Monoalkylation of cyclopentadiene

Abstract

The present disclosure provides an improved method for preparing monoalkylated cyclopentadiene species in high yield and high selectivity. In this method, a solution of either dicyclopentadiene magnesium or cyclopentadiene magnesium halide is reacted with an alkylating agent in the presence of a modifier to provide a monoalkylated product. In the method of the present disclosure, only monoalkylated species are produced and no detectable amount of dialkylated product is observed.

Description

Technical Field

[0001] This disclosure generally relates to methods for preparing monoalkylated cyclopentadiene compounds.

Background Art

[0002] Cyclopentadiene is useful as an intermediate to many other useful organic compounds. Certain alkyl-substituted cyclopentadienes are useful as synthetic lubricants. (See, e.g., U.S. Patent Nos. 5,144,095 and 5,012,022.) In addition, the cyclopentadiene structure can also be found in many of the so-called single-site metallocene catalysts used to make polyolefins such as polyethylene and polypropylene. (See, e.g., U.S. Patent No. 7,579,415.)

[0003] One unique problem in the handling of cyclopentadiene is its tendency to dimerize through the Diels-Alder reaction. This dimerization proceeds over a period of several hours at room temperature, but can be reversed by the use of heat, so in some cases a cracking treatment is required. In addition, in alkylation reactions utilizing cyclopentadiene anion species, the formation of di- and tri-alkyl species can occur, leading to a decrease in yield and further complicating the synthetic regime due to the need for additional separation and purification.

[0004] Accordingly, an improved methodology for the monoalkylation of the cyclopentadiene structure is needed.

Summary of the Invention

[0005] In summary, the present disclosure provides an improved method for preparing monoalkylated cyclopentadiene species in high yield and high selectivity. In this method, a solution of either dicyclopentadienemagnesium or cyclopentadienemagnesium halide is reacted with an alkylating agent in the presence of a modifier to provide a monoalkylated product. In the method of the present disclosure, only monoalkylated species are produced, and no detectable amount of dialkylated product is observed by gas chromatography measurement.

BEST MODE FOR CARRYING OUT THE INVENTION

[0006] As used in this specification and the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. As used in this specification and the appended claims, the term "or" is generally used in the sense of "and / or" unless the context clearly dictates otherwise.

[0007] The term "about" generally refers to a range of numerical values that are considered equivalent to the recited value (e.g., having the same function or result). In many instances, the term "about" may include numerical values that are rounded to the nearest significant figure.

[0008] Numerical ranges expressed using endpoints include all numbers within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5).

[0009] In a first aspect, the present disclosure provides a method for preparing a compound of formula (I): TIFF2025522111000001.tif23170[wherein R 1 is a linear or branched C1-C8 alkyl group] comprising reacting a solution of either a compound of formula (A) or (B): TIFF2025522111000002.tif43170[wherein X is halo] ​Contact a solution of the compound with a modifier, followed by treatment with a compound of the formula R 1 -X 1 [wherein X 1 is halo, or an alkyl or aromatic sulfonate] to provide a method.

[0010] In the method of the present disclosure, desirably, first, alone or in combination with other solvents described below, a compound of formula (A) or (B) is dissolved or suspended in a solvent effective to at least partially dissolve a cyclopentadiene magnesium species or a cyclopentadiene magnesium halide species. In one embodiment, tetrahydrofuran (THF) is utilized. In particular, attempting to dissolve (A) in dimethyl sulfoxide (DMSO) at room temperature results in an exothermic reaction and a black / brown residue at room temperature. In the method of this disclosure, the exotherm of this reaction can be controlled at low temperature to result in the formation of the desired product (e.g., monoalkylated cyclopentadiene). In the method of the present disclosure, after dissolution of the starting material (A) or (B), a modifier is added, which is selected to yield a cyclopentadienyl anion ring associated with a magnesium cation, followed by the formula R 1 -X 1A compound is added, and the 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. 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 dialkylated (or trialkylated) products that are 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 are 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., but the only consideration is 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. A number of 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 the compound of formula (A) or (B) present. In other embodiments, the modifier is present in an amount of from 3 molar equivalents to about 50 molar equivalents based on the amount of the compound of formula (A) or (B) present, and in other embodiments, the modifier is present in an amount of from about 6 to about 15 molar equivalents based on the amount of the compound of formula (A) or (B) present.

[0015] As described above, the alkylating agent is a compound of the formula R 1 -X [wherein R 1 is a straight or branched C1-C8 alkyl group and X is halo, for example bromo or iodo]. In certain embodiments, R 1 is selected from methyl, ethyl, n-propyl, n-butyl, sec-butyl, etc. In certain embodiments, R 1 is a branched chain group, for example isopropyl. Surprisingly, the result of the reaction is monoalkylation of the cyclopentadiene ring and no dialkylated species are detected by gas chromatography.

[0016] In various embodiments, R 1 is selected from methyl, ethyl and isopropyl.

Examples

[0017] Example 1 - Synthesis of Bis(η 5 -cyclopentadienyl)magnesium(II)-Cp2Mg Freshly cracked cyclopentadiene (50 g, 0.76 mol) was slowly added with stirring at room temperature in a 1 L Schlenk flask under nitrogen to 0.7 M di- n butylmagnesium [350 mL, di- n butylmagnesium, or di- sec butylmagnesium, or n butyl sec butylmagnesium can be used] in hexanes. The temperature during the 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 h and then cooled to 10 °C, and the product precipitated in the flask. The mother liquor was removed by using a cannula. All volatile substances were removed under reduced pressure, and 44.2 g of Cp2Mg was produced in 82% yield. 1 1H NMR (C6D6): 6.00 ppm (s, 12H, Cp-H); 13 13C NMR (C6D6): 107.6 - 107.8 ppm (bm, Cp-CH)

[0018] Examples 2 - 5 - Synthesis of 5-isopropyl-CpH (iPrCpH) As shown in Table 1 below, PrCpH was synthesized under four conditions. For Examples 2 and 3, under nitrogen at room temperature, a 250 mL Schlenk flask was charged with the amounts of Cp2Mg shown in Table 1, followed by THF (46.7 g) with stirring until Cp2Mg was completely dissolved. The amounts of i PrBr (isopropyl bromide) shown in Table 1 were slowly added to the Cp2Mg solution with stirring. The resulting mixture was stirred for the times and at the temperatures shown in Table 1 and then quenched with 5% HCl solution (50 mL). The organic phase was separated and the percentage conversion to PrCpH was shown by gas chromatography (GC) analysis. i PrBr (isopropyl bromide) shown in Table 1 were slowly added to the Cp2Mg solution with stirring. The resulting mixture was stirred for the times and at the temperatures shown in Table 1 and then quenched with 5% HCl solution (50 mL). The organic phase was separated and the percentage conversion to PrCpH was shown by gas chromatography (GC) analysis. i PrCpH was shown by gas chromatography (GC) analysis.

[0019] In the case of Examples 4 and 5, under nitrogen at room temperature, a 250 mL Schlenk flask was charged with the amounts of Cp2Mg shown in Table 1, followed by stirring while charging THF (46.7 g). Cp2Mg was completely dissolved, and the amount of anhydrous DMSO shown in Table 1 was slowly added to the Cp2Mg solution while stirring. The resulting mixture / slurry was stirred for 30 minutes or until a homogeneous, freely flowing liquid was formed. The amount of i PrBr (isopropyl bromide) was slowly added to the Cp2Mg / DMSO slurry while stirring. The resulting mixture was stirred at the times and temperatures shown in Table 1 and then quenched with 5% HCl solution (50 mL). The organic phase was separated and the percentage conversion to i PrCpH was shown by GC analysis. No detectable amount of dialkylated (or trialkylated) species was 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 a higher conversion rate of i PrCpH (greater than 90%) than in Examples 2 and 3 where no modifier such as DMSO was added. TIFF2025522111000003.tif101170

[0021] Examples 6 - 7 - Synthesis of 7 - ethyl - Cp (EtCpH) As shown in Table 2 below, EtCpH was synthesized under two conditions. In the case of Example 6, under nitrogen at room temperature, Cp2Mg was charged into a 250 mL Schlenk flask, followed by THF while stirring. Cp2Mg was completely dissolved, and anhydrous DMSO was slowly added to the Cp2Mg solution while stirring. The resulting mixture / slurry was stirred for 30 minutes or until a homogeneous, freely flowing liquid was formed. Ethyl bromide (EtBr) was slowly added to the Cp2Mg / DMSO slurry while stirring. The resulting mixture was stirred at room temperature for 1 hour and then quenched with 5% HCl solution (50 mL). The organic phase was separated and the percentage conversion to EtCpH was shown by gas chromatography (GC) analysis. No detectable amount of dialkylated (or trialkylated) species was observed by gas chromatography (GC) analysis.

[0022] In the case of Example 7, under nitrogen at room temperature, Cp2Mg was charged into a 250 mL Schlenk flask, followed by THF while stirring. 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 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 results in a higher conversion rate of EtCpH (over 90%) than in Example 7 where no modifier such as DMSO was added. TIFF2025522111000004.tif58170

[0024] Aspect In a first aspect, the present disclosure provides a method for preparing a compound of formula (I): TIFF2025522111000005.tif23170[wherein R 1 is a linear or branched C1-C8 alkyl group] comprising: Formula (A) or (B): TIFF2025522111000006.tif41170 [wherein X is halo] Contact a solution of the compound of with a modifier, and then treat with a compound of the formula R 1 -X 1 [wherein X 1 is halo, or alkyl or aromatic sulfonate], to provide a method.

[0025] In a second aspect, the present 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 alkylated and alkylamino derivatives thereof, such as dimethylaminopyridine (DMAP); crown ether; and combinations thereof.

[0026] In a third aspect, the present disclosure provides a method of the first or second aspect, wherein R 1 is isopropyl.

[0027] In a fourth aspect, the present disclosure provides a method according to claim 1, wherein the alkyl or aryl sulfonate is mesylate or tosylate.

[0028] In a fifth aspect, the present disclosure provides a method of any 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 the compound of formula (A) or (B) present.

[0029] In a sixth aspect, the present disclosure provides a method of any one of the first to fourth aspects, wherein the modifier is present in an amount of 3 molar equivalents to about 50 molar equivalents based on the amount of the compound of formula (A) or (B) present.

[0030] In a seventh aspect, the present disclosure provides a method of any 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 the compound of formula (A) or (B) present.

[0031] In an eighth aspect, the present disclosure provides a method according to any one of the first to seventh aspects, wherein the modifier is dimethyl sulfoxide.

[0032] In a ninth aspect, the present disclosure relates to a method for preparing a compound of formula (I): TIFF2025522111000007.tif23170[wherein R 1 is a linear or branched C1-C8 alkyl group] comprising contacting a solution of a compound of formula (A): TIFF2025522111000008.tif40170with a modifier and subsequently treating with a compound of formula TIFF2025522111000008.tif40170 R 1 -X 1 [wherein X 1 is halo, or an alkyl or aromatic sulfonate].

[0033] In a tenth aspect, the present disclosure provides a method according to the ninth aspect, wherein the modifier is dimethyl sulfoxide.

[0034] In an eleventh aspect, the present disclosure provides a method according to the ninth or tenth aspect, wherein R 1 is selected from methyl, ethyl, isopropyl, n-butyl or sec-butyl.

[0035] In a twelfth aspect, the present disclosure provides a method according to the ninth, tenth or eleventh aspect, wherein R 1 is isopropyl.

[0036] In a thirteenth aspect, the present disclosure provides a method according to the ninth, tenth or eleventh aspect, wherein R 1 is ethyl.

[0037] In a fourteenth aspect, the present disclosure relates to a method for preparing a compound of formula (I): TIFF2025522111000009.tif23170[wherein R 1is a linear or branched C1-C8 alkyl group A method for preparing a compound of Formula (B): TIFF2025522111000010.tif23170[wherein X is halo] Contacting a solution of the compound of with a modifier, followed by treatment with a compound of the formula R 1 -X 1 [wherein X 1 is halo, or an alkyl or aromatic sulfonate], is provided.

[0038] In a fifteenth aspect, the present disclosure provides the method of the fourteenth aspect, wherein the modifier is dimethyl sulfoxide.

[0039] In a sixteenth aspect, the present disclosure provides the method of the fourteenth or fifteenth aspect, wherein R 1 is selected from methyl, ethyl and isopropyl.

[0040] In a seventeenth aspect, the present disclosure provides the method of the fourteenth, fifteenth or sixteenth aspect, wherein R 1 is isopropyl.

[0041] In an eighteenth aspect, the present disclosure provides any of the preceding methods, wherein the dialkylated compound formed 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.

[0042] In a nineteenth aspect, the present disclosure provides any of the preceding methods, wherein 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.

[0043] Although several illustrative embodiments of the present disclosure have been described as above, those skilled in the art can easily understand that other embodiments can still be made and used within the scope of the claims appended hereto. Many advantages of the disclosure contained in this document are described in the above description. However, it is understood that this disclosure is merely for explanatory purposes in many respects. The scope of the present disclosure is, of course, defined in the language expressed by the appended claims.

Claims

1. A compound of formula (I): [wherein, R １ is a linear or branched C １ -C ８ alkyl group], which is a method for preparing a compound of A compound of formula (A): contacting a solution of the compound with a modifier to form a mixture, and Treat the mixture with a compound of the formula R １ -X １ [wherein X １ is halo, or alkyl or aromatic sulfonate] to thereby form a compound of formula (I). A method comprising

2. The method according to claim 1, wherein the dialkylated compound formed is 1.0% or less as measured by gas chromatography.

3. The method according to claim 1, wherein the conversion rate to the compound of formula (I) can be 80% or more.

4. The method according to claim 1, wherein the modifier is selected from the group consisting of dimethyl sulfoxide; dimethylacetamide; N-methyl-2-pyrrolidone; hexamethylphosphoramide; pyridine, and its alkylated derivatives and alkylamino derivatives; crown ethers; and combinations thereof.

5. The method according to claim 4, wherein the modifier is dimethyl sulfoxide.

6. R １ The method according to claim 1, wherein R is selected from methyl, ethyl, isopropyl, n-butyl or sec-butyl.

7. R １ The method according to claim 6, wherein R is isopropyl.

8. R １ The method according to claim 6, wherein R is ethyl.

9. The method according to claim 1, wherein the alkyl or aryl sulfonate is mesylate or tosylate.

10. The method according to claim 1, wherein the modifier is present in an amount of at least about 3 molar equivalents based on the amount of the compound of formula (A).

11. The method according to claim 10, wherein the modifier is present in an amount of about 3 to about 50 molar equivalents based on the amount of the compound of formula (A) present.

12. The method according to claim 10, wherein the modifier is present in an amount of about 6 to about 15 molar equivalents based on the amount of the compound of formula (A).

13. A compound of formula (I): [wherein, R １ is a linear or branched C １ -C ８ alkyl group], which is a method for preparing a compound of A compound of formula (B): [wherein X is halo] contacting a solution of the compound with a modifier to form a mixture, and Treat the mixture with a compound of the formula R １ -X １ [wherein X １ is halo, or alkyl or aromatic sulfonate] A method comprising

14. The method according to claim 13, wherein the dialkylated compound formed is 1.0% or less as measured by gas chromatography.

15. The method according to claim 13, wherein the conversion rate to the compound of formula (I) can be 80% or more.

16. The method according to claim 13, wherein the modifier is selected from the group consisting of dimethyl sulfoxide; dimethylacetamide; N-methyl-2-pyrrolidone; hexamethylphosphoramide; pyridine, and its alkylated derivatives and alkylamino derivatives; crown ethers; and combinations thereof.

17. The method according to claim 13, wherein the modifier is dimethyl sulfoxide.

18. R １ The method according to claim 13, wherein R is selected from methyl, ethyl, isopropyl, n-butyl or sec-butyl.

19. R １ The method according to claim 18, wherein R is isopropyl.

20. R １ The method according to claim 18, wherein R is ethyl.

21. The method according to claim 13, wherein the alkyl or aryl sulfonate is mesylate or tosylate. **Claim 22** The method according to claim 13, wherein the modifier is present in an amount of at least about 3 molar equivalents based on the amount of the compound of formula (A). **Claim 23** The method according to claim 22, wherein the modifier is present in an amount of about 3 to about 50 molar equivalents based on the amount of the compound of formula (A) present. **Claim 24** The method according to claim 22, wherein the modifier is present in an amount of about 6 to about 15 molar equivalents based on the amount of the compound of formula (A).

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