JP5728781B2 - Method for producing lactide - Google Patents

Description

  The present invention relates to a method for producing lactide by depolymerizing and cyclizing a lactic acid oligomer.

  Polyhydroxycarboxylic acid typified by poly-L-lactic acid is excellent in mechanical properties, physical properties, and chemical properties, and is decomposed in a natural environment, and finally converted into water and carbon dioxide by microorganisms. In recent years, it has been attracting attention in various fields such as medical materials and alternatives to general-purpose resins, and it is expected that the demand will increase greatly in the future.

  Examples of the method for producing poly-L-lactic acid include a direct dehydration polycondensation method of lactic acid (Patent Document 1), a ring-opening polymerization method of L-lactide, which is a cyclic diester monomer of lactic acid (lactide method), or an L-lactic acid Indirect polymerization methods such as via oligomers (“lactide method” is also included in the broad indirect polymerization method).

  Among these production methods, the lactide method is generally a process in which a lactic acid oligomer obtained by polycondensation of lactic acid is depolymerized and cyclized to form lactide, which is then subjected to ring-opening polymerization to obtain polylactic acid. Compared with the direct dehydration polycondensation method, the lactide method is disadvantageous in that the production process is long and the equipment cost and the production cost are high, but a technique for obtaining a high molecular weight poly-L-lactic acid was developed early. Therefore, it has become mainstream in the industrial production of polylactic acid.

  In the lactide method, lactide is produced by a method in which a lactic acid oligomer is depolymerized and cyclized (sometimes referred to as thermal decomposition) in the presence of a catalyst to produce lactide, which is distilled off (for example, And Patent Documents 2 to 4). As a catalyst for the depolymerization / cyclization (hereinafter referred to as a depolymerization catalyst), various metals and metal compounds are known to have activity, and among them, tin compounds are preferred. A typical example is tin (II) di (2-ethylhexane) ate, that is, so-called tin octylate (described in Patent Document 2 under the compound name of tin dioctoate). Tin octylate is said to be excellent in that it has a high catalytic activity, is easy to handle in a liquid state even at room temperature, and is easily dissolved in an organic compound such as an organic solvent or a molten polymer compound.

  The higher the optical purity of polylactic acid, the better the performance in terms of heat resistance, etc., so lactic acid or lactide with high optical purity is used as a raw material and racemization in the middle of the process is suppressed as much as possible. It is important to produce highly pure polylactic acid (Patent Document 2 or Patent Document 4).

International Publication No. 2007/145195 Pamphlet (US Application Publication No. 2009/0176963) JP 63-101378 A (US Pat. No. 5,053,522) Japanese Patent Laid-Open No. 5-105745 JP-A-9-327625

  As mentioned above, the production of polylactic acid by the lactide method has been industrialized, but there are problems that the production process is long, and the equipment cost and production cost increase, which is one of the factors that hinder the spread of polylactic acid products. ing.

  Furthermore, the present inventors have found that there is a potential problem in the production of lactide using a tin compound catalyst as follows.

  First, tin octylate frequently used as a depolymerization catalyst has relatively high volatility, and the conditions for distillation purification (for example, in paragraph [0036] of JP-A-2001-288141, preferably 1 torr or less, It is similar to the conditions for distilling the lactide produced in lactide production. Therefore, in lactide production, part of tin octylate is vaporized together with lactide, and a small amount of tin octylate is mixed into the lactide separated after generation, or it is scattered in the reactor for depolymerization and cyclization. There is a risk that tin octylate adhering to the walls and ceiling inside the vessel deteriorates and decomposes to become foreign matter.

  In order to avoid the risks described above, even if an inorganic tin compound having a high melting point and a high boiling point and extremely low volatility is used, many of these inorganic tin compounds are soluble in organic solvents and molten organic compounds. Is not good, causing another problem in which the risk of staying or deteriorating in the reactor or the transport pipe and sticking as a solid foreign object, causing clogging, or causing the pump failure is increased. , It does not lead to a fundamental solution.

  In the lactide method, lactide generated by depolymerization and cyclization is distilled off under reduced pressure. If the depolymerization catalyst remains in the residue (nonvolatile reaction residue), this is recovered and reused. This is theoretically possible, and it is preferable to reuse the depolymerization catalyst from the viewpoint of suppressing the production cost. However, the drawbacks of the tin compound catalyst as described above can seriously hinder the reuse of the depolymerization catalyst. Furthermore, the present inventors considered that when a continuous lactide production process is used in order to further increase production efficiency, the risk of process troubles due to the defects of the tin compound catalyst is further increased.

  In order to solve the above problems, the present inventors have intensively studied. As a result, a non-metal depolymerization catalyst does not cause such a problem, and a lactide production process capable of continuous operation over a long period of time is more efficient. I thought it could be completed. The present inventors have further studied and, as described in Patent Document 1, since the catalytic activity for promoting the direct dehydration polycondensation reaction of lactic acid is extremely high, even if it acts on a lactic acid oligomer, it is more effective than depolymerization / cyclization. It was discovered that organic onium salts, which were considered unsuitable for lactide production due to the progress of dehydration polycondensation, unexpectedly show high catalytic activity for depolymerization and cyclization of lactic acid oligomers. Surprisingly, when an optically active lactic acid oligomer consisting of only one of L-lactic acid or D-lactic acid is depolymerized and cyclized using an organic onium salt, no mesolactide is produced, and thus racemic The present inventors have found that lactide having high chemical purity and optical purity can be obtained, and the present invention has been completed. The gist of the present invention is shown below.

1. In the presence of at least one organic onium salt selected from the group consisting of the following general formulas (1) to (4), the lactic acid oligomer is heated in a reduced pressure atmosphere to depolymerize and cyclize to produce lactide. A process for producing lactide characterized by the above.

（前記一般式（１）において、Ｚは窒素原子またはリン原子である。
前記一般式（１）において、Ｒ^Ａ、Ｒ^Ｂ、およびＲ^Ｃは、それぞれ独立して水素原子、無置換もしくは置換基を有する炭素原子数１〜２０の脂肪族炭化水素基、無置換もしくは置換基を有する炭素数６〜１８のアリール基、または無置換もしくは置換基を有する炭素数３〜２２の複素環基である。また、水素原子でないＲ^Ａ、Ｒ^Ｂ、Ｒ^Ｃのうち２以上が非芳香族環を形成してもよく、その際、置換基を有していても良い。
前記一般式（１）において、Ｘ⁻は炭素数１〜１８のアルキルスルホン酸イオン、炭素数６〜１８のアリールスルホン酸イオン、炭素数４〜１８の複素環スルホン酸イオン、炭素数１〜８のフッ化アルキルスルホン酸イオン、または硫酸水素イオンである。）

(In the general formula (1), Z represents a nitrogen atom or a phosphorus atom.
In the general formula (1), R ^A , R ^B and R ^C are each independently a hydrogen atom, an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 20 carbon atoms, unsubstituted or substituted. An aryl group having 6 to 18 carbon atoms having a group, or a heterocyclic group having 3 to 22 carbon atoms having no substituent or a substituent. In addition, two or more of R ^A , R ^B , and R ^C that are not hydrogen atoms may form a non-aromatic ring and may have a substituent.
In the general formula (1), X ^- represents an alkyl sulfonate ion having 1 to 18 carbon atoms, an aryl sulfonate ion having 6 to 18 carbon atoms, a heterocyclic sulfonate ion having 4 to 18 carbon atoms, 1 to 8 carbon atoms Of fluorinated alkyl sulfonate ions or hydrogen sulfate ions. )

（前記一般式（２）において、Ｚ’およびＺ’’はそれぞれ独立に窒素原子またはリン原子であり、Ｑは単結合、無置換もしくは置換基を有する炭素原子数１〜１２の直鎖状もしくは分岐状のアルキレン基、無置換もしくは置換基を有する炭素数４〜１２のシクロアルキレン基、無置換もしくは置換基を有する炭素数６〜１２のアリーレン基、炭素数３〜１２の複素環基である。
前記一般式（２）において、Ｒ^Ｄ、Ｒ^Ｅ、Ｒ^Ｆ、およびＲ^Ｇは、それぞれ独立して水素原子、無置換もしくは置換基を有する炭素原子数１〜２０の脂肪族炭化水素基、無置換もしくは置換基を有する炭素数６〜１８のアリール基、または無置換もしくは置換基を有する炭素数３〜２２の複素環基である。また、水素原子でないＲ^Ｄ、Ｒ^Ｅ、Ｒ^Ｆ、およびＲ^Ｇのうち２以上が非芳香族環を形成してもよく、その際、置換基を有していても良い。
前記一般式（２）において、Ｘ’⁻およびＸ’’⁻はそれぞれ独立に、炭素数１〜１８のアルキルスルホン酸イオン、炭素数６〜１８のアリールスルホン酸イオン、炭素数４〜１８の複素環スルホン酸イオン、炭素数１〜８のフッ化アルキルスルホン酸イオン、または硫酸水素イオンである。）

(In the general formula (2), Z ′ and Z ″ are each independently a nitrogen atom or a phosphorus atom, and Q is a straight chain of 1 to 12 carbon atoms having a single bond, unsubstituted or substituted, or A branched alkylene group, an unsubstituted or substituted cycloalkylene group having 4 to 12 carbon atoms, an unsubstituted or substituted aryl group having 6 to 12 carbon atoms, and a heterocyclic group having 3 to 12 carbon atoms. .
In the general formula (2), R ^D , R ^E , R ^F and R ^G are each independently a hydrogen atom, an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 20 carbon atoms, It is a substituted or substituted aryl group having 6 to 18 carbon atoms, or an unsubstituted or substituted heterocyclic group having 3 to 22 carbon atoms. Further, two or more of R ^D , R ^E , R ^F , and R ^G that are not hydrogen atoms may form a non-aromatic ring, and may have a substituent.
In the general formula (2), X ^'- and X'^'- are each independently an alkyl sulfonate ion having 1 to 18 carbon atoms, 6 to 18 carbon atoms aryl sulfonate ion, a complex of 4 to 18 carbon atoms It is a ring sulfonate ion, a fluorinated alkyl sulfonate ion having 1 to 8 carbon atoms, or a hydrogen sulfate ion. )

[Het] ⁺ H X ′ ″ ⁻ (3)
(In the general formula (3), [Het] represents an unsubstituted or substituted nitrogen-containing aromatic heterocyclic group having 3 to 65 carbon atoms, and in the general formula (3), X ″ ^'- alkyl sulfonate ion having 1 to 18 carbon atoms, an aryl sulfonate ion having 6 to 18 carbon atoms, a heterocyclic sulfonate ion having 4 to 18 carbon atoms, 1 to 8 carbon atoms fluorinated alkylsulfonate ion, Or hydrogen sulfate ion.)

（前記一般式（４）において、［Ｈｅｔ’］およびは［Ｈｅｔ’’］、同一または異なってもよい、炭素数３〜６５の無置換もしくは置換基を有する含窒素芳香族複素環基であり、［Ｈｅｔ’］と［Ｈｅｔ’’］が結合し環を形成していてもよい。
前記一般式（４）において、Ｑ’は単結合、無置換もしくは置換基を有する炭素原子数１〜１２の直鎖状もしくは分岐状のアルキレン基、無置換もしくは置換基を有する炭素数４〜１２のシクロアルキレン基、無置換もしくは置換基を有する炭素数６〜１２のアリーレン基、炭素数３〜１２の複素環基である。
前記一般式（４）において、Ｘ’’’’⁻およびＸ’’’’’⁻はそれぞれ独立に、炭素数１〜１８のアルキルスルホン酸イオン、炭素数６〜１８のアリールスルホン酸イオン、炭素数４〜１８の複素環スルホン酸イオン、炭素数１〜８のフッ化アルキルスルホン酸イオン、または硫酸水素イオンである。）

(In the general formula (4), [Het ′] and [Het ″] are the same or different, nitrogen-containing aromatic heterocyclic groups having 3 to 65 carbon atoms, which are unsubstituted or substituted. , [Het ′] and [Het ″] may combine to form a ring.
In the general formula (4), Q ′ represents a single bond, an unsubstituted or substituted linear or branched alkylene group having 1 to 12 carbon atoms, an unsubstituted or substituted carbon group having 4 to 12 carbon atoms. A cycloalkylene group, an unsubstituted or substituted arylene group having 6 to 12 carbon atoms, and a heterocyclic group having 3 to 12 carbon atoms.
In the general formula (4), X ″ ″ ⁻ and X ′ ″ ″ ⁻ are each independently an alkyl sulfonate ion having 1 to 18 carbon atoms, an aryl sulfonate ion having 6 to 18 carbon atoms, or carbon. It is a heterocyclic sulfonate ion having 4 to 18 carbon atoms, a fluorinated alkyl sulfonate ion having 1 to 8 carbon atoms, or a hydrogen sulfate ion. )

2. The organic onium salt of the general formula (1) is

なる群から選ばれる少なくとも１種である前記の項１．記載のラクチドの製造方法。

Item 1 is at least one member selected from the group consisting of The manufacturing method of lactide as described.

3. The organic onium salt of the general formula (2) is

（前記右側の一般式において、ｍおよびｎはそれぞれ独立に０〜４のいずれかである。）
よりなる群から選ばれる少なくとも１種である前記の項１．記載のラクチドの製造方法。

(In the general formula on the right side, m and n are each independently 0-4.)
Item 1 is at least one member selected from the group consisting of: The manufacturing method of lactide as described.

4). In the organic onium salt of the general formula (3), [Het] ⁺ H is

（前記一般式において、Ｒ^１〜Ｒ^７はそれぞれ独立に、水素原子、炭素数１〜９の脂肪族炭化水素基、炭素数６〜１０のアリール基、または炭素数３〜９の複素環基である。）
よりなる群から選ばれる少なくとも１種である前記の項１．記載のラクチドの製造方法。

(In the general formula, R ^{1 to} R ⁷ are each independently a hydrogen atom, an aliphatic hydrocarbon group having 1 to 9 carbon atoms, an aryl group having 6 to 10 carbon atoms, or a heterocyclic group having 3 to 9 carbon atoms. .)
Item 1 is at least one member selected from the group consisting of: The manufacturing method of lactide as described.

5. In the organic onium salt of the general formula (3), [Het] ⁺ H is

よりなる群から選ばれる少なくとも１種である前記の項１．記載のラクチドの製造方法。

Item 1 is at least one member selected from the group consisting of: The manufacturing method of lactide as described.

6). The organic onium salt of the general formula (3) is

よりなる群から選ばれる少なくとも１種である前記の項１．記載のラクチドの製造方法。

Item 1 is at least one member selected from the group consisting of: The manufacturing method of lactide as described.

7). The organic onium salt of the general formula (4) is represented by ([Het ′] ⁺ H) -Q ′-([Het ″] ⁺ H)

（前記一般式において、Ｒ^１１〜Ｒ^２２はそれぞれ独立に、水素原子、炭素数１〜９の脂肪族炭化水素基、炭素数６〜１０のアリール基、または炭素数３〜９の複素環基である。）よりなる群から選ばれる少なくとも１種である前記の項１．記載のラクチドの製造方法。

(In the general formula, R ^{11 to} R ²² are each independently a hydrogen atom, an aliphatic hydrocarbon group having 1 to 9 carbon atoms, an aryl group having 6 to 10 carbon atoms, or a heterocyclic group having 3 to 9 carbon atoms. The above item 1. which is at least one selected from the group consisting of: The manufacturing method of lactide as described.

8). The organic onium salt of the general formula (4) is

よりなる群から選ばれる少なくとも１種である前記の項１．記載のラクチドの製造方法。

Item 1 is at least one member selected from the group consisting of: The manufacturing method of lactide as described.

9. Item 1. The average degree of polymerization of the lactic acid oligomer is 3 or more and 100 or less. ~ 8. The method for producing lactide according to any one of the above.

Item 1. The depolymerization and cyclization are carried out by heating to a temperature of 10.140 to 200 ° C. ~ 9. The method for producing lactide according to any one of the above.

11. Lactic acid oligomer has an optical purity of 99% e.e. e. Item 1. The above item 1, which is a polycondensation of the above optically active lactic acid. -10. The method for producing lactide according to any one of the above.

12 Item 1. The lactic acid oligomer is obtained by heating and polycondensing lactic acid in the presence of at least one organic onium salt selected from the general formulas (1) to (4). ~ 11. The method for producing lactide according to any one of the above.

13. At least one organic onium salt selected from the general formulas (1) to (4) is obtained by adding lactic acid and / or water to a residue obtained by separating lactide from a depolymerization / cyclization reaction product of a lactic acid oligomer or polylactic acid. Item 1, which is heated and regenerated in the presence of lactic acid oligomer as a raw material for depolymerization / cyclization. -10. The method for producing lactide according to any one of the above.

14 Lactide has a meso-lactide content of 1% or less and an optically active lactide selectivity defined by the following formula (A) of 99% or more, and lactic acid has the same optical activity as the lactic acid component constituting the optically active lactide With an optical purity of 99% e.e. e. The above-mentioned item 13. The manufacturing method as described in.
Optically active lactide selectivity [%] = (mass of LL-lactide or DD-lactide) / (mass of LL-lactide + mass of meso lactide + mass of DD-lactide) × 100 (A)

  According to the present invention, lactide having high optical purity and chemical purity can be stably and efficiently produced without using a metal compound catalyst that may be converted into a foreign substance in the process.

About the lactide obtained in Example 4-1 and Comparative Example 4-3, it is an extract around 1.7 ppm of the chart obtained by performing ¹ H-homocoupling NMR measurement (left side: Example 4-1, Right: Comparative Example 4-3). Thereby, the integrated value of the peak of 1.66 ppm and 1.77 ppm used in order to calculate the ratio (henceforth a meso-body ratio) in which this lactide contains meso-lactide can be confirmed. In the continuous lactide production of Example 5, the lactide yield (LA base) based on the total amount of L-lactic acid charged each time and the lactide yield (OLA base) based on the total oligomer amount are shown. It is a bar graph.

Hereinafter, the present invention will be described in detail.
In the present invention, lactide is depolymerized and cyclized by heating a lactic acid oligomer in a reduced-pressure atmosphere in the presence of at least one organic onium salt selected from the group consisting of the general formulas (1) to (4). Is a method for producing lactide.

<Organic onium salt>
First, the organic onium salt represented by the general formula (1) will be described.
In the organic onium salt represented by the general formula (1), when R ^A , R ^B , or R ^C is an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 20 carbon atoms, Examples of the aromatic hydrocarbon group include an unsubstituted or substituted linear or branched alkyl group having 1 to 20 carbon atoms, and an unsubstituted or substituted linear or branched group having 2 to 20 carbon atoms. -Like alkenyl group, unsubstituted or substituted linear or branched alkynyl group having 2 to 20 carbon atoms, unsubstituted or substituted cycloalkyl group having 4 to 12 carbon atoms, unsubstituted or substituted Any one selected from linear or branched aralkyl groups having 7 to 20 carbon atoms having a group is preferred.

  Examples of the alkyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, isopentyl, neopentyl, tertiary pentyl, hexyl, heptyl, Examples include octyl group, 2-ethylhexyl group, nonyl group, decyl group, undecyl group, dodecyl group, tridecyl group, isotridecyl group, myristyl group, palmityl group, stearyl, icosyl group and the like.

  Examples of the alkenyl group include vinyl, allyl, propenyl, isopropenyl, butenyl, isobutenyl, pentenyl, isopentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, An undecenyl group, a dodecenyl group, a tetradecenyl group, an oleyl group, an icocenyl group, etc. are mentioned.

  Examples of the alkynyl group include propargyl group, 2-butynyl group, 3-butynyl group, 1-methyl-2-propynyl group, 3-pentynyl group, 4-pentynyl group, 19-icosinyl group and the like.

  Examples of the cycloalkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cyclooctyl group, a methylcyclohexyl group, a decahydronaphthyl group, and a perhydrobiphenyl group.

  Examples of the aralkyl group include a benzyl group, a methylbenzyl group, an (α- / β-) phenethyl group, a methylphenethyl group, a phenylbenzyl group, a naphthylmethyl group, and a triphenylethyl group.

  In addition, regarding the structure of the organic onium salt of the general formulas (1) to (4) used in the production method of the present invention, the “substituent” in the case of “unsubstituted or having a substituent” means a fluoro group Chloro group, bromo group, iodo group, cyano group, thiocyano group, methoxy group, ethoxy group, phenoxy group, methylthio group, ethylthio group, phenylthio group, methylsulfonyl group, ethylsulfonyl group, phenylsulfonyl group When referring to one or more kinds, such as “a linear or branched alkyl group having 1 to 20 carbon atoms having a substituent”, the number of carbon atoms is for the alkyl group, This does not include the carbon atoms possessed by.

In the organic onium salt represented by the general formula (1), when two or more of R ^A , R ^B , or R ^C form a ring instead of a hydrogen atom, the cyclic structure includes a pyrrolidine ring, a piperidine ring 1 or more selected from the group consisting of morpholine ring, piperazine ring, 2-azaadamantane ring, quinuclidine ring, and the like.

In the organic onium salt represented by the general formula (1), when R ^A , R ^B , or R ^C is an unsubstituted or substituted aryl group having 6 to 18 carbon atoms, A phenyl group, a toluyl group, a xylyl group, an (α-, β-) naphthyl group, a biphenyl group, an anthranyl group, a fluorenyl group, a terphenyl group, a phenanthryl group, an acenaphthyl group, etc. are preferred, and these aryl groups are unsubstituted or Those in which one or more hydrogens are substituted with a fluoro group or a chloro group are preferable.

In the organic onium salt represented by the general formula (1), when R ^A , R ^B , or R ^C is an unsubstituted or substituted heterocyclic group having 3 to 22 carbon atoms, the aryl group is Preferred examples include aziridyl group, furyl group, chenyl group, pyrrolyl group, pyridyl group, quinolyl group, benzofuryl group, oxazolyl group, thiazolyl group, imidazolyl group, pyrazyl group, pyrimidyl group, quinazolinyl group, purinyl and the like.

In the general formula (1), X ^- represents an alkyl sulfonate ion having 1 to 18 carbon atoms, an aryl sulfonate ion having 6 to 18 carbon atoms, a heterocyclic sulfonate ion having 4 to 18 carbon atoms, 1 to 8 carbon atoms Fluorinated alkyl sulfonate ions or hydrogen sulfate ions of methane sulfonate ion, ethane sulfonate ion, octane sulfonate ion, dodecane sulfonate ion, p-toluene sulfonate ion, benzene sulfonate ion, One or more kinds selected from the group consisting of naphthalene sulfonate ion, dodecyl benzene sulfonate ion, decyl benzene sulfonate ion, perfluoroalkyl sulfonate ion having 1 to 6 carbon atoms and hydrogen sulfate ion are preferable, and 1 to 6 carbon atoms are preferable. Perfluoroalkyl sulfonate ion Fluoromethanesulfonic acid ions, perfluoroethanesulfonic acid ions, perfluorobutanesulfonic acid ions, perfluorohexanesulfonic acid ions, and the like are particularly preferable.

  Examples of the organic onium salt represented by the general formula (1) include cation having aliphatic ammonium such as trimethylammonium, triethylammonium, ethyldimethylammonium and diethylmethylammonium, aromatic ammonium such as anilinium and diphenylammonium, and N-methyl. Preferred are those that are monophosphonium such as alicyclic ammonium such as pyrrolidinium, N-methylpiperidinium, N-methylmorpholinium, triarylphosphonium, aryldialkylphosphonium, diarylalkylphosphonium, trialkylphosphonium. It is done.

  In particular, the general formula (1) in which the cation is fluorine-substituted anilium, chlorine-substituted, specifically dichloroanilinium at any substitution position, trichloroanilinium, diphenylammonium, triarylammonium at any substitution position. The organic onium salt represented by these is preferable, and what shows a structure below is mentioned as a more preferable thing.

ここで、ＴＰＰ−Ｔはトリフェニルホスホニウムトルフルオロメタンスルホネート、ＴＰＰ−Ｓはトリフェニルホスホニウムハイドロジェンサルフェート、ＰＦＰＡＴはペンタフルオロフェニルアンモニウムトルフルオロメタンスルホネート、２，４−ＤＣＡ−Ｔは２，４−ジクロロフェニルアンモニウムトルフルオロメタンスルホネート、２，５−ＤＣＡ−Ｔは２，５−ジクロロフェニルアンモニウムトルフルオロメタンスルホネート、２，４，６−ＤＣＡ−Ｔは２，４，６−トリクロロフェニルアンモニウムトルフルオロメタンスルホネート、ＤＰＡＴはジフェニルアンモニウムトリフルオロメタンスルホネート、ＤＰＡ−Ｓはジフェニルアンモニウムハイドロジェンサルフェートの略号である。

Here, TPP-T is triphenylphosphonium trifluoromethanesulfonate, TPP-S is triphenylphosphonium hydrogen sulfate, PFPAT is pentafluorophenylammonium trifluoromethanesulfonate, and 2,4-DCA-T is 2,4-dichlorophenyl. Ammonium trifluoromethanesulfonate, 2,5-DCA-T is 2,5-dichlorophenylammonium trifluoromethanesulfonate, 2,4,6-DCA-T is 2,4,6-trichlorophenylammonium trifluoromethanesulfonate, DPAT Is an abbreviation for diphenylammonium trifluoromethanesulfonate, and DPA-S is an abbreviation for diphenylammonium hydrogen sulfate.

Next, the organic onium salt represented by the general formula (2) will be described.
As the organic onium salt represented by the general formula (2), those in which Q is a single bond or an unsubstituted linear or branched alkylene group having 1 to 12 carbon atoms are preferable.

Preferred groups of R ^D , R ^E , R ^F , and R ^{G in} the general formula (2) are the same as those shown for R ^A , R ^B , and R ^C in the general formula (1). However, in the case where two or more of R ^D , R ^E , R ^F , and R ^G form a ring instead of a hydrogen atom, the cyclic structure includes, for example, the pyrrolidine ring shown for the general formula (1), A 1,3-diadamantane ring and the like are also included.

X in the general formula (2) ^'-, and ^X''- preferred are the X in the general formula (1) ^- are the same as those shown for.

  Particularly preferred examples of the organic onium salt represented by the general formula (2) include the following.

（前記右側の一般式において、ｍおよびｎはそれぞれ独立に０〜４のいずれかである。）

(In the general formula on the right side, m and n are each independently 0-4.)

Next, the organic onium salt represented by the general formula (3) will be described.
In addition, regarding the structure of the organic onium salt of the general formulas (3) to (4) used in the production method of the present invention, the term “substituent” in the case of “unsubstituted or having a substituent” A linear or branched alkyl group having 1 to 20 carbon atoms, an unsubstituted linear or branched alkenyl group having 2 to 20 carbon atoms, an unsubstituted straight chain having 2 to 20 carbon atoms Or a branched alkynyl group, an unsubstituted cycloalkyl group having 4 to 12 carbon atoms, an unsubstituted linear or branched aralkyl group having 7 to 20 carbon atoms, a fluoro group, a chloro group, a bromo group, and an iodo group Group, cyano group, thiocyano group, methoxy group, ethoxy group, phenoxy group, methylthio group, ethylthio group, phenylthio group, methylsulfonyl group, ethylsulfonyl group, phenylsulfonyl group, amino group It refers to one or more selected from the group consisting of groups, and when it is referred to as “an unsubstituted or substituted nitrogen-containing aromatic heterocyclic group having 3 to 65 carbon atoms”, the carbon number of the substituent is carbon Includes atoms.

Preferable X ^{′ ″ −} in the general formula (3) is the same as that shown for X ⁻ in the general formula (1).

As the organic onium salt represented by the general formula (3), [Het] ⁺ H is

（前記一般式において、Ｒ^１〜Ｒ^７はそれぞれ独立に、水素原子、ハロゲン原子、炭素数１〜９の脂肪族炭化水素基、炭素数６〜１０のアリール基、または炭素数３〜９の複素環基である。）よりなる群から選ばれる少なくとも１種であるものが好ましく、具体例として、ピリジニウム、ピリダジニウム、ピラジニウム、ピリミジニウム、ピラゾリウム、イミダゾリウム、オキサゾリウム、イソオキサゾリウムなどの含窒素の単環又は縮合環化合物を挙げることができる。これら含窒素芳香族複素環化合物にはアルキル基、アラルキル基、ハロゲン基、アルコキシ基などの置換基が結合していても良い。

(In the general formula, R ^{1 to} R ⁷ are each independently a hydrogen atom, a halogen atom, an aliphatic hydrocarbon group having 1 to 9 carbon atoms, an aryl group having 6 to 10 carbon atoms, or an aryl group having 3 to 9 carbon atoms. And at least one selected from the group consisting of a heterocyclic group), and specific examples include nitrogen-containing compounds such as pyridinium, pyridazinium, pyrazinium, pyrimidinium, pyrazolium, imidazolium, oxazolium, and isoxazolium. A monocyclic or condensed ring compound can be mentioned. These nitrogen-containing aromatic heterocyclic compounds may be bonded to a substituent such as an alkyl group, an aralkyl group, a halogen group, or an alkoxy group.

As the organic onium salt represented by the general formula (3), [Het] ⁺ H is

よりなる群から選ばれる少なくとも１種であるとより好ましく、かつＸ^’’’−が炭素数１〜６のパーフルオロアルキルスルホン酸イオンであると一層好ましい。更に言うと、前記一般式（３）で表される有機オニウム塩としては、

It is more preferable that it is at least one selected from the group consisting of the above, and it is more preferable that X ^{′ ″ −} is a perfluoroalkylsulfonic acid ion having 1 to 6 carbon atoms. Furthermore, as the organic onium salt represented by the general formula (3),

よりなる群から選ばれる少なくとも１種が特に好ましい。

Particularly preferred is at least one selected from the group consisting of:

Next, the organic onium salt represented by the general formula (4) will be described.
Preferable Q ′ in the general formula (4) is the same as that shown for Q in the general formula (2).

Formula (4) X ^'in''of the preferred X in the general formula (1) ^{- -' -} and X ^'''''is similar to that shown for.

The organic onium salt of the general formula (4) has ([Het ′] ⁺ H) -Q ′-([Het ″] ⁺ H)

（前記一般式において、Ｒ^１１〜Ｒ^２２はそれぞれ独立に、水素原子、炭素数１〜９の脂肪族炭化水素基、炭素数６〜１０のアリール基、または炭素数３〜９の複素環基である。）
よりなる群から選ばれる少なくとも１種であることが好ましい。好ましいものの具体例としては、２，２’−ビピリジニウム、４，４’ −ビピリジニウム、５，５’−ジメチル−２，２’−ビピリジニウム、が挙げられる。また、ビスホスホニウムも好ましいものとして挙げることができる。

(In the general formula, R ^{11 to} R ²² are each independently a hydrogen atom, an aliphatic hydrocarbon group having 1 to 9 carbon atoms, an aryl group having 6 to 10 carbon atoms, or a heterocyclic group having 3 to 9 carbon atoms. .)
It is preferably at least one selected from the group consisting of: Specific examples of preferable ones include 2,2′-bipyridinium, 4,4′-bipyridinium, and 5,5′-dimethyl-2,2′-bipyridinium. Bisphosphonium can also be mentioned as a preferable one.

  Furthermore, as the organic onium salt represented by the general formula (4),

よりなる群から選ばれる少なくとも１種が特に好ましい。

Particularly preferred is at least one selected from the group consisting of:

  In the following description, unless otherwise specified, the sulfonates of the above chemical formulas (5) to (9) are pyridinium trifluoromethanesulfonate, methylimidazolium trifluoromethanesulfonate, 5,5′-dimethyl-2,2 respectively. '-Bispyridinium trifluoromethanesulfonate, 2,2'-bispyridinium trifluoromethanesulfonate, 4,4'-bispyridinium trifluoromethanesulfonate, PyH-T, Me-Imid-T, 5,5'-diMe, respectively. It shall be abbreviated as -2,2'-BiPy-T, 2,2'-BiPy-T, and 4,4'-BiPy-T.

  The organic onium salts of the general formulas (1) to (4) have sufficient stability under the conditions for depolymerizing and cyclizing the lactic acid oligomer to produce lactide, but the general formulas (5) to (5) Since the organic onium salt 9) is particularly excellent in heat resistance, the reaction temperature can be further increased.

As a method for producing an organic onium salt of the general formula (1) to (4), a nitrogen-containing compound or a phosphorus-containing compound of cationic components, X ^- a method of reacting a sulfonic acid as the anionic component, such as it is convenient is there. Specifically, the organic onium salts of the general formulas (7), (8), and (9) are expressed as follows. The organic onium salt of the general formula (7) is represented by 5,5′-dimethyl-2,2′-bipyridine. It is obtained by dissolving in methylene chloride, neutralizing by adding 2 equivalents of trifluoromethanesulfonic acid, and then recrystallizing by adding diethyl ether.

  In the organic onium salt of the general formula (8), 2,2′-bipyridine is dissolved in methylene chloride, neutralized by adding 2 equivalents of trifluoromethanesulfonic acid, and then recrystallized by adding diethyl ether. Can be obtained.

  Further, the organic onium salt of the general formula (9) is obtained by dissolving 4,4′-bipyridine in methylene chloride, adding 2 equivalents of trifluoromethanesulfonic acid to neutralize, and then recrystallizing with diethyl ether. Can be obtained.

  The synthesis method of the organic onium salt of the general formula (8) is described in “Barbara Milani, Anna Anzilutti, Lidia Vicentini, Andrea Sessanta o Santi, Ennio Zangrando, Silvano Geremia, and Giovanni Mestroni Organometallics 1997, 16, 5064-5075”. Details are shown.

  The amount of the organic onium salt used in the production method of the present invention is preferably such that the catalyst concentration based on the lactic acid oligomer is 0.01 to 10 mol%, more preferably 0.1 to 5 mol%, and 0.2 to 2 mol%. Is particularly preferred. If the amount is less than 0.01 mol%, the yield of lactide tends to be insufficient, and if the amount exceeds 10 mol%, the effect hardly changes.

In the present invention, the “catalyst concentration based on lactic acid oligomer” is determined by dividing the mass of the lactic acid oligomer by 72 of the formula amount of lactic acid residue (—O—CH (CH ₃ ) —C (═O) —). The ratio of the molar amount of the organic onium salt to the molar amount of the lactic acid residue (organic onium salt / lactic acid residue). The same applies to “polylactic acid-based catalyst concentration” and “lactide residue-based catalyst concentration”.

<Depolymerization / Cyclization>
In the production method of the present invention, it is preferable to use a lactic acid oligomer having an average degree of polymerization of 3 to 100. If a lactic acid oligomer with an average polymerization degree of less than 3 is used, low molecular weight oligolactic acid tends to distill before the lactide is formed. If a lactic acid oligomer with an average polymerization degree of more than 100 is used, depolymerization and cyclization will occur during heating. This is because the polycondensation proceeds more preferentially and the yield of lactide decreases. Here, the average degree of polymerization can be measured by ¹ H-NMR spectrum measurement, and the obtained number average degree of polymerization is referred to as the average degree of polymerization unless otherwise specified. The lactic acid oligomer used in the production method of the present invention is more preferably one having an average degree of polymerization of 3 to 50, and still more preferably one having an average degree of polymerization of 6 to 15.

  In the depolymerization / cyclization of the production method of the present invention, the reduced pressure may be a pressure lower than the atmospheric pressure (101.3 kPa), preferably 0.013-1.3 kPa, more preferably 0.133- 0.533 kPa.

  In the production method of the present invention, the temperature for performing depolymerization / cyclization is preferably 140 to 200 ° C, more preferably 160 to 180 ° C. This is because if the heating temperature is lower than 140 ° C., depolymerization and cyclization hardly proceed, and if the heating temperature is higher than 200 ° C., side reactions are likely to occur, which is not preferable.

  In the production method of the present invention, the reaction time for depolymerization / cyclization is preferably shorter from the viewpoint of productivity, but it is necessary to carry out the reaction sufficiently, so that it is 0.5 to 75 hours. Preferably, it is 1 to 35 hours, more preferably 2 to 10 hours.

  In the production method of the present invention, the depolymerization and cyclization of the lactic acid oligomer may be performed using a solvent or without a solvent. Unless otherwise specified, the term “solvent-free” in the present invention means a reaction condition in which a solvent for azeotropic removal of water generated by a dehydration condensation reaction is not added.

  In addition, in the manufacturing method of this invention, in addition to the said organic onium salt, it is also possible to use together well-known metal compound catalysts, such as a tin compound, to such an extent that the effect of this invention is not impaired.

<Lactic acid oligomer>
In the production method of the present invention, as the raw material lactic acid oligomer, those produced by a known method can be used. For example, a typical example is a lactic acid oligomer obtained by direct dehydration condensation of lactic acid. In that case, the reaction mixture in which lactic acid is directly dehydrated and condensed to form a lactic acid oligomer may be used as a raw material in the production method of the present invention, or the lactic acid oligomer may be used after being separated and purified from the reaction mixture. Also good.

  In order to obtain high-performance polylactic acid, high-purity lactide is required, and in order to obtain high-purity lactide, D-lactic acid or L-lactic acid used as a raw material for lactic acid oligomers must have high optical purity. It is preferable to use it.

Here, the optical purity can be represented by a value obtained by subtracting the smaller amount from the larger amount of D-lactic acid or L-lactic acid and dividing the result by the total amount. For example, when the amount of L-lactic acid is “L”, the amount of D-lactic acid is “D”, and the amount of L-lactic acid is excessive, the optical purity is expressed by the following formula.
Optical purity (% ee) = [(LD) / (L + D)] × 100

  The optical purity of D-lactic acid or L-lactic acid can be calculated from the peak area ratio of the D / L form of lactic acid using a high performance liquid chromatographic method (HPLC method).

  In the present invention, the optically active lactic acid used as a raw material for the lactic acid oligomer, that is, D-lactic acid or L-lactic acid has an optical purity of 99% e.e. e. The above are more preferable, and 99.5% e.e. e. The above is more preferable.

  In the production method of the present invention, of course, a lactic acid oligomer obtained by ring-opening polymerization of lactide may be used as a raw material.

  As described above, if the degree of polymerization of the lactic acid oligomer is too high, dehydration polycondensation is more likely to proceed preferentially than depolymerization and cyclization even when heated under reduced pressure together with the organic onium salt. As described above, direct dehydration polycondensation of lactic acid so that the degree of polymerization of the lactic acid oligomer is preferably 100 or less, more preferably 50 or less, particularly preferably 15 or less, and preferably 3 or more, more preferably 6 or more. It is preferable to select these conditions.

  The pressure for direct dehydration polycondensation of lactic acid is preferably 2.5 to 9.3 kPa, and more preferably 4.0 to 6.7 kPa. If the pressure is higher than 9.3 kPa, it may be difficult to distill water. In addition, a lower pressure is preferable because the reaction temperature can be lowered. However, if the pressure is lower than 2.5 kPa, a high vacuum device is required and problems such as clogging of the piping may occur easily. .

  The temperature for direct dehydration polycondensation of lactic acid is preferably 120 to 160 ° C, more preferably 130 to 150 ° C. If the temperature of direct dehydration polycondensation is lower than 120 ° C, dehydration condensation may not proceed easily, and if it is higher than 160 ° C, the degree of polymerization may become too high.

  The reaction time for the direct dehydration polycondensation of lactic acid is preferably shorter from the viewpoint of productivity, but it is necessary to carry out the reaction sufficiently, and it is preferably 0.5 to 75 hours, and preferably 1 to 35 hours. More preferably, it is more preferably 2 to 10 hours.

  When obtaining a lactic acid oligomer by directly dehydrating polycondensation of lactic acid, the reaction may be carried out only with a mixture of lactic acid and a polycondensation catalyst without using a solvent, and azeotropic removal of water generated by the dehydration polycondensation reaction may be performed. A solvent may be added. As such a solvent, benzene, toluene, xylene and the like can be used, and the amount used is preferably about 1 to 3 times (volume) with respect to lactic acid from the viewpoint of operability.

  As a polycondensation catalyst for obtaining a lactic acid oligomer by directly dehydrating polycondensation of lactic acid, known compounds such as metal compound catalysts represented by tin octylate can be used. Use of at least one of the organic onium salts shown in 4) is preferable because it can be used as a raw material for producing lactide without isolating lactic acid oligomers or removing metal compound catalysts. The amount of the polycondensation catalyst used in the direct dehydration polycondensation is preferably such that the concentration of the polycondensation catalyst relative to lactic acid (polycondensation catalyst / lactic acid) is 0.01 to 10 mol%, and more preferably 0.1 to 5 mol%. Preferably, it is especially preferable in it being 0.2-2 mol%.

  In the production method of the present invention, the raw lactic acid oligomer may be a residue obtained by separating lactide from a reaction product obtained by depolymerizing and cyclizing the lactic acid oligomer (hereinafter sometimes referred to as a lactide residue) and / or lactic acid and / or You may use what was regenerated by adding water and heating. The lactide residue contains lactic acid oligomers having a high degree of polymerization and polylactic acid, and acid degradation by lactic acid and / or hydrolysis by water occurs to lower the molecular weight. A lactic acid oligomer suitable as a raw material is regenerated.

  Furthermore, as a lactic acid oligomer used as a raw material in the production method of the present invention, a lactic acid and / or water regenerated by adding lactic acid and / or water to a polylactic acid may be used (hereinafter referred to as a lactide residue or a polylactic acid). Lactic acid oligomers regenerated from lactic acid may be referred to as regenerated lactic acid oligomers). In this case, the polylactic acid may be isolated from the above-mentioned lactide residue, may be a non-quality product during the polycondensation reaction, may be a molding waste generated when spinning or molding polylactic acid, A product that is sold as a polylactic acid product and discarded after use can be recovered to remove foreign substances and other materials. The lactic acid and / or water used when regenerating the lactic acid oligomer from the polylactic acid or lactide residue is preferably a lactic acid aqueous solution. An aqueous lactic acid solution may be prepared in advance and mixed with polylactic acid or a lactide residue, or lactic acid and water may be mixed separately.

  As described above, by adding lactic acid and / or water to lactide residue or polylactic acid and heating, the lactic acid oligomer is regenerated, and this is depolymerized and cyclized to produce lactide. In this case, lactide is a meso-lactide. The content is 1% or less, and the optically active lactide selectivity defined by the above formula is 99% or more. The lactic acid exhibits the same optical activity as the lactic acid component constituting the optically active lactide, and the optical purity is 99. % E. e. The above is preferable.

  In the present invention, for the sake of convenience, those having an average polymerization degree exceeding 100 are referred to as polylactic acid, those having 3 to 100 are referred to as lactic acid oligomers, and acyclic dimers are referred to as dimers. The upper limit of the average degree of polymerization of the polylactic acid is not particularly limited, but if the average degree of polymerization is too high, it is difficult for the acidolysis to proceed. Therefore, the average degree of polymerization is preferably 7000 or less, more preferably 5000 or less, More preferably, it is 1000 or less.

  The temperature at which the lactic acid oligomer is regenerated by adding lactic acid and / or water to the lactide residue or polylactic acid and heating it is preferably 100 ° C. or higher and 200 ° C. or lower, and 120 ° C. or higher and 160 ° C. or lower. And more preferred.

  The pressure for regenerating the lactic acid oligomer by adding lactic acid and / or water to the lactide residue or polylactic acid and heating is not particularly limited, but it may be an atmospheric pressure atmosphere of 0.096 to 0.106 MPa or 0 A pressurized atmosphere exceeding 106 MPa is preferred. The upper limit of the pressure when regenerating the lactic acid oligomer in a pressurized atmosphere is preferably 5 MPa or less, and preferably 1 MPa or less.

  The reaction time when regenerating the lactic acid oligomer by adding lactic acid and / or water to the lactide residue or polylactic acid and heating it is preferable in terms of productivity, but it is necessary to carry out the reaction sufficiently. Therefore, it is preferably 0.5 to 75 hours, more preferably 1 to 35 hours, and even more preferably 2 to 10 hours.

  When the lactic acid oligomer is regenerated by adding lactic acid and / or water to the lactide residue or polylactic acid and heating, the amount of lactic acid and / or water relative to the lactide residue or polylactic acid is 100 parts by weight of lactide residue or polylactic acid. It is preferable that it is 10 to 2500 mass parts with respect to polylactic acid, and it is still more preferable that it is 25 to 1000 mass parts. In the production method of the present invention, the lactic acid and / or water is preferably a lactic acid aqueous solution. When the total amount of lactic acid and water is 100% by mass, the lactic acid aqueous solution has a lactic acid concentration of more than 0% to less than 100% by mass and a lactic acid concentration of 50% by mass to 99% by mass. It is preferable, and it is more preferable in it being 80 to 95 mass%.

  The lactic acid and / or water used in the production method of the present invention may contain other components that do not hinder the purpose of the present invention, such as inhibiting the regeneration of lactic acid oligomers, in addition to lactic acid and water. .

  When lactic acid oligomer is regenerated by adding lactic acid and / or water to lactide residue or polylactic acid and heating, the reaction may be carried out without a catalyst, and a metal compound catalyst typified by tin octylate is added with acid. Although it may be used as a decomposition catalyst, when at least one of the organic onium salts represented by the general formulas (1) to (4) is used as an acid decomposition catalyst, the lactic acid oligomer is isolated and the metal compound catalyst is removed. It is preferable because it can be used as a raw material for producing lactide without having The amount of the hydrolysis catalyst used to regenerate the lactic acid oligomer by adding lactic acid and / or water to the lactide residue or polylactic acid, and heating, the catalyst concentration based on the lactide residue or polylactic acid is 0.01 to The amount is preferably 10 mol%, more preferably 0.1 to 5 mol%, and particularly preferably 0.2 to 2 mol%.

<Manufacturing process>
As is clear from the above description, in the lactide production method of the present invention, lactic acid is polycondensed to produce a lactic acid oligomer, and the lactic acid oligomer is depolymerized and cyclized to produce lactide. The process of adding lactic acid and / or water to the residue obtained by separating the lactide from the isomerization reaction product to cause acidolysis and / or hydrolysis to regenerate the lactic acid oligomer, which is also depolymerized and cyclized, The organic onium salt can be used. The amount of the organic onium salt can be added as appropriate in the process, and can be reduced by purging the reaction mixture out of the process. Each reactor constituting the process may be a batch type, a semi-batch type or a continuous type, and a known apparatus for polycondensation of lactic acid or depolymerization / cyclization of lactic acid oligomers can be adopted.

<Lactide>
With the lactide production method of the present invention, extremely high purity lactide can be obtained.
For example, 100% e. e. In addition to LL-lactide, which is a cyclic dimer of L-lactic acid, if the depolymerization and cyclization conditions are inappropriate even if the oligomer obtained using L-lactic acid is used as a raw material, first, meso lactide (DL-lactide) is produced, and further DD-lactide is produced.

  Of course, 100% e.e. e. In addition to DD-lactide, which is a cyclic dimer of D-lactic acid, if the depolymerization and cyclization conditions are inappropriate even if the oligomer obtained using D-lactic acid is used as a raw material, first meso lactide It is known that (DL-lactide) is produced and further LL-lactide is produced.

Therefore, for a certain lactide sample, in order to formally express the purity of a certain optically active lactide, that is, either the LL-form or the DD-form, the optical activity of the subject represented by the following formula (A): Indicators such as the proportion of lactide in the total amount of LL-lactide, meso-lactide, and DD-lactide (optically active lactide selectivity) are required. In the following formula (A), calculation may be performed by replacing all the masses with molar amounts.
Optically active lactide selectivity [%] = (mass of LL-lactide or DD-lactide) / (mass of LL-lactide + mass of meso lactide + mass of DD-lactide) × 100 (A)

With respect to lactide obtained by the production method of the present invention using lactic acid having a high optical purity as described above as a raw material, optically active lactides (LL-lactide and DD-lactide are analyzed by ¹ H- or ¹³ C-NMR analysis of lactide. When the abundance ratio of meso-lactide is determined and the meso form ratio determined by the following formula (B) is 1% or less, the total amount of the optically active lactide is the cyclic disaccharide of the optically active lactic acid used as a raw material. Mer, that is, the optical purity is 100% e.e. e. The above formula (A) can be simplified as the following formula (A ′).
Mesobody ratio [%] = {integral value of peak of meso lactide / (integral value of peak of optically active lactide + integral value of peak of meso lactide)} × 100 (B)

Optically active lactide selectivity [%] = (mass of LL-lactide or DD-lactide) / (mass of LL-lactide + mass of meso lactide + mass of DD-lactide) × 100≈100−meso body fraction (A ′)

  For example, when LL-lactide is produced by the production method of the present invention using an L-lactic acid oligomer as a raw material, the ratio of LL-lactide to the total amount of LL-lactide, meso-lactide, and DD-lactide (LL-lactide selectivity and Is expressed by the following formula (C). Of course, in the following formula (C), all the masses may be replaced with molar amounts.

  LL-lactide selectivity [%] = (mass of LL-lactide) / (mass of LL-lactide + massolactide mass + mass of DD-lactide) × 100≈100-meso body fraction (C)

  Patent Document 2 and Patent Document 4 mentioned above also have an optical purity of 100% e.e. e. Alternatively, a process for obtaining an optically active lactide close to that is disclosed, but as is clear from the description of Examples in Patent Document 4, the optically active lactide obtained by this method has a meso lactide of at least about 2 to 3%. In order to obtain highly heat-resistant polylactic acid, it was necessary to further purify and separate meso lactide.

  In the production method of the present invention, the meso form ratio, that is, the mixing ratio of meso lactide is 1% or less, the optically active lactide selectivity is 99% or more, and the optical purity is 99% e.e. e. Since the above-described highly pure optically active lactide is obtained, the above-described purification step of lactide can be omitted or simplified. As described above, polylactic acid production by the lactide method has a long production process, which causes high costs. Therefore, shortening the production process by the lactide production method of the present invention is extremely important.

  Known methods, apparatuses, and processes for obtaining high molecular weight polylactic acid by ring-opening polymerization of lactide obtained by the production method of the present invention can be used.

  The lactide production method of the present invention can be applied to the production of glycolide, which is a cyclic dimer of glycolic acid. That is, in the method for producing lactide, except for those relating to optical activity, lactic acid is replaced with glycolic acid, lactic acid oligomer is replaced with glycolic acid oligomer, lactide is glycolide, and polylactic acid is replaced with polyglycolic acid. By using the organic onium salt of (4), it becomes an invention of a method for producing glycolide in which the problem in the case of using a metal compound catalyst such as tin octylate as described above is solved.

  EXAMPLES Hereinafter, although this invention is demonstrated further in detail using an Example, this invention is not limited to a following example, A various improvement and deformation | transformation are possible within the scope of the present invention.

  The analysis and physical property measurement methods performed in this example and the raw materials used are as follows.

1) tetramethylsilane (TMS) A sample was dissolved in CDC1 ₃ solvent containing 0.03Vol% as meso ratio and LL- lactide selectivity standard compound of lactide, Bruker DRX500 (500 MHz) NMR spectrometer (Bruker Co.) ¹ H-homocoupling NMR measurement is performed, and the meso body fraction is obtained from the integrated value of 1.66 ppm and 1.77 ppm by the following formula (D), and further from the meso body percentage by the following formula (E). The LL-lactide selectivity was determined.

Mesobody ratio [%] = (integrated value of 1.77 ppm) / {(integrated value of 1.66 ppm) + (integrated value of 1.77 ppm)} × 100 (D)

LL-lactide selectivity [%] = 100-meso body ratio (E)

2) tetramethylsilane (TMS) as the average degree of polymerization of standard compound of lactic acid oligomers and polylactic acid of a sample was dissolved in 0.03Vol% including CDC1 ₃ solvent, using a Bruker DRX500 (500 MHz) NMR spectrometer (Bruker Co.) Then, ¹ H-NMR spectrum measurement was performed and calculated from the area ratio of CH (δ4.3) on the OH terminal side and internal CH (δ5.2).

3) Thermal decomposition temperature measurement of organic onium salt 5 when the sample was heated from room temperature to 600 ° C. in air at a heating rate of 10 ° C./min using a thermogravimetric measuring device manufactured by Texas Instruments. % Mass reduction temperature was defined as the thermal decomposition temperature.

4) Optical purity of L-lactic acid The 90 mass% (hereinafter abbreviated as 90 wt%) L-lactic acid aqueous solution used in this example has an optical purity of L lactic acid of 99% e. e. That's all. The measurement conditions of optical purity by the HPLC method are shown below.
Measurement condition:
Column: SUMICHIRAL OA-5000 (4.5 mmφ × 15 cm, Sumika Chemical Analysis Center)
Column oven temperature: 40 ° C
Mobile phase: 1 mM CuSO 4 aqueous solution flow rate: 1.0 mL / min
Measurement time: 30 minutes Oven: Shodex Oven AO-30
Pump: Shodex DS-4
Detector: Shodex UV-41 (measurement wavelength 254 nm)

5) PyH-T catalyst As a PyH-T catalyst used in this example, product code P1627 manufactured by Tokyo Chemical Industry Co., Ltd. was used.

[Synthesis of organic onium salts]
Synthesis Example 1 (Synthesis of TPP-T catalyst)
In a 200 mL eggplant flask, 2.3 g of triphenylphosphine (manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in 25 mL of methylene chloride, and 0.9 ml of trifluoromethanesulfonic acid was added dropwise little by little while cooling with ice. Crystals precipitated from a solvent of methylene chloride / diethyl ether / hexane = 2/2/1 were suction filtered and dried under reduced pressure to obtain the PP-T catalyst shown below in a yield of 78.9%. The thermal decomposition temperature of the TPP-T catalyst was 178 ° C.
Reference: van der Akker, M. Jellinek, Recl. Trav. Chim. Pays-Bas, 1967, 86, 275-288.

Synthesis Example 2 (Synthesis of TPP-S catalyst)
In 30 mL of methylene chloride, 2.62 g (10 mmol) of triphenylphosphine was dissolved, and 1.0 mL (9.7 mmol) of concentrated sulfuric acid was added little by little with ice cooling and stirring. After concentration, crystals precipitated from 30 mL of ethyl acetate were suction filtered and dried under reduced pressure to obtain 2.31 g of the TPP-S catalyst shown below (yield 64%). The thermal decomposition temperature of the TPP-S catalyst was 173 ° C.
¹³ C NMR (CDCl ₃ ) δ119.02 (d, J = 69.8 Hz), 129.9 (d, J = 12.5), 134.4 (d, J = 9.5), 134.6 (d, J = 3.4 Hz)
³¹ P NMR (CDCl ₃ ) δ20.89

Synthesis Example 3 (Synthesis of PyH-S catalyst)
In a 200 mL eggplant flask, 5.2 g (65 mmol) of pyridine was dissolved in 15 mL of methylene chloride, and 3.6 mL (65 mmol) of concentrated sulfuric acid was added dropwise little by little while cooling with ice. Crystals precipitated from diethyl ether (150 mL) were filtered and dried under reduced pressure to obtain 8 g of the following PyHS catalyst (yield 69.0%).
¹³ C NMR (CDCl ₃ ) δ 127.34, 141.82, 146.43

Synthesis Example 4 (Synthesis of Me-Imid-T catalyst)
In a 200 mL eggplant flask, 4 mL (50.2 mmol) of N-methylimidazole was dissolved in 25 mL of methylene chloride, and 5 mL (53.3 mmol) of trifluoromethanesulfonic acid was added dropwise little by little while stirring on ice. Crystals precipitated from diethyl ether (150 mL) were suction filtered and dried under reduced pressure to obtain 12 g of the Me-Imid-T catalyst shown below (yield 95.9%). The thermal decomposition temperature of the Me-Imid-T catalyst was 276 ° C.
¹³ C NMR (CD ₃ COCD ₃ ) δ35.53, 119.88, 121.05 (q, J = 319.0), 123.49, 135.91
¹⁹ F NMR (CD ₃ COCD ₃ ) δ98.68

Synthesis Example 5 (Synthesis of 5,5′-diMe-2,2′-BiPy-T catalyst)
In a 200 mL eggplant flask, 9 g (48 mmol) of 5,5′-dimethyl-2,2′-bipyridine (manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in 25 mL of methylene chloride, and 9 mL (96 mmol) of trifluoromethanesulfonic acid was stirred with ice cooling. ) Was added dropwise little by little. Crystals precipitated from diethyl ether (150 mL) were suction filtered and dried under reduced pressure to obtain 11 g of 5,5′-Me-2,2′-BiPy-T catalyst shown below (yield 47.7%). . The thermal decomposition temperature of the 5,5′-Me-2,2′-BiPy-T catalyst was 235 ° C.
¹³ C NMR (CDCl ₃ ) δ18.04, 120.08 (q, J = 319.7), 122.28, 137.71, 143.19, 144.21, 145.88
¹⁹ F NMR (CD ₃ COCD ₃ ) δ98.68

Synthesis Example 6 (Synthesis of 2,2′-BiPy-T catalyst)
In a 200 mL eggplant flask, 4.5 g (28.8 mmol) of 2,2′-bipyridine (manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in 25 mL of methylene chloride, and 5 mL (53.3 mmol) of trifluoromethanesulfonic acid was stirred with ice cooling. Was added dropwise little by little. Crystals precipitated from diethyl ether (150 mL) were suction filtered and dried under reduced pressure to obtain 12 g of 2,2′-BiPy-T catalyst shown below (yield 95.9%). The thermal decomposition temperature of the 2,2′-BiPy-T catalyst was 208 ° C.
¹³ C NMR (CDCl ₃ ) δ119.95 (q, J = 319.0), 123.54, 127.20, 143.41, 145.71, 14.96
¹⁹ F NMR (CDCl ₃ ) δ-78.75

Synthesis Example 7 (Synthesis of 4,4′-BiPy-T)
In a 200 mL eggplant flask, 4.5 g of 4,4′-bipyridine (manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in 25 mL of methylene chloride, and 5 mL of trifluoromethanesulfonic acid was added dropwise little by little while stirring with ice cooling. Crystals precipitated from diethyl ether (150 mL) were suction filtered and dried under reduced pressure to obtain 12 g of 4,4′-BiPy-T catalyst shown below (yield 93.7%). The thermal decomposition temperature of this 4,4′-BiPy-T catalyst was 300 ° C.
¹³ C NMR (CDCl ₃ ) δ120.75 (q, J = 320.0), 126.07, 126.33, 126.54, 143.72, 151.68
¹⁹ F NMR (CD ₃ COCD ₃ ) δ98.34

Synthesis Example 8 (Synthesis of 3-methylpyridinium trifluoromethanesulfonate (hereinafter abbreviated as 3-Me-PyH-T))
In a 200 mL eggplant flask, 3.0 mL (30.8 mmol) of 3-methylpyridine was dissolved in 25 mL of methylene chloride, and 3.0 mL (33.9 mmol) of trifluoromethanesulfonic acid was added dropwise little by little while cooling with ice. Crystals precipitated from diethyl ether (150 mL) were suction filtered and dried under reduced pressure to obtain 7.2 g of 3-Me-PyH-T catalyst (yield 96.7%).
¹ H NMR (CDCl ₃ ) δ 7.95 (dd, 1H, J = 6.1, 1.7), 8.33 (d, 1H, J = 8.0), 8.69 (s, 1H),
8.72 (d, 1H, J = 6.1)
¹³ C NMR (CDCl ₃ ) δ 18.30, 122.72 (q, J = 319.0), 127.04, 138.77, 139.00, 140.97, 147.37
¹⁹ F NMR (CDCl ₃ ) δ-78.64
mp 72.6-73.8 ℃

Synthesis Example 9 (Synthesis of 3-chloropyridinium trifluoromethanesulfonate (hereinafter abbreviated as 3-Cl-PyH-T))
In a 200 mL eggplant flask, 3.0 mL (26.8 mmol) of 3-chloropyridine was dissolved in 25 mL of methylene chloride, and 3.0 mL (33.9 mmol) of trifluoromethanesulfonic acid was added dropwise little by little while cooling with ice. Crystals precipitated from diethyl ether (150 mL) were suction filtered and dried under reduced pressure to obtain 7.3 g of 3-Cl-PyH-T catalyst (yield 96.0%).
¹ H NMR (CDCl ₃ ) δ8.11 (dd, 1H, J = 5.8,2.7), 8.54 (m, 1H), 8.65 (m, 2H)
¹³ C NMR (CDCl ₃ ) δ120.08 (q, J = 318.8), 128.43 (dJ = 4.4), 135.60, 140.66 (d, J = 6.0),
141.11, 146.33 (d, J = 7.4)
¹⁹ F NMR (CDCl ₃ ) δ-78.67
mp 103.0-105.2 ℃

Synthesis Example 10 (Synthesis of 3-phenylpyridinium trifluoromethanesulfonate (hereinafter abbreviated as 3-Ph-PyH-T))
In a 200 mL eggplant flask, 3.0 mL (20.9 mmol) of 3-phenylpyridine was dissolved in 25 mL of methylene chloride, and 1.7 mL (19.2 mmol) of trifluoromethanesulfonic acid was added dropwise little by little while cooling with ice. Crystals precipitated from diethyl ether (150 mL) were suction filtered and dried under reduced pressure to obtain 4.8 g of 3-Ph-PyH-T catalyst (yield 82.8%).
¹ H NMR (CDCl ₃ ) δ 7.58 (m, 3H), 7.66 (m, 2H), 8.10 (m, 1H,), 8.66 (m, 1H), 8.92 (m, 1H),
9.08 (t, 1H, J = 1.4)
¹³ C NMR (CDCl ₃ ) δ120.29 (q, J = 319.0), 127.26, 127.48, 129.96, 130.70, 132.81,
139.59, 139.94, 141.29, 143.89
¹⁹ F NMR (CDCl ₃ ) δ-78.39
mp63.5-64.0 ℃

Synthesis Example 11 (Synthesis of 4-phenylpyridinium trifluoromethanesulfonate (hereinafter abbreviated as 4-Ph-PyH-T))
In a 200 mL eggplant flask, 3.0 g (19.3 mmol) of 4-phenylpyridine was dissolved in 25 mL of methylene chloride, and 2.0 mL (22.6 mmol) of trifluoromethanesulfonic acid was added dropwise little by little while cooling with ice. Crystals precipitated from diethyl ether (150 mL) were suction filtered and dried under reduced pressure to obtain 5.7 g of 4-Ph-PyH-T catalyst (yield 96.9%).
¹ H NMR (CDCl ₃ ) δ7.63 (m, 3H), 8.82 (m, 2H), 8.21 (d, 2H, J = 4.7), 8.89 (d, 2H, J = 4.7)
¹³ C NMR (CDCl ₃ ) δ120.29 (q, J = 319.0), 124.38, 127.83, 129.94, 132.36, 134.03,
141.64, 158.47
¹⁹ F NMR (CDCl ₃ ) δ-78.41
mp 106.5-108.3 ℃

Synthesis Example 12 (Synthesis of 2,6-dimethylpyridinium trifluoromethanesulfonate (hereinafter abbreviated as 2,6-diMe-PyH-T))
In a 200 mL eggplant flask, 3.3 mL (28.0 mmol) of 2,6-lutidine was dissolved in 25 mL of methylene chloride, and 2.5 mL (28.3 mmol) of trifluoromethanesulfonic acid was added dropwise little by little while stirring on ice. Crystals precipitated from diethyl ether (150 mL) were suction filtered and dried under reduced pressure to obtain 6.0 g of 2,6-diMe-PyH-T catalyst (yield 84.0%).
¹ H NMR (CDCl ₃ ) δ 2.88 (s, 6H), 7.53 (d, 2H, J = 7.8), 8.20 (t, 1H, J = 7.8)
¹³ C NMR (CDCl ₃ ) δ19.49, 122.80 (q, J = 319.4), 124.94, 127.20, 145.99, 153.84
¹⁹ F NMR (CDCl ₃ ) δ-78.43
mp 68.2-71.0 ℃

[Production Example 1-1] Production of lactic acid oligomer using TPP-T catalyst (no solvent)
A 90 wt% L-lactic acid aqueous solution 5 g (L-lactic acid net amount 4.5 g) and TPP-T catalyst 104 mg (catalyst concentration 0.5 mol%) were placed in a 50 mL round bottom flask (reaction flask), and a Kugelrohr distillation apparatus. And heated at 4 kPa and 130 ° C. for 12 hours for direct dehydration polycondensation. In the meantime, water and lactic acid were distilled from the cooling glass bulb. After completion of the reaction, the mass of the lactic acid oligomer remaining in the reaction flask was 3.3 g (oligomer yield 92%), and the degree of polymerization was 16.5. The results are shown in Table 1.

[Production Examples 1-2 to 1-4] Production of lactic acid oligomer using TPP-T catalyst (no solvent)
The procedure was the same as in Production Example 1-1 except that the pressure and reaction time were as shown in Table 1. The results are shown in Table 1. In Production Example 1-2, the amount of distillate was slightly higher, and the yield of lactic acid oligomer was reduced. The distillate was mainly lactic acid (60-70%) and dimer (20-30%) and also contained a small amount of lactide (<10%).

[Production Example 1-5] Production of lactic acid oligomer using PyH-T catalyst (no solvent)
Production example except that PyH-T catalyst (catalyst concentration 0.5 mol%) was used instead of TPP-T catalyst and reacted at 130 ° C. and 6.7 kPa for 6 hours and then reacted at 150 ° C. and 6.7 kPa for 3 hours. The same operation as in 1-1 was performed. The results are shown in Table 1.

[Example 1-1] Production of lactide using TPP-T catalyst After completion of the reaction of Production Example 1-2, the glass bulb for cooling was replaced, the pressure was reduced to 0.013 kPa, and the reaction flask was heated at 140 ° C for 63 hours in the reaction flask. The lactic acid oligomer of was depolymerized and cyclized by heating, and 1.35 g of lactide was distilled into a cooling glass bulb. The yield based on the lactic acid oligomer was 74% (the yield based on the amount of L-lactic acid used in Production Example 1-2 was 37%). The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more.

  The lactide residue remaining in the flask was 0.47 g (26% with respect to the lactic acid oligomer), which was measured by NMR and found to be polylactic acid having an average degree of polymerization of 270 or more. The results are shown in Table 2.

[Example 1-2] Production of lactide using TPP-T catalyst After completion of the reaction in Production Example 1-3, the glass bulb for cooling was replaced, and the same operation as in Example 1-1 was performed. The results are shown in Table 2. The lactide residue was polylactic acid having an average degree of polymerization of 300 or more in an amount of 61% based on the lactic acid oligomer.

[Example 1-3] Production of lactide using TPP-T catalyst After completion of the reaction in Production Example 1-1, the glass bulb for cooling was replaced, and the same operation as in Example 1-1 was performed. The results are shown in Table 2. The lactide residue was polylactic acid having 83% of the lactic acid oligomer and an average degree of polymerization of 870 or more.

[Example 1-4] Production of lactide using TPP-T catalyst In a toluene solvent, a 90 wt% L-lactic acid aqueous solution was used as a raw material, and a TPP-T catalyst (0.5 mol%) was used. Atmospheric pressure atmosphere, toluene reflux Under the conditions, direct dehydration polycondensation was performed for 18 hours to obtain a lactic acid oligomer having an average degree of polymerization of 25.3. After removing toluene from the reaction mixture, the reaction was carried out under the same conditions as in Example 1-1. The results are shown in Table 2. The lactide residue was polylactic acid having an average polymerization degree of 874 and 80% with respect to the lactic acid oligomer.

[Example 1-5] Production of lactide using TPP-T catalyst Same as Example 1-4, except that a lactic acid oligomer having an average polymerization degree of 9.0 was prepared and the reaction time for depolymerization / cyclization was 19 hours. The operation was performed. The results are shown in Table 2.

[Example 1-6] Production of lactide using TPP-T catalyst Same as Example 1-4, except that a lactic acid oligomer having an average degree of polymerization of 22.0 was prepared and the reaction time for depolymerization / cyclization was 19 hours. The operation was performed. The results are shown in Table 2.

[Example 1-7] Production of lactide using TPP-T catalyst The same operation as in Example 1-4 was performed except that a lactic acid oligomer having an average polymerization degree of 115 was prepared and the reaction time for depolymerization and cyclization was 19 hours. Went. The results are shown in Table 2.

[Example 2-1] Production of lactide using PyH-T catalyst (average degree of polymerization of lactic acid oligomer = 9)
Using a 90 wt% L-lactic acid aqueous solution as a raw material in a xylene solvent, direct dehydration polycondensation was carried out for 24 hours in a non-catalytic manner under atmospheric pressure and xylene reflux conditions to obtain a lactic acid oligomer having an average polymerization degree of 9. After removing xylene from the reaction mixture, 1.0 mol% of PyH-T catalyst is added based on the lactic acid oligomer, and depolymerization and cyclization of the lactic acid oligomer is carried out using a Kugelrohr apparatus at 0.4 kPa and 180 ° C. for 20 hours. The lactide was obtained. The yield of lactide based on the lactic acid oligomer was 55%. The results are shown in Table 3.

[Example 2-2] Production of lactide using PyH-T catalyst (average degree of polymerization of lactic acid oligomer = 50)
In direct dehydration polycondensation of L-lactic acid, toluene was used as a solvent, and a TPP-T catalyst (0.5 mol% with respect to L-lactic acid) was used as a catalyst to obtain a lactic acid oligomer having an average polymerization degree of 50. The same operation as in Example 2-1 was performed except that it was used for depolymerization and cyclization (PyH-T catalyst was also used in the depolymerization and cyclization of lactic acid oligomer). Lactide was obtained at a yield of 33% based on the lactic acid oligomer. The results are shown in Table 3.

[Example 2-3] Production of lactide using PyH-T catalyst (average degree of polymerization of lactic acid oligomer = 70)
In the direct dehydration polycondensation of L-lactic acid, toluene is used as a solvent, a TPP-T catalyst (0.5 mol% with respect to L-lactic acid) is used as a catalyst, the reaction time of direct dehydration polycondensation is 30 hours, and the average A lactic acid oligomer having a polymerization degree of 70 was obtained, and the same operation as in Example 2-1 was performed except that this was used for depolymerization and cyclization (PyH-T catalyst was also used in the depolymerization and cyclization of the lactic acid oligomer). did). Lactide was obtained at a yield of 26% based on the lactic acid oligomer. The results are shown in Table 3.

[Example 2-4] Production of lactide using PyH-T catalyst (polymerization degree of lactic acid oligomer = 200)
In direct dehydration polycondensation of L-lactic acid, toluene is used as a solvent, a TPP-T catalyst (0.5 mol% with respect to L-lactic acid) is used as a catalyst, the reaction time of direct dehydration polycondensation is 72 hours, and polymerization is performed. The same procedure as in Example 2-1 was performed except that a polylactic acid having a degree of 200 was obtained and used for depolymerization and cyclization (PyH-T catalyst was also used in the depolymerization and cyclization of polylactic acid. ). Lactide was obtained with a yield of 18% based on polylactic acid. The results are shown in Table 3.

[Example 3-1] Production of lactide using PyH-T catalyst (depolymerization / cyclization reaction temperature = 180 ° C)
After carrying out dehydration polycondensation directly under xylene reflux conditions, 5.0 g of 90 wt% L-lactic acid aqueous solution, 1 mol% of PyH-T catalyst with respect to L-lactic acid, and 25 mL of xylene are placed in a 50 mL round bottom flask. Then, xylene was removed to obtain a lactic acid oligomer having an average degree of polymerization of 10.6. This lactic acid oligomer was depolymerized and cyclized for 5 hours at 0.013 kPa and 180 ° C. using a Kugelrohr apparatus to obtain lactide in a yield of 50% with respect to the lactic acid oligomer. The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more. The results are shown in Table 4.

[Example 3-2] Production of lactide using PyH-T catalyst (depolymerization / cyclization reaction temperature = 160 ° C)
The same procedure as in Example 3-1 was performed except that the temperature for depolymerization / cyclization was 160 ° C., and lactide was obtained at a yield of 46% with respect to the lactic acid oligomer. The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more. The results are shown in Table 4.

[Example 3-3] Production of lactide using PyH-T catalyst (depolymerization / cyclization reaction temperature = 140 ° C)
The same procedure as in Example 3-1 was performed except that the temperature for depolymerization / cyclization was 140 ° C., and lactide was obtained with a yield of 30% based on the lactic acid oligomer. The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more. The results are shown in Table 4.

[Example 4-1] Production of lactide using PyH-T catalyst (comparison of catalytic activity under the same reaction conditions)
Using a 90 wt% L-lactic acid aqueous solution as a raw material in a xylene solvent, direct dehydration polycondensation was carried out for 24 hours in a non-catalytic manner under atmospheric pressure and xylene reflux conditions to obtain a lactic acid oligomer having an average polymerization degree of 9. After removing xylene from the reaction mixture, 1.0 mol% of PyH-T catalyst is added based on the lactic acid oligomer, and depolymerization and cyclization of the lactic acid oligomer is performed at 0.4 kPa and 180 ° C. for 3 hours using a Kugelrohr apparatus. The lactide was obtained. The yield of lactide based on the lactic acid oligomer was 42%. The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more. The results are shown in Table 5. In addition, when the NMR measurement of the lactide residue was performed, it was a lactic acid oligomer with an average polymerization degree of 90.

[Example 4-2] Production of lactide using 5,5'-diMe-2,2'-BiPy-T catalyst (comparison of catalytic activity under the same reaction conditions))
Example except that 1.0 mol% of 5,5′-diMe-2,2′-BiPy-T catalyst based on lactic acid oligomer was used instead of PyH-T catalyst as a catalyst for depolymerization / cyclization reaction The same operation as in 4-1 was performed to obtain lactide. The yield of lactide based on the lactic acid oligomer was 23%. The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more. The results are shown in Table 5. In addition, when the NMR measurement of the lactide residue was performed, it was a lactic acid oligomer with an average polymerization degree of 20.

[Example 4-3] Production of lactide using 4,4'-BiPy-T catalyst (comparison of catalytic activity under the same reaction conditions)
The same operation as in Example 4-1 was conducted except that 1.0 mol% of 4,4′-BiPy-T catalyst based on lactic acid oligomer was used instead of the PyH-T catalyst as a catalyst for the depolymerization / cyclization reaction. To obtain lactide. The yield of lactide based on the lactic acid oligomer was 20%. The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more. The results are shown in Table 5. In addition, when the NMR measurement of the lactide residue was performed, it was a lactic acid oligomer with an average degree of polymerization of 25.

[Example 4-4] Production of lactide using TPP-S catalyst (comparison of catalytic activity under the same reaction conditions)
The same procedure as in Example 4-1 was performed except that 1.0 mol% of the TPP-S catalyst based on the lactic acid oligomer was used instead of the PyH-T catalyst as a catalyst for the depolymerization / cyclization reaction, and lactide was obtained. Obtained. The yield of lactide based on the lactic acid oligomer was 18%. The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more. The results are shown in Table 5. In addition, when the NMR measurement of the lactide residue was performed, it was a lactic acid oligomer having an average degree of polymerization of 27.

[Example 4-5] Production of lactide using PyH-S catalyst (comparison of catalytic activity under the same reaction conditions)
The same procedure as in Example 4-1 was performed except that a 1.0 mol% PyH-S catalyst based on the lactic acid oligomer was used instead of the PyH-T catalyst as a catalyst for the depolymerization / cyclization reaction. Obtained. The yield of lactide based on the lactic acid oligomer was 25%. The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more. The results are shown in Table 5. In addition, when the NMR measurement of the lactide residue was performed, it was a lactic acid oligomer with an average degree of polymerization of 83.

[Example 4-6] Production of lactide using Me-Imid-T catalyst (comparison of catalytic activity under the same reaction conditions)
As the catalyst for the depolymerization / cyclization reaction, the same procedure as in Example 4-1 was performed except that 1.0 mol% of Me-Imid-T catalyst based on the lactic acid oligomer was used instead of the PyH-T catalyst. Lactide was obtained. The yield of lactide based on the lactic acid oligomer was 31%. The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more. The results are shown in Table 5. In addition, when the NMR measurement of the lactide residue was performed, it was a lactic acid oligomer with an average degree of polymerization of 60.

[Example 4-7] Production of lactide using 3-Me-PyH-T catalyst (comparison of catalytic activity under the same reaction conditions)
The same operation as in Example 4-1 was performed except that 1.0 mol% of 3-Me-PyH-T catalyst based on lactic acid oligomer was used instead of the PyH-T catalyst as a catalyst for the depolymerization / cyclization reaction. The lactide was obtained. The yield of lactide based on the lactic acid oligomer was 28%. The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more. The results are shown in Table 5. In addition, when the NMR measurement of the lactide residue was performed, it was a lactic acid oligomer with an average degree of polymerization of 83.

[Example 4-8] Production of lactide using 3-Cl-PyH-T catalyst (comparison of catalytic activity under the same reaction conditions)
The same operation as in Example 4-1 was performed except that 1.0 mol% of 3-Cl-PyH-T catalyst based on lactic acid oligomer was used instead of the PyH-T catalyst as a catalyst for the depolymerization / cyclization reaction. The lactide was obtained. The yield of lactide based on the lactic acid oligomer was 39%. The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more. The results are shown in Table 5. In addition, when the NMR measurement of the lactide residue was performed, it was a lactic acid oligomer with an average polymerization degree of 90.

[Example 4-9] Production of lactide using 3-Ph-PyH-T catalyst (comparison of catalytic activity under the same reaction conditions)
The same operation as in Example 4-1 was performed except that 1.0 mol% 3-Ph-PyH-T catalyst based on lactic acid oligomer was used instead of the PyH-T catalyst as a catalyst for the depolymerization / cyclization reaction. The lactide was obtained. The yield of lactide based on the lactic acid oligomer was 37%. The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more. The results are shown in Table 5. In addition, when the NMR measurement of the lactide residue was performed, it was a lactic acid oligomer with an average degree of polymerization of 44.

[Example 4-10] Production of lactide using 4-Ph-PyH-T catalyst (comparison of catalytic activity under the same reaction conditions)
The same operation as in Example 4-1 was performed except that 1.0 mol% of 4-Ph-PyH-T catalyst based on lactic acid oligomer was used instead of the PyH-T catalyst as a catalyst for the depolymerization / cyclization reaction. The lactide was obtained. The yield of lactide based on the lactic acid oligomer was 38%. The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more. The results are shown in Table 5. In addition, when the NMR measurement of the lactide residue was performed, it was a lactic acid oligomer with an average degree of polymerization of 42.

[Example 4-11] Production of lactide using 2,6-diMe-PyH-T catalyst (comparison of catalytic activity under the same reaction conditions)
As in Example 4-1, except that 1.0 mol% of 2,6-diMe-PyH-T catalyst based on lactic acid oligomer was used as the catalyst for the depolymerization / cyclization reaction instead of the PyH-T catalyst. The operation was performed to obtain lactide. The yield of lactide based on the lactic acid oligomer was 41%. The meso form ratio of this lactide was 1% or less, and the LL-lactide selectivity was 99% or more. The results are shown in Table 5. In addition, when the NMR measurement of the lactide residue was performed, it was a lactic acid oligomer with an average degree of polymerization of 65.

[Comparative Example 4-1] Production of lactide without catalyst (comparison of catalytic activity under the same reaction conditions)
Lactide was obtained in the same manner as in Example 4-1, except that the catalyst for depolymerization / cyclization reaction was not used. The yield of lactide based on the lactic acid oligomer was 12%. The results are shown in Table 5. In addition, when the NMR measurement of the lactide residue was performed, it was a lactic acid oligomer with an average degree of polymerization of 22.

[Comparative Example 4-2] Production of lactide using tin (II) chloride catalyst (comparison of catalytic activity under the same reaction conditions)
As a catalyst for the depolymerization / cyclization reaction, a 1.0 mol% tin (II) chloride catalyst (SnCl ₂ ) based on the lactic acid oligomer is used instead of the PyH-T catalyst, and the time for the depolymerization / cyclization reaction is increased. The operation was performed in the same manner as in Example 4-1 except for changing to 1 hour, to obtain lactide. The yield of lactide based on the lactic acid oligomer was 92.2%. The meso form ratio of this lactide was 3.0%. The results are shown in Table 5. In addition, when the NMR measurement of the lactide residue was performed, it was a lactic acid oligomer with an average degree of polymerization of 58.

[Comparative Example 4-3] Production of lactide using tin (II) octylate catalyst (comparison of catalytic activity under the same reaction conditions)
As a catalyst for the depolymerization / cyclization reaction, 1.0 mol% of tin (II) octylate catalyst (Sn (Oct) ₂ ) based on the lactic acid oligomer is used instead of the PyH-T catalyst, and the depolymerization / cyclization is performed. The operation was carried out in the same manner as in Example 4-1 except that the reaction time was changed to 1 hour to obtain lactide. The yield of lactide based on the lactic acid oligomer was 73.6%. The meso form ratio of this lactide was 3.2%. The results are shown in Table 5. In addition, when the NMR measurement of the lactide residue was performed, it was a lactic acid oligomer with an average degree of polymerization of 50.

[Example 5] Continuous lactide synthesis First time: 44 g of 90 wt% L-lactic acid aqueous solution and PyH-T (1.0 g) were placed in a 100 mL flask and reacted at 150 ° C. and 3.3 kPa for 6 hours to average polymerization. A lactic acid oligomer having a degree of 6 (32 g) was obtained. When the obtained lactic acid oligomer was depolymerized and cyclized at 160 ° C. and a pressure of 0.066 to 0.13 kPa, lactide (8.0 g) was distilled. An NMR measurement of the residue from which lactide was separated revealed that it was a lactic acid oligomer (23 g) having an average degree of polymerization of 20.

  Second time: 60 wt% L-lactic acid aqueous solution (18.0 g) was added to lactic acid oligomer (23 g) having a polymerization degree of 20 and the pressure was reduced to 3.3 kPa at 135 ° C. for 15 hours under a nitrogen atmosphere. The mixture was reacted at 150 ° C. for 3 hours to obtain a lactic acid oligomer (31 g) having an average polymerization degree of 6. When the obtained lactic acid oligomer was depolymerized and cyclized under the same conditions as described above, lactide (7.2 g) was distilled. The residue from which lactide was separated was a lactic acid oligomer (23 g) having an average degree of polymerization of 45.

  Third time: A 60 wt% L-lactic acid aqueous solution (17.3 g) was added to the lactic acid oligomer having a polymerization degree of 45 (23 g), and a reaction similar to the above was carried out. Obtained. When the obtained lactic acid oligomer was depolymerized and cyclized under the same conditions as described above, lactide (7.1 g) was distilled. The residue from which lactide was separated was a lactic acid oligomer (23 g) having an average degree of polymerization of 30.

  Fourth time: A 60 wt% L-lactic acid aqueous solution (17.3 g) was added to the lactic acid oligomer (23 g) having a polymerization degree of 30 to perform the same reaction as above to obtain a lactic acid oligomer (31 g) having an average polymerization degree of 7. It was. When the obtained lactic acid oligomer was depolymerized and cyclized under the same conditions as described above, lactide (7.6 g) was distilled. The residue from which lactide was separated was a lactic acid oligomer (22 g) having an average polymerization degree of 33.

  5th time: A 60 wt% L-lactic acid aqueous solution (18.2 g) was added to the lactic acid oligomer (22 g) having a polymerization degree of 33, and the same reaction as described above was carried out to obtain a lactic acid oligomer (31 g) having an average polymerization degree of 7 Obtained. When the obtained lactic acid oligomer was depolymerized and cyclized under the same conditions as described above, lactide (7.7 g) was distilled. The residue from which lactide was separated was a lactic acid oligomer (22 g) having an average polymerization degree of 32.

  The results are shown in FIG. In FIG. 2, the lactide yield (OLAbase) based on the total amount of oligomers and the lactide yield (LAbase) based on the L-lactic acid added in the second and subsequent times are shown. In addition, the meso form ratio of the obtained lactide was 1% or less, and the LL-lactide selectivity was 99% or more.

  The production method of the present invention can efficiently produce high-purity optically active lactide, and is extremely effective for improving the productivity of polylactic acid production by the lactide method.

LA base: Lactide yield based on the total amount of L-lactic acid introduced in each round OLA base: Lactide yield based on the total amount of oligomer

Claims (8)

A method for producing lactide, characterized in that in the presence of at least one organic onium salt selected from the following organic onium salts , lactide is produced by depolymerization and cyclization by heating a lactic acid oligomer in a reduced-pressure atmosphere. .

( However, the anion component of TPP-T may be a C 2-6 perfluoroalkylsulfonic acid ion.)

(However, an anion component is a C1-C6 perfluoroalkylsulfonic acid ion or a hydrogen sulfate ion.)

(However, an anion component is a C1-C6 perfluoroalkylsulfonic acid ion or a hydrogen sulfate ion.)

(However, an anion component is a C1-C6 perfluoroalkylsulfonic acid ion or a hydrogen sulfate ion.) The method for producing lactide according to claim 1, wherein the average degree of polymerization of the lactic acid oligomer is 3 or more and 100 or less. The method for producing lactide according to claim 1 or 2 , wherein depolymerization and cyclization are carried out by heating to a temperature of 140 to 200 ° C. Lactic acid oligomer has an optical purity of 99% e.e. e. The method for producing lactide according to any one of claims 1 to 3 , wherein the optically active lactic acid is polycondensed. Lactic acid oligomer, lactic acid, one by heating in the presence of an organic onium salt according to any one of claims 1-4 is obtained by polycondensation of lactide even without less of claim 1, wherein Production method. The residue or polylactic acid lactide from depolymerization, cyclization reaction was separated lactic acid oligomer, in addition to lactic acid and / or water and heated in the presence of one organic onium salt even without less of claim 1, wherein The method for producing lactide according to any one of claims 1 to 3 , wherein the regenerated product is used as a lactic acid oligomer as a raw material for depolymerization and cyclization. Lactide has a meso-lactide content of 1% or less and an optically active lactide selectivity defined by the following formula (A) of 99% or more, and lactic acid has the same optical activity as the lactic acid component constituting the optically active lactide With an optical purity of 99% e.e. e. The manufacturing method according to claim 6 , which is the above.
Optically active lactide selectivity [%] = (mass of LL-lactide or DD-lactide) / (mass of LL-lactide + mass of meso lactide + mass of DD-lactide) × 100 (A) The production method according to any one of claims 1 to 3, wherein the lactide has a meso-lactide content of 1% or less and an optically active lactide selectivity defined by the following formula (A) of 99% or more.
Optically active lactide selectivity [%] = (mass of LL-lactide or DD-lactide) / (mass of LL-lactide + mass of meso lactide + mass of DD-lactide) × 100 (A)

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