WO2010061025A1 - Fonctionnalisation de 1-vinyl-2-pyrrolidone en position 3 au moyen de l'ouverture de précurseurs cycliques - Google Patents

Fonctionnalisation de 1-vinyl-2-pyrrolidone en position 3 au moyen de l'ouverture de précurseurs cycliques Download PDF

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WO2010061025A1
WO2010061025A1 PCT/ES2009/070521 ES2009070521W WO2010061025A1 WO 2010061025 A1 WO2010061025 A1 WO 2010061025A1 ES 2009070521 W ES2009070521 W ES 2009070521W WO 2010061025 A1 WO2010061025 A1 WO 2010061025A1
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vinyl
pyrrolidone
group
compound according
formula
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PCT/ES2009/070521
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English (en)
Spanish (es)
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Helmut Reinecke
Rodrigo Navarro Crespo
Alberto Gallardo Ruiz
Mónica PÉREZ PERRINO
Myriam GÓMEZ TARDAJOS
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Consejo Superior De Investigaciones Científicas (Csic)
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
    • C07D207/267—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F226/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen
    • C08F226/06—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen by a heterocyclic ring containing nitrogen
    • C08F226/10—N-Vinyl-pyrrolidone
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F26/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen
    • C08F26/06—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen by a heterocyclic ring containing nitrogen
    • C08F26/10—N-Vinyl-pyrrolidone

Definitions

  • the present invention relates to a process for the functionalization of 1-vinyl-2-pyrrolidone in position 3 by opening cyclic precursors and in a single step reaction.
  • the present invention relates to functionalized VP compounds and polymers or copolymers that include them, as well as their different uses.
  • Poly-1-vinyl-2-pyrrolidone is a non-ionic and water soluble polymer that is used in many applications. It is used for example in cosmetics, personal hygiene items, paints, adhesives, contact lenses as well as in the medical area. PVP has even been used as a blood plasma substitute due to its known biocompatibility. It is also used as a nutritional additive, stabilizer (E1201), excipient of pharmacological compounds or, in combination with iodine, for the preparation of betadine®.
  • the PVP is, due to its water solubility and biocompatibility, a very interesting polymer. It can serve as a carrier of bioactive or pharmacological compounds or to prepare water soluble and pharmacologically active polymeric compounds.
  • a modification of the side chain a certain group of monomer units carries the functional group in the side chain.
  • the modifications in the side chain are multifunctional and allow the control of the number of functional groups since it is controlled by the degree of modification of the monomer units.
  • PVP is a polymer that contains cyclic amide groups that can be opened, for example, by hydrolysis with which multifunctional side chain copolymers are obtained in which, however, the integrity of the rings is not maintained.
  • the bromination of PVP at high temperatures has also been described, which leads to a polymer with a rather little specific modification.
  • the best alternative for the preparation of multifunctional side chain PVP derivatives with a versatile control of the number of functional groups and of the composition and which also have a random distribution of functional groups is the modification of the VP monomer followed by homo- or copolymerization with unmodified VP (strategy B2).
  • substrategy B2 unmodified VP
  • main chains made of pure PVP can be obtained while maintaining the integrity of the pyrrolidone rings.
  • the reactivities of the original VP and modified VP will be very similar and thus the inconveniences in copolymerization caused by differential reactivities mentioned above can be avoided.
  • the VP contains a strongly polarized carbon-hydrogen bond in the ⁇ position of the carbonyl group. With strong bases this hydrogen can be abstracted, forming the anion of the enolato of the carboxamide.
  • This intermediate compound can be used to attack alkyl halides in a nucleophilic manner.
  • This reaction can be used to connect groups consisting of pure hydrocarbons to the VP and it has been used to rent the monomer or to synthesize alkyl crosslinkers carrying two VP units (Engstrom JUA, Helgee B. Macromol. Chem. Phvs. 2006, 207 : 536-544; White, LA, Jonson, S, Hoyle, CE, et al., Polvmer, 1999, 40 (23): 6597-6605 or even to connect a biomolecule such as cholesterol (Cho, I, Jeong, Sw ., Macromol Chem Phvsic.
  • the present invention provides a method for synthesizing VP containing functional groups, such as carboxylic, hydroxy, mercapto, amino or sulfo, in its side chain. This procedure gives rise to functional groups in a one-step reaction by opening rings of appropriate cyclic compounds. These functionalized compounds can, in a second stage, react under mild conditions with an active compound to obtain conjugates of different nature.
  • functional groups such as carboxylic, hydroxy, mercapto, amino or sulfo
  • the process of the present invention allows the VP to be functionalized in position 3 directly in a single step with groups such as thiol, amino, hydroxy, mercapto, carboxyl or sulfo, by reaction of the anion of the carboxamide of the VP with different precursors cyclic of these functionalities.
  • groups such as thiol, amino, hydroxy, mercapto, carboxyl or sulfo
  • the nature and length of the spacer can be chosen between the VP group and the reactive functional group.
  • a first aspect of the present invention refers to functionalized VP of general formula (I) or any of its salts (from now on compounds of the invention):
  • A is a CR 1 R 2 group, a carbonyl group (CO) or a sulfone group
  • R 1 and R 2 are the same or different and represent a hydrogen (H) or a methyl group (CH 3 );
  • X is a radical selected from the group comprising a hydroxyl (OH), a thiol (SH), a sulfonyl (SO 3 H), an amine (NR 3 R 4 , NHR 3 or NH 2 ) or a carboxyl (CO 2 H );
  • R, R 3 and R 4 are a non-functional moiety in the reaction, are the same or different and represent an aryl group (C 6 -Ci 8 ) or an alkyl group
  • alkyl group refers, in the present invention, to aliphatic, linear or branched chains, having 1 to 10 carbon atoms, for example, this group can be methyl, ethyl, n-propyl, / -propyl, n-butyl, tere-butyl, sec-butyl, n-pentyl, etc.
  • the alkyl group has 1, 2, 3, 4, 5 or 6 carbon atoms.
  • aryl refers in the present invention to an aromatic carbocyclic chain, having from 6 to 18 carbon atoms, being able to be single or multiple ring, in the latter case with separate and / or condensed rings.
  • a non-limiting example of aryl is a phenyl, naphthyl, indenyl, etc. group.
  • the aryl group is a phenyl.
  • X is a hydroxyl group, whereby the compound is selected from those of formula 3- (hydroxyalkyl) -1-vinyl-2-pyrrolidone when A is a CR 1 R 2 group , or 3- ( 1-oxo- ⁇ -hydroxyalkyl) -1-vinyl-2-pyrrolidone, when A a carbonyl group (CO).
  • the compounds are, for example, but not limited to, 3- (2-hydroxyethyl) -1-vinyl-2-pyrrolidone, 3- (1-oxo-5- hydroxypentyl) -1-vinyl-2-pyrrolidone or 3- ( 1 -oxo-6-hydroxyhexyl) -1-vinyl-2-pyrrolidone.
  • X is a thiol group, giving rise to compounds such as, but not limited to, formula 3- (2-mercaptoethyl) -1-vinyl- 2-pyrrolidone.
  • X is a sulfonyl group, giving rise to compounds such as, but not limited to, formula 3- (3- sulfopropyl) -1-vinyl-2-pyrrolidone.
  • A is a carbonyl group and X an aromatic amine (NHR 3 or NH2) giving rise to compounds of formula 3- (1-oxo- ⁇ -aminoaryl) -1-vinyl-2-pyrrolidone, 3- ( 1-oxo- ⁇ -alkylaminoaryl) -1-vinyl-2-pyrrolidone or 3- (1-oxo- ⁇ -arylaminoaryl) -1-vinyl-2-pyrrolidone, where the number ⁇ will depend on the aryl group.
  • the aryl and alkyl groups refer respectively to the terms "aryl" and "alkyl” described above.
  • the compounds are, for example, but not limited to, the compounds 3- (2- aminobenzoyl) -1-vinyl-2-pyrrolidone or 3- (N-methyl-2-aminobenzoyl) -1-vinyl-2-pyrrolidone.
  • A is a carbonyl group and X is a non-aromatic amine (NHR 3 or NH 2 ), giving rise to compounds of formula 3- (1-oxo- ⁇ -aminoalkyl) -1-vinyl-2-pyrrolidone or 3- (1-Oxo- ⁇ -alkylaminoalkyl) -1-vinyl-2-pyrrolidone, where the number ⁇ will depend on the alkyl group and the alkyl group refers to the term described above.
  • the compounds are, for example, but not limited to 3- (1-oxo-2-aminopropyl) -1-vinyl-2-pyrrolidone.
  • A is a CR 1 R 2 group and X is an amine (NR 3 R 4 or NHR 3 or NH 2 ), giving rise to compounds of formula 3- ( ⁇ -aminoalkyl) -1-vinyl-2- pyrrolidone, 3- ( ⁇ -alkylaminoalkyl) -1 -vinyl-2-pyrrolidone, 3- ( ⁇ - arylaminoalkyl) -1 -vinyl-2-pyrrolidone, 3- ( ⁇ -dialkylaminoalkyl) -1 -vinyl-2-pyrrolidone, 3- ( ⁇ -diarylaminoalkyl) -1-vinyl-2-pyrrolidone, 3- ( ⁇ - alkylaminoalkyl) -1-vinyl-2-pyrrolidone, where the number ⁇ will depend on the alkyl group R.
  • aryl and alkyl groups refer respectively to the terms "aryl” and “alkyl” described above.
  • the compounds are 3 - (- 2-aminoethyl) -1-vinyl-2-pyrrolidone or 3- (2-Dimethylaminoethyl) -1-vinyl-2-pyrrolidone.
  • A is a carbonyl group and X is a carboxyl (CO 2 H), giving rise to compounds of formula 3- (1-oxo- ⁇ -carboxyalkyl) -1-vinyl-2-pyrrolidone, where the number ⁇ It will depend on the alkyl group and the alkyl group refers to the term described above. As for example, but not limited, the compound is 3- (1-oxo-2-carboxyethyl) -1-vinyl-2-pyrrolidone.
  • A is a sulfone group (-
  • SO 2 -) and X is an amino group (NH 2 or NHR 3 ), giving rise to compounds of formula 3- ( ⁇ -aminoalkylsulfonyl) -1-vinyl-2-pyrrolidone or 3- ( ⁇ -alkylaminosulfonyl) -1- vinyl-2-pyrrolidone or 3- ( ⁇ -arylaminosulfonyl) -1-vinyl-2-pyrrolidone.
  • the compound is 3- (2- aminoethylsulfonyl) -1-vinyl-2-pyrrolidone.
  • a second aspect of the present invention refers to the process for obtaining the compounds of general formula (I) comprising the following steps: a. deprotonation in position 3 of 1-vinyl-2-pyrrolidone (VP) by the addition of a base; b. The reaction of a precursor ring of formula (II) with 1-vinyl-2-pyrrolidone obtained in step (a).
  • VP 1-vinyl-2-pyrrolidone
  • Scheme 1 represents the synthesis of the compounds of formula (I) described according to the process of the invention:
  • A is the group susceptible to attack and R indicates the type and length of the spacer.
  • X ' is a precursor of the reactive group (X), usually an X group that has been deprotonated or carboxylated and is selected from an N-carboxyanhydride, ether, thioether, cyclic amine, ester, amide or anhydride group.
  • the compound of formula (2) can be selected from the list comprising a cyclic compound that contains as part of the cycle a group, such as, but not limited to, N-carboxyanhydride, ether, thioether, amine, amide, ester, sultone , sultama or anhydride.
  • a group such as, but not limited to, N-carboxyanhydride, ether, thioether, amine, amide, ester, sultone , sultama or anhydride.
  • Non-limiting examples of these X'-A groups, which form the above compounds, may be: CH 2 -O, CH 2 -S (for small rings of 3 or 4 links), OCO (lactone), OSO 2 (sultone) , OCN (lactam), SO 2 N (sultama) for rings of 4, 5, 6 or 7 links.
  • the addiction to the reaction of an excess of the cyclic compound can give rise to an oligomerization process obtaining macromonomers.
  • the cycle is a lactone and is added in excess, VP-oligo (lactone) could be obtained.
  • a preferred embodiment of the process of the invention comprises bringing the reaction to a temperature between -10O 0 C and 5O 0 C, more preferably at a temperature between -85 0 C and -20 0 C.
  • the first step of the synthetic route of the process of the invention consists in the formation of activated 1-vinyl-2-pyrrolidone, such as an enolate of carboxamide by the action of a base.
  • the functionalization of VP is achieved by nucleophilic attack of the enolate and the corresponding ring opening to cycles susceptible to this attack as shown in scheme 1.
  • the main driving force of the reaction is the high annular tension, while in the case of larger cycles such as lactones or sultones of 5 or 6 links - among others - the electrophilic susceptibility associated with the functional group It is the main responsible for the attack and the opening.
  • the optimal temperature range lies between 85 0 C and -2O 0 C, more preferably at a temperature of about -78 0 C.
  • ethylene oxide, ethylene sulfide or 1, 3-propane sultone in the cases that result products where vinylpyrrolidone contains or a unit of 2-hydroxyethylene or 2-mercaptoethylene respectively.
  • vinylpyrrolidone contains or a unit of 2-hydroxyethylene or 2-mercaptoethylene respectively.
  • a vinyl pyrrolidone with a single 3-sulfopropyl group is obtained.
  • monomer units with functional groups are obtained that have a short spacer of two or three methylene groups between the functional group and the VP.
  • This reaction can also be carried out with cyclic lactones as examples of larger cycles in which the annular tension is no longer the driving force of the reaction. In this case, longer spacers are obtained and the overall yields of the reactions are between 30 and 60%.
  • the precursor ring of formula (II) may be of the lactam type, lactones of different sizes, cyclic ethers or thioethers of 3 or 4 carbon atoms, cyclic amines of 3 or 4 carbon atoms, cyclic alkylultones, alkyl sulfonamides cyclic or cyclic ammonium salts.
  • precursor rings where R is different from a linear alkyl chain can be used, such as but not limited to propylene oxide [to give 3- (2-hydroxypropyl) -1-vinyl-2-pyrrolidone), or a aromatic ring in ortho.
  • the monomers corresponding to the compounds of general formula (I), for example, but not limited to VP functionalized with amine, carboxyl, sulfo, hydroxy, or mercapto groups, can be homopolymerized or copolymerized with 1-vinyl-2-pyrrolidone to form polymers or copolymers whose main chain consists exclusively of vinyl pyrrolidone units, that is, to form functionalized polypyrrolidone.
  • these functional groups can be used before or after homo- or copolymerization to covalently anchor active compounds such as drugs or nutraceuticals.
  • a third aspect of the present invention refers to the use of the compounds of general formula (I) for obtaining polymers or copolymers.
  • Another aspect of the present invention relates to polymers or copolymers comprising a compound of general formula (I) as a monomer.
  • the compounds of general formula (I), when X is a thiol group, can be a very useful tool in polymerization because it is difunctional, since SH is a very reactive transfer agent and, therefore, can be used to obtain macromonomers, grafts or crosslinks.
  • Fig. 1.- Represents a 1 H NMR spectrum of the 1: 1 copolymer of VP and VP- (CH 2 ) S -SO 3 Li (D 2 O, 300 MHz).
  • This product was prepared with a 35% yield, from VP (5.0 ml_, 47 mmol, 1.08 equiv) and ethylene sulfide (2.8 g, 47 mmol, 1.0 equiv) following the methodology described for the compound (1).
  • This product was obtained with a 28% yield, from VP (5.0 ml_, 47 mmol, 1.08 equiv) and ⁇ -valerolactone (4.0 ml_, 43.5 mmol, 1.0 equiv) as starting products.
  • the route used was the one described for the product (3).
  • reaction mass was maintained for 30 minutes at - 78 0 C. After this time, a solution of 11.7g of 1, 3- propanosultone (93 mmol, 2 equivalents) was dripped in 30 ml_ of THF anhydrous. During the addition the temperature should not exceed -76 0 C.
  • EXAMPLE 2 Polymerization and copolymerization of vinyl pyrrolidone (VP) and VP derivatives.
  • VP vinyl pyrrolidone
  • VP derivatives a polymer formed from polystyrene (PS) and polystyrene (PS)
  • monomers were dissolved in a total concentration of 1 M and initiator in a concentration of 1.5 x 10 ⁇ 2 M.
  • the oxygen present in the solution was displaced by bubbling with N 2 for 30 minutes It was then allowed to polymerize for the appropriate time and temperature.
  • the polymer or copolymer was isolated and purified by precipitation in a non-solvent. If it is soluble in water, it was purified by dialysis in 3000 cut-off membranes.
  • Reaction example 55 mg of VP (previously distilled) and 196 mg of VP- (CH 2 ) 3 -S ⁇ 3 Li (1: 1 molar ratio) were dissolved in 1 ml_ distilled water. 2.5 mg of azobisisobutyro nitrile (AIBN) was added. N 2 (carefully) was bubbled in the solution for 30 minutes and then the vial was closed and left in a closed oven at 50 ° C for 48 hours. After this time, the reaction was slowly precipitated in a large excess of acetone. The solid precipitated product was filtered, washed with acetone, and dried in vacuo to constant temperature. The 1 H NMR spectrum of this copolymer (D 2 O, 300 MHz) is shown in Figure 1.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Pyrrole Compounds (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)

Abstract

Des composés 1-vinyl-2-pyrrolidone fonctionnalisés avec des groupes hydroxyle, thiol, sulfonyle, amino ou carboxyle. De plus, la présente invention concerne le procédé de fonctionnalisation de 1-vinyl-2-pyrrolidone en position 3 au moyen de l'ouverture de précurseurs cycliques et dans une réaction en une étape. L'invention concerne aussi des polymères ou des copolymères comprenant ces composés ainsi que diverses utilisations de ceux-ci.
PCT/ES2009/070521 2008-11-27 2009-11-23 Fonctionnalisation de 1-vinyl-2-pyrrolidone en position 3 au moyen de l'ouverture de précurseurs cycliques WO2010061025A1 (fr)

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ESP200803380 2008-11-27
ES200803380A ES2340130B1 (es) 2008-11-27 2008-11-27 Funcionalizacion de 1-vinil-2 pirrolidona en posicion 3 mediante apertura de precursores ciclicos.

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109134404A (zh) * 2018-09-27 2019-01-04 湖南恒泰化工有限公司 3-吗啉丙磺酸的制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1184372A1 (fr) * 2000-08-31 2002-03-06 Pfizer Limited Dérivés hétérocycliques de phénoxyphényl, inhibiteurs de réabsorption de sérotonine

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Publication number Priority date Publication date Assignee Title
EP1184372A1 (fr) * 2000-08-31 2002-03-06 Pfizer Limited Dérivés hétérocycliques de phénoxyphényl, inhibiteurs de réabsorption de sérotonine

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BABUDRI, F. ET AL.: "Organometallic induced self-condensation of carboxamides", TETRAHEDRON, vol. 38, no. 4, 1982, pages 557 - 561 *
ENGSTROM, J.U.A. ET AL.: "Hydrophilic Polymer Supports for Solid-Phase Synthesis: Hydroxy-Functional Beads of Poly(vinylpyrrolidone)", JOURNAL OF COMBINATORIAL CHEMISTRY, vol. 8, 2006, pages 355 - 360 *
NENAJDENKO, V.G. ET AL.: "Synthesis and the keto-enol equilibrium of 2-acyl lactams", RUSSIAN CHEMICAL BULLETIN, INTERNATIONAL EDITION, vol. 52, no. 11, 2003, pages 2473 - 2482 *
PEREZ PERRINO, M. ET AL.: "''''One-pot'' Synthesis of 1-Vinyl-2-pyrrolidone with Protic Functional Groups in 3-Position''.", MACROMOLECULAR CHEMISTRY AND PHYSICS, vol. 210, 2009, pages 1973 - 1978 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109134404A (zh) * 2018-09-27 2019-01-04 湖南恒泰化工有限公司 3-吗啉丙磺酸的制备方法

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