JPS5857377A - Novel aminomethyl crown ether and its preparation - Google Patents

Abstract

NEW MATERIAL:The aminomethyl crown ether of formulaI(R is alkyl, aryl or aralkyl; m is 0-2; n is 1-5). EXAMPLE:3-Hexylaminomethyl-15-crown-5. USE:It can be applied in the synthesis of various substituted crown ethers or the polymerization or resin immobilization of the ethers, and is useful in the industrial fields. PROCESS:The compound of formulaIcan be prepared by reacting the amino- substituted diol compound of formula II with a polyethylene glycol derivative of formula III (X is halogen or O-SO2-R<1>; R<1> is alkyl, aryl or aralkyl) in the presence of a metallic compound having template effect, e.g. metallic sodium, metallic potassium, potassium hydroxide, etc., preferably in a solvent such as diethyl ether, etc. at 40-80 deg.C. The compound of formula III is e.g. diethylene glycol.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a crown ether having a secondary 7-mino group on the outside of the ring, 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, - represents an integer of O to 2, and - represents an integer of 1 to 5.) What is crown ether (crown @th@r)?
Atte is the name conventionally given to macrocyclic polyethers.
As it has become clear that it has the ability to form complexes with various cations, it has begun to be used in a wide range of fields such as organic synthesis, separation analysis, biochemistry, and pharmaceuticals, making it an industrially interesting compound.

In recent years, in the chemistry of crown ethers, the synthesis of crown ethers with functional groups that serve as important tin compounds for the synthesis of various functional crown ethers has been attracting attention. The present inventor has been engaged in research on the synthesis and utilization of crown ethers for some time, and has previously published a new method for producing crown ethers having a hydroxyl group as crown ethers having a functional group (Japanese Unexamined Patent Publication No. 56-12384) and a new Synthesis method of mehew chill crown ether (J, C, yrn,
.

1981, 219), we have now succeeded in synthesizing a crown ether having a secondary amino group outside the ring, which is represented by the following general formula.

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, and m is an integer of 0 to 2, preferably 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 (1) (wherein R is an alkyl group, an aryl group, or an aralkyl group, and m is an integer from O to 2). Amino-substituted diol compound and general formula value represented by -R'
(R' it furkyl group, 7-aryl group or aralkyl group), n is an integer of i-5] by reacting it with a polyethylene glycol derivative represented by the following in the presence of a metal compound having a template effect. Can you get it manufactured?

Amino-substituted diol compound (1) used in the present invention
), the substituents represented by RC include methyl, ethyl, propyl, butyl, t-butyl, hexyl,
Examples include furkyl groups of carbon JICa 1 to 10 such as octyl, nonyl, and decyl, 7-aryl groups such as phenyl, tolyl, and xylyl, and 7-ralkyl groups such as benzyl. These substituents may be further substituted with a functional group inert to the reaction (e.g. amino group).
It may have.

Furthermore, as the polyethylene glycol derivative (■) which is one of the starting materials, diethylene glycol, triethylene glycol, tetraethylene glycol, pentaethylene glycol, hexaethylene glycol respective dichlorides (e.g. dichloride, dichloride, etc.), sialkanesulfonates (e.g. dimethane sulfonate,
(dimethanesulfonate), sialenesulfonate (for example, schichensensulfonate, g-p-)luenesulfonate (ditosylate)), or dibenzylsulfonate.

In addition, in general formula (L), m is O, 3-substituted amino-1
, 2-propanediol, a polyethylene glycol derivative in which n is at least 2 is used as the polyethylene glycol derivative to be reacted with the polyethylene glycol.

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, lithium hydroxide, sodium hydride, potassium hydride, lithium hydride, calcium hydroxide, calcium hydride, sodium -[- butoxide, potassium
Examples include t-butoxide. The amount of these metal compounds used may be a chemical equivalent to a slight excess amount relative to the two hydroxyl groups of the dialkanolamine.
In the case of an alkali metal compound, it is 2 to 2.4 times the mole.

The reaction according to the invention is usually carried out in an inert organic solvent. Examples of suitable solvents include diethyl ether, tetrahydrofuran, dioxane, monoglyme, diglyme, dimethyl sulfoxide, N,N-dimethylformamide, t-butanol, hexamethylphosphoric triamide, and mixed solvents thereof.

In the present invention, the amino-substituted diol compound (1) and the polyethylene glycol derivative Ql) 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 Ql) is gradually dropped into a solution containing the amino-substituted diol compound (1) and a predetermined amount of the above metal compound while stirring. Alternatively, separately prepared solutions of the amino-substituted diol compound (1) 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 (1), but ranges from room temperature to the reflux temperature of the solvent, preferably about 40 to
It is 80C.

After completion of the reaction, the target product can be easily isolated by liquid-liquid extraction of the reaction mixture or by pyrolytic distillation,
Furthermore, if necessary, it can be fractionated as a complex compound and thermally decomposed to produce #1 product.

Hereinafter, this will be explained in detail using examples.

Example 1 Preparation of 3-hexylaminomethyl-15-crown-5 3.22 f (0,14
After completely dissolving mol ) of metal IJium under reflux,
3-hexylamino-1,2-propanediol (12
, 27F, 0.07 mol) was added thereto, and the mixture was further heated under reflux for 1 hour. While maintaining the internal temperature at 40 tl'C, tetraethylene glycol ditosylate (35,1 at% 0.
0711161 )/dioxane 80d mixture at 1.5
The mixture was added dropwise over time, and the mixture was further reacted at 40C for 2.5 hours. The generated salt was filtered, the solvent was distilled off, and then the solvent was distilled using a Kugelrohr distillation apparatus.
Pyrolytic distillation was carried out at
1) was obtained. It was confirmed by elemental analysis, M8° IR, and NMR spectra that it was the desired product.

Actual value (calculated value) C61,05(61,23)H1
0,59 (10,58) N 4.30 (4,2o) NMR (CDCl, , δ) o, 5s (t, 3H
)+1.2a (m, 8H), 2.21 (8, IH), 2
．． 60 (at.

4H), 3.66 (8+m, 19H).

M8 (m/・) 333 (M ), 262 (14
L144(9), 133(15), 114(100)1
89 (28), 8g (13), 87 (16).

IR(neat) 3320(W), 2930(
8).

286G (8), 1470 (m), 1350 (m).

1130cm” (8).

Example 2 Preparation of 3-ethylaminomethyl-15-crown-5 1.84 ml of sodium metal in 350 ml of t-butanol
f (0.08 mol) under reflux, 3-ethyl 7 minnow 1.2-propanediol 4.77 F (0
, 04 mol) was added thereto, and the mixture was further heated under reflux for 1 hour. Tetraethylene glycol dichloride (9,24f) under reflux
, 0.04 mol)/geokey? 750-mixture was added dropwise over 1 hour, and the reaction was continued for another 17 hours. Treated in the same manner as in Example 1 to obtain a pale yellow viscous liquid 3.25
f (29%) was obtained.

b, p, 129 Cl 0.02 Torr (
kugeluru).

NMR (CDCI, , δ) 1.12 (t, 3H)
, 2.66 (m, 15H) + 3.64 (8 + m, 19H
) aMS (m/e) 277 (M”), 133 (1
3).

8G (27), 88 (15), 87 (16), 58 (1
00), 57(14).

Preparation of 3-phenylaminomethyl-15-crown-5 In 100w1l of dimethylformamide, NaHO,96
1 (-0,04 mol), followed by 3-phenylamino-1,2-propanediol 3.34 t (0,0
2 mol) was added, stirred and heated at 50C for 1 hour,
Tetraethylene glycol ditosylate 10.051 (
A mixture of 0.02 mol )/30 m of dimethylform 7i was gradually added dropwise over 1 hour, and the reaction was continued for an additional hour of FnlO. The precipitated salt was filtered through an open bale, dimethylform 7mide was recovered under reduced pressure, and the residue was subjected to thermal decomposition distillation using a Kugelrohr distillation apparatus to obtain 2.93 t (45 t) of a pale yellow viscous liquid.

150 r/o, o 55 Torr (Kugerrohr).

NMR (CDCl, , δ) 3.18 (m, 3H)
, 3.64 (S+m, 19H), 6.68 (m, 3H)
, 7.14 (m, 2H).

M8 (m/・) 325 (M, 17), 1
(16 (100), 105 (72), 93 (13), 8
9(11), 87(12), 77(11).

IR (n@at) 3370 (!11), 3070
(!11).

2930(8), 28(1G(S), 161G(S')
.

150G(8), 1360(L11oo(s).

7SIS(S), 700(8).

Example 4 Preparation of 3-decylaminomethyl-15-crown-5 Dimethylformamide 200mlml Central American powdered NaO
H2,Of (0.05 mol) and then 7-aza were added, and after stirring and heating at 60C for 1 hour, 8.61 t (0.02 n
5ot)/dimethylformamide (30 ml) was added dropwise over 2 hours, and the reaction was continued at that temperature for 200 hours. It was treated in the same manner as in Example 1 to obtain a pale yellow liquid of 2.8 at (s 69k).

b, p, I S 7 Cl 0.02 Torr
(kugelrohr).

NMR (CDCl, , δ) 0.87 (t, 3H
).

1.25 (8+m, 16Tl), 2.65 (m, 4H)
, 2.98 (8, IH), 3.64 (S+m.

19H).

Example 5 Production of 3-t-butyl 7minomethyl-18-crown-6 Powdered KOH2.8f to 180d dimethyl sulfoxide
(0,05 mol), followed by 3-4-butylamino-1,2-propanediol 2.94 F (0,02
10.93 F (0.02
mol)/dimethyl sulfoxide 30su mixed solution
It dripped over time. After further reacting with HlsoC for 5 hours, the salt was filtered off and dimethyl sulfoxide was recovered.

The residue was subjected to thermal decomposition distillation using a Kugelrohr distillation apparatus to obtain 3.54 t (519b) of a pale yellow liquid. b, p,
150 c/ 004↑orr (Kugel 11 Le).

NMR (CDCl, , δ) 1.08 (8,9H)
, 2.30 (8 + IH) + 2.64 (m +
211) + 3.66 (S+m.

19H).

Example 6 Preparation of 3-hexylaminomethyl-18-crown-6 In t-butanoP 360+wj, 3.1% potassium metal was added.
After completely dissolving 3 f (0.08 mol), add 10.54 f (0.04 mol) and heat at 40C.
The mixture was stirred for 1 hour. 18.34 t (0.04m(11)7'dioquine SOm mixed solution was added dropwise over 1 hour, and then 40
The reaction was carried out at C for 4 hours. It was treated in the same manner as in Example 1 to obtain a pale yellow liquid at 8.78F (58 degrees). b, p160
C/ 0.01 Torr (Kugerrohr).

NMR (CDCl, Tδ) 0.88 (t, 3M
), 1.28(+su)+z, go(s, tH), 2.
sz (m+4fl), 3.68 (8+m, 23H).

Example 7 Production of 3-benzylaminomethyl-18-crown-6
．． 61 F (0,05 mol) followed by 3-benzylamino-1,2-propanediol 3.62 F (0
, 02 mol) and stirred at 60C for 1 hour, 1 G, 93 t (
A mixed solution of 0.02 mol )/dimethyl sulfoxide 30d was gradually added dropwise over 1 hour. 4 more at 60r
After the time reaction, the same treatment as in Example 5 was carried out, and a pale yellow liquid 3.
30 f (43 chi) was obtained. b, p.

170 r/o, o 6 Torr (Kugerrohr).

NMR (CDCl, δ) 2.34 (8, IH)
, 2.66 (tn, 2H), 3.66 (S+ta, 25
H), 7.28 (8,6H).

Example 8 Preparation of 3-(6-aminohexyl)aminomethyl-15-crown-5 1.38 d of sodium metal in 270 d of t-butanol
After completely dissolving f (0.06 mol), 10- was added and stirred at 40C for 1 hour. While maintaining 40tll'C, tetophethylene νcol ditosylate 15.08
? A mixed solution of (0,03 nusl)/dioxane 40 was gradually added dropwise over 1 hour, and the reaction was further allowed to proceed for 4 hours. The same treatment as in Example 1 was carried out to obtain 2.31 t (22%) of a pale yellow liquid. b, p.

165 C/0.02 Torr (Kugerrohr).

NMR (CDCI, δ) 1.18 (m, 4H)
, 1.36 (m, 4H), 2. s3 (m, c+a), 3
, 5s (s ar + 19 H).

Example 9 Preparation of 3-ethylaminomethyl-21-crown-7 3.13 f potassium metal in 350 t-butanol
After completely dissolving 3-ethylamino-1,2-propanediol (0.08 mol), 4.771 (0.08 mol) of 3-ethylamino-1,2-propanediol
, 04 mol) was added and stirred for 1 hour at soc, hexaethylene glycol ditosylate 23.63F (0,
A mixed solution of 0.04 mol)/dioxane 60 was gradually added dropwise over 1 hour. After reacting for another 3 hours at that temperature,
Treated in the same manner as in Example 1, a pale yellow liquid 6.7
2t (46%) was obtained. b, p, 1a o
c/0.02 Torr (Kugerrohr).

NMR (CDCl, , δ) 1.10 (t13H)
12.68 (m, 5H), 3J6 (8+s+a, 27H
).

Actual IO Production of 3-octylaminomethyl-12-crown-4 360wj of t-butanol and 0.56f of metallic lithium (
After completely dissolving 0, Ollmol) under reflux, 3-
Octylamino-1,2-butanediol s, la
((0,04mot)) was added and heated under reflux for 1 hour.

Under stirring under reflux, triethylene glycol ditosylate l
G, 34 f (0.04 mol) / dioxane 50 sl mixed solution was gradually added dropwise over 2 hours, and then C
The reaction was allowed to proceed for 20 hours at that temperature. It was treated in the same manner as in Example 1 to obtain a pale yellow liquid s,y lt (45%). b
, p 135 C/ 0.03 Torr (Kugerrohr).

NMR(CDC1g+δ) 0.88(t,
38) 11.25 (m, 12H'), 2.30 (8, l
H).

2.64 (m, 4H) + 3.64 (m + 153f).

Patent applicant: Ajinomoto Co., Inc.

Claims (1)

[Claims] (1) Aminomethyl crown ether represented by the following general formula (in the formula, m is an alkyl group, an aryl group, or a 7-aralyl group, m is an integer of O to 2, and C is an integer of 1 to D) ). (V) An amino-substituted diol compound represented by C and the general formula (fl ) [In the formula, X 42 ha pf v also) 10-8o, -
R' (RJi alkyl group, aryl group or aralkyl group), 1 represents an integer of 1 to 5] (characterized by reacting a polyethylene glycol derivative represented by A method for producing aminomethyl crown ether represented by the general formula (in the formula, Rlm and kan have the same meanings as above). tl+ The metal compound having a template effect is an alkali metal alkoxide, an alkali metal hydroxide, The manufacturing method according to claim 1, which is an alkaline metal hydride, an alkaline earth metal hydroxide, or an alkaline earth metal hydride.