JPH0150229B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a crown ether having an extracyclic secondary amino group, represented by the following general formula, and a method for producing the same. (In the formula, R is an alkyl group, an aryl group, or an aralkyl group, m is an integer of 0 to 2, and n is an integer of 1 to 5.) Crown ether is a compound commonly attached to a macrocyclic polyether. As it became clear that it has the ability to form complexes with various cations, it began to be used in a wide range of fields such as organic synthesis, separation analysis, biochemistry, and pharmaceuticals, making it an industrially interesting product. It is a compound. In recent years, the synthesis of crown ethers with functional groups, which are important key compounds for the synthesis of various functional crown ethers, has been attracting attention in the chemistry of crown ethers. The present inventor has been engaged in research on the synthesis and utilization of crown ethers for some time, and has previously developed a novel method for producing crown ethers having a hydroxyl group as crown ethers having a functional group (Japanese Unexamined Patent Publication No. 12384/1984) and a novel method for producing crown ethers having a hydroxyl group (Japanese Patent Application Laid-open No. 12384/1984) and a novel bromomethyl crown ether. Synthesis method of crown ether (JCSChem.
Comm., 1981 , 219), we have now succeeded in synthesizing a crown ether having a secondary amino group outside the ring, represented by the general formula below. This compound is a useful compound that is expected to be applied to the synthesis of various substituted crown ethers, polymerization, immobilization to resins, etc. by utilizing the reactivity of its secondary amino group. (In the formula, R is an alkyl group, an aryl group, or an aralkyl group, m is an integer of 0 to 2, and n is an integer of 1 to 5). The secondary aminomethyl crown ether represented by the general formula above is a new substance that has not been described in any literature, and has the general formula () (In the formula, R is an alkyl group, an aryl group, or an aralkyl group, m is an integer of 0 to 2) and an amino-substituted diol compound represented by the general formula () [In _the formula, It can be easily produced and obtained by reacting in the presence of a metal compound having . In the amino-substituted diol compound () used in the present invention, substituents represented by R include methyl, ethyl, propyl, butyl,
Examples include alkyl groups having 1 to 10 carbon atoms such as t-butyl, hexyl, octyl, nonyl, and decyl, aryl groups such as phenyl, tolyl, and xylyl, and aralkyl groups such as benzyl. These substituents may further have a functional group inert to the reaction (for example, an amino group). Furthermore, as one of the starting materials, polyethylene glycol derivatives (), diethylene glycol,
Dihalogenides (e.g. dichloride, dibromide, etc.) of triethylene glycol, tetraethylene glycol, pentaethylene glycol, hexaethylene glycol, dialkanesulfonates (e.g. dimethane sulfonate, diethanesulfonate), dialnesulfonates [e.g. Examples include benzenesulfonate, di-p-toluenesulfonate (ditosylate), and dibenzylsulfonate. In addition, when using 3-substituted amino-1,2-propanediol in which m is O in the general formula (), a polyethylene glycol derivative in which n is at least 2 is used as the polyethylene glycol derivative to be reacted with it. be done. Further, as the metal compound having a template effect that is allowed to coexist in the reaction system, alkali metals, their hydroxides, hydrides, alkoxides, and alkaline earth metal hydroxides and hydrides are preferably used. Specifically, metallic sodium, metallic potassium, metallic lithium, sodium hydroxide, potassium hydroxide,
Examples include lithium hydroxide, sodium hydride, potassium hydride, lithium hydride, calcium hydroxide, calcium hydride, sodium t-butoxide, potassium t-butoxide, and the like. The amount of these metal compounds to be used may be a chemical equivalent to a slight excess of the two hydroxyl groups of the dialkanolamine, and in the case of an alkali metal compound, it is 2 to 2.4 times the molar amount. The reaction according to the invention is usually carried out in an inert organic solvent. Suitable solvents include, for example, diethyl ether, tetrahydrofuran, dioxane, monoglyme, diglyme, dimethyl sulfoxide,
Examples include N,N-dimethylformamide, t-butanol, hexamethylphosphoric acid triamide, and a mixed solvent thereof. In the present invention, an amino-substituted diol compound () and a polyethylene glycol derivative () are reacted at a molar ratio of 1:1 in the presence of a metal compound having a template effect. Usually, a solution of the polyethylene glycol derivative (2) is gradually dropped into a solution containing the amino-substituted diol compound (2) and a predetermined amount of the above metal compound while stirring. Alternatively, separately prepared solutions of the amino-substituted diol compound () and the polyethylene glycol derivative may be simultaneously dropped into the solution of the metal compound. The reaction temperature varies depending on the type of polyethylene glycol derivative to be reacted with the amino-substituted diol compound (), but is from room temperature to the reflux temperature of the solvent, preferably about 40 to 80°C. After the reaction is completed, the target product can be easily isolated by liquid-liquid extraction of the reaction mixture or by thermal decomposition distillation, and if necessary, it can be separated as a complex compound and purified by thermal decomposition. It can also be made into a product. Hereinafter, this will be explained in detail using examples. Example 1 3-hexylaminomethyl-15-crown-5
After completely dissolving 3.22 g (0.14 mol) of metallic sodium in 640 ml of t-butanol under reflux, 3-hexylamino-1,2-propanediol (12.27
g, 0.07 mol) was added thereto, and the mixture was further heated under reflux for 1 hour. While keeping the internal temperature at 40°C and stirring, add tetraethylene glycol ditosylate (35.18g, 0.07mol)/
Add 80ml of dioxane mixture dropwise over 1.5 hours.
The reaction was further carried out at 40°C for 2.5 hours. The generated salt was filtered, the solvent was distilled off, and then thermal decomposition distillation was performed at 147℃/0.007Torr using a Kugelrohr distillation apparatus.
1192 g (51%) of a pale yellow viscous liquid was obtained. It was confirmed to be the desired product through elemental analysis, MS, IR, and NMR spectra. Actual value (calculated value) C 61.05 (61.23) H 10.59 (10.58) N 4.30 (4.20) NMR (CDCl ₃ , δ) 0.88 (t, 3H), 1.26 (m,
8H), 2.21 (S, 1H), 2.60 (m, 4H), 3.66 (S
+m, 19H). MS (m/e) 333 (M ⁺ ), 262 (14), 144 (9), 133
(15), 114 (100), 89 (28), 88 (13), 87 (16). IR (neat) 3320 (W), 2930 (S), 2860 (S),
1470 (m), 1350 (m), 1130cm ^-1 (S). Example 2 Preparation of 3-ethylaminomethyl-15-crown-5 1.84 ml of sodium metal in 350 ml of t-butanol
g (0.08 mol) under reflux, 4.77 g (0.04 mol) of 3-ethylamino-1,2-propanediol
was added, and the mixture was further heated under reflux for 1 hour. Tetraethylene glycol dichloride (9.24 g,
A mixture of 0.04 mol)/dioxane (50 ml) was added dropwise over 1 hour, and the reaction was continued for an additional 17 hours. 3.25g of pale yellow viscous liquid treated in the same manner as in Example 1
(29%). bp129℃/0.02Torr (Kugerrohr). NMR (CDCl ₃ , δ) 1.12 (t, 3H), 2.66 (m,
5H), 3.64 (S+m, 19H). MS (m/e) 277 (M ⁺ ), 133 (13), 89 (27), 88
(15), 87 (16), 58 (100), 57 (14). Example 3 3-phenylaminomethyl-15-crown-5
Production of 0.96 g of NaH in 100 ml of dimethylformamide
(0.04mol), followed by 3-phenylamino-1,
Add 3.34g (0.02mol) of 2-propanediol,
After stirring and heating at 50° C. for 1 hour, a mixed solution of 10.05 g (0.02 mol) of tetraethylene glycol ditosylate/30 ml of dimethylformamide was gradually added dropwise over 1 hour, and the mixture was allowed to react for an additional 10 hours. After filtering off the precipitated salt, dimethylformamide was recovered under reduced pressure, and the residue was subjected to thermal decomposition distillation using a Kugelrohr distillation apparatus to obtain 2.93 g (45%) of a pale yellow viscous liquid. 150℃/0.055Torr (Kugerrohr). NMR (CDCl ₃ , δ) 3.18 (m, 3H), 3.64 (S+
m, 19H), 6.68 (m, 3H), 7.14 (m, 2H). MS (m/e) 325 (M ⁺ , 17), 106 (100), 105
(72), 93(13), 89(11), 87(12), 77(11). IR (neat) 3370 (m), 3070 (m), 2930 (S),
2890(S), 1610(S), 1500(S), 1360(m),
1100(S), 755(S), 700(S). Example 4 Preparation of 3-decylaminomethyl-15-crown-5 Powdered in 200 ml of dimethylformamide
2.0 g (0.05 mol) of NaOH, followed by 7-aza-1,
5-dihydroxy-3-oxa-heptadecane

[Formula] Add 5.51g (0.02mol), stir and heat at 60℃ for 1 hour,
Triethylene glycol dibenzene sulfonate
8.61g (0.02mol)/30ml dimethylformamide
The mixed solution was gradually added dropwise over 2 hours, and the reaction was continued at that temperature for another 20 hours. It was treated in the same manner as in Example 1 to obtain 2.83 g (36%) of a pale yellow liquid. bp157℃/0.02Torr (Kugerrohr). NMR (CDCl ₃ , δ) 0.87 (t, 3H), 1.25 (S+
m, 16H), 2.65 (m, 4H), 2.95 (S, 1H),
3.64 (S+m, 19H). Example 5 3-t-butylaminomethyl-18-crown-
Production of 6: Powdered KOH2.8 in 180ml of dimethyl sulfoxide
g (0.05 mol), followed by 3-t-butylamino-
After adding 2.94 g (0.02 mol) of 1,2-propanediol and stirring at 50°C for 1 hour, a mixed solution of 10.93 g (0.02 mol) of pentaethylene glycol ditosylate/30 ml of dimethyl sulfoxide was added dropwise over 2 hours. Furthermore, after reacting at 50°C for 5 hours, the salt was filtered off and dimethyl sulfoxide was recovered. The residue is pyrolyzed and distilled using a Kugelrohr distillation apparatus.
3.54 g (51%) of pale yellow liquid was obtained. bp150℃/
004Torr (kugelrohr). NMR (CDCl ₃ , δ) 1.08 (S, 9H), 2.30 (S,
1H), 2.64 (m, 2H), 3.66 (S+m, 19H). Example 6 3-hexylaminomethyl-18-crown-6
Production of metallic potassium 3.13 in 360 ml of t-butanol
After completely dissolving g (0.08 mol), 10-aza-1,8-dihydroxy-3,6-dioxahexadecane 10.54g (0.04mol) was added and stirred at 40°C for 1 hour. Triethylene glycol ditosylate 18.34
A mixed solution of g (0.04 mol)/50 ml of dioxane was added dropwise over 1 hour, and the mixture was further reacted at 40°C for 4 hours. Treated in the same manner as in Example 1, yielding 8.78 g of pale yellow liquid.
(58%). b.p160℃/0.01Torr (Kugerrohr). NMR (CDCl ₃ , δ) 0.88 (t, 3H), 1.28 (m,
8H), 2.30 (S, 1H), 2.62 (m, 4H), 3.68 (S
+m, 23H). Example 7 3-benzylaminomethyl-18-crown-6
Preparation of 5.61 g (0.05 mol) of tert-butanol in 180 ml of dimethyl sulfoxide followed by 3.62 g (0.02 mol) of 3-benzylamino-1,2-propanediol.
After stirring at 60° C. for 1 hour, a mixed solution of 10.93 g (0.02 mol) of pentaethylene glycol ditosylate/30 ml of dimethyl sulfoxide was gradually added dropwise over 1 hour. After further reaction at 60°C for 4 hours, the same treatment as in Example 5 was carried out, and 3.30g (43
%) was obtained. bp170℃/0.06Torr (Kugerrohr). NMR (CDCl ₃ , δ) 2.34 (S, 1H), 2.66 (m,
2H), 3.66 (S+m, 25H), 7.28 (S, 5H). Example 8 3-(6-aminohexyl)aminomethyl-15
-Manufacture of Crown-5 Metallic sodium 1.38 in 270ml of t-butanol
After completely dissolving 10-amino-4
-aza-1,2-dihydroxydecane

[Formula] 5.71g (0.03mol) was added and stirred at 40°C for 1 hour. 40
While maintaining the temperature at °C, a mixed solution of 15.08 g (0.03 mol) of tetraethylene glycol ditosylate/40 ml of dioxane was gradually added dropwise over 1 hour, and the mixture was allowed to react for an additional 4 hours. Perform the same treatment as in Example 1,
2.31 g (22%) of pale yellow liquid was obtained. bp165℃/
0.02Torr (kugelrohr). NMR (CDCl ₃ , δ) 1.18 (m, 4H), 1.36 (m,
4H), 2.63 (m, 9H), 3.65 (S+m, 19H). Example 9 Production of 3-ethylaminomethyl-21-crown-7 3.13 g of metallic potassium in 350 ml of t-butanol
After completely dissolving (0.08 mol), 4.77 g of 3-ethylamino-1,2-propanediol
(0.04 mol) and stirred at 50℃ for 1 hour, 23.63 g of hexaethylene glycol ditosylate.
(0.04 mol)/dioxane (60 ml) was gradually added dropwise over 1 hour. After reacting for an additional 3 hours at that temperature, it was treated in the same manner as in Example 1 to obtain 6.72 g (46%) of a pale yellow liquid. bp160℃/
0.02Torr (kugelrohr). NMR (CDCl ₃ , δ) 1.10 (t, 3H), 2.68 (m,
5H), 3.66 (S+m, 27H). Example 10 3-octylaminomethyl-12-crown-4
Production of 0.56 g of metallic lithium in 360 ml of t-butanol
After completely dissolving (0.08 mol) under reflux, 3-
Octylamino-1,2-propanediol 8.13
g (0.04 mol) was added thereto, and the mixture was heated under reflux for 1 hour. Triethylene glycol ditosylate under reflux stirring
A mixed solution of 18.34 g (0.04 mol)/50 ml of dioxane was gradually added dropwise over 2 hours, and the reaction was continued at that temperature for an additional 20 hours. It was treated in the same manner as in Example 1 to obtain 5.71 g (45%) of a pale yellow liquid. b.p135℃/
0.03Torr (kugelrohr). NMR (CDCl ₃ , δ) 0.88 (t, 3H), 1.25 (m,
12H), 2.30 (S, 1H), 2.64 (m, 4H), 3.64
(m, 15H).

Claims (1)

[Claims] 1. Aminomethyl crown ether represented by the following general formula: (In the formula, R is an alkyl group, an aryl group, or an aralkyl group, m is an integer of 0 to 2, and n is an integer of 1 to 5). 2 General formula () (In the formula, R is an alkyl group, an aryl group, or an aralkyl group, m is an integer of 0 to 2) and an amino-substituted diol compound represented by the general formula () [In _the formula, General formula (), characterized in that the reaction is carried out in the presence of a metal compound having A method for producing aminomethyl crown ether represented by the formula (wherein R, m and n have the same meanings as above). 3. Claim 2, wherein the metal compound having a template effect is an alkali metal alkoxide, an alkali metal hydroxide, an alkali metal hydride, an alkaline earth metal hydroxide, or an alkaline earth metal hydride.
Manufacturing method described in section.