Halogenated triisobutylene compound and manufacturing method therefor

Abstract

The present invention provides a halogenated triisobutylene compound useful as a synthetic raw material of phosphine, and a manufacturing method therefor. More specifically, the present invention provides a compound represented by formula (1). (In formula (1), R represents one halogen atom selected from the group consisting of a chlorine atom, a bromine atom, and an iodine atom.)　Moreover, provided is a manufacturing method for a compound, the method comprising synthesizing a compound represented by formula (1) by reacting a raw material compound represented by formula (2) and a halogen-containing compound.

Description

Halogenated triisobutylene compounds and methods for producing the same REFERENCE TO RELATED APPLICATIONS

[0001] This patent application claims priority based on Japanese Patent Application No. 2024-133400, filed on August 8, 2024, the entire disclosure of which is incorporated herein by reference.

[0002] The present invention relates to a novel halogenated triisobutylene compound (hereinafter also referred to as a compound represented by formula (1)). The present invention also relates to a method for producing the halogenated triisobutylene compound.

[0003] Numerous phosphines have been designed and synthesized and used in various catalytic reactions. Phosphines play a major role in improving activity and controlling chemoselectivity or stereoselectivity. In particular, the structural design of trisubstituted alkylphosphines is important for controlling the activity of homogeneous transition metal catalysts.

[0004] In recent years, it has been reported that trisubstituted phosphines bearing bulky substituents at remote positions exhibit high activity in cross-coupling reactions. For example, the CyTyrranoPhos ligand has bulky substituents at the 3,5-positions of the phenyl group on phosphorus, giving it the steric characteristic of occupying a remote space rather than near the metal (Non-Patent Document 1). This allows for high catalytic reaction efficiency in Suzuki-Miyaura (SM) coupling. On the other hand, Non-Patent Document 2 describes how N-heterocyclic carbene ligands achieve high catalytic activity by imparting flexibility to the bulky substituents of the aryl group linked to the imidazole ring (Non-Patent Document 2). Based on the above findings, introducing flexible and bulky substituents into remote positions in phosphine ligands may be one method for dramatically improving catalytic activity.

[0005] Newman-Stonebraker, SH et al., Science 2021, 374, pp.301-308Altenhoff, G. et al., J. Am. Chem. Soc. 2004, 126, pp.15195-15201

[0006] However, no examples of phosphines having such flexible and bulky substituents at remote positions have been known, and no raw materials for synthesizing such phosphines have been known. Therefore, there is a demand for raw materials for synthesizing the above phosphines.

[0007] An object of the present invention is to provide a halogenated triisobutylene compound useful as a raw material for synthesizing phosphine, and a method for producing the same.

[0008] As a result of intensive research conducted by the present inventors to solve the above-mentioned problems, they found that the halogenated triisobutylene compound of the present invention can be obtained by reacting a compound represented by the following formula (2) with a specific halogen-containing compound, and thus completed the present invention.

[0009] That is, according to the present invention, the following inventions are provided: [1] A compound represented by the following formula (1): (In formula (1), R represents one halogen atom selected from the group consisting of a chlorine atom, a bromine atom, and an iodine atom.) [2] A compound represented by the following formula (1): (wherein R represents one halogen atom selected from the group consisting of a chlorine atom, a bromine atom, and an iodine atom), the method comprising the steps of: and a first raw material compound represented by the following formulas (3) to (5): (In formula (3), R has the same meaning as in formula (1)). (In formula (4), R has the same meaning as in formula (1). Note that P in formula (1) represents a phosphorus atom), and (In formula (5), R has the same meaning as in formula (1). Note that C in formula (1) represents a carbon atom.) by reacting a halogen-containing compound represented by a chemical formula selected from the group consisting of: [3] A method for producing a compound according to [2], wherein in the reaction step, triphenylphosphine is further present when the halogen-containing compound is a compound represented by formula (3), pyridine is further present when the halogen-containing compound is a compound represented by formula (4), and iodine is further present when the halogen-containing compound is a compound represented by formula (5).

[0010] According to the present invention, a novel halogenated triisobutylene compound and a method for producing the same can be provided. Such a novel halogenated triisobutylene compound is useful as a raw material for synthesizing various phosphine compounds.

[0011] The compound represented by formula (2) obtained in Example 1 １ 1H-NMR spectrum of the compound represented by formula (2) obtained in Example 1. １３ 1 is a C-NMR spectrum of the halogenated triisobutylene compound represented by formula (1-1) obtained in Example 2-1. １ 1H-NMR spectrum of the halogenated triisobutylene compound represented by formula (1-1) obtained in Example 2-1. １３ C-NMR spectrum.

[0012] [Halogenated Triisobutylene Compound] The halogenated triisobutylene compound is represented by the following formula (1): It is a compound represented by the formula:

[0013] In formula (1), R represents one halogen atom selected from the group consisting of a chlorine atom, a bromine atom, and an iodine atom. R is preferably a bromine atom or a chlorine atom, and more preferably a bromine atom. Here, a halogenated triisobutylene compound in which R is a bromine atom is also called 1-bromo-2-(2,2-dimethylpropyl)-4,4-dimethylpentane or a brominated triisobutylene compound. Using the halogenated triisobutylene compound represented by formula (1), a phosphine ligand having two or more bulky tert-butyl groups positioned away from the phosphorus atom can be synthesized.

[0014] As used herein, the term "triisobutylene (hereinafter also referred to as TIB) group" refers to an isobutylene trimer structure (having 12 carbon atoms). Specific examples of TIB include TIB groups derived from the structure of formula (7-1) below (2,2,6,6-tetramethyl-4-methyleneheptane). Examples of TIB groups derived from the structure of formula (7-1) below include TIB groups represented by formula (7). Therefore, compounds represented by formula (2) are also referred to as hydroxide triisobutylene compounds or TIB-OH compounds hereinafter. Brominated triisobutylene compounds, which are halogenated triisobutylene compounds represented by formula (1), are also referred to as TIB-Br compounds hereinafter.

[0015] [Method for Producing Halogenated Triisobutylene Compound] The method for producing a halogenated triisobutylene compound represented by formula (1) of the present invention is not particularly limited, but may include, for example, a step of reacting a TIB-OH compound represented by formula (2) with a halogen-containing compound represented by a chemical formula selected from the group consisting of formulas (3) to (5) to synthesize the halogenated triisobutylene compound represented by formula (1). The production method is described in detail below.

[0016] (Compound Represented by Formula (2)) The compound represented by the following formula (2) is also called 2-(2,2-dimethylpropyl)-4,4-dimethyl-1-pentanol. The compound represented by the above formula (2) is not particularly limited, but can be synthesized, for example, in accordance with the method described in International Publication No. 2020 / 017141 (Patent Document 1).

[0017] (Halogen-containing compound) The halogen-containing compound used in the present invention is represented by the following formulas (3) to (5): The compound is represented by a chemical formula selected from the group consisting of:

[0018] R in the above formulas (3), (4), and (5) has the same meaning as in formula (1), and preferred embodiments are also the same.

[0019] Preferred embodiments of the halogen-containing compound include the compound represented by the above formula (3) or the compound represented by the above formula (4), and more preferably the compound represented by the above formula (3).

[0020] The amount of the halogen-containing compound used is not particularly limited as long as it does not impair the effects of the present invention, but may be, for example, 0.5 to 2.0 times by mole, and preferably 1.0 to 1.8 times by mole, per mole of the TIB-OH compound.

[0021] (Solvent) The solvent used in the reaction step is not particularly limited, but examples thereof include halogenated solvents such as dichloromethane, chloroform, 1,2-dichloroethane, chlorobenzene, and o-dichlorobenzene; aromatic hydrocarbon solvents such as toluene, benzene, o-, m-, and p-xylene and mesitylene; aliphatic hydrocarbon solvents such as hexane and cyclohexane; ether solvents such as cyclopentyl methyl ether (hereinafter also referred to as CPME), tetrahydrofuran (hereinafter also referred to as THF), dioxane, diethyl ether, glyme, and diglyme; and fluorinated organic solvents such as hexafluorobenzene, m-bis(trifluoromethyl)benzene, p-bis(trifluoromethyl)benzene, α,α,α-trifluoromethylbenzene, and dichloropentafluoropropane. Among these, from the viewpoints of shortening the reaction time, improving the purification efficiency, and improving the yield, dichloromethane, toluene, CPME, and mixtures thereof are preferred, and dichloromethane is more preferred. As a preferred embodiment of the halogen-containing compound and solvent of the present invention, when the halogen-containing compound is a compound represented by the chemical formula (3), the solvent may be dichloromethane or chloroform, more preferably dichloromethane, and when the halogen-containing compound is a compound represented by the chemical formula (4), the solvent may be toluene or CPME, more preferably toluene.

[0022] The amount of the solvent used is not particularly limited, but may be, for example, 0.01 to 10,000 parts by mass, preferably 0.03 to 6,000 parts by mass, per 100 parts by mass of the TIB-OH compound and the halogen-containing compound combined. According to one embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (3), the amount of the solvent used is preferably 100 to 10,000 parts by mass, more preferably 400 to 6,000 parts by mass, and even more preferably 300 to 1,200 parts by mass or 4,000 to 6,000 parts by mass, per 100 parts by mass of the TIB-OH compound and the halogen-containing compound combined. According to another embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (4), the amount of the solvent used is preferably 0.1 to 200 parts by mass, more preferably 1 to 70 parts by mass, per 100 parts by mass of the TIB-OH compound and the halogen-containing compound combined.

[0023] (Reaction Conditions) The temperature at which the TIB-OH compound and the halogen-containing compound are reacted is not particularly limited, but is, for example, −30° C. or higher, and from the viewpoint of shortening the reaction time, is preferably −30 to 150° C. According to one embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (3), the temperature at which the TIB-OH compound and the halogen-containing compound are reacted is preferably −30 to 100° C., more preferably −20 to 50° C., and even more preferably room temperature or 35 to 50° C. Here, room temperature is 20 to 30° C. According to another embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (4), the temperature at which the TIB-OH compound and the halogen-containing compound are reacted is preferably 80 to 150° C., more preferably 90 to 100° C.

[0024] The time for reacting the TIB-OH compound with the halogen-containing compound is not particularly limited, but is, for example, 0.1 hour or more. From the viewpoint of shortening the reaction time, it is preferably 0.5 hours to 3 days, more preferably 1 hour to 2 days. According to one embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (3), the temperature for reacting the TIB-OH compound with the halogen-containing compound is preferably 0.1 hours to 3 days, more preferably 1 hour to 2 days, and even more preferably 0.5 to 4 hours or 1 day to 2 days. According to another embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (4), the temperature for reacting the TIB-OH compound with the halogen-containing compound is preferably 0.5 hours to 4 hours, more preferably 1 hour to 3 hours.

[0025] According to a preferred embodiment of the present invention, in the method for producing a halogenated triisobutylene compound represented by formula (1) of the present invention, when the halogen-containing compound is a compound represented by formula (3), the solvent used in the reaction step is dichloromethane or chloroform, preferably dichloromethane, and the reaction temperature of the TIB-OH compound and the halogen-containing compound is 35 to 50°C, the reaction time is 0.5 to 4 hours, and the amount of the solvent used is 300 to 1200 parts by mass per 100 parts by mass of the total of the TIB-OH compound and the halogen-containing compound. In particular, when the reaction temperature is within the above range, it is possible to reduce the amount of solvent and shorten the reaction time.

[0026] According to one embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (3), it is preferable to further add triphenylphosphine when reacting the TIB-OH compound with the halogen-containing compound. The amount of triphenylphosphine used is not particularly limited as long as it does not impair the effects of the present invention, but it is, for example, 0.5 to 2.0 times by mole, and preferably 1.0 to 1.8 times by mole, per mole of the TIB-OH compound.

[0027] According to another embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (4), it is preferable to further add pyridine to the TIB-OH compound when reacting the compound with the halogen-containing compound. The amount of pyridine used is not particularly limited as long as it does not impair the effects of the present invention, but may be, for example, 0.5 to 2.0 moles, and preferably 1.0 to 1.8 moles, per mole of the TIB-OH compound.

[0028] According to another embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (5), it is preferable to further add iodine to the reaction of the TIB-OH compound with the halogen-containing compound. The amount of iodine used is not particularly limited as long as it does not impair the effects of the present invention, but may be, for example, 0.5 to 2.0 times by mole, and preferably 1.0 to 1.8 times by mole, per mole of the TIB-OH compound.

[0029] [Method for Purifying a Halogenated Triisobutylene Compound] According to one embodiment of the present invention, the method for producing a halogenated triisobutylene compound of the present invention may further include a step of purifying the halogenated triisobutylene compound synthesized above. The purification method is not particularly limited, and conventionally known purification methods can be applied. Examples of purification methods include filtration (e.g., silica gel filtration), preparative chromatography, vacuum filtration, recrystallization, liquid separation, solvent distillation, washing with a solvent, and ultrasonic washing, and preferably filtration (e.g., silica gel filtration) or preparative chromatography.

[0030] The column used in the above-mentioned chromatography is not particularly limited, but a normal phase column is preferred. Examples of conditions for preparative chromatography include the following: Developing solvent: a mixed solvent of ethyl acetate / hexane = 10 / 90 (volume %) Column: normal phase silica gel (preferably Universal Column L size (manufactured by Yamazen Co., Ltd.)) Instrument: Smart Flash AKROS (manufactured by Yamazen Co., Ltd.) Temperature: room temperature Detection wavelength: 254 nm

[0031] According to one embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (3), filtration (e.g., silica gel filtration) is preferred as a method for purifying the halogenated triisobutylene compound synthesized above. For example, by distilling off the polar solvent, such as dichloromethane, used in the reaction step after completion of the reaction, and adding a nonpolar solvent, such as hexane, it becomes possible to utilize the difference in solubility between the target halogenated triisobutylene compound and the by-product. By using a nonpolar solvent, by-products that are insoluble in the nonpolar solvent can be removed by silica gel filtration alone, and the target halogenated triisobutylene compound can be isolated.

[0032] According to another embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (4), the halogenated triisobutylene compound synthesized above is preferably purified by preparative chromatography.

[0033] The present invention will be specifically explained below with reference to examples, but the present invention is not limited to these examples.

[0034] The compounds represented by formula (1) and (2) obtained by the following method were structurally analyzed under the following conditions: １ H-NMR measurement and １３ C-NMR measurement was carried out. １ H-NMR conditions] NMR measurement device: spectrometer AVANCE NEO, magnet Ascend 600 (manufactured by BRUKER JAPAN) １ H-NMR measurement conditions: frequency 600.03 MHz, CDCl ３ Solvent / measurement time: about 30 minutes １３ C-NMR conditions] NMR measurement device: spectrometer AVANCE NEO, magnet Ascend 600 (manufactured by BRUKER JAPAN) １３ C-NMR measurement conditions: frequency 150.89 MHz, CDCl ３ Solvent / measurement time: Approximately 60 minutes

[0035] Example 1 Production of Compound Represented by Formula (2) (TIB-OH Compound) A compound represented by formula (2) was synthesized with reference to the description of Synthesis Example 1 in WO 2020 / 017141.

[0036] Specifically, the reaction was carried out by the following method. In a reaction vessel under a nitrogen stream, 60 mL of anhydrous THF was added to 10.00 g (59.4 mmol) of a triisobutylene raw material (manufactured by TCI) containing a compound represented by the following formula (6-1) (sometimes abbreviated as "compound (6-1)") and a compound represented by the following formula (6-2) (sometimes abbreviated as "compound (6-2)"), and the mixture was stirred. 9-Borabicyclo[3.3.1]nonane (9-BBN) (89.1 mmol) was added dropwise to the mixture at 0°C under ice cooling, and the mixture was heated to 35°C after 30 minutes (Reaction Scheme I).

[0037] The reaction mixture was cooled again on ice, and 79 mL (238 mmol) of 3M NaOH aq was added dropwise. ２ O ２ The solution (80 mL) was added dropwise and allowed to react overnight (Reaction Scheme II).

[0038] After separating the organic and aqueous layers, the organic layer was added with K ２ CO ３ The water remaining in the organic solvent was separated by adding MgSO. After separating the aqueous layer, the same procedure was repeated two more times. The aqueous layers were combined and extracted three times with ethyl acetate. Finally, the organic layers were combined and extracted with MgSO. ４ The drying agent was filtered off, and the solvent was distilled off under reduced pressure to obtain 18.22 g of a colorless, transparent, oily crude product. Note that the unreacted internal olefin structure was removed during the distillation under reduced pressure.

[0039] The crude product was roughly purified by vacuum distillation (bath temperature: 100°C, top temperature: 45°C, vacuum level: 1.3 kPa), and then purified on a silica gel column (Silicagel: 92.8 g, eluent: Heptane / Ethyl acetate = 7 / 1) to obtain a white solid TIB-OH compound. The yield was 2.74 g (14.7 mmol), 25%.

[0040] <Compound represented by formula (2) (TIB-OH compound) １ H-NMR measurement and １３ C-NMR measurement of the obtained TIB-OH compound １ H-NMR measurement and １３C-NMR measurement was carried out. １ The H-NMR spectrum is shown in FIG. １３ The C-NMR spectrum is shown in Figure 2. １ H-NMR spectral data and １３ C-NMR spectrum data was obtained. Spectral analysis confirmed that the compound was the compound represented by formula (2). 1 H-NMR(600.03MHz,CDCl3): δ 0.93(s,18H), 1.14-1.39(d,4H), 1.23 (s, 1H), 1.64(m,1H), 3.52(t,2H) 13 C-NMR(150.89MHz,CDCl3): δ 67.9, 47.5, 33.9, 31.2, 30.3

[0041] <Production of Compound Represented by Formula (1-1) (TIB-Br Compound)-1> [Example 2] [Example 2-1] The compound represented by formula (2) (TIB-OH compound) (1.24 g, 6.65 mmol) obtained in Example 1 and 120 mL of dichloromethane were placed in a 100 mL recovery flask and stirred while cooling with ice water. ３ ) (2.61 g, 9.98 mmol) was added and dissolved by stirring. N-bromosuccinimide (NBS) (1.72 g, 9.98 mmol) was added to the resulting solution, and the mixture was stirred at room temperature for 2 days to allow the reaction to proceed (Reaction Formula III). After the reaction, the solvent was distilled off, and the product was extracted with hexane and then purified by filtration using silica gel. After distilling off the solvent, 1.40 g (85%) of the target TIB-Br compound was obtained (Table 1).

[0042]

[0043] The chemical structure of the isolated TIB-Br compound was determined by NMR measurement. １ The H-NMR spectrum is shown in FIG. １３ The C-NMR spectrum is shown in Figure 4. １ H-NMR spectral data and １３C-NMR spectrum data was obtained. Spectral analysis confirmed that the compound was the compound represented by formula (1-1). 1 H-NMR(600.03MHz,CDCl3): δ 0.94(s,18H),1.23-1.44(dd,4H),1.85(m,1H),3.47(d,2H) 13 C-NMR(150.89MHz,CDCl3): δ 49.1, 44.1, 33.2, 31.1, 30.2

[0044] [Examples 2-2 to 2-3] In Examples 2-2 and 2-3, TIB-Br compounds were synthesized in the same manner as in Example 2-1, except that the amounts of TIB-OH compound, dichloromethane, triphenylphosphine, and N-bromosuccinimide used were the amounts shown in Table 1. The yields of the TIB-Br compounds obtained in Examples 2-2 and 2-3 are shown in Table 1.

[0045] [Example 2-4] The compound represented by formula (2) (TIB-OH compound) (1.24 g, 6.65 mmol) obtained in Example 1 and 13.3 mL of dichloromethane were placed in a 25 mL Schlenk flask and stirred while cooling with ice water. ３ ) (2.61 g, 9.98 mmol) was added and then stirred to dissolve. N-bromosuccinimide (NBS) (1.72 g, 9.98 mmol) was added to the resulting solution, and the mixture was stirred at 40°C (under solvent reflux) for 3 hours to allow the reaction to proceed (Reaction Formula III). After the reaction, the dichloromethane solvent was distilled off, and hexane was added, followed by filtration and purification using a small amount of silica gel. After the hexane solvent was distilled off, 1.40 g (85%) of the target TIB-Br compound was isolated. The results are shown in Table 2.

[0046]

[0047] The yield (85%) of the TIB-Br compound in Example 2-4 was similar to that in Example 2-1. Meanwhile, the amount of solvent used in Example 2-4 was significantly reduced from that in Example 2-1, and the reaction time in Example 2-4 was also significantly shortened from that in Example 2-1. Therefore, the production method in Example 2-4 can reduce the production cost of the TIB-Br compound. Furthermore, the production cost of the TIB-Br compound can be reduced by avoiding expensive column fractionation as a purification method and employing an inexpensive silica gel filtration method.

[0048] <Production of Compound Represented by Formula (1-1) (TIB-Br Compound)-2> [Example 3] [Example 3-1] A 25 mL Schlenk flask was charged with a TIB-OH compound (a compound represented by formula (2)) (2.79 g, 15 mmol) and 4 mL of CPME as a solvent, and the resulting mixture was cooled to -10°C and stirred. ３ (4.47 g, 16.5 mmol) was added and dissolved with stirring. After stirring at room temperature for 30 minutes, the mixture was heated to 100°C and reacted for 2 hours. After that, the reaction solution was cooled to -10°C, and water was gradually added. After that, the organic layer was recovered by extraction and separation, and the solvent was distilled off to obtain a crude product. Next, the obtained crude product was purified by preparative chromatography (column: normal phase silica gel (Universal Column L size (Yamazen Corporation)), instrument: Smart Flash AKROS (Yamazen Corporation)), temperature: room temperature, detection wavelength: 254 nm). As the developing solution for preparative chromatography, a mixed solution of ethyl acetate / hexane was used, and the ethyl acetate concentration was gradually changed to 5% by volume and 10% by volume. As a result, when the ethyl acetate concentration of the chromatographic developing solution (ethyl acetate / hexane) was 10% by volume, the target substance (TIB-Br compound) was isolated (yield: 36%). The chemical structure of the TIB-Br compound isolated in Example 3-1 was assigned by NMR measurement, and it was confirmed to be the same as that of Example 2-1 and to be the compound represented by formula (1-1).

[0049] [Example 3-2] A TIB-Br compound was synthesized in the same manner as in Example 3-1, except that the solvent used in Example 3-2 was changed from CPME to toluene. As a result, the yield was 49%.

Claims

1. The following formula (1): (wherein R represents one halogen atom selected from the group consisting of a chlorine atom, a bromine atom, and an iodine atom).

2. A compound represented by the following formula (1): (wherein R represents one halogen atom selected from the group consisting of a chlorine atom, a bromine atom, and an iodine atom), the method comprising the steps of: and a compound represented by the following formulas (3) to (5): (In formula (3), R has the same meaning as in formula (1)). (In formula (4), R has the same meaning as in formula (1)), and (wherein R has the same meaning as in formula (1)), and a halogen-containing compound represented by a chemical formula selected from the group consisting of:

3. The method for producing a compound according to claim 2, wherein in the reaction step, when the halogen-containing compound is a compound represented by formula (3), triphenylphosphine is further present, when the halogen-containing compound is a compound represented by formula (4), pyridine is further present, and when the halogen-containing compound is a compound represented by formula (5), iodine is further present.

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