JPS58154565A - Preparation of diazacrown ethers - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as a carrier for ionic selective electrode, etc. by one process industrially advantageously, by reacting a diamino polyether with a polyethylene glycol derivative using a metal compound having a template effect. CONSTITUTION:A diamino polyether shown by the formulaI(m, n and p are 0-4) is reacted with a polyethylene glycol derivative shown by the formula II X is halogen or formula III (R<1> is alkyl, aryl, or aralkyl); q is 1-5 in a molar ratio of 1:1 in an inert organic solvent in the presence of a metal compound showing a template effect, to give the desired compound such as 1,10- diaza-21-crown-7, etc. shown by the formula IV. A hydroxide, hydride, or alkoxide of an alkali metal or alkaline(earth) metal is preferably used as the metal compound. EFFECT:It is obtained not by way of an intermediate of ring formation through condensation, processes for introduction of protecting group and deprotection step can be omitted, and the reaction process is shortened.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing diaza crown ethers.

Crown ethers are the names conventionally given to macrocyclic polyethers, which are known to have complex-forming ability with various cations, and are used in organic synthesis, It is beginning to be used in a wide range of fields such as separation analysis, biochemistry, and pharmaceuticals, and is an industrially used compound.

Compounds in which the oxygen atom of ethers is substituted with a atomic group that is generally condensed into azacrown ether (azacrown ether@) are similar to crown ethers. ,
In recent years, it is a very different compound that has been attracting attention from the viewpoint of synthesis and physical properties. Azacrown ether chains have a much greater ability to form complexes with soft transition metal and heavy metal ions than crown ethers, and are expected to be used in various fields by utilizing their ζ0% property. A conductor with a long-chain alkyl radical in % exhibits a peculiar pixel pattern in the presence of metal ions (M, Okaharm et ml, , J, C,
8, Ckaa, Collll11.4jjlJl.

586) There is also interest from the picture of surface active action.

In recent years, in the chemistry of crown ethers, the synthesis of crown ethers having a functional group t, which is an important key compound for the synthesis of various functional crown ethers, has been attracting attention. (For example, for dimethyl crown ether in hydrogen, F, Moatamariet ml, + Te
trabedron Left, 197L 505S
sB.

Czech+Tetrahedron Lett, 1
98 (L 4197; Hiro0kahara et m
l,,J,Org,Cbem,+45*535
5 (1980 M. for bromomethyl crown ether).

0kabara et al., ,J,C,8,Chem.
, Conm-+1981s219)
,8alberland et ml, ,J,C,8
゜Ckem, Comn,, 1979e 307), polymerization, and constantization into resins (J, &ni
d, Ind, Rug.

Ckasa, Prod, '&em, Dew, I
Possible applications include T, 364 (1980)). ζ, bis(2/ether) is a crown ether that is linked by an appropriate linking group and has a completely new metal ion monoselectivity that is different from ordinary crown ethers, so it is biochemically important. One model compound is, for example, a carrier of an ion-selective electrode.

xml, Ckaa, t 44; 37G (1972))
It is expected that there will be a new level of success. First, polymerization, resin O
If it is possible to reduce the size of the solvent and increase its mechanical strength through Il conversion, it will be easy to collect, collect, and reuse it, for example, as a phase transfer catalyst heavy metal ion extractant, etc.)
The industrial value is also high.

The N-unsubstituted diaza crown ether chain is a functional crown ether that has the above characteristics due to the presence of two secondary amino groups (NH) that determine its reactivity, and is of interest both theoretically and industrially. Compounds, furthermore, cryptand compounds (crypt-' tands)
), Larjat ether A54t (ml, /
It is also useful as an intermediate for the synthesis of two heptadides.

Several rounding methods for preparing Shea's Crown Ether II have already been proposed. 11 For example, as shown in the following equation,
The most common method is to condense the -1--cya i nobolyether with polyether dicarboxylic acid chloride under high dilution and reduce the resulting free-form cya with water-volcanized lithium aluminum cum (J, M, Lekxs et
ml *Tetrabedron Letters
el 969.

2885).

However, this method requires several steps to prepare the starting materials, and requires a long reaction time under high dilution in the case of in-situ combined reactions. There are various drawbacks such as the use of expensive water-volcanized lithium aluminum as a reducing agent for the L and L intermediate products and ll-type diamide, and the overall yield is low due to the large number of pre-processes.
Large-scale manufacturing does not necessarily require a single step.

In addition to this method, the starting material is ditrifluoroacetocytosyland, which is reacted with polyethylene dalycol ditosylate or polyethylene glycol dichloride to produce the corresponding N-substituted diamine ether.
Next, a method is known in which the N-bonding group of the excipient compound is eliminated (Kumiden・tml, J, 0.c, 39.131
5(11174)sV”agt le, mnm.

Ckem, 1977, 1344, etc.), but such a method involves the introduction of an N-substituent on the starting diamide and the rounding via the elimination process of the carrier group from the intermediate N-substituted diaza crown ethers. However, in addition to the inevitable increase in the number of knees, the introduction and elimination operations of the binding groups themselves are extremely troublesome, the total dissolution rate is low, and the manufacturing cost is also extremely high, so it is not suitable for industrial use. Difficult to apply hawk.

The present invention has been made in view of the above, and an object of the present invention is to provide a new method for manufacturing industrially advantageous KN-N-unsubstituted digurane ether. According to the present invention, from a diamino polyether represented by the following general formula α), which can be obtained in various ways by the reaction of d polyethylene glycol diamine and chlorohydrin, and a polyethylene glycol trout conductor represented by the following general formula (II), - It is possible to produce the targeted diaza crown ether @ta, and it is unique in that it does not involve any separation or cyclization condensation intermediates, which is different from conventional methods.

That is, the present invention relates to a diamino polyether represented by the general formula (1) (wherein the middle of the formula is 0 to 4, p indicates the number of O to 4, and θ to 4), and a diamino polyether represented by the general formula () [ However, in the formula, X is )・rogen atom or -〇-80! -14
(R' represents an alkyl group, an aryl group, or an aralkyl group), and q represents the constitution of 1-Is] in the presence of a metal compound having casting effect ijk. General formula (厘) to react with t4I mold (however, 1 m in 1 formula @ If a p
Iden is a prepared aqueous solution of sheazu taraqun ethers represented by -[,(
The diamino polyether shown in I) is an oligoethylene dalicol dichloride represented by the general formula d (Xu (where p has the same meaning as above) and the general formula Φ) (or m) (However, Feng (or Ugly) reaction with oligoethylene glycolamine represented by the general formula (C) (same meaning as in the company's preface), It can be produced by reaction with chlorohydrin represented by the formula @) (or m) (where a (or m) has the same meaning as above).

The following are representative examples.

The polyethylene glycol trout conductor represented by the general formula (2), which is the starting material for the first step, may be diethylene glycol, triethylene glycol, tetraethylene glycol, pentaethylene glycol, hexaethylene glycol, or each dichloride (e.g., dichloride, dichloride, etc.), sialkanesulfonate (for example,
dimethane sulfonate, dimethane sulfonate, etc.),
Syarene sulfonate (e.g. dibenzyl sulfonate, di-p-)ruene sulfonate (ditosylate)
, or dibenzyl sulfonate.

Further, as the metal compound having a template effect that is allowed to coexist in the reaction system, alkali metals, their hydroxides, hydroxides, 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 water hydride, potassium hydride, lithium hydride, calcium hydroxide, calcium hydride, sodium- Examples include 1-butoxide and potassium-1-butoxide. The amount of these metal compounds used is 21
It is sufficient that the amount is at least chemically equivalent to 1 hydroxyl group, and in the case of an alkali metal compound, it is at least twice the molar amount, preferably L
It is 5 to 4 times the mole.

The reaction according to the invention is usually carried out in an inert organic solvent. Suitable solvents include, for example, diethyl ether, tetrahydrofuran, dioxane, monogutime, diglyme, dimethylsulfonoxide, N,N-dimethylformand, t-pumenol, hexamethylphosphoric triamide,
Examples include methylene chloride, carbon tetrachloride, pyridine, chlorine, and mixed solvents thereof.

In the present invention, diaminopolyether α) and polyethylene glycol tli4 bodies lDt molar ratio 1 j IK
It is reacted in the presence of a metal compound that has a template effect.

Usually, a cast wave of polyethylene glycol trout conductor (2) is gradually poured into a solution containing diamino polyether α) and a predetermined amount of the above metal compound while stirring. Alternatively, they may be prepared separately and dropped into the fII solution of the metal compound at the time of *5ntlii of the nine diamino polyether (1) and the polyethylene glycol conductor (2).

! The reaction temperature varies depending on the Iil[K of the polyethylene glycol trout conductor (2) to be reacted with the diaminopolyether α), and in the case of polyethylene glycol ditosylate, it ranges from room temperature to the degree of reduction of the solvent, preferably about 40 to 8
A temperature of about 60°C to 120°C is suitable for storing polyethylene glycol dichloride at 0°C.

After the completion of the reaction, the target product can be isolated by single-liquid extraction of the reaction mixture or by thermal decomposition vaporization method, and if necessary, it can be fractionated as a sulfur complex compound, and this can be thermally decomposed. It can also be made into a tank product.

According to the present invention, unlike conventional methods, there is no need to go through a cyclization and combination intermediate, and furthermore, the introduction and elimination steps of a holding group are omitted.
Since the target N-unsubstituted diaza crown ethers can be easily produced while shortening the reaction process, it can be said that its industrial significance is deceptively large.

This will be explained in detail below using F% reference examples and examples.

Reference example 16.9-dioxa-3,12-diaza-1,1
4 Tetradecanol.

Seven ethanolamine 451.1 F (1-1 l) and carbonic power 9131.1 F (0,225%k)t!
Into a 0.0-d eggplant flask, 1 and 7 t (11 mol) of triethylene glycol dichloride were slowly added dropwise under stirring. After the addition of 1 drop, the reaction was carried out at 120°C for 24 hours, and the reaction solution was then filtered to remove the by-product salt. By tr/Ta. Wash the salt with a small amount of methanol, combine the washing solution and P solution, and compress under reduced pressure! Fractional distillation with I moat 2L 6tf Kugelrohr, 170℃~17s℃/Q, OI Tor
r () fraction tlIftlle. Yield: 49-0 Furthermore, when this fraction is left to stand, it forms a sphere, and ether-methanol (99:
1) Recrystallized from the warm combination to a melting point of @1. S~62.5
Obtain a white solid at °C.

Reference example 2 6.9112-) sr+t-3,1! i~Diaza-1,17-heptadecane.

Reference Example IK* Instead of triethylene glycol dichloride, tetraethylene glycol dichloride 23.1F
(Other than using (11 mol), the same operation sound as in Reference Example 1 was repeated to make diaminopolyether 180~Il1℃/
0.01 Torr f1! L4 was obtained, yield 2
4-0 Reference example 3 6,9,12,15-tetraochina 3t18
-Diaza-1,20-eicosandiol.

In reference example IK#, in place of triethylene glycol dichloride, pentaethylene glycol dichloride 27.5
? (0.1 mol) The same operation as in Reference Example 1 was repeated except for the friend, and diamino polyether 120-125℃/
0.005 Torr f 14. Art and Friends/Yield 4
5s.

Reference Example 43-Oimasu-6,9-Diaza-"l.

11-Undeca/diol.

H N-(2-hydroxyethyl)ethylenecyanene 104
9 (1.0 mol) tosyethylene glycol\ can be synthesized from 12.5 f (0.14 mol) monochloride in the same manner as in Reference Example 1, yield [2S t (・S-
).

Example 1 Preparation of 1.10-diaza-21-crown-7 Metallic potassium 1.6f in t-butanol 30011j
(0,068 mol), 8.00 t (0,034 mol) of 3,12-diaza-6,9-dioxa-1,14-tetradecanediol was added, and diethylene glycol ditosiloxane was added under stirring at 40°C. Rate 141f (0
, 034 mol) NODI*++7100 dlli[t'' was gradually added dropwise over 2 hours. After further reaction at 40° C. for 2 hours, the precipitated salt was separated by IP and the solvent was distilled off.

Add 300 dl of water to the residue and extract with 150 ml of n-hexane to remove the hexane-soluble matter.

After CkhC4* was distilled off, the residue was subjected to thermal decomposition distillation at 120-125°C/0.005 Torr using a Kugelrohr distillation apparatus to obtain 2.10 ft of a light colored viscous liquid. Yield 2
0-0 elemental analysis, M8. It was confirmed from NMR and IR spectra that it was the desired product.

Elemental analysis (s) Actual value (calculated value) C55,01(54,88)H9
,65 (9,87) N 8.97 (9,14) NMR (CDCjm, a) 2.57 (s, 2H)
2.70 (t.

3.65 (s+m, 20H) MS (m/e) 306 (M), 275.23
8゜231.217,187. IT2e 12 IR(neat) 338G(W)2920(1
)241110(s)144G(s) 1358(so)111G(s)cm-”Example 2 1
．． 8H) Dissolve the metal potassium L33f (0,034 mol) in i-butanol 150-, add 12.2 f of sodium bromide (04)85 mole) and 3,1
Add 4.00 f (0JJ17%k) of 2-cyaz-6,9-dios-1,14-tetradecanediol and heat at 40°C? ``Diethylene glycol dichloride 2 under stirring
．． 42F (0,017 mol) in dioxane 5014@
Nine drops *t2 hours Vrl! It was added dropwise and reacted for an additional 10 hours. Thereafter, it was treated in the same manner as in Example 1 to obtain 1.10
-Diaza-21-crown-7i0.38F was obtained. Yield 7-0 Example 3 Preparation of 1,7-diaza-18-crown-6 10sf of metallic potassium (0,
052% Le) tie, to which s,I-diaza-6-
Add oxa-1,11-undecanediol and 40℃
While stirring at
Q, 8 f (0,0!@Kamuru)'s Geokis 7100a
gll*tIt took 2 hours to drip. After further reacting at 40℃ for 2 hours, the same operation as in Example 1 was repeated to obtain the desired product! I got 42f.

b, p, 105-110℃/0.00! Torr
(Kugej'1zo-ru) + m, p, 101-1
03℃.

'i(NMR(CDC1s,s) 5L31(1,2)
1) λ75 (t, aH) 3.60FI (1+Peng #1@H
) M8 (wn/e) 262(M), 19
4.171162.132 I R332G(W), 292G(1) 52870
('), 148G (1).

1360 (sn), 111G (turtle) Example 4 Preparation of l,7-diaza-21-talalan-7 Metallic potassium 103F (0
,052 mol) After t-hydrolysis, 3 + 9-diaza-
6-Oxa-1,11-undecanediol5. Of
(0,026 mol) and stirred at 40°C, 11.9 t (0,02 mol) of triethylene glycol ditosylate was added.
6 mol) of 1 dioquine was dissolved in 100 mol of dioquine and added dropwise for 95 atz hours, followed by further reaction for 2 hours. Thereafter, the same operation as in Example 1 was carried out.
2H) 4711(t, 8H)L@2(s+as, 20
H) MS (n/e) sos (M+), zss,
zys.

23g! 20,208,1718 IR(neat) 332G(W), 2930
(1).

zssBs), l4@O(&> 11350
(an)-1110 (M'P45 1,10-Schiff f-24-1'jpfp
Potassium hydroxide A 5 in dimethyl sulfoxide 200
．． 1F (0,034%k) and 3.12-cyaz-6,9-dioxa-1,14-tetradecanedio-k
4. Of (Q, 017 moles) f plus 40T, -
7. Triethylene glycol ditosylate under stirring.
8f (0,017(l)t dimethyl sulfoxide 501
Ilt dissolved #l solution [Stand for 2 hours and drip, then add 2 more
Allowed time to react. Thereafter, the same operation as in Example 1 was performed to obtain the target object 0.89f[-1. j[K15111゜b
, p, 135~l 40'C/0.005 To
rr (Kugerrohr) 'HNMR (CDCl5.a) 2.42 (s, 2H)
, 2.74 (t, 8H) 3, εz ya (s-+-m
, 2<H') MS (m/e) 350
(M+)IR(neat) 3360(W)
, 2920(”).

1460(1), 1350(m).

1110 (m) Example 61.4 - Preparation of Sheazu-21-Crown-7 Metallic force 9951 in t-butanol 600. Lu f(0
.
50% of tetraethylene glycol tosylate under stirring.
2 f (0,1 mok) with dioxane 150+jl (@
The solution was added dropwise over a period of 2 hours and reacted for an additional 2 hours.Then the same procedure as in Example 1 was carried out to obtain the desired product as a pale yellow liquid with a yield of 45. dl
k, b, p, 16G~155℃/0.005
Torr.

'I(NMR(CDCha,a) z3z(sp2n),
tss (ipan) 2.68 (t, 4H) 3.48-3.82 (m, 20H) Example 7 Preparation of l,4-diaza-21-crown-7 Metallic potassium 3 in t-butanol 200- .1st(
0,079 mol) and then 3,6-diazu-9-
Oxygen-1.11-Undeca/Diol 9.61F (0
, 05 mol) was added, and while stirring at 40°C, the triethylene glycol cytosine) 138f (0.03 mol) [dioquine] was dissolved in 50 ml. 3.49 fl of the target product was obtained. Yield 3g11
゜Patent Applicant: Kuro no Koritishiki★Shadai Tsujin Michio Goto

Claims (1)

[Claims] (1) General formula (I) (wherein mkio~4, p is 0~4, n is 0
(indicates an integer of ~4) and the general formula (n) [wherein X is a halogen atom, or -α4α5-Rl (R' represents an alkyl group, an aryl group, or an aralkyl group)] , qG''! indicates 1 to 5 lk ridges] In the presence of a polyethylene conductor and a metallized food having a lid effect (where IEI
@ m e p and q have the same meanings as above) A method for producing a sheazu crown ether chain represented by: 2) The production method according to claim (1), wherein the metallized food having a cast pot effect is a leveled product or a water bulked product of an alkali metal or alkaline earth metal. (3) The manufacturing method according to item (1) of the patent claim, wherein the metal compound having a cast lid effect is an alkali metal alkoxide. (4) At least 2 based on diamino polyether
Claim II fil ( The manufacturing method described in section 1).