JP5885159B2 - Method for producing cyclic urethane - Google Patents

Description

  The present invention relates to a method for producing cyclic urethane.

In recent years, attention has been focused on converting carbon dioxide (CO ₂ ) into useful compounds and using them as chemical products and fuels. Since carbon dioxide can be recovered from exhaust gas from a factory or the like, if carbon dioxide is used, carbon resources can be recycled. It is also known that carbon dioxide has low toxicity and nonflammability and can be used in place of highly toxic organic reagents such as isocyanate and phosgene. Therefore, when high-efficiency carbon dioxide fixation is possible, an organic synthesis process with a low environmental load is realized.

As a reaction for fixing carbon dioxide, it is widely used for synthesizing urethane, urea and the like useful as synthetic intermediates for pharmaceuticals, agricultural chemicals and the like.
Among these, as a method for producing urethane, a method for producing chain urethane by reacting amine and carbon dioxide, a method for producing cyclic urethane by reacting amino alcohol and carbon dioxide, and the like are known.

Non-Patent Document 1 discloses a method for producing a chain urethane by reacting an amine and carbon dioxide in the presence of an alkyl halide such as benzyl chloride, cesium carbonate, and tetrabutylammonium iodide.
Non-Patent Document 2 discloses a method for producing a chain urethane by reacting an amine and carbon dioxide under high pressure conditions in the presence of a catalyst such as an alkali metal carbonate, fluoride or acetate.
Non-Patent Document 3 includes organic phosphorus compounds such as tri-n-butylphosphine, bases such as 1,8-diazabicyclo [5.4.0] undec-7-ene, and dialkyls such as dibenzylazodicarboxylate. A method for producing a cyclic urethane by reacting amino alcohol and carbon dioxide in the presence of azodicarboxylate is disclosed.
Non-Patent Documents 4 and 5 disclose methods for producing cyclic urethane by reacting amino alcohol and carbon dioxide in the presence of tosyl chloride and an electrically generated base.
Non-Patent Document 6 discloses a method for producing cyclic urethane by reacting amino alcohol and carbon dioxide under high pressure conditions in the presence of an organic antimony compound such as triphenylantimony oxide.
Non-Patent Document 7 discloses a method for producing cyclic urethane by reacting amino alcohol and carbon dioxide in methanol under high pressure conditions.
Non-Patent Document 8 discloses that cyclic reaction is caused by reacting amino alcohol and carbon dioxide under high pressure conditions in the presence of an ionic fluid such as butyl-3-methylimidazolium bromide and an alkali metal salt such as potassium carbonate. A method for producing urethane is disclosed.

J. et al. Org. Chem. 66 (2007) 1035 Green Chem. 10 (2008) 111 Org. Lett. 17 (2004) 2885 J. et al. Org. Chem. 65 (2000) 4759 Tetrahedron Lett. 43 (2002) 5863 Ind. Eng. Chem. Prod. Res. Dev. 24 (1985) 239 Green Chem. 5 (2003) 340 Int. J. et al. Mol. Sci. 7 (2006) 438

  As described above, when an organochlorine compound, an organometallic compound, or the like is used as a catalyst, the reaction needs to be performed under a high pressure condition, for example, and there is a problem related to a disposal method of by-products derived from the catalyst. May occur. For example, the adverse effect on the environment of an organic chlorine compound has become a big problem, and it is required to advance a chemical reaction that does not use or does not occur a compound harmful to the environment under mild conditions.

  An object of the present invention is to provide a method for efficiently producing a cyclic urethane by setting the pressure and the like to mild conditions.

The present invention reacts an amino alcohol with carbon dioxide in the presence of a compound represented by the following general formula (11) (hereinafter referred to as “specific compound”) in a reaction system including a polar organic solvent. comprising a reaction step, a method for producing a cyclic urethane is a dipole moment of the organic solvent is 3.60 or more, the pressure of the reaction system you being a 0.5～30Atm.
(M ⁺ ) _m X ^m− (11)
[Wherein M ⁺ represents Li ⁺ , Na ⁺ , K ⁺ , Rb ⁺ , Cs ⁺ , or a general formula R ¹¹ ₄ N ⁺ , wherein each R ¹¹ is independently of each other a number of carbon atoms of 1 X ^m− is CO ₃ ²⁻ , HCO ₃ ⁻ , HO ⁻ , HCOO ⁻ , or CH ₃ COO ⁻ , and m is 1 Or 2. ]

（式中、ｎは１〜３の整数であり、Ｒ、Ｒ^１、Ｒ^２及びＲ^３は、互いに独立して、水素原子、炭素原子数１〜２０の置換若しくは非置換の炭化水素基；カルボニル基；アルコキシメチル基、アリールオキシメチル基、アルキルアミノメチル基、アリールアミノメチル基、アリールチオメチル基若しくはアルキルチオメチル基又はこれらの誘導体基である。Ｒ^２は、窒素原子から２つ目の炭素原子に結合する１つのＲと結合して２価の有機基を形成していてもよい。）

（式中、ｓは１〜１０の整数であり、Ｒ^９は、互いに独立して、水素原子、炭素原子数１〜１０の置換若しくは非置換の炭化水素基、カルボニル基、アルコキシ基、アリールオキシ基、アルキルアミノ基、アリールアミノ基、アリールチオ基、又は、アルキルチオ基である。） The reaction scheme according to the present invention is shown below, and the amino alcohol represented by the following general formula (1A) or (1B) is a cyclic urethane represented by the following general formula (3A) or (3B), respectively. Converted.

(In the formula, n is an integer of 1 to 3, and R, R ¹ , R ² and R ³ are each independently a hydrogen atom, a substituted or unsubstituted hydrocarbon group having 1 to 20 carbon atoms; An alkoxymethyl group, an aryloxymethyl group, an alkylaminomethyl group, an arylaminomethyl group, an arylthiomethyl group, an alkylthiomethyl group, or a derivative group thereof, R ² is the second carbon from the nitrogen atom; (It may be bonded to one R bonded to an atom to form a divalent organic group.)

(In the formula, s is an integer of 1 to 10, and R ⁹ is independently of each other a hydrogen atom, a substituted or unsubstituted hydrocarbon group having 1 to 10 carbon atoms, a carbonyl group, an alkoxy group, aryloxy. Group, alkylamino group, arylamino group, arylthio group, or alkylthio group.)

According to the present invention, cyclic urethane can be produced efficiently by reacting a specific compound as a catalyst and reacting amino alcohol with carbon dioxide under mild conditions of 0.5 to 30 atm. In addition, since the specific compound is hardly deactivated after the reaction, the reaction system can be used repeatedly. Therefore, the method of the present invention is simple and economical.

The present invention provides a step of reacting amino alcohol with carbon dioxide in the presence of a specific compound in a reaction system including a polar organic solvent having a dipole moment of 3.60 or more (hereinafter referred to as “reaction step”). It is a manufacturing method of cyclic urethane provided.
In this invention, the process of collect | recovering cyclic urethane, the process of refine | purifying cyclic urethane, etc. can be further provided after a reaction process.

（一般式（１Ａ）において、ｎは１〜３の整数であり、Ｒ、Ｒ^１、Ｒ^２及びＲ^３は、互いに独立して、水素原子、炭素原子数１〜２０の置換若しくは非置換の炭化水素基；カルボニル基；アルコキシメチル基、アリールオキシメチル基、アルキルアミノメチル基、アリールアミノメチル基、アリールチオメチル基若しくはアルキルチオメチル基又はこれらの誘導体基である。Ｒ^２は、窒素原子から２つ目の炭素原子に結合する１つのＲと結合して２価の有機基を形成していてもよい。一般式（１Ｂ）において、ｓは１〜１０の整数であり、Ｒ^９は、互いに独立して、水素原子、炭素原子数１〜１０の置換若しくは非置換の炭化水素基、カルボニル基、アルコキシ基、アリールオキシ基、アルキルアミノ基、アリールアミノ基、アリールチオ基、又は、アルキルチオ基である。） The amino alcohol used in the reaction step is represented by the following general formulas (1A) and (1B). In the present invention, amino alcohol having an optical isomer can be used as a reaction raw material.

(In General Formula (1A), n is an integer of 1 to 3, and R, R ¹ , R ² and R ³ are each independently a hydrogen atom, a substituted or unsubstituted group having 1 to 20 carbon atoms. A hydrocarbon group, a carbonyl group, an alkoxymethyl group, an aryloxymethyl group, an alkylaminomethyl group, an arylaminomethyl group, an arylthiomethyl group, an alkylthiomethyl group, or a derivative group thereof, R ² represents a nitrogen atom to 2 It may combine with one R bonded to the first carbon atom to form a divalent organic group, In the general formula (1B), s is an integer of 1 to 10, and R ⁹ is Independently, a hydrogen atom, a substituted or unsubstituted hydrocarbon group having 1 to 10 carbon atoms, a carbonyl group, an alkoxy group, an aryloxy group, an alkylamino group, an arylamino group, an arylthio group. Group, or an alkylthio group.)

In the general formula (1A), when R, R ¹ , R ² and R ³ are substituted hydrocarbon groups having 1 to 20 carbon atoms, hydrogen in the hydrocarbon group having 1 to 20 carbon atoms It means that one or more of the atoms are organic groups substituted with other atoms or functional groups. Examples of other atoms include a halogen atom, an oxygen atom, a nitrogen atom, a sulfur atom, a silicon atom, and a phosphorus atom. Examples of the functional group include an alkoxy group, a carbonyl group, a carboxyl group, a mercapto group, a sulfonyl group, and an amino group.

（式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ｒ^５、Ｒ^６及びＲ^７は、互いに独立して、水素原子、炭素原子数１〜２０の置換若しくは非置換の炭化水素基；カルボニル基；アルコキシメチル基、アリールオキシメチル基、アルキルアミノメチル基、アリールアミノメチル基、アリールチオメチル基若しくはアルキルチオメチル基又はこれらの誘導体基である。Ｒ^２及びＲ^４は、互いに結合して、２価の有機基を形成していてもよい。） In the present invention, preferable compounds as the amino alcohol represented by the general formula (1A) are the compounds of n = 1 and the compound of n = 2 in the general formula (1A). It is represented by Formula (1A-1) and (1A-2).

(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ are each independently a hydrogen atom, a substituted or unsubstituted hydrocarbon group having 1 to 20 carbon atoms; An alkoxymethyl group, an aryloxymethyl group, an alkylaminomethyl group, an arylaminomethyl group, an arylthiomethyl group, an alkylthiomethyl group, or a derivative group thereof R ² and R ⁴ are bonded to each other; (It may form a divalent organic group.)

  Examples of the amino alcohol represented by the general formula (1A) include 2-aminoethanol, 2-aminopropanol, 3-aminopropanol, 2-aminobutanol, 1-amino-2-propanol, and 3-amino-1-propanol. 2-amino-3-methyl-1-butanol, 2-amino-1-butanol, 2-amino-3-methyl-1-pentanol, 2-amino-4-methyl-1-pentanol, 2-amino -3,3-dimethyl-1-butanol, 2-aminocyclohexanol, 2-amino-3-phenyl-1-propanol, 2-phenyl-2-aminoethanol, 1-phenyl-2-aminoethanol, 2,2 -Diphenyl-2-aminoethanol, 1,2-diphenyl-2-aminoethanol, 1,1-diphenyl-2-aminoe Nord, 2-aminophenol, N- methylethanolamine, and the like.

On the other hand, in the general formula (1B), when R ⁹ is a substituted hydrocarbon group having 1 to 10 carbon atoms, one or two hydrogen atoms in the hydrocarbon group having 1 to 10 carbon atoms The above means an organic group substituted by another atom or functional group. Examples of other atoms include a halogen atom, an oxygen atom, a nitrogen atom, a sulfur atom, a silicon atom, and a phosphorus atom. Examples of the functional group include an alkoxy group, a carbonyl group, a carboxyl group, a mercapto group, a sulfonyl group, and an amino group.
Moreover, s is preferably 1-8.

  Examples of the amino alcohol represented by the general formula (1B) include 2-pyrrolidinemethanol, 2-piperidinemethanol, azepan-2-yl methanol, azocan-2-yl methanol, azonan-2-yl methanol, and azecan-2- yl methanol, azacyclinedecan-2-yl methanol, etc. are mentioned.

In the reaction step, a specific compound represented by the following general formula (11), that is, carbonate, hydrogen carbonate, hydroxide, formate or acetate is used as a catalyst.
(M ⁺ ) _m X ^m− (11)
[Wherein M ⁺ represents Li ⁺ , Na ⁺ , K ⁺ , Rb ⁺ , Cs ⁺ , or a general formula R ¹¹ ₄ N ⁺ , wherein each R ¹¹ is independently of each other a number of carbon atoms of 1 X ^m− is CO ₃ ²⁻ , HCO ₃ ⁻ , HO ⁻ , HCOO ⁻ , or CH ₃ COO ⁻ , and m is 1 Or 2. ]

R ¹¹ ₄ N ⁺ in the general formula (11) is a tetraalkylammonium ion containing a hydrocarbon group having 1 to 20 carbon atoms, and includes a tetramethylammonium ion, a tetraethylammonium ion, a tetrabutylammonium ion, and a tetraoctylammonium ion. Ion, trimethylethylammonium ion, benzyltrimethylammonium ion, methyltrioctylammonium ion, ethyltrioctylammonium ion, methyltridecylammonium ion, methyltridodecylammonium ion and the like.

Hereinafter, specific compounds will be exemplified.
Examples of the carbonate include lithium carbonate, sodium carbonate, potassium carbonate, rubidium carbonate, cesium carbonate and the like.
Examples of the hydrogen carbonate include sodium hydrogen carbonate, potassium hydrogen carbonate, cesium hydrogen carbonate and the like.
Examples of the hydroxide include cesium hydroxide.
Examples of the formate include cesium formate.
Moreover, as said acetate, cesium acetate etc. are mentioned.
The said specific compound may be used only 1 type and may be used in combination of 2 or more type.

  As the specific compound, carbonates and bicarbonates are preferable. Moreover, a potassium compound and a cesium compound are more preferable, and a cesium compound is particularly preferable.

  Since the usage-amount of the said specific compound is more practical as a catalytic reaction, Preferably it is 0.0001-0.5 mol with respect to 1 mol of said amino alcohol, More preferably, it is 0.001-3 mol, Furthermore Preferably it is 0.01-0.1 mol.

In the above reaction step, a polar solvent is used as the reaction solvent. The polar solvent is an organic solvent having a dipole moment of 3.60 or more, more preferably 4.00 or more.
Examples of the polar solvent include dimethyl sulfoxide, dimethylacetamide, dimethylformamide, 1,3-dimethyl-2-imidazolidinone, and N-methylpyrrolidone. Of these, dimethyl sulfoxide is particularly preferable because cyclic urethane is obtained in high yield.

In the present invention, when the specific compound is a carbonate, a chelating agent composed of a polar organic molecule capable of complexing with the M ⁺ ion in the general formula (11) may be added to the reaction system. preferable. Thereby, the production | generation efficiency of cyclic urethane can be improved.

As the chelating agent, cyclic polyethers, cyclic polythioethers, cyclic azaethers and the like are preferable. The chelating agent may be used alone or in combination of two or more.
Examples of the cyclic polyether include 12-crown-4-ether (1,4,7,10-tetraoxacyclododecane) and 15-crown-5-ether (1,4,7,10,13-pentaoxacyclo). Pentadecane), 18-crown-6-ether (1,4,7,10,13,16-hexaoxacyclooctadecane), 21-crown-7-ether (1,4,7,10,13,16,19) -Heptaoxacycloheneicosadecane), 24-crown-8-ether (1,4,7,10,13,16,19,22-octaoxacyclotetraeicosadecane) and the like.
The cyclic polythioether is a compound in which part or all of the oxygen atoms of the cyclic polyether is replaced with a sulfur atom, and includes 12-thiacrown-4-ether, 15-thiacrown-5-ether, 18-thia Examples include crown-6-ether, 1-thia-15-crown-5-ether, 1-thia-18-crown-6-ether, 1,4,8,11-tetrathiacyclotetradecane.
The cyclic azaether is a compound in which some or all of the oxygen atoms of the cyclic polyether are replaced with nitrogen atoms, and includes 1-aza-15-crown-5-ether, 1-aza-18-crown-6 Ether, 4,10-diaza-12-crown-4-ether, 4,10-diaza-15-crown-5-ether, 4,13-diaza-18-crown-6-ether, N, N′-dibenzyl Examples include -4,13-diaza-18-crown-6-ether.

  Since the usage-amount of the said chelating agent is more practical as a catalytic reaction, Preferably it is 0.0001-0.5 mol with respect to 1 mol of said specific compounds, More preferably, it is 0.001-0.3. Mol, more preferably 0.01 to 0.1 mol.

  In the above reaction step, in order to facilitate the reaction between amino alcohol and carbon dioxide, the reaction system can be subjected to deoxygenation treatment in advance, for example, by freeze degassing.

In the reaction step, amino alcohol and carbon dioxide easily react in the presence of the specific compound . Production of cyclic urethane can proceed under both normal pressure and high pressure conditions, but in the present invention, a high yield is obtained under mild conditions of 0.5 to 30 atm, more preferably 1 to 10 atm. be able to.
Moreover, although reaction temperature is suitably selected by the kind of amino alcohol, Preferably it is 60 to 200 degreeC, More preferably, it is 100 to 160 degreeC.

In the said reaction process, when the compound shown by the said general formula (1A-1) is used as amino alcohol, the cyclic urethane represented by the following general formula (3A-1) can be obtained.

In addition, when the amino alcohol is a compound in which R ² and R ⁴ are bonded to each other to form a divalent organic group in the general formula (1A-1), the structure of the resulting cyclic urethane Are, for example, compounds represented by the following general formulas (3A-1a) to (3A-1c).

Moreover, when the compound shown by the said general formula (1A-2) is used as amino alcohol, the cyclic urethane represented by the following general formula (3A-2) can be obtained.

  The reaction liquid obtained by the above reaction step usually contains the produced cyclic urethane, unreacted amino alcohol, specific compound and water. In the case of isolating the cyclic urethane, the reaction solution may be subjected to a conventionally known recovery process or purification process including filtration, distillation and the like. Moreover, since the specific compound contained in the reaction solution can be reused, the same reaction system can be used when continuously producing cyclic urethane.

  According to the production method of the present invention, the yield of the cyclic urethane represented by the general formula (3) is preferably 60% or more, more preferably 65% or more, and further preferably 80% or more in a preferred embodiment. can do. The “yield” is a value calculated based on the molar amount of amino alcohol used as a reaction raw material.

The present inventors conducted an experiment using L-valinol and carbon dioxide (C ¹⁸ O ₂ ) labeled with ¹⁸ O as an oxygen atom as a reaction raw material, and the present invention has the reaction mechanism shown in the following scheme. The action of the specific compound was estimated.
That is, using 1 atm of C ¹⁸ O ₂ , reaction with L-valinol was conducted under a certain reaction condition [L-valinol (1.0 mmol), C ¹⁸ O ₂ (1 atm) atmosphere, Cs ₂ CO ₃ (0. 1 mmol), DMSO-d6 (1 mL), 150 ° C., 24 h], the product cyclic urethane was obtained in an isolated yield of 86%. As a result of examining the isotope introduction rate of this cyclic urethane, there were three types: one with ¹⁸ O introduced, one with ¹⁸ O introduced, and one without ¹⁸ O introduced at all. It could be identified by a gas chromatography mass spectrometry (GC-MS) apparatus that it was produced at a ratio of approximately 0.01: 1: 0.1. Moreover, the measured value of the infrared absorption spectrum (IR) of the product cyclic urethane showed a tendency closer to the calculated value of the molecular structure of the product shown on the right side of the following scheme in which one ¹⁸ O was introduced. From these experimental results, after passing through the carbamic acid intermediate shown in the center of the following scheme, the hydroxyl group undergoes nucleophilic attack on the carbonyl carbon of carbamic acid in the molecule, so that the ¹⁸ OH group is removed as H ₂ ¹⁸ O. The separation mechanism is presumed to be the most preferred reaction process.

  Hereinafter, the present invention will be specifically described with reference to examples. The present invention is not limited to these examples.

Example 1
In a Schlenk container dried under reduced pressure and substituted with nitrogen gas, a stir bar, cesium carbonate (8.1 mg, 0.025 mmol), deuterated dimethyl sulfoxide (1.0 mL) and L-valinol (0.11 mL, 1.0 mmol) were added. Housed and freeze degassed. Next, 0.10 MPa of carbon dioxide gas was added to the Schlenk container and reacted at 150 ° C. for 12 hours with stirring to obtain (S) -4-isopropyl-2-oxazolidinone. After completion of the reaction, 1,1,1,2-tetrachloroethane was added as a standard substance, and ¹ H NMR measurement was performed using a heavy dimethyl sulfoxide solvent to obtain a yield of 98%.

(S) -4-Isopropyl-2-oxazolidinone:
¹ H NMR (CDCl ₃ , 400 MHz): δ 6.42 (br.s, 1H), 4.44 (t, J = 8.3 Hz, 1H), 4.10 (dd, J = 8.3, 6.3 Hz, 1H), 3.61 (dd , J = 14.6 Hz, 6.8 Hz, 1H), 1.68-1.80 (m, 1H), 0.97 (d, J = 6.8 Hz, 3H), 0.90 (d, J = 6.8 Hz, 3H); [α] _D ²⁰ +8.2 (c 1.0, CHCl ₃ ).

Example 2
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 1 except that rubidium carbonate (5.8 mg, 0.025 mmol) was used instead of cesium carbonate. The yield was 51%.

Example 3
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 1 except that potassium carbonate (3.5 mg, 0.025 mmol) was used instead of cesium carbonate. The yield was 47%.

Example 4
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 1 except that sodium carbonate (2.6 mg, 0.025 mmol) was used instead of cesium carbonate. The yield was 36%.

Example 5
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 1 except that lithium carbonate (1.8 mg, 0.025 mmol) was used instead of cesium carbonate. The yield was 22%.

Comparative Example 1
A reaction similar to Example 1 was attempted without using cesium carbonate, but (S) -4-isopropyl-2-oxazolidinone could not be obtained.

Comparative Example 2
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 1 except that calcium carbonate (25 mg, 0.025 mmol) was used instead of cesium carbonate. The yield was 2%.

Comparative Example 3
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 1 except that barium carbonate (4.9 mg, 0.025 mmol) was used instead of cesium carbonate. The yield was 3%.

Comparative Example 4
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 1 except that strontium carbonate (3.7 mg, 0.025 mmol) was used instead of cesium carbonate. The yield was 4%.

Example 6
In a Schlenk container dried under reduced pressure and replaced with nitrogen gas, a stir bar, cesium carbonate (33 mg, 0.1 mmol), deuterated dimethyl sulfoxide (1.0 mL) and L-valinol (0.11 mL, 1.0 mmol) were placed. Then, freeze deaeration was performed. Next, 0.10 MPa of carbon dioxide gas was added to the Schlenk container and reacted at 150 ° C. for 12 hours with stirring to obtain (S) -4-isopropyl-2-oxazolidinone. The yield was 99%.

Example 7
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 6 except that cesium hydrogen carbonate (19 mg, 0.1 mmol) was used instead of cesium carbonate. The yield was 98%.

Example 8
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 6 except that cesium hydroxide (15 mg, 0.1 mmol) was used instead of cesium carbonate. The yield was 51%.

Example 9
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 6 except that cesium acetate (19 mg, 0.1 mmol) was used instead of cesium carbonate. The yield was 47%.

Example 10
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 6 except that cesium formate (18 mg, 0.1 mmol) was used instead of cesium carbonate. The yield was 16%.

Comparative Example 5
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 6 except that cesium chloride (17 mg, 0.1 mmol) was used instead of cesium carbonate. The yield was 4%.

Comparative Example 6
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 6 except that cesium bromide (21 mg, 0.1 mmol) was used instead of cesium carbonate. The yield was 3%.

Comparative Example 7
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 6 except that cesium iodide (26 mg, 0.1 mmol) was used instead of cesium carbonate. The yield was 3%.

Comparative Example 8
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 6 except that cesium methanesulfonate (23 mg, 0.1 mmol) was used instead of cesium carbonate. The yield was 3%.

Comparative Example 9
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 6 except that cesium sulfate (36 mg, 0.1 mmol) was used instead of cesium carbonate. The yield was 2%.

Example 11
(S) -4-Isopropyl-2-oxazolidinone was changed in the same manner as in Example 6 except that 1,3-dimethyl-2-imidazolidinone was used in place of dimethyl sulfoxide and the reaction time was 24 hours. Obtained. The yield was 63%.

Example 12
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 6 except that N-methylpyrrolidone was used in place of dimethyl sulfoxide and the reaction time was 24 hours. The yield was 40%.

Example 13
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 6 except that dimethylformamide was used in place of dimethyl sulfoxide and the reaction time was 24 hours. The yield was 21%.

Example 14
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 6 except that dimethylacetamide was used in place of dimethylsulfoxide and the reaction time was 24 hours. The yield was 20%.

Example 15
In the same manner as in Example 6 except that 1,3-dimethyl-2-imidazolidinone was used instead of dimethyl sulfoxide, potassium carbonate was used instead of cesium carbonate, and the reaction time was 24 hours, ( S) -4-Isopropyl-2-oxazolidinone was obtained. The yield was 42%.

Comparative Example 10
A similar reaction to Example 6 was attempted except that dioxane was used instead of dimethyl sulfoxide and the reaction time was 24 hours, but (S) -4-isopropyl-2-oxazolidinone could not be obtained. .

Comparative Example 11
A similar reaction to Example 6 was attempted except that toluene was used instead of dimethyl sulfoxide and the reaction time was 24 hours, but (S) -4-isopropyl-2-oxazolidinone could not be obtained. .

Comparative Example 12
A reaction similar to that of Example 6 was attempted without using dimethyl sulfoxide and a reaction time of 24 hours. However, (S) -4-isopropyl-2-oxazolidinone could not be obtained.

  In Examples 16 to 19 below, cyclic urethane was obtained by changing the amount of cesium carbonate used and setting the reaction time to 12 hours or 24 hours. The results combined with Example 1 are shown in Table 1.

Example 16
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 1 except that the amount of cesium carbonate used was 16 mg (0.05 mmol). The yield was 99% (see Table 1).

Example 17
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 1 except that the amount of cesium carbonate used was changed to 33 mg (0.1 mmol). The yield was 99% (see Table 1).

Example 18
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 1 except that the amount of cesium carbonate used was changed to 3.3 mg (0.01 mmol). The yield was 63% (see Table 1).

Example 19
In a Schlenk container dried under reduced pressure and substituted with nitrogen gas, a stir bar, cesium carbonate (3.3 mg, 0.01 mmol), deuterated dimethyl sulfoxide (1.0 mL) and L-valinol (0.11 mL, 1.0 mmol) were added. Housed and freeze degassed. Next, 1 atm of carbon dioxide gas was added to the Schlenk container, and the mixture was reacted at 150 ° C. for 24 hours with stirring to obtain (S) -4-isopropyl-2-oxazolidinone. The yield was 99% (see Table 1).

Examples 20 to 35 below are examples in which cyclic urethane was produced by changing the type of amino alcohol, the amount of cesium carbonate used, and the like. The results are shown in Tables 2 and 3 together with the results of Example 19.

Example 20
The reaction was carried out in the same manner as in Example 19 except that D-valinol (0.11 mL, 1.0 mmol) was used instead of L-valinol to obtain (R) -4-isopropyl-2-oxazolidinone. . The yield was 99% (see Table 2).

(R) -4-Isopropyl-2-oxazolidinone:
¹ H NMR (CDCl ₃ , 400 MHz): δ 6.20 (br.s, 1H), 4.45 (t, J = 8.8 Hz, 1H), 4.11 (dd, J = 8.8, 6.8 Hz, 1H), 3.61 (dd , J = 14.7 Hz, 6.8 Hz, 1H), 1.68-1.79 (m, 1H), 0.97 (d, J = 6.8 Hz, 3H), 0.91 (d, J = 6.8 Hz, 3H); [α] _D ²⁰ -8.4 (c 1.0, CHCl ₃ ).

Example 21
The reaction was conducted in the same manner as in Example 19 except that 2-amino-3,3-dimethyl-1-butanol (0.13 mL, 1.0 mmol) was used instead of L-valinol, and (R)- 4-tert-butyl-2-oxazolidinone was obtained. The yield was 99% (see Table 2).

(R) -4-tertiarybutyl-2-oxazolidinone:
¹ H NMR (CDCl ₃ , 400 MHz): δ 6.58 (br.s, 1H), 4.37 (t, J = 8.8 Hz, 1H), 4.19 (dd, J = 8.8 Hz, 6.8 Hz, 1H), 3.60 ( m, 1H), 0.91 (s, 9H); [α] _D ²⁰ +7.1 (c 1.0, CHCl ₃ ).

Example 22
The reaction was conducted in the same manner as in Example 19 except that D-leucinol (0.13 mL, 1.0 mmol) was used instead of L-valinol and the amount of cesium carbonate used was 8.3 mg (0.025 mmol). And (R) -4-isobutyl-2-oxazolidinone was obtained. The yield was 98% (see Table 2).

(R) -4-isobutyl-2-oxazolidinone:
¹ H NMR (CDCl ₃ , 400 MHz): δ 5.95 (br. S, 1H), 4.50 (t, J = 7.8 Hz, 1H), 3.90-4.01 (m, 2H), 1.52-1.71 (m, 2H) , 1.34-1.45 (m, 1H), 0.94 (t, J = 5.9 Hz, 6H); [α] _D ²⁰ -10.9 (c 1.0, CHCl ₃ ).

Example 23
The reaction was conducted in the same manner as in Example 19 except that L-alaninol (0.68 mL, 1.0 mmol) was used instead of L-valinol and the amount of cesium carbonate used was 8.3 mg (0.025 mmol). And (R) -4-methyl-2-oxazolidinone was obtained. The yield was 99% (see Table 2).

(R) -4-Methyl-2-oxazolidinone:
¹ H NMR (CDCl ₃ , 400 MHz): δ 5.30 (br.s, 1H), 4.51 (t, J = 7.8 Hz, 1H), 3.99-4.09 (m, 1H), 3.96 (dd, J = 7.8 Hz , 6.3 Hz, 1H), 1.31 (d, J = 5.8 Hz, 3H); [α] _D ²⁰ -5.9 (c 1.0, CHCl ₃ ).

Example 24
The reaction was conducted in the same manner as in Example 19 except that D-alaninol (0.079 mL, 1.0 mmol) was used instead of L-valinol and the amount of cesium carbonate used was 8.3 mg (0.025 mmol). And (S) -4-methyl-2-oxazolidinone was obtained. The yield was 92% (see Table 2).

(S) -4-Methyl-2-oxazolidinone:
¹ H NMR (CDCl ₃ , 400 MHz): δ 5.45 (br.s, 1H), 4.52 (t, J = 7.8 Hz, 1H), 3.98-4.09 (m, 1H), 3.95 (dd, J = 7.5 Hz , 6.5 Hz, 1H), 1.30 (d, J = 5.9 Hz, 3H); [α] _D ²⁰ +5.8 (c 1.0, CHCl ₃ ).

Example 25
The same as Example 19 except that 2-amino-1-butanol (0.094 mL, 1.0 mmol) was used instead of L-valinol and the amount of cesium carbonate used was 16.6 mg (0.05 mmol). The reaction was performed to obtain (R) -4-ethyl-2-oxazolidinone. The yield was 93% (see Table 2).

(R) -4-Ethyl-2-oxazolidinone:
¹ H NMR (CDCl ₃ , 400 MHz): δ 5.78 (br. S, 1H), 4.49 (t, J = 8.8 Hz, 1H), 4.04, (dd, J = 8.8 Hz, 5.8 Hz, 1H), 3.76 -3.86 (m, 1H), 1.55-1.69 (m, 2H), 0.95 (t, J = 7.3 Hz, 3H); [α] _D ²⁰ -5.1 (c 1.0, CHCl ₃ ).

Example 26
The reaction was carried out in the same manner as in Example 19 except that 2-amino-3-methyl-1-pentanol (0.13 mL, 1.0 mmol) was used instead of L-valinol, and (S) -1 -Methylisopropyl-2-oxazolidinone was obtained. The yield was 98% (see Table 2).

(S) -1-Methylisopropyl-2-oxazolidinone:
¹ H NMR (CDCl ₃ , 400 MHz): δ 6.37 (br.s, 1H), 4.43 (t, J = 8.8 Hz, 1H), 4.11, (dd, J = 8.8 Hz, 6.8 Hz, 1H), 3.70 (m, 1H), 1.45-1.62 (m, 2H), 1.09-1.21 (m, 1H), 0.93 (t, J = 7.3 Hz, 3H), 0.88 (d, J = 6.8 Hz, 3H); (α ] _D ²⁰ +1.6 (c 1.0, CHCl ₃ ).

Example 27
The reaction was conducted in the same manner as in Example 19 except that L-phenylalaninol (151 mg, 1.0 mmol) was used instead of L-valinol and the amount of cesium carbonate used was 33.2 mg (0.1 mmol). And (R) -4-benzyl-2-oxazolidinone was obtained. The yield was 90% (see Table 2).

(R) -4-Benzyl-2-oxazolidinone:
¹ H NMR (CDCl ₃ , 400 MHz): δ 7.15-7.55 (m, 5H), 5.33 (br.s, 1H), 4.46 (t, J = 7.8 Hz, 1H), 4.15 (dd, J = 8.8 Hz , 5.9 Hz, 1H), 4.04-4.13 (m, 1H), 2.88 (dd, J = 13.4 Hz, 6.0 Hz, 1H), 2.84 (dd, J = 13.4 Hz, 8.1 Hz, 1H); [α] _D ²⁰ +60.1 (c 1.0, CHCl ₃ ).

Example 28
The reaction was conducted in the same manner as in Example 19 except that D-phenylalaninol (151 mg, 1.0 mmol) was used instead of L-valinol and the amount of cesium carbonate used was 33.2 mg (0.1 mmol). And (S) -4-benzyl-2-oxazolidinone was obtained. The yield was 95% (see Table 3).

(S) -4-Benzyl-2-oxazolidinone:
¹ H NMR (CDCl ₃ , 400 MHz): δ 7.10-7.50 (m, 5H), 5.27 (br.s, 1H), 4.47 (t, J = 7.8 Hz, 1H), 4.16 (dd, J = 8.3 Hz , 5.8 Hz, 1H), 4.04-4.14 (m, 1H), 2.89 (dd, J = 13.5 Hz, 5.9 Hz, 1H), 2.85 (dd, J = 13.5 Hz, 8.2 Hz, 1H); [α] _D ²⁰ -59.9 (c 1.0, CHCl ₃ ).

Example 29
1-amino-2-propanol (0.079 mL, 1.0 mmol) was used instead of L-valinol, the amount of cesium carbonate used was 33.2 mg (0.1 mmol), and the reaction time was 72 hours. Reacted in the same manner as in Example 19 to obtain (S) -5-methyl-2-oxazolidinone. The yield was 94% (see Table 3).

Example 30
Instead of L-valinol, 2-aminoethanol (0.060 mL, 1.0 mmol) was used, the amount of cesium carbonate used was 16.6 mg (0.05 mmol), and the pressure of carbon dioxide gas was 9 atm. The reaction was carried out in the same manner as in Example 19 to obtain 2-oxazolidone. The yield was 52% (see Table 3).

Example 31
Instead of L-valinol, 3-amino-1-propanol (0.076 mL, 1.0 mmol) was used, the amount of cesium carbonate used was 16.6 mg (0.05 mmol), and the pressure of carbon dioxide gas was 9 atm. Except for this, the reaction was carried out in the same manner as in Example 19 to obtain 2-oxazinanone. The yield was 28% (see Table 3).

Example 32
Instead of L-valinol, trans-2-aminocyclohexanol (115 mg, 1.0 mmol) was used and the amount of cesium carbonate used was changed to 33.2 mg (0.1 mmol). Reaction was performed to obtain trans-cyclohexano-2-oxazolidinone. The yield was 96% (see Table 3).

Example 33
Instead of L-valinol, N-methylethanolamine (0.080 mL, 1.0 mmol) was used, the amount of cesium carbonate used was 33.2 mg (0.1 mmol), and the reaction time was 120 hours. The reaction was conducted in the same manner as in Example 19 to obtain 3-methyl-2-oxazolidone. The yield was 85% (see Table 3).

Example 34
N-methylethanolamine (0.080 mL, 1.0 mmol) was used instead of L-valinol, the amount of cesium carbonate used was 33.2 mg (0.1 mmol), and the pressure of carbon dioxide gas was 9 atm. Reacted in the same manner as in Example 19 to obtain 3-methyl-2-oxazolidone. The yield was 99% (see Table 3).

Example 35
Instead of L-valinol, L-prolinol (0.097 mL, 1.0 mmol) was used, the amount of cesium carbonate used was 33.2 mg (0.1 mmol), and the pressure of carbon dioxide gas was 9 atm. The reaction was conducted in the same manner as in Example 19 to obtain tetrahydro-2H-1,3-oxazin-2-one. The yield was 96% (see Table 3).

Examples 36 to 42 below are examples in which (S) -4-isopropyl-2-oxazolidinone was produced by adding a chelating agent to the reaction system. The results are shown in Table 4.

Example 36
In a Schlenk container dried under reduced pressure and substituted with nitrogen gas, a stir bar, potassium carbonate (3.5 mg, 0.025 mmol), 18-crown-6-ether (6.6 mg, 0.025 mmol), deuterated dimethyl sulfoxide (1 0.0 mL) and L-valinol (0.11 mL, 1.0 mmol) were housed and freeze degassed. Next, 0.10 MPa of carbon dioxide gas was added to the Schlenk container and reacted at 150 ° C. for 12 hours with stirring to obtain (S) -4-isopropyl-2-oxazolidinone. The yield was 98% (see Table 4).

Example 37
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 36 except that the amount of 18-crown-6-ether used was 13.2 mg (0.05 mmol). The yield was 76% (see Table 4).

Example 38
Example 36 was repeated except that sodium carbonate was used instead of potassium carbonate, and 5.5 mg (0.025 mmol) of 15-crown-5-ether was used instead of 18-crown-6-ether. , (S) -4-isopropyl-2-oxazolidinone was obtained. The yield was 46% (see Table 4).

Example 39
Except that lithium carbonate was used instead of potassium carbonate, and 4.4 mg (0.025 mmol) of 12-crown-4-ether was used instead of 18-crown-6-ether, the same as Example 36 was performed. , (S) -4-isopropyl-2-oxazolidinone was obtained. The yield was 23% (see Table 4).

Example 40
In a Schlenk container dried under reduced pressure and substituted with nitrogen gas, a stir bar, cesium carbonate (14.0 mg, 0.1 mmol), 18-crown-6-ether (26.4 mg, 0.1 mmol), 1,3-dimethyl 2-Imidazolidinone (1.0 mL) and L-valinol (0.11 mL, 1.0 mmol) were accommodated and freeze degassed. Next, 0.10 MPa of carbon dioxide gas was added to the Schlenk container and allowed to react at 150 ° C. for 24 hours with stirring to obtain (S) -4-isopropyl-2-oxazolidinone. The yield was 80% (see Table 4).

Example 41
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 40 except that 31 mg (0.1 mmol) of 21-crown-7-ether was used instead of 18-crown-6-ether. Obtained. The yield was 78% (see Table 4).

Example 42
(S) -4-isopropyl-2-oxazolidinone was obtained in the same manner as in Example 40 except that potassium carbonate was used instead of cesium carbonate. The yield was 65% (see Table 4).

The method for producing a cyclic urethane according to the present invention is an environment-friendly production method in which carbon dioxide, which is a global warming gas, is used as a raw material and is immobilized on a product, and is useful. It can also be used to form amino alcohol protecting groups and asymmetric auxiliary groups for asymmetric synthesis.
The produced cyclic urethane is suitable as a raw material for producing pharmaceuticals, methanol and the like.

Claims (4)

In a reaction system including a polar organic solvent, in the method for producing a cyclic urethane compound comprising a step of reacting amino alcohol and carbon dioxide in the presence of a compound represented by the following general formula (11) :
The dipole moment of the organic solvent is 3.60 or more,
The method for producing a cyclic urethane compound, wherein the pressure of the reaction system is 0.5 to 30 atm .
(M ⁺ ) _m X ^m− (11)
[Wherein M ⁺ represents Li ⁺ , Na ⁺ , K ⁺ , Rb ⁺ , Cs ⁺ , or a general formula R ¹¹ ₄ N ⁺ , wherein each R ¹¹ is independently of each other a number of carbon atoms of 1 X ^m− is CO ₃ ²⁻ , HCO ₃ ⁻ , HO ⁻ , HCOO ⁻ , or CH ₃ COO ⁻ , and m is 1 Or 2. ] The cyclic urethane compound according to claim 1, wherein the polar solvent is at least one selected from dimethyl sulfoxide, dimethylacetamide, dimethylformamide, 1,3-dimethyl-2-imidazolidinone and N-methylpyrrolidone. Method. The method for producing a cyclic urethane compound according to claim 1 or 2 , wherein the compound represented by the general formula (11) is a cesium compound. The compound represented by the general formula (11) is a salt containing Li, Na, K, Rb or Cs, and a chelating agent for a metal element constituting the salt is added to the reaction system. The manufacturing method of the cyclic urethane compound as described in any one of 1-3 .