CN1066979C - Linear high molecular super-nucleophilic catalyst, and inclusion-forming method therefor - Google Patents

Abstract

A novel polymeric supernucleophilic catalyst for accelerating acylation reactions was synthesized. That is to use 4-aminopyridine as the main raw material to make linear heterochain polymer compounds such as epoxy type through polycondensation reaction, and to form a highly active acylation catalyst that is easily soluble in the reaction system through chemical modification, and use this as the object Embedded in cross-linked or heterogeneous polymer hosts in the form of grids and microcapsules, a new type of reusable polymer catalyst is obtained. It is characterized by a simple synthesis route of the guest, high catalytic activity; low cost of the main body, easy adjustment of diffusivity; easy separation of embedded products from the system, and low residual rate of the catalyst in the catalyzed system. In accelerating acylation, esterification, hydrolysis and other organic reactions, it can be used as an alternative catalyst for acid-base, ion exchange resin, molecular sieve, DMAP, etc.

Description

Linear polymer supernucleophilic catalyst and embedding method

The present invention prepares and embeds a new type of polymer catalyst, more specifically, it is obtained through polycondensation reaction and chemical modification, and is used for catalyzing organic chemical reactions such as acylation, esterification, hydrolysis, and silylation. , a linear heterochain polymer compound containing pyridinamine supernucleophilic catalytic groups, and its grid and microcapsule embeddings obtained by imitating the method of solid-phase enzymes.

Early acylation reactions were generally accelerated by acid-base catalysts and later pyridine, so-called nucleophilic catalysts. For example, for the benzoylation of m-chloroaniline, the addition of pyridine increased the rate by a factor of 568. In the 1960s, pyridine amine derivatives were discovered as a "super nucleophilic catalyst", and its small molecule representative N,N-dimethyl-4-aminopyridine (DMAP) was placed in the above-mentioned benzoylation reaction , can also increase its rate up to 3.14×10 ⁶ times [Chem.Soc.Rev,1983,12(2),129], also have different reactions to esterification, hydrolysis, alkylation, silylation, etc. degree of catalytic ability. At present, it has been widely used in the synthesis of pharmaceuticals, dyes, fragrances and other fine chemicals, especially to solve the problem of low yield and rate in the acylation reaction of highly hindered alcohols and amines in organic synthesis.

In order to reduce the residual rate of the catalyst in the product of the catalyzed system and enable the repeated use of such relatively expensive catalysts, the researchers carried out the covalent linkage of the pyridinamine supernucleophilic group on the polymer carrier ( Such as polystyrene, etc.) [Polymer, 1987, 28 (4), 825], we have also synthesized polydiallylamine derivatives containing pyridine amine groups, polyurethane, etc. [J.Appl.Polym. Sci.,1994,53(10),1391][Macromol.Rep.,1995,A32(Suppl.3),319], the supernucleophilic group is firmly connected to the carrier by covalent bonding, The catalytic active center is not easy to fall off. However, the bonding reaction may destroy the structure of the active center; the microenvironment of the carrier and the diffusion effect sometimes hinder the approach of the substrate to the active site, and the network polymer catalyst makes it difficult for the substrate to diffuse due to the continuous network obstruction from the surface to the core. Reach deep inside the catalyst; the substrate can only be affected by the surface and shallow active sites, leading to the general result that cross-linked polymer catalysts are less active than their linear analogues. For example, linear homopolymers and copolymers of N,N-diallyl-4-aminopyridine have even higher catalytic activity than small molecule DMAP as homogeneous catalysts [J.Am.Chem.Soc.,1986 ,108,5514], while the activity of cross-linked polymer carriers to bond supernucleophilic groups is usually lower than that of DMAP.

Grid embedding and microcapsule embedding have been found in the immobilization technology of enzymes, cells and microorganisms. They have the characteristics of simple preparation and operation, only physical interaction between the coating and the coated catalyst, and low cost of the coating. The macromolecular network of the coating can prevent the linear macromolecules of the catalyst from permeating-dissolving into the reaction system solution, while being permeable to the entry and exit of the substrate and product small molecule organic compounds. Embeddings are generally cheap and well-studied polymers whose molecular mesh sizes are easy to adjust, while microcapsules only involve diffusion barriers in the outer shell. As an immobilization technology parallel to the covalent bonding method, it is also a novel and feasible method to embed non-biological enzymes and high-efficiency polymer catalysts by using grids and microcapsules.

The purpose of the present invention is to prepare a linear macromolecular supernucleophilic catalyst with high catalytic activity to the acylation reaction, and to embed the molecular chain containing catalytic groups in the heterogeneous macromolecules to make it with good accessibility, A highly efficient acylation catalyst that can be used repeatedly. Furthermore, by adjusting the cross-linking density, hydrophobicity and microcapsule film thickness of the coating, its permeability and sustained release can be improved.

Polymer catalyst provided by the present invention has the following characteristics:

(1) Has catalytic activity equivalent to that of N,N-dialkyl-4-aminopyridine.

(2) The catalyst is insoluble in the acylation reaction system. It is easy to separate from the catalyzed system and can be reused.

(3) The embedding polymer can adjust the molecular diffusivity, which is beneficial to the catalysis of the substrate inside the polymer.

(4) It has the property of not polluting products and not corroding reaction equipment.

(5) The synthesis steps are simple and the preparation conditions are mild.

(6) The product cost is relatively low.

The method of the invention is composed of three preparation steps: (A) preparation of linear macromolecules containing pyridine amine groups; (B) chemical modification of molecular chains; (C) embedding of macromolecule catalysts.

The good accessibility of the active site to the substrate requires that the linear macromolecular coil containing the catalytic group be in an extended state in the catalyzed reaction system, which requires that the molecular chain has similar polarity and hydrophobicity to the substrate and the solution. and solubility parameters. For the acylation reaction, both reactants and solvent molecules have certain polarity and hydrophilicity. Generally speaking, the solubility of heterochain polymers in the acylation reaction system is better than that of carbon chain polymers. Polyamides, polyesters, polyurethanes, polydiallylamines, and epoxy resins containing pyridylamine can all be used as excellent catalysts for acylating polymers. Among them, the most convenient known preparation method is to use 4-aminopyridine and strictly equimolar epichlorohydrin to synthesize linear epoxy polymer in one step under mild conditions.

However, there are a large number of hydroxyl groups on the epoxy polymer chain containing pyridylamine, and these hydroxyl groups can compete with the substrate and act together with the acylating reagent, thereby affecting the progress of the catalytic reaction. Therefore, the side groups need to be chemically modified to eliminate the hydroxyl groups. For example, use aliphatic acid chlorides such as acetyl chloride and n-octadecanoyl chloride; use aromatic acid chlorides such as benzoyl chloride, phenylacetyl chloride, and cinnamoyl chloride; or use dimethyl sulfate to perform esterification or etherification reactions with hydroxyl groups. In addition, this type of epoxy polymer is extremely hydrophilic and suitable for catalyzing hydrolysis reactions. However, in order to be compatible with various acylation reaction systems, the main chain must be chemically modified to change the hydrophobicity of the main chain. For example, adding a certain amount of aniline to 4-aminopyridine, and then polycondensing it with epichlorohydrin, can introduce aniline structural units into the main chain of the epoxy polymer, thereby increasing the hydrophobicity of the polymer chain.

After chemical modification of the side group and the main chain, the hydrophobicity of the linear macromolecule is adjusted so that it has considerable solubility in the catalyzed system. High catalytic activity. The gas chromatography tracking reaction experiment confirmed that the catalytic activity of this type of linear polymer catalyst surpassed that of the general-purpose small molecule supernucleophilic catalyst DMAP in the acetylation reaction of tert-butanol. Table 1 Comparison of the catalytic activity of epoxy polymer catalysts containing pyridylamine groups and DMAP in the acetylation reaction of tert-butanol t 0 10 20 30 40 50 60 70 C _P C _DMAP C _PC 000 016.831.3 029.753.4 040.568.8 1.550.278.9 2.157.985.8 2.564.390.4 2.970.493.3 t 80 90 100 110 120 140 160 180 C _P C _DMAP C _PC 3.274.895.4 3.878.797.1 4.282.398.2 4.585.298.9 4.887.599.4 5.791.199.8 6.493.6100.0 7.395.4100.0 Note: t - reaction time (min); C _p - in the presence of pyridine, the conversion rate of tert-butanol (%); C _DMAP - in the presence of DMAP, the conversion rate of tert-butanol (%); C _PC - containing pyridine In the presence of amine group epoxy polymer catalyst, the conversion rate (%) of tert-butanol (PC-Polymeric Catalyst polymer catalyst).

Linear polymer catalysts (considered as "guests") can still be dissolved in the catalyzed system, pollute the product and cannot be reused. Therefore, it is necessary to use a cross-linked or insoluble polymer coating (considered as the main body) for embedding. The host polymer can be a natural resin or a synthetic polymer. Such as polyacrylamide, poly Styrene, polyvinyl alcohol, polyurethane, ethyl cellulose, melamine-formaldehyde, starch, carrageenan, soybean protein, white gelatin, gum arabic, etc. Among them, polyacrylamide and ethyl cellulose have high strength and good chemical stability , low cost, and relatively mature research on its physical and chemical properties, it is the preferred material for coating the main body.

Embedding methods mainly include grid embedding and microcapsule embedding. Grid embedding is to dissolve or disperse the guest chain in the host monomer, and then aggregate the monomer into a three-dimensional grid structure. In this way, the guest as a linear polymer catalyst is embedded in the host molecular network and cannot be dissolved in the solution of the catalyzed system. For example, using acrylamide-N,N-methylenebisacrylamide as a polymerized monomer, the linear supernucleophilic epoxy polymer catalyst was used for network embedding. Since the macromolecular network of polyacrylamide swells in the acylation reaction system such as acetic anhydride, the substrate and product molecules can penetrate deeper into the catalyst. But at the same time, swelling aggravates the leakage of the guest from the host. Since the size of the guest macromolecules is much larger than the substrate and product molecules, the problem can be solved by adjusting the appropriate cross-linking density of the host.

Microcapsule embedding is to make the host molecules insoluble in the guest and system solution into a thin film, forming tiny particles with the guest molecules as the inner flesh and the host molecules as the outer skin. For example, [W/O]W emulsion-solvent evaporation technology is used for preparation. In this way, the polymer catalyst in the capsule still maintains a linear structure, and as long as the substrate and product molecules can diffuse in the host molecular film, it can maintain high catalytic activity like a homogeneous catalyst.

The embedding product of the linear polymer supernucleophilic catalyst obtained by the invention also has good catalytic activity for the acetylation reaction of tert-butanol. At the same time, the catalytic activity did not decrease significantly during repeated use.

Table 2 Catalytic activities of grid-embedded and microcapsule-embedded catalysts in the acetylation reaction of tert-butanol t 0 10 20 30 40 50 60 70 C _N C _E 00 12.911.5 24.121.4 33.930.4 42.838.5 49.745.6 56.151.7 61.557.1 t 80 90 100 110 120 140 160 180 C _N C _E 66.562.1 70.666.2 80.670.2 77.873.7 80.776.8 85.481.6 88.985.8 91.488.7 Note: t-reaction time (min); in the presence of _CN -grid-embedded catalyst, the conversion rate (%) of tert-butanol; in the presence of C _E -microcapsule-embedded catalyst,

Conversion rate of tert-butanol (%)

Below by example the present invention will be further described:

Characterization method: Nicolet 205 FTIR was used for infrared spectrum measurement. ¹ H-nuclear magnetic resonance was carried out using Bruker AP-P200 (200MHz). The elemental analyzer is PE-2400. The gas chromatograph (GLC) used to track the acylation reaction is Beifen SQ206, ion flame detection, 2m stainless steel column, GD×101 10% polyethylene glycol 20M, 170°C.

1. Preparation of linear poly(ρ-aminopyridine-epichlorohydrin-aniline)

25.00 g of 4-aminopyridine and 24.73 g of aniline were dissolved in 50 mL of DMF. After stirring for 5 minutes, 49.15 g of epichlorohydrin was added. Stir at room temperature for 3 h, distill under reduced pressure, dissolve the residue in water, precipitate in acetone, filter, and dry in vacuo to obtain 60.5 g of light yellow colloidal solid (yield 76%).

2. Benzoyl chloride modified poly(rho-aminopyridine-epichlorohydrin-aniline)

Take 50.0 g of poly(ρ-aminopyridine-epichlorohydrin-aniline) and dissolve it in 40 mL of DMF, slowly add 70 g of benzoyl chloride, and stir at room temperature for 2 h. Washed 3 times with ether, distilled under reduced pressure, and the residue was precipitated in acetone. Filter and dry in vacuo to obtain 78.0g light yellow colloidal solid (92% yield)

3. Grid embedding of linear supernucleophilic resin

Heat and stir a mixture of 75 g of acrylamide, 4 g of N,N-methylenebisacrylamide and 100 mL of 5% dimethylaminopropionitrile until dissolved. Add 60 g of benzoyl chloride-modified poly(ρ-aminopyridine-epichlorohydrin-aniline) and 2 g of potassium persulfate, cover the reaction system with N ₂ , and stir at a temperature of 50° C. until a gel appears. Soak the gel in flowing distilled water for 2 hours to remove the surface adherents. Vacuum dry.

4. Microencapsulation of linear supernucleophilic resin

50g of benzoyl chloride modified poly(ρ-aminopyridine-epichlorohydrin-aniline) was dissolved in 30 mL of water to obtain a core material solution; 12g of ethyl cellulose was dissolved in 80mL of dichloromethane to obtain a membrane material solution ; Dissolve 1.6g of gelatin in 200mL of water to obtain a continuous phase liquid.

Under stirring, slowly drop the core material liquid into the membrane material liquid to form an emulsion.

Add the emulsion to the continuous phase liquid under high-speed homogenization and stirring. After emulsification, the stirring rate was reduced and 1.4 g of adipoyl chloride were added. Keep stirring at above 40°C for 5 hours, and slowly volatilize dichloromethane until the system coagulates to form microcapsules. Soak the microcapsules in flowing distilled water for 1 hour to remove surface adherents. Vacuum dry.

5. Evaluation of Catalysts in the Acetylation of Tert-Butanol

Add 40.8 g of acetic anhydride, 15 mL of n-heptane (internal standard) and supernucleophilic catalyst equivalent to 10.0 mmol of active groups. At 25°C, put it into a thermostat, add 15.0 g of tert-butanol, and keep stirring. Sample 0.02 μL at regular intervals for gas chromatographic testing to track the progress of the reaction.

Claims (5)

1. A polymer super nucleophilic catalyst, characterized in that (1) The polymer supernucleophilic catalyst consists of two parts: guest and host; (2) The guest is a linear polymer of epoxy resin polymer; (3) The guest molecular chain contains a pyridinamine supernucleophilic catalytic group; (4) The hydroxyl group in the molecular chain of the guest is chemically modified with an acid chloride; (5) The host is a cross-linked polymer, and the host physically immobilizes the guest in the form of embedding and microcapsules, and the interaction between the guest and the host is intermolecular. 2. The macromolecular catalyst as claimed in claim 1 is characterized in that 4-aminopyridine is used as the main raw material, and the linear epoxy macromolecular compound as the guest is made through condensation polymerization. 3. The polymer catalyst according to claim 1, characterized in that the linear polymer can eliminate residual reactive groups and adjust its hydrophobicity through chemical modification, so that it is easy to dissolve in the acylation reaction system and has chemical stability sex. 4. The polymer catalyst according to claim 1, characterized in that the main body is insoluble in the acylation reaction system. 5. Polymer catalyst as claimed in claim 1, is characterized in that acylation reaction has catalytic activity, and its linear bad oxygen polymer also has catalytic activity to acylation reaction.