Method for producing polyalkylene glycol derivative with narrow molecular weight distribution, and acetal group-containing alcohol compound for use therein and alkali metal salt thereof

Patent metadata

Field	Value
Publication number	US-9284408-B2
Application number	US-201514596685-A
Country	US
Kind code	B2
Filing date	Jan 14, 2015
Priority date	Jan 16, 2014
Publication date	Mar 15, 2016
Grant date	Mar 15, 2016

Abstract

A method for producing a narrow molecular weight distribution polyalkylene glycol derivative having an amino group at an end is provided and allows for polymerization of ethylene oxide under mild conditions with suppressed occurrence of diol polymer impurities includes at least the steps of polymerizing ethylene oxide by using a compound represented by the following general formula (2) and converting a polymer end to R 3 :

wherein R 1 represents a linear, branched, or cyclic monovalent hydrocarbon group having 1 to 10 carbon atoms;
R 2 represents a linear or branched divalent hydrocarbon group having 1 to 5 carbon atoms;
R 3 represents a linear, branched, or cyclic monovalent hydrocarbon group having 1 to 20 carbon atoms;
M represents sodium or potassium;
m represents an integer of 1 to 5;
n represents an integer of 1 to 450; and
k represents an integer of 1 to 5.

First claim

What is claimed is:

1. A method for producing a narrow molecular weight distribution polyalkylene glycol derivative having an amino group at an end represented by a general formula (7) by using a compound represented by the following general formula (2) as a polymerization initiator:

wherein R 1 each independently represents a linear, branched, or cyclic monovalent hydrocarbon group having 1 to 10 carbon atoms;
R 2 represents a linear or branched divalent hydrocarbon group having 1 to 5 carbon atoms;
m each independently represents an integer of 1 to 5; and
M represents sodium or potassium;
H 2 N—CH 2 —R 2 —(OCH 2 CH 2 ) n —OR 3   (7)

wherein R 2 is the same as defined in the general formula (2);
R 3 represents a linear, branched, or cyclic monovalent hydrocarbon group having 1 to 20 carbon atoms; and
n represents an integer of 1 to 450;
comprising the steps of:
a) reacting a compound represented by the formula (2) with ethylene oxide;
b) reacting a reaction product of the step a) with a compound represented by a general formula (8):
R 3 (OCH 2 CH 2 ) k X  (8)

wherein R 3 is the same as defined in the general formula (7);
k represents an integer of 0 to 5; and
X represents a halogen atom or a leaving group; and

c) reductively aminating a reaction product of the step b).

2. A method for producing a narrow molecular weight distribution polyalkylene glycol derivative having an amino group at an end represented by a general formula (7) comprising the following steps of:
1) a step of reacting a compound represented by the following general formula (2) with ethylene oxide in an organic solvent to obtain a compound represented by the following general formula (3):

wherein R 1 each independently represents a linear, branched, or cyclic monovalent hydrocarbon group having 1 to 10 carbon atoms;
R 2 represents a linear or branched divalent hydrocarbon group having 1 to 5 carbon atoms;
m each independently represents an integer of 1 to 5; and
M represents sodium or potassium;

wherein R 1 , R 2 , m, and M are the same as defined in the general formula (2);
n represents an integer of 1 to 450; and
k represents an integer of 0 to 5;
2) a step of reacting a compound represented by the following general formula (3) with a compound represented by the following general formula (8) to obtain a compound represented by the following general formula (4):
R 3 (OCH 2 CH 2 ) k X  (8)

wherein k is the same as defined in the general formula (3);
R 3 represents a linear, branched, or cyclic monovalent hydrocarbon group having 1 to 20 carbon atoms; and
X represents a halogen atom or a leaving group;

wherein R 1 , R 2 , m, and n, are the same as defined in the general formula (3); and
R 3 is the same as defined in the general formula (8);
3) a step of reacting a compound represented by the general formula (4) with water in the presence of an acid catalyst to obtain a compound represented by the following general formula (5):

wherein R 2 , R 3 , and n are the same as defined in the general formula (4);
4) a step of reacting a compound represented by the general formula (5) with ammonia or hydroxylamine to obtain a compound represented by the following general formula (6):

wherein R 2 , R 3 , and n are the same as defined in the general formula (5); and
R 4 represents a hydrogen atom or a hydroxyl group; and
5) a step of producing a compound represented by the following general formula (7) by a reduction reaction of a compound represented by the general formula (6):
H 2 N—CH 2 —R 2 —(OCH 2 CH 2 ) n —OR 3   (7)

wherein R 2 , R 3 , and n are the same as defined in the general formula (6).

3. The method according to claim 2 , wherein the organic solvent for use in the step 1) is a single solvent or a mixed solvent selected from the group consisting of cyclic ether compounds having 4 to 10 carbon atoms.

4. The method according to claim 2 , wherein the step 1) is performed without an alcohol co-solvent.

5. The method according to claim 2 , further comprising a preceding step of producing a compound represented by the general formula (2) by reacting a compound represented by the following general formula (1) with an alkali metal compound selected from M, M + H − , and R 21 O − M + (wherein M represents sodium or potassium, and R 21 represents an alkyl group having 1 to 6 carbon atoms) prior to the step 1):

wherein R 1 represents a linear, branched, or cyclic monovalent hydrocarbon group having 1 to 10 carbon atoms;
R 2 represents a linear or branched divalent hydrocarbon group having 1 to 5 carbon atoms; and
m represents an integer of 1 to 5.

6. The method according to claim 5 , wherein the reaction is performed so as to have a mass ratio between the compound represented by the general formula (1) and the compound represented by the general formula (2) of 0:100 to 20:80, after completion of the preceding step.

7. The method according to claim 5 , further comprising a step of synthesizing a compound represented by the general formula (1) prior to the preceding step.

8. A narrow molecular weight distribution polyalkylene glycol derivative having an amino group at an end represented by a general formula (7) produced by the method according to claim 1 :
H 2 N—CH 2 —R 2 —(OCH 2 CH 2 ) n —OR 3   (7)

wherein R 2 represents a linear or branched divalent hydrocarbon group having 1 to 5 carbon atoms;
R 3 represents a linear, branched, or cyclic monovalent hydrocarbon group having 1 to 20 carbon atoms; and
n represents an integer of 1 to 450.

9. An acetal group-containing alcohol compound represented by the following general formula (1):

wherein R 1 each independently represents a linear, branched, or cyclic monovalent hydrocarbon group having 1 to 10 carbon atoms;
R 2 represents a linear or branched divalent hydrocarbon group having 1 to 5 carbon atoms; and
m each independently represents an integer of 1 to 5.

10. A metal salt of an acetal group-containing alcohol compound represented by the following general formula (2):

wherein R 1 each independently represents a linear, branched, or cyclic monovalent hydrocarbon group having 1 to 10 carbon atoms;
R 2 represents a linear or branched divalent hydrocarbon group having 1 to 5 carbon atoms;
m each independently represents an integer of 1 to 5; and
M represents sodium or potassium.

11. The method according to claim 3 , wherein the step 1) is perfor

Assignees

• Shinetsu Chemical Co

Inventors

• Suka Yuki
• Harada Yuji
• Watanabe Takeru
• Watanabe Osamu

Classifications

• C08G65/322

  containing hydrogen · CPC title

• C07C43/315

  containing oxygen atoms singly bound to carbon atoms not being acetal carbon atoms · CPC title

• C08G2650/44

  containing acetal or formal groups · CPC title

• A61K47/48215

  Human Necessities · mapped topic

• C07C217/08

  the oxygen atom of the etherified hydroxy group being further bound to an acyclic carbon atom · CPC title