Polyoxyethylene derivatives having optionally protected...

Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – From silicon reactant having at least one...

Reexamination Certificate

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C528S026000, C528S027000, C528S038000, C528S407000, C528S409000, C528S421000, C556S401000, C556S412000, C560S125000, C560S170000, C560S189000, C560S190000, C560S198000, C560S200000, C564S475000

Reexamination Certificate

active

06388041

ABSTRACT:

TECHNICAL FIELD
This invention relates to polyoxyethylene derivatives having an optionally protected amino group at one end and a process for producing the same. More particularly, this invention relates to polymers or oligomers containing a polyoxyethylene segment and having at one end an amino group which may optionally be protected by an organosilyl type amino-protecting group, and a process for producing the same, as well as living polymerization initiators which can be used in the process.
In this description, the derivatives of the present invention are generically referred to as polyoxyethylene derivatives by prefixing “poly” thereto. However, this concept is used in the broadest sense so as to comprehend polyoxyethylene segment-containing derivatives and oligo-oxyethylene segment-containing derivatives.
BACKGROUND ART
Polyoxyethylene itself, and compounds or block copolymers containing a polyoxyethylene segment, are being extensively used as surfactants, drug carriers and medical materials. For example, it has been proposed that copolymers of ethylene oxide and propylene oxide (e.g., Poloxamer) and the like may be used for the prevention of adhesion of biological tissues [Holtz, Fertil. Steril., 41(1984), 497-507] and as blood flow improvers or the like.
Moreover, in order to impart further functions to polyoxyethylene having such diverse actions, there have been proposed heterotelechelic polyoxyethylenes having various functional groups introduced at both ends of the polyoxyethylene molecule (see, for example, WO96/32434). Among such functional groups, amino and aldehyde groups are stable in water when each of them is present alone. On the other hand, an amino group reacts rapidly, for example, with carboxyl, epoxy and like groups, and an aldehyde group reacts rapidly, for example, with amino, hydroxyl and like groups. Accordingly, they can significantly enhance the functionality of polyoxyethylene derivatives.
However, when such a derivative has amino and aldehyde group at both ends of the molecule, it forms a Schiff base and, therefore, the characteristics of these functional groups cannot be fully utilized. Consequently, if a polyoxyethylene segment-containing derivative having amino and aldehyde groups protected separately by protecting groups which permit the amino and aldehyde groups to be selectively liberated as required could be provided, it would be possible to utilize the amino and aldehyde groups individually at any time according to the intended purpose.
DISCLOSURE OF THE INVENTION
Accordingly, an object of the present invention is to provide polyoxyethylene segment-containing derivatives which have optionally protected amino and aldehyde groups at both ends of the molecule and in which the protecting groups therefor, if present, may be eliminated under different conditions, as well as a process for producing such derivatives.
In order to accomplish the above object, the present inventors have searched for an amine compound which can provide a polymer or oligomer containing a polyoxyethylene segment of a desired chain length, which has a protecting group capable of being eliminated under conditions significantly different from those for the elimination of an acetal group commonly used as a protecting group for the aldehyde group, and in which the propagation reaction of the polyoxyethylene chain can advantageously be initiated on the aminic nitrogen atom by anionic living polymerization. As a result, it has now been found that the above object can be accomplished by using amine compounds protected with certain organosilyl type amino-protecting groups. Moreover, it has also been found that such amine compounds may be extensively used as living polymerization initiators in the form of alkali metal complexes.
Accordingly, the present invention relates to an extensively useful living polymerization process, and more particularly to a process for producing a polyoxyethylene derivative of the formula (I)
wherein:
A′ and B′ each independently represent an organosilyl type amino-protecting group, or represent organosilyl type amino-protecting groups capable of combining with the nitrogen atom adjacent thereto to form a four- to seven-membered disila-azacyclo heterocyclic ring,
Y represents a hydrogen atom, an alkali metal, or an organic group which, when Y is an alkali metal, can be introduced by replacing the alkali metal therewith according to a suitable reaction,
R represents a hydrogen atom or a C
1-6
alkyl group,
n is an integer of 1 to 20,000, and
m is an integer of 0 to 20,000,
the process comprising the steps of polymerizing ethylene oxide in a suitable organic solvent in the presence of a living polymerization initiator of the formula (II)
wherein A′ and B′ have the same meanings as defined for formula (I), and M represents an alkali metal; if necessary, further polymerizing the resulting product with a cyclic diester of the formula (III)
wherein each R independently represents a hydrogen atom or a C
1-6
alkyl group; and, if necessary, reacting the resulting product with a compound having an organic group which, when Y is an alkali metal, can be introduced by replacing the alkali metal therewith.
Some of the derivatives produced by the above-described process are novel and have a unique structure. Accordingly, the present invention also relates to a polyoxyethylene derivative of the following formula (I-a).
wherein:
A and B each independently represent a hydrogen atom or an organosilyl type amino-protecting group, or represent organosilyl type amino-protecting groups capable of combining with the nitrogen atom adjacent thereto to form a four- to seven-membered disila-azacyclo heterocyclic ring,
Y represents a hydrogen atom, an alkali metal, or an organic group which, when Y is an alkali metal, can be introduced according to a suitable reaction,
R represents a hydrogen atom or a C
1-6
alkyl group,
n is an integer of 1 to 20,000, and
m is an integer of 0 to 20,000,
provided that, when both A and B are hydrogen atoms, Y is a group of the formula
wherein D and E each independently represent an alkoxy group, or represent groups capable of combining with the carbon atom adjacent thereto to form 1,3-dioxolane that may be substituted by a lower alkyl group at the 4- or 5-position, or D and E are united together to form an oxo radical (═O), and l is an integer of 0 to 10.
Furthermore, the present invention relates to the use of a compound of the following formula (II) as a living polymerization initiator.
wherein A′ and B′ each independently represent an organosilyl type amino-protecting group, or represent organosilyl type amino-protecting groups capable of combining with the nitrogen atom adjacent thereto to form a four- to seven-membered disila-azacyclo heterocyclic ring, and M represents an alkali metal.


REFERENCES:
patent: 5483008 (1996-01-01), Sakurai et al.
patent: 5493038 (1996-02-01), Hall et al.
patent: 6121474 (2000-09-01), Schwindeman et al.

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