JP2003183324A - Method for producing polymeric benzyl lithium reagent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a polymeric benzyl lithium reagent at good efficiency. <P>SOLUTION: This method for producing the polymeric benzyl lithium reagent containing monomer units represented by formula (2) and comprises reacting a styrene/divinylbenzene copolymer containing monomer units represented by general formula (1) with a lithium compound represented by formula R<SP>4</SP>Li (wherein R<SP>4</SP>is a 1-6C linear, cyclic, or branched alkyl or an aryl). In formulae (1) and (2), R<SP>1</SP>, R<SP>2</SP>, and R<SP>3</SP>are each H, a 1-6C linear, cyclic, or branched alkyl, an aryl, or the like. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a reactive cross-linked polymer in which an organometallic reagent capable of reacting with an electrophilic agent is generated in the cross-linked polymer.

[0002]

Solid phase synthesis and combinatorial chemistry are useful in accelerating the drug development process. However, compared to conventional solution chemistry, the solid phase synthesis approach is still incomplete. In the liquid phase, it has been widely practiced to lithiate an aromatic compound to generate a carbanion, and to react this with an electrophile, but there have been limited examples of applying this technique to the solid phase. . Therefore, it is considered that widening the variation of the lithiation of the aromatic substrate supported on the solid phase and the method of generating the carbanion is useful for the development of the solid phase functional material having various functional substituents.

The method that has been used so far in the lithiation reaction for polymers is the exchange reaction between a proton and lithium or the exchange reaction between a halogen and lithium. As an example of using the exchange reaction of a proton and lithium, direct lithiation of polystyrene has been reported (reaction formula (1), J. Org. Chem. 1976, 41,
3877, J. Am. Chem. Soc. 1997, 1
19, 7607). Lithiation of polymer bound 3-furyl and 3-thienylmethanol is also one example of a proton-lithium exchange reaction (Scheme (2), Sy.
nlett, 1998, 405). On the other hand, in the example using the exchange reaction of halogen and lithium, lithiation of brominated polystyrene has been reported (reaction formula (3)
J. Org. Chem. 1976, 41, 3877).

[0004]

[Chemical 4]

[0005]

Other than the proton-lithium exchange reaction and the halogen-lithium exchange reaction, as a method for lithiation and generation of a carbanion, another carbanion is externally added to the carbon-carbon double bond. There is a method of attacking and adding (reaction formula (4)). While this procedure is a common reaction in the liquid phase, it has never been used for the purpose of synthesizing polymeric lithium and polymeric carbanion reagents in the solid phase. Therefore, if a method of converting a carbon-carbon double bond into a carbanion can be applied to a solid phase, it is considered to be a new means for generating a polymeric organolithium reagent.

In the polystyrene type polymer, the method of generating the polymer lithium reagent by using the halogen-lithium exchange reaction also has a problem that side reactions such as the Wurtz reaction occur simultaneously. However, polystyrene-based polymers
Since it is relatively inexpensive, increasing the number of variations as a raw material for the polymeric organolithium reagent has also been an issue.

[0007]

In order to solve the above-mentioned problems, the present invention uses a polystyrene polymer as a raw material,
The present invention provides a method for generating a new carbanion intermediate, and an inexpensive and efficient method for providing a polymeric organolithium reagent. That is, the present invention provides the following general formula (1)
A styrene-divinylbenzene-based copolymer containing a monomer unit represented by the general formula R ⁴ Li (R ⁴ has 1 to 6 carbon atoms)
Represents a linear, cyclic or branched alkyl group or aryl group. ) A method for producing a benzyllithium reagent containing a monomer unit represented by the following general formula (2), which comprises reacting a lithium compound represented by

[0008]

[Chemical 5]

(In the formula, R ¹ , R ² and R ³ are independently a hydrogen atom, an optionally substituted linear or cyclic alkyl group having 1 to 6 carbon atoms, or Represents an aryl group which may have a substituent, and ring A may have another substituent, and may form a condensed ring together with other groups.) Is.

The substance used as a raw material for the polymeric organolithium reagent in the present invention is a copolymer of styrene and divinylbenzene. The copolymer of styrene and divinylbenzene usually has a residual double bond of divinylbenzene that does not participate in crosslinking. By reacting such a residual double bond with an organic lithium reagent such as normal butyl lithium, it is possible to generate a carbanion intermediate having a carbanion center at the benzyl position of the divinylbenzene moiety. It is considered that such a carbanion is stabilized by the conjugation between the carbanion center and the aromatic ring. An example of utilizing such a carbanion intermediate is anionic polymerization of styrene with n-butyllithium. In this case, n-butyl anion is added to styrene and a carbanion intermediate is generated at the benzyl position to initiate polymerization.

In the present invention, as described above, the method of utilizing the residual vinyl group of the styrene-divinylbenzene copolymer to generate the benzylic carbanion is used.
This method can be extended to a polymer in which a double bond is introduced at the benzyl position by chemically modifying a general polystyrene polymer. That is, the general formula (3)

[0012]

[Chemical 6]

(In the formula, R ¹ and ring A have the same meanings as in formula (1).) Various substituents are introduced into R ¹ by way of the monomer unit. It becomes possible. Particularly, in the case of a benzyllithium reagent having a monomer unit of the general formula (2) in which a substituent such as an aryl group is introduced into R ¹ , more efficient generation of carbanion is possible. As described above, in the case of the monomer unit of the general formula (2) having an aryl group in R ¹ , the generated carbanion is considered to be stabilized by conjugation with two benzene rings, and the carbanion can be efficiently prepared. Can be generated.

As described above, the poly (styrene-divinylbenzene) copolymer was limited in the means for generating the lithium reagent and the yield was low, so that the poly (styrene-divinylbenzene) copolymer was functionally functionalized. The introduction of groups has been a challenge. On the other hand, in the present invention, since the benzyllithium reagent can be efficiently generated inside the copolymer, it becomes possible to introduce a functional functional group by reacting it with various electrophiles. As an electrophile, p
When a reagent such as -chloro (chloromethyl) benzene, bis (p-chloromethyl) benzene, p-chlorobenzaldehyde is used, an aryl group containing a chloromethyl group is introduced into a poly (styrene-divinylbenzene) copolymer. be able to. Such a chloromethyl group is used as a reactive substituent.

It is also possible to introduce a substrate having a silyl group such as 2- (p-chlorophenyl) ethyldimethylchlorosilane and dimethylchlorosilane. When a silyl group is introduced into a poly (styrene-divinylbenzene) copolymer, it can be used for modifying the polymer. It is also possible to introduce a carboxylic acid at the benzyl position by reacting with carbon dioxide. Since the carboxylic acid group can be used as a weakly acidic ion exchange group, a new method for producing a weakly acidic ion exchange resin can be provided.

[0016]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below. Examples of the monomer that can be used for producing the styrene-divinylbenzene copolymer used as a raw material in the present invention include alkyl-substituted styrenes such as styrene, methylstyrene and ethylstyrene, and halogen-substituted styrenes such as bromostyrene. . Of these, styrene or a monomer containing styrene as a main component is preferable. Also,
Examples of the crosslinkable aromatic monomer including divinylbenzene include divinylbenzene, trivinylbenzene, divinyltoluene, divinylnaphthalene, and divinylxylene. Of these, divinylbenzene is preferred. Industrially produced divinylbenzene usually contains a large amount of by-product ethylvinylbenzene (ethylstyrene), but such divinylbenzene can also be used in the present invention.

In the present invention, when a styrene-divinylbenzene copolymer is reacted with an alkyllithium reagent to produce a benzyllithium reagent, when the amount of the crosslinkable aromatic monomer is too small, the double bond remaining after the crosslink copolymerization is produced. And the number of residual double bonds that can react with the organolithium reagent decreases, which makes it practically difficult to use. On the other hand, when the proportion of the crosslinkable aromatic monomer is high, many residual double bonds are present, so that the reaction of the organolithium reagent occurs efficiently. Therefore, the amount of the crosslinkable aromatic monomer used is preferably 50 to 99% by weight. Industrially produced divinylbenzene usually contains a large amount of by-product ethylvinylbenzene (ethylstyrene),
In the present invention, it is preferable to use such a polymer of divinylbenzene alone.

In the present invention, the styrene-divinylbenzene copolymer has the general formula R ⁴ Li (R ⁴ represents a linear, cyclic or branched alkyl group having 1 to 6 carbon atoms or an aryl group). The reaction temperature when reacting the lithium compound represented by is preferably -120 ° C to 50 ° C,
More preferably, it is -20 ° C to 10 ° C. Temperature is 25
When the temperature exceeds ℃, the reaction rate decreases, and when the temperature is -50 ° C or lower, the reaction rate also decreases.

When the polymeric benzyllithium reagent is generated from the styrene-divinylbenzene copolymer in the present invention, the introduction rate is about 3% to 30%. If a purer divinylbenzene is used in the synthesis of the copolymer, the introduction rate of the polymer benzyllithium reagent exceeds 10%. The polymerization time of the copolymer is 10 minutes to 10 hours, more preferably 30 minutes to 2 hours. If it exceeds 2 hours, the yield of the polymer benzyllithium reagent decreases.

In the present invention, the monomer unit represented by the general formula (1) is obtained by subjecting the monomer unit represented by the general formula (3) to a Peterson alkenylation reaction. In the case of, a method for producing a copolymer having a monomer unit represented by the general formula (3) is
A known Friedel-Crafts reaction technique can be used. That is, poly (styrene-divinylbenzene)
A (co) polymer having a styrenic monomer unit such as a cross-linked copolymer is suspended in an organic solvent, aluminum chloride,
Alternatively, it can be obtained by reacting an acyl halide compound such as an aromatic carboxylic acid halide in the presence of a Friedel-Crafts reaction catalyst such as iron chloride. As the organic solvent for suspending the cross-linked copolymer, preferably, dichloromethane, chloroform, chlorine-based solvent such as dichloroethane,
Aromatic hydrocarbons such as toluene, benzene, xylene,
Alcohols such as methanol, ethanol, propanol and butanol can be used. As the catalyst of the Friedel-Crafts reaction, the same catalyst as in the ordinary liquid phase reaction can be used.

[0021]

[Chemical 7]

In the present invention, when the monomer unit represented by the following general formula (3) is subjected to the Peterson alkenylation reaction to obtain the monomer unit represented by the general formula (1), various alkenylation is carried out. The reaction can be applied. When the Wittig reaction, which is a typical alkenylation reaction, is applied, known phosphorus ylides can be used as the Wittig reagent. The phosphorus ylides can be synthesized by a known method. For example, a phosphonium salt is derived from triphenylphosphine and an alkyl halide and converted to phosphorus ylide with a strong base such as butyllithium, sodium amide, sodium hydride, or sodium alkoxide. A known method can be applied to the reaction between the monomer unit represented by the general formula (3) and phosphorus ylide.

In the present invention, when the monomer unit represented by the general formula (3) is subjected to the Peterson alkenylation reaction to obtain the monomer unit represented by the general formula (1), the following general formula (4) A method of reacting the Grignard reagent represented by the formula (4) with the monomer unit represented by the general formula (3) and passing through the monomer unit represented by the following general formula (6) can also be used.
In this method, first, a Grignard reagent represented by the general formula (4) is reacted with a monomer unit represented by the general formula (3) to form a monomer unit represented by the general formula (6). It can be converted and converted into an olefin by dehydration reaction to be converted into a monomer unit represented by the general formula (1).

First, the Grignard reagent represented by the general formula (4) is reacted with the monomer unit represented by the general formula (3) to convert it into the monomer unit represented by the general formula (6). When
R ⁸ in the Grignard reagent represented by the general formula (4)
As the above, a methylene group is preferable, but it may have one substituent. R ⁸ is preferably a methylene group having at least one hydrogen atom, and a methylene group having no hydrogen atom may be difficult to undergo the dehydration reaction in the next step.

The substituents R ^{5 to} R ⁷ of the silyl group of the Grignard reagent represented by the general formula (4) are preferably methyl groups, but ethyl groups, propyl groups, butyl groups, isopropyl groups, or t-butyl. A known silyl compound which may be a group can be used. As a raw material of the Grignard reagent represented by the general formula (4), R ⁵ corresponding to it can be used.
To R ⁷ substituted silyl methyl halide can be used. A known method can be used as a method for producing the Grignard reagent. In the production of the Grignard reagent, it is also possible to generate R ^{5 to} R ⁷ -substituted silylmethyllithium using magnesium, metallic lithium, or a commercially available alkyllithium or aryllithium reagent, and use this as the Grignard reagent.

[0026]

[Chemical 8]

(In the formula, R ² , R ³ and R ⁴ have the same meanings as in the above general formulas (1) and (2), and R ⁵ ,
R ⁶ and R ⁷ represent a hydrogen atom, a linear or cyclic alkyl group having 1 to 6 carbon atoms which may have a substituent, or an aryl group which may have a substituent, R ⁸
Represents a linear, cyclic, or branched alkylene group having 1 to 6 carbon atoms which may have a substituent, and X represents a halogen atom. )

When converting the monomer unit represented by the general formula (6) into the monomer unit represented by the general formula (1), a known dehydration reaction can be applied. Preferably, a method of reacting with dilute hydrochloric acid having a concentration of about 2 N can be used. When converting the monomer unit represented by the general formula (3) into the monomer unit represented by the general formula (1), a known method of converting a carbonyl group into a methylene group can be used. Preferably, Peterson alkenylation reaction or Wittig reaction can be used.

A lithium reagent represented by the general formula (2) is produced by reacting an alkyllithium with a styrene-divinylbenzene copolymer containing a monomer unit represented by the general formula (1). At this time, a known lithiation reaction can be applied. The alkyllithium is preferably methyllithium, ethyllithium, propyllithium, butyllithium, t-butyllithium, phenyllithium, and a commercially available lithium reagent can be used, or alkyllithium can be generated by a known method. It can also be used. The solvent used in the reaction is preferably tetrahydrofuran, diethyl ether, 1,4-
An ethereal solvent such as dioxane can be used. Hydrocarbon solvents such as hexane and pentane can also be used. The temperature is preferably -120 ° C to 50 ° C,
More preferably, it is -80 ° C to 30 ° C.

The benzyllithium reagent having a monomer unit represented by the general formula (2) of the present invention is a monomer unit represented by the general formula (2) based on all monomer units constituting the reagent. Is preferably 10 to 50 mol% from the viewpoint of reagent efficiency. The benzyllithium reagent of the present invention is
It can be reacted with various electrophiles. As the electrophile, 2- (p-chlorophenyl) ethyldimethylchlorosilane, p-chloro (chloromethyl) benzene, bis (p-chloromethyl) benzene, p-chlorobenzaldehyde, dimethylchlorosilane, carbon dioxide, etc. may be used. it can. When a benzyllithium reagent having a monomer unit represented by the general formula (2) and R ¹ is an aryl group is reacted with an electrophile, the reaction rate to all the monomer units is 50 to 99%. .

[0031]

EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to the following examples as long as the gist thereof is not exceeded. Example 1 [Synthesis of poly (divinylbenzene) resin] In a reaction vessel equipped with a stirrer, a thermometer, and a reflux condenser, 1.5 g of completely saponified polyvinyl alcohol (polymerization degree 1700) and partially saponified polyvinyl alcohol (polymerization degree 1700) were used. , Acetic acid group (10 mol%), water (210 g), benzoyl peroxide (0.9 g) and 96% divinylbenzene (containing 4% ethylstyrene) (90 g) were added, and the mixture was stirred at 70 ° C. for 1 hour to carry out polymerization. The obtained spherical resin was filtered, washed with water, and then dried with a vacuum dryer.

[Synthesis of benzyllithium resin from poly (divinylbenzene) resin and reaction with (p-chloromethyl) chlorobenzene] 0.2 g (0.5 mmol) of the obtained polydivinylbenzene resin was dried with THF (1 m).
After suspending in l) and cooling to 0 ° C., butyllithium (1.6M, 0.5 ml, 0.8 mmol) was added.
Immediately after butyllithium was dropped, the color of the resin changed to deep red. After slowly stirring at 0 ° C. for another 20 minutes, (p-chloromethyl) chlorobenzene (1 mmo
1, 0.23 g) was added. The reaction mixture was filtered using a glass filter. The resin obtained on the filter was thoroughly washed with an organic solvent (THF, MeOH, CH ₂ Cl ₂ ) and water, water-THF, water-MeOH, and finally MeOH, and then the resin was dried under reduced pressure at 40 ° C. at 20 ° C. It was dried for an hour. The chlorine content in the obtained resin is 20% (1.2 m
mol / g).

Example 2 A benzyllithium reagent was obtained in the same manner as in Example 1 except that the obtained polydivinylbenzene resin was suspended in THF and the temperature when butyllithium was added was set to -78 ° C. . The resin was reacted with (p-chloromethyl) chlorobenzene. The chlorine content in the obtained resin is 14
% (0.84 mmol / g).

Example 3 A benzyllithium reagent was obtained in the same manner as in Example 1 except that the obtained polydivinylbenzene resin was suspended in THF and the temperature when butyllithium was added was 25 ° C. This was reacted with (p-chloromethyl) chlorobenzene. Chlorine content in the obtained resin is 4.1%
(0.25 mmol / g).

Example 4 A benzyllithium reagent was obtained in the same manner as in Example 1 except that the polymerization time of divinylbenzene was changed to 2 hours. This was reacted with (p-chloromethyl) chlorobenzene. Chlorine content in the obtained resin is 16%
(0.96 mmol / g).

Example 5 55% divinylbenzene (45% as divinylbenzene)
A benzyllithium reagent was obtained by the same operation as in Example 1 except that (containing ethyl styrene) was used. This was reacted with (p-chloromethyl) chlorobenzene. The chlorine content of the obtained resin was 6.5% (0.45 mmol / g).

[Reference Example] [Synthesis of poly (p-benzoylstyrene) resin] 2.0 g (19.2 mm) of crosslinked polystyrene resin (degree of crosslinking 2%)
ol Ph ring) was added to 1,2-dichloroethane (25 ml)
Suspended in. Benzoyl chloride (7.7 mmol,
1.08 g, 0.89 ml) was added, and AlCl was added at 0 ° C.
₃ (9 mmol, 12 g) was added. After that, gentle reflux was continued in the oil bath. After 12 hours, the reaction was returned to room temperature and filtered using a glass filter. The resin obtained on the filter was treated with dioxane-2N HCl (2:
1), dioxane-water (3: 1), organic solvent (THF,
MeOH, CHCl ₃₎ and water, water-THF, water -Me
After thorough washing with OH and finally with MeOH, the resin was dried under reduced pressure at 40 ° C. for 20 hours.

Yield: 2.7 g IR: 1658 cm ^-1 [Trimethylsilylmethylation of poly (p-benzoylstyrene) resin] Chloromethyltrimethylsilane (3.7
5 mmol, 460 mg, 0.523 ml) and Mg
A Grignard reagent (THF solution) was prepared from (0.1 g), and the above poly (p-benzoylstyrene) was prepared at room temperature.
Resin (0.5 g, 1.25 mmol) was added. After reacting for 24 hours at room temperature, water was added to the reaction system to stop the reaction.
The reaction mixture was filtered using a glass filter. The trimethylsilylmethylated resin obtained on the filter was treated with an organic solvent (THF, MeOH, CH ₂ Cl ₂ ) and water, water-
Thoroughly wash with THF, water-MeOH and finally MeOH,
Then, the resin was dried under reduced pressure at 40 ° C. for 20 hours.

Yield: 0.6 g IR: 3400 cm ^-1 , 1247 cm ^-1 (1658 cm
^-1 disappears) [Synthesis of poly ((phenylethenyl) styrene) resin from trimethylsilylmethylated poly (p-benzoylstyrene) resin] Trimethylsilylated poly (p-
Benzoylstyrene) resin (0.4g, 2.04mmo
1 / g, 0.82 mmol) was suspended in dry THF (2 ml), 2N HCl (2 ml) was added, and the mixture was stirred at room temperature for 6 hr. The reaction mixture was filtered using a glass filter. The resin obtained on the filter is mixed with an organic solvent (TH
F, MeOH, CH ₂ Cl ₂ ) and water, water-THF, water-
After thorough washing with MeOH and finally with MeOH, the resin was dried under reduced pressure at 40 ° C. for 20 hours. Yield: 0.3 g (2.51 mmol (phenylethenyl) styrene monomer unit ^{/ g) IR: 901cm -1 (} 1600cm around ^-1 overlaps with Ph) (3400cm ^-1, 1247cm ^-1 is disappeared)

Example 6 [Synthesis of benzyllithium resin from poly ((phenylethenyl) styrene) resin and reaction of benzyllithium resin with 2- (p-chlorophenyl) ethyldimethylchlorosilane poly ((phenylethenyl) styrene) ) Resin (0.2
g, 0.5 mmol) was suspended in dry THF (1 ml) and cooled to 0 ° C. before butyllithium (1.6 M,
0.5 ml, 0.8 mmol) was added. Immediately after butyllithium was dropped, the color of the resin changed to deep red.
After slowly stirring at 0 ° C. for another 20 minutes, 2- (p-
Chlorophenyl) ethyldimethylchlorosilane (1 mm
ol, 0.23 g) was added. Upon addition of 2- (p-chlorophenyl) ethyldimethylchlorosilane, the resin returned colorless again. The reaction mixture was filtered using a glass filter. The resin obtained on the filter is mixed with an organic solvent (T
HF, MeOH, CH ₂ Cl ₂ ) and water, water-THF, water-MeOH and finally MeOH, and then the resin was dried under reduced pressure at 40 ° C. for 20 hours. Based on the chlorine elemental analysis value of the resin, the generation rate of the benzyllithium reagent relative to the total number of monomer units and the reaction yield with the electrophile [2- (p-chlorophenyl) ethyldimethylchlorosilane] were determined. The reaction yield is 35% (1.53 mmol
/ G). Yield: 0.3 g IR: 1249 cm ^-1 , 840 cm ^-1 , 810 cm ^-1 Elemental analysis: C 82.33, H 7.98, Cl 5.
41 1.53 mmol Cl / g loading% = 35%

Example 7 2 as electrophile to be reacted with benzyllithium reagent
A resin was obtained in the same manner as in Example 6 except that p-chlorobenzaldehyde was used instead of-(p-chlorophenyl) ethyldimethylchlorosilane. Based on the chlorine elemental analysis value of the resin, the generation rate of the benzyllithium reagent with respect to the total number of monomer units and the reaction yield with the electrophile [p-chlorobenzaldehyde] were determined. Reaction yield is 34%
(1.48 mmol / g).

Example 8 2 as electrophile to be reacted with benzyllithium reagent
A resin was obtained in the same manner as in Example 6 except that 1,4-dibromobutane was used instead of-(p-chlorophenyl) ethyldimethylchlorosilane. Based on the elemental bromine analysis value of the resin, the generation rate of the benzyllithium reagent and the electrophile [1,4-dibromobutane] with respect to the total number of monomer units
The reaction yield with was determined. The reaction yield is 34% (1.48
mmol / g).

Example 9 2 as electrophile to be reacted with benzyllithium reagent
A resin was obtained in the same manner as in Example 6 except that chlorodimethylsilane was used instead of-(p-chlorophenyl) ethyldimethylchlorosilane. Based on comparison with the IR of polystyrene resin with a known Si-H content, the generation rate of the benzyllithium reagent with respect to the total number of monomer units and the reaction yield with the electrophile (chlorodimethylsilane) were determined. The reaction yield was 35% (1.53 mmol / g). Yield: 0.2 g IR: 2111 cm ^-1 , 1250 cm ^-1 Si-H content Comparison with IR of known polystyrene resin Loading% = 35%

Example 10 2 as electrophile to be reacted with benzyllithium reagent
A resin was obtained in the same manner as in Example 6 except that 1- (chloromethyl) -4-chlorobenzene was used instead of-(p-chlorophenyl) ethyldimethylchlorosilane. Based on the bromine elemental analysis value of the resin, the generation rate of the benzyllithium reagent and the electrophile [1,4
-Dibromobutane]. The reaction yield was 34% (1.48 mmol / g).

Example 11 2 as electrophile to be reacted with benzyllithium reagent
A resin was obtained in the same manner as in Example 6 except that 1- (chloromethyl) -4-chlorobenzene was used instead of-(p-chlorophenyl) ethyldimethylchlorosilane. Based on the bromine elemental analysis value of the resin, the generation rate of the benzyllithium reagent and the electrophile [1,4
-Dibromobutane]. The reaction yield was 34% (1.48 mmol / g).

Example 12 2 as electrophile to be reacted with benzyllithium reagent
A resin was obtained in the same manner as in Example 6 except that dry ice was used instead of-(p-chlorophenyl) ethyldimethylchlorosilane. Based on the titration, the generation rate of the benzyllithium reagent with respect to the total number of monomer units and the reaction yield with the electrophile [carbon dioxide] were determined. Reaction yield is 3
It was 4% (1.48 mmol / g).

[0047]

The method of the present invention makes it possible to efficiently produce a polymeric benzyllithium reagent,
Moreover, a polymer type benzyllithium reagent having a practical concentration can be obtained.

Claims (10)

[Claims] 1. A styrene-divinylbenzene copolymer containing a monomer unit represented by the following general formula (1) is added to the general formula R ⁴ Li (R ⁴ is a straight chain having 1 to 6 carbon atoms, A benzyllithium reagent containing a monomer unit represented by the following general formula (2), characterized in that a lithium compound represented by a cyclic or branched alkyl group or an aryl group is reacted. Production method. [Chemical 1] (In the formula, R ¹ , R ² and R ³ independently represent a hydrogen atom, a linear or cyclic alkyl group having 1 to 6 carbon atoms which may have a substituent, or a substituent. It represents an aryl group which may be possessed, and ring A may further have a substituent, and may form a condensed ring together with other groups.) 2. The ratio of the monomer unit represented by the general formula (2) to the total monomer units of the benzyllithium reagent is 10.
It is -50 mol%, The manufacturing method of the benzyl lithium reagent of Claim 1. 3. A monomer unit represented by the general formula (1) is obtained by subjecting a monomer unit represented by the following general formula (3) to a Peterson alkenylation reaction. The method for producing the benzyllithium reagent according to claim 1. [Chemical 2] (In the formula, R ¹ and ring A have the same meanings as in the general formula (1).) 4. The method for producing a benzyllithium reagent according to claim 3, wherein the Peterson alkenylation reaction is carried out using a Grignard reagent represented by the following general formula (4). [Chemical 3] (In the formula, R ^{5 to} R ⁷ may have a hydrogen atom, a linear or cyclic alkyl group having 1 to 6 carbon atoms which may have a substituent, or a substituent. Represents an aryl group, R ⁸ represents a linear, cyclic, or branched alkylene group having 1 to 6 carbon atoms which may have a substituent, and X represents a halogen atom.) 5. The monomer unit represented by the general formula (3),
The styrene monomer unit is obtained by subjecting an acyl halide compound to a Friedel-Crafts acylation reaction in the presence of a Friedel-Crafts reaction catalyst.
The method for producing the benzyllithium reagent according to 1. 6. The method for producing a benzyllithium reagent according to claim 1, wherein all of R ¹ , R ² and R ^{3 in} the general formulas (1) and (2) are hydrogen atoms. 7. A styrene-divinylbenzene copolymer containing a monomer unit represented by the general formula (1) is a monomer forming a monomer unit represented by the general formula (1). 50
The method for producing a benzyllithium reagent according to claim 1 or 2, which is obtained by copolymerizing a monomer mixture containing about 99% by weight. 8. R ⁴ in the general formula (2) has 1 to 1 carbon atoms.
The method for producing a benzyllithium reagent according to claim 1 or 2, wherein the alkyl group is 6. 9. The method for producing a benzyllithium reagent according to claim 4, wherein R ⁵ , R ⁶ and R ⁷ in the general formula (4) are all methyl groups. 10. The method for producing a benzyllithium reagent according to claim 4, wherein R ⁸ in the general formula (4) is a methylene group which may have a substituent.