Synthesis of N-vinyl compounds by reaction of NH-compounds with acetylene in the presence of homogeneous phosphine catalysts.

Abstract

A method for producing N-vinyl compounds by homogeneous catalysis, which comprises reacting a compound having at least one nitrogen atom having a replaceable hydrogen residue with acetylene in the liquid phase in the presence of at least one phosphine as a catalyst.

Description

[Technical field]

[0001] The object of the present invention is a method for producing N-vinyl compounds using a homogeneous catalyst, which comprises reacting a compound containing nitrogen substituted with hydrogen with acetylene in the liquid phase in the presence of a phosphine as a catalyst. [Background technology]

[0002] Traditionally, the industrial vinylation of NH compounds with acetylenes has typically been catalyzed by strong alkaline bases (see Chemical Reviews, 2014, 114, 1761-1782 and Liebigs Annalen der Chemie, 1956, 601, 81-138). In many cases, the alkaline base catalyst needs to be prepared in a separate process step immediately before the reaction ("base preparation"). A drawback of this prior art approach is the harsh and strongly basic conditions, which result in reduced yields, especially when base-sensitive substrates such as cyclic carbamates or lactams are used to prepare the corresponding N-vinyl compounds.

[0003] To overcome these inherent drawbacks and to carry out the vinylation under milder conditions, various approaches have been reported that use more efficient catalysts capable of promoting the N-vinylation with acetylene under milder conditions.

[0004] From EP 512656 it is known to prepare vinyl compounds by reacting acetylene with a Brönsted acid in the presence of a heterogeneous supported catalyst containing ruthenium.

[0005] EP-A-646571 discloses the homogeneous catalytic reaction of acetylene with ammonia or primary or secondary amino compounds at 1-30 bar, 20 bar being used in the examples. Various catalysts are disclosed, in particular ruthenium-based catalysts.

[0006] Chemical Communications, 2020, 56, 5977-5980 discloses homogeneous catalytic N-vinylation of cyclic amides and related cyclic compounds using a ruthenium catalyst bearing a phosphine ligand under low acetylene pressure of 1.5 bar.

[0007] A drawback of the aforementioned system is the use of the expensive noble metal ruthenium as the active catalyst. To overcome this drawback, a noble metal-free catalytic system that operates under mild reaction conditions (e.g., low basicity and acidity) would be beneficial.

[0008] Journal of the American Chemical Society, 1997, 119, 7595-7596 describes the use of phosphines as catalysts in the addition of internal and external alkynoates to activated NH-compounds as phthalimides and sulfonamides to the corresponding N-vinyl compounds. The drawback of this system is the need for large amounts (>50 mol%) of acidic cocatalysts such as acetic acid or phenol. It was also not possible to show that this catalytic system works for the vinylation of less acidic NH-compounds with simple acetylenes as alkynes.

[0009] Since acetylene is a gas, reactions with acetylene are usually carried out under pressure. From an economic and reaction safety standpoint, it is desirable to keep the pressure as low as possible. Summary of the Invention [Problem to be solved by the invention]

[0010] The object of the present invention was to provide a process for the synthesis of N-vinyl compounds which can be carried out under low pressure, basic or less acidic conditions, does not require base preparation as described in the prior art, and gives the N-vinyl compounds in high yield and selectivity. [Means for solving the problem]

[0011] As a result, the above method was discovered. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] NH-compound NH-compounds are organic nitrogen-containing compounds in which at least one nitrogen has a replaceable hydrogen residue, and the pKa determined in dimethyl sulfoxide is in the range of 14 to 28. a Values ​​were taken from the literature and were measured spectrophotometrically in DMSO at 25° C. against indicators, see J. Am. Chem. Soc. 1975, 97, 7006-7014 and J. Org. Chem. 1980, 46, 3295-3299. The corresponding experimental pKa values ​​were taken from the following references: FG Bordwell, H.E. Fried, J. Org. Chem. 1991, 56, 4218-4223; B. Valter, M.I. Terekhova, E.S. Petrov, J. Stehlicek, J. Sebenda, Collect. Czech. Chem. Commun. 1985, 50, 834-839; FG Bordwell, Acc. Chem. Res. 1988, 21, 456-463; FG Bordwell, G.E. Drucker, H.E. Fried, J. Org. Chem. 1981, 46, 632-635. For the substrates, pK a If values ​​are not available experimentally, the corresponding pK in DMSO is a The values ​​were calculated by DFT calculations according to the following method:

[0013] All geometry optimizations were performed using BP86 / def2-SV(P). 1 The stationary points were verified by analysis of vibrational frequencies at the geometry optimization level. The final electronic energies were calculated using Grimme's D3 dispersion correction incorporating Becke-Johnson damping. 3 PBE0-D3(BJ) / def2-QZVPP 2 This was obtained by single-point calculation using the theory of the level. 4All quantum chemical calculations were performed using the resolution-of-identity (RI) approximation implemented in the program. 6 and the corresponding auxiliary basis set 7 Using the TURBOMOLE program 5 (version 7.3). Zero-point vibrational energies and thermodynamic corrections were obtained at the geometry optimization level (T = 298.15 K and p = 1 bar). Solvent corrections for the Gibbs free energy in DMF were performed using the COS-MOtherm program. 9 (Version 18.0.0; Revision 4360) running the conductor-like screen model (COSMO-RS) on real solvents 8 All pKas were calculated for all species using the proton exchange scheme with either 2-pyrrolidone or 2-oxazolidinone as the standard, which has been widely used previously, e.g. by Ho et al. 10 .

number

[0014] pK aReferences for calculations: [1](a) Perdew, J.P., Density-functional approximation for the correlation energy of the inhomogeneous electron gas. Phys. Rev. B 1986, 33, 8822 - 8824; (b) Becke, A.D., Density-functional exchange-energy approximation with correct asymptotic behavior. Phys. Rev. A 1988, 38, 3098 - 3100; (c) Weigend, F.; Ahlrichs, R., Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: Design and assessment of accuracy. Phys. Chem. Chem. Phys. 2005, 7, 3297 - 3305. [2] Ernzerhof, M.; Scuseria, G.E., Assessment of the Perdew - Burke - Ernzerhof exchange - correlation functional. J. Chem. Phys. 1999, 110, 5029 - 5036; (b) Weigend, F.; Furche, F.; Ahlrichs, R., Gaussian basis sets of quadruple zeta valence quality for atoms H - Kr. J. Chem. Phys. 2003, 119, 12753 - 12762; (c) Weigend, F.; Ahlrichs, R., Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: Design and assessment of accuracy. Phys. Chem. Chem. Phys. 2005, 7, 3297 - 3305. [3] Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H.,A consistent and accurate ab initio parametrization of density functional dispersion correction(DFT-D)for the 94 elements H-Pu.J.Chem.Phys.2010,132,154104-154119.[4]Grimme,S.;Ehrlich,S.;Goerigk,L.,Effect of the damping function in dispersion corrected density functional theory.J.Comput.Chem.2011,32,1456-1465.[5](a)Ahlrichs,R.;Baer,M.;Haeser,M.;Horn,H.;Koelmel,C.,Electronic structure calculations on workstation computers:The program system turbomole.Chem.Phys.Lett.1989,162,165-169;(b)TURBOMOLE V7.3 2018,a development of University of Karlsruhe and Forschungszentrum Karlsruhe GmbH,TURBOMOLE GmbH,available from http: / / www.turbomole.com;(c)Treutler,O.;Ahlrichs,R.,Efficient molecular numerical integration schemes.Chem.Phys.1995,102,346-354.[6](a)Weigend,F.,Accurate Coulomb-fitting basis sets for H to Rn.Phys.Chem.Chem.Phys.2006,8,1057-1065;(b)Vahtras,O.;Almloef,J.;Feyereisen,M.W.,Integral approximations for LCAO-SCF calculations.Chem.Phys.Lett.1993,213,514-518;(c)Eichkorn,K.;Treutler,O.;Oehm,H.;Haeser,M.;Ahlrichs,R.,Auxiliary basis sets to approximate Coulomb potentials.Chem.Phys.Lett.1995,240,283-290;(d)Deglmann,P.;May,K.;Furche,F.;Ahlrichs,R.,Nuclear second analytical derivative calculations using auxiliary basis set expansions.Chem.Phys.Lett.2004,384,103-107.[7](a)Weigend,F.;Haeser,M.;Patzelt,H.;Ahlrichs,R.,RI-MP2:optimized auxiliary basis sets and demonstration of efficiency.Chem.Phys.Lett.1998,294,143-152;(b)Hellweg,A.;Haettig,C.;Hoefener,S.;Klopper,W.,Optimized accurate auxiliary basis sets for RI-MP2 and RI-CC2 calculations for the atoms Rb to Rn.Theor.Chem.Acc.2007,117,587-597.[8](a)Klamt,A.,Conductor-like Screening Model for Real Solvents:A New Approach to the Quantitative Calculation of Solvation Phenomena.J.Phys.Chem.1995,99,2224-2235;(b)Klamt,A.;Jonas,V.;Buerger,T.;Lohrenz,J.C.W.,Refinement and Parametrization of COSMO-RS.J.Phys.Chem.A 1998, 102, 5074-5085.[9](a)COSMOtherm Version 18.0.0(Revision 4360),COSMOlogic GmbH & Co KG,available from http: / / www.cosmologic.de;(b)Eckert,F.;Klamt,A.,Fast solvent screening via quantum chemistry:COSMO-RS approach.AIChE J.2002,48,369-385.

[10] (a)Ho,J.;Ertem,MZ,Calculating Free Energy Changes in Continuum Solvation Models.J.Phys.Chem.B 2016,120,1319-1329;(b)Ho,J.;Zwicker,VE;Yuen,KKY;Jolliffe,KA,Quantum Chemical Prediction of Equilibrium Acidities of Ureas,Deltamides,Squaramides,and Croconamides.J.Org.Chem.2017,82,10732-10736.

[0015] In particularly preferred embodiments, the NH-compound is a linear amide, a lactam, a cyclic carbamate, a pyrrole, an imidazole, a carbazole, an indole, a triazole, a urea, or a diarylamine.

[0016] A linear amide contains the amide group -NH-C(=O)-CR2-.

[0017] Cyclic amides contain the amide group -NH-C(=O)-CR2- as a member of the ring system.

[0018] Cyclic carbamates contain the carbamate group --NH--C(.dbd.O)--O-- as a ring system element.

[0019] Imidazole comprises an imidazole unit having an NH-functional group.

[0020] Pyrrole comprises a pyrrole unit having an NH-functional group.

[0021] The diarylamine contains an Ar2NH functional group.

[0022] The carbazole contains an NH-functional group.

[0023] Indole contains an NH-functional group.

[0024] Urea contains the -NRH-C(=O)-NRH- functional group.

[0025] Pyrazoles contain an NH-functional group.

[0026] The triazole contains an NH-functional group.

[0027] The additional carbon atom of the aryl group of a straight chain or ring system, an imidazole, or a diarylamine may be substituted or unsubstituted. The substituents on the carbon atom may be, for example, a carbonyl group (=O), an aliphatic or aromatic hydrocarbon group which may contain a heteroatom, especially oxygen in the form of an ether group, and the two adjacent carbon atoms may be part of an additional ring system, for example an alicyclic or aromatic ring system.

[0028] Preferred linear amides are N-methylacetamide (experimental pKa=25.9).

[0029] Preferred cyclic amides are 2-Pyrrolidone (experimental pKa = 24.2), 2-piperidinone (experimental pKa = 26.6), caprolactam (experimental pKa = 27.1), 8-octanlactam (experimental pKa = 27.3), 2,3-dihydro-1H-isoindol-1-one (calculated pKa = 19.4), 2,5-piperazinedione (calculated pKa = 20.9), 2-thiazolidinone (calculated pKa = 18.6).

[0030] Preferred cyclic carbamates are 2-oxazolidinone (calculated pKa = 20.8), 4-methyl-2-oxazolidinone (calculated pKa = 18.4), 5-methyl-2-oxazolidinone (calculated pKa = 19.2), tetrahydro-2H-1,3-oxazin-2-one (calculated pKa = 22.4).

[0031] Preferred pyrroles are Pyrrole (experimental pKa = 23), indole (experimental pKa = 21.0).

[0032] Preferred imidazoles are Imidazole (experimental pKa = 18.6), benzimidalazole (experimental pKa = 16.4).

[0033] Preferred pyrazoles are 1H-pyrazole (experimental pKa=19.8).

[0034] Preferred triazoles are 1H-1,2,4-triazole (experimental pK a =14.8) and its derivatives.

[0035] Preferred diarylamines are Diphenylamine (experimental pKa=25).

[0036] Preferred carbazoles are Carbazole (experimental pKa=19.9).

[0037] The preferred urea is Ethylene urea (calculated pKa=24.4), propylene urea (calculated pKa=26.2), and their derivatives.

[0038] In the process of the invention, an NH-compound containing nitrogen substituted with hydrogen is reacted with acetylene in the presence of at least one phosphine as catalyst (hereinafter also referred to as vinylation catalyst).

[0039] Phosphine Catalyst Phosphines suitable as catalysts for the vinylation in the process according to the invention are, for example, monodentate, bidentate, tridentate and tetradentate phosphines of the formulae I and II shown below: [ka] (In the formula, n is 0 or 1; R 1 ~R 9 are each independently unsubstituted or at least monosubstituted C1-C 30 Alkyl, C3-C 10 Cycloalkyl, C3-C containing at least one heteroatom selected from N, O, and S 10 Heterocycles, C5-C 14 Aryl or C5-C containing at least one heteroatom selected from N, O, and S 10 is heteroaryl, The substituents here are F, Cl, Br, OH, CN, NH2, and C1-C 10 selected from the group consisting of alkyl; A is, i) Unsubstituted or at least monosubstituted N, O, P, C1-C6 alkanes, C3-C 10 Cycloalkanes, C3-C containing at least one heteroatom selected from N, O, and S 10 Heterocycloalkanes, C5-C 14 a bridging group selected from aromatic and C5-C6 heteroaromatic groups containing at least one heteroatom selected from N, O, and S; The substituents here are C1-C4 alkyl, phenyl, F, Cl, Br, OH, OR 15 , NH2, NHR 15 , or N(R 15 ) 2 selected from the group consisting of R 15 is C1~C 10 Alkyl and C5-C 10 aryl; or ii) a bridging group of formula (III) or (IV): [ka] (wherein m and q are, independently of each other, 0, 1, 2, 3, or 4; R 10 , R11 are independent of each other, C1 to C 10 Alkyl, F, Cl, Br, OH, OR 18 , NH2, NHR 18 , and N(R 18 )2 groups; R 18 is C1~C 10 Alkyl and C5-C 10 aryl; X 1 , X 2 are, independently of each other, NH, O, or S; X 3 is a bond, NH, NR 17 , O, S, or CR 18 R 19 and; R 17 is unsubstituted or at least monosubstituted C1-C 10 Alkyl, C3-C 10 Cycloalkyl, C3-C containing at least one heteroatom selected from N, O, and S 10 Heterocycles, C5-C 14 Aryl or C5-C containing at least one heteroatom selected from N, O, and S 10 is heteroaryl, The substituents here are F, Cl, Br, OH, CN, NH2, and C1-C 10 selected from the group consisting of alkyl; R 18 , R 19 are each independently unsubstituted or at least monosubstituted C1-C 10 Alkyl, C1-C 10 Alkoxy, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkoxy, C3-C containing at least one heteroatom selected from N, O, and S 10 Heterocycloalkyl, C5-C 14 Aryl, C5-C 14 Aryloxy or C5-C containing at least one heteroatom selected from N, O, and S 10 is heteroaryl, The substituents here are F, Cl, Br, OH, CN, NH2, and C1-C 10 selected from the group consisting of alkyl; Y 1 , Y 2 , Y 3 are each independently a bond, unsubstituted or at least monosubstituted methylene, ethylene, trimethylene, tetramethylene, pentamethylene, or hexamethylene, The substituents here are F, Cl, Br, OH, OR 15 , CN, NH2, NHR 16 , N(R 16 )2, and C1~C 10 is selected from the group consisting of alkyl, R 16 is C1~C 10 Alkyl and C5-C 10 aryl).

[0040] A is a bridging group. A is an unsubstituted or at least monosubstituted C1-C6 alkane, C3-C 10 Cycloalkanes, C3-C 10 Heterocycloalkanes, C5-C 14 When selected from aromatic and C5-C6 heteroaromatic groups, when (n=0), the two hydrogen atoms of the bridging group are adjacent to the substituent Y 1 and Y 2 In the case of (n=1), the three hydrogen atoms of the bridging group are replaced by bonds to the adjacent substituent Y 1 , Y 2 , and Y 3 is replaced by three bonds to

[0041] When A is P (phosphorus), (n=0), phosphorus is adjacent to the substituent Y 1 and Y 2 and one bond to a substituent selected from the group consisting of C1-C4 alkyl and phenyl. In the case where (n=1), phosphorus is adjacent to the substituent Y 1 , Y 2 , and Y 3 Forms three bonds to

[0042] When A is N (nitrogen), (n=0), the nitrogen is adjacent to the substituent Y 1 and Y 2 and forms one bond to a substituent selected from the group consisting of C1-C4 alkyl and phenyl. In the case of (n=1), the nitrogen is adjacent to the substituent Y 1 , Y 2 , and Y 3 Forms three bonds to

[0043] When A is O (oxygen), n=0. Oxygen is adjacent to the substituent Y 1 and Y 2 Forms two bonds to

[0044] In a preferred embodiment, the process according to the invention is carried out in the presence of at least one phosphine catalyst of general formula (V) [ka] (In the formula, R 4 ~R 7 are each independently unsubstituted or at least monosubstituted C1-C 10 Alkyl, C3-C 10 Cycloalkyl, C3-C containing at least one heteroatom selected from N, O, and S 10 Heterocycloalkyl, C5-C 14 Aryl or C5-C containing at least one heteroatom selected from N, O, and S 10 is heteroaryl, The substituents here are F, Cl, Br, OH, CN, NH2, and C1-C 10 selected from the group consisting of alkyl; A is, i) Unsubstituted or at least monosubstituted N, O, P, C1-C6 alkanes, C3-C 10 Cycloalkanes, C3-C containing at least one heteroatom selected from N, O, and S 10 Heterocycloalkanes, C5-C 14a bridging group selected from a C5-C6 heteroaromatic group containing at least one heteroatom selected from aromatic, N, O, and S; The substituents here are C1-C4 alkyl, phenyl, F, Cl, Br, OH, OR 16 , NH2, NHR 16 , or N(R 16 ) 2 selected from the group consisting of R 16 is C1~C 10 Alkyl and C5-C 10 aryl).

[0045] In a preferred embodiment, the process according to the invention is carried out in the presence of a phosphine catalyst of formula I, the phosphine catalysts of formula I which are preferred herein are those in which R 1 , R 2 , and R 3 is phenyl or alkyl, each optionally having one or two C1-C4 alkyl substituents, and R 1 , R 2 , and R 3 are each C5 to C8 cycloalkyl or C2 to C 10 The group R is an alkyl group. 1 ~R 3 may be different or the same. Preferably, the group R 1 ~R 3 are identical and are selected from the substituents described herein and from the substituents indicated as particularly preferred.

[0046] As a catalyst with compound (I) in which R1, R2, and R3 are alkyl groups, a trialkylphosphine is preferred, and compound (I) in which R1, R2, and R3 are the same alkyl group is particularly preferred.

[0047] In a preferred embodiment, the trialkylphosphine used as catalyst is tri-n-butyl-phosphine or tri-n-octyl-phosphine.

[0048] In the context of the present invention, C1 to C30 Alkyl is understood to mean branched, unbranched, saturated and unsaturated groups. Alkyl groups having 1 to 10 carbon atoms (C1-C 10 An alkyl group having 4 to 8 carbon atoms (C4 to C8 alkyl) is preferred. An alkyl group having 4 to 8 carbon atoms (C4 to C8 alkyl) is more preferred.

[0049] Examples of saturated alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, amyl, hexyl, n-octyl, and isomers thereof.

[0050] Examples of unsaturated alkyl groups (alkenyl, alkynyl) are vinyl, allyl, butenyl, ethynyl and propynyl.

[0051] C1~C 30 The alkyl group may be unsubstituted or may be selected from the group consisting of F, Cl, Br, hydroxy (OH), C1-C 10 Alkoxy, C5-C 10 Aryloxy, C5-C 10 C5-C alkylaryloxy containing at least one heteroatom selected from N, O, and S 10 Heteroaryloxy, oxo, C3-C 10 C5-C containing at least one heteroatom selected from cycloalkyl, phenyl, N, O, and S 10 Heteroaryl, C5-C containing at least one heteroatom selected from N, O, and S 10 Heterocycle, naphthyl, amino, C1-C 10 Alkylamino, C5-C 10 C5-C containing at least one heteroatom selected from arylamino, N, O, and S 10 Heteroarylamino, C1-C 10 Dialkylamino, C 10 ~C 12 Diarylamino, C 10 ~C 20 Alkylarylamino, C1-C 10 Acyl, C1-C 10 Acyloxy, NO2, C1-C 10Carboxy, carbamoyl, carboxamide, cyano, sulfonyl, sulfonylamino, sulfinyl, sulfinylamino, thiol, C1-C 10 Alkylthiol, C5-C 10 Arylthiol or C1-C 10 It may be substituted with one or more substituents selected from alkylsulfonyl groups.

[0052] In this case, C3~C 10 Cycloalkyl is understood to mean saturated and unsaturated monocyclic and polycyclic radicals. 10 Examples of cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. Cycloalkyl groups are C1-C 10 It can be unsubstituted or substituted with one or more substituents as defined above in connection with the alkyl group.

[0053] The reaction according to the invention uses at least one phosphine as catalyst. In a preferred process, only one or different phosphines are used, particularly preferably only one phosphine is used.

[0054] In a preferred method, the reaction according to the invention uses one phosphine as a catalyst and no metal atom or ion is bonded to the phosphine as a ligand.

[0055] In the process of the present invention, the amount of vinylation catalyst used based on the NH-compound can vary within a wide range. Usually, the vinylation catalyst is used in less than stoichiometric amounts relative to the NH-compound. Typically, the amount of vinylation catalyst is 50 mol% or less, often 20 mol% or less, in particular 10 mol% or less or 5 mol% or less, based on the amount of NH-compound. An amount of vinylation catalyst of 0.001 to 50 mol%, often 0.001 mol% to 20 mol%, in particular 0.005 to 10 mol%, based on the amount of NH-compound, is preferably used in the process of the present invention.

[0056] The reaction of NH-compounds with acetylene can in principle be carried out according to all processes known to the skilled worker which are suitable for the reaction of NH-compounds with acetylene.

[0057] The acetylene used in the vinylation reaction can be used in pure form or, if desired, in the form of a mixture with other, preferably inert, gases such as nitrogen, argon, or propane, ethane, methane. The acetylene can be added without pressure or dissolved in a suitable solvent such as dimethylacetamide, dimethylformamide, NMP, toluene, benzene, or other solvent suitable for dissolving sufficient amounts of acetylene.

[0058] Acetylene can be applied discontinuously or continuously, for example, by bubbling acetylene gas into the reaction mixture or into the reactor, or by continuously feeding acetylene into the reactor as a reactant or dissolved in a solvent.

[0059] The reaction is typically carried out at cold acetylene pressures in the range of 0.1 to 20 bar, preferably in the range of 0.5 to 6 bar, more preferably in the range of 1 to 1.5 bar.

[0060] In one embodiment of the invention, the process according to the invention is characterized in that the reaction of the NH-compound with acetylene is carried out at a pressure in the range from 1 to 20 bar.

[0061] The reaction can in principle be carried out continuously, semi-continuously or discontinuously.

[0062] The vinylation reaction according to the present invention is carried out in liquid phase. This can be achieved by adding one or more solvents, preferably from the group of aliphatic and aromatic hydrocarbons, linear and cyclic ethers, linear and cyclic amides, sulfoxides, nitriles, and halogenated hydrocarbons. Preferred solvents are toluene, DMF, dimethylacetamide, and diglyme. The liquid phase can also be formed by NH-compounds without using additional solvents.

[0063] This reaction can in principle be carried out in all reactors known to those skilled in the art for this type of reaction. Suitable reactors are described and reviewed in the relevant prior art, for example in K. Henkel, "Reactor Types and Their Industrial Applications", Ullmann's Encyclopedia of Industrial Chemistry, 2005, Wiley-VCH Verlag GmbH & Co. KGaA, chapter 3.3: "Reactors for gas-liquid reactions".

[0064] The process of the present invention can be carried out in a wide temperature range. Preferably, the reaction is carried out at a temperature in the range of 20°C to 200°C, more preferably in the range of 50°C to 180°C, and particularly in the range of 100°C to 170°C. EXAMPLES

[0065] Experiments in ACE tubes: In a glove box (Ar), an ACE tube (4 mL volume, thick-walled glass tube with a Teflon screw cap, sealed with a Teflon O-ring) was charged with the substrate (usually: pyrrolidinone, 85.1 mg, 1.00 mmol, 1.00 equiv.) and the phosphine catalyst (usually: tributylphosphine, 20.2 mg, 0.100 mmol, 10.0 mol %). The tubes were charged with a freshly prepared solution of acetylene in dimethylacetamide (DMAA) (3.50 mL, 0.70 M / 1.90 wt, 2.45 mmol, 2.45 equiv.) prepared by bubbling dry, solvent-free acetylene into anhydrous DMAA, or with a freshly prepared solution of acetylene in dimethylformamide (DMF) (3.50 mL, 0.60 M / 1.65 wt, 2.10 mmol, 2.10 equiv.) prepared by bubbling dry, solvent-free acetylene into anhydrous DMF (substrate concentration: 0.286 M). The tubes were then sealed and heated at 120, 130, or 140° C. for 16 hours in a metal heating block. The tubes were then cooled to room temperature and mesitylene (30.0 μL) was added as an internal GC standard. The reaction mixture is then filtered through a syringe filter and analyzed by calibrated GC or 1 It was analyzed by GC coupled with H-NMR.

[0066] The analysis was performed on an Agilent Technologies 6890N gas chromatograph equipped with a split / splitless injector and an FID detector. The column used was an Agilent Technologies DB-1 capillary column (30m*0.25mm, 1μm) with helium as the carrier gas.

[0067] GC method: split: 50 / 1, 2.0 mL / min, constant pressure, 80°C-1 min-15°C / min-250°C-5 min.

[0068] NMR analysis was performed using a 60MHz 1The NMR spectra were performed on a Magritek Spinsolve60 Phosphorus Ultra NMR spectrometer at H frequency. Samples were measured in non-deuterated DMAA as the solvent. Proton spectra were performed with 4 scans, an acquisition time of 6.4 seconds per scan, a repetition time of 30 seconds, and a pulse angle of 90°. Conversion to vinyl compounds was detected by the three characteristic proton resonances of the vinyl group.

[0069] Feature examples (in ppm): 1 H-NMR (60MHz, DMAA) δ=6.85 (dd, 3 J HH =16.2Hz, 3 J HH =9.5Hz,1H,NCH),4.10(d, 3 J HH =16.6Hz,1H,NCHCH2),3.85(d, 3 J HH =9.5Hz,1H,NCHCH2).

[0070] NMR tube experiments: In a glove box (Ar), a solution (600 μL, 0.250 M) of the substrate (0.150 mmol, 1.00 equiv.) and tributylphosphine (6.1 mg, 30 μmol, 20 mol %) in anhydrous dimethylacetamide (DMAA) was placed in a J.Young NMR tube. The tube was sealed with a septum cap and solvent-free dry acetylene was bubbled through a steel cannula. The septum cap was then replaced with a J.Young cap in the glove box. The NMR tube was then heated to 110 °C in a metal heating block for 1 h, after which it was analyzed by NMR spectroscopy ( 1 H and 31 P) The process was repeated at 120°C, 130°C, 140°C, and once more at 140°C.

[0071] NMR analysis was performed using a 60MHz 1The NMR spectra were performed on a Magritek Spinsolve60 Phosphorus Ultra NMR spectrometer at H frequency. Samples were measured in non-deuterated DMAA as the solvent. Proton spectra were performed with 4 scans, an acquisition time of 6.4 seconds per scan, a repetition time of 30 seconds, and a pulse angle of 90°. Conversion to vinyl compounds was detected by the three characteristic proton resonances of the vinyl group.

[0072] Feature examples (in ppm): 1 H-NMR (60MHz, DMAA) δ=6.85 (dd, 3 J HH =16.2Hz, 3 J HH =9.5Hz,1H,NCH),4.10(d, 3 J HH =16.6Hz,1H,NCHCH2),3.85(d, 3 J HH =9.5Hz,1H,NCHCH2). [ka] Analyzed by ACE tube and calibrated GC

[0073] [Table 1] [ka] Analyzed by ACE tube and calibrated GC

[0074] [Table 2] [ka]

[0075] [Table 3] [Table 4]

[0076] The unisolated yield is usually calculated by adding the GC-NMR-integrals of the starting material and the product and normalizing the corresponding integrals by this value. Overlapping GC signals are integrated as is done automatically by the ChemStation software. This usually results in a slight bias towards product formation (broader signal of the underlying starting material).

[0077] Experiments in a Premex(tall) stainless steel autoclave: In a glove box (Ar), the substrate (usually: pyrrolidinone, 170.2 mg, 2.00 mmol, 1.00 equiv.) and the phosphine catalyst (usually: tributylphosphine, 20.2 mg, 0.100 mmol) were placed in a crimp vial (glass, 10 mL volume). Dimethylacetamide (DMAA) was added as required (0.185 mL or 0.930 mL, 2.00 mmol or 10.0 mmol, 1.00 equiv. or 5.00 equiv. %). A Teflon-coated magnetic stir bar was added, the vial was sealed with a septum cap, the septum was pierced with a stainless steel cannula, and placed in a Premex (tall) stainless steel autoclave (60 mL volume) equipped with a Kalrez O-ring. The autoclave was then sealed under argon, purged three times with solvent-free dry acetylene, and finally filled with acetylene (1.5 bar). The autoclave was then heated at 110-150 °C by a metal heating block for 16 h. The autoclave was then cooled to room temperature and depressurized via a bubble counter. After opening the autoclave, mesitylene (30.0 μL) was added to the crimp vial as an internal GC standard, and the reaction mixture was diluted with DMAA (1.5 mL). The reaction mixture was then filtered through a syringe filter and analyzed by a calibrated GC or 1 It was analyzed by GC coupled with H-NMR.

[0078] The analysis was performed on an Agilent Technologies 6890N gas chromatograph equipped with a split / splitless injector and an FID detector. The column used was an Agilent Technologies DB-1 capillary column (30m*0.25mm, 1μm) with helium as the carrier gas.

[0079] GC method: split: 50 / 1, 2.0 mL / min, constant pressure, 80°C-1 min-15°C / min-250°C-5 min. The measured GC signal areas, unless properly calibrated, are likely to be only estimates due to overlap of starting material and product. However, differentiation of both species is clearly possible. 1 This was confirmed by H-NMR spectroscopy.

[0080] NMR analysis was performed using a 60MHz 1 The NMR spectra were performed on a Magritek Spinsolve60 Phosphorus Ultra NMR spectrometer at H frequency. Samples were measured in non-deuterated DMAA as the solvent. Proton spectra were performed with 4 scans, an acquisition time of 6.4 seconds per scan, a repetition time of 30 seconds, and a pulse angle of 90°. Conversion to vinyl compounds was detected by the three characteristic proton resonances of the vinyl group.

[0081] Feature examples (in ppm): 1 H-NMR (60MHz, DMAA) δ=6.85 (dd, 3 J HH =16.2Hz, 3 J HH =9.5Hz,1H,NCH),4.10(d, 3 J HH =16.6Hz,1H,NCHCH2),3.85(d, 3 J HH =9.5Hz,1H,NCHCH2).

[0082] Autoclave Experiments: [ka] (Premex Tall2), analysis by calibrated GC

[0083] [Table 5] [ka] Premex Tall 2, GC analysis Starting material / product GC area: 81-19 [ka] Premex Tall 2, GC analysis

[0084] [Table 6] [ka] (Premex Tall 2), GC analysis

[0085] [Table 7]

[0086] Experiments in a stainless steel autoclave at high acetylene pressures (VMOX): Under an inert atmosphere, 100 g of 5-methyl-1,3-oxazolidin-2-one (MOX, 0.989 mol, 1 eq.) and 16.3 g (0.0396 mol, 4 mol%) of trioctylphosphine (90%, technical grade) were placed in a 0.3 liter autoclave. The reactor was closed, filled with acetylene up to an acetylene pressure of 5 bar, heated to 140° C., and then acetylene was passed at a rate of 25 standard liters / hour under a pressure of 17 bar for a reaction time of 16 hours. A standard liter is 1 liter of gas at 0° C. and 1013 mbar. The composition of the mixture obtained in the reactor after 16 hours of reaction was analyzed by gas chromatography and quantitative NMR. [ka]

[0087] [Table 8]

[0088] Experiments in a stainless steel autoclave at high acetylene pressure (NVP): Under an inert atmosphere, 100 g of 2-pyrrolidinone (1.175 mol, 1 eq.) and 7.3 g (0.018 mol, 1.5 mol%) of trioctylphosphine (90%, technical grade) were placed in a 0.3 liter autoclave. The reactor was closed, filled with nitrogen to 0.5 bar, heated to 140° C., and then filled with acetylene until the pressure in the reactor was 6.5 bar. During the vinylation reaction, the reactor pressure was maintained at 6.5 bar by adding acetylene. After the reaction was finished, the reactor was cooled to room temperature and depressurized. The composition of the mixture obtained in the reactor after 6 hours of reaction was analyzed by gas chromatography and quantitative NMR. [ka]

[0089] [Table 9]

Claims

1. A method for producing an N-vinyl compound by homogeneous catalysis, comprising the steps of: in the presence of at least one phosphine as catalyst, in the presence of a solvent selected from linear ethers, cyclic ethers, linear amides, cyclic amides, sulfoxides, nitriles, and halogenated hydrocarbons, or without a solvent, in the absence of a metal atom or ion bound to the phosphine as a ligand, A method for reacting a compound having at least one nitrogen atom having a replaceable hydrogen residue with acetylene in a liquid phase.

2. 2. The method of claim 1, comprising a compound having at least one nitrogen bearing a replaceable hydrogen residue, the pKa of which ranges from 14 to 28 as measured in dimethylsulfoxide.

3. 2. The process of claim 1, wherein the phosphine used as a catalyst is a trialkylphosphine.

4. The method of claim 3, wherein the trialkylphosphine is tri-n-butylphosphine or tri-n-octylphosphine.

5. The method of claim 3, wherein no additional catalyst is used apart from the trialkylphosphine.

6. 10. The process of claim 1, carried out in the presence of a solvent selected from dimethylformamide, dimethylacetamide, and diglyme, or without a solvent.

7. 2. The method of claim 1, wherein the N-vinyl compounds produced are 3-vinyl-5-methyl-1,3-oxazolidin-2-one and N-vinylpyrrolidinone.

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