Method for producing amino acid aminoalkyl ester or inorganic acid salt thereof

Abstract

The present invention provides a method for producing an amino acid aminoalkyl ester or an inorganic acid salt thereof by reacting a compound represented by general formula (I) shown below or a compound represented by general formula (III) shown below, or a salt thereof, and at least one compound selected from the group consisting of compounds represented by general formula (IV-I) shown below, compounds represented by general formula (IV-II) shown below, compounds represented by general formula (IV-III) shown below and compounds represented by general formula (IV-IV) shown below, or an inorganic acid salt thereof. ##STR00001##

Claims

1. A method for producing an amino acid aminoalkyl ester or an inorganic acid salt thereof by reacting: a compound represented by general formula (I) shown below or a compound represented by general formula (III) shown below, or a salt thereof, and at least one compound selected from the group consisting of compounds represented by general formula (IV-I) shown below, compounds represented by general formula (IV-II) shown below, compounds represented by general formula (IV-III) shown below and compounds represented by general formula (IV-IV) shown below, or an inorganic acid salt thereof: ##STR00204## wherein in general formula (I), R.sup.11 represents a hydrogen atom, a monovalent aliphatic hydrocarbon group having at least 1 but not more than 10 carbon atoms which may have a substituent, or a monovalent aromatic cyclic group having at least 6 but not more than 10 carbon atoms which may have a substituent; the substituent is a group selected from the group consisting of monovalent aliphatic hydrocarbon groups having at least 1 but not more than 10 carbon atoms, monovalent aromatic cyclic groups having at least 6 but not more than 10 carbon atoms, groups represented by general formula (II-1) shown below and groups represented by general formula (II-2) shown below; R.sup.12 represents a group selected from the group consisting of groups represented by general formula (II-1) shown below and groups represented by general formula (II-2) shown below; R.sup.13 represents a hydrogen atom; and n11 is 1, ##STR00205## wherein in general formula (II-1), R.sup.21 represents a monovalent aliphatic hydrocarbon group having at least 1 but not more than 10 carbon atoms which may have a substituent, or a monovalent aromatic cyclic group having at least 6 but not more than 10 carbon atoms which may have a substituent; and in general formula (II-2), R.sup.22 represents a monovalent organic group; ##STR00206## wherein in general formula (III), n31 is an integer of at least 2 but not more than 4; R.sup.31 represents an n31-valent aliphatic hydrocarbon group having at least 1 but not more than 10 carbon atoms which may have a substituent, or an n31-valent aromatic cyclic group having at least 6 but not more than 10 carbon atoms which may have a substituent; the substituent is a group selected from the group consisting of monovalent aliphatic hydrocarbon groups having at least 1 but not more than 10 carbon atoms, monovalent aromatic cyclic groups having at least 6 but not more than 10 carbon atoms, groups represented by the general formula (II-1), groups represented by the general formula (II-2), groups represented by the general formula (II-3), and groups represented by the general formula (II-4); R.sup.32 represents a group selected from the group consisting of groups represented by the general formula (II-1), groups represented by the general formula (II-2) and groups represented by the general formula (II-3); and R.sup.33 represents a hydrogen atom or a monovalent organic group, ##STR00207## wherein in general formula (II-3), each of R.sup.23 and R.sup.24 independently represents a monovalent aliphatic hydrocarbon group having at least 1 but not more than 10 carbon atoms which may have a substituent, or a monovalent aromatic cyclic group having at least 6 but not more than 10 carbon atoms which may have a substituent; and ##STR00208## wherein in general formula (II-4), R.sup.25 represents a hydrogen atom or a monovalent organic group, ##STR00209## wherein in general formula (IV-I), Y.sup.401 represents a divalent aliphatic hydrocarbon group having at least 1 but not more than 10 carbon atoms or a divalent aromatic cyclic group having at least 6 but not more than 10 carbon atoms; and R.sup.401 represents a group selected from the group consisting of an amino group, —NHCONH.sub.2, groups represented by the general formula (II-1), groups represented by the general formula (II-2), and groups represented by the general formula (II-3), ##STR00210## wherein in general formula (IV-II), each of Y.sup.402 and Y.sup.403 independently represents a divalent aliphatic hydrocarbon group having at least 1 but not more than 10 carbon atoms or a divalent aromatic cyclic group having at least 6 but not more than 10 carbon atoms; and each of R.sup.402 and R.sup.403 independently represents a group selected from the group consisting of a hydrogen, an amino group, —NHCONH.sub.2, groups represented by the general formula (II-1), groups represented by the general formula (II-2), and groups represented by the general formula (II-3), provided that R.sup.402 and R.sup.403 do not simultaneously represent a hydrogen, ##STR00211## wherein in general formula (IV-III), each of Y.sup.404, Y.sup.405 and Y.sup.406 independently represents a divalent aliphatic hydrocarbon group having at least 1 but not more than 10 carbon atoms or a divalent aromatic cyclic group having at least 6 but not more than 10 carbon atoms; and each of R.sup.404, R.sup.405 and R.sup.406 independently represents at I act one a group selected from the group consisting of a hydrogen, an amino group, —NHCONH.sub.2, groups represented by the general formula (II-1), groups represented by the general formula (II-2), and groups represented by the general formula (II-3), provided that R.sup.404, R.sup.405 and R.sup.406 do not simultaneously represent a hydrogen, ##STR00212## wherein in general formula (IV-IV), each of Y.sup.407, Y.sup.408, Y.sup.409 and Y.sup.4010 represents a divalent aliphatic hydrocarbon group having at least 1 but not more than 10 carbon atoms or a divalent aromatic cyclic group having at least 6 but not more than 10 carbon atoms; at least one of R.sup.407, R.sup.408, R.sup.409 and R.sup.4010 represents a hydroxyl group, and each of the others represents a group selected from the group consisting of a hydrogen, an amino group, —NHCONH.sub.2, groups represented by the general formula (II-1), groups represented by the general formula (II-2), and groups represented by the general formula (II-3), provided that R.sup.407, R.sup.408, R.sup.409 and R.sup.4010 do not simultaneously represent a hydrogen, wherein the reaction is conducted in presence of at least one acid catalyst selected from the group consisting of organic acids and inorganic acids having a normal boiling point of 0° C. or higher, and the inorganic acid used as an acid catalyst is at least one acid selected from the group consisting of sulfuric acid, phosphoric acid, nitric acid and boric acid.

2. The method according to claim 1, wherein the salt of the compound represented by general formula (I) or general formula (III) is obtained from an acid, which is the same as the acid catalyst.

3. The method according to claim 1, wherein the compound represented by general formula (I) or the compound represented by general formula (III), or a salt thereof, is reacted with the compound represented by general formula (IV-I) or an inorganic acid salt thereof.

4. The method according to claim 3, wherein in the general formula (I): R.sup.11 represents a hydrogen atom or a monovalent aliphatic hydrocarbon group having at least 1 but not more than 10 carbon atoms which may have a substituent, the substituent is a group represented by the general formula (II-1), R.sup.12 is a group represented by the general formula (II-1), and R.sup.13 is a hydrogen atom; and in the general formula (IV-I): Y.sup.401 is a divalent aliphatic hydrocarbon group having at least 1 but not more than 10 carbon atoms, and R.sup.401 is a group represented by the general formula (II-1).

5. The method according to claim 1, wherein the acid catalyst is included in an amount of 3 to 80% by mass relative to a total mass of the reaction liquid.

Description

EXAMPLES

(1) Embodiments of the present invention are described below in further detail using specific examples, but the embodiments of the present invention are in no way limited by the following examples, provided they do not exceed the scope of the invention.

[Synthesis Example 1] Synthesis of Compound (A-20)

(2) A glass flask with an internal capacity of 500 mL was charged with 200 g of lysine monohydrochloride, 34 g of urea and 100 g of water, and the resulting mixture was heated at 120° C. for 2 hours while being stirred under a nitrogen atmosphere at atmospheric pressure. The reaction liquid was then cooled, the reaction liquid was poured into 2-propanol, and the precipitated solid was collected by filtration. Analysis by .sup.1H-NMR revealed that the collected solid was a compound in which the amino group of the lysine had been substituted with a urea linkage. This compound was used as compound (A-20) as a raw material in Example 22 described below.

[Example 1] Production of Compound (E-1)

(3) A glass flask with an internal capacity of 1,000 mL fitted with a distillation device was charged with 200 g of a compound (A-1) (glycine) shown as the raw material 1 in Table 1 below, 171 g of a compound (B-1) (ethanolamine) shown as the raw material 2 in Table 1 below, 200 g of toluene and 214 g of phosphoric acid, and a reaction was conducted under reduced pressure at 100° C., with the toluene being distilled off while additional toluene was added to keep the liquid level substantially constant. After continuing the reaction for 8 hours, collection of the reaction liquid and analysis by liquid chromatography revealed that a compound (E-1) shown as the product in Table 1 below had been produced at a yield of 84% relative to the amount added of the compound (A-1) (glycine). Analysis of the amount of phosphoric acid contained in the compound (E-1) (excluding the counter anion component) by a conventional method revealed 350 wtppm of phosphoric acid relative to the compound (E-1).

[Examples 2 to 48] Production of Compound (E-2) to Compound (E-48)

(4) With the exceptions of adding the raw material 1, the raw material 2 and the solvent in the combinations shown below in Tables 1 to 8, and setting the reaction temperature, pressure and time as shown below in Tables 1 to 8, the same method as Example 1 was used to produce compounds (E-2) to (E-48).

Comparative Example 1

(5) With the exception of replacing the acid used in Example 9 from phosphoric acid to hydrogen chloride, a reaction was conducted using the same method as Example 9. The method for supplying the hydrogen chloride involved supplying hydrogen chloride gas from a hydrogen chloride cylinder using a flow meter that used a corrosion-resistant material of stainless steel or glass, introducing the hydrogen chloride gas into the reaction system while controlling the supply rate and conducting the reaction by bubbling the gas through the liquid phase, and following completion of the reaction, calculating the amount of hydrogen chloride gas introduced into the system to calculate the weight of hydrogen chloride supplied. In this reaction, the yield of the produced compound (E-9) was 55%.

Comparative Example 2

(6) With the exception of replacing the acid used in Example 10 from methanesulfonic acid to hydrogen chloride, a reaction was conducted using the same method as Example 10. The hydrogen chloride was supplied to the reaction system using the same method as Comparative Example 1. In this reaction, the yield of the produced compound (E-10) was 50%.

(7) TABLE-US-00001 TABLE 1 Raw material 1: Compound (I) or Compound (III) Amount Molecular Examples Compound Structural formula added (g) weight Example 1 A-1 200  75 Example 2 A-1 200  75 Example 3 A-2 200  75 Example 4 A-3 200  75 Example 5 A-4 200  89 Example 6 A-4 200  89 Example 7 A-5 0 150 297 Raw material 2: Compound (IV-I) to (IV-IV) Structural Amount Molecular Examples Compound formula added (g) weight molar ratio Example 1 B-1 170  61 0.96 Example 2 B-2 430 159 0.99 Example 3 B-2 430 159 0.99 Example 4 B-2 430 159 0.99 Example 5 B-1 143  61 0.96 Example 6 B-1 143  61 0.96 Example 7 B-3 119  75 0.32 Acid Solvent Reaction conditions Compound Amount Compound Amount Temperature Pressure Time Examples name added (g) name added (g) (° C.) (kPa) (hr) Example phosphoric acid 214 toluene 200 100 80  8 1 Example phosphoric acid 210 toluene 200 100 80 10 2 Example phosphoric acid 210 toluene 200 100 80 10 3 Example phosphoric acid 210 toluene 200 100 80 10 4 Example phosphoric acid 180 toluene 200 100 80  8 5 Example sulfuric acid 270 toluene 200 100 80  8 6 Example p-toluene 432 o-dichloro benzene 100 110 10  6 7 sulfonic acid Product Amount of Yield acid in product Examples Compound Structural formula (%) wt % Example 1 E-1 84 0.05 Example 2 E-2 82 0.03 Example 3 E-3 0 82 0.08 Example 4 E-4 82 0.06 Example 5 E-5 78 0.04 Example 6 E-6 76 0.08 Example 7 E-7 68 0.06

(8) TABLE-US-00002 TABLE 2 Raw material 1: Compound (I) or Compound (III) Amount Molecular Examples Compound Structural formula added (g) weight Example  8 A-6 150 201 Example  9 A-7 200 182 Example 10 A-8 150 223 Example 11 A-9 150 223 Example 12 A-10 300 178 Example 13 A-11 0 130 147 Example 14 A-12 300 207 Raw material 2: Compound (IV-I) to (IV-IV) Structural Amount Molecular molar Examples Compound formula added (g) weight ratio Example  8 B-4  57 148 1.94 Example  9 B-1  70  61 0.96 Example 10 B-5 120 181 1.01 Example 11 B-5 120 181 1.01 Example 12 B-4 121 148 2.06 Example 13 B-6 181  97 0.47 Example 14 B-7 138 101 1.06 Acid Solvent Reaction conditions Compound Amount Compound Amount Temperature Pressure Time Examples name added (g) name added (g) (° C.) (kPa) (hr) Example trifluoro-methane 134 o-dichloro 200 100 10  8  8 sulfonic acid benzene Example phosphoric 130 toluene 200 100 80  8  9 acid Example methane sulfonic 277 toluene 200 100 80  8 10 acid Example methane sulfonic 277 toluene 200 100 80  8 11 acid Example phosphoric  46 xylene 300 130 40  5 12 acid Example phosphoric 348 xylene 100 130 40  8 13 acid Example sulfuric 147 toluene 200 100 80 10 14 acid Product Amount of Com- Yield acid in product Examples pound Structural formula (%) wt % Example   8 E-8 73 0.04 Example  9 E-9 0 79 0.05 Example 10 E-10 73 0.06 Example 11 E-11 73 0.07 Example 12 E-12 83 0.06 Example 13 E-13 79 0.04 Example 14 E-14 78 0.08

(9) TABLE-US-00003 TABLE 3 Raw material 1: Compound (I) or Compound (III) Amount Molecular Examples Compound Structural formula added (g) weight Example 15 A-13 200 187 Example 16 A-14 200 442 Example 17 A-15 300 386 Example 18 A-16 150 231 Example 19 A-17 00 150 204 Example 20 A-18 01 150 205 Example 21 A-19 02 200 175 Example 22 A-20 03 150 — Raw material 2: Compound (IV-I) to (IV-IV) Structural Amount Molecular molar Examples Compound formula added (g) weight ratio Example 15 B-8 04 179 181 1.08 Example 16 B-5 05 135 181 0.61 Example 17 B-5 06 135 181 1.04 Example 18 B-9 07 114 160 0.91 Example 19 B-4 08 239 148 0.46 Example 20 B-7 09  78 101 0.95 Example 21 B-8 0 143 147 1.1  Example 22 B-5 103 181 1.1  relative to carboxy Acid Solvent Reaction conditions Compound Amount Compound Amount Temperature Pressure Time Examples name added (g) name added (g) (° C.) (kPa) (hr) Example sulfuric 106 toluene 200 100 80 10 15 acid Example phosphoric 181 toluene 200 100 80 10 16 acid Example phosphoric 181 toluene 200 100 80 10 17 acid Example phosphoric 173 xylene 300 130 40  5 18 acid Example phosphoric  46 xylene 200 130 40  5 19 acid Example methane  40 toluene 200 100 80  8 20 sulfonic acid Example phosphoric 180 toluene 200 100 80  8 21 acid Example phosphoric 139 toluene 200 100 80 10 22 acid Product Amount of acid in Ex- Com- Yield product amples pound Structural formula (%) wt % Ex- ample 15 E-15 79 0.05 Ex- ample 16 E-16 80 0.06 Ex- ample 17 E-17 81 0.07 Ex- ample 18 E-18 82 0.06 Ex- ample 19 E-19 81 0.04 Ex- ample 20 E-20 79 0.03 Ex- ample 21 E-21 80 0.04 Ex- ample 22 E-22 81 0.05

(10) TABLE-US-00004 TABLE 4 Raw material 1: Compound (I) or Compound (III) Amount Molecular Examples Compound Structural formula added (g) weight Example 23 A-21 0 150 260 Example 24 A-21 200 386 Example 25 A-21 200 386 Example 26 A-21 200 386 Example 27 A-21 300 386 Raw material 2: Compound (IV-I) to (IV-IV) Structural Amount Molecular molar Examples Compound formula added (g) weight ratio Example 23 B-5 103 181 1.01 Example 24 B-9  41  75 0.95 Example 25 B-10  48  89 0.96 Example 26 B-11  35 330 4.88 Example 27 B-12  50 479 4.96 Acid Solvent Reaction conditions Compound Amount Compound Amount Temperature Pressure Time Examples name added (g) name added (g) (° C.) (kPa) (hr) Example phosphoric 139 toluene 200 100 80 10 23 acid Example phosphoric 139 o-dichloro benzene 100 110 10  6 24 acid Example phosphoric 139 o-dichloro benzene 100 110 10  6 25 acid Example phosphoric 139 o-dichloro benzene 100 110 10  6 26 acid Example phosphoric 139 o-dichloro benzene 100 110 10  6 27 acid Product Amount Yield of acid in Examples Compound Structural formula (%) product wt % Example 23 E-23 0 80 0.06 Example 24 E-24 79 0.04 Example 25 E-25 78 0.04 Example 26 E-26 77 0.05 Example 27 E-27 78 0.06

(11) TABLE-US-00005 TABLE 5 Raw material 1: Compound (I) or Compound (III) Amount Molecular Examples Compound Structural formula added (g) weight Example 28 A-21 200 386 Example 29 A-21 200 386 Example 30 A-21 200 386 Example 31 A-21 200 386 Example 32 A-21 200 386 Raw material 2: Compound (IV-I) to (IV-IV) Structural Amount Molecular molar Examples Compound formula added (g) weight ratio Example 28 B-13 0 75 493 3.40 Example 29 B-9 41  75 0.95 Example 30 B-10 48  89 0.96 Example 31 B-11 35 330 4.88 Example 32 B-12 50 479 4.96 Acid Solvent Reaction conditions Compound Amount Compound Amount Temperature Pressure Time Examples name added (g) name added (g) (° C.) (kPa) (hr) Example phosphoric 139 o-dichloro benzene 100 110 10 6 28 acid Example p-toluene 432 o-dichloro benzene 100 110 10 6 29 sulfonic acid Example p-toluene 432 o-dichloro benzene 100 110 10 6 30 sulfonic acid Example p-toluene 432 o-dichloro benzene 100 110 10 6 31 sulfonic acid Example p-toluene 432 o-dichloro benzene 100 110 10 6 32 sulfonic acid Product Amount of Yield acid in product Examples Compound Structural formula (%) wt % Example 28 E-28 76 0.07 Example 29 E-29 77 0.06 Example 30 E-30 79 0.05 Example 31 E-31 75 0.04 Example 32 E-32 74 0.06

(12) TABLE-US-00006 TABLE 6 Raw material 1: Compound (I) or Compound (III) Amount Molecular Examples Compound Structural formula added (g) weight Example 33 A-21 0 200 386 Example 34 A-21 200 386 Example 35 A-21 200 386 Example 36 A-21 200 386 Example 37 A-21 200 386 Raw material 2: Compound (IV-I) to (IV-IV) Structural Amount Molecular molar Compound formula added (g) weight ratio Example 33 B-13 75 493 3.40 Example 34 B-14 41 75 0.95 Example 35 B-15 48 89 0.96 Example 36 B-16 35 330 4.88 Example 37 B-17 50 479 4.96 Acid Solvent Reaction conditions Compound Amount Compound Amount Temperature Pressure Time Examples name added (g) name added (g) (° C.) (kPa) (hr) Example p-toluene 432 o-dichloro benzene 100 110 10  6 33 sulfonic acid Example p-toluene 432 toluene 200 100 80 10 34 sulfonic acid Example p-toluene 432 toluene 200 100 80 10 35 sulfonic acid Example p-toluene 432 toluene 200 100 80 10 36 sulfonic acid Example p-toluene 432 toluene 200 100 80 10 37 sulfonic acid Product Amount Yield of acid in Examples Compound Structural formula (%) product wt % Example 33 E-33 0 75 0.03 Example 34 E-34 80 0.04 Example 35 E-35 82 0.05 Example 36 E-36 78 0.06 Example 37 E-37 79 0.05

(13) TABLE-US-00007 TABLE 7 Raw material 1: Compound (I) or Compound (III) Amount Molecular Examples Compound Structural formula added (g) weight Example 38 A-21 200 386 Example 39 A-22 200 195 Example 40 A-22 200 195 Example 41 A-22 200 195 Example 42 A-22 200 195 Example 43 A-22 0 200 195 Example 44 A-22 200 195 Raw material 2: Compound (IV-I) to (IV-IV) Structural Amount Molecular molar Compound formula added (g) weight ratio Example 38 B-18 75 493 3.40 Example 39 B-9 41 75 1.87 Example 40 B-10 48 89 1.9  Example 41 B-11 35 330 9.66 Example 42 B-12 50 479 9.82 Example 43 B-13 75 493 6.74 Example 44 B-14 41 175 4.37 Acid Solvent Reaction conditions Compound Amount Compound Amount Temperature Pressure Time Examples name added (g) name added (g) (° C.) (kPa) (hr) Example p-toluene 432 toluene 200 100 80 10 38 sulfonic acid Example phosphoric 139 xylene 200 130 40  5 39 acid Example phosphoric 139 xylene 200 130 40  5 40 acid Example phosphoric 139 xylene 200 130 40  5 41 acid Example phosphoric 139 xylene 200 130 40  5 42 acid Example phosphoric 139 xylene 200 130 40  5 43 acid Example phosphoric 139 xylene 200 130 40  5 44 acid Product Amount of Com- Yield acid in product Examples pound Structural formula (%) wt % Example 38 E-38 77 0.04 Example 39 E-39 0 81 0.06 Example 40 E-40 80 0.04 Example 41 E-41 81 0.06 Example 42 E-42 80 0.06 Example 43 E-43 78 0.07 Example 44 E-44 81 0.06

(14) TABLE-US-00008 TABLE 8 Raw material 1: Compound (I) or Compound (III) Amount Molecular Examples Compound Structural formula added (g) weight Example 45 A-22 200 195 Example 46 A-22 200 195 Example 47 A-22 200 195 Example 48 A-22 200 195 Comparative Example 1 A-7 0 200 182 Comparative Example 2 A-8 150 223 Raw material 2: Compound (IV-I) to (IV-IV) Com- Structural Amount Molecular molar pound formula added (g) weight ratio Example 45 B-15  48 189 4.03 Example 46 B-16  35 290 8.49 Example 47 B-17  50 419 8.59 Example 48 B-18  75 433 5.92 Comparative Example 1 B-1  70 61 0.96 Comparative Example 2 B-5 120 181 1.01 Acid Solvent Reaction conditions Compound Amount Compound Amount Temperature Pressure Time Examples name added (g) name added (g) (° C.) (kPa) (hr) Example phosphoric 139 xylene 200 130 40 5 45 acid Example phosphoric 139 xylene 200 130 40 5 46 acid Example phosphoric 139 xylene 200 130 40 5 47 acid Example phosphoric 139 xylene 200 130 40 5 48 acid Comparative hydrogen 130 toluene 200 100 80 8 Example 1 chloride Comparative hydrogen 277 toluene 200 100 80 8 Example 2 chloride Product Amount of Com- Yield acid in product Examples pound Structural formula (%) wt % Example 45 E-45 79 0.07 Example 46 E-46 77 0.04 Example 47 E-47 00 77 0.03 Example 48 E-48 01 78 0.06 Comparative Example 1 E-8 02 88 0.01 Comparative Example 1 E-10 03 50 0.01

(15) As is evident from Examples 1 to 48, the yield of every products was at least 67%, with the target product able to be obtained in high yield. Further, the acid was in a liquid state during the production process, and was not contained in the distilled gaseous component.

INDUSTRIAL APPLICABILITY

(16) The production method of an embodiment of the present invention can produce an amino acid aminoalkyl ester or an inorganic acid salt thereof in high yield without acid distillation.