JPS60184093A - Preparation of monomer similar to phospholipid - Google Patents

Abstract

PURPOSE:To obtain the titled starting monomer suitable as a high polymer for a material of an active transport membrane simply in high yield, by reacting a specific vinyl compound with chloro-oxo-dioxaphosphorane in the presence of a tertiary amine, reacting further the reaction product with an amine. CONSTITUTION:A compound (e.g., compound shown by the formula II, etc.) shown by the formula I (R<1> is H, or alkyl; A is organic group) is reacted with 2- chloro-2-oxo-1,3,2-dioxophosphorane shown by the formula III in the presence of a tertiary amine such as triethylamine, etc. usually in a solvent such as THF, etc. preferably at -50-0 deg.C for 30min- several hr, to prepare a compound shown by the formula IV first. Then this compound is reacted with an amine [preferably shown by the formula VI (R' is 6-30C alkyl)] shown by the formula V(R<2> is H, CH3, or C2H5; B<1> is alkyl, alkenyl, etc.; B<2> is >=3C alkyl, alkenyl, etc.), to give the desired compound shown by the formula VII.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a phospholipid-like monomer, and more particularly, to a method for producing a compound other than the compound represented by the following general formula (1).

[In the formula (I), R1 represents a hydrogen atom or an alkyl group,
A represents an organic group, R2 represents a hydrogen atom, a methyl group, or an ethyl group, Bl represents an alkyl group, an alkenyl group, or an alkyloxyalkyl group; 732 represents an alkyl group, an alkenyl group, or an alkyl group having 3 or more carbon atoms; The purpose of the present invention is to provide an extremely simple and high-yield production process for the above-mentioned phospholipid-like monomer, and this purpose is to provide a process for producing the above-mentioned phospholipid-like monomer, which is expressed by the following general formula (...) according to the method of the present invention. with compounds.

on, = c-A-on (11) ■ ] (1 [(...) in the formula, R1 and A have the same meaning as in the front leg general formula (1) K] 2 Goriroi---oxy/,!, , 2-dioxaphosphorane in the presence of a tertiary amine to produce a compound represented by the following general formula (II), [(m) where R1 and A are paw to mosquito formula ( Same meaning as in 1)] Next, a compound represented by general formula (1).

This is achieved by a process of reacting with an amine represented by the following general formula (■).

\B2 [(■) In the formula, R2, Bl and B2 are the front leg general formula (
The same meaning as in 1)] To describe the present invention in detail, the forepaw general formula (n) (n represents an integer from 7 to 7.2).

-0-NH+OH2+m (here, m indicates an integer from / to evening).

Knee O-0+OHJ, OH+OH, ), 0H3 (Kokote,
A represents an integer of /~311, J- represents an integer of θ~ko) or p
, R1 is a hydrogen atom or a methyl group. A concrete example is the first order υ.

OH3 0H,=O-co,, (OH2)20HCH1 ■ an2=a-co, (C!H2)e OHH8 0H, 0-Co, (OH,), oOHO)i,,
0H-0ONHO Horse 0H OH,=OR-Co,OH,0HOH3OH Co-chloro-co-oxo to be reacted with the above compound/,
! , 2-dioxaphosphorane is a compound represented by the following formula (V).

As a tertiary amine used in the reaction.

Examples include trialkylamines such as trimethylamine and triethylamine.

The amounts of both forefoot reaction components and tertiary amine used are r/1 of each other! Equimolar amounts are sufficient. The solvent used during the reaction is ML, which dissolves the first component, tertiary amine, and reaction product.
Preferably something wet.

Examples include diethyl ether, tetrahydrofuran, and the like. The reaction may be carried out by mixing the image component and the tertiary amine in a solvent, and allowing the reaction to occur at a temperature of 0.degree. C. to 0.degree. C. for 30 minutes to several hours.

By the reaction represented by the following reaction formula, general formula (III)
A compound represented by can be obtained quantitatively.

1 (II) (Ill) Since the by-product tertiary amine hydrochloride 1 usually precipitates,
Can be easily separated.

Next, a method for reacting the compound represented by general formula (m) with an amine will be discussed.

The amine used here is a compound represented by the general formula (IV), where R2 represents a hydrogen atom, a methyl group, or an ethyl group, and B1 represents an alkyl group, an alkenyl group, or an alkyloxyalkyl group. 332 indicates carbon number 3
1. Indicates the above alkyl group, alkenyl group or alkyloyloxyalkyl group. As the alkyl group of B1, various saturated or unsaturated alkyl groups having carbon number/~3° are used.
The alkenyl group of 31 and B2 has a carbon number of 2 to 3Q
Various alkenyl groups of B1 and B2 are various saturated or unsaturated alkyls having carbon number/~3θ as the corresponding alkyl moieties constituting the alkyloxyalkyl groups of B.
As the alkyl group for y, a saturated or unsaturated alkyl group having 3 or more carbon atoms can be used.

The amine is preferably water-insoluble, and from a four-body perspective, amines having 6 or more carbon atoms are preferred in terms of the number of carbon atoms mentioned above.

Particularly preferred amines are compounds represented by the following general formulas (a) to (d).

In the above formula (a), R' represents a long chain saturated or unsaturated alkyl group having 6 to 3 θ carbon atoms, specifically hexyl, hegetyl, octyl, nonyl, tecyl, pentadecyl, eicosyl, triacontyl, or any of these. represents an unsaturated alkyl group corresponding to

In the above He(1)) to (d) formulas, R" represents a saturated or unsaturated alkyl group having 6 to 3[theta] carbon atoms as described above.

The alkyloyloxyalkylamines represented by formulas (1) to (1) above can be easily obtained, for example, by the following reaction according to a known method.

R"0OOH-4R"OOOA Use of the amine represented by the general formula (IV) is:

It may be at least equimolar to the compound represented by the general formula (Ill).

Solvents used during the reaction include acetonitrile,
Methanol, dimethylformamide (N,N-dimethylacetamide or N-methyl-copyrrolidone) are preferred. The reaction is carried out by mixing the image components in a solvent at room temperature to 6θ
If the reaction is carried out at a temperature of about 0.degree. C. for several hours to more than ten hours, the compound represented by the general formula (1) can be obtained in high yield by the reaction represented by the following reaction formula.

The reaction product, the compound of formula (1), is dissolved in chloroform or methanol and then added to a large amount of acetone to precipitate it.

Can be easily purified.

The compound of formula (1) thus obtained can be easily polymerized by radical polymerization to obtain a vinyl polymer having a phospholipid polar group in its side chain. The polymer is expected to be used as a material for active transport membranes.

Next, the present invention will be explained in more detail based on examples.

Reference example-/-2-chloro-1-co-oxo/, 3. KoO
bemiStry and engineering industry, Oet
,,20. (/96.2).

/J', 2/ g ty) R08, Edmunde
I followed the method on.

Corkrollo/, 3. ．． 2-Dioxaphosphorane O and 2-dioxaphosphorane were dissolved in dry benzene/θθ-.

Add dry oxygen to this solution at room temperature! The time passed.

The solution became slightly exothermic. After the oxidation reaction, it is distilled.

9! α) was obtained from the yield of rice cake. The melting point was 39-4t2°C, which was consistent with the literature.

Hydroxyethyl methacrylate/3. θ2(0,1
mole) totriethylamine 9.34-f(0,705
mol) was placed in dry diethyl ether/tOtnl, and while cooling to -20°C, the compound λSt (0.1 mol) synthesized in Reference Example-7 was added dropwise. During the dropping, the temperature of the reaction water was maintained at 0 to -10°C. After the dropwise addition was completed, stirring was continued for 2 hours under water cooling. Further, the circle was allowed to react for 3θ minutes at room temperature. After the reaction was completed, the triethylamine salt #salt was removed, and diethyl ether was completely distilled off to obtain (2). This stuff was a viscous liquid. Confirmation is by elemental analysis and NMR engineering
I went there. Elemental analysis: O (total 111-value 4toB, analysis value 4t/, / / ) H (calculated value!, evening/1 analysis value s
, ts). Revenue is 9! It was Chi.

■y synthesized in Reference Example-2, 4t4tf (0,04t
mole) and dimethyldodecylamine/θ, 72 (θ, O!
mol) and acetonitrile trotn1 were placed in a pressure-resistant reaction tube, and reacted with shaking at 20° C. for 4 trr.

Immediately after the reaction started, the mixture was concentrated under reduced pressure, and n-hexane was added thereto to remove the precipitated pale brown liquid. Washing with n-hexane was repeated several times to obtain ■. ! What's the yield? θchi. Confirmation was performed by elemental analysis and engineering R.

Elemental analysis 20 (calculated value jza, lθ1 analytical value j?, /J-
), H (calculated value, ?θ1 analysis value?, z, r).

N (calculated value 3./, 2. analyzed value 3.4t r ). Engineering R
is the same as in Figure 1. Example 3 was obtained in the same manner as in Example 1, except that the same number of moles of dimethyloctadecylamine was used instead of dimethyldodecylamine. yield? ! blood.

Elemental analysis (calculated value: analytical value) a (6i, θg.

Niko, θ4t) IIH (io, j/, 9.90) SN (
2, t 3. s, io). Engineering R is the pick-up point in Figure 2.

Using the same number of moles of oleic acid dimethylaminoethyl ester instead of dimethyldodecylamine, one reaction time was 1.
The same procedure as in Example 1 was carried out except that the time was changed to 10 hours, and ■ was obtained. Yield 70%.

Elemental analysis (calculated value; analytical value) ○ (4/, /ko.

1 0, ta? ), H (wa,!/, ?0.?/), N
(2,31°2.3.Engine R is the same as shown in Figure 3.

[Brief explanation of drawings]

1st. Figures J and J are 2-(methacryloyloxy)ethyl-'(dimethyldodecyl ammonium), respectively.
Ethyl phosphate, 2-(methacryloyloxy)ethyl-,2'-(dimethyloctatecylammonium)ethyl phosphate 1.2-(methacryloyloxy)ethyl-2
It is a process chart of '-(oleyloxyethyldimethylammonium)ethyl phosphoric acid. Patent applicant Mitsubishi Chemical Industries, Ltd. Agent Patent attorney Hase - Haka/First name

Claims (1)

[Claims] (1) A compound represented by the following general formula (II). OH, = 0-A-OH (1)
A represents an organic group] A compound represented by the following general formula (1) is produced by reacting cochloro-oxo/, j,, 2-dioxaphosphorane in the presence of a tertiary amine. death. RI O [(Ill) where ・'R1 and All1, front paw (Ill)
) has the same meaning as in the formula] Furthermore, a compound represented by the general formula (1). 2 N-B' (1v) \B nitrogen [V represents a hydrogen atom, a methyl group, or a methyl group; %BI represents an alkyl group, an alkenyl group, or an alkyloyloxyalkyl [(■ ), where R', A, R'', B' and B2
is the same as the meaning in the front leg general formulas (1) and (ff)]