Method for the continuous synthesis of polyoxazolines using a spiral tube reactor

Abstract

The present invention relates to the continuous synthesis of polyoxazoline. The subject of protection relates to a method for continuously synthesizing polyoxazoline, the steps of which are - including the step of introducing at least one oxazoline monomer into a spiral tube reactor under the action of heat, wherein the spiral tube reactor comprises at least one spirally wound tube having an inner diameter of the tube and a diameter of the spiral winding, and the method is · the inner diameter of the tube is in the range of 4.5 mm to 34 mm, and · the lambda ratio as the ratio of the inner diameter of the tube to the diameter of the spiral winding is in the range of 0.11 to 0.17, and · the spirally wound tube is a stainless steel tube, and also relates to the use of a spiral tube reactor for the continuous synthesis of polyoxazoline, wherein the spiral tube reactor is a use comprising the following components, namely a spirally wound tube having an inner diameter of the tube and a diameter of the spiral winding, · the inner diameter of the tube is in the range of 4.5 mm to 34 mm, and, · the lambda ratio as the ratio of the inner diameter of the tube to the diameter of the spiral winding is in the range of 0.11 to 0.17, and · the spirally wound tube is a stainless steel tube, characterized by.

Description

Technical Field

[0001] The present invention relates to a method for continuously polymerizing oxazoline into polyoxazoline (hereinafter referred to as poly(2-oxazoline)). These are also called poly(N-acetylenimine) and are composed of polymerized 2-oxazoline monomer units.

Background Art

[0002] It is known that oxazoline, particularly 2-substituted 2-oxazoline, can be polymerized into polyoxazoline by living polymerization via a cationic ring-opening reaction. Synthesis by batch methods, such as using microwaves, is also possible and is widely used. However, there is a drawback that the product varies slightly from batch to batch (also called batch-to-batch variation). Furthermore, in the batch process, there is a limit to the batch size.

[0003] Spiral tube reactors (also called coiled flow reactors) have also been known for a long time. On an industrial scale, regardless of the polymerization mechanism, there is great interest in further improving the processing capacity (conversion amount) of the polymerization method. Furthermore, for example, in medical applications, it is required that the dispersity of polyoxazoline be less than 1.5, preferably less than 1.3.

[0004] WO2014 / 191171A1 discloses a method for continuously producing polyoxazoline in a tube flow reactor equipped with a static mixer in the shape of a "metal grid". This process has various advantages compared to known batch processes. However, in the only example described, only a polymer with a high dispersity of 1.6 and a molecular weight of 4850 g / mol (equivalent to 30 repeating units when setting 33 repeating units) is obtained. This result suggests that mixing increases in the flow direction in the tube reactor, resulting in a non-uniform polymer. The dispersity of this polymer is insufficient for medical applications.

[0005] WO2017 / 182610A1 describes a method for producing polymers from cyclic iminoethers and polyoxazolines in a spiral tube reactor, for example, with a linear flow velocity of at least 120 cm / min. A drawback is that in tube-flow reactors without a stirring device, the polymer is not homogeneous despite the relatively high flow velocity. The dispersion was good, ranging from 1.10 to 1.20. The reactors used have small inner diameters, ranging from 0.75 to 2.4 mm. In this system, it has been shown that dispersibility improves as the tube diameter increases, regardless of other parameters. As explained in Comparative Example 4 and calculated in Table 3 / row 2, the maximum lambda value is 0.06, and when PTFE is used as the tube material, it is a maximum of 0.027 (Table 3 / row 26). The lambda ratio represents the ratio of the inner diameter of the tube to the diameter of the spiral tube coil.

[0006] EP2719452A1 describes spiral tube reactors with very low lambda ratios of 0.03 to 0.1 in other related fields such as crystallization, emulsion polymerization, and heterogeneous catalytic reactions.

[0007] CN212942950U describes a bundle of helical reaction tubes in relation to ring-cleavage polymerization.

[0008] CN1390240A describes the use of helical reaction tubes in connection with the production of polyether polyols.

[0009] Reis et al. (2020) describe a spiral tube reactor for the synthesis of block copolymers using modular structures.

[0010] Therefore, a continuous tube reactor is suitable for producing polyoxazolines with low dispersion. This is because, in a so-called "steady state," a homogeneous product can be provided without interruption of production, and unlike many studies, there is no variation between batches.

[0011] It is known that achieving very low dispersion requires low agitation in the flow direction. However, in spiral tube reactors through which fluid flows, laminar flow often occurs. This laminar flow, due to the difference in flow velocity between the wall and the center of the tube, results in agitation in the flow direction.

[0012] However, turbulent tube reactors are also used. However, these have so far only had very small diameters, less than <1 mm. Such small-diameter tube reactors are unsuitable for achieving high product processing volumes, meaning they cannot be scaled up. Increasing the diameter is expected to change turbulence to laminar flow. It is known that only laminar flow occurs in tube reactors with a diameter of ≥1 mm.

[0013] Furthermore, in turbulent tube reactors, the residence time within the reactor is often too short for the reactants to react completely. Therefore, laminar tube reactors, i.e., slow-flow reactors, have been used in living polymerization until now.

[0014] In summary, in known methods, increasing the inner diameter of the tube to obtain a high processing rate (i.e., the amount of material converted per unit time) promotes mixing in the direction of flow, and as a result, the dispersion of the resulting polymer increases.

[0015] EP0944431B1 describes an apparatus for continuously carrying out chemical reactions, particularly a curved tubular fluid reactor having a basically circular or elliptical cross-section. This apparatus is characterized by having multiple curvatures in which the direction of curvature alternates, and the change in the direction of curvature occurs when the distance from the starting point of the curve through the centroid of the tube's cross-sectional area reaches 200 times the tube diameter. One curvature may include up to three rotations around the axis of curvature.

[0016] DE10125583A1 describes a method for producing homopolymers and copolymers of isobutene by continuous cationic polymerization of isobutene or a mixture of isobutene and ethylene unsaturated comonomer in the presence of an initiator system, characterized in that the polymerization is carried out in a tubular fluid reactor having multiple curvatures in which the direction of curvature alternates. [Prior art documents] [Patent Documents]

[0017] [Patent Document 1] WO2014 / 191171A1 [Patent Document 2] WO2017 / 182610A1 [Patent Document 3] EP2719452A1 [Patent Document 4] CN212942950U [Patent Document 5] CN1390240A [Patent Document 6] EP0944431B1 [Patent Document 7] DE10125583A1 [Non-patent literature]

[0018] [Non-Patent Document 1] Reis MH, Leibfarth FA, Pitet LM (2020), Polymerizations in Continuous Flow: Recent Advances in the Synthesis of Diverse Polymeric Materials. ACS Macro Lett. 9, 123-133. [Overview of the Initiative] [Problems that the invention aims to solve]

[0019] Therefore, an object of the present invention is to develop a new method for continuously producing polyoxazoline on an industrial scale, and in this case, it is desirable that the conversion amount (throughput) per unit time is as large as possible. However, this method must be able to simultaneously achieve good and controllable properties for the resulting polyoxazoline. The polymer should be homogeneous, have a low dispersity, preferably <1.5 (less than 1.5), particularly preferably <1.3 (less than 1.3). The spiral tube reactor to be used should sufficiently mix the mixture flowing inside it orthogonally to the flow direction, cancel out the mixing in the flow direction due to the laminar flow state, and be resistant to corrosive media.

Means for Solving the Problem

[0020] This problem is solved by the features of the independent patent claims. Preferred embodiments are described by the dependent claims.

[0021] The present invention is a method for the continuous synthesis of polyoxazoline, particularly poly(2-oxazoline), and includes the following steps: - introducing at least one oxazoline monomer (in the reaction mixture) into a spiral tube reactor under the action of heat, the spiral tube reactor comprising at least one spirally wound tube having an inner diameter of the tube and a diameter of the spiral winding, · the inner diameter of the tube (of the spirally wound tube) being in the range of 4.5 mm to 34 mm, and · the lambda ratio as the ratio of the inner diameter of the tube to the diameter of the spiral winding being in the range of 0.11 to 0.17, and · the spirally wound tube being a stainless steel tube.

[0022] The spiral winding of the tube forms the so-called coil of the spiral tube reactor.

[0023] According to the present invention, the formed spiral (formed by the wound tube) has a constant diameter in the main portion of the spiral's length. This is referred to as a spiral tube reactor. The diameter of this spiral is the same as the diameter of the helically wound tube according to the present invention. That is, the spiral tube reactor is cylindrical rather than conical, and may also include a stepwise change in diameter within the range of values ​​defined in the present invention.

[0024] The "lambda ratio" is the ratio of the inner diameter of the tube to the diameter of the helical winding.

[0025] To achieve an appropriate lambda ratio within a given tube inner diameter, it is reasonable to set the diameter of the helical winding in the range of 35 mm to 305 mm.

[0026] Furthermore, the present invention also relates to the use of a spiral tube reactor in a method for the continuous synthesis of polyoxazolines (a reaction mixture comprising at least one oxazoline monomer), the reactor being composed of a spirally wound tube having an inner diameter and a diameter of the helical winding (a spirally wound tube), • The inner diameter of the tube ranges from 4.5 mm to 34 mm. • The lambda ratio, which is the ratio of the inner diameter of the tube to the diameter of the helical winding (helical tube), is in the range of 0.11 to 0.17, and The spirally wound tube is characterized by being made of stainless steel. In particular, this includes use in the manner according to the present invention.

[0027] During use, it is appropriate to pass at least one type of oxazoline monomer (in the reaction mixture) through the spiral tube reactor under the action of heat (heating). The term "under the action of heat" means raising the temperature to a range of 100°C to 180°C. Preferably, the tube is heated by the action of heat from at least one heating element. "Heating element" means a component for supplying thermal energy. In embodiments, the heating element is an electric heater. In embodiments, the spirally wound tube is at least partially in contact with the heating element. In embodiments, the spirally wound tube is almost completely or completely surrounded by the heating element.

[0028] The same applies to the use of this method.

[0029] In the present invention, "at least one oxazoline monomer" should be understood not as at least one single molecule, but as "a monomer having at least one chemical structure," that is, it explicitly means many individual molecules. In embodiments, the oxazoline monomer is 2-alkyl-2-oxazoline, preferably 2-methyl-2-oxazoline, 2-ethyl-2-oxazoline, or 2-butyl-2-oxazoline.

[0030] Furthermore, it is explicitly stated that the entire tube of a spiral tube reactor does not need to be wound in a spiral shape. However, "spiral-wound tube" refers to the spirally wound portion, and may include straight sections in between.

[0031] In this context, this also includes the case where other tubes (which also have a configuration according to the present invention) are present.

[0032] Furthermore, linearly extending start, end, and intermediate sections are also conceivable. Laminar flow may also occur in these sections. These sections are not the main part of polymerization and, in some cases, are used only for post-reactions, reactions of small amounts of residual monomers, or cooling of the reaction mixture. However, in the spiral tube reactor according to the present invention, at least 80% of the stainless steel tube is wound in a spiral shape.

[0033] Similarly, it is explicitly stated that only a portion of the tube may be heatable, or, if there are multiple tubes, not all of them may be heatable. Generally, heating will cause polymerization to occur at these locations.

[0034] There is an important correlation between the relatively large tube diameter according to the present invention and the required homogeneous mixing, because it has been observed that the flow pattern is stabilized by secondary flow (flow perpendicular to the primary flow). This secondary flow likely stabilizes the laminar primary flow (primary flow in the direction of tube flow), allowing for higher flow velocities while maintaining good mixing as it flows through the spiral tube reactor. "Flow velocity" refers to the rate at which the reaction mixture (containing at least one type of oxazoline monomer) passes through the spiral tube reactor. This minimizes mixing in the direction of flow, which increases dispersibility. Nevertheless, the residence time appears to be long enough to allow for complete polymerization of oxazoline, because if the residence time is too short where heat acts, polymerization will be incomplete. For example, when producing a block copolymer, the reaction mixture may still contain the first monomer, and when a second monomer is added, the block consisting of the second monomer component may be contaminated with the first monomer component that has not yet been consumed. On the other hand, if the residence time is too long, many side reactions occur, such as chain transitions due to proton elimination and the initiation of new polymer chains by the generated substances.

[0035] This invention minimizes mixing in the flow direction, which enhances dispersibility.

[0036] This invention makes it possible to obtain in 5 minutes the amount of polyoxazoline that could only be obtained in one week using conventional batch synthesis. This applies to the synthesis of 1g to 30g.

[0037] The present invention makes it possible for the first time to achieve high (substance) processing and conversion rates of polyoxazolines, i.e., in the range of 6 mmol / min to 480 mmol / min, while simultaneously achieving good dispersibility in the range of 1.23 to 1.3 (demonstrated here in three exemplary examples, here at 41 mmol / min). The terms "processing rate" or "conversion rate" refer to the amount of monomer in the reaction mixture that is converted within a given time. Good dispersibility would be based on sufficient mixing while passing through the spiral tube reactor. However, in the prior art, increasing the inner diameter of the tube to achieve a high processing rate (amount of substance converted per unit time) results in insufficient mixing and increased dispersibility of the resulting polymer.

[0038] Achieving high processing volumes with the inner diameter of the tube according to the present invention often requires high pressure. While stainless steel provides the necessary pressure stability, this changes the minimum possible helical diameter, resulting in changes to the flow pattern and thus to the mixing and dispersibility of the polymers.

[0039] The stainless steel according to the present invention, which combines the aforementioned tube inner diameter with a very large lambda ratio (meaning a small diameter of the helical winding), is a spiral tube reactor design that is remarkably advantageous for the polymerization of oxazoline.

[0040] The stabilization of the primary laminar flow by vortex secondary flow (perpendicular to the primary flow) within the helically wound tube is one reason for this remarkable result. In any case, the design according to the present invention enables higher flow velocities (in the polymerization of polyoxazoline) than laminar flow without the shape according to the present invention. Stainless steel can withstand the high pressures that may arise at such high flow velocities. It is clear that the shape of the helically wound tube and the flow behavior that can be achieved therein depend heavily on the material of the tube.

[0041] The present invention makes it possible to optimally balance both high yield per unit time and suppression of side reactions that may occur, for example, due to excessive residence time or heat in the reactor. Advantageously, the method according to the present invention allows for the complete consumption of oxazoline monomers present in the reaction mixture using the tube reactor according to the present invention. The term "reaction mixture" refers to the mixture that is passed through the tube reactor during continuous operation for the purpose of producing polyoxazoline. At the same time, good mixing is achieved, which is essentially necessary to obtain a homogeneous polymer with a minimum dispersion degree of 1.0. This means that each molecule of the polymer has the most uniform molecular weight distribution composition possible. The resulting polyoxazoline polymer is also homogeneous.

[0042] As mentioned above, the present invention has the advantage of improving the transport of matter, heat, and energy, thereby increasing the yield per unit time. A more homogeneous reaction mixture is obtained in the reactor, resulting in polydispersity of <1.5, and often <1.3.

[0043] The tube length should preferably be between 2m and 5m.

[0044] Due to its relatively large inner diameter, the production volume per unit time can be increased, and as a result, the proportion of labor costs in the product price is also reduced. This invention can also be applied to large-scale production. Continuous operation allows for the production of polymers of a defined, consistent quality.

[0045] The geometric shape according to the present invention (i.e., the tube inner diameter and the lambda ratio of the stainless steel tube) enables space-saving arrangements and even modular structures. In other words, if the spiral tube reactor comprises a plurality of helically wound tubes connected linearly, preferably detachably, then the production of copolymers, particularly block copolymers, can be carried out very simply.

[0046] The specific inclination of the helix does not affect the present invention.

[0047] In the embodiment, the inner diameter of the helically wound tube is in the range of 6.35 mm to 38.1 mm, preferably in the range of 8 mm to 12 mm, particularly preferably in the range of 9 mm to 10 mm, and particularly 10 mm. In the embodiment, the inner diameter of the tube is 10 mm ± 1 mm.

[0048] In the embodiment, the lambda ratio is in the range of 0.11 to 0.16.

[0049] In this embodiment, the diameter of the helical winding is in the range of 50 mm to 300 mm, preferably in the range of 50 mm to 120 mm, particularly preferably in the range of 70 mm to 95 mm, and especially 72 mm.

[0050] In the embodiment, the wall thickness of the stainless steel tube (helically wound tube) is in the range of 0.9 mm to 2.2 mm, particularly in the range of 1 mm to 2.2 mm. This is optimal for realizing the spiral tube reactor design according to the present invention using this material.

[0051] In the embodiment example, the lambda ratio is 0.13 ± 0.01.

[0052] In a preferred embodiment, • The inner diameter of the tube is 10mm ± 1mm. The diameter of the spiral is 72mm ± 7mm. This is a particularly favorable parameter for stabilizing the primary flow of laminar flow in a helically wound stainless steel tube.

[0053] In the embodiment, the wall thickness (of the spirally wound tube) is particularly preferably in the range of 1 mm ± 0.2 mm, and more preferably in the range of 0.9 mm to 1.1 mm.

[0054] In the embodiment, the flow rate of the oxazoline monomer when it is introduced into the helically wound tube is in the range of 6 mmol / min to 480 mmol / min. Preferably, the concentration of the oxazoline monomer at the start of introduction, i.e., when the oxazoline monomer is introduced into the spiral tube reactor, is in the range of 4 mol / L ± 2.5 mol / L, preferably 4 mol / L ± 1.5 mol / L, and particularly 3 mol / L to 5 mol / L.

[0055] In this embodiment, it is preferable that the flow rate (passage rate) of oxazoline monomer flowing through the spiral tube reactor according to the present invention is 10 mL / min. "Flow rate" refers to the volume of oxazoline monomer in the reaction mixture that is transported through the spiral tube reactor within a certain period of time.

[0056] In embodiments of the present invention, the concentration of the oxazoline monomer at the start of conduction, i.e., when the oxazoline monomer is introduced into the spiral tube reactor, is in the range of 1 mol / L to 10 mol / L, particularly 3 mol / L to 5 mol / L.

[0057] Furthermore, a preferred embodiment of the present invention is that the lambda ratio is 0.13 ± 0.01 and the pressure during conduction is 40 bar ± 5 bar, preferably in the range of 39 bar to 41 bar.

[0058] This offers the advantage of achieving optimal flow characteristics in the (helically wound) stainless steel tube according to the present invention.

[0059] In a preferred embodiment, the temperature inside the helical tube is in the range of 130°C to 150°C. This range is particularly preferred for achieving complete polymerization of all oxazoline monomers at the high yield according to the present invention. The temperature of the tube to be selected also depends on the inner diameter, but this range is optimized for the design of the helical tube reactor according to the present invention. Furthermore, by using stainless steel, more pressure can be applied, and therefore more heat can be applied (i.e., higher temperatures of 130-150°C can be applied), and the reaction mixture will not boil depending on the solvent.

[0060] In a preferred embodiment, the lambda ratio is 0.13 ± 0.01, the concentration of oxazoline monomer at the start is 4 mol / L ± 1.5 mol / L, and the monomer processing rate of oxazoline monomer is in the range of 6 mmol / min to 480 mmol / min, preferably in the range of 50 mmol / min ± 5 mmol / min. In particular, this can be methyl oxazoline.

[0061] In the embodiments of the present invention, when the reactor is conductive, the first oxazoline monomer passes through the spiral tube reactor first, and then a second oxazoline monomer different from the first, so that the resulting polyoxazoline is a block copolymer having at least two blocks.

[0062] After passing at least one first oxazoline monomer through a spiral tube reactor, it is appropriate to add at least one second oxazoline monomer, different from the first, under the action of heat. In the embodiment, the reaction mixture containing the additional oxazoline monomer is passed through a helically wound tube of the spiral tube reactor, or another helically wound tube.

[0063] In another preferred embodiment for block polymerization, the spiral tube reactor comprises at least two helically wound tubes, each having an inlet for adding monomers in the flow direction, forward of the first tube and between at least one first tube and at least one second tube.

[0064] This block structure can be easily realized through the space-saving design of the spiral tube reactor according to the present invention.

[0065] Furthermore, it is possible to provide inlets between each tube for adding monomers (monomer supply).

[0066] The "first tube" refers to the first heated tube in which polymerization takes place. These monomer feed ports allow monomers with the same or different chemical structures to be introduced into the tube reactor. This arrangement is ideal for the production of block copolymers, where polymer blocks are formed by supplying different types of monomers to various monomer feed ports.

[0067] In one variation of this embodiment, since all the spirally wound tubes are the same length, a different number of tubes (without monomer supply in between) can be used in a continuous arrangement depending on the length of the polymer block to be manufactured. Thus, the length of the polymer block is controlled by the amount of monomer (with the same chemical structure) supplied and the number of subsequent tubes. Subsequently, in the next monomer supply, for example, monomers with a different chemical structure can be supplied, which polymerize into an "elongating polymer chain" in the subsequent tubes.

[0068] Furthermore, the flow velocity during conduction according to the present invention is preferably in the range of 0.1 cm / sec to 1 cm / sec, and particularly preferably 0.21 cm / sec (±0.05 cm / sec).

[0069] In the embodiment, the flow rate (flow velocity) during conduction is in the range of 9 mL / min to 11 mL / min, and the inner diameter of the tube is 9 mm to 11 mm. The length of the tube is preferably 1 m (±10%).

[0070] The reaction mixture, comprising at least one oxazoline monomer according to the present invention and passing through a tube reactor, preferably also contains initiators capable of initiating each polymerization reaction. The same applies to termination agents capable of stopping polymerization or terminating chain growth, which are preferably used at the end of the tube where polymerization takes place or further down the line.

[0071] In the method according to the present invention, the solvent added to the oxazoline monomer and flowing through the tube reactor as part of the reaction mixture is preferably a non-nucleophilic solvent. Preferably, it is a polar, aprotic solvent, selected from acetonitrile, chlorobenzene, chloroform, 1,2-dichlorobenzene, dichloromethane, dimethylformamide, dimethyl sulfoxide, and mixtures thereof, and particularly a mixture of acetonitrile and chlorobenzene. As is well known, other solvents such as methanol, ethanol, and water can also be used when terminating, i.e., interrupting polymerization at the end of the process according to the present invention.

[0072] All embodiments can be combined with each other in any way. [Examples]

[0073] Examples Examples 1-3: High-volume synthesis: The initiator was weighed and dissolved in a mixture of 19 mL of dry benzene chloride and 20 mL of dry acetonitrile. The calculated amount of 2-methyl-2-oxazoline (oxazoline monomer) was added to the solution. After mixing, 50 mL of the solution was fed into a spiral tube reactor. The inner diameter of the spiral tube reactor was 10 mm, and the diameter of the spiral winding (coil) was 72 mm.

[0074] The flow rate was 10 mL / min, the reactor temperature was 130–150°C, and the pressure was 40 bar. After flowing for 30–35 minutes, the product was collected for 90 minutes in a bottle pre-added with a small amount of piperidine. The resulting mixture was concentrated, dissolved in methanol, and precipitated with 15 times its volume of diethyl ether. This procedure was repeated, the product dissolved in water, and freeze-dried.

[0075] Spiral tube reactor used: The inner diameter was 10 mm. The flow rate was calculated based on the following: The radius r = 5 mm = 0.05 dm, and the volume of the cylinder is V = r^2 * pi * h, where h corresponds to the length of the tube, and h = 1 m = 10 dm. V = 0.05 * 0.05 * 3.141 * 10 dm³ = 78.5 ml → For a length of 1 m, the volume is 78.5 ml / m. The flow rate was set to 10 mL / min. From the calculated cylinder volume, the following results were obtained. 0.1274m / min=12.74cm / min=0.212cm / sec

[0076] The monomer flow rate was calculated as follows: m (monomer) = 21 g, M (monomer) = 85.1 g / mol, n (monomer) = 247 mmol V (Solution: Chlorobenzene + Acetonitrile + Monomer) = 19 ml + 20 ml + 21 ml = 60 ml c (monomer) = 247 mmol / 60 ml = 4 mol / L 247 mmol in 60 ml of solution A flow rate of 10 ml / min (for 5 minutes) → 247 / 5 mmol / min = 49.4 mmol / min. Maintain a safety margin to prevent air from entering the device. Table 1 shows various examples.

[0077] [Table 1]

[0078] [Table 2]

[0079] Regarding the spiral tube reactor being used:

[0080] [Table 3]

[0081] Table 3 lists the dimensions of the helical tubes, based on the specifications of the manufacturer, Swagelok®. The units listed in each column, with the exception of the "Outer Diameter [inches]" and "Bending Radius [inches]" columns, are understood as decimal values ​​in millimeters and inches. Exceptions exist where dimensions are expressed as standard fractions (in inches).

[0082] The goal was to obtain the largest possible lambda value = (inner diameter) / (winding diameter). To achieve this, it was necessary to make the inner diameter as large as possible and the windings as narrow as possible, i.e., the winding diameter small. Since the manufacturer specifies values ​​for each outer and inner diameter, it is easy to reproduce these lambda values.

[0083] In the case of stainless steel, it is assumed that the respective bending radii for the corresponding wall thickness are similar across many manufacturers, based on the material parameters. The lambda value was calculated from the manufacturer-specified bending radius and inner radius information. Here, the coil diameter is twice the bending radius. It can be seen that a lambda value of 0.10 to 0.17 can be obtained at the minimum bending radius. However, this requires precisely adjusting the tube to this bending radius.

[0084] Comparative Example 4-WO2017 / 182610A1: The second item (second row) in Table 3 shows the calculated maximum lambda value for the tube reactor in WO2017 / 182610A1. If these bending radii are not specified (as described in the Ghent University application documents, namely WO2017 / 182610A1), the bending should be considered unintentional. This is considered reasonable, especially since tubes with outer diameters of 1 / 16 inch and 1 / 8 inch can be wound manually. This results in a maximum lambda value of 0.06 obtained from the Ghent University data (inner diameter and bending radius from the disclosed example). Row 26 of Table 3 shows the calculation results for the maximum lambda value when PTFE is used as the tube material, based on WO2017 / 1812610A1. However, WO2017 / 182610A1 lists PTFE with an even smaller lambda value of up to 0.026 as an additional material, and b) does not specify the bending radius or winding diameter. Therefore, it can be assumed that this disclosure is simply intended to save space by winding.

[0085] Cited non-patent literature Reis MH, Leibfarth FA, Pitet LM (2020), Polymerizations in Continuous Flow: Recent Advances in the Synthesis of Diverse Polymeric Materials. ACS Macro Lett. 9, 123-133.

Claims

1. This is a method for the sequential synthesis of polyoxazolines. - The process includes the step of introducing at least one oxazoline monomer into a spiral tube reactor under the action of heat, Here, the spiral tube reactor is a method comprising at least one helically wound tube having an inner diameter of the tube and a diameter of the helical winding, - The inner diameter of the tube is in the range of 4.5 mm to 34 mm, and - The lambda ratio, which is the ratio of the inner diameter of the tube to the diameter of the helical winding, is in the range of 0.11 to 0.17, and - The spirally wound tube is made of stainless steel. The method characterized by the above.

2. The method according to claim 1, characterized in that the inner diameter of the tube is 10 mm ± 1 mm.

3. The method according to claim 1 or 2, characterized in that the lambda ratio is 0.13 ± 0.

01.

4. The method according to any one of claims 1 to 3, characterized in that the diameter of the helical winding is 72 mm ± 7 mm.

5. The method according to any one of claims 1 to 4, characterized in that the wall thickness of the spirally wound tube is 1 mm ± 0.2 mm.

6. The method according to any one of claims 1 to 5, characterized in that the processing rate of oxazoline monomer passing through the spiral tube reactor is in the range of 6 mmol / min to 480 mmol / min.

7. The method according to any 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. The method according to any one of claims 1 to 7, characterized in that the flow rate of oxazoline monomer passing through the spiral tube reactor is in the range of 9 mL / min to 11 mL / min.

9. The method according to any one of claims 1 to 8, characterized in that the pressure inside the spiral tube reactor is 40 bar ± 5 bar.

10. After the first oxazoline monomer has been supplied to the spiral tube reactor, at least one further step is performed: The method according to any one of claims 1 to 9, wherein the further step includes adding at least one further oxazoline monomer different from the first oxazoline monomer to the reaction mixture comprising polyoxazoline from the first oxazoline monomer, and passing the reaction mixture through the helically wound tube of the spiral tube reactor, or another helically wound tube.

11. The method according to any one of claims 1 to 10, characterized in that the spiral tube reactor comprises at least two helically wound tubes, and in the flow direction, has inlets for adding monomers, one in front of the first tube and one between at least one first tube and at least one second tube.

12. The method according to any one of claims 1 to 11, characterized in that the flow velocity during conduction is in the range of 0.1 cm / second to 1 cm / second.

13. In the use of a spiral tube reactor for the continuous synthesis of polyoxazolines, the spiral tube reactor comprises the following components: a helically wound tube having an inner diameter and a diameter of the helix; - The inner diameter of the tube is in the range of 4.5 mm to 34 mm, and, - The lambda ratio, which is the ratio of the inner diameter of the tube to the diameter of the helical winding, is in the range of 0.11 to 0.17, and - The spirally wound tube is made of stainless steel. The aforementioned use, characterized by the above.

14. The 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.

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