WO2008142101A1

WO2008142101A1 - Method for producing urethanes having multiple carbonate end groups

Info

Publication number: WO2008142101A1
Application number: PCT/EP2008/056244
Authority: WO
Inventors: Andreas Job; Lars Rodefeld
Original assignee: Saltigo Gmbh
Priority date: 2007-05-21
Filing date: 2008-05-21
Publication date: 2008-11-27
Also published as: DE102007023868A1

Abstract

The invention relates to an improved method for producing carbonate-terminated urethanes using di- or polyisocyanates. The method according to the invention is characterized by high yields with no phenol being produced as a secondary component.

Description

Process for the preparation of polycarbonate-terminated urethanes

The present invention relates to a process for preparing polycarbonate-terminated urethanes.

For a variety of materials and applications, the permanent functionalization of surfaces is important. Material surfaces can be made biocompatible, for example, by coating with heparin. Other applications include antisoiling and bacteriostatic finishing and improving the adhesion of adhesives and paints.

The targeted modification of biomolecules is desirable in many cases. For example, it is known that the biological half-life of various drugs can be improved by adding polyoxyalkylene radicals.

From EP-A-I 541 568, for example, reactive cyclic carbonates of the general formula 1 are known,

where R ^'is Ci-Ci ₂ alkylene and R "can represent a variety of organic radicals These reactive cychschen carbonates can be reacted with nucleophiles, such as hydroxy or primary or secondary amino groups of biomolecules, polymers or on substrate surfaces, where it is used to open the cyclic carbonation comes with simultaneous covalent attachment to the biomolecule, the polymer or other substrate surfaces.

The preparation of the reactive cybernic carbonates of the formula (1) takes place by reaction of the phenyl-substituted cyan carbonates of the general formula (2),

with amines of the general formula (3) H ₂ NR ^" (3) A disadvantage of this synthesis is the release of phenol as a by-product of the substitution with the amine in equimolar amounts. Depending on the obtained reaction product of the formula (1), the separation of the toxicologically problematic phenol is associated with great expense.

US-A-5,115,045 relates to isocyanate-reactive compositions useful in the preparation of

Polyurethanes are used. These isocyanate-reactive compositions are based on the reaction product of (a) a di- or polychloroformate ester of the type Q- [X-CO Y] _n , where X can be oxygen and Y is chlorine, n is at least 2 and Q is an organic radical, with (b) a multifunctional compound which, in addition to the functional groups which react with the di- or polychloroformate ester (a), must contain at least one

Enammogroup must contain. No di- or polychloroformate esters (a) are described which have cyclic carbonate groups. The di- or polychloroformate esters are prepared by reacting polyols with acylating agents such as phosgene. From the imino and / or enamino groups contained in the multi-functional compound (b), an isocyanate-reactive amino group can later be obtained by hydrolysis.

From DE-A-26 095 02 a method is known in which a bi-functional isocyanate can be reacted with a polyoxyalkylenepolyamine. This coupling products are obtained, which are interconnected via urea groups.

From EP-A-0 328 150 a process is known which describes the reaction of cyclocarbonate-terminated alcohols with carboxylic acid anhydrides. Cyclocarbonate-terminated esters are obtained which can be used for a variety of other reactions. Also described in Example 18 is the reaction of hexamethylene diisocyanate with glycerol cyclocarbonate in dimethoxyethane. Here is a clear surplus of 3

Equivalent hexamethylene diisocyanate based on 1 equivalent Glycerincyclocarbonat used. The removal of the remaining after the reaction hexamethylene diisocyanate is an economically and environmentally undesirable addition step.

Since there is a high demand for reactive cyclic carbonates for surface treatment, this invention has the object to provide an improved manufacturing process.

The invention relates to a process for the preparation of compounds of general formula (I),

embedded image in which

R ^{1 is} dC-alkylene, k is an integer greater than 1 and

R is a k-valent aliphatic, cycloaliphatic, aromatic or araliphatic hydrocarbon radical which optionally contains one or more heteroatoms, by reaction of a compound of the general formula (II)

wherein R ^{1 has} the meaning given for general formula (I), with a compound of general formula (III),

[° ^CN i FT (III)

wherein k and R ^{2 have} the meanings given for the general formula (I), wherein 1-2 equivalents of the compound of the general formula (II) based on 1 equivalent of the

Compound of the general formula (IH) can be used.

An advantage of the inventive method is the avoidance of phenol as a minor component. It is particularly advantageous that this reaction is an addition reaction in which, in principle, no further secondary components are formed. It is thus a process which yields a complete atomic-economical yield. In addition, it is not necessary to use the di- or polyisocyanate of the general formula (III) in an excess. A separation of excess di- or polyisocyanate according to the inventive implementation is therefore usually not required. Nevertheless, excellent yields of the desired compound of the general formula (I) are obtained

The isocyanates of the general formula (III) can be prepared by reacting the corresponding amines of the general formula (IV) with phosgene,

wherein k and R have the meanings given for the general formula (I),

If the term "substituted" is used in this application, this means for the purposes of this application that a hydrogen atom on a specified radical or atom is replaced by one of the groups indicated, with the proviso that the valence of the atom indicated does not is exceeded and the substitution leads to a stable compound

In the context of this application and invention, all definitions of residues, parameters or explanations mentioned above, and also referred to below, general or preferred ranges, may be combined with one another in a meaningful manner, ie also between the respective ranges and preferred ranges.

In the process according to the invention, preference is given to using compounds of the general formula (II) in which R ¹ denotes a C ₁ -C ₆ -alkylene radical, particularly preferably a methylene, ethylene,

Propylene, n-butylene or n-hexamethylene radical represents.

Suitably in the process according to the invention are compounds of the general formula

(πi) used, wherein k is an integer greater than 1, in particular 2 or 3,

R ^{2 is} a k-valent, especially dl- or trivalent, aliphatic, cycloahphatic, aromatic or araliphatic hydrocarbon radical which optionally contains one or more heteroatoms.

Preference is given to using compounds of the general formula (III) in which k is 2 or 3,

R ^{2 is} a di- or trivalent, ahphatischen, cycloaliphaüschen, aromatic or araliphatic hydrocarbon radical containing only one or more oxygen atoms as heteroatoms.

Particular preference is furthermore given to using compounds of the general formula (III) in which k is 2, R ^{2 is} a - [(C ₂ -C ₆ -alkylene-O-) χ- (C ₂ -C ₆ -alkylene)] - group in which the two

Alkylene units are the same or different and x = 1-50, preferably x = 1-40, or is a

- [(C ₂ -C ₆ -alkylene-O-) _x - (C ₂ -C ₆ -alkylene-O-) _y - (C ₂ -C ₆ -alkylene-O-) _z -C _r C ₆ -alkylene] - Group is, wherein the three Alkylenemheiten different smd or the first may be identical to the third, and wherein x = 0-50, in particular x = 1-40, y = 1-50, in particular y = 1-40, and z = 1-50, in particular z = 1-40.

Suitable amines of the general formula (IV) which can be used for the preparation of the compounds of the general formula (III) are, for example, the following:

Polyether diamides, ethylene diamine, propylene diamine, butylene diamine, hexamethylene diamine, MDA, TDA, diarmnobenzene, diammocyclohexane, diammomethylcyclohexane, TCD-Diamm, 1,4-bis- (3-ammopropyloxy) butane, Tπs- (2-ammoethyl) amm, l, 4- Bis (3-ammopropyl) prperazm, bis (3-ammopropyl) amm and triethylene.

Examples of suitable polyetherdiams of the general formula (IV) which can be used to prepare the compounds of the general formula (III) are commercial products of the Huntsman Corporation such as Jeffamm D-230, Jeffamm D-400, Jeffamm D-2000, Jeffamm D-4000, Jeffamm ED-600, Jeffamm ED-2003 and Jeffamm EDR-148.

In the process according to the invention, 1 to 2 equivalents of the compound of the general formula (II) are used relative to 1 equivalent of the compound of the general formula (III). Preference is given to using 1 to 1.5 equivalents, more preferably 1 to 1.2 equivalents and in particular 1 equivalent of the compound of general formula (IT) based on 1 equivalent of the compound of general formula (III).

The erfmdungsgemäße process is usually carried out at a temperature in the range of 0 ⁰ C to 22O ⁰ C. Preferably, the erfmdungsgemäße process at a temperature in the range of 10 ⁰ C to 200 ⁰ C and particularly preferably in the range of 20 ⁰ C to 15O ⁰ C performed

The inventive method can be carried out so that the compound of general formula (III), optionally dissolved in an inert solvent, and then the compound of general formula (II), optionally also dissolved in the same or m a different inert solvent to which isocyanate is added. In an alternative embodiment, the compound of the general formula (Η) is initially charged and then the compound of the general formula (III) is added, where both substances may optionally be diluted with the same or different inert solvent.

The method according to the invention can also be operated continuously. In doing so, the

Addition of the di- or polyisocyanate of the general formula (III) simultaneously with the addition of the compound of the general formula (H) in a suitable apparatus.

It should be expressly mentioned that both of the aforementioned embodiments can also be carried out in the absence of solvents.

Suitable solvents are, for example, toluene, xylenes, chlorobenzene, 1,2-dichlorobenzene, tetrahydrofuran, diethyl ether, dioxane, methyltetrahydrofuran, cyclopentylmethyl ether, dibutyl ether, 1,2-dichloroethane, dichloromethane, chloroform, dimethoxyethane, acetonitrile, cyclohexane, methylcyclohexane, cyclopentane, heptane, Hexane, diethylene glycol dimethyl ether,

Ethylbenzene and methyl tert-butyl ether.

The isolation of the compounds of the general formula (I) can be carried out by distillation, crystallization, chromatography or freeze-drying.

The compounds of the general formula (I) obtained by the process according to the invention can be reacted with functional groups, such as hydroxy groups or primary or secondary amino groups, which are contained in biomolecules, polymers or substrate surfaces. The cyclic carbonate ring is opened with covalent bonding to the Biomolecule, the polymer or the substrate surface. In this way it is possible to introduce the above-defined plurality of radicals R ² and R ³ into biomolecules or polymers or to bind them to substrate surfaces.

The term "biomolecule" is intended to encompass all molecules which can be isolated from biological systems and / or which can interact with biological systems or parts thereof, in particular peptides, proteins, proteoglycans, enzymes, markers, antibodies, receptor molecules, Antigens and drugs Specific examples are heparin, tissue plasminogen activator, streptokinase and prostaglandins.

As polymers, for example, polyamines or polyols can be used. Examples of polyamines are

Polyvinylamine, polyallylamine, polyethylene, chitosan, polyamide-epichlorohydrin resins (available as "Hercosett®" products), polyammostyrene, peptides or proteins such as gelatin. As surfaces that can be treated by this method, for example, the surfaces of materials are suitable which have ammo and / or hydroxyl groups, or surfaces which have been treated by methods known per se with Ammosilanen

In particular, the compounds of the general formula (I) obtained by the process according to the invention can be reacted with diamines to form so-called block copolymers. Suitable diameters are, for example, polyether diamines or diammopolysiloxanes. The latter implementation is disclosed in a German patent application filed on the same day by the Momentive Performance Mateπals.

EXAMPLES

Example 1 (Preparation of the diisocyanate)

In a 1 liter reactor equipped with stirrer, condenser (0 ⁰ C) dropping funnel and gas inlet tube are charged with 300 ml of chlorobenzene and cooled to -10 ⁰ C. 121 g of phosgene are condensed into the cooled solvent. In 42 minutes, a solution of 150 g of Jeffamine ED-600 in 150 g of chlorobenzene is added to this mixture so that the temperature of + 3 ° C is not exceeded. After complete addition, the mixture is continuously heated to 130 ⁰ C within 2 hours. At the temperature of 20 ^° C., a phosgene flow of 55 g / h is started. After reaching the temperature of 130 ⁰ C is stirred for a further hour at this temperature with phosgene. A total of 160 g of phosgene are added. To remove the excess of phosgene of the radiator is now operated at a temperature of 2O ⁰ C and an nitrogen stream of 25 l / h through the reaction mixture. Subsequently, the mixture is cooled to 80 ⁰ C and at reduced pressure (20 mbar) chlorobenzene is distilled off until core distillate can be collected more 162.5 g Dπsocyanat (100% of theory) are obtained.

Example 2 (according to the invention)

In a 0.5 liter reactor with stirrer, condenser (9 ° C) and dropping funnel are charged 27.6 g of glycerol carbonate (90%) in 50 g of chlorobenzene. About the dropping funnel 70.0 g of the diisocyanate from Example 1 dissolved in 60 g of chlorobenzene are added dropwise at 20 ⁰ C. Subsequently, the

Mixture heated to reflux (134 ° C). The conversion is monitored by means of IR spectroscopy. After 38 hours of reaction time no NCO band is detectable by IR spectroscopy more. The mixture is heated to 13O ⁰ C and all volatiles are removed under reduced pressure (2 mbar). There are obtained 93.5 g (98% of theory) of the desired product.

Claims

claims:

1. Process for the preparation of compounds of general formula (I),

wherein R ^{1 is} Ci-C _{] 2} alkylene, k is an integer greater than 1 and R ^{2 is} a k-valent aliphatic, cycloaliphatic, aromatic or araliphatic hydrocarbon radical, optionally one or more

Contains heteroatoms,

by reacting a compound of general formula (II)

wherein R ^{1 has} the meaning given for general formula (I), with a compound of general formula (UT),

OCN 4 J - R (!) K wherein k and R ^{2 have} the meanings given for the general formula (I), where 1-2 equivalents of the compound of the general formula (II) with reference to 1

Equivalent to the compound of the general formula (III) can be used.

2. The method according to claim 1, wherein the compounds of general formula (III) are obtainable by reacting the corresponding amines of general formula (IV) with phosgene

wherein k and R ² have the meanings given for the general formula (I).

3. The method according to claim 1 or 2, wherein compounds of the general formula (II) are used, embedded image in which R ^{1 is} a C] _-C6 alkylene radical, particularly preferably a methylene, ethylene, n-propylene, n-butylene - Represents or n-hexamethylene radical.

4. The method according to one or more of claims 1 to 3, wherein compounds of general formula (III) are used, where kn is an integer greater than 1, in particular 2 or 3, and

R ^{2 is} a k-valent, especially di- or trivalent, aliphatic, cycloaliphatic, aromatic or arahpatic hydrocarbon radical which optionally contains one or more heteroatoms.

5. The method according to one or more of claims 1 to 4, wherein compounds of the general formula (III) are used, in which k is 2 or 3 and R ^{2 is} a di- or trivalent, aliphatic, cycloaliphatic, aromatic or arachphatic hydrocarbon Rest which contains only one or more oxygen atoms as heteroatoms.

6. The method according to one or more of claims 1 to 5, wherein compounds of general formula (III) are used, in which k is 2 and

R ^{2 represents} a - [(C ₂ -C ₆ -alkylene-O-) _X - (C ₂ -C ₆ -alkylene)] - group, the two

Alkylene units are the same or different and x = 1-50, preferably x = 1-40 or for a - [(C ₂ -C ₆ -alkylene-O-) _s - (C ₂ -C ₆ -alkylene-O-) _y - (C ₂ -C ₅ -alkylene-O-) _z -C ₁ -C ₆ -alkylene] -

Group is, wherein the three alkylene units are different or the first may be identical to the dπtten, and wherein x = 0-50, in particular x = 1-40, y = 1-50, in particular y = 1-40, and z = 1-50, in particular z = 1-40.

7. The method according to claim 2, wherein for the preparation of the compounds of the general

Formula (III) as Amme of the general formula (IV) Polyetherdiamme, ethylenediamm, propylenediamine, butylenediamine, hexamethylenediamine, MDA, TDA, diammobenzene, diammocyclohexane, diaminomethylcyclohexane, TCD-diamine, l, 4-bis (3-ammopropyloxy) butane, Tπs - (2-aminoethyl) amm, l, 4-bis (3-ammopropyl) piperazine, bis (3-aminopropyl) amine or triethylenetetramine.

8. The method according to one or more of claims 1 to 7, wherein 1 to 2 equivalents of the compound of general formula (H) based on 1 equivalent of the compound of general formula (III) are used, preferably 1 to 1.5 equivalents, especially preferably 1 to 1.2 equivalents and in particular 1 equivalent of the compound of the general formula (II) based on 1 equivalent of the compound of the general formula

9. The method according to one or more of claims 1 to 8, wherein the method at a temperature in the range of 0 ⁰ C to 220 ° C, preferably in the range of 10 ⁰ C to 200 ⁰ C and particularly preferably in the range of 20 ⁰ C. until 15O ⁰ C is performed.