Selective alkylation of cyclopentadiene.

Abstract

A process for the monoalkylation of cyclopentadiene is provided that utilizes a cyclopentadiene magnesium halide and a metal salt of an alkyl or aryl sulfonate as a co-reactant with an alkyl halide alkylation reactant. The process provides a facile methodology for the monoalkylation of cyclopentadiene, with conversions as high as about 96% and selectivities for monoalkylation (over higher levels of alkylation, such as di- or tri-) as high as about 99%.

Description

[Technical field]

[0001] The present disclosure relates to a process for the selective monoalkylation of cyclopentadiene. [Background technology]

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

[0003] One inherent difficulty in working with cyclopentadiene is its tendency to dimerize via the Diels-Alder reaction. This dimerization proceeds over several hours at room temperature but can be reversed by the application of heat, and in some cases requires a cracking step. Furthermore, when attempting to make alkyl-substituted cyclopentadiene structures, the synthesis regime is further complicated by the formation of di- and trialkyl species, which reduces yields and requires further purification.

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

[0005] In summary, the present disclosure relates to an improved process for the monoalkylation of cyclopentadiene, in which a cyclopentadienyl magnesium halide is reacted with a compound of formula MO3SR', where M is selected from alkali metals and alkaline earth metals, and R' is a C1-C8 alkyl, phenyl, or phenyl substituted with one or more C1-C8 alkyl groups or phenyl. This step is believed to form a reactive intermediate in situ, which then reacts with an alkyl halide of formula R-X' to provide a compound of formula (I): TIFF0007663683000001.tif20170In the formula, R is selected from C1 to C8 alkyl.

[0006] Thus, the process provides a facile methodology for the monoalkylation of cyclopentadiene, with a conversion of at least about 96% and a selectivity of at least about 99% for monoalkylation (over higher levels of alkylation such as di- or tri-). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0007] 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.

[0008] The term "about" generally refers to a range of numbers that are considered equivalent to a recited value (e.g., having the same function or result). In many cases, the term "about" can include numbers that are rounded to the nearest significant figure.

[0009] Numeric ranges expressed using endpoints include all numbers subsumed within that range (eg, 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5).

[0010] In a first aspect, the present disclosure provides a compound of formula (I): TIFF0007663683000002.tif20170, wherein R is selected from C1-C8 alkyl, the method comprising: (A)(a) a compound of the formula: TIFF0007663683000003.tif24170, where X is chloro or bromo, and (b) a reaction product of a compound of formula MOSR', where M is selected from alkali metals and alkaline earth metals, and R' is C1-C8 alkyl; phenyl; or phenyl substituted with one or more C1-C8 alkyl groups or phenyl; and (B) contacting a compound of formula R-X', where X' is selected from chloro, bromo, iodo, or an alkyl- or aryl-sulfonate:

[0011] In one embodiment, R is isopropyl.

[0012] In one embodiment, M is selected from alkaline earth metals.

[0013] In one embodiment, M is selected from alkali metals.

[0014] In another embodiment, M is selected from sodium, lithium, or potassium.

[0015] In certain embodiments, R' is selected from trifluoromethyl, p-methylphenyl, or 1,3,5-trimethylphenyl.

[0016] In certain embodiments, the alkyl sulfonate is selected from C1 to C6 alkyl sulfonates, and in other embodiments, the aryl sulfonate is a phenyl sulfonate.

[0017] Advantageously, the disclosed method can be carried out to prepare monoalkylated products in high yield and high selectivity (in monoalkylation). The inventors have found that the utilization of a co-reactant of formula MO3SR' results in monoalkylation of cyclopentadiene-type structures with conversions of at least about 70, 75, 80, 85, 90, or 96%, and selectivities for monoalkylation of at least about 70, 75, 80, 85, 90, 95, or 99%. Thus, the product so produced is also substantially free of bis-alkylation by-products, thereby allowing the direct product of the method to be utilized in further reactions with minimal processing.

[0018] The process may be carried out in a polar aprotic solvent such as an ether. Exemplary ethers include dimethyl ether, diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 3-methyltetrahydrofuran, 1,4-dioxane, methyl t-butyl ether, methyl n-butyl ether, and the like. The process may be carried out at room temperature or at elevated temperatures, for example, from about 23° C. to about 60° C., and at atmospheric pressure.

[0019] In this reaction, a compound of formula R-X' is believed to react with a reactive intermediate species which is itself the reaction product of (i) a compound of formula CpMgX (Cp = cyclopentadiene) and (ii) a compound of formula MO3SR'. In this regard, the inventors believe that this intermediate reactive species has the formula: TIFF0007663683000004.tif32170, wherein R' is selected from C1-C8 alkyl, phenyl, or phenyl substituted with one or more C1-C8 alkyl or phenyl, which is then advantageously reacted with a compound of formula R-X' to provide the monoalkylated product of formula (I).

[0020] Thus, in another aspect, the present disclosure provides an intermediate reactive species having the formula: TIFF0007663683000005.tif31170 where R' is selected from C1-C8 alkyl, phenyl, or phenyl substituted with one or more C1-C8 alkyl or phenyl. EXAMPLES

[0021] Preparation of cyclopentadiene magnesium chloride Cyclopentadiene magnesium chloride can be prepared from methylmagnesium chloride and cyclopentadiene using the methodology described in U.S. Pat. No. 6,175,027, which is incorporated herein by reference.

[0022] NMR (1H-NMR, protonated THF, internal standard 1,5-cyclooctadiene): 6.01 ppm (5H,b, Cp-H), 2.75 ppm (2H,b, residual Cp-CH2), 0.2 ppm (4H,b, CH4 produced from reaction), -2.06 ppm (3H,b, excess MeMgCl).

[0023] Example 1 CpMgCl solution (1.0M; 50mL, 50mmol) was reacted with sodium p-toluenesulfonate (9.71g, 50mmol) at 55°C for several hours (2-6). The reaction mixture was then cooled to room temperature and neat isopropyl bromide (6.76g, 55mmol) was added slowly to the slurry. The reaction was monitored by GC over a period of 20 hours and the data is shown in Table 1 below.

[0024] Example 2 CpMgCl (1.0 M; 65 mL, 65 mmol) was heated to 60° C. and transferred over 10 min to isopropyl bromide (7.86 g, 64 mmol) and THF (1.83 g, 25 mmol), also at 60° C. The reaction was refluxed at 65° C. for 4 h and monitored by GC over a day with the data shown in Table 1.

[0025] The data in Table 1 show that the addition of tosylate to the reaction of CpMgCl with iPrBr substantially increases the conversion at 4 hours and eliminates the formation of the iPr2Cp by-product.

[0026] Example 3 CpMgCl solution (1.0 M; 50 mL, 50 mmol) was reacted with sodium p-toluenesulfonate (9.71 g, 50 mmol) at 55 °C for several hours (2 - 6). The reaction mixture was then cooled to room temperature and neat butyl bromide (7.54 g, 55 mmol) was added slowly to the slurry. The reaction was monitored by GC over a period of 20 hours and the data are shown in Table 2.

[0027] Example 4 CpMgCl solution (1.0 M; 50 mL, 50 mm) was cooled to room temperature and neat butyl bromide (7.54 g, 55 mmol) was added slowly to the clear solution. The reaction was monitored by GC for 20 h and the data are shown in Table 2.

[0028] The data in Table 2 show that the addition of tosylate to the reaction of CpMgCl with nBuBr results in a slight increase in conversion after 4 hours. Rate Increase: TIFF0007663683000006.tif31170TIFF0007663683000007.tif31170

[0029] Example 5 A solution of CpMgCl (1.0M; 1L, 1mol) was reacted with sodium p-toluenesulfonate (194g, 1mol) at 55°C for several hours (2-6). The reaction mixture was then cooled to 10°C and neat isopropyl bromide (135.3g, 1.1mol) was slowly added to the slurry. The reaction was monitored by GC until the amount of free Cp relative to the product was less than 5%. Upon completion, it was quenched by transferring it to a solution of 1.5 equivalents of hydrocarbon and dilute acetic acid. The organic layer was separated and washed with sodium carbonate. The low boiling compounds were then removed to give a 10-20% isopropylcyclopentadiene in THF / hydrocarbon solution. Solution analysis of this solution found less than 0.1% Cp relative to iPrCp and less than 0.1% iPr2Cp.

[0030] NMR (1H, C6D6): 1.08 ppm (6H, d, isopropyl CH3), 2.62 ppm (1H, m, isopropyl CH), 2.82 ppm (2H, b, Cp-CH2), 5.85-6.5 (5H, m, Cp-H)

[0031] Residual isopropyl bromide: 1.62 ppm (6H,d), 4.25 ppm (1H,m)

[0032] Aspects In a first aspect, the present disclosure provides a compound of formula (I): TIFF0007663683000008.tif21170, wherein R is selected from C1-C8 alkyl, the method comprising: (A)(a) a compound of the formula: TIFF0007663683000009.tif25170, where X is chloro or bromo, and (b) a reaction product of a compound of formula MOSR', where M is selected from alkali metals and alkaline earth metals, and R' is C1-C8 alkyl; phenyl; or phenyl substituted with one or more C1-C8 alkyl groups or phenyl; and (B) contacting a compound of formula R-X', where X' is selected from chloro, bromo, iodo, alkylsulfonate, or arylsulfonate, to produce a compound of formula (I).

[0033] In a second aspect, the disclosure provides the method of the first aspect, wherein R is isopropyl.

[0034] In a third aspect, the disclosure provides the method of the first aspect, wherein R is sec-butyl.

[0035] In a fourth aspect, the disclosure provides the method of the first, second or third aspect, wherein M is selected from sodium, lithium or potassium.

[0036] In a fifth aspect, the disclosure provides the method of any one of the first to fourth aspects, wherein R' is 1,3,5-trimethylphenyl.

[0037] In a sixth aspect, the disclosure provides the method of any one of the first to fourth aspects, wherein R' is trifluoromethyl.

[0038] In a seventh aspect, the present disclosure provides the method of any one of the first to fourth aspects, wherein R' is p-methylphenyl.

[0039] In an eighth aspect, the disclosure provides the method of any one of the first to seventh aspects, wherein the compound of formula (I) is produced in at least about 70, 80, 90, or 96% conversion.

[0040] In a ninth aspect, the disclosure provides the method of any one of the first to eighth aspects, wherein the compound of formula (I) is produced in up to about 96% conversion.

[0041] In a tenth aspect, the disclosure provides a compound of the formula: TIFF0007663683000010.tif32170 where R' is selected from C1-C8 alkyl, phenyl, or phenyl substituted with one or more C1-C8 alkyl groups or phenyl.

[0042] In an eleventh aspect, the disclosure provides a compound according to the tenth aspect, wherein R' is selected from 1,3,5-trimethylphenyl, trifluoromethyl, or 4-methylphenyl.

[0043] In a twelfth aspect, the present disclosure provides a compound according to the tenth or eleventh aspect, wherein R' is 4-methylphenyl.

[0044] In a thirteenth aspect, the present disclosure provides a compound according to the tenth or eleventh aspect, wherein R' is 1,3,5-trimethylphenyl.

[0045] In a fourteenth aspect, the present disclosure provides a compound according to the tenth or eleventh aspect, wherein R' is trifluoromethyl.

[0046] Having thus described several exemplary embodiments of the present disclosure, those skilled in the art will readily appreciate that still other embodiments may be made and used within the scope of the appended claims. Numerous advantages of the disclosure to which this document is directed have been set forth in the foregoing description. It will be understood, however, that the disclosure is in many respects merely illustrative. The scope of the present disclosure is, of course, to be defined in the language in which the appended claims are expressed.

Claims

1. Compounds of formula (I): (Wherein, R is C １ ~C ８ a) a substituted or unsubstituted alkyl group selected from the group consisting of aryl, ... and alkyl; (A) (a) a compound of the formula: (b) a compound of formula MO ３ SR′, where M is selected from an alkali metal or an alkaline earth metal, and R′ is C １ ~C ８ Alkyl, phenyl, or one or more C １ ~C ８ the reaction product of a phenyl substituted with an alkyl group or a phenyl group; and (B) contacting a compound of formula R-X', where X' is selected from chloro, bromo, iodo, alkylsulfonate, or arylsulfonate, to produce a compound of formula (I).

2. 2. The method of claim 1 , wherein R is isopropyl.

3. The method of claim 1 , wherein R is sec-butyl.

4. 4. The method of claim 1, 2 or 3, wherein M is selected from sodium, lithium or potassium.

5. The method of any one of claims 1 to 4, wherein R' is 1,3,5-trimethylphenyl.

6. 5. The method of any one of claims 1 to 4, wherein R' is trifluoromethyl.

7. The method of any one of claims 1 to 4, wherein R' is p-methylphenyl.

8. 8. The process of any one of claims 1 to 7, wherein the compound of formula (I) is produced with at least 70% conversion.

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