Method for preparing electron-deficient olefin monomer

Abstract

The invention relates to a method for preparing an electron-deficient olefin monomer. According to the method, the electron-deficient monomer is directly synthesized by catalyzing a reaction between an active methylene compound and a mixture of a formaldehyde source and carboxylic acid anhydride or a reaction between the active methylene compound and carbonyl condensation ester, and an adopted catalyst system is an acid-based catalyst system. The obtained product is a high-purity reactive monomer, and has application value in the field of rapid curing adhesives.

Description

Technical Field

[0001] The invention relates to a method for preparing an electron-deficient olefin monomer comprising a nitrile, a carboxylic acid ester or a carboxylic acid functional group. The method has application value in the field of fast-curing adhesives. Background Art

[0002] Electron-deficient monomers carry two electron-withdrawing groups (EWG) on the same carbon atom of their olefinic bond. These monomers are highly susceptible to polymerization initiated by electron-rich species due to the polarization of the double bond. One example is cyanoacrylate monomers (CA), represented by the general formula (I), where R is usually an alkyl group. Although various different CAs are known, only ethyl cyanoacrylate (ECA) of formula (II) is produced on a large scale due to the high demand, as it is the main component of commercially important instant adhesives.

[0003]

[0004] The high reactivity of electron-deficient monomers is very attractive for application purposes, such as fast-curing adhesives, but faces challenges in production, especially in large-scale production. The long-standing traditional production method of CA utilizes the Knoevenagel condensation reaction of nitrogen-based (N-based or N-based) cyanoacetate starting materials with paraformaldehyde to first form oligomers, which are then thermally decomposed back to monomers.

[0005] Cyanoacetate belongs to the class of active methylene compounds and is represented by the general formula (III), wherein EWG and Z 1 Can be the same or different electron withdrawing groups:

[0006] EWGCH2 1 (III).

[0007] For example, ethyl cyanoacetate (NC-CH2-CO2Et) is the starting material for the production of ECA.

[0008] Such starting materials are considered "active" because the acidity of the central methylene hydrogen atom is easily eliminated by base. Therefore, the relative reactivity of active methylene compounds depends on the conditions in which they are used and the type, strength and combination of geminal EWGs they possess, as explained in Sankar et al., Current Chemistry Letts., 2012, 1(3), 123-132.

[0009] Cyanoacetates are highly reactive under base-catalyzed reaction conditions.

[0010] In the Knoevenagel reaction, the use of various types of amine and ammonium / immonium salt organocatalysts in the formation of α,β-unsaturated compounds by the reaction of aldehydes with active methylene compounds has been widely described in general synthetic organic chemistry, especially recently, for example, in van Beurden et al., Green Chemistry Letts. and Reviews, 2020, 13 (4), 349-364, and in List, B., Angew. Chem. Int. Ed., 2010, 49, 1730-1734. These N-based organocatalysts can activate active methylene compounds and form carbanion nucleophiles.

[0011] There is a dichotomy in the synthesis of electron-deficient olefin monomers from active methylene compounds, because on the one hand, bases promote the reactivity of active methylene compounds, but on the other hand, the monomers derived from them are very unstable in the presence of base. In the case of CA, traditional production methods have solved this problem by first producing oligomers rather than monomers, neutralizing the basic amine catalyst, and then pyrolyzing or "cracking" the oligomers under acidic conditions before the monomers can be released. This two-step process reduces the possibility of free monomers interacting with trace amounts of base. Therefore, the cleavage or pyrolysis of the oligomers described above is an "indirect" production method because the monomers are not obtained from the initial reaction environment. Similar cleavage methods have been applied to the synthesis of various other electron-deficient olefins, for example, vinyl dione and cyano vinyl ketone monomers described in US Patent 9828324 and GB Patent 1168000, respectively. However, due to its commercial importance, most of the attention paid to using this method is focused on CA processing, for example, as outlined in patents US 2721858, US 2756251, US 2763677, US 4364876, US 5455369, US 5624699, US 6245933 and US 9828324. The patents disclose that in the synthesis of CA and vinyl diketone, N-based catalysts specifically promote the oligomerization of the starting materials. The oligomerization process is further explained in Chorbadjiev et al., Eur. Polym. J., 1991, 27 (4 / 5), 439-443.

[0012] Although pyrolysis can solve the problem of free monomer exposure to alkali, the harshness of the pyrolysis conditions creates disadvantages. This method is impractical for CA esters with higher boiling points and is not suitable at all for the synthesis of monomers with thermosensitive moieties, including monomers with multiple or mixed polymerizable functional groups, whose oligomers are cross-linked. In addition, traditional CA production methods produce a large amount of difficult-to-handle polymers, or so-called pyrolysis residues, which limit monomer yields, are costly to handle, and are environmentally unfriendly.

[0013] To address these shortcomings, efforts have focused on producing electron-deficient monomers through "direct" synthesis and discovering methods to obtain a wider range of this important class of monomers under milder conditions. These methods generally utilize a methylation reaction that involves the direct formation of a double-bonded methylene group (CH2=) on an active methylene compound substrate after transfer of a saturated methylene group (-CH2-) from a methylene transfer agent. Unlike traditional indirect methods, direct methods face unique challenges associated with maintaining the stability of free reactive monomers in the reaction environment and in all subsequent process steps.

[0014] In the CA case, patents US 8022251 and US 8053589 disclose a direct process using a Mannich adduct that exploits the volatility difference between a distillable monomer and a non-distillable by-product derived from the adduct. The adduct is composed of a cyanoacetic acid ester and a stoichiometric amount of a specialized imine-type methylene transfer reagent (CH2=N + HRX - , where R = branched alkyl, X = sulfonate) are reacted, these reagents are prepared from amines in a separate process. This method produces a large amount of ammonium salt byproduct in stoichiometric amounts. et al., Pharmazie, 1985, 40(10), 697-701 reported the use of imide salts for methylation of vinyl diketone monomers.

[0015] In another direct method, in contrast, an iminium salt or an ammonium salt is used as an organic catalyst, rather than a reagent, for the reaction of an active methylene compound with at least one stoichiometric amount of methylene diacetate (MeCOOCH2OOCMe, an acylal, i.e., a compound containing a gem-dicarboxy or gem-bis(acyloxy) moiety), which acts as a methylene transfer reagent, as disclosed in US Pat. No. 9670145. This method reports the highest isolated monomer yields of CA when the acylal is first prepared in a separate process.

[0016] Since all of the aforementioned direct or indirect methods rely on some nitrogen-based (N-based) species or catalysts, a large excess of acid must be applied at some stage of any type of process to avoid interaction with free basic amines, which are highly unstable to the target electron-deficient olefin monomers. This excess produces a large amount of residues and a large number of by-products, which must also be completely removed. Protic acids are usually used to neutralize or acidify the reaction or process environment.

[0017] Although bases can cause instability in electron-deficient monomers, polymerization of electron-deficient monomers can be inhibited by acids. Since the Knoevenagel reaction is also known to be catalyzed by Lewis acids, acid-catalyzed methods have been described in three related patents for the direct synthesis of CA using paraformaldehyde to transfer the methylene group.

[0018] In patent US10913707, the relative conversion of cyanoacetate to cyanoacrylate was only 14% after 6 hours at 90°C in a nitromethane-acetonitrile mixed solvent using a high loading (10 mol%) of a lanthanide Lewis acid catalyst. The conversion of the starting material to the monomer was also low (<27%). A similar process is described in patent US10889542, but the results did not improve with the increase in reaction time. In the latter two cases, in the first step, the specific cyanoacetate was prepared in situ by esterification of cyanoacetic acid or by transesterification of ethyl cyanoacetate, respectively, using the same catalyst, before attempting monomer synthesis in the second step. In a third variant of the same reaction method described in patent US10927071, a preformed cyanoacetate was used instead, and the reaction time was as long as 23 hours. In the latter case, 20-30% of the cyanoacetate starting material was not converted into monomer, and the monomer remained in solution. To date, attempts at this acid-catalyzed Knoevenagel synthesis of CA have shown low efficiency even in solution. In none of the three aforementioned patents has isolation of the unprotected electron-deficient monomer been demonstrated from a water-miscible solvent system generated in the reaction.

[0019] Although various methods for preparing electron-deficient olefin monomers are disclosed in the prior art, there is a lack of an efficient method for preparing said monomers from readily available starting materials under acid catalysis in a stable environment, avoiding the use of N-based catalysts and directly isolating the reactive monomers from the reaction medium. Summary of the invention

[0020] The object of the present invention is a method for preparing electron-deficient olefin monomers. DETAILED DESCRIPTION

[0021] The object of the present invention is a method for preparing electron-deficient olefin monomers, wherein an active methylene compound of the general formula (III) is reacted with any one of a) or b) in the presence of a catalyst system;

[0022] EWGCH2 1 (III)

[0023] Among them, EWG and Z 1 Two electron withdrawing groups represented by are selected from nitrile, carboxylate and carboxylic acid functional groups;

[0024] wherein a) is a mixture of a formaldehyde source and a carboxylic anhydride of the general formula (IV),

[0025]

[0026] Among them, Q 1 and Q 2 is independently selected from linear and branched C1-C4 alkyl, optionally, the H atom is replaced by a F atom; preferably, Q 1 and Q 2 are independently Me or Et; more preferably, Q 1 and Q 2 Independently for Me;

[0027] The catalyst system comprises:

[0028] i) at least one acid, or,

[0029] ii) at least one acid and at least one promoter,

[0030] wherein the acid is selected from the group of Lewis acids and Bronsted acids, and the at least one co-catalyst is selected from the group of phenolic compounds having one or more substituents, and quinone compounds;

[0031] b) is a methylene diester of the general formula (V),

[0032]

[0033] Among them, Q 1 and Q 2 independently selected from C1-C4 straight chain and branched alkyl groups,

[0034] The catalyst system comprises a Bronsted acid and at least one co-catalyst, wherein the co-catalyst is selected from the group consisting of a phenolic compound having one or more substituents, and a quinone compound.

[0035] The authors of the present invention have developed a simple protocol for the preparation of electron-deficient olefin monomers by using an acid-based catalyst system, preferably together with a promoter for the Knoevenagel reaction, to convert active methylene compounds into said olefin monomers.

[0036] The authors of the present invention have developed a method for preparing electron-deficient olefin monomers which allows the direct preparation of the monomers without the need to include a thermal depolymerization step of a prepolymer. This is an efficient method for preparing the monomers from readily available starting materials under acid catalysis in a stable environment to avoid the use of N-based catalysts and to separate the reactive monomers directly from the reaction medium. Since all CA methods produce large amounts of by-products from various reagents that transfer or otherwise provide saturated methylene groups, an atom-efficient method is most desirable, wherein the by-products can be used to regenerate key reagents in the monomer formation reaction itself. The electron-deficient olefin compounds are reactive monomers with application value in the field of fast-curing adhesives. These compounds include cyanoacrylates and others.

[0037] The process of the present invention allows the preparation of high purity monofunctional and polyfunctional electron-deficient olefin monomers, whether they are liquid or solid.

[0038] In this specification, as well as in the claims, the singular forms "a", "an" and "the" include plural references unless the context clearly indicates otherwise. The term "about" refers to a deviation of plus / minus 10%, preferably plus / minus 5%. Unless otherwise indicated, percentages are expressed in weight % (wt%). The range defined by the term "between ... and ..." or the term "from ... to ..." is meant to include the stated endpoints as well as any narrower sub-ranges.

[0039] The present invention includes two main embodiments. One embodiment is referred to as the "three-component embodiment" and the other is referred to as the "two-component embodiment." However, for simplicity, both embodiments include additional minor components that form the catalyst system and stabilizer, and these components are described separately for clarity.

[0040] Three-component implementation plan

[0041] The three-component embodiment is a preferred embodiment. Because it includes three groups of reactants, it is called a three-component embodiment:

[0042] (i) active methylene compounds,

[0043] (ii) a formaldehyde source, and

[0044] (iii) Carboxylic anhydrides.

[0045] In a preferred embodiment, the active methylene compound is a cyanoacetate, the formaldehyde source is 1,3,5-trioxane, and the carboxylic acid anhydride is a symmetrical carboxylic acid anhydride, for example, acetic anhydride.

[0046] The reaction of the three component embodiment is catalyzed by a catalyst system comprising at least one acid, or at least one acid and at least one co-catalyst.

[0047] The catalyst system allows the in situ formation of carbonyl esters by the reaction of a formaldehyde source and a carboxylic anhydride. The reaction between the carbonyl esters and the active methylene compound produces an electron-deficient olefin monomer.

[0048] For the above preferred embodiment, the three-component embodiment of the method of the present invention can be represented according to Scheme I, taking the preparation of ethyl cyanoacrylate as a specific example:

[0049] Scheme I

[0050]

[0051] Active methylene compounds

[0052] The active methylene compound in the method of the present invention is a reactant that determines the type of electron-deficient olefin monomer produced.

[0053] In the present invention, the active methylene compound has the general formula (III):

[0054] EWGCH2 1 (III).

[0055] EWG and Z in the compound of general formula (III) 1 The electron withdrawing functional group in the active methylene compound of the present invention represented by is preferably selected from the group of nitrile (-CN), carboxylate (-CO2R) and carboxylic acid (-CO2H), more preferably selected from nitrile and carboxylate. In a preferred embodiment, the active methylene compound includes nitrile and carboxylate as electron withdrawing functional groups.

[0056] Preferred carboxylate groups (-CO2R) are selected from the following, wherein R is selected from a linear C1-C 18 Alkyl, alkenyl or alkynyl, branched C3-C8 alkyl, cyclic or condensed cycloaliphatic C3-C 20 , linear or branched C1-C4 alkoxyethyl, C1-C4 trialkylsilyloxyethyl, tetrahydrofuranyl, C1-C4 trialkylsilyl, -C2H4CO2H, -(CH2) n OC(O)CH2CN (wherein n=2-4), -(CH2)2OC(O)CH=CH2, and -(CH2)2OC(O)C(CH3)=CH2.

[0057] Active methylene compounds of general formula (III) are well known. Many such compounds are commercially available, for example, various alkyl cyanoacetates and 1,3-dicarbonyl compounds, and there are also many references to the preparation of other compounds in the literature. For example, in US 3092611, US 4202920, US 4364876, US 4528357, US 5140084, US 5175337, US 6096848, US 6271410, US 6281310, US 7262313, EP-A-0 459 617. WO-A-2007 / 046647, WO-A-2008 / 069515, WO-A-2009 / 053482; Vijayalaskhmi et al., J. Adhesion Sci. Tech., 1990, 4(9), 733-750, Guseva et al. al.,Izv.Akad.Nauk.,Ser.Khim.,1993,3,523-525,Kotzev et al.,Die Makromol.Chem.,1980,92(1421),41-52,Blanco et al. al.,Bull.Soc.Chim.Belg.,1989,98(12),923-929,Renner et al.,J.Polym.Sci.,Polym.Chem Ed.,1985,23,2341-2359,Senchenya et al.,Izv.Akad.Nauk.Ser Khim.,1993,42(5),909-911,Urankar etal.,J.Chem.Mater.,1997,9,2861-2868,Nicolas et al. The preparation of specialized cyanoacetic acid esters which may also be multifunctional or include mixed functionalities is described in Nakanishi et al., Macromolecules, 2008, 41, 8418-8428 or Nakanishi et al., Chemistry Letts., 2007, 36(3), 452-453, all of which are incorporated herein by reference.

[0058] In some embodiments of the present invention, the active methylene compound of formula (III) includes a carboxylic acid group in an ester group, for example, via NCCH2COO - Na + Reaction with bromoacetic acid produces a carboxylic acid group.

[0059] In some embodiments of the present invention, the active methylene compound of general formula (III) includes an electron withdrawing group, i.e., a carboxylic acid group, and another electron withdrawing group is preferably selected from nitrile and carboxylate. Some of the latter compounds are commercially available, such as cyanoacetic acid. For example, the preparation of other compounds is described in Levonis, et al., Aust. J. Chem., 2007, 60, 821–82, Xia et al., J. Chem. Res., 2005, 332-334, Kimura, M., Tetrahedron Lett., 2018, 59, 1295-1300, Mao et al., Eur. J. Org. Chem. 2020, (5), 525-538 or Bew et al., Chemistry, 2017, 23 (19), 4557-4569, and the above documents are incorporated herein by reference.

[0060] Regardless of type, one or more active methylene compounds may be used in the three component embodiment.

[0061] The concentration of the active methylene compound serves as a reference for the concentrations of the other components expressed as mole percentages or stoichiometry / molar ratios relative to the compound of formula (III).

[0062] In an embodiment, the preferred active methylene compound is a cyanoacetate, or a mixture of cyanoacetates, or a mixture of cyanoacetates and cyanoacetic acid. In a more preferred embodiment, the preferred active methylene compound is a cyanoacetate.

[0063] Formaldehyde Source

[0064] The realization of the three-component embodiment depends on the formation of carbonyl esters, which requires the presence of an aldehyde source and a carboxylic acid anhydride. In the present invention, the aldehyde source is a formaldehyde source.

[0065] The formaldehyde source is selected from dry formaldehyde gas, paraformaldehyde and 1,3,5-trioxane. The preferred formaldehyde source is 1,3,5-trioxane, whether or not recrystallized; more preferably, the formaldehyde source is in dry form in any convenient manner, such as recrystallization from acetone, ethyl acetate, petroleum ether and mixtures thereof, or sublimation.

[0066] The preferred molar concentration of 1,3,5-trioxane relative to the compound of formula (III) is 1.25:1; more preferably, the molar concentration is 1.1:1; most preferably, the molar concentration is 1:1.

[0067] Carboxylic anhydride

[0068] As noted above, the three-component embodiment of the process of the present invention requires the presence of a formaldehyde source and a carboxylic anhydride to obtain the carbonyl ester in situ, which is further reacted with an active methylene compound of formula (III) under Knoevenagel reaction conditions to obtain an electron-deficient olefin monomer.

[0069] The method of the present invention uses a carboxylic acid anhydride of the general formula (IV),

[0070]

[0071] Among them, Q 1 and Q 2 independently selected from linear and branched C1-C4 alkyl groups; optionally, the H atom is replaced by a F atom; preferably, Q 1 and Q 2 are independently Me or Et; more preferably, Q 1 and Q 2 Independently for Me.

[0072] In a preferred embodiment, Q 1 and Q 2 Belong to the same group, i.e. the carboxylic anhydride is symmetrical. In a more preferred embodiment, the carboxylic anhydride is selected from acetic anhydride and propionic anhydride. In another more preferred embodiment, the carboxylic anhydride is acetic anhydride.

[0073] Trifluoromethanesulfonic anhydride can also be used in the present invention and promotes a faster reaction than acetic anhydride. However, acetic anhydride is more convenient to handle.

[0074] As is well known in the art, carboxylic anhydrides can be readily prepared from carboxylic acids, for example, by the mild methods described in Synthetic Comm., 2001, 31(3), 395-399 and references cited therein.

[0075] In the preferred embodiment using acetic anhydride, acetic acid is produced as a by-product in the process of the invention and acetic anhydride can therefore be produced again for use in the process by using these methods.

[0076] The process of the invention is atom efficient in this respect, unlike indirect or direct processes using paraformaldehyde or direct processes forming salts, all of which produce residues as waste.

[0077] In the method of the present invention, the carboxylic anhydride in the three-component embodiment is generally used in a molar concentration ratio of 1:5; preferably, it is used in a molar concentration ratio of 1:3; more preferably, it is used in a molar concentration ratio of 1:2.5; more preferably, it is used in a molar concentration ratio of 1:2; wherein the ratio refers to the ratio between the active methylene compound of the general formula (III) and the acid anhydride compound of the general formula (IV), that is, the ratio of (III) to (IV).

[0078] Catalyst system

[0079] In the process of the present invention, the reaction of the three-component embodiment is catalyzed by a catalyst system comprising at least one acid, or at least one acid and at least one co-catalyst selected from the group consisting of phenolic compounds having one or more substituents, and quinone compounds.

[0080] The catalyst system also acts as a stabilizer system, although polymerization inhibitors may be additionally added.

[0081] The purpose of the present invention is to use a novel and highly efficient acid-based catalyst system to directly prepare electron-deficient olefin monomers through the reaction between an active methylene compound and an in-situ formed or preformed carbonyl ester.

[0082] Promoting the reaction by forming the carbonyl ester in situ, as well as using catalysts with multiple roles, can help improve the efficiency of the reaction. It may be the case that a catalyst known to promote carbonyl ester formation is not an efficient catalyst for the Knoevenagel reaction, and vice versa. For example, Bronsted acids readily catalyze the formation of carbonyl esters, but are not preferred catalysts for the stand-alone Knoevenagel reaction.

[0083] On the other hand, in the Knoevenagel reaction, compounds such as hydroquinone can catalyze the nucleophilic addition of active methylene compounds activated by benzoquinone, even at concentrations as low as 0.05 mol%, which is similar to the concentration of substituted aldehydes, as pointed out in Takakura et al., Org. Biomol. Chem., 2020, 18, 6594-6597, but neither hydroquinone nor benzoquinone can independently catalyze the formation of carbonyl esters.

[0084] In the present invention, the acid-based catalyst system generates electron-deficient olefin monomers by promoting the reaction between carbonyl condensation ester and the active methylene compound, no matter whether the components forming the catalyst system independently catalyze the formation of carbonyl condensation ester or Knoevenagel reaction. The catalyst system suitable for the inventive method provides a variety of activation modes of all reactants, and is preferably provided by the combination of an acid catalyst and a co-catalyst, particularly when an acid catalyst or a co-catalyst can not independently affect the formation of carbonyl condensation ester and Knoevenagel reaction. The catalyst system comprising this type of combination also promotes the direct reaction between the active methylene compound and the preformed carbonyl condensation ester. Surprisingly found that for Lewis acid or Bronsted acid catalyst, an effective co-catalyst is selected from phenolic compounds and quinone compounds.

[0085] Thus, the catalyst systems described herein include specific Lewis acids, combinations of Lewis acids and Bronsted acids, combinations of Lewis acids or Bronsted acids with the aforementioned cocatalysts, or combinations of Lewis acids and Bronsted acids with the described cocatalysts.

[0086] In a three-component embodiment of the present invention, the catalyst system is selected from:

[0087] 1) a Lewis acid, preferably a late transition metal Lewis acid,

[0088] 2) a combination of a Lewis acid and a Bronsted acid, wherein the Lewis acid is preferably a late transition metal Lewis acid,

[0089] 3) a combination of a Lewis acid and a co-catalyst, wherein the Lewis acid is preferably a late transition metal Lewis acid, and the co-catalyst is selected from phenolic compounds having one or more substituents, quinone compounds and mixtures thereof,

[0090] 4) a combination of a Bronsted acid and a promoter, wherein the promoter is selected from a phenolic compound having one or more substituents, a quinone compound and a mixture thereof, and

[0091] 5) A combination of a Lewis acid, a Bronsted acid and a co-catalyst, wherein the Lewis acid is preferably a late transition metal Lewis acid, and the co-catalyst is selected from phenolic compounds having one or more substituents, quinone compounds and mixtures thereof.

[0092] Preferably, the co-catalyst is selected from phenol, hydroquinone, p-methoxyphenol, p-trifluoromethylphenol, 1,4-benzoquinone, 1,4-naphthoquinone and mixtures thereof. More preferably, the co-catalyst is hydroquinone.

[0093] In a preferred three-component embodiment of the invention, the catalyst system catalyzes the reaction between the active methylene compound cyanoacetate and in situ generated methylene diacetate (a carbonyl ester) via an acid catalyzed reaction between acetic anhydride and a formaldehyde source (preferably 1,3,5-trioxane).

[0094] The use of the catalyst system in combination with carboxylic anhydrides for the direct synthesis of cyanoacrylates from cyanoacetates has not been described before.

[0095] The acidic catalyst system present in the process of the present invention also stabilizes the cyanoacrylate against polymerization.

[0096] In the most preferred three-component embodiment of the present invention, the catalyst system includes a combination of a Lewis acid, a Bronsted acid and a co-catalyst, the Lewis acid is preferably a late transition metal Lewis acid, and the co-catalyst is selected from phenolic compounds, quinone compounds and mixtures thereof having one or more substituents; preferably, the co-catalyst is selected from phenol, hydroquinone, p-methoxyphenol, p-trifluoromethylphenol, 1,4-benzoquinone, 1,4-naphthoquinone and mixtures thereof.

[0097] In a very preferred embodiment of the present invention, alkyl cyanoacetate is used as the active methylene compound, a formaldehyde source (preferably 1,3,5-trioxane), acetic anhydride and a catalyst system, wherein the catalyst system comprises a combination of a Lewis acid, a Bronsted acid and a co-catalyst, wherein the Lewis acid is preferably a late transition metal Lewis acid, and the co-catalyst is selected from phenolic compounds having one or more substituents, quinone compounds and mixtures thereof; preferably, the co-catalyst is selected from phenol, hydroquinone, p-methoxyphenol, p-trifluoromethylphenol, 1,4-benzoquinone, 1,4-naphthoquinone and mixtures thereof.

[0098] In the catalyst system of the three component embodiment of the present invention, various Lewis acids and Bronsted acids or mixtures thereof may be used.

[0099] Lewis acids suitable for use in the process of the present invention are selected from transition metal halides, post-transition metal-based halides (preferably trihalides), alkaline earth metal-based perchlorates (such as Mg(ClO4)2) and lanthanide metal-based Lewis acids (such as Yb(OTf)3). In a preferred embodiment, the Lewis acid is selected from the group of post-transition metal-based halides; more preferably, the Lewis acid is selected from the trihalides of indium(III) and the trihalides of gallium(III); preferably, the Lewis acid is selected from trichlorides; most preferably, the Lewis acid is InCl3.

[0100] In the three-component embodiment, the Lewis acid catalyst can be used in a concentration range of 0.05 mol% to 10 mol% relative to the active methylene compound of formula (III). Preferably, it is used in a concentration range of 0.1 mol% to 5 mol%; most preferably, it is used in a concentration range of 0.5 mol% to 1.5 mol%. The use of such a low catalyst loading further increases the convenience of handling, because the catalyst does not need to be separated from the reaction mixture in the subsequent distillation, and the reaction can be carried out in a continuous mode.

[0101] Various Bronsted acids are suitable for use in the process of the present invention. Preferably, they are selected from p-toluenesulfonic acid, benzenesulfonic acid and aralkylsulfonic acids. Most preferably, the Bronsted acid is p-toluenesulfonic acid in anhydrous form or in the form of a monohydrate.

[0102] In the three-component embodiment, the concentration range of the Bronsted acid catalyst relative to the active methylene compound of formula (III) may include 2.5 mol% to 15 mol%; preferably, the concentration range of the Bronsted acid catalyst includes 4 mol% to 6 mol%.

[0103] As mentioned above, in most cases a combination of a Lewis acid and / or a Bronsted acid with at least one cocatalyst is preferred.

[0104] Preferably, the concentration of the co-catalyst is in the range of 0.01 mol% to 10 mol% relative to the active methylene compound of formula (III); more preferably, the concentration of the co-catalyst is in the range of 0.01 mol% to 6 mol%.

[0105] In the combined catalyst system, the preferred concentrations of Lewis acid and Bronsted acid include 0.5 mol% to 1 mol% and 2 mol% to 8 mol% respectively, relative to the active methylene compound of general formula (III). The preferred concentrations of Lewis acid and co-catalyst include 0.5 mol% to 1 mol% and 0.02 mol% to 8 mol% respectively, relative to the active methylene compound of general formula (III); the preferred concentrations of Bronsted acid and co-catalyst include 1 mol% to 5 mol% and 0.02 mol% to 8 mol% respectively, relative to the active methylene compound of general formula (III); and the preferred concentrations of Lewis acid, Bronsted acid and co-catalyst include 0.5 mol% to 1 mol%, 2 mol% to 8 mol% and 0.02 mol% to 8 mol% respectively, relative to the active methylene compound of general formula (III).

[0106] Stabilizer

[0107] Electron-deficient olefin monomers such as CA are easily polymerized by electron-rich species. Since they are vinyl monomers, CA are also easily polymerized by free radicals, even though this is not a preferred mechanism. The synthesis and handling of these reactive monomers in all process steps requires special attention to stabilization in both the liquid and gas phases. This, in turn, requires the use of non-volatile and volatile stabilizers to prevent polymerization by any mechanism.

[0108] Furthermore, as is well known to those skilled in the art, equipment that comes in direct contact with the monomer must be passivated, for example, glassware or stainless steel components must be pre-cleaned with a strong Bronsted acid such as sulfuric acid, rinsed thoroughly with distilled water and dried.

[0109] Liquid CA monomer separated by distillation is typically collected into a certain amount of combined acidic and free radical stabilizers, the amount of which is predetermined based on the expected volume of monomer collected. Although the catalyst system of the three-component embodiment of the present invention itself has stabilizing properties that inhibit the polymerization of highly reactive monomers, additional stabilizers can optionally be used during the reaction and distillation process and in the final distilled product of the reaction.

[0110] In embodiments, the methods of the present invention comprise the use of a stabilizer selected from the group consisting of acid stabilizers and free radical stabilizers.

[0111] Volatile acid stabilizers are well known in the art and are used to inhibit the polymerization of electron-deficient monomers in the vapor trajectory during distillation. Lewis acids or Bronsted acids such as boron trifluoride etherate, SO2, trifluoroacetic acid can be used; most preferably, boron trifluoride etherate is used, and its concentration range in the batch reaction environment and distillation tank includes 0wt% to 0.05wt%, and its concentration range in the monomer distillate includes 0.0005wt% to 0.005wt%.

[0112] In a batch reaction environment and a distillation pot, non-volatile free radical stabilizers (such as 2,2'-methylenebis(6-tert-butyl-p-cresol) (stabilizer "2246"), pentaerythritol tetrakis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate) ) may be used in a concentration range of 0.01wt% to 3.0wt%; preferably, its concentration range is 0.01wt% to 1.5wt%.

[0113] Volatile free radical stabilizers may also be used in the process of the present invention. The stabilizers include, for example, hydroquinone (HQ), 4-methoxyphenol (MeHQ), butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), which may be used in a concentration range of 0.01 wt% to 3.0 wt% in a batch reaction environment and a distillation tank; preferably, the concentration range includes 0.01 wt% to 1.5 wt%; and the concentration range in the monomer distillate includes 0.1 wt% to 0.5 wt%.

[0114] Solvents

[0115] The three-component embodiment can be carried out in the absence of a solvent or in the presence of a solvent, such as toluene, p-xylene or 1,4-dioxane.

[0116] Hydrocarbon solvents also provide a useful means of pre-drying the reaction components, if desired, by forming an azeotrope with any water that may be present, using a Dean-Stark apparatus well known to those skilled in the art.

[0117] If a solvent is used, the reaction mixture is generally diluted 1.5 to 10 times by volume, preferably, diluted 2 times by volume.

[0118] Three-component method

[0119] Typically, the reaction mixture is continuously agitated by any suitable means, such as by stirring and / or shearing in a batch reaction, or by using a static or dynamic mixer or a rotating disk in a continuous or flow reactor.

[0120] In a batch reactor, the reaction is typically carried out in a time range of 1 hour to 10 hours, depending on the reactivity of the substrate, the catalyst system and the reaction temperature.

[0121] Usually, the preferred reaction temperature range includes 60°C to 140°C, and the reaction time range includes 0.5 hour to 10 hours. More preferably, the reaction temperature is 100°C to 130°C, and the reaction time is 1 hour to 5 hours; more preferably, the reaction temperature is 115°C to 125°C, and the reaction time is 1 hour to 2 hours.

[0122] In a preferred embodiment, a catalyst system comprising 1 mol% InCl3, 5 mol% p-toluenesulfonic acid and 5 mol% hydroquinone is used, and the reaction is carried out at 120°C within 2 hours.

[0123] By scaling up the batch process, the skilled person can adjust the reaction conditions using common general knowledge.

[0124] The parameters required to optimize the continuous reaction depend on the type of reactor employed and are determined by methods known to those skilled in the art by following the product conversion as a function of time by sampling and systematic variation of the reaction component flow rates and agitation speed. 1 H-NMR (Spinsolve 60 MHz, Magritek Ltd.) is particularly helpful for rapid feedback. A preferred continuous reactor is the SpinPro reactor (Flowid bv) because of its ability to handle heterogeneous mixtures and excellent mixing.

[0125] Two-component implementation scheme

[0126] The two-component embodiment includes two sets of reactants, hence the name:

[0127] (i) an active methylene compound, and

[0128] (ii) Methylene diesters (carbonyl esters).

[0129] In a preferred embodiment, the active methylene compound is a cyanoacetate and the methylene diester is selected from the group consisting of methylene diacetates, such as methylene diacetate.

[0130] The reaction of the two-component embodiment is catalyzed by a catalyst system comprising a Bronsted acid and at least one co-catalyst selected from the group consisting of phenolic compounds having one or more substituents, and quinone compounds.

[0131] The catalyst system also functions as a stabilizer system, although polymerization inhibitors may additionally be added.

[0132] With respect to the above-mentioned specific preferred embodiments, the two-component embodiment of the method of the present invention can be represented according to Scheme II for the specific preparation of ethyl cyanoacrylate.

[0133] Solution II

[0134]

[0135] Active methylene compounds

[0136] The active methylene compounds used in the three-component embodiment are also applicable to the two-component embodiment.

[0137] Carbonyl ester compounds

[0138] An acylal compound is a compound containing a geminal dicarboxyl or geminal bis(acyloxy) moiety, such as methylene diacetate.

[0139] In the three-component embodiment of the present invention, the carbonyl ester is generated in situ; while in the two-component embodiment, the carbonyl ester is provided after being preformed in a separate reaction. As with the three-component embodiment, a method for activating the active methylene compound using a suitable catalyst system to promote its reaction with the carbonyl ester is also required.

[0140] The terms carbonyl ester, methylene diester, methylene diacetate, 1,1-geminal diacetate are used interchangeably to describe compounds of general formula (V):

[0141]

[0142] Among them, Q 1 and Q 2 Independently selected from C 1- C4 straight chain and branched chain alkyl.

[0143] And the term also refers to the following carbonyl esters, wherein the central methylene group is substituted as shown in the general formula (VI):

[0144]

[0145] Among them, R a Selected from alkyl, aryl and aralkyl.

[0146] Methylene diesters of the formula (VI) carrying substituents on the central methylene group, formed by reaction of carboxylic anhydrides with substituted aldehydes, have been extensively reviewed in Sydnes et al., PINSA, 2002, 68(2), 141-174.

[0147] Carbonyl esters are usually prepared by the acid-catalyzed reaction of carboxylic anhydrides with aldehydes, however, they can also be prepared by transferring a methylene group to a carboxylic ester from a donor such as a methyl dihalide (eg, dichloromethane or diiodomethane).

[0148] Methylene diacetates containing an unsubstituted central group (thus -OCH2O-) are obtained by reacting a carboxylic anhydride with a linear or cyclic formaldehyde source (such as paraformaldehyde or 1,3,5-trioxane) in the presence of an acid or a metal-based catalyst and are described, for example, in US 3927078, Hoffmann et al., Catal. Sci. Technol., 2018, 8, 5594-5603 and It is also described in et al., Angew. Chem. Int. Edn., 1962, 1(4), 211.

[0149] In the two-component embodiment of the present invention, the carbonyl ester preferably used comprises only unsubstituted central methylene groups (-OCH2O-). 1 and Q2 The carbonyl groups are equivalent in the selected carbonyl esters and are selected from C1-C4 straight chain and branched chain alkyl groups.

[0150] Dalpozzo et al., ARKIVOC, 2006, (vi), 181-189 disclose carbonyl esters derived from propionic anhydride.

[0151] Carbonyl esters derived from butyric anhydride, isobutyric anhydride and pivalic anhydride have been described in Sumida et al., Synletts, 2001, 1921-1922, and Samitha et al., Tetrahedron, 2003, 59, 9571-9576. The most preferred methylene diesters in any embodiment of the present invention are methylene diacetates, wherein Q in formula (V) is 1 and Q 2 It's methyl.

[0152] A wide variety of protic acids, Lewis acids and heterogeneous catalysts are described in the literature for the independent synthesis of carbonyl esters, for example, AlCl3, Amberlyst, Envirocatsw, montmorillonite, zeolite, Nafion-H, 50WX4, Caro's acid, Wells-Dawson heteropoly acid, Mo / TiO2-ZrO2 solid acid, P2O5 / SiO2, P2O5 / montmorillonite, FeSO4, FeCl3, AlCl3, TMSCl-NaI, Sc(OTf)3, I2, NBS, PCl3, H2SO4, Cu(OTf)2, LiBF4, H2NSO3H, BF3, (NH4)2Ce(NO3)6, LiOTf, Zn(BF4)2, AlPW 12 O 40, ZrCl4, Bi(NO3)3.5H2O, Bi(CF3SO3).4H2O, zirconium sulfohexyl phosphonate, sulphated zirconia, poly(N,N-dibromo-N-ethyl-benzene-1,3-disulfonamide) [PBBS], N,N,N,N-tetrabromobenzene-1,3-disulfonamide [TBBDA], tetrabromo-2,5-cyclohexanedione (TABCO), tetrabutylammonium tribromide (TBATB), saccharin sulfonic acid, zirconium hydroxide, Fe2(SO4)3·xH2O, alum [KAl(SO4)2.12H2O], sulfated zirconium oxide (sulfated zirconia) zirconia), KHCO3, sulfuric acid, H2SO4-silicon, HClO4-SiO2, lithium perchlorate, zinc perchlorate (II), [Hmim][HSO4][Brønsted acidic ionic liquid], Al(HSO4)3.

[0153] Preferred catalysts for forming carbonyl esters are selected from catalysts known to work under mild conditions in independent reactions, such as, alkali metal-based Lewis acids LiBr described in Sampath Kumar et al., J. Chemical Research (S), 2000, 86-87; alkaline earth metal-based Lewis acids Mg(ClO4)2 described in Yang, in J. Chemical Research, 2006, 199-202; and lanthanide metal-based Lewis acids (such as Yb(OTf)3 and Er(OTf)3) described in Dalpozzo et al., op. cit.; transition metal Lewis acid catalysts (such as FeCl3) described in Rezayati et al., Research on Chemical Intermediates, 2020, DOI: 10.1007 / s11164-020-04176-x, and Yin et al., Tetrahedron, 2007, 48, 3119-3122, and Kumar et al. Late transition metal Lewis acid catalysts (such as indium and gallium trihalides) as described in et al., ARKIVOC, 2007, 27-33.

[0154] Catalyst system

[0155] In the two-component embodiment of the process of the present invention, the catalyst system enables the reaction between the carbonyl ester and the active methylene compound to form the electron-deficient olefin monomer.

[0156] The catalyst system comprises a Bronsted acid and at least one co-catalyst.

[0157] Various Bronsted acids are suitable for use in the process of the present invention. Preferably, they are selected from p-toluenesulfonic acid, benzenesulfonic acid and aralkylsulfonic acids. Most preferably, the Bronsted acid is p-toluenesulfonic acid in anhydrous form or in the form of a monohydrate.

[0158] The co-catalyst is selected from phenolic compounds having one or more substituents and quinone compounds. Preferably, the co-catalyst is selected from phenol, hydroquinone, p-methoxyphenol, p-trifluoromethylphenol, 1,4-benzoquinone, 1,4-naphthoquinone and mixtures thereof. More preferably, the co-catalyst is hydroquinone.

[0159] The catalyst and cocatalyst present are also polymerization stabilizers.The use of a Bronsted acid catalyst in combination with hydroquinone as a cocatalyst for the direct synthesis of electron-deficient olefin monomers such as cyanoacrylates has not been described before.

[0160] Preferred concentrations of the Bronsted acid catalyst and the co-catalyst include 2 mol% to 5 mol% and 0.02 mol% to 8 mol%, respectively, relative to the active methylene compound of the general formula (III).

[0161] The conditions that apply in the three-component embodiment also apply in the two-component embodiment. The preferred ratio of active methylene compound to carbonyl acetal is 1:1.

[0162] Optionally, the two-component embodiment may also utilize additional stabilizers, as described for the three-component embodiment.

[0163] Industrial Applicability

[0164] In addition to avoiding the intensive lysis required by the former, the method of the present invention has many advantages over the indirect and direct methods of the prior art.

[0165] First, in relatively fast and solvent-free reactions such as in the present invention, the use of an acidic catalyst can provide protection, especially when the starting material achieves a high conversion level and reaches a high concentration of reactive monomers. The catalyst system of the present invention also includes compounds known to be used as free radical stabilizers, which are co-catalysts. Acids inhibit polymerization, which is particularly necessary in methods where the monomers are not protected in the reaction environment and subsequent process steps. It is necessary to avoid the use of N-based catalysts because under process conditions, even in the presence of excess protic acids, the accidental release of basic compounds in ammonium salts or imine salts can also pose a risk. Even trace amounts of basic compounds are effective initiators for initiating the polymerization of these monomers. Hofmann elimination, Knoevenagel and Mannich type reactions are well known, in which a certain equilibrium exists between the N-based salt and the parent free amine, as reported in van Beurden et al., op.cit. and Dalessandro, et al., Phys. Chem., B, 2017, 121(20), 5300-5307, and these reactions form the basis of several of the previously mentioned direct methods.

[0166] In the present invention, the preference for using a suitable acid catalyst over an N-based catalyst is not the only advantage, since the deployment and operation of some specific Lewis acid catalysts in the unpromoted Knoevenagel reaction has not previously resulted in an effective method for isolating directly synthesized CA monomers. The present invention uses lower catalyst loadings than any previously reported method, thereby reducing costs, reaction residues and waste, improving reaction efficiency and selectivity, and facilitating continuous processing steps including monomer separation. Further reaction byproducts can be reused in the present method to produce promoters or reagents for the monomer formation reaction itself.

[0167] The process of the present invention can be used industrially for the simple one-pot preparation of reactive monomers for adhesives, sealants and coatings. The described process employs simple commercially available catalysts and cocatalysts at low loadings, which contribute to the stability of the reaction even under concentrated conditions. Standard methods are known to convert carboxylic acids into their anhydrides, which have been shown to be promoters for the monomer formation reaction itself, or which in turn are known reactants that can be used to preform carbonyl esters, which can be used in the monomer formation reaction.

[0168] The output of any embodiment of the present invention, whether a batch reactor or a flow reactor, can be directly fed into a continuous vacuum evaporation or distillation system. The electron-deficient monomers are separated by fractionation, preferably by vapor trajectory stabilization using a volatile free radical and a Lewis acid stabilizer, and the monomers are collected onto the stabilizer at the concentration levels previously indicated. Since the boiling point is much lower than that of the target monomer, volatile reaction components (such as solvents and / or excess reagents) (if present) and by-products (such as carboxylic acids) can be easily removed by evaporation and fractionation. Typically, all evaporation or distillation equipment used to condense vapors and collect reactive monomers is passivated prior to use, for example, by pre-washing with 10% sulfuric acid, rinsing with distilled water and thoroughly drying prior to use.

[0169] The process demonstrates the separation of pure highly reactive monomers by direct distillation from the reaction medium without any intermediate processing steps when the starting material is converted. The need for interrupted processing from synthesis to distillation is avoided, making the process of the invention suitable for batch or continuous processing. This process has high yields even for the most reactive ethyl cyanoacrylate monomer, whether or not additional solvent is used. The process does not generate large amounts of residues or wastes (such as cleavage residues that must be disposed of or large amounts of salts that are difficult to handle).

[0170] The present invention includes the following embodiments:

[0171] 1. A method for preparing an electron-deficient olefin monomer, characterized in that an active methylene compound of the general formula (III) is reacted with any one of a) or b) in the presence of a catalyst system;

[0172] EWGCH2 1 (III)

[0173] Among them, EWG and Z 1 Two electron withdrawing groups represented by are selected from nitrile, carboxylate and carboxylic acid functional groups;

[0174] wherein a) is a mixture of a formaldehyde source and a carboxylic anhydride of the general formula (IV),

[0175]

[0176] Among them, Q 1 and Q 2 is independently selected from linear and branched C1-C4 alkyl, optionally, the H atom is replaced by a F atom; preferably, Q 1 and Q 2 are independently Me or Et; more preferably, Q 1 and Q 2 Independently for Me;

[0177] The catalyst system comprises:

[0178] i) at least one acid, or,

[0179] ii) at least one acid and at least one promoter,

[0180] wherein the acid is selected from the group of Lewis acids and Bronsted acids, and the at least one co-catalyst is selected from the group of phenolic compounds having one or more substituents, and quinone compounds;

[0181] b) is a methylene diester of the general formula (V),

[0182]

[0183] Among them, Q 1 and Q 2 independently selected from C1-C4 straight chain and branched alkyl groups,

[0184] The catalyst system comprises a Bronsted acid and at least one co-catalyst, wherein the co-catalyst is selected from the group consisting of a phenolic compound having one or more substituents, and a quinone compound.

[0185] 2. The method according to embodiment 1, characterized in that the active methylene compound of the general formula (III) is reacted with a mixture of a formaldehyde source and a carboxylic anhydride of the general formula (IV) in the presence of a catalyst system;

[0186] EWGCH2 1 (III)

[0187] Among them, EWG and Z 1 The two electron withdrawing groups represented by are selected from nitrile, carboxylate and carboxylic acid functional groups,

[0188]

[0189] Among them, Q 1 and Q 2 is independently selected from linear and branched C1-C4 alkyl, optionally, the H atom is replaced by a F atom; preferably, Q 1 and Q 2 are independently Me or Et; more preferably, Q 1 and Q 2 Independently for Me;

[0190] The catalyst system comprises:

[0191] i) at least one acid, or,

[0192] ii) at least one acid and at least one promoter,

[0193] Wherein, the acid is selected from the group consisting of Lewis acids and Bronsted acids, and the at least one co-catalyst is selected from the group consisting of phenolic compounds having one or more substituents, and quinone compounds.

[0194] 3. The method according to embodiment 1 or 2 is characterized in that the active methylene compound of general formula (III) includes nitrile and carboxylic acid ester as electron-withdrawing functional groups.

[0195] 4. The method according to any one of embodiments 1 to 3, characterized in that the carboxylic acid ester group (-CO2R) is selected from the following substances, wherein R is selected from a linear C1-C 18 Alkyl, alkenyl or alkynyl, branched C3-C8 alkyl, cyclic or condensed cycloaliphatic C3-C 20 , linear or branched C1-C4 alkoxyethyl, C1-C4 trialkylsilyloxyethyl, tetrahydrofuranyl, C1-C4 trialkylsilyl, -C2H4CO2H, -(CH2) n OC(O)CH2CN (wherein n=2-4), -(CH2)2OC(O)CH=CH2, and -(CH2)2OC(O)C(CH3)=CH2.

[0196] 5. The method according to any one of embodiments 1 to 4, characterized in that the active methylene compound is cyanoacetate, or a mixture of cyanoacetate, or a mixture of cyanoacetate and cyanoacetic acid; preferably, the active methylene compound is cyanoacetate.

[0197] 6. The method according to any one of embodiments 1 to 5, characterized in that the formaldehyde source is selected from dry formaldehyde gas, paraformaldehyde and 1,3,5-trioxane; preferably, the formaldehyde source is 1,3,5-trioxane.

[0198] 7. The method according to any one of embodiments 1 to 6, characterized in that the molar concentration of 1,3,5-trioxane relative to the compound of general formula (III) is 1.25:1; preferably, the molar concentration is 1.1:1; more preferably, the molar concentration is 1:1.

[0199] 8. A method according to any one of embodiments 1 to 7, characterized in that a carboxylic anhydride of the general formula (IV) is used, wherein Q 1 and Q 2 are the same group.

[0200] 9. The method according to embodiment 8 is characterized in that the carboxylic anhydride of general formula (IV) is selected from acetic anhydride and propionic anhydride; preferably, the carboxylic anhydride is acetic anhydride.

[0201] 10. The method according to any one of embodiments 1 to 9, characterized in that the carboxylic anhydride is used in a molar concentration ratio of 1:5; preferably, it is used in a molar concentration ratio of 1:3; more preferably, it is used in a molar concentration ratio of 1:2.5; more preferably, it is used in a molar concentration ratio of 1:2; wherein the ratio refers to the ratio between the active methylene compound of general formula (III) and the acid anhydride compound of general formula (IV).

[0202] 11. The method according to any one of embodiments 1 to 10, characterized in that the catalyst system is selected from: a Lewis acid, preferably a late transition metal Lewis acid; a combination of a Lewis acid and a Bronsted acid, preferably a late transition metal Lewis acid; a combination of a Lewis acid and a co-catalyst, preferably a late transition metal Lewis acid, and the co-catalyst is selected from phenolic compounds, quinone compounds and mixtures thereof having one or more substituents; a combination of a Bronsted acid and a co-catalyst, wherein the co-catalyst is selected from phenolic compounds, quinone compounds and mixtures thereof having one or more substituents; and a combination of a Lewis acid, a Bronsted acid and a co-catalyst, wherein the Lewis acid is preferably a late transition metal Lewis acid, and the co-catalyst is selected from phenolic compounds, quinone compounds and mixtures thereof having one or more substituents; preferably, the catalyst system is a combination of a Lewis acid, a Bronsted acid and a co-catalyst, wherein the Lewis acid is preferably a late transition metal Lewis acid, and the co-catalyst is selected from phenolic compounds, quinone compounds and mixtures thereof having one or more substituents.

[0203] 12. The method according to any one of embodiments 1 to 11 is characterized in that the co-catalyst is selected from phenol, hydroquinone, p-methoxyphenol, p-trifluoromethylphenol, 1,4-benzoquinone, 1,4-naphthoquinone and a mixture thereof; preferably, the co-catalyst is hydroquinone.

[0204] 13. A method according to any one of embodiments 1 to 12, characterized in that alkyl cyanoacetate is used as an active methylene compound, a formaldehyde source (preferably 1,3,5-trioxane), acetic anhydride and a catalyst system, the catalyst system comprising a combination of a Lewis acid, a Bronsted acid and a co-catalyst, the Lewis acid is preferably a late transition metal Lewis acid, and the co-catalyst is selected from phenolic compounds having one or more substituents, quinone compounds and mixtures thereof; preferably, the co-catalyst is selected from phenol, hydroquinone, p-methoxyphenol, p-trifluoromethylphenol, 1,4-benzoquinone, 1,4-naphthoquinone and mixtures thereof.

[0205] 14. A method according to any one of embodiments 1 to 13, characterized in that the Lewis acid is selected from transition metal halides, post-transition metal-based halides (preferably trihalides), alkaline earth metal-based perchlorates and lanthanide metal-based Lewis acids; preferably, the Lewis acid is selected from the group of post-transition metal-based halides; more preferably, the Lewis acid is selected from indium (III) trihalides and gallium (III) trihalides; preferably, the Lewis acid is selected from trichlorides; even more preferably, the Lewis acid is InCl3.

[0206] 15. The method according to any one of embodiments 1 to 14 is characterized in that, relative to the active methylene compound of general formula (III), the Lewis acid catalyst is used in a concentration range of 0.05 mol% to 10 mol%; preferably, the concentration range is 0.1 mol% to 5 mol%; more preferably, the concentration range is 0.5 mol% to 1.5 mol%.

[0207] 16. The method according to any one of embodiments 1 to 15, characterized in that the Bronsted acid is selected from p-toluenesulfonic acid, benzenesulfonic acid and aralkylsulfonic acid; preferably, the Bronsted acid is p-toluenesulfonic acid in anhydrous form or in monohydrate form.

[0208] 17. A method according to any one of embodiments 1 to 16, characterized in that the concentration range of the Bronsted acid catalyst is 2.5 mol% to 15 mol% relative to the active methylene compound of general formula (III); preferably, the concentration range is 4 mol% to 6 mol%.

[0209] 18. The method according to any one of embodiments 1 to 17 is characterized in that, relative to the active methylene compound of general formula (III), the concentration range of the co-catalyst is 0.01 mol% to 10 mol%; more preferably, the concentration range is 0.01 mol% to 6 mol%.

[0210] 19. The method according to embodiment 1 or 2 is characterized in that, in the combined catalyst system, the Lewis acid and the Bronsted acid are used in concentrations of 0.5 mol% to 1 mol% and 2 mol% to 8 mol%, respectively, relative to the active methylene compound of the general formula (III); the Lewis acid and the co-catalyst are used in concentrations of 0.5 mol% to 1 mol% and 0.02 mol% to 8 mol%, respectively; the Bronsted acid and the co-catalyst are used in concentrations of 1 mol% to 5 mol% and 0.02 mol% to 8 mol%, respectively, relative to the active methylene compound of the general formula (III); and, relative to the active methylene compound of the general formula (III), the Lewis acid, the Bronsted acid and the co-catalyst are used in concentrations of 0.5 mol% to 1 mol%, 2 mol% to 8 mol% and 0.02 mol% to 8 mol%, respectively.

[0211] 20. The method according to any one of embodiments 1 to 19 is characterized in that it includes the use of a stabilizer, wherein the stabilizer is selected from an acid stabilizer and a free radical stabilizer; preferably, the acid stabilizer is selected from boron trifluoride etherate, SO2, and trifluoroacetic acid; more preferably, the acid stabilizer is boron trifluoride etherate; preferably, the free radical stabilizer is selected from 2,2'-methylenebis(6-tert-butyl-p-cresol), pentaerythritol tetrakis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate], hydroquinone, 4-methoxyphenol, butylated hydroxyanisole and butylated hydroxytoluene.

[0212] 21. The method according to embodiment 1, characterized in that the active methylene compound of the general formula (III) and the methylene diester of the general formula (V) are reacted in the presence of a catalyst system;

[0213] EWGCH2 1 (III)

[0214] Among them, EWG and Z 1 The two electron withdrawing groups represented by are selected from nitrile, carboxylate and carboxylic acid functional groups,

[0215]

[0216] Among them, Q 1 and Q 2 independently selected from C1-C4 straight chain and branched alkyl groups,

[0217] The catalyst system comprises a Bronsted acid and at least one co-catalyst, wherein the co-catalyst is selected from the group consisting of a phenolic compound having one or more substituents, and a quinone compound.

[0218] 22. The method according to embodiment 21, characterized in that an active methylene compound of the general formula (III) as defined in any one of embodiments 3 to 5 is used.

[0219] 23. The method according to embodiment 21 or 22, characterized in that the methylene diester is methylene diacetate.

[0220] 24. The process according to any one of embodiments 21 to 23, characterized in that a Bronsted acid as defined in embodiment 16 is used.

[0221] 25. The process according to any one of embodiments 21 to 24, characterized in that a co-catalyst as defined in embodiment 12 is used.

[0222] 26. The method according to any one of embodiments 21 to 25, characterized in that the concentrations of the Bronsted acid catalyst and the co-catalyst are respectively 2 mol% to 5 mol% and 0.02 mol% to 8 mol% relative to the active methylene compound of formula (III).

[0223] 27. The method according to any one of embodiments 21 to 26, characterized in that the ratio between the active methylene compound of general formula (III) and the carbonyl ester of general formula (V) is 1:1.

[0224] 28. The method according to any one of embodiments 21 to 26, characterized in that it includes a stabilizer as defined in embodiment 20.

[0225] Several examples are provided next, which are illustrative embodiments of the present invention but are not limiting of the present invention.

[0226] Example

[0227] Methodology

[0228] In either embodiment, the process of the invention is carried out in air, although an inert gas atmosphere, such as that provided by nitrogen or argon, may be used.

[0229] The reagents and catalyst are simply mixed in a one-pot process and allowed to react at a specific time and temperature.

[0230] In the three-component embodiment of the present invention, because the anhydride is sensitive to moisture, reasonable standard measures commonly used by those skilled in the art are taken to avoid excess moisture from the raw materials or the reaction environment; however, it is not necessary to use strictly anhydrous conditions in any embodiment.

[0231] Lewis acids such as InCl3 are deliquescent solids ready for use.

[0232] The Bronsted acid p-toluenesulfonic acid was used ex situ as the monohydrate.

[0233] The use of a non-nucleophilic solvent (such as toluene, p-xylene) is optional.

[0234] The reaction was carried out under stirring.

[0235] Comparative Examples 1a-1d: Incomplete Reaction System

[0236] Control experiments were performed which did not include all technical elements of the method of the present invention.

[0237] pass 1 The reaction progress was continuously monitored by H-NMR.

[0238] The following comparative examples were performed:

[0239] 1a: Equimolar amounts of ethyl cyanoacetate and acetic anhydride or trifluoromethanesulfonic anhydride and 1,3,5-trioxane were heated together at 120°C for 2 hours. No trace of monomer was produced.

[0240] 1b: Equimolar amounts of ethyl cyanoacetate and methylene diacetate were heated together at 120°C for 2 hours. No trace of monomers was produced.

[0241] 1c: Equimolar amounts of ethyl cyanoacetate and methylene diacetate were heated together at 120°C for 1 hour in the presence of 5 mol% p-TsOH.H2O. No traces of monomers were produced and the starting material was still present. This Bronsted acid is very effective in preforming the carbonyl acetal in a separate reaction, but when the carbonyl acetal has been obtained, this Bronsted acid does not catalyze further reactions between the active methylene compound and the carbonyl acetal.

[0242] 1d: Equimolar amounts of ethyl cyanoacetate and methylene diacetate were heated together at 120°C for 1 hour in the presence of 5 mol% of hydroquinone. No trace of monomers was produced and the starting material was still present. Even though the substituted phenolic compound hydroquinone is known to facilitate the Knoevenagel reaction, it cannot independently promote the reaction with the preformed methylene diacetate.

[0243] These comparative experiments show that the lack of the technical elements of the method of the present invention makes it impossible to prepare electron-deficient olefin monomers.

[0244] Comparative Examples 2a-2d: Incomplete Reaction System

[0245] According to patent US10927071, electron-deficient olefins can be prepared by reacting cyanoacetate with an aldehyde source in the presence of certain lanthanide or transition metal Lewis acid catalysts.

[0246] The patent states that the aldehyde compound is selected from the group consisting of paraformaldehyde, formalin, 1,3,5-trioxane, methylene diacetate, dimethoxymethane and acrolein. Some of these reactants have been tested in comparative experiments.

[0247] 2a: 1 mol% InCl3 was used as a catalyst for the reaction of equimolar amounts of ethyl cyanoacetate and dimethoxymethane. The boiling point of dimethoxymethane at atmospheric pressure is about 41°C. In order to achieve a higher reaction temperature and try to promote the Knoevenagel reaction, acetic anhydride (boiling point of about 140°C) was mixed with dimethoxymethane as a reagent and solvent. After heating at 120°C for 2 hours, no reaction occurred and no monomer formation was observed. The unconverted ethyl cyanoacetate was recovered. When dimethoxymethane as an aldehyde source was used as a reactant, acetic anhydride did not promote the reaction.

[0248] 2b: Another experiment was conducted to test the performance of other examples of aldehyde sources (forms) listed above. In the experiment, cyanoacetic acid was used instead of cyanoacetic acid ester as substrate, paraformaldehyde was used instead of dimethoxymethane, and 5 mol% InCl3 was used for the experiment at 60°C for 2 hours. Only a viscous solution was obtained. 1 Various broad, unclear peaks were produced in the 3.3-7.6 ppm region of the H-NMR spectrum, indicating the presence of unidentified polymer and water / OH. Acetic anhydride was not used in this experiment.

[0249] 2c: Another experiment was performed using ethyl cyanoacetate as substrate and an equimolar amount of 1,3,5-trioxane, using a catalyst system including a lanthanide Lewis acid Yb(OTf)3, p-TsOH and hydroquinone (all at 5 mol%) at 120°C for 2 hours. Even with 100% conversion of the starting materials, no monomer was produced. No acetic anhydride was present in this experiment.

[0250] 2d: When using the late transition metal catalyst InCl3 and the same p-TsOH and hydroquinone as before, even increasing the Lewis acid catalyst concentration to 10 mol%, lowering the reaction temperature to 60 °C and extending the reaction time to 18 h, only similar results to 2c were obtained. When acetic anhydride was not present,

[0251] No carbonyl condensate is formed and the catalyst system used does not promote the direct production of stable monomers.

[0252] Comparative Examples 3a to 3e: Incomplete Reaction System

[0253] According to the examples disclosed in patent US 9670145 (US'145 patent), the active methylene compound n-butyl cyanoacetate (BCAc) can be reacted with the carbonyl ester methylene diacetate (MDAc) or its source using an ammonium salt or iminium salt catalyst (N-based organic catalyst), wherein the reaction time is 2 hours and the temperature is in the range of 120-130°C. The reaction efficiency is independent of the preparation method of the N-based organic catalyst, but is related to the preparation method of MDAc. The patent describes a method for preparing MDAc in situ from polyformaldehyde and acetic anhydride and excess p-TsOH.H2O in the presence of cyanoacetate, which is a three-component method described as a "direct method" in Example 3 of the patent. The product MDAc can also be preformed by a separate reaction using sulfuric acid as a catalyst (Example 1 of the patent), and MDAc is reacted with n-butyl cyanoacetate in a two-component method. When MDAc is prepared according to the former case and used in an N-based organocatalytic reaction, the disclosed product monomer n-butyl cyanoacrylate (BCA) selectivity is generally as high as about 70-75%. When MDAc is preformed, the disclosed product monomer n-butyl cyanoacrylate (BCA) selectivity from the N-based organocatalytic reaction is generally very high, about >90%. The yield of the two-component reaction is the highest.

[0254] First, experiments were performed using pure preformed MDAc prepared in an independent reaction to establish a reference point for subsequent comparisons. et al., op. cit., but using p-TsOH.H2O as the catalyst. The preformed MDAc was reacted with equimolar stoichiometric amounts of various cyanoacetic acid esters at 120°C for 2 hours using an N-based organocatalyst (5 mol% piperazine, 15 mol% p-TsOH.H2O) prepared as described in the US'145 patent. No hydroquinone was used in the reaction. Under these conditions, the reaction was carried out using an internal standard for the two-component reaction. 1 The results of the direct conversion of the starting materials into the corresponding cyanoacrylate products (i.e., the specific selectivity for the monomer) obtained by H-NMR measurement are shown in Table I.

[0255] Table I

[0256]

[0257] *10 mmol of tetrachloroethane was used as internal standard.

[0258] The N-based organocatalytic reaction described in Comparative Examples 3a-3d above (5 mol% piperazine, 15 mol% p-TsOH.H2O) was repeated again this time in a three-component reaction, with in situ formation of MDAc and using only ethyl cyanoacetate. No hydroquinone was used in the reaction.

[0259] In this three-component experiment (Example 3e), MDAc was formed by reacting 1,3,5-trioxane recrystallized from a 1:1 mixture of ethyl acetate and petroleum ether with acetic anhydride and excess p-TsOH.H2O. Ethyl cyanoacetate, 1,3,5-trioxane and acetic anhydride were used in a mixture in a molar equivalent of 1:1:2, respectively. The mixture was heated to 120°C and maintained at this temperature for 1.5 to 2 hours. 1 H-NMR measurement revealed that the direct conversion of ethyl cyanoacetate into the corresponding ethyl cyanoacrylate (ie, selectivity to the monomer only) was only 15%.

[0260] Examples 1a to 1e: Preparation of different cyanoacrylates

[0261] In the following examples, equimolar amounts of a particular cyanoacetate and 1,3,5-trioxane were reacted at 120° C. with two molar equivalents of acetic anhydride in the presence of a Lewis acid indium trichloride (InCl3) catalyst at a concentration of 1 mol% relative to the cyanoacetate, 5 mol% hydroquinone and 5 mol% p-TsOH.H2O for 1.5-2 hours.

[0262] Examples 1 to 4 were solvent-free; whereas, in Example 5, the reaction mixture also included a volume of p-xylene approximately equal to the total volume of all reagents.

[0263] The reaction mixture was stirred vigorously. Tetrachloroethane was used as an internal standard. 1 The progress of the reaction was continuously monitored by H-NMR. The analytical results of the direct conversion of the starting materials into the corresponding cyanoacrylate products in the reaction medium (i.e., the specific selectivity for the monomers) are shown in Table II and demonstrate how low loadings of specific Lewis acid catalysts in the catalyst system can directly generate high yields of various cyanoacrylate monomers in a stable environment without the need for pre-formation of MDAc (a separate reaction that requires additional time).

[0264] Table II

[0265]

[0266] *10 mmol of tetrachloroethane was used as internal standard.

[0267] It can be observed that the selectivity obtained in Example 1 is much better than the selectivity obtained in the equivalent three-component reaction catalyzed by N-based organocatalysis (Comparative Example 3e).

[0268] When ethyl 2-methoxycyanoacetate was used as the active methylene compound, the catalyst system was adjusted to include InCl3, p-TsOH.H2O and hydroquinone (all at 5 mol%), and the reaction time was shortened to 1 hour at 120°C. Without the addition of solvent, the conversion of cyanoacetate to 2-methoxycyanoacrylate was 88% and the yield was 40%.

[0269] The one-pot three-component reaction is simple and convenient to carry out from readily available starting materials, and 1 H-NMR confirmed the presence of acetic acid as a byproduct in the reaction mixture.

[0270] As shown in Example 1e, when p-xylene is added as solvent to the reaction mixture, 1 H-NMR measurements showed that the selectivity and conversion were even further improved to 75% and 90%, respectively.

[0271] In the two-component method using preformed MDAc, it is also possible to use other solvents (such as 1,4-dioxane) in the InCl3-catalyzed reaction, and efficient reactions can be achieved with lower InCl3 loadings (such as 0.5 mol%), although the reaction time is longer, up to 5 h.

[0272] Examples 2a to 2e: Preparation of ethyl cyanoacrylate using different co-catalysts

[0273] The cocatalyst of the three-component embodiment was tested using a catalyst system of 1 mol% InCl3, 5 mol% p-TsOH.H2O and various cocatalysts (concentrations as shown in Table III), and the results of Example 1a and Example 1e are also included in Table III for comparison. The molar ratio between ethyl cyanoacetate, 1,3,5-trioxane and acetic anhydride was 1:1:2, the reaction time was 2 hours, and the temperature was 120°C.

[0274] Table III

[0275]

[0276] *10 mmol of tetrachloroethane was used as internal standard.

[0277] Examples 3a to 3e: Preparation of ethyl cyanoacrylate using different Lewis acids and loadings

[0278] Different Lewis acids of the three-component embodiment were tested using a catalyst system comprising 5 mol% p-TsOH.H2O and 5 mol% hydroquinone (as shown in Table IV), and the results of Example 1a and Example 1e are also included in Table IV for comparison. The molar ratio between ethyl cyanoacetate, 1,3,5-trioxane and acetic anhydride was 1:1:2, the reaction time was 2 hours, and the temperature was 120°C. In Example 3d and Example 3e, 1,3,5-trioxane was recrystallized from a 1:1 ethyl acetate-petroleum ether mixture, and the reaction time was shortened to 1.5 hours.

[0279] Table IV

[0280]

[0281]

[0282] *10 mmol of tetrachloroethane was used as internal standard.

[0283] The results show that various Lewis acids are able to generate monomers in a stable environment using a three-component embodiment.

[0284] It can be further observed that the results indicate that the catalyst system for the reaction is highly efficient even with as low as 0.1 mol% loading of the InCl3 component.

[0285] Example 4: Preparation of ethyl cyanoacrylate

[0286] A mixture including 10 g of ethyl cyanoacetate, 9 g of 1,3,5-trioxane and 20 g of acetic anhydride was stirred in the presence of a catalyst system including 1 mol% InCl3, 5 mol% hydroquinone and 5 mol% p-TsOH.H2O and heated to 120°C for 5 hours.

[0287] At the end of the reaction, once ethyl cyanoacetate has been completely consumed, the reaction mixture is directly fractionated and then 1 H-NMR measurement. No separation of the catalyst was required before distillation. The acetic acid byproduct was first distilled. After distillation at 110°C and 10 mbar without the use of volatile acid stabilizers, pure ethyl cyanoacrylate (in acetone-d6) 1 H-NMR showed that the product was free of ethyl cyanoacrylate and was isolated in a bulk state. The yield of pure ethyl cyanoacrylate was higher than 60%.

[0288] Example 5: Preparation of ethyl cyanoacrylate

[0289] In the presence of a catalyst system comprising 5 mol% hydroquinone and 5 mol% p-TsOH.H2O, a mixture comprising 1100 mg of ethyl cyanoacetate and 1300 mg of methylene diacetate was stirred and heated to 120°C for 1 hour.

[0290] according to 1 According to H-NMR data, the conversion rate of ethyl cyanoacrylate was 46%.

Claims

1. A method for preparing an electron-deficient olefin monomer, characterized in that: The active methylene compound of the general formula (III) is reacted with any one of a) or b) in the presence of a catalyst system; EWGCH2Z 1 (III), Among them, EWG and Z 1 Two electron withdrawing groups represented by are selected from nitrile, carboxylate and carboxylic acid functional groups; wherein a) is a mixture of a formaldehyde source and a carboxylic anhydride of the general formula (IV), Among them, Q 1 and Q 2 Independently selected from linear and branched C1-C4 alkyl groups, optionally, the H atoms are replaced by F atoms; Preferably, Q 1 and Q 2 are independently Me or Et; more preferably, Q 1 and Q 2 Independently for Me; The catalyst system comprises: i) at least one acid, or, ii) at least one acid and at least one promoter, wherein the acid is selected from the group of Lewis acids and Bronsted acids, and the at least one co-catalyst is selected from the group of phenolic compounds having one or more substituents, and quinone compounds; b) is a methylene diester of the general formula (V), Among them, Q 1 and Q 2 independently selected from C1-C4 straight chain and branched alkyl groups, The catalyst system comprises a Bronsted acid and at least one co-catalyst, wherein the co-catalyst is selected from the group consisting of a phenolic compound having one or more substituents, and a quinone compound.

2. The method according to claim 1, characterized in that The active methylene compound of the general formula (III) reacts with a mixture of a formaldehyde source and a carboxylic anhydride of the general formula (IV) in the presence of a catalyst system; EWGCH2Z 1 (III), Among them, EWG and Z 1 The two electron withdrawing groups represented by are selected from nitrile, carboxylate and carboxylic acid functional groups, Among them, Q 1 and Q 2 is independently selected from linear and branched C1-C4 alkyl, optionally, the H atom is replaced by a F atom; preferably, Q 1 and Q 2 are independently Me or Et; more preferably, Q 1 and Q 2 Independently for Me; The catalyst system comprises: i) at least one acid, or, ii) at least one acid and at least one promoter, Wherein, the acid is selected from the group consisting of Lewis acids and Bronsted acids, and the at least one co-catalyst is selected from the group consisting of phenolic compounds having one or more substituents, and quinone compounds.

3. The method according to claim 1 or 2, characterized in that: The active methylene compound of the general formula (III) includes nitrile and carboxylic acid ester as electron-withdrawing functional groups.

4. The method according to any one of claims 1 to 3, characterized in that The formaldehyde source is selected from dry formaldehyde gas, paraformaldehyde and 1,3,5-trioxane; preferably, the formaldehyde source is 1,3,5-trioxane.

5. The method according to any one of claims 1 to 4, characterized in that The catalyst system is selected from: a Lewis acid, preferably a late transition metal Lewis acid; a combination of a Lewis acid and a Bronsted acid, preferably a late transition metal Lewis acid; a combination of a Lewis acid and a co-catalyst, preferably a late transition metal Lewis acid, and the co-catalyst is selected from phenolic compounds, quinone compounds and mixtures thereof having one or more substituents; a combination of a Bronsted acid and a co-catalyst, and the co-catalyst is selected from phenolic compounds, quinone compounds and mixtures thereof having one or more substituents; and a combination of a Lewis acid, a Bronsted acid and a co-catalyst, preferably a late transition metal Lewis acid, and the co-catalyst is selected from phenolic compounds, quinone compounds and mixtures thereof having one or more substituents; preferably, the catalyst system is a combination of a Lewis acid, a Bronsted acid and a co-catalyst, preferably a late transition metal Lewis acid, and the co-catalyst is selected from phenolic compounds, quinone compounds and mixtures thereof having one or more substituents.

6. The method according to any one of claims 1 to 5, characterized in that The co-catalyst is selected from phenol, hydroquinone, p-methoxyphenol, p-trifluoromethylphenol, 1,4-benzoquinone, 1,4-naphthoquinone and a mixture thereof; preferably, the co-catalyst is hydroquinone.

7. The method according to any one of claims 1 to 6, characterized in that The Lewis acid is selected from transition metal halides, post-transition metal-based halides, alkaline earth metal-based perchlorates and lanthanide metal-based Lewis acids; preferably, the post-transition metal-based halides are trihalides; preferably, the Lewis acid is selected from the group of post-transition metal-based halides; more preferably, the Lewis acid is selected from the trihalides of indium (III) and trihalides of gallium (III); preferably, the Lewis acid is a trichloride; more preferably, the Lewis acid is InCl3.

8. The method according to any one of claims 1 to 7, characterized in that The Bronsted acid is selected from p-toluenesulfonic acid, benzenesulfonic acid and aralkylsulfonic acid; preferably, the Bronsted acid is p-toluenesulfonic acid in anhydrous form or in monohydrate form.

9. The method according to any one of claims 1 to 8, characterized in that The method comprises using a stabilizer, wherein the stabilizer is selected from an acid stabilizer and a free radical stabilizer; preferably, the acid stabilizer is selected from boron trifluoride etherate, SO2, and trifluoroacetic acid; more preferably, the acid stabilizer is boron trifluoride etherate; preferably, the free radical stabilizer is selected from 2,2'-methylenebis(6-tert-butyl-p-cresol), pentaerythritol tetrakis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate], hydroquinone, 4-methoxyphenol, butylated hydroxyanisole, and butylated hydroxytoluene.

10. The method according to claim 1, characterized in that The active methylene compound of the general formula (III) reacts with the methylene diester of the general formula (V) in the presence of a catalyst system; EWGCH2Z 1 (III), Among them, EWG and Z 1 The two electron withdrawing groups represented by are selected from nitrile, carboxylate and carboxylic acid functional groups, Among them, Q 1 and Q 2 independently selected from C1-C4 straight chain and branched alkyl groups, The catalyst system comprises a Bronsted acid and at least one co-catalyst, wherein the co-catalyst is selected from the group consisting of a phenolic compound having one or more substituents, and a quinone compound.

11. The method according to claim 10, characterized in that An active methylene compound of the general formula (III) as defined in any one of claims 3 to 5 is used.

12. The method according to claim 10 or 11, characterized in that: The methylene diester is methylene diacetate.

13. The method according to any one of claims 10 to 12, characterized in that A Bronsted acid as defined in claim 8 is used.

14. The method according to any one of claims 10 to 13, characterized in that A cocatalyst as defined in claim 6 is used.

15. The method according to any one of claims 10 to 14, characterized in that Comprising a stabilizer as defined in claim 9.

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