, 92% or more, or 95% or more.
[0043] While several explanatory embodiments of this disclosure have been described, those skilled in the art will readily understand that other embodiments can still be constructed and used within the scope of the claims attached herein. Many of the advantages of the disclosure contained herein are stated above. However, it will be understood that this disclosure is, in many respects, for illustrative purposes only. The scope of this disclosure is, naturally, defined in the language in which the attached claims are expressed.
Claims
1. Equation (I): [In the formula, R １ C is a linear or branched chain. １ ~C ８ A method for preparing a compound which is an alkyl group, Formula (A): The process involves contacting a solution of the compound with a modifier to form a mixture, and The mixture, formula R １ -X １ [In the formula, X １ The compound is treated with a compound of [a halo, or an alkyl sulfonate or aromatic sulfonate] to form a compound of formula (I). Includes, The modifier is selected from the group consisting of dimethyl sulfoxide; dimethylacetamide; N-methyl-2-pyrrolidone; hexamethylphosphoramide; pyridine; dimethylaminopyridine; crown ether; and combinations thereof. method.
2. The method according to claim 1, wherein a dialkylated compound of 1.0% or less is formed as measured by gas chromatography.
3. The method according to claim 1, wherein the conversion rate to the compound of formula (I) is 80% or more.
4. The method according to claim 1, wherein the modifier is dimethyl sulfoxide.
5. R １ The method according to claim 1, wherein the selected element is methyl, ethyl, isopropyl, n-butyl, or sec-butyl.
6. R １ The method according to claim 5, wherein isopropyl.
7. R １ The method according to claim 5, wherein R is ethyl.
8. The method according to claim 1, wherein the alkyl sulfonate or aromatic sulfonate is a mesylate or a tosylate.
9. The method according to claim 1, wherein the modifier is present in an amount of at least 3 molar equivalents based on the amount of the compound of formula (A).
10. The method according to claim 9, wherein the modifier is present in an amount of 3 to 50 molar equivalents based on the amount of compound of formula (A) present.
11. The method according to claim 9, wherein the modifier is present in an amount of 6 to 15 molar equivalents based on the amount of the compound of formula (A).
12. Equation (I): [In the formula, R １ C is a linear or branched chain. １ ~C ８ A method for preparing a compound which is an alkyl group, Formula (B): The process involves contacting a solution of the compound [wherein X is a halo] with a modifier to form a mixture, and The mixture, formula R １ -X １ [In the formula, X １ Treatment with a compound that is a halo, alkyl, or aromatic sulfonate. Includes, The modifier is selected from the group consisting of dimethyl sulfoxide; dimethylacetamide; N-methyl-2-pyrrolidone; hexamethylphosphoramide; pyridine; dimethylaminopyridine; crown ether; and combinations thereof. method.
13. The method according to claim 12, wherein the modifier is dimethyl sulfoxide.
14. R １ The method according to claim 12, wherein the selected element is methyl, ethyl, isopropyl, n-butyl, or sec-butyl.
15. The method according to claim 12, wherein the alkyl sulfonate or aromatic sulfonate is a mesylate or a tosylate.
16. The method according to claim 12, wherein the modifier is present in an amount of at least 3 molar equivalents based on the amount of the compound of formula (A).
17. The method according to claim 16, wherein the modifier is present in an amount of 3 to 50 molar equivalents based on the amount of compound of formula (A) present.
18. The method according to claim 12, wherein the modifier is present in an amount of 6 to 15 molar equivalents based on the amount of the compound of formula (A).