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EP-4739729-A1 - PROCESS FOR THE CONTINUOUS SYNTHESIS OF POLYOXAZOLINES USING A SPIRAL TUBE REACTOR

EP4739729A1EP 4739729 A1EP4739729 A1EP 4739729A1EP-4739729-A1

Abstract

The invention relates to the continuous synthesis of polyoxazolines. The invention also relates to a process for the continuous synthesis of polyoxazolines comprising the step of: conducting at least one oxazoline monomer through a spiral tube reactor under the influence of heat, the spiral tube reactor comprising a helically-wound tube having a tube inner diameter and a diameter of the helical winding, characterised in that: • the tube inner diameter is 4.5 mm to 34 mm and the lambda ratio, as the ratio of the tube inner diameter to the diameter of the helical winding, is in the range of 0.11-0.17, and • the helically-wound tube is a stainless steel tube. The invention also relates to the use of a spiral tube reactor for the continuous synthesis of polyoxazolines, the spiral tube reactor comprising: a helically-wound tube having a tube inner diameter and a diameter of the helical winding, characterised in that: • the tube inner diameter is 4.5 mm to 34 mm and the lambda ratio, as the ratio of the tube inner diameter to the diameter of the helical winding, is in the range of 0.11-0.17, and • the helically-wound tube is a stainless steel tube.

Inventors

  • Wegener, Erik
  • JORDAN, RAINER
  • KIRCHHOF, Lisa
  • THOMAS, Anita

Assignees

  • Technische Universität Dresden Körperschaft des öffentlichen Rechts

Dates

Publication Date
20260513
Application Date
20240611

Claims (14)

  1. 1. Process for the continuous synthesis of polyoxazolines comprising the following step: Passing at least one oxazoline monomer through a spiral tube reactor under the influence of heat, wherein the spiral tube reactor has at least one spirally wound tube with an inner tube diameter and a diameter of the spiral winding, characterized in that: • the pipe inner diameter is in the range of 4.5 mm to 34 mm, and • the lambda ratio as the ratio of the inner pipe diameter to the diameter of the spiral winding is in the range of 0.11 to 0.17, and • the spiral wound pipe is a stainless steel pipe.
  2. 2. Method according to claim 1, characterized in that the pipe inner diameter is 10 mm ± 1 mm.
  3. 3. Method according to claim 1 or 2, characterized in that the lambda ratio is 0.13 ± 0.01.
  4. 4. Method according to one of claims 1 to 3, characterized in that the diameter of the spiral winding is 72 mm ± 7 mm.
  5. 5. Method according to one of claims 1 to 4, characterized in that the wall thickness of the spirally wound tube is 1 mm ± 0.2 mm.
  6. 6. Process according to one of claims 1 to 5, characterized in that the throughput of the oxazoline monomer through the spiral tube reactor is in the range from 6 mmol/min to 480 mmol/min.
  7. 7. Process according to one of claims 1 to 6, characterized in that the concentration of the oxazoline monomer when introduced into the spiral tube reactor is 4 mol/L ± 1.5 mol/L.
  8. 8. Method according to one of claims 1 to 7, characterized in that the Flow rate of the oxazoline monomer through the spiral tube reactor is in the range of 9 mL/min to 11 mL/min.
  9. 9. Process according to one of claims 1 to 8, characterized in that the pressure in the spiral tube reactor is 40 bar ± 5 bar.
  10. 10. The method according to any one of claims 1 to 9, characterized in that after passing a first oxazoline monomer through the spiral tube reactor, at least one further step is carried out, the further step comprising adding at least one further oxazoline monomer different from the first to a reaction mixture comprising the polyoxazoline from the first oxazoline monomer and passing the reaction mixture through the spirally wound tube of the spiral tube reactor or another spirally wound tube.
  11. 11. The process according to any one of claims 1 to 10, characterized in that the spiral tube reactor has at least two spirally wound tubes and has an inlet for the addition of the monomer in front of the first tube and between the at least one first and at least one second tube in the flow direction.
  12. 12. Method according to one of claims 1 to 11, characterized in that when passing through the flow velocity is in the range of 0.1 cm/s to 1 cm/s.
  13. 13. Use of a spiral tube reactor for the continuous synthesis of polyoxazolines, wherein the spiral tube reactor comprises the following components: a spirally wound tube with an inner tube diameter and a diameter of the spiral winding, characterized in that: • the pipe inner diameter is in the range of 4.5 mm to 34 mm, and • the lambda ratio as the ratio of the inner pipe diameter to the diameter of the spiral winding is in the range of 0.11 to 0.17, and • the spiral wound pipe is a stainless steel pipe.
  14. 14. Use of a spiral tube reactor for the continuous synthesis of polyoxazolines according to claim 13, characterized in that the spiral tube reactor includes a heating element.

Description

Process for the continuous synthesis of polyoxazolines using a spiral tube reactor The invention relates to a process for the continuous polymerization of oxazolines to polyoxazolines (hereinafter referred to as poly(2-oxazolines)). These are also called poly(N-acetylene imines) and consist of polymerized 2-oxazoline monomer units. It is known that oxazolines, especially 2-substituted 2-oxazolines, can be polymerized to polyoxazolines in a cationic ring-opening, living polymerization. Batch syntheses, including in the microwave, are possible and common. The disadvantage, however, is that the products vary slightly from batch to batch (also called batch-to-batch variation). Furthermore, the batch sizes in the batch process are limited. Spiral tube reactors (also called coiled flow reactors) have also been known for a long time. Regardless of the mechanism of polymerization, there is great interest on a large scale in further increasing the throughput of polymerization methods. In addition, the polyoxazolines should have a dispersity of <1.5, preferably <1.3, for medical applications, for example. WO 2014/191171 A1 describes a continuous process for producing polyoxazolines in a tubular flow reactor that includes a static mixer in the form of a "metal grid". Various advantages over the known batch processes are mentioned. However, the only example mentioned only produces a polymer with a molecular weight of 4850 g/mol (corresponds to 30 repeat units, with a set value of 33 repeat units) and a high dispersity of 1.6. These results suggest that there is increased mixing in the tubular reactor in the direction of flow, which leads to inhomogeneous polymers. The dispersity of this polymer would not be sufficient for medical use. WO 2017/182610 A1 describes a process for producing polymers from cyclic imino ethers, polyoxazolines, in a wound tubular reactor, for example, where the linear flow rate is at least 120 cm/min. The disadvantage is that in the tubular flow reactor without a mixing device, the polymer is not homogeneous despite comparatively very high flow rates. The dispersity is good at 1.10-1.20. The reactors used only have small internal diameters of 0.75 to 2.4 mm. It is disclosed that with increasing pipe diameters in the present system, the dispersity increases independently of other parameters. This results, as explained here under Comparative Example 4 and in Table 3/line 2 calculates a maximum lambda value of 0.06 - for PTFE as pipe material even a maximum of 0.027 (Table 3/line 26). The lambda ratio is the ratio of the pipe's inner diameter to the diameter of the spiral pipe's turns. EP 2 719 452 A1 describes a spiral tube reactor with a very low lambda ratio of 0.03-0.1 in other contexts, such as crystallizations, emulsion polymerizations or heterogeneous catalysis. CN212942950U describes a bundle of spiral-shaped reaction tubes in the context of a ring-opening polymerization. CN1390240A describes the use of spiral reaction tubes in the production of polyether polyols. Reis et al. (2020) describe spiral-shaped tubular reactors for the synthesis of block-like copolymers using a modular design. Continuous tubular reactors are therefore suitable for producing polyoxazolines with low dispersities, since in the so-called “steady state” they deliver homogeneous products without interruption in production and, unlike in numerous examples from research, there can be no batch-to-batch differences. As is well known, a low level of mixing in the direction of flow is necessary to achieve very low dispersities. In the case of a flow-through spiral tube reactor, however, a laminar flow is often present. This laminar flow leads to mixing in the direction of flow due to the different flow velocities at the wall and the middle of the tube. But turbulent flow tube reactors are also used. However, these have so far had very small diameters in the range of <1 mm. Tube reactors with such small diameters are not suitable for enabling a high product throughput, i.e. they cannot be upscaled. If the diameter is increased, it is to be expected that the turbulent flow will change into a laminar flow. As is known, tube reactors with diameters of >1 mm are only able to achieve a laminar flow. Furthermore, in turbulent flow tubular reactors, the residence times in the reactor are often too short to achieve complete conversion of the reactants, so that so far in the living polymerization relied on laminar, and consequently slower, flow tubular reactors. In summary, with known methods, when the pipe inner diameters are enlarged to obtain high throughputs (i.e., amount of substance converted per unit time), the mixing in the flow direction and consequently the dispersity of the resulting polymer increases. EP 0 944 431 B1 describes a device for continuously carrying out chemical reactions, in particular a curved tubular flow reactor with a substantially circular or ellipsoidal cross-section, characterized in that it has seve