阅读说明：本技术 制备双环胍及其衍生物的方法 (Process for preparing bicyclic guanidines and derivatives thereof ) 是由 尤西·海尔米纳 阿利斯泰尔·金 伊尔卡·基佩莱纳 于 2018-11-08 设计创作，主要内容包括：本发明涉及双环胍及其衍生物的生产方法。特别地,本发明涉及生产三氮杂双环癸烯(TBD)及其衍生物,特别是烷基衍生物,例如甲基三氮杂双环癸烯(MTBD)和MTBD衍生的离子液体的方法。本发明还涉及所述化合物在纤维素溶解和随后加工中的应用。(The present invention relates to a process for the production of bicyclic guanidines and derivatives thereof. In particular, the present invention relates to a process for the production of Triazabicyldecene (TBD) and derivatives thereof, especially alkyl derivatives, such as Methyltriazabicyclodecene (MTBD) and MTBD derived ionic liquids. The invention also relates to the use of said compounds for cellulose dissolution and subsequent processing.)

1. A method of making bicyclic guanidine and derivatives thereof comprising contacting cyanamide and a polyamine at an elevated temperature to react the cyanamide with the polyamine, wherein the method is substantially free of added solvent and produces the base form of the bicyclic guanidine.

2. The method of claim 1, wherein the bicyclic guanidine consists of unsubstituted or substituted rings comprising at least 5 members or ring atoms, wherein the number of members in each ring is the same or different.

3. The method of claim 1 or 2, wherein the derivative of bicyclic guanidine comprises a compound wherein one or more ring atoms of bicyclic guanidine are substituted with a substituent such as alkyl, substituted alkyl, alkenyl, hydroxyalkyl, alkoxy or substituted alkoxy, mono or dialkylamino, aminoalkyl or substituted aminoalkyl.

4. The process according to claim 1 for the preparation of 1,5, 7-triazabicyclo [4.4.0] dec-5-ene (TBD) and its derivatives, in particular alkyl derivatives, such as methyl and ethyl derivatives.

5. The method of any one of the preceding claims, wherein the cyanamide comprises dicyandiamide.

6. The process of any of the preceding claims, wherein the polyamine comprises a triamine or a tetramine, such as bis (3-aminopropyl) amine or Dipropylenetriamine (DPTA), diethylenetriamine, triethylenetetramine, tripropylenetetramine, ethylenepropylenetriamine, 3- (2-aminoethylamino) propylamine, or a combination thereof.

7. The method of claim 6, in which the triamine comprises bis (3-aminopropyl) amine or Dipropylenetriamine (DPTA).

8. The method of claim 6, wherein the polyamine comprises 3- (2-aminoethylamino) propylamine.

9. The process of any one of the preceding claims, wherein the cyanamide is dissolved in a first solution of the polyamine and the first solution is gradually added to a second solution of the polyamine, wherein the second solution of the polyamine is maintained at an elevated temperature.

10. The method of any one of the preceding claims, wherein the elevated temperature is the boiling point of the polyamine under applied pressure.

11. The method according to any of the preceding claims, wherein the elevated temperature is 150-.

12. The process of any one of the preceding claims, wherein the cyanamide is contacted with the polyamine in the presence of an acid catalyst such as p-toluenesulfonic acid.

13. A process for preparing 1,5, 7-triazabicyclo [4.4.0] dec-5-ene (TBD) and derivatives thereof, comprising the step of contacting dicyandiamide with bis (3-aminopropyl) amine in a bis (3-aminopropyl) solution at a temperature of at least 150 ℃ and reacting said dicyandiamide with said bis (3-aminopropyl) amine to form TBD in the base form.

14. The method of claim 13, wherein the first solution of bis (3-aminopropyl) amine comprises dicyandiamide and the first solution comprising bis (3-aminopropyl) amine and dicyandiamide is added stepwise to the second solution of bis (3-aminopropyl) amine maintained at a temperature of at least 150 ℃.

15. The method according to claim 13 or 14, wherein the temperature is 150-.

16. The method of any one of claims 13-15, which is substantially free of added solvent.

17. The process of any one of claims 13-16, wherein the step of contacting dicyandiamide with bis (3-aminopropyl) amine is carried out in the presence of an acid catalyst.

18. The process according to any one of the preceding claims, wherein less than 2 wt.%, preferably less than 0.2 wt.% melamine is formed as a by-product of the reaction.

19. The process according to any one of the preceding claims, for the preparation of alkyl derivatives of TBD, such as methyl and ethyl derivatives of TBD, in particular methyl derivatives of TBD (MTBD).

20. The method according to any one of the preceding claims, wherein the bicyclic guanidine is further processed to form an analogue or conjugate thereof, in particular an acid-base conjugate or an ionic liquid.

21. Use of a bicyclic guanidine or a derivative thereof produced by the method according to any one of claims 1 to 20 for the production of an analogue or conjugate thereof, in particular an ionic liquid or an acid-base conjugate.

22. An ionic liquid comprising a bicyclic guanidine or derivative thereof formed according to the method of any one of claims 1-20.

23. An ionic liquid according to claim 22, wherein the bicyclic guanidine is 1,5, 7-triazabicyclo [4.4.0] dec-5-ene (TBD) or a derivative thereof, in particular a methyl derivative, formed according to the method of any one of claims 1 to 19.

Technical Field

The invention relates to a method for producing bicyclic guanidine and derivatives thereof. In particular, the present invention relates to a process for the production of Triazabicyldecene (TBD) and derivatives thereof, especially alkyl derivatives, such as Methyltriazabicyclodecene (MTBD) and MTBD derived ionic liquids. The invention also relates to the use of said compounds in cellulose dissolution and processing.

Background

Triazabicyldecene or 1,5, 7-triazabicyclo [4.4.0] dec-5-ene (TBD) is a bicyclic strong guanidine base. It is an organic superbase that can be used as an organic catalyst and metal ligand precursor with potentially broad applications, such as for various base-mediated organic transformations. For example, it is a known catalyst for esterification, epoxy resin formation, and cyclic carbonate ring opening chemistry.

Methyl derivatives of TBD (MTBD) and MTBD-derived ionic liquids (acid-base conjugates) find particular use in cellulose dissolving applications. It has been determined that ionic liquids derived from MTBD, particularly [ mTBDH ] [ OAc ], have greater hydrolytic stability than ionic liquids previously used for cellulose dissolution (e.g., [ DBNH ] [ OAc ]).

The synthesis of TBD, its methyl derivative (MTBD) and related ionic liquids has been thoroughly investigated.

WO 2011/112594a1 describes the synthesis of TBD from dicyandiamide and bis (3-aminopropyl) amine (or dipropylenetriamine, DPTA) in the presence of a weak acid using a near stoichiometric amount of carbon dioxide as the acid. The disclosed synthesis is carried out in the presence of added solvent and yields TBD in salt form. WO 2011/079041a1 discloses a process for preparing polycyclic guanidines in which a triamine compound is reacted with a guanidine, cyanamide or melamine compound in a solvent. The process produces TBD as a salt, such as a mesylate or carbonate. In the process of WO2012/116080a1, bicyclic guanidine salts are prepared in an aqueous medium by reacting a guanidine carbonate salt or dicyandiamide with an acid and dipropylene triamine.

Finally, WO 2013/163130A1 discloses a process for the production of 1,5, 7-triazabicyclo [4.4.0] dec-5-ene by reaction of disubstituted carbodiimides, dipropylenetriamines with ether solvents and/or alcohols.

In the current process, TBD is obtained as the free base, unlike TBD which is usually obtained as a salt thereof in previous processes. Since there is no need to release TBD from the salt form prior to methylation, work-up and methylation (derivatization) can be carried out easily. Furthermore, it is thus possible to obtain various salts of TBD, which are reacted with acids. Furthermore, the existing processes for the synthesis of TBD involve considerable costs associated with the synthesis and purification steps, with only moderate or low yields. In addition, many prior art methods also involve toxic reagents or produce byproducts that are difficult to separate or may themselves be hazardous.

Thus, there is a general need for a cost-effective TBD preparation process for further conversion to MTBD and MTBD-derived ionic liquids without the formation of undesirable by-products. The MTBD-derived ionic liquids are designed for cellulose dissolution and subsequent processing purposes, such as lyocell-type fiber spinning or chemical modification.

Disclosure of Invention

It is an object of the present invention to provide a novel method for the synthesis of bicyclic guanidines, particularly TBD, to maximize yield and reduce costs associated with synthesis and expensive purification steps.

It is another object of the present invention to provide a novel TBD synthesis process which avoids the formation of large amounts of undesirable by-products and produces TBD in the base form, which can be used for isolation or further processing. TBD and its methylated derivative MTBD obtained in base form by the process of the invention are also of high purity.

It is yet another object of the present invention to provide a novel method of synthesizing bicyclic guanidines, particularly TBD, substantially free of added solvents.

According to a first aspect of the present invention there is provided a process for the preparation of bicyclic guanidines, particularly 1,5, 7-triazabicyclo [4.4.0] dec-5-ene (TBD) and derivatives thereof, which process comprises the step of contacting a cyanamide with a polyamine at elevated temperature, particularly in the liquid phase formed by the polyamine, to react the cyanamide with the polyamine.

According to a second aspect of the present invention there is provided the use of bicyclic guanidine or a derivative thereof produced by the method according to the invention in the production of an analogue or conjugate thereof, in particular an ionic liquid or acid base conjugate.

According to a third aspect of the present invention there is provided an ionic liquid comprising a compound formed according to the method of the present invention, in particular for use in cellulose dissolution.

The invention is defined by the features of the independent claims. Some specific embodiments are defined in the dependent claims.

Significant advantages are obtained by the present invention. Thus, the synthetic method of the present invention maximizes yields and reduces costs associated with current synthesis and purification steps of bicyclic guanidines, particularly TBD.

Furthermore, the process avoids the formation of large amounts of melamine as an unwanted by-product, while generating TBD in the base form, which can be used for isolation or further processing. Thus, there is no need to release TBD from a stoichiometric or near stoichiometric amount of the salt-forming acid. (e.g., HCl, p-toluenesulfonic acid, carbonate, bicarbonate, or carbonic acid/carbamic acid derivatives).

The invention also improves the stability of the MTBD derived ionic liquid through fiber spinning. Higher stability means that the recovery of ionic liquid is more efficient.

Drawings

Figure 1 illustrates a reaction scheme for MTBD in accordance with at least some embodiments of the present invention. Figure 1 also shows that DPTA can be produced at low cost from ammonia and acrylonitrile.

Detailed Description

Definition of

As used herein, the term "bicyclic guanidine" refers to a guanidine consisting of an unsubstituted or substituted ring, which contains at least 5 members, i.e., atoms, located in the ring structure. The bicyclic guanidine can thus have, for example, a 5-membered ring, a 6-membered ring, and/or a 7-membered ring. The number of members in each ring of the cyclic guanidine can be the same or different.

As used herein, a "derivative" of a bicyclic guanidine includes, but is not limited to, compounds in which one or more ring atoms of the bicyclic guanidine are substituted with a substituent such as alkyl, substituted alkyl, alkenyl, hydroxyalkyl, alkoxy or substituted alkoxy, mono-or dialkylamino, aminoalkyl or substituted aminoalkyl groups. Derivatives of bicyclic guanidines also include substituted or unsubstituted bicyclic guanidines that have been further processed to form, for example, acid-base conjugates (ionic liquids).

The present technology, including embodiments discussed in more detail below, is applicable to the preparation of bicyclic guanidines and derivatives thereof, particularly TBD and derivatives thereof, such as alkyl derivatives.

As used herein, the term "alkyl" refers to a saturated, straight or branched chain hydrocarbon radical containing from one to eight carbon atoms. In certain embodiments, the alkyl group contains 1 to 6 carbon atoms or 1 to 5 carbon atoms. In some embodiments, the alkyl group contains 1 to 4 carbon atoms, 1 to 3 carbon atoms, or 1 to 2 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, pentyl, hexyl, and the like.

As used herein, the term "alkenyl" refers to a straight or branched chain hydrocarbon group having at least one carbon-carbon double bond. In certain embodiments, alkenyl groups contain 2-12 carbon atoms. In some embodiments, an alkenyl group contains 2 to 8 carbon atoms, 2 to 6 carbon atoms, or 2 to 5 carbon atoms. In some embodiments, an alkenyl group contains 2 to 4 carbon atoms or 2 to 3 carbon atoms. Examples of alkenyl groups include, but are not limited to, ethenyl, propenyl, butenyl, 1-methyl-2-buten-1-yl, and the like.

In one embodiment of the invention, cyanamide and a polyamine are contacted at an elevated temperature to react the cyanamide with the polyamine to form a bicyclic guanidine.

Cyanamide refers to cyanamide and dicyandiamide or 2-cyanoguanidine, preferably dicyandiamide.

The polyamine is preferably a triamine, but may also be a tetraamine. Examples of suitable polyamines include, but are not limited to, bis (3-aminopropyl) amine or Dipropylenetriamine (DPTA), diethylenetriamine, triethylenetetramine, tripropylenetetramine, ethylenepropylenetriamine, 3- (2-aminoethylamino) propylamine, or combinations thereof.

By "high temperature" is meant a temperature range that includes the boiling point of the polyamine under an applied pressure, e.g., at atmospheric pressure or under an overpressure. In one embodiment of the invention, the temperature range is 150-. To avoid the formation of undesirable by-products, such as melamine, it is preferred to carry out the reaction at a temperature above about 150 ℃.

The time allowed for the reaction to proceed can be adjusted to maximize the yield of the desired product and minimize the formation of by-products. Such adjustments will be apparent to those skilled in the art. For example, the reaction time of dicyandiamide with DPTA may be 0.5 to 24 hours, or preferably 4 to 8 hours.

In one embodiment, the present invention takes advantage of the new finding that bis (3-aminopropyl) amine or Dipropylenetriamine (DPTA) is an unexpectedly good solvent for dicyandiamide (DCD), which is otherwise difficult to dissolve. Unexpectedly, the amount of DCD dissolved by DPTA exceeded the stoichiometric ratio of the reaction. In one embodiment, another unexpectedly good solvent for dicyandiamide is 3- (2-aminoethylamino) propylamine (N3-amine), which dissolves DCD in an amount exceeding the stoichiometric ratio for the reaction. Other complex solvents would require additional purification steps, which would add significantly to the overall cost.

In one embodiment, the process of the invention therefore comprises contacting dicyandiamide (DCD) with bis (3-aminopropyl) amine (DPTA), in particular in the liquid phase. Preferably, DCD is contacted in a liquid phase consisting of or consisting essentially of bis (3-aminopropyl) amine. As mentioned above, the reaction is carried out at elevated temperature, preferably in the presence of an amount of polyamine which exceeds the stoichiometric ratio of the reaction.

In a preferred embodiment, the cyanamide is thus contacted with a stoichiometric excess of the polyamine, in particular with a molar amount of the polyamine of from 1.5 to 1000 times, for example from 2 to 500 times, in particular from 2 to 50 times, for example from 3 to 10 times the molar amount of the cyanamide.

In another embodiment, the process of the present invention comprises contacting dicyandiamide (DCD) with 3- (2-aminoethylamino) propylamine (N3-amine), particularly in the liquid phase consisting of N3-amine or consisting essentially of N3-amine.

Dicyandiamide can be added stepwise in powder form when it is contacted with DPTA or N3-amine, or as a solution of DPTA or N3-amine in liquid form. As a typical by-product of the reaction, gaseous ammonia is formed. In some embodiments, ammonia may be recovered and recycled, thereby eliminating a possible waste stream.

In one embodiment, the process of the present invention comprises dissolving cyanamide in a first solution of a polyamine and gradually adding the solution to a second solution of a polyamine, wherein the second solution of polyamine is maintained at an elevated temperature.

In one embodiment, contacting the cyanamide with the polyamine is performed in the presence of an acid catalyst. Suitable acid catalysts may include, but are not limited to, inorganic acids such as hydrochloric acid, sulfuric acid, or phosphoric acid, and organic acids such as sulfonic acid or acetic acid. Suitable sulfonic acids include alkyl or aryl sulfonic acids known to those skilled in the art. Exemplary sulfonic acids include, but are not limited to, methane sulfonic acid, trifluoromethane sulfonic acid, and p-toluene sulfonic acid, and mixtures thereof. Suitable acetic acids include, but are not limited to, fluoroacetic acids, such as trifluoroacetic acid. However, the process of the present invention can be accomplished without the addition of an acid catalyst or in the presence of a small amount of an acid catalyst.

In one embodiment of the invention, the synthesis of TBD is carried out by contacting dicyandiamide (DCD), preferably in a bis (3-aminopropyl) amine (DPTA) solution, with DPTA and preferably an acid catalyst (e.g. p-toluenesulfonic acid) at elevated temperature (e.g. 220 ℃) with gaseous ammonia as a by-product.

The process of the present invention also comprises an embodiment wherein dicyandiamide is dissolved in a first solution of bis (3-aminopropyl) amine and the first solution comprising bis (3-aminopropyl) amine and dicyandiamide is gradually added to a second solution of bis (3-aminopropyl) amine maintained at a temperature of at least 150 ℃, preferably at least 200 ℃.

In one embodiment, dicyandiamide is dissolved in a liquid phase formed from bis (3-aminopropyl) amine to form a solution, and dicyandiamide and bis (3-aminopropyl) amine are reacted in the presence of an acid catalyst to produce TBD. The acid catalyst may be added before or after adding dicyandiamide to the liquid phase formed by bis (3-aminopropyl) amine.

Preferably, the acid catalyst used is soluble in bis (3-aminopropyl) amine, in which case a homogeneous reaction mixture is obtained.

Generally, in the above embodiments, no or a small amount of melamine is formed as a by-product of the reaction. The term "melamine-free" is to be interpreted such that the amount of melamine after completion of the reaction is less than 2% by weight, preferably less than 0.2% by weight, of the liquid phase.

In one embodiment, the reaction scheme for MTBD is shown in figure 1.

TBD can be alkylated to its alkyl derivatives, such as methyl and ethyl derivatives, by mixing it with a suitable solvent and adding an alkylating agent, such as an alkyl carbonate, alkyl halide, alkyl sulfate, alkyl sulfonate or alkyl phosphonate. Thus, TBD is methylated to MTBD, for example, by reacting TBD with methyl carbonate, methyl halide, methyl sulfate, methyl sulfonate, or methyl phosphonate. Similar ethylating reagents are suitable for ethylation of TBD.

In one embodiment, methylation of TBD is performed with dimethyl carbonate.

The process of the invention can be carried out batchwise or continuously.

The TBD or its methyl derivative MTBD formed according to the process of the present invention can be obtained in an extremely pure form. In some embodiments, the TBD obtained by the process of the present invention may be subjected to sublimation, distillation, or crystallization.

With the process of the invention, TBD yields of greater than 60% or greater than 65-70% can be obtained. Furthermore, the process produces much lower amounts of by-products, in particular melamine, than the prior art processes for the preparation of TBD.

Surprisingly, in the process of the present invention DPTA can act as both a reagent and a solvent, thus eliminating the need for an external solvent to be added to the reaction mixture. Alternatively, the ammonia formed in the reaction may act as a solvent for the cyanamide, for example in a continuous process.

The preparation of TBD and subsequent conversion to MTBD, and then to an MTBD-derived ionic liquid (acid-base conjugate) in a cost-effective manner has advantages in cellulose dissolution. The ionic liquids are designed for the purpose of cellulose dissolution and subsequent processing, such as lyocell-type fibre spinning or chemical modification. It has been determined that MTBD-derived ionic liquids, particularly [ mTBDH ] [ OAc ], are more stable to hydrolysis than the previous IONCELL-F generation (e.g., [ DBNH ] [ OAc ]).

It is to be understood that the disclosed embodiments of the invention are not limited to the particular structures, process steps, or materials disclosed herein, but extend to equivalents thereof as will be recognized by those skilled in the art. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment.

As used herein, a plurality of items, structural elements, compositional elements, and/or materials may be presented in a common list for convenience. However, these lists should be construed as though each member of the list is individually identified as a separate and unique member. Thus, no single member of such list should be construed as a de facto equivalent of any other member of the same list solely based on their presentation in a common group without indications to the contrary. In addition, reference may be made herein to various embodiments and examples of the invention and alternatives for various components thereof. It should be understood that such embodiments, examples and alternatives are not to be construed as actual equivalents of each other, but are to be considered as independent and autonomous representations of the present invention.

Furthermore, the described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. In the following description, numerous specific details are provided, such as examples of lengths, widths, shapes, etc., to provide a thorough understanding of embodiments of the invention. One skilled in the relevant art will recognize, however, that the invention can be practiced without one or more of the specific details, or with other methods, components, materials, and so forth. In other instances, well-known structures, materials, or operations are not shown or described in detail to avoid obscuring aspects of the invention.