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

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.

Description

[0001] Process for the continuous synthesis of polyoxazolines using a spiral tube reactor

[0002] The invention relates to a process for the continuous polymerization of oxazolines to polyoxazolines (hereinafter referred to as poly(2-oxazoline)s). These are also called poly(N-acetyleneimine)s and consist of polymerized 2-oxazoline monomer units.

[0003] 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 microwave synthesis, are possible and widespread. However, a disadvantage is that the products vary slightly from batch to batch (also known as batch-to-batch variation). Furthermore, batch sizes are limited in batch processes.

[0004] Coiled flow reactors have also been known for some time. Regardless of the polymerization mechanism, there is great interest on a large scale in further increasing the throughput of polymerization methods. Furthermore, the polyoxazolines, for example, for medical applications, should have a dispersity of <1.5, preferably <1.3.

[0005] WO 2014 / 191171 A1 describes a continuous process for producing polyoxazolines in a tubular flow reactor containing a static mixer in the form of a "metal grid." Various advantages over known batch processes are cited. However, the only example cited yields only a polymer with a molecular weight of 4850 g / mol (corresponding to 30 repeat units, with a set number of 33 repeat units) and a high dispersity of 1.6. These results suggest that increased mixing in the tubular reactor occurs in the flow direction, leading to inhomogeneous polymers. The dispersity of this polymer would be insufficient for medical applications.

[0006] WO 2017 / 182610 A1 describes a process for producing polymers from cyclic imino ethers, polyoxazolines, in a coiled tubular reactor, for example, where the linear flow rate is at least 120 cm / min. A 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 have only small internal diameters of 0.75 to 2.4 mm. It is disclosed that with increasing tube diameters in the present system, the dispersity increases independently of other parameters. As explained here under Comparative Example 4 and calculated in Table 3 / line 2, the maximum lambda value is 0.06 – for PTFE as the tube material, even a maximum of 0.027 (Table 3 / line 26). The lambda ratio is the ratio of the inner diameter of the pipe to the diameter of the coils of the spiral pipe.

[0007] 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.

[0008] CN212942950U describes a bundle of spiral reaction tubes in the context of a ring-opening polymerization.

[0009] CN1390240A describes the use of spiral reaction tubes in the context of the production of polyether polyols.

[0010] Reis et al. (2020) describe spiral tubular reactors for the synthesis of block copolymers using a modular design.

[0011] Continuous tubular reactors are therefore suitable for producing polyoxazolines with low dispersities, as they produce homogeneous products in the so-called “steady state” without interruption of production and, unlike in numerous examples from research, there can be no batch-to-batch differences.

[0012] To achieve very low dispersities, it is well known that a low degree of mixing in the flow direction is necessary. However, in the case of a flow-through spiral tube reactor, laminar flow is often present. This laminar flow leads to mixing in the flow direction due to the different flow velocities at the wall and the center of the tube.

[0013] Turbulent-flow tubular reactors are also used. However, these currently have very small diameters, in the range of <1 mm. Tubular reactors with such small diameters are not suitable for high product throughput, meaning they cannot be scaled up. Increasing the diameter is likely to result in the turbulent flow transforming into laminar flow. It is known that tubular reactors with diameters >1 mm are only capable of achieving laminar flow.

[0014] 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 laminar, and consequently slower flow, tubular reactors have been used for living polymerization.

[0015] In summary, with known methods, when the pipe inner diameters are enlarged to obtain high throughputs (i.e., molar conversion per unit time), the mixing in the flow direction and consequently the dispersity of the resulting polymer increases.

[0016] 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 a plurality of bends with alternating curvature directions, wherein a change in the curvature direction occurs at the latest when the distance traversed by the center of gravity of the tube cross-sectional area from the beginning of a bend is 200 times the tube diameter, wherein a bend can comprise up to three revolutions around the axis of curvature.

[0017] DE 101 25 583 A1 describes a process for the preparation of homo- and copolymers of isobutene by continuous cationic polymerization of isobutene or mixtures of isobutene with ethylenically unsaturated comonomers in the presence of an initiator system, characterized in that the polymerization is carried out in a tubular flow reactor which has a plurality of bends with alternating curvature directions.

[0018] The object of the invention is therefore to develop a novel process by which polyoxazolines can be produced on an industrial scale and continuously, with the conversion per unit time (throughput) being as high as possible. At the same time, the process should allow good and controllable properties of the resulting polyoxazoline. The polymer should be homogeneous and have a low dispersity, preferably in the range of <1.5, particularly preferably <1.3. The spiral tube reactor used should ensure thorough mixing of the mixtures flowing through it orthogonal to the flow direction, thus counteracting mixing in the flow direction due to the laminar regime and be resistant to aggressive media.

[0019] The problem is solved by the features of the independent patent claims. Preferred embodiments are described by the dependent claims.

[0020] The invention relates to a process for the continuous synthesis of polyoxazolines, in particular poly(2-oxazolines), comprising the step

[0021] - passing at least one oxazoline monomer (in a reaction mixture) through a spiral tube reactor under the action of heat, comprising a spirally wound tube having an inner tube diameter and a diameter of the spiral winding (of the tube), characterized in that,

[0022] • the inner diameter of the tube (of the spiral wound tube) is 4.5 mm to 34 mm, and

[0023] • the lambda ratio as the ratio of the inner pipe diameter to the diameter of the spiral winding is in the range of 0.11-0.17, and

[0024] • the spiral wound pipe is a stainless steel pipe.

[0025] The spiral winding of the tube forms so-called coils of the spiral tube reactor.

[0026] According to the invention, the formed spiral (formed by the wound tube) has a constant diameter over the majority of its length. This is called a spiral tube reactor. This constant diameter of the spiral corresponds to the diameter of the spirally wound tube according to the invention. This means that the spiral tube reactor does not form a cone, but rather a cylinder, although the diameter can also vary gradually – within the limits defined by the invention.

[0027] The “lambda ratio” is the ratio of the inner diameter of the tube to the diameter of the spiral winding.

[0028] In order to achieve the corresponding lambda ratio for the given pipe inner diameter, the diameter of the spiral windings could sensibly be in the range of 35 mm to 305 mm.

[0029] The invention further relates to the use of a spiral tube reactor in a process for the continuous synthesis of polyoxazolines (from a reaction mixture containing at least one oxazoline monomer), which comprises: a spirally wound tube having a tube inner diameter and a diameter of the spiral winding (of the spirally wound tube), characterized in that,

[0030] • the pipe inner diameter is 4.5 mm to 34 mm, and

[0031] • 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

[0032] • the spirally wound tube is a stainless steel tube; in particular, the use in the method according to the invention.

[0033] During use, at least one oxazoline monomer (in a reaction mixture) is expediently passed through the spiral tube reactor under the influence of heat. The term "heat exposure" refers to an increase in temperature to a temperature in the range from 100°C to 180°C. The heat exposure to heat the tube is expediently carried out by at least one heating element. A "heating element" is understood to be a component for supplying thermal energy. In embodiments, the heating element is an electric heating strip. 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.

[0034] Statements concerning the procedure apply equally to the use and vice versa.

[0035] For the purposes of the invention, "at least one oxazoline monomer" does not mean at least a single molecule, but rather "monomers of at least one chemical structure," meaning explicitly many individual molecules. In embodiments, the oxazoline monomer is a 2-alkyl-2-oxazoline, preferably 2-methyl-2-oxazoline, 2-ethyl-2-oxazoline, or 2-butyl-2-oxazoline.

[0036] It is also explicitly stated that not the entire tube of the spiral tube reactor needs to be spirally wound. However, "spirally wound tube" refers to the part that is spirally wound, although straight intermediate sections may also be provided.

[0037] In this context, it is also encompassed that there may be further pipes (also designed according to the invention).

[0038] Linear initial, final, or intermediate regions are also possible. Laminar flow may also be present in these regions. These regions do not serve the main part of the polymerization, but may only serve for post-reactions, for the final small amounts of monomer to react, or for cooling the reaction mixture. However, in a spiral tube reactor according to the invention, at least 80% of the stainless steel tube sections are spirally wound. Likewise, it is explicitly included that only part of the tube is heatable or that, if there are multiple tubes, not all of them are heatable. Generally, heating ensures that polymerization can take place at these points.

[0039] There is an important connection between the relatively large internal tube diameters according to the invention and the homogeneous mixing required. A stabilization of the flow regime by a secondary flow (orthogonal to the primary flow) was observed. This secondary flow most likely stabilizes the laminar primary flow (primary flow in the direction of tube flow), allowing higher flow velocities while still maintaining good mixing while flowing through the spiral tube reactor. The term "flow velocity" refers to the velocity of the reaction mixture comprising the at least one oxazoline monomer through the spiral tube reactor. Mixing in the flow direction, which leads to an increase in dispersity, is thus minimized. The residence time nevertheless appears to be long enough to enable complete oxazoline polymerization.If the residence time during flow is too short at the points exposed to heat, the polymerization is incomplete. For example, if a block copolymer is to be produced, it could happen that some of the first monomer is still present in the reaction mixture, so that after the addition of the second monomer, the block made up of the second monomer building blocks becomes contaminated with the first monomer building blocks, since these have not yet been consumed. If, on the other hand, the residence time is too long, side reactions occur more frequently, such as chain transfer through proton abstraction and the subsequent initiation of new polymer chains by the resulting species.

[0040] The mixing in the flow direction, which leads to an increase in dispersity, is minimized by the invention.

[0041] The invention allows for the production of as much polyoxazoline in 5 minutes as would only be possible in 1 week with conventional batch syntheses. These are 1g-30g syntheses.

[0042] The invention makes it possible for the first time to produce polyoxazolines at a high (mass) throughput or conversion, namely in the range from 6 mmol / min to 480 mmol / min, while at the same time achieving good dispersity in the range from 1.23 to 1.3 (as demonstrated in the three exemplary embodiments, here 41 mmol / min). The term “throughput” or “conversion” refers to the amount of monomer in the reaction mixture that is converted within a period of time. The good dispersity is evidently based on sufficiently good mixing while passing through the spiral tube reactor. In the prior art, however, when the inner tube diameters are enlarged in order to achieve high throughputs (i.e. amount of substance converted per unit time), mixing becomes insufficient and the dispersity of the resulting polymer becomes high.

[0043] To achieve high throughputs with the pipe inner diameter according to the invention, high pressures are often required. The stainless steel material allows for the necessary pressure stability, but changes the possible minimum diameter of a spiral winding, which in turn changes the flow conditions and thus also the mixing and consequently the dispersity of the polymer.

[0044] The inventive combination of stainless steel with the mentioned tube inner diameters and the very large lambda ratio, which in turn specifies a small diameter of the spiral winding, is a surprisingly favorable spiral tube reactor design for the polymerization of oxazolines.

[0045] The stabilization of the laminar primary flow by a vortex-like secondary flow (orthogonal to the primary flow) in the spirally wound tube is one possible reason for the surprising results. In any case, the inventive design allows higher flow velocities (during the polymerization of polyoxazolines) than would be possible in laminar flow without this inventive geometry. The stainless steel withstands the high pressure that can occur at such high flow velocities. It is obvious that the geometry of a spirally wound tube and the resulting flow behavior depend significantly on the tube material.

[0046] The invention allows (for the synthesis of polyoxazolines) an optimal balance between high yield per unit time and the simultaneous suppression of side reactions, which could occur, for example, due to excessively long residence times in the reactor under the influence of heat. Advantageously, it is possible to achieve complete consumption of the oxazoline monomer present in the reaction mixture using the tubular reactor according to the invention in the process according to the invention. The term "reaction mixture" refers to the mixture which is passed through the tubular reactor in continuous operation with the aim of producing the polyoxazoline. At the same time, thorough mixing is achieved, which is fundamentally necessary to obtain a homogeneous polymer with a minimum dispersity of 1.0. This means that the polymer has as uniform a composition as possible in each molecule. The resulting polyoxazoline polymer is also homogeneous.

[0047] As already indicated above, the invention advantageously allows for improved mass, heat, and energy transfer, thus increasing the conversion per unit time. A more homogeneous reaction mixture is achieved in the reactor, so that the polydispersity is <1.5, often even <1.3.

[0048] The pipe is preferably 2 m to 5 m long.

[0049] The relatively large inner diameter allows for the production of larger quantities per unit time, which consequently also reduces the proportion of labor costs in the product price. The invention is applicable on an industrial scale. Continuous operation allows the production of a polymer of defined and consistent quality.

[0050] The geometry according to the invention (this refers to the above-mentioned inner tube diameter and the lambda ratio for the stainless steel tube) also allows for a space-saving arrangement and thus a modular design. This means that if the spiral tube reactor has several spirally wound tubes that are linearly and preferably separably connected to one another, the very simple production of copolymers, especially block copolymers, is possible.

[0051] The actual pitch of the spirals has no influence on the invention.

[0052] In some embodiments, the inner diameter of the spirally 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 in particular even 10 mm. In some embodiments, the inner diameter of the tube is 10 mm ± 1 mm.

[0053] In embodiments, the lambda ratio is in the range of 0.11 to 0.16.

[0054] In embodiments, the diameter of the spiral 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, in particular 72 mm.

[0055] In embodiments, the stainless steel tube (spirally wound tube) has a wall thickness in the range of 0.9 mm to 2.2 mm, in particular in the range of 1 mm to 2.2 mm. This is optimal for achieving the inventive design of the spiral tube reactor with this material.

[0056] In versions the lambda ratio is 0.13 ± 0.01.

[0057] It is also a preferred version if

[0058] • the pipe inner diameter at 10 mm ± 1 mm, and

[0059] • the diameter of the spiral winding is 72 mm ± 7 mm.

[0060] These are particularly favorable parameters for the spiral-wound stainless steel pipe to stabilize the laminar primary flow.

[0061] In this embodiment, the wall thickness (of the spirally wound tube) is most preferably 1 mm ± 0.2 mm, preferably in the range from 0.9 mm to 1.1 mm.

[0062] In embodiments, the monomer throughput when passing the oxazoline monomer through the spirally wound tube is in the range from 6 mmol / min to 480 mmol / min. Preferably, the concentration of the oxazoline monomer at the beginning of the passage, i.e., when introducing the oxazoline monomer into the spiral tube reactor, is 4 mol / L ± 2.5 mol / L, preferably 4 mol / L ± 1.5 mol / L; in particular, in the range from 3 mol / L to 5 mol / L.

[0063] In this embodiment, it is preferred if the flow rate of the oxazoline monomer during passage through the spiral tube reactor according to the invention is 10 mL / min. The term "flow rate" refers to the volume of oxazoline monomer in the reaction mixture that is transported through the spiral tube reactor within a given period of time.

[0064] In embodiments of the invention, the concentration of the oxazoline monomer at the beginning of the passage, ie when the oxazoline monomer is introduced into the spiral tube reactor, is in the range from 1 mol / L to 10 mol / L, in particular in the range from 3 mol / L to 5 mol / L.

[0065] It is also a preferred embodiment of the invention if the lambda ratio is 0.13 ± 0.01 and the pressure during passage is 40 bar ± 5 bar, preferably in the range from 39 bar to 41 bar.

[0066] This advantageously achieves the very best flow behavior in the (spirally wound) stainless steel pipe according to the invention.

[0067] In a preferred embodiment, the temperature in the spirally wound tube during passage lies in the range of 130°C to 150°C. This range is particularly favorable for achieving complete polymerization of all oxazoline monomers at the high throughputs according to the invention. The temperature to be selected for the tube also depends on the internal diameter, with this range being an optimized one for the spiral tube reactor design according to the invention. The stainless steel also advantageously allows for more pressure to be applied, so that more heat can be applied (i.e., a higher temperature of 130 to 150°C can be applied) without the reaction mixture already boiling, depending on the solvent.

[0068] In preferred embodiments, the lambda ratio is 0.13 ± 0.01, and the initial concentration of the oxazoline monomer during passage is 4 mol / L ± 1.5 mol / L, and the monomer flow rate of the 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 could be methyloxazoline.

[0069] In embodiments of the invention, during the passage, first a first oxazoline monomer and then a second oxazoline monomer different from the first are passed through the spiral tube reactor, so that the resulting polyoxazoline is a block copolymer having at least two blocks.

[0070] The addition of the at least one further oxazoline monomer, different from the first, is expediently carried out under the action of heat as a further step after passing at least one first oxazoline monomer through the spiral-tube reactor. In embodiments, the reaction mixture comprising the further oxazoline monomer is passed through the spiral-wound tube of the spiral-tube reactor or through another spiral-wound tube.

[0071] Another preferred embodiment for block-wise polymerization is designed such that the spiral tube reactor has at least two spirally wound tubes and has an inlet for the addition of the monomer in the flow direction upstream of the first tube and between the at least one first and at least one second tube.

[0072] This block construction is easily possible with the space-saving design of the spiral tube reactor according to the invention.

[0073] It is also possible to have an inlet for the addition of the monomer (monomer feed) between each tube.

[0074] The "first tube" refers to the first heated tube in which the polymerization is to take place. Monomers of the same or different chemical structure can be introduced into the tubular reactor at these multiple monomer feeds. This arrangement is ideal for the production of block copolymers, with different monomer types being added at the different monomer feeds, thus forming polymer blocks.

[0075] In a variant of this design, all spirally wound tubes are the same length, so that depending on the length of the polymer block to be produced, a different number of consecutively arranged tubes (here without a monomer feed in between) are used. The length of a polymer block is thus controlled by the amount of monomer supplied (of the same chemical structure) and the number of subsequent tubes. Subsequently, a monomer of a different chemical structure, for example, can be added to the next monomer feed, which polymerizes onto the "growing polymer chain" in the subsequent tubes.

[0076] It is also preferred if, during passage according to the invention, the flow velocity is in the range from 0.1 cm / s to 1 cm / s, particularly preferably 0.21 cm / s (±0.05 cm / s).

[0077] In embodiments, the flow rate during passage is in the range of 9 mL / min to 11 mL / min and the inner tube diameter is 9 mm to 11 mm. The tube length is preferably 1 m (±10%).

[0078] The reaction mixture containing the at least one oxazoline monomer according to the invention and passed through the tubular reactor can expediently also contain an initiator capable of initiating the respective polymerization reaction. The same applies to terminating reagents capable of stopping the polymerization or terminating chain growth, which are preferably used at the end of the tube in which the polymerization takes place, or only afterward.

[0079] The solvent in the process according to the invention, which is expediently added to the oxazoline monomer, i.e., which flows through the tubular reactor as part of the reaction mixture, is preferably a non-nucleophilic solvent. It is particularly preferably a polar, non-protic solvent, in particular selected from acetonitrile, chlorobenzene, chloroform, 1,2-dichlorobenzene, dichloromethane, dimethylformamide, dimethyl sulfoxide, and mixtures thereof, in particular a mixture of acetonitrile and chlorobenzene. As is known, other solvents such as methanol, ethanol, or water can also be used for termination, i.e., for terminating the polymerization at the end of the process according to the invention.

[0080] All embodiments can be combined with each other in any way.

[0081] Implementation examples

[0082] Examples 1-3: High-throughput synthesis:

[0083] The initiator was weighed and dissolved in a mixture of 19 mL of dry chlorobenzene 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 pumped into a spiral-tube reactor.

[0084] The spiral tube reactor had an inner tube diameter of 10 mm and the coils had a diameter of 72 mm.

[0085] The flow rate was 10 mL / min, the reactor temperature was between 130 and 150 degrees Celsius, and the pressure was 40 bar. After 30 to 35 minutes of flow, the product was collected in a bottle with a small amount of piperidine for 90 minutes. The resulting mixture was concentrated, taken up in methanol, and precipitated with a 15-fold excess of diethyl ether. The process was repeated, the product was dissolved in water, and freeze-dried.

[0086] About the spiral tube reactor used:

[0087] The inner diameter was 10 mm. The flow is calculated as follows:

[0088] Radius r = 5 mm = 0.05 dm, cylinder volume: V = r A 2 * pi * h, where h corresponds to the pipe length and is at h= 1 m = 10 dm.

[0089] V = 0.05 * 0.05 * 3.141 * 10 dm A 3 = 78.5 ml For a length of 1 m, the result is 78.5 ml / m.

[0090] The flow rate was set to 10 mL / min. The calculated cylinder volume is: 0.1274 m / min = 12.74 cm / min = 0.212 cm / s

[0091] The monomer throughput is calculated as follows: m(monomer) = 21 g, M(monomer) = 85.1 g / mol, n(monomer) = 247 mmol

[0092] 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 solution

[0093] 10 ml / min flow (in 5 minutes) 247 / 5 mmol / min = 49.4 mmol / min. A safety margin is maintained to prevent air from entering the system. Table 1 shows various design examples.

[0094] Table 1 shows the batch sizes of three examples, each using methyloxazoline (MeOx) with the terminating reagent piperidine.

[0095] Table 2 shows the corresponding analytical results of the obtained polyoxazoline (Mn... number average molecular weight, Pn... degree of polymerization, D... dispersity of the polymer). About the spiral tube reactors used:

[0096] Table 3: Tube designs: Lines 2 and 26 show tube designs from the prior art, preferred embodiments of the invention in lines 4-8, 13-20 and 22-24 and in line 14 the spirally wound tube used in the embodiments 1 to 3 as a spiral tube reactor. Table 3 shows the respective dimensions of the spiral-wound tubing according to the manufacturer's specifications, Swagelok®. The units listed in the columns are decimal values ​​for measurements in mm and inches, except for the "Outer Diameter [inch]" and "Bend Radius [inch]" columns. In these exceptions, the dimensions are given in standard (imperial) fractions.

[0097] The goal was to achieve the largest possible lambda (inner diameter) / coil diameter. To achieve this, the inner diameter should be as large as possible, while maintaining a tight coil length and a small coil diameter. Since the manufacturer specifies values ​​for each outer and inner radius, these lambda values ​​are easily reproducible.

[0098] It can be assumed that the respective bending radii for stainless steel with the corresponding wall thicknesses are similar for many manufacturers due to the material parameters. The lambda value was calculated from the manufacturer's specifications for the bending radii and inner radii. The coil diameter is twice the bending radius.

[0099] It is evident that lambda values ​​of 0.10 to 0.17 can be achieved with a minimal bending radius. However, the pipes must be specifically shaped to these bending radii.

[0100] Comparative example 4 - according to WO 2017 / 182610 A1 :

[0101] Table 3 shows in the second entry (line 2) the calculation of the maximum lambda value for the tubular reactor from WO 2017 / 182610 A1.

[0102] If these bending radii are not specified (as in the application from Ghent University, i.e., WO 2017 / 182610 A1), it must be assumed that the bending was done unintentionally. This is plausible, since pipes with outer diameters of 1 / 16" and 1 / 8", in particular, can be wound by hand. This results in a maximum lambda value of 0.06, obtained from the data from Ghent University (inner diameters and bending radii from the examples in the disclosure). Table 3, line 26, shows a calculation of the maximum lambda value according to WO 2017 / 1812610 A1 for PTFE as the pipe material.

[0103] However, since WO2017 / 182610A1 a) specifies PTFE as an additional material with an even smaller lambda value of 0.026 at most, and b) does not specify a bending radius or winding diameter, it can be assumed that the present disclosure was purely used to save space by winding. Cited non-patent literature

[0104] Reis MH, Leibfarth FA, Pitet LM (2020)

[0105] Polymerizations in Continuous Flow: Recent Advances in the Synthesis of Diverse Polymerie Materials. ACS Macro Lett. 9, 123-133.

Claims

Patent claims 1. A process for the continuous synthesis of polyoxazolines comprising the following step: Passing at least one oxazoline monomer through a spiral tube reactor under the action 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. Method according to claim 1, characterized in that the pipe inner diameter is 10 mm ± 1 mm.

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

01.

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. 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. 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. 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. 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. 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. The process 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 a further spirally wound tube.

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 upstream of the first tube and between the at least one first and at least one second tube.

12. Method according to one of claims 1 to 11, characterized in that the flow velocity during passage is in the range from 0.1 cm / s to 1 cm / s.

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 having 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 pipe inner 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. Use of a spiral tube reactor for the continuous synthesis of polyoxazolines according to claim 13, characterized in that the A spiral tube reactor includes a heating element.

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