Method for producing glycolaldehyde dialkyl acetal

Abstract

The present invention provides a method for producing glycolaldehyde dialkyl acetal in high yield. This method for producing a glycolaldehyde dialkyl acetal comprises: a glycolaldehyde formation step in which paraformaldehyde is converted into glycolaldehyde in an ether solvent in the presence of an N-heterocyclic carbene catalyst; an acetalation step in which glycolaldehyde is treated with an alcoholic solution of hydrogen chloride to obtain a glycolaldehyde dialkyl acetal; the N-heterocyclic carbene catalyst is a compound represented by formula (I) or (II) (in the formula, R1, R2, R3, R4, R5, R6, R7, R8 and A-have the meanings described in the description and claims), and the glycolaldehyde formation step and the acetalation step are carried out in a single container. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to a method for producing dialkyl acetals of glycolaldehyde. Background Art

[0002] Glycolaldehyde is a dimerization product of formaldehyde. Glycolaldehyde can be used as a synthetic intermediate for useful compounds such as amino acids, sugars, ethylene glycol, and ethanol. However, glycolaldehyde has high reactivity and easily dimerizes. Therefore, glycolaldehyde is difficult to separate and store.

[0003] Dialkyl acetals of glycolaldehyde are obtained by acetalization of glycolaldehyde. Dialkyl acetals of glycolaldehyde have higher stability than glycolaldehyde. Therefore, dialkyl acetals of glycolaldehyde can be used as raw materials for producing useful compounds.

[0004] For example, Patent Document 1 describes a catalytic production method of a condensation product of formaldehyde, in which formaldehyde or a compound that generates formaldehyde is reacted using a catalyst produced from a triazole salt or a tetrazole salt in the presence of an auxiliary base.

[0005] Patent Document 2 describes a hydroformylation method of aqueous formaldehyde using a rhodium-tricyclic phosphine catalyst system, which is a method of reacting formaldehyde, carbon monoxide, and hydrogen in the presence of a rhodium composite catalyst under hydroformylation conditions to produce glycolaldehyde.

[0006] Prior Art Documents

[0007] Patent Documents

[0008] Patent Document 1: Japanese Patent Laid-Open No. 6-211723

[0009] Patent Document 2: Japanese Patent Laid-Open No. 1-272543 Summary of the Invention

[0010] Problems to be Solved by the Invention

[0011] Glycolaldehyde has high reactivity and easily dimerizes. Therefore, it is expected to use dialkyl acetals of glycolaldehyde with higher stability as raw materials for producing useful compounds. However, a method for producing dialkyl acetals of glycolaldehyde in high yield is unknown.

[0012] Therefore, an object of the present invention is to provide a method for producing dialkyl acetals of glycolaldehyde in high yield.

[0013] Means for Solving the Problems

[0014] The present inventors have conducted various studies on means for solving the above problems. The present inventors have found that by converting paraformaldehyde into glycolaldehyde using a specific N-heterocyclic carbene catalyst and then carrying out a reaction for acetalizing glycolaldehyde in a single vessel, the desired dialkyl acetal of glycolaldehyde can be obtained in a high yield. Based on the above findings, the present inventors have completed the present invention.

[0015] That is, the present invention includes the following aspects and embodiments.

[0016] (Embodiment 1) A method for producing a dialkyl acetal of glycolaldehyde, comprising: a glycolaldehyde formation step of converting paraformaldehyde into glycolaldehyde in an ether solvent in the presence of an N-heterocyclic carbene catalyst; an acetalization step of treating glycolaldehyde with an alcoholic solution of hydrogen chloride to obtain a dialkyl acetal of glycolaldehyde;

[0017] and carrying out the glycolaldehyde formation step and the acetalization step in a single vessel;

[0018] wherein the N-heterocyclic carbene catalyst is a compound represented by formula (I) or (II),

[0019]

[0020] In the formula, R 1 and R 4 are each independently an unsubstituted C3-C6 alkyl group or a C1-C6 alkyl group substituted with a C6-C 18 aryl group;

[0021] R 2 and R 5 are each independently an unsubstituted C3-C6 alkyl group or a C1-C6 alkyl group substituted with a C6-C 18 aryl group;

[0022] R 3 and R 6 are each independently H, an unsubstituted C1-C6 alkoxy group, an unsubstituted C3-C6 alkyl group or a C1-C6 alkyl group substituted with a C6-C 18 aryl group;

[0023] R 7 and R 8 are both H or together with the carbon atom to which they are bonded form a C6-C 18 aryl group;

[0024] A - is a halogen anion or a carbon dioxide radical anion.

[0025] (Embodiment 2) The method according to Embodiment 1, wherein the ether solvent is selected from cyclopentyl methyl ether (CPME), tert-butyl methyl ether (TBME), diethyl ether, 1,4-dioxane, tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), and anisole.

[0026] (Embodiment 3) The method according to Embodiment 1 or 2, which is carried out in the presence of the following N-heterocyclic carbene catalyst, wherein,

[0027] R 1 and R 4 are each independently an unsubstituted C3 to C6 alkyl group,

[0028] R 2 and R 5 are each independently an unsubstituted C3 to C6 alkyl group,

[0029] R 3 and R 6 and R 7 and R 8 are all H,

[0030] A - is a halogen anion or a carbon dioxide radical anion.

[0031] (Embodiment 4) The method according to any one of Embodiments 1 to 3, which is carried out in the presence of the following N-heterocyclic carbene catalyst, wherein,

[0032] R 1 and R 4 and R 2 and R 5 are all isopropyl groups,

[0033] R 3 and R 6 and R 7 and R 8 are all H,

[0034] A - is a chloride anion or a carbon dioxide radical anion.

[0035] (Embodiment 5) The method according to any one of Embodiments 1 to 4, wherein the ether solvent is cyclopentyl methyl ether (CPME), tert-butyl methyl ether (TBME), diethyl ether, or 1,4-dioxane;

[0036] The N-heterocyclic carbene catalyst is 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride, or 1,3-bis(2,6-diisopropylphenyl)imidazolium-2-carboxylate.

[0037] Advantages of the Invention

[0038] According to the present invention, a method for producing glycolaldehyde dialkyl acetal in a high yield can be provided. Detailed Description of Embodiments

[0039] Hereinafter, preferred embodiments of the present invention will be described in detail.

[0040] One aspect of the present invention relates to a method for producing glycolaldehyde dialkyl acetal. The method of this aspect includes a glycolaldehyde formation step and an acetalization step. Hereinafter, each step will be described in detail.

[0041] [1: Glycolaldehyde Formation Step]

[0042] This step includes converting paraformaldehyde into glycolaldehyde in an ether solvent in the presence of an N - heterocyclic carbene catalyst.

[0043] In this step, the N - heterocyclic carbene catalyst is a compound represented by formula (I) or (II).

[0044]

[0045] In formula (I) and (II), R 1 and R 4 are each independently an unsubstituted C3 - C6 alkyl group or a C1 - C6 alkyl group substituted with a C6 - C 18 aryl group;

[0046] R 2 and R 5 are each independently an unsubstituted C3 - C6 alkyl group or a C1 - C6 alkyl group substituted with a C6 - C 18 aryl group;

[0047] R 3 and R 6 are each independently H, an unsubstituted C1 - C6 alkoxy group, an unsubstituted C3 - C6 alkyl group or a C1 - C6 alkyl group substituted with a C6 - C 18 aryl group;

[0048] R 7 and R 8 are both H or together with the carbon atom to which they are bonded form a C6 - C 18 aryl group;

[0049] A - is a halogen anion or a carbon dioxide radical anion.

[0050] In formula (I) and (II), preferably R 1 and R 4 are each independently an unsubstituted C3 - C6 alkyl group,

[0051] R 2 and R 5 each independently represents an unsubstituted C3 - C6 alkyl group,

[0052] R 3 and R 6 and also R 7 and R 8 are all H,

[0053] A - is preferably a halogen anion or a carbon dioxide radical anion;

[0054] More preferably, R 1 and R 4 and also R 2 and R 5 each independently represents isopropyl, tert - butyl or sec - butyl,

[0055] R 3 and R 6 and also R 7 and R 8 are all H,

[0056] A - is a chlorine, bromine or iodine anion or a carbon dioxide radical anion;

[0057] Even more preferably, R 1 and R 4 and also R 2 and R 5 are all isopropyl,

[0058] R 3 and R 6 and also R 7 and R 8 are all H,

[0059] A - is a chlorine anion or a carbon dioxide radical anion.

[0060] In formula (I) and (II), when R 1 and R 4 and also R 2 and R 5 are the groups exemplified above, side reactions such as dimerization can be suppressed by steric bulk. Thus, glycolaldehyde can be obtained in high yield and / or high selectivity.

[0061] The N - heterocyclic carbene catalyst used in this step is 1,3 - bis(2,6 - diisopropylphenyl)imidazol - 2 - ylidene (i.e., in formula (I), R 1 and R 4 and also R 2and R 5 are both isopropyl groups, R 3 and R 6 and also R 7 and R 8 are both H), 1,3 - bis(2,6 - diisopropylphenyl)imidazolium chloride (that is, in formula (II), R 1 and R 4 and also R 2 and R 5 are both isopropyl groups, R 3 and R 6 and also R 7 and R 8 are both H, A - is a chloride anion) or 1,3 - bis(2,6 - diisopropylphenyl)imidazolium - 2 - carboxylate (that is, in formula (II), R 1 and R 4 and also R 2 and R 5 are both isopropyl groups, R 3 and R 6 and also R 7 and R 8 are both H, A - is a carbon dioxide radical anion). By carrying out this step using the above - exemplified N - heterocyclic carbene catalyst, glycolaldehyde can be obtained in particularly high yields and / or high selectivity.

[0062] When the N - heterocyclic carbene catalyst used in this step is a compound represented by formula (II), it is preferred to use this compound together with a base. The preferred base is selected from triethylamine, diisopropylethylamine, 1,8 - diazabicyclo[5.4.0]undec - 7 - ene (DBU), 1,5 - diazabicyclo[4.3.0]-5 - nonene (DBN), 7 - methyl - 1,5,7 - triazabicyclo[4.4.0]dec - 5 - ene (MTBD), lithium diisopropylamide (LDA), and phosphazene base, and more preferably DBU, DBN, MTBD, LDA, or phosphazene base. Alternatively, the base can also be a base in an immobilized form supported on a carrier such as a resin. As the base in an immobilized form, an immobilized base formed by binding the above - exemplified base to a carrier and an ion - exchange resin can be cited. By carrying out this step using the N - heterocyclic carbene catalyst represented by formula (II) together with the above - exemplified base, glycolaldehyde can be obtained in high yields.

[0063] Regarding the N - heterocyclic carbene catalyst used in this step, the molar amount thereof is in the range of 0.01 to 5 mol%, more preferably in the range of 0.05 to 2 mol%, and still more preferably in the range of 0.1 to 1 mol% relative to the molar amount of paraformaldehyde as the raw material. By carrying out this step using the N - heterocyclic carbene catalyst in the exemplified amount range above, glycolaldehyde can be obtained in high yield.

[0064] In this step, it is preferred that the ether solvent is selected from cyclopentyl methyl ether (CPME), tert - butyl methyl ether (TBME), diethyl ether, 1,4 - dioxane, tetrahydrofuran (THF), 2 - methyltetrahydrofuran (2 - MeTHF), and anisole, and more preferably is cyclopentyl methyl ether (CPME), tert - butyl methyl ether (TBME), diethyl ether, or 1,4 - dioxane. By carrying out this step using the exemplified ether solvent above, glycolaldehyde can be obtained in high yield. In addition, the exemplified ether solvents above are known to be inexpensive and industrially safe. Therefore, by carrying out this step using the exemplified ether solvent above, glycolaldehyde can be obtained inexpensively and / or industrially safely.

[0065] Regarding the reaction temperature and reaction time of this step, they can be appropriately set based on the boiling point of the ether solvent used. For the reaction temperature, a temperature above room temperature is preferred, more preferably 25°C or higher, and still more preferably 30°C or higher. In addition, for the reaction temperature, a temperature exceeding the boiling point of the ether solvent used is preferred, more preferably 100°C or lower, and still more preferably 90°C or lower. The reaction time is preferably 5 minutes or longer, more preferably 10 minutes or longer, and still more preferably 30 minutes or longer. In addition, the reaction time is preferably 200 minutes or shorter, more preferably 100 minutes or shorter, and still more preferably 60 minutes or shorter. By carrying out this step under the exemplified reaction conditions above, glycolaldehyde can be obtained in high yield.

[0066] [2: Acetalization step]

[0067] This step includes treating glycolaldehyde with an alcohol solution of hydrogen chloride to obtain a glycolaldehyde dialkyl acetal.

[0068] In this step, the alcohol solvent in the alcohol solution of hydrogen chloride is preferably selected from methanol, ethanol, benzyl alcohol, and phenol, and more preferably is methanol. By carrying out this step using the alcohol solution of hydrogen chloride containing the exemplified alcohol solvent above, a glycolaldehyde dialkyl acetal can be obtained in high yield.

[0069] Regarding the concentration of the alcohol solution of hydrogen chloride used in this step, the molar amount thereof is in the range of 0.01 to 1 M, preferably in the range of 0.05 to 0.1 M relative to the molar amount of paraformaldehyde as the raw material. By carrying out this step using the alcohol solution of hydrogen chloride in the exemplified concentration range above, a glycolaldehyde dialkyl acetal can be obtained in high yield.

[0070] In the method of this embodiment, the glycolaldehyde formation step and the acetalization step are carried out in a single container. Preferably, the glycolaldehyde formation step and the acetalization step are continuously carried out in a single container. For example, preferably, after the glycolaldehyde formation step is carried out, the reaction mixture containing glycolaldehyde is not purified, and the acetalization step is directly carried out in the same reaction vessel. Glycolaldehyde, which is the product of the glycolaldehyde formation step, has high reactivity and is prone to dimerization. Therefore, when the glycolaldehyde formation step and the acetalization step are carried out in different containers (i.e., sequentially), before the acetalization step is carried out, there may be undesirable side reactions such as dimerization of glycolaldehyde. Therefore, by carrying out the glycolaldehyde formation step and the acetalization step in a single container, undesirable side reactions can be substantially suppressed, and glycolaldehyde dialkyl acetal can be obtained in high yield.

[0071] As described in detail above, by the method of this embodiment, glycolaldehyde dialkyl acetal can be produced in high yield. It is expected that the glycolaldehyde dialkyl acetal obtained by the method of this embodiment can be used as a raw material for manufacturing useful compounds such as amino acids, sugars, ethylene glycol, and ethanol. Therefore, by the method of this embodiment, raw materials for these useful compounds can be provided.

[0072] Examples

[0073] Hereinafter, the present invention will be described in more detail using examples. However, the technical scope of the present invention is not limited to these examples.

[0074] Experiment 1

[0075]

[0076] In a reaction vessel, paraformaldehyde (0.5 mmol / HCHO) was reacted in cyclopentyl methyl ether (CPME) solvent (1 mL) at 80 °C for 30 minutes in the presence of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene catalyst (1 mol%) to be converted into glycolaldehyde (glycolaldehyde formation step). The reaction mixture containing glycolaldehyde was not purified, and was directly treated with a methanol solution of 0.05 M hydrogen chloride (0.6 mL) at 60 °C for 20 minutes in the same reaction vessel (acetalization step). The glycolaldehyde dialkyl acetal contained in the obtained crude reaction product was analyzed by 1 1H NMR and GC. Through this reaction, glycolaldehyde dialkyl acetal was obtained in a yield of 83%.

[0077] Experiment 2: Solvent optimization

[0078] In the steps of Experiment 1, glycolaldehyde dialkyl acetal was synthesized according to the same steps as in Experiment 1, except that the solvent was changed to the one shown below. The solvents used and the yields (%) of glycolaldehyde dialkyl acetal are shown in Table 1.

[0079] Table 1

[0080] Solvent Yield (%) tert-Butyl methyl ether (TBME) 69 Diethyl ether 53 1,4-Dioxane 58 Tetrahydrofuran (THF) 61 2-Methyltetrahydrofuran (2-MeTHF) 40

[0081] Solvent Yield (%) Toluene 32 Diisopropylethyl ether 14 Anisole <1 Dimethyl ether <1 Ethyl acetate 20 Trifluoroethanol <1 Dichloromethane 19 N,N-Diethylformamide <1 N-Methylpyrrolidone <1 Methanol <1 tert-Butanol 7 Water <1 N,N-Dimethylformamide <1 Dimethylacetamide <1 Acetonitrile 5

[0082] As shown in Table 1, by carrying out the glycolaldehyde formation step using an ether solvent, glycolaldehyde dialkyl acetal can be obtained in a high yield.

[0083] Experiment 3: Catalyst Optimization (1)

[0084] Except for changing the catalyst in the steps of Experiment 1, glycolaldehyde dialkyl acetal was synthesized according to the same steps as in Experiment 1. When using an N-heterocyclic carbene catalyst in which the side chain group bonded to the nitrogen atom of the imidazole ring of the catalyst used in Experiment 1 is an alkyl group, an N-heterocyclic carbene catalyst in which the imidazole ring is an imidazolidine ring, or an N-heterocyclic carbene catalyst in which the side chain group of the phenyl group bonded to the nitrogen atom of the imidazole ring is a methyl group or a diphenylmethyl group, the reaction hardly proceeds (yield less than 4%). In addition, when using a triphenyltriazolylidene catalyst (Japanese Patent Laid-Open No. 06-211723), the reaction also hardly proceeds (yield less than 1%).

[0085] [Experiment 4: Scale-up of the Reaction and Reduction of the Catalyst Amount]

[0086]

[0087] Except for changing the reaction conditions as shown in the above route in the steps of Experiment 1, glycolaldehyde dialkyl acetal was synthesized according to the same steps as in Experiment 1. The solvents used, reaction conditions, and yields (%) of glycolaldehyde dialkyl acetal are shown in Table 2. In the table, reaction condition (a) represents the condition of carrying out the glycolaldehyde formation step at 80 °C for 60 minutes, and reaction condition (b) represents the condition of carrying out the glycolaldehyde formation step at 100 °C for 30 minutes.

[0088] Table 2

[0089]

[0090] As shown in Table 2, even when the catalyst amount is reduced to 1 / 10 compared with Experiment 1, by increasing the reaction temperature or increasing the reaction time, glycolaldehyde dialkyl acetal can be obtained in a high yield.

[0091] Experiment 5: Catalyst Optimization (2)

[0092]

[0093] In the steps of Experiment 4, the catalyst was changed to the combination of the above-mentioned imidazolium salt and base, and the reaction conditions were changed as shown in the above route. Other than that, glycolaldehyde dialkyl acetal was synthesized according to the same steps as in Experiment 1. The bases and solvents used, as well as the yields (%) of glycolaldehyde dialkyl acetal, are shown in Table 3. In the table, DBU represents 1,8-diazabicyclo[5.4.0]undec-7-ene, DBN is 1,5-diazabicyclo[4.3.0]-5-nonene, MTBD is 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene, and LDA is lithium diisopropylamide.

[0094] Table 3

[0095] Base Solvent Yield (%) DBU 1,4-Dioxane 72 DBN 1,4-Dioxane 63 MTBD 1,4-Dioxane 71 LDA 1,4-Dioxane 70 DBU CPME 70 DBN CPME 62 MTBD CPME 60 LDA CPME 68

[0096] As shown in Table 3, by using the combination of imidazolium salt and base as the catalyst to carry out the glycolaldehyde formation process, glycolaldehyde dialkyl acetal can be obtained in a high yield.

[0097] Experiment 6: Catalyst Optimization (3)

[0098]

[0099] In the steps of Experiment 4, the catalyst was changed to the combination of the above-mentioned imidazolium salt and immobilized base (ion exchange resin), and the reaction conditions were changed as shown in the above scheme. Other than that, glycolaldehyde dialkyl acetal was synthesized according to the same steps as in Experiment 1. The bases used and the yields (%) of glycolaldehyde dialkyl acetal are shown in Table 4.

[0100] Table 4

[0101]

[0102] As shown in Table 4, even when using the combination of imidazolium salt and immobilized base as the catalyst to carry out the glycolaldehyde formation process, glycolaldehyde dialkyl acetal can be obtained in a high yield.

[0103] Experiment 7: Catalyst Optimization (4)

[0104]

[0105] In the steps of Experiment 4, the catalyst was changed to the above-mentioned 1,3-bis(2,6-diisopropylphenyl)imidazolium-2-carboxylate, and the reaction conditions were changed as shown in the above scheme. Except for this, glycolaldehyde dialkyl acetal was synthesized according to the same steps as in Experiment 1. The glycolaldehyde dialkyl acetal contained in the obtained crude reaction product was analyzed by GC. Through this reaction, glycolaldehyde dialkyl acetal was obtained in a yield of 73%.

[0106] It should be noted that the present invention is not limited to the above-mentioned embodiments and includes various modification examples. For example, the above embodiments are detailed descriptions of the present invention in an easy-to-understand manner and are not limited to having all the configurations described. In addition, for some configurations of each embodiment, addition, deletion, and / or replacement of other configurations can also be carried out.

Claims

1. A method for producing a dialkyl acetal of glycolaldehyde, comprising: a glycolaldehyde formation step of converting paraformaldehyde into glycolaldehyde in an ether solvent in the presence of an N - heterocyclic carbene catalyst; an acetalization step of treating glycolaldehyde with an alcoholic solution of hydrogen chloride to obtain a dialkyl acetal of glycolaldehyde; and the glycolaldehyde formation step and the acetalization step are carried out in a single vessel; Among them, the N - heterocyclic carbene catalyst is a compound represented by formula (I) or (II), wherein, R 1 and R 4 are each independently an unsubstituted C3 to C6 alkyl group or a C1 to C6 alkyl group substituted with a C6 to C 18 aryl group; R 2 and R 5 each independently is an unsubstituted C3 to C6 alkyl group or a C1 to C6 alkyl group substituted with a C6 to C 18 aryl group; R 3 and R 6 each independently is H, unsubstituted C1-C6 alkoxy, unsubstituted C3-C6 alkyl or C1-C6 alkyl substituted with C6-C 18 aryl; R 7 and R 8 are each H or, together with the carbon atoms to which they are attached, form a C6 to C 18 aryl group; A - is a halogen anion or a carbon dioxide radical anion.

2. The method according to claim 1, wherein the ether solvent is selected from cyclopentyl methyl ether (CPME), tert - butyl methyl ether (TBME), diethyl ether, 1,4 - dioxane, tetrahydrofuran (THF), 2 - methyltetrahydrofuran (2 - MeTHF), and anisole.

3. The method according to claim 1, which is carried out in the presence of the following N - heterocyclic carbene catalyst, wherein, R 1 and R 4 each independently is an unsubstituted C3 to C6 alkyl group, R 2 and R 5 each independently is an unsubstituted C3 to C6 alkyl group, R 3 and R 6 as well as R 7 and R 8 are all H, A - is a halogen anion or a carbon dioxide radical anion.

4. The method according to claim 1, which is carried out in the presence of the following N-heterocyclic carbene catalyst, wherein, R 1 and R 4 as well as R 2 and R 5 are both isopropyl groups, R 3 and R 6 as well as R 7 and R 8 are both H, A - is a chloride anion or a carbon dioxide radical anion.

5. The method according to claim 1, wherein the ether solvent is cyclopentyl methyl ether (CPME), tert - butyl methyl ether (TBME), diethyl ether, or 1,4 - dioxane; the N - heterocyclic carbene catalyst is 1,3 - bis(2,6 - diisopropylphenyl)imidazol - 2 - ylidene, 1,3 - bis(2,6 - diisopropylphenyl)imidazolium chloride, or 1,3 - bis(2,6 - diisopropylphenyl)imidazolium - 2 - carboxylate.

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