Monoalkylation of cyclopentadiene

Abstract

The present disclosure provides an improved process for the preparation of monoalkylated cyclopentadiene species in high yield and selectivity. In the process, a solution of 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 methods of the present disclosure, only monoalkylates are produced without observing detectable amounts of dialkylates.

Description

Technical Field

[0001] The present disclosure generally relates to a method for preparing monoalkylated cyclopentadiene compounds. Background Art

[0002] Cyclopentadiene can be used as an intermediate for many other useful organic compounds. Certain alkyl-substituted cyclopentadienes can be used as synthetic lubricants. (See, for example, U.S. Pat. Nos. 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 make polyolefins such as polyethylene and polypropylene. (See, for example, U.S. Pat. No. 7,579,415).

[0003] An inherent difficulty in handling cyclopentadiene is its tendency to dimerize via the Diels-Alder reaction. This dimerization occurs at room temperature for several hours but can be reversed by the application of heat, which in some cases requires a cracking process. Additionally, in alkylation reactions utilizing cyclopentadienyl anionic species, the formation of di- and tri-alkyl species may be encountered, which further complicates the synthetic scheme by reducing yields and requiring further separation and purification.

[0004] Therefore, there is a need for improved processes for the monoalkylation of cyclopentadiene structures. Summary of the invention

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

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

[0007] The term "about" generally refers to a range of numbers that are considered equivalent to the stated value (eg, having the same function or result). In many cases, the term "about" can include numbers that are rounded to the nearest significant figure.

[0008] The recitation of numerical ranges using endpoints includes all numbers subsumed within that range (eg, 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):

[0010]

[0011] Where R 1 is a straight chain or branched C1-C8 alkyl group,

[0012] It comprises making a solution of a compound of formula (A) or (B):

[0013]

[0014] Where X is a halogen,

[0015] contact with a modifier and then with a 1 -X 1 Compound treatment,

[0016] Where X 1 is a halogen or an alkyl or aromatic sulfonate group.

[0017] In the method of the present disclosure, the compound of formula (A) or (B) is ideally first dissolved or suspended in a solvent alone or in combination with other solvents as described below, which solvent is effective to at least partially dissolve the cyclopentadienyl magnesium material or cyclopentadienyl magnesium halide material. In one embodiment, tetrahydrofuran (THF) is used. It is worth noting that attempts to dissolve (A) in dimethyl sulfoxide (DMSO) at room temperature result in an exothermic reaction that produces a black / brown residue at room temperature. In the method of the present disclosure, the exothermicity of the reaction can be controlled at a lower temperature to result in the formation of the desired product (e.g., monoalkylated cyclopentadiene). In the method of the present disclosure, after the raw material (A) or (B) is dissolved, a modifier is added, wherein the modifier is selected to produce a cyclopentadienyl anion ring associated with a magnesium cation, and then a compound of formula R is added. 1 -X 1The invention relates to a method for preparing a compound of formula I, wherein the desired product (i.e., a compound of formula I) is obtained in high yield, wherein no detectable amount of dialkylated (or trialkylated) material is observed by gas chromatography. In certain embodiments, the modifier is selected from a solvent such as dimethyl sulfoxide; dimethylacetamide; N-methyl-2-pyrrolidone; hexamethylphosphoramide; pyridine and its alkylated derivatives and alkylamino derivatives, an example of the latter being dimethylaminopyridine (DMAP); crown ethers; and combinations thereof. In one embodiment, the modifier is dimethyl sulfoxide. In some embodiments, the method may produce 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 of dialkylated (or trialkylated) products as measured by gas chromatography. In some embodiments, the conversion to the compound of Formula I as measured by gas chromatography can be 80% or greater, 82% or greater, 85% or greater, 87% or greater, 90% or greater, 92% or greater, or 95% or greater.

[0018] Formula-X 1 The group is a suitable leaving group, such as halogen, mesylate, tosylate, etc. 1 -X 1 Exemplary compounds include methyl bromide, methyl iodide, ethyl bromide, ethyl iodide, isopropyl bromide, isopropyl iodide, ethyl toluenesulfonate, isopropyl toluenesulfonate, ethyl methanesulfonate, isopropyl methanesulfonate, and the like.

[0019] Exemplary solvents for 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 at least partially soluble in the solvent.

[0020] As used herein, the term "crown ether" refers to those cyclic compounds containing several ether groups. Exemplary crown ethers include cyclic oligomers of ethylene oxide, including nitrogen-containing macrocycles. Examples include 12-crown-4, 15-crown-5, 18-crown-6, dibenzo-18-crown-6, and aza-crown. Many crown ethers are commercially available from Sigma Aldrich.

[0021] 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 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 about 6 molar equivalents to about 15 molar equivalents based on the amount of the compound of formula (A) or (B) present.

[0022] As mentioned above, the alkylating agent is of the formula R1 -X compound, wherein R 1 is a linear or branched C1-C8 alkyl group, and X is a halogen, such as bromine or iodine. 1 is selected from methyl, ethyl, n-propyl, n-butyl, sec-butyl, etc. In certain embodiments, R 1 is a branched group, such as isopropyl. Surprisingly, the result of the reaction is monoalkylation of the cyclopentadiene ring, while no dialkylated species are detected by gas chromatography.

[0023] In various embodiments, R 1 Selected from methyl, ethyl and isopropyl.

[0024] Examples

[0025] Example 1-Bis(η 5 Synthesis of -cyclopentadienyl)magnesium(II)-Cp2Mg

[0026] Freshly cracked cyclopentadiene (50 g, 0.76 mol) was slowly added to a hexane solution containing 0.7 M di-n-butyl magnesium [350 mL, a hexane or heptane solution of di-n-butyl magnesium or di-sec-butyl magnesium or n-butyl-sec-butyl magnesium] at room temperature in a 1 L Schlenk flask under nitrogen and stirring. The temperature during the addition was maintained at 22 ± 3 ° C using an isopropanol / dry ice bath. After the addition was complete, the reactants were stirred at room temperature for 6 hours and then cooled to 10 ° C, which precipitated the product in the flask. The mother liquor was removed by using a cannula. All volatiles were removed in vacuo to give 44.2 g of CP2Mg with a yield of 82%.

[0027] 1 H NMR(C6D6):6.00ppm(s,12H,Cp-H); 13 C NMR(C6D6):107.6-107.8ppm(bm,Cp-CH).

[0028] Example 2 Synthesis of 5-isopropyl-CpH (iPrCpH)

[0029] As shown in Table 1, the synthesis was carried out under four conditions. i For Examples 2 and 3, a 250 mL Schlenk flask was charged with the amount of Cp2Mg shown in Table 1 under nitrogen at room temperature, and then THF (46.7 g) was charged under stirring. The Cp2Mg was completely dissolved. The amount of i PrBr (isopropyl bromide) was slowly added to the Cp2Mg solution. The resulting mixture was stirred for the time and temperature shown in Table 1 and then quenched with 5% HCl solution (50 mL). The organic phase was separated and gas chromatography (GC) analysis showed that the i Percent conversion of PrCpH.

[0030] For Examples 4 and 5, a 250 mL Schlenk flask was charged with the amount of Cp2Mg shown in Table 1 under nitrogen at room temperature, followed by THF (46.7 g) under stirring. The Cp2Mg was completely dissolved, and the amount of anhydrous DMSO shown in Table 1 was slowly added to the Cp2Mg solution under stirring. The resulting mixture / slurry was stirred for 30 minutes or until a consistent free-flowing liquid was formed. The amount of DMSO shown in Table 1 was added under stirring. i PrBr (isopropyl bromide) was slowly added to the Cp2Mg / DMSO slurry. The resulting mixture was stirred for the time and temperature shown in Table 1 and then quenched with 5% HCl solution (50 mL). The organic phase was separated and GC analysis showed i Percent conversion of PrCpH. No detectable amount of dialkylated (or trialkylated) material was observed by gas chromatography.

[0031] The results in Table 1 show that the addition of DMSO as a modifier in Examples 4 and 5 resulted in higher i PrCpH conversion (greater than 90%).

[0032] Table 1: i Synthesis results of PrCpH

[0033]

[0034] Example 6 Synthesis of 7-ethyl-Cp (EtCpH)

[0035] As shown in Table 2 below, EtCpH was synthesized under two conditions. For Example 6, Cp2Mg was loaded into a 250mL Schlenk flask under nitrogen at room temperature, and then THF was loaded under stirring. Cp2Mg was completely dissolved, and anhydrous DMSO was slowly added to the Cp2Mg solution under stirring. The resulting mixture / slurry was stirred for 30 minutes or until a consistent free-flowing liquid was formed. Ethyl bromide (EtBr) was slowly added to the Cp2Mg / DMSO slurry under stirring. The resulting mixture was stirred at room temperature for 1 hour, and then quenched with 5% HCl solution (50mL). The organic phase was separated, and gas chromatography (GC) analysis showed a percentage conversion to EtCpH. No detectable amount of dialkylated (or trialkylated) substances was observed by gas chromatography (GC) analysis.

[0036] For Example 7, Cp2Mg was loaded into a 250mL Schlenk flask under nitrogen at room temperature, and then THF was loaded under stirring. Cp2Mg was completely dissolved. Ethyl bromide (EtBr) was slowly added to the Cp2Mg solution under stirring. The resulting mixture was stirred at room temperature for 1 hour, and then quenched with 5% HCl solution (50mL). The organic phase was separated, and gas chromatography (GC) analysis showed the percentage conversion to EtCpH.

[0037] The results in Table 1 show that the addition of DMSO as a modifier in Example 6 resulted in a higher conversion rate of EtCpH (greater than 90%) than Example 7 without the addition of a modifier such as DMSO.

[0038] Table 2: Selected results for the synthesis of ethyl-cyclopentadiene

[0039]

[0040] aspect

[0041] In a first aspect, the present disclosure provides a method for preparing a compound of formula (I):

[0042]

[0043] Where R 1 is a straight chain or branched C1-C8 alkyl group,

[0044] It comprises making a solution of a compound of formula (A) or (B):

[0045]

[0046] Where X is a halogen,

[0047] contact with a modifier and then with a 1 -X 1 Compound treatment,

[0048] Where X 1 is a halogen or an alkyl or aromatic sulfonate group.

[0049] In a second aspect, the present disclosure provides the 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 its alkylated derivatives and alkylamino derivatives, such as dimethylaminopyridine (DMAP); crown ethers; and combinations thereof.

[0050] In a third aspect, the present disclosure provides a method of the first or second aspect, wherein R 1 It is isopropyl.

[0051] In a fourth aspect, the present disclosure provides a method according to claim 1, wherein the alkyl or aryl sulfonate group is a mesylate group or a tosylate group.

[0052] In a fifth aspect, the present disclosure provides the 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.

[0053] In a sixth aspect, the present disclosure provides the 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.

[0054] In a seventh aspect, the present disclosure provides the method of any one of aspects 1 to 4, 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.

[0055] In an eighth aspect, the present disclosure provides the method of any one of the first to seventh aspects, wherein the modifying agent is dimethyl sulfoxide.

[0056] In a ninth aspect, the present disclosure provides a method for preparing a compound of formula (I):

[0057]

[0058] Where R 1 is a straight chain or branched C1-C8 alkyl group,

[0059] It comprises making a solution of a compound of formula (A):

[0060]

[0061] contact with a modifier and then with a 1 -X 1 Compound treatment,

[0062] Where X 1 is a halogen or an alkyl or aromatic sulfonate group.

[0063] In a tenth aspect, the present disclosure provides the method of the ninth aspect, wherein the modifying agent is dimethyl sulfoxide.

[0064] In an eleventh aspect, the present disclosure provides a method according to the ninth or tenth aspect, wherein R 1 Selected from methyl, ethyl, isopropyl, n-butyl or sec-butyl.

[0065] In a twelfth aspect, the present disclosure provides a method of the ninth, tenth or eleventh aspect, wherein R 1 It is isopropyl.

[0066] In a thirteenth aspect, the present disclosure provides a method of the ninth, tenth or eleventh aspect, wherein R 1 It is ethyl.

[0067] In a fourteenth aspect, the present disclosure provides a method for preparing a compound of formula (I):

[0068]

[0069] Where R 1 is a straight chain or branched C1-C8 alkyl group,

[0070] It comprises making a solution of a compound of formula (B):

[0071]

[0072] Where X is a halogen,

[0073] contact with a modifier and then with a 1 -X 1 Compound treatment,

[0074] Where X 1 is a halogen or an alkyl or aromatic sulfonate group.

[0075] In a fifteenth aspect, the present disclosure provides the method of the fourteenth aspect, wherein the modifying agent is dimethyl sulfoxide.

[0076] In a sixteenth aspect, the present disclosure provides a method according to the fourteenth or fifteenth aspect, wherein R 1 Selected from methyl, ethyl and isopropyl.

[0077] In a seventeenth aspect, the present disclosure provides a method according to the fourteenth, fifteenth or sixteenth aspect, wherein R 1 It is isopropyl.

[0078] In an eighteenth aspect, the present disclosure provides a method of any preceding aspect, wherein 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 of dialkylated compounds are formed as measured by gas chromatography.

[0079] In a nineteenth aspect, the present disclosure provides a method of any preceding aspect, wherein the conversion rate to the compound of formula (I) as measured by gas chromatography can be 80% or greater, 82% or greater, 85% or greater, 87% or greater, 90% or greater, 92% or greater, or 95% or greater.

[0080] Having thus described several illustrative embodiments of the present disclosure, it will be readily apparent to those skilled in the art that other embodiments may also be made and used within the scope of the appended claims. Many advantages of the present disclosure encompassed by this document have been set forth in the foregoing description. However, it should be understood that the present disclosure is in many respects merely illustrative. Of course, the scope of the present disclosure is defined in the language in which the appended claims are expressed.

Claims

1. A method for preparing a compound of formula (I), Where R 1 is a linear or branched C1-C8 alkyl group, the method comprising: Make a solution of a compound of formula (A): contacting with a modifying agent to form a mixture; and Formula R 1 -X 1 The mixture is treated with a compound wherein X 1 is a halogen or an alkyl or aromatic sulfonate group, thereby forming a compound of formula (I).

2. The method according to claim 1, wherein 1.0% or less of dialkylated compounds are formed as measured by gas chromatography.

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

4. The method of claim 1, wherein the modifying agent 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. The method according to claim 4 , wherein the modifying agent is dimethyl sulfoxide.

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

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

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

9. The method of claim 1, wherein the alkyl or aryl sulfonate group is a mesylate group or a tosylate group.

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

12. The method of 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 method for preparing a compound of formula (I), Where R 1 is a straight chain or branched C1-C8 alkyl group, The method comprises: Make a solution of a compound of formula (B): wherein X is a halogen, contacted with a modifier to form a mixture; and Formula R 1 -X 1 The mixture is treated with a compound wherein X 1 is a halogen or an alkyl or aromatic sulfonate group.

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

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

16. The method of claim 13, wherein the modifying agent 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 of claim 13, wherein the modifying agent is dimethyl sulfoxide.

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

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

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

21. The method of claim 13, wherein the alkyl or aryl sulfonate group is a mesylate group or a tosylate group.

22. The method of 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).

23. The method of claim 22, wherein the modifier is present in an amount of about 3 molar equivalents to about 50 molar equivalents based on the amount of the compound of formula (A) present.

24. The method of 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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