JPH0347257B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for esterifying α-substituted acrylic acids such as acrylic acid and methacrylic acid, that is, carboxylic acids having a vinyl group, with alcohols having a large molecular weight and steric hindrance near the hydroxyl group. Such highly sterically hindered esters cannot be synthesized by conventional methods, such as the reaction of methacrylic acid chloride and alcohol. Conventional esterification methods in such systems include:
Method for reacting silver (meth)acrylate and chloride in ether (NAAdrova and LK
Prokhorova, Vysokomol Soedin, 3, 1509
(1961)) is known. However, this method has the following drawbacks. That is, silver salt is expensive, and esters cannot be synthesized because chloride is difficult to obtain. On the other hand, it is known to produce esters from acid chlorides and lithium alkoxides. However, the esterified products obtained by these known methods were as follows. (1) The organic acids that make up the acid residues of acid chloride are mainly saturated aliphatic acids such as acetic acid and aromatic acids such as benzoic acid, and organic acids that contain polymerizable vinyl groups such as (meth)acrylic acid No studies have been conducted on organic acids. (2) The molecular weight and bulk of the alcohol constituting the lithium alkoxide, such as aliphatic alcohol or aromatic alcohol such as benzine alcohol, were not as large as the alcohols targeted by the present invention. In other words, the method of the present invention has not been carried out at all with respect to alcohol. In addition, a method for producing esters from methacrylic acid chloride and sodium alkoxide (RONa) is known (J. Niezette, V. Desreux, Makromol
Chem., 149 , 177 (1971)). However, those synthesized by these known methods are those in which R is not very bulky, such as alkyl, phenyl, naphthyl, etc., and alcohols such as those of the present invention have not been synthesized at all. On the contrary, it has been predicted that it would be difficult to produce a special ester such as the one obtained by the present invention using the known methods described above due to the following points. That is, the solubility of RONa is low, and the reaction with acid chloride does not proceed. For example, the reaction of (C ₆ H ₅ ) ₃ CONa with methacrylic acid chloride does not yield the corresponding ester. Under these circumstances, the present inventors have conducted intensive studies on an industrially advantageous method for producing an ester compound with a special structure, which is the object of the present invention.
This completes the present invention. That is, the present invention is based on the general formula () When reacting the acid chloride represented by the formula () with the alkoxide represented by the general formula () R ² OLi (), an equivalent amount of butyllithium is added to an alcohol solution represented by the general formula R ² OH at -78°C, and the reaction is carried out. Acrylic acid represented by the general formula () characterized in that the acid chloride is added to a solution of the alkoxide obtained in such a manner that no butyllithium remains, and the reaction is carried out at a temperature from -78°C to the boiling point of the solvent. A method for producing an acid ester compound. However, R ¹ :H, CH ₃ , C ₂ H ₅ or phenyl group R ² is the formula In the group represented by R ⁴ , R ⁵ and R ⁶ may be the same or different and are selected from the following groups (1) to (4), but among R ⁴ , R ⁵ and R ⁶ At least two are (1) and (2)
and (4). (1) Aromatic group (2) Alkyl group or aralkyl group having an aromatic group (3) Aliphatic group having 1 to 18 carbon atoms or hydrogen (4)

The group represented by [Formula] [R ⁷ is

[Formula] (R ⁹ and R ¹⁰ are hydrogen or an alkyl group having 1 to 18 carbon atoms, an acyl group, or an alkoxycarbonyl group), R ⁸ is hydrogen or an alkyl group having 1 to 18 carbon atoms, an aryl group, or It is an aralkyl group, but in R ⁷ and R ⁸ -(CH ₂ ) _n -NR ¹¹
A ring represented by -(CH ₂ ) _o - (where m+n=2 to 4 and R ¹¹ is hydrogen or an alkyl group having 1 to 18 carbon atoms, an acyl group, or an alkoxycarbonyl group) may be formed. ]. General formula () used in the present invention The acid chloride represented by can be produced by a conventionally known method. For example, there is a method in which a corresponding carboxylic acid is reacted with phosphorus trichloride. Here, R ¹ is H, CH ₃ , C ₂ H ₅ and a phenyl group. Further, the compound represented by the general formula (R ² Li ()) can be produced from the corresponding alcohol according to the following formula (a). R ² OH+BuLi→R ² OLi+BuH (a) If the alcohol (R ² OH) is solid during production, use an appropriate solvent. The solvent is R ² OLi,
A substance that does not react with BuLi must be used.
Preferred solvents are those that dissolve R ² OLi. Furthermore, R ² OLi has high solubility in solvents. In this case, it is undesirable that BuLi (butyllithium) used for producing R ² OLi remains in the reaction product. This is because if even a small amount of BuLi remains, the ester produced in the esterification reaction of the present invention will be polymerized. Therefore, in the present invention, BuLi was checked and removed by the following method. That is, in the reactions shown by the following formulas (1) and (2), R ² OH + BuLi → R ² OLi + BuH (1) Since reaction (1) proceeds overwhelmingly more than reaction (2), R ² OH
Reaction (2) progresses only when the fluorine (F) has completely reacted, and the colorless fluorene (F) turns into the red-orange fluorenyllithium (FLi). Therefore, when the system turns reddish-orange, it means that reaction (1) has finished and BuLi is in excess, so stop adding BuLi and add a small amount of BuLi.
It is important to add R ² OH to eliminate the coloration of the system and to ensure that no BuLi remains. In the present invention, R ² forming R ² OLi is represented by the following formula. R ⁴ , R ⁵ , R ⁶ may be the same or different,
It is selected from the following groups (1) to (4). (1) Aromatic groups (aryl groups) (e.g. phenyl groups,
pyridyl group) (2) Alkyl group or aralkyl group having an aromatic group (e.g.

【formula】

【formula】

[Formula]) (3) An aliphatic group having 1 to 18 carbon atoms or hydrogen (e.g. -
CH ₃ , −C ₂ H ₅ ) (4)

[Formula] At least two of R ⁴ , R ⁵ and R ⁶ are (1), (2) and
It is necessary to choose from among (4). Conversely, the number of groups in (3) is 0 to 1. Specifically, there are the following. [R ⁷ is

[Formula] (R ⁹ and R ¹⁰ are hydrogen or an alkyl group having 1 to 18 carbon atoms, an acyl group, or an alkoxycarbonyl group), R ⁸ is hydrogen or an alkyl group having 1 to 18 carbon atoms, an aryl group, or It is an aralkyl group, but in R ⁷ and R ⁸ -(CH ₂ ) _n -NR ¹¹
A ring represented by -(CH ₂ ) _o - (where m+n=2 to 4 and R ¹¹ is hydrogen or an alkyl group having 1 to 18 carbon atoms, an acyl group, or an alkoxycarbonyl group) may be formed. ] Generally, it is difficult to synthesize methacrylic acid esters of general formula () having R ² exemplified by (B), (C) and (D). The reasons for this are that such methacrylic esters cannot be obtained by reacting the corresponding alcohol with methacrylic acid chloride, and that it is not easy to synthesize the corresponding halide required for reaction with methacrylic acid silver salt. . For example, methacrylic acid 1 in which R ² is the above (B),
In the case of 2,2,2-tetraphenylethyl, 1,
The reaction between 2,2,2-tetraphenylethanol and methacrylic acid chloride does not proceed at all, and 1,
Synthesis of 2,2,2-tetraphenylethyl chloride is extremely difficult. In addition, in the case of 1,1-diphenylethyl methacrylate where R ² is the above (C), the reaction between 1,1-diphenylethyl alcohol and methacrylic acid chloride does not proceed at all,
When synthesized via 1,1-diphenylethyl chloride, the yield is only about 10% (Polymer, 17 , 618 (1976)). However, in the method of the present invention, as described above, esters in which R ² is (B) or (C) can be obtained directly in good yield by converting alcohol into alkoxide. Furthermore, the alcohol necessary to synthesize the ester in which R ² is (D) above can be synthesized from an α-amino acid by the method shown by the following formula, and may be optically active. (R ⁹ is alkyl, acyl or alkoxycarbonyl) (R ¹¹ is alkyl, acyl, alkoxycarbonyl) (Note: Ph represents phenyl) Examples of alcohols in which R ² is (D) include the following. Preferred reaction conditions for the esterification reaction method of the present invention are as follows. <Solvent> Tetrahydrofuran, diethyl ether, dimethoxyethane, dimethyl sulfoxide. <Addition method> R ² OLi is prepared at a low temperature such as -78℃, and R ² OLi
Acid chloride is added to this to prevent them from associating and precipitating. <Reaction temperature> React from -78℃ to the boiling point of the solvent. In the synthesis of triphenylmethyl methacrylate,
It is important to synthesize R ² OLi at −78° C., add acid chloride to it, and then increase the temperature of the reaction system. When R ² OLi is synthesized at room temperature, the yield of ester is very low. According to the method of the present invention, the special ester compound disclosed in the present invention can be produced by an industrially advantageous method. The acrylic acid ester compound obtained in the present invention can be homopolymerized by itself, or can be copolymerized with other vinyl monomers. Polymers and copolymers using the monomers of the present invention are useful as functional polymers, particularly as resins for optical resolution. Next, examples of the present invention will be shown, but the present invention is not limited to these examples. Example 1 Triphenylmethyl alcohol (3g) and fluorene (0.003g) are dissolved in dry tetrahydrofuran (30ml) and cooled to -78°C. Add to this a hexane solution of butyllithium (1.55 mol/)
An equivalent amount (7.4 ml) of was added. If yellow coloration due to fluorenyl lithium is observed, add a very small amount of methanol to erase the coloration. To this was added 1.05 equivalents (1.16 ml) of methacrylic acid chloride, and after reacting for 30 minutes, the reaction solution was boiled. After 16 hours, a small amount of saturated aqueous sodium carbonate solution was added to the reaction mixture, and the mixture was extracted with ether. The ether layer was dried over magnesium sulfate, the solvent was distilled off, and the crude product was recrystallized from ether. The yield is 2.4g (65
%) and the melting point was 96-100°C. Its infrared absorption spectrum completely matched that of separately synthesized triphenylmethyl methacrylate. Note that although sodium hydride was used in place of butyllithium in this example, triphenylmethyl methacrylate was not obtained. Also,
When fluorene was not used, it was difficult to control the reaction, and in some cases, the polymer was produced quantitatively. Example 2 1,1-diphenylethyl alcohol (3g)
and fluorene (0.003g) were dissolved in THF (30ml), and a hexane solution of butyllithium (1.55g) was dissolved in THF (30ml).
mol/) was added at −78° C. (9.7 ml). If coloration (yellow) due to fluorenyl lithium is observed, add a very small amount of methanol to erase the coloration. To this was added 1.05 equivalents (1.5 ml) of methacrylic acid chloride, and the mixture was allowed to react for 30 minutes, and then for 1 hour at room temperature. Saturated sodium carbonate was added to the reaction solution, and the mixture was extracted with ether. The ether layer was dried over magnesium sulfate, the solvent was distilled off, and the crude product was recrystallized from ether. The yield was 3.1 g (77%), and the melting point was 33-34.5°C. Its infrared absorption spectrum completely matched that of separately synthesized diphenylethyl methacrylate. Example 3 1,2,2,2-tetraphenylethyl alcohol (3 g) and fluorene (0.003 g) were dissolved in tetrahydrofuran (30 ml), and a hexane solution of butyllithium (1.55 mol/) was added to this at -78°C.
An equivalent amount (5.5 ml) was added. If coloring due to fluorenyl lithium is observed, add methanol until the coloring disappears. After adding 1.05 equivalents (0.9 ml) of methacrylic acid chloride to this and reacting for 1 hour, a small amount of saturated aqueous sodium carbonate solution was added to the reaction solution, and the mixture was extracted with ether. After drying the ether layer over magnesium sulfate and distilling off the solvent, the crude product was recrystallized from ether. Yield is 2.5g
(70%), and the melting point was 162-163°C. The results of NMR, IR, and elemental analysis were as follows, and it was confirmed that it was 1,2,2,2-tetraphenylethyl methacrylate. ¹ H-NMR (CDCl ₃ ): δ1.79 (α-methyl) 5.41 and 5.93 (double bond protons) 6.7-7.4 (phenyl group and O-CH proton) IR (nudyl): 1715 cm ^-1 carbonyl elemental analysis : Calculated value Actual value C 86.09% 86.25% H 6.28% 6.35% In addition, 1, 2,
Although 2,2-tetraphenylethyl alcohol and methacrylic acid chloride were reacted, the desired ester could not be obtained. Example 4 (2S,3R)-(10)-4-dimethylamino-1,2
-diphenyl-3-methyl-2-butanol (20
g) in tetrahydrofuran (200ml),
0.02 g of fluorene was added to this, and the mixture was cooled to -78°C. A hexane solution (1.72 mol/) of butyllithium was added dropwise to this until a stable orange color appeared. Add a small amount of methanol to eliminate the orange color, add methacrylic acid chloride (7.1 ml), and add 1
Allowed time to react. The reaction mixture was washed with 1N sodium carbonate,
Extracted with ether. After drying the ether layer, the solvent was distilled off to obtain 25 g of crude product. Recrystallization from hexane gave 17 g (yield 70%) of the desired product. The melting point was 85.5-86.0°C. The results of IR, NMR, elemental analysis, etc. were as follows. IR: 1725 cm ^-1 (C=0) ¹ H-NMR (CCl ₄ ): 1.0 (m, 3H), 1.5-2.5 (m, 11H), 2.9 (s,
1H), 3.8 (s, 2H), 5.3, 5.9 (w, 2H), 6.8~
7.4 (m, 10H) [α] ²⁵ _D : +56.8 (C=1, THF) Elemental analysis: Calculated value Actual value C 78.59% 78.62% H 8.32% 8.27% N 3.99% 3.98%

Claims (1)

[Claims] 1 General formula () When reacting the acid chloride represented by the formula () with the alkoxide represented by the general formula () R ² OLi (), an equivalent amount of butyllithium is added to an alcohol solution represented by the general formula R ² OH at -78°C, and the reaction is carried out. Acrylic acid represented by the general formula () characterized in that the acid chloride is added to a solution of the alkoxide obtained in such a manner that no butyllithium remains, and the reaction is carried out at a temperature from -78°C to the boiling point of the solvent. A method for producing an acid ester compound. However, R ¹ :H, CH ₂ , C ₂ H ₅ or phenyl group R ² has the formula In the group represented by R ⁴ , R ⁵ and R ⁶ may be the same or different and are selected from the following groups (1) to (4), but among R ⁴ , R ⁵ and R ⁶ At least two are (1) and (2)
and (4). (1) Aromatic group (2) An alkyl group or aralkyl group having an aromatic group (3) An aliphatic group having 1 to 18 carbon atoms or hydrogen (4) A group represented by [Formula] [R ⁷ is [Formula] ] (R ⁹ and R ¹⁰ are hydrogen or an alkyl group having 1 to 18 carbon atoms, an acyl group, or an alkoxycarbonyl group), R ⁸ is hydrogen or an alkyl group having 1 to 18 carbon atoms, an aryl group, or an aralkyl group. group, but with R ⁷ and R ⁸ -(CH ₂ ) _n -NR ¹¹
A ring represented by -(CH ₂ ) _o - (where m+n=2 to 4 and R ¹¹ is hydrogen or an alkyl group having 1 to 18 carbon atoms, an acyl group, or an alkoxycarbonyl group) may be formed. ]